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Cryo crystal structure determination and application to intermediates Dietmar Stalke Ever since Wilhelm Conrad R�ontgen discovered X-rays a century ago and von Laue Friedrich Knipping Braggs and Braggs developed an analytical method almost nine decades ago single crystal structure analysis has become the most powerful analytical tool used to elucidate unequivocally the three dimensional structure of solid matter. New X-ray detectors like image plates or CCD-detectors permit the collection of two datasets a day. However this recent development should not only result in a higher ‘turn-over’ of crystal structure determinations but should also be utilized in new research approaches. One can think of monitoring chemical reactions in terms of Echtzeit crystallography.The challenge is to synthesize crystallize and analyze reaction intermediates by cryo crystal structure determination. Alkali organometallic compounds are omnipresent in any chemical laboratory where they are used as highly reactive starting materials in a vast number of reactions. It would be of great use to be able to freeze out intermediates along a reaction pathway in order to deduce new synthetic routes and concepts from the structural knowledge obtained by single crystal structure determinations. 1 Introduction Reading the leading journals in chemical science the perception might arise that about seventy percent of the published articles present or at least refer to new compounds characterized by single crystal structure analysis.In fact single crystal structure analysis is more and more regarded as the ultimate proof of the synthesis of a new compound. Furthermore authors currently discuss the reactivity of molecules largely in terms of their Dietmar Stalke born in 1958 in Melle Germany studied chemistry and philosophy at G�ottingen University. In 1987 he received his PhD for his thesis on fluorosilylamines. Subsequently he started his Habilitation (higher doctorate) in the group of Professor G. M. Sheldrick in G�ottingen. His major interest was to synthesise and isolate reactive intermediates in alkali organometallic chemistry. At the same time his intention was to employ single crystal structure analysis to investigate reactive and low melting compounds by cryo techniques.He spent some time in the group of Professor P. v. R. Schleyer at Erlangen (1989) and a year in Cambridge UK with Dr R. Snaith and Dr P. R. Raithby (1991). In 1995 he became an associate professor at the University of W�urzburg. His main areas of research are the syntheses of alkaline earth organometallic compounds and sulfur–nitrogen chemistry both with their main emphasis on materials science. Institut f�ur Anorganische Chemie der Universit�at W�urzburg Am Hubland D-97074 W�urzburg Germany structural features. For instance the basic understanding needed to comprehend the physiological effects of proteins is their structural determination. Although limited in the variety of chemical elements present their enormous conformational freedom makes the structural information a condition sine qua non.Current developments in organometallic chemistry increasingly lead to unstable compounds. Synthetically oriented chemists tend to work in more and more shallow depressions of the energy hyperface because thermodynamically unstable compounds promise a wider variety of reaction pathways. This opens up new synthetic routes to target materials. This is one of the reasons why alkali organometallics are an outstanding class of compounds. Unfortunately their high reactivity in most cases prevents their isolation and characterization by classical single crystal structure analysis hence they are almost exclusively used in situ. Knowledge about the reaction intermediates is mostly deduced afterwards from knowledge about the stable starting material and/or the products.However we aimed to get first hand structural information from thermodynamically unstable intermediates to facilitate the planning of organometallic syntheses. Classical single crystal structure analysis at room temperature is widely used to study compounds in deep depressions of the energy hyperface. Nevertheless up to now the derived experimental knowledge about the structural parameters of the solid state is unattained by any other analytical method. However results from NMR spectroscopic experiments in solution may be used more unambiguously because in many cases the synthesis is performed in solution as well. This brings up a well known dilemma on the one hand compounds sometimes have to be crystallized to obtain a single crystal structure analysis to be able to interpret unequivocally the NMR solution spectra.On the other hand it is not guaranteed that the results from the solid state structure can directly be transferred to solution. This experimental gap is closed by solid state NMR spectroscopy. Hence single crystal structure analysis in combination with NMR spectroscopy in solution and in the solid state are the three experiments which describe most chemical compounds completely. Certainly single crystal structure analysis still plays the leading r�ole among the three methods. The fundamental principles of cryogenic single crystal structure analysis have had to be extended to reactive intermediates and thermally unstable precursors.A ‘snap-shot’ structure analysis at different positions along a reaction pathway necessarily requires that one maintains a cold chain all the way from the synthesis to the end of the data collection. Special attention was turned to the requirements of the synthetic chemist as well as those of the crystallographer. To achieve a high degree of acceptance the method has had to be as simple and reliable as possible. Complicated and time consuming devices and techniques commonly not used in a synthetic and/ or X-ray laboratory would not have promoted the aim of determining structures of intermediates. The present article tries to encourage both synthetic chemists and crystallographers to have a closer look at reaction intermediates.Section 2 presents the devices and methods for manipulating reactive and/or low melting single crystals. Section 3 describes a home-made low-cost low temperature device to maintain the 171 Chemical Society Reviews 1998 volume 27 crystal at cryogenic temperatures during data collection at the diffractometer. Finally in section 4 some chemical examples from our work are presented in which all three of the above mentioned analytical tools have successfully been used to study phase transitions and reorganizations of reaction intermediates in the solid state. 2 Crystal handling at low temperature The advantages of crystal structure determination at low temperature compared to conventional room temperature measurements are well known.1 Crystals unstable under ambient conditions as well as compounds which are liquids or gases under these conditions can be studied in the solid state.Many compounds cocrystallize with solvent. The vapor pressure of crystal solvent is still high and allows diffusion out of the lattice. Normally this destroys the crystal or at least the intensities of the reflections change during data collection. Cooling of the crystal prevents the solvent from escaping the lattice. Cooling of proteins protects them from radiation damage even with high power synchrotron radiation.2 Therefore in most cases only one crystal is needed to collect the complete dataset. Moreover the problem of intensity decay with increasing sin q/l is less severe when cooling the crystal and hence the quality of the data set is improved resulting in a more accurate structure determination.At low temperature the atoms vibrate more isotropically and the residual electron density map is less contaminated by the diffuse electron density arising from anharmonic behavior. Thus the location of hydrogen atoms and electron deformation density work is facilitated. There are several home-made devices for maintaining a cold environment for thea are collected.3 Other devices are commercially available. However to get the most out of low temperature data collection it is essential to handle the compounds at low temperature continuously i.e. from crystallization until and during data collection. 2.1 Method The overall aim of crystal handling techniques should be to keep operations as simple as possible so that they can readily be taught to beginners.This is the only way of guaranteeing that the know-how will stay in the X-ray laboratory even though specialists may leave. Many methods have been employed by crystallographers to select a crystal and to transfer it to the diffractometer at temperatures below room temperature. B�arnighausen and Veith published a paper where they described a nitrogen cooled half pipe in which crystals can be handled below ambient temperatures.4 Laube and Dunitz constructed a closed glass apparatus to grow and transfer single crystals into capillaries at low temperatures.5 Boese and Bl�aser developed special techniques to manipulate single crystals and to transfer capillaries to the diffractometer at dry ice temperatures.6 Another technique is the in situ crystallization of samples in capillaries on the diffractometer.Simon initiated the method of zone melting by moving the capillary through heated apertures in a cold gas stream.7 Mootz and Boese developed a technique to grow single crystals by scanning the shock cooled sample in a capillary with an IR light focus.8 More recently Boese utilized an IR laser instead.9 Blake and others use a heated wire loop to melt partially a shock cooled sample in a capillary.10 No doubt there are many other laboratory-specific unpublished strategies to grow or to handle crystals below ambient temperatures. Unfortunately in situ crystallization is limited.For organometallic compounds for instance it is impossible to predict how much donating solvent is required to coordinate a metal. In general the synthetic work has to be done in a chemical laboratory in a Schlenk flask with reasonable amounts of starting material. Furthermore in our opinion sealing of crystals in capillaries at low temperature is not facile. Manipulating capillaries at low temperature requires sophisticated glassware Chemical Society Reviews 1998 volume 27 172 commonly not available to the working synthetic chemist. Moreover such manipulations normally need months or years of practice. Because of this we have not used any capillaries over the last ten years. Instead we have constructed a low temperature device from easily available parts which is a symbiosis of the nitrogen cooled half pipe published by Veith and B�arnighausen4 and the oil-drop mounting technique pioneered by Hope.11 It enables the crystallographer to investigate the crystal quality using a polarizing microscope as well as to mount the crystal at a fixed temperature ranging from room temperature down to 2100 °C.12 Fig.1 shows the device. Boil-off from liquid nitrogen is directed through glass tubing towards the microscope slide on which the sample resides. Fig. 1 Low temperature device for crystal handling At the beginning of crystal manipulation the sample is located in an ordinary Schlenk flask as generally used in a chemical laboratory. The whole batch of crystals in their mother liquor and the Schlenk gas is cooled down.The Schlenk flask with the sample is almost entirely immersed in the cooling agent (normally ethanol–dry ice) preventing the vessel from icing on the outside. Through the neck of the flask a small spoon is allowed to cool down in the mother liquor. Afterwards a portion of crystals is scooped up and covered with cold inert oil from a syringe. (If the crystals dry out very quickly this can even be done within the mother liquor preventing the crystals from being dried by the cold Schlenk gas). In Fig. 2 the nozzle of the mounting device can be seen in more detail. The microscope slide is provided with a small depression. This indentation is filled with oil and cooled by the nitrogen gas stream.The crystals on the small spoon are now rapidly transferred to the microscope and immersed in the oil. Fig. 2 The nozzle at the microscope slide The cold inert gas atmosphere and the surrounding oil prevent the crystals from being attacked by moisture and/or oxygen. Fig. 3 shows the mounting device in a laboratory environment. Fig. 3 The mounting device at the bench The oil allows washing splitting and selecting of crystals of suitable quality. When a suitable crystal has been selected an electrical pistol drill is used to drill a hole into a dry ice block. With a fiber which is already fixed on a goniometer pin the crystal is picked out of the oil captured on the tip of the fiber and transferred into the hole in the dry ice block.Under these conditions most of the crystals survive the short transportation to the low temperature nozzle at the diffractometer. There the crystal mount can easily be detached from the dry ice block and screwed onto the goniometer head. If lower temperatures are required a copper block with a hole cooled with liquid nitrogen can be used instead. When subjected to the lower temperature of the diffractometer cooling device the oil freezes and the crystal orientation is fixed. This technique provides several striking advantages compared to the use of capillaries free access to the sample (no limitations of glass joints rubber stoppers etc.) no mechanical stress to the crystal by pushing down into a (possibly too narrow) capillary no fixing problems (since we started using the technique we have never observed a wobbling crystal) the crystal cannot dry up because there is no capillary volume which can be filled with crystal solvent.Two kinds of oil which differ in viscosity are used in our laboratory. Both are perfluorinated polyethers. They can be regarded as ‘liquid Teflon’ (PTFE); neither have reacted with a compound nor shown miscibility with a solvent. These two oils are miscible with each other in any ratio therefore a mixture suitable for crystal manipulation in the temperature range between room temperature and 280 °C can be obtained. The high transparency of both oils even allows the employment of a polarizing microscope to investigate the crystal quality over the whole temperature range.2.2 Device used A schematic overview of the device used is given in Fig. 4. Cold nitrogen gas is generated from liquid nitrogen stored in a 7 l glass dewar. The main heater immersed in the liquid nitrogen causes nitrogen to evaporate. The gas flows through doublewalled glass tubes with a silvered vacuum jacket and is directed towards the microscope slide by a Teflon nozzle. The nitrogen gas is generated in a metal cylinder without a base and recooled in a copper tube projecting into the liquid nitrogen. This copper tube is attached to the vertical glass tube via a Teflon tube. The glass tubes are connected via a silicon o-ring and held together by a screw cap to prevent glass breakage. The nozzle is fixed to the horizontal glass tube.The shape of the nozzle causes the gas stream to flatten and to spread at the Fig. 4 Scheme of the low temperature device for crystal handling; gasstream pipe (1a,b) bottom element (2) taking the main heaters (4) thermoinsulation container (3) level sensors (5a,b) evaporation tube (6) thermoinsulated lid (7) refill tube (8) teflon adapter (9) gas-stream heater (10) gas-stream Teflon nozzle (11) internal thermocouple (12) external thermocouple (13) controller (14) outlet. Hence the whole slide is surrounded by cold gas. The shape of the nozzle the aerodynamic favourable shape of the sample immersed in a ‘puddle’ of oil and the relatively high flow rate of the cold gas stream prevent the sample from icing. The nozzle is equipped with an integrated heater preventing the outlet from icing.The whole device is supplied with direct current from an electronic controller. Any constant temperature between room temperature and 2100 °C can be reached by either tuningpower of the main heater causing more or less liquid nitrogen to be evaporated or tuning the power of the stream heater (10 in Fig. 4). The electric parts are protected against overheating by a level sensor integrated in a safety circuit arrangement. The safety circuit guarantees the power supply being switched off if the nitrogen level becomes too low. The nitrogen flow rate and the temperature of the stream heater are adjusted by two potentiometers. In our experience the mounting device is easy to make and even easier to maintain.However the device is now commercially available. With a single filling it can operate for up to 5 hours usually long enough to find a suitable crystal. It is refilled by simply adding liquid nitrogen without interrupting the investigation. 2.3 Conclusion The combination of cooling the sample and using the oil drop mounting technique facilitates the handling of very sensitive crystals. With some practice the transfer of the crystal from the mother liquor to the diffractometer can be realized within 30 seconds. It is very easy for beginners to learn the technique (much easier than mounting crystals in capillaries) and therefore it is accepted in the laboratory. Now there are crystallographers in our laboratory who have never had the experience of mounting a crystal in a capillary.With the suitable cryoprotectants and mounting techniques even the structure determination of very fragile proteins is facilitated.2 3 Low temperature set-up at the diffractometer Once a single crystal of a sensitive and low melting material has been transferred to the diffractometer a very reliable cooling device is required to keep the crystal at cryogenic conditions during data collection. Again the aim of simplicity determines the device to be robust and easy to maintain at low running 173 Chemical Society Reviews 1998 volume 27 costs. We have constructed a low temperature device which can readily be modified to suit any diffractometer type. It can be used at any constant temperature in the range of +50 to 2190 °C and ours has run for five years without being switched off.3.1 Cold gas stream generation The cold gas stream generation is based on the same principles already discussed in section 2.2 boil-off from liquid nitrogen is directed through double-walled silvered glass tubing with a vacuum jacket towards the crystal. The whole device consists of three main parts the storage dewar the transfer line and the nozzle (Fig. 5).13 Fig. 5 Scheme of the low temperature device at the diffractometer The storage dewar of the evaporator is a commercially available 30 l glass dewar. Cold nitrogen gas is generated in a brass cylinder immersed in liquid nitrogen. The bottom of the cylinder is fitted with a heating element made up from ceramic power resistors (main heater).The gas is directed through a helix of copper tubing which is immersed in the liquid phase for recooling. The gas leaves this tubing at a temperature only marginally higher than the boiling point of liquid nitrogen. The copper tubing is connected with the glass transfer line. It is formed like an upside down ‘u’ with an outer diameter of 40 mm and an inner diameter of 8 mm. Hence the inner cold gas stream is thermoinsulated by a concentric vacuum jacket of about 15 mm thickness. A heating element is centered inside the inner tube to warm the gas stream temperature to the required value. In a feed-back system it is connected to the main heater. Best results are obtained with transfer lines where the length of the horizontal part is minimized (150 to 200 mm) and the length of the leaving leg connected to the nozzle is 1300 to 1500 mm long.These dimensions have two basic advantages the whole device can be positioned above the diffractometer to prevent glass breakage and the leaving gas stream is extremely laminar because of the long outlet. The gas falls down the nozzle rather than being pumped. This saves liquid nitrogen and a homogeneous and constant gas stream is one of the best precautions to prevent icing of the crystal during data collection. The device uses 0.6 l liquid nitrogen per hour almost independent of the required temperature. We decided to have a stationary jet13 rather than to move the nozzle along with the crystal. In most diffractometer types (especially with an area detector system but also with a Huber off-set chi circle Nonius CAD4 or axs platform) there is plenty of space ‘above’ the crystal and even at a full four circle machine the stationary jet can be directed in at a 45° angle above the collimator without causing severe angle limitations.A transfer line made of a single piece guarantees the best achievable thermoinsulation. The ‘thermal leakage’ at connections in flexible arrangements causes drastically higher Chemical Society Reviews 1998 volume 27 174 liquid nitrogen consumption and the minimum temperature is much higher. In addition due to the crystal mounting technique discussed in section 2.1 moving the nozzle along with the goniometer main axis is unnecessary.The oil drop mounting technique ensures the crystal is always fixed at the tip of the glass fiber [Fig. 6(a)]. Nothing reaches up in the warm gas coating stream to cause turbulence. The stream is only disturbed by the lower part of the fiber but the thermal gradient is always directed away from the crystal and does not cause any changes in the crystal’s orientation. Mounting a crystal in a capillary leaves the upper part towering in the warm gas coating stream and causes a thermal gradient directed towards the crystal [Fig. 6(b)]. The temperature at the crystal (i.e. its orientation) is dependent on the orientation of the capillary in the cold gas stream. Icing and the loss of the orientation of the crystal relative to the diffractometer geometry are the consequences.Since we do not mount crystals in capillaries we do not move our low temperature nozzle. The aerodynamically favourable shape of a drop and the thin glass fiber cause a minimum of turbulence. Fig. 6 Crystal mounting with a stationary 45° dual stream low temperature nozzle; oil drop mounting on the tip of a fiber (a) causing less turbulence than a crystal in a capillary (b) 3.2 Nozzle We found the design of the low temperature nozzle crucial for good results. It should provide a laminar warm gas coating stream to preclude condensation of humidity on the cold gas stream. Likewise the cold gas area should be as large as possible to tolerate a slight misalignment of the nozzle without any effect on the crystal orientation.The two commercially available nozzle types—the one chamber and the two chamber nozzle—do not match these two basic requirements. In the one chamber nozzle the metal tip is electrically heated to generate the warm gas coating stream. In fact however our experience shows that the cold gas stream is compressed by the heating to such an extent that nearly no cold gas area remains. We mounted a thermocouple of the size of a single crystal on the goniometer head and the measurements revealed that the temperature at the crystal position is up to 50 °C higher than the reading on the instrumentation display (depending on the nozzle heater power setting). We suspect that the nozzle design prevents icing of the crystal by raising the temperature of the complete gas stream although the nozzle tip is conical to prevent this effect.The tip of the two chamber nozzle is not heated but needs a separate dry gas supply. The coating stream is generated by a second gas flow. Even to provide dry compressed air requires considerable effort. Furthermore the flow adjustment of both gas streams relative to each other is quite complicated and turns out to be irreproducible. Therefore we constructed our own nozzle to combine the advantages of both known designs. Simple electrical heating and a single gas source lead to the dual stream nozzle. The dual stream nozzle13 consists of three parts the stainless steel nozzle tip an outer Teflon tube and a thin walled inner tube (Fig. 7). The steel nozzle tip is fitted with a circular groove in which the heating coil resides.Two holes take the sensors for the thermostat which provides temperature constancy better Fig. 7 The dual stream nozzle at the diffractometer than ±1 °C to guarantee a constant flow rate of the coating stream relative to the inner cold gas stream. The steel nozzle tip is screwed flush into the outer Teflon tube which is connected to the vertical leg of the transfer line. A thin walled inner tube is placed concentrically in the steel–Teflon outlet dividing the whole gas stream into an inner (6 mm diameter) and an outer (1 mm concentric thickness) region. Because it is not trivial to machine very thin walled Teflon tubing we looked for a substitute. An ordinary plastic straw is now operating as the inner tube.It is held by three sharpened nylon screws placed in two ring sections. This arrangement physically separates the coating stream from the cold gas stream. Only the concentric stream between the inner and the outer tube is electrically heated to +30 °C. The inner tube precludes the inner stream from being compressed. The heating (i.e. expansion) accelerates the flow rate of the coating stream relative to the inner and more dense cold gas stream. This causes the stretching of the cold gas lip further out from the nozzle tip. This effect as used by a Bunsen burner permits small gas flow rates and relative long distances between the nozzle tip and the crystal. The adjustment of both streams is simply achieved by electronic regulation of the heating power.No additional gas supply is needed. The whole set-up required for sample cooling at the diffractometer is commercially available as well. 4 Applications to metastable compounds and reaction intermediates 4.1 Butyllithium Alkyllithium compounds are particularly important in synthetic chemistry as deprotonating and substituting reagents and as catalysts in polymerization.14 As long ago as 1917 Schlenk and Holtz reported the first synthesis of alkyllithium compounds;15 but until very recently no information about the crystal structures of ButLi and of donor-free BunLi has been available. This is probably due to the fact that these compounds (especially ButLi) are pyrophoric and that BunLi is an oil at room temperature.Without doubt the single crystal structure analysis of these frequently used organolithium reagents requires cryogenic techniques for crystal handling under protective conditions as discussed in the previous two sections. They facilitate the crystallization and the single crystal structure determination of donor-free BunLi ButLi and also of the metastable adduct of ButLi with one equivalent of diethyl ether.16 For the crystallization a temperature was chosen at which the nearly saturated solution could be prepared; this should be as low as possible to avoid phase transitions during low temperature data collection (here 290 °C). The limiting values taken into account were the melting point of BunLi [276 °C according to literature the melting point of the crystals investigated here however was 234(2) °C] and the temperature at which decomposition of ButLi·Et2O might occur (240 °C for ButLi·Et2O).To achieve a gradual and controlled crystallization all solutions were prepared at 280 °C. The crystallization period was extended to one week by redissolving crystals initially formed thus leaving a small number of nucleation sites in the solution.17 During the preparation of crystals for data collection (selecting and mounting a crystal and transporting it to the diffractometer) the temperature of a sample never exceeded 245 °C. The use of inert gas Schlenk techniques and sealing with inert oil were necessary to prevent the extremely oxygen- and moisture-sensitive crystals from reacting with air.All three compounds are discrete aggregates and no interactions between oligomers were found such as have been observed for example in the solid-state structure of MeLi (the shortest Li–C distance between two oligomeric units is 382 pm found in BunLi; in MeLi it is 252 pm18). The framework of BunLi consists of six Li atoms in a trigonal antiprismatic (distorted octahedral) conformation (approximately D3d symmetry) with six short (av. 242.9 pm) and six long (av. 293.9 pm) Li–Li distances (Fig. 8 top left). Analogous to various lithium organics18 six faces of the octahedron are each capped by a single Bun unit; two almost equilateral (and opposite) triangular faces with the longest edges remain unoccupied. Each a-carbon atom is coordinated to two Li atoms positioned at the corners of one of these (non-capped) triangles through short bonds (av.215.9 pm) whereas the bond to the Li atom at the corner of the opposite triangle is significantly longer (av. 227.0 pm). Hence the Bun moieties do not lie centrally over the isosceles Li triangles but are shifted to one edge (Fig. 8 right). As a result of this short distances occur between the b-C atoms and the Li atoms which may be interpreted as electrostatic interactions (Li–Cb distance av. 228.7 pm; notice that they are in the range of the longer Li–Ca bonds). At the same time this conformation has short Li–Ha and Li–Hb distances [204(2) and 203(2) pm]. The hydrogen atoms at the a–C and b–C atoms are arranged staggered with respect to the nearest Li atom.In conclusion BunLi shows similar structural characteristics to the cyclic alkyllithium compounds mentioned above. Apparently a fourfold coordination of the Li atoms by including b–C atoms is preferred in spite of the elongation of a Li–Ca bond. It is this disposition of the lithium to the Cb carbon that causes short Li···H contacts. They are due to steric strain rather than to agostic Li···H interactions. The arrangement of the short metal hydrogen distances in kite shaped Li(m–H)2C four-membered rings indicates that the hydrogen atoms have to avoid the lithium rather than have to be coordinated to the metal. Otherwise an almost linear Li···H–C arrangement with even shorter Li···H contacts would have been preferred. ButLi consists of tetrameric units of almost Td symmetry (Fig.8 top right) in the crystal. Each face of the Li4 tetrahedron 175 Chemical Society Reviews 1998 volume 27 Fig. 8 The structures of [BunLi]6 [ButLi]4 and [ButLi·Et2O]2 is capped by a But group so that the (terminal) Me groups are eclipsed with respect to the corresponding Li atoms of the (within the standard deviation) equilateral triangles. This conformation again involves comparatively short Li–Cb distances (av. 237.4 pm). Thus the structure of ButLi is essentially different from that of MeLi in which the hydrogen atoms of the Me groups (in contrast to the conformation of Cb atoms in ButLi) are staggered relative to the Li atoms.16 As in BunLi Li– Cb interactions may participate in determining the conformation of ButLi especially since the b–C atoms would preferentially be staggered for steric reasons.Moreover these contacts provide solubility of the tetrahedral monomers in hydrocarbons different to the polymeric structure of [(MeLi)4]H. The Li–Ca bond lengths (av. 224.6 pm) are in the range of the values observed in similar compounds while the Li–Li distances in ButLi (av. 241.2 pm) are significantly shorter [Li–Li and Li–C (pm) in MeLi:18 256 and 227 respectively]. Compared to methyl and ethyl groups the more electron releasing But group supplies more electron density to the Li4 core of the complex. As a consequence the repulsion of the four Li cations is less pronounced than in MeLi or EtLi. Although ButLi is known to cleave diethyl ether in a vigorous reaction to give EtOLi C2H4 and various other products we crystallized ButLi from diethyl ether.The colorless crystals melt at 238 °C. It should be noted that solutions of ButLi in diethyl ether are stable even with a large excess of ether (Et2O ButLi Å 6 1). Over a wider temperature range (up to about 240 °C) as observed in NMR studies ButLi·Et2O is a dimer which is generated crystallographically from the monomeric unit through a two-fold axis (Fig. 8 bottom left). The central four-membered ring consisting of two Li and two bridging a–C atoms of the But groups is folded along the C···C diagonal by about 30°. A staggered arrangement of the eight substituents along the C···C vector (six methyl groups and two lithium atoms) can only be achieved by this fold (Fig.8 bottom right). This steric crowding provides as well a possible explanation for the absence of a second donating Et2O molecule per Li atom in the solid state as postulated for ButLi in diethyl ether solution. 4.2 Lithium silylcuprates The last example in section 4.1 clearly demonstrates that in the structural investigation of intermediates and metastable compounds not only cryogenic techniques are required but also substituents with sufficient steric demand to stabilize kinetically the products. It is vital to freeze out a molecule ‘at the right time’ (i.e. for instance before the ether cleavage reaction in the [ButLi·Et2O]2 complex16) but it is also necessary to stabilize the system with bulky groups to get the chance to isolate intermediates.The Me3C-group is probably a good choice but the (Me3Si)3Si-group provides considerably more steric demand. Since the development of the tris(trimethylsilyl)silyl Chemical Society Reviews 1998 volume 27 176 3)3 ligand by Gilman and Smith19 it is widely used both in transition metal chemistry and main group metal chemistry.20 The good solubility of the products in hydrocarbons makes it a versatile ligand. Taking the electron releasing properties of –Si(SiMe into account we thought of this ligand as a good candidate to capture unstable products. On the one hand the importance of silyl groups in organic synthesis is undoubted and on the other hand very few structural details are known of the species involved in the lithium cuprate reactions.More commonly these species have been employed as in situ reagents predominantly in organic syntheses.21 The growing interest in organocopper compounds in particular the consideration of the theoretical aspects,22 encouraged us to react the tris(trimethylsilyl)silyl ligand with copper(i) halides.23 (Me3Si)3SiLi(thf)3 24 was reacted with CuICl and CuIBr at 278 °C. The different reactivity of CuICl compared with that of CuIBr (it shows for example a lower tendency than CuICl to disproportionate) should give rise to different unprecedented lithium silylcuprates. (Me3Si)3SiLi(thf)3 was reacted with CuICl in the ratio of 1 2 and with CuIBr in a 1 1 ratio in THF.23a Pure (Me3Si)3Si- Li(thf)3 is extremely pyrophoric and should be handled with care.All manipulations should be performed under an inert atmosphere of dry argon. Both reaction mixtures were immediately transferred to a deep freeze at 230 °C. THF [Li(thf)4][Cu5Cl4{Si(SiMe3)3}2] 5 CuCl + 2 (Me3Si)3SiLi(thf)3 –LiCl THF 2 CuBr + 2 (Me [Cu2{Si(SiMe3)3}2BrLi(thf)3] 3Si)3SiLi(thf)3 –LiBr Scheme 1 Under these conditions the first two lithium silylcuprates were isolated and structurally characterized. The complexes were found to be extremely air- and moisture-sensitive. During crystal selection and mounting the flask and the flushing argon was cooled down to ca. 250 °C. At temperatures slightly above 230 °C both compounds decompose instantaneously. The structure analysis of the first complex reveals the formula [Li(thf)4][Cu5Cl4{Si(SiMe3)3}2],23a (Fig.9 left). This non-predictable formula can be rationalized with hindsight as a [Li(thf)4][Cu{Si(SiMe3)3}2] containing an excess of 4 CuCl units. Fig. 9 The structures of the lithiumsilylcuprates [Cu5Cl4{Si(SiMe3)3}2]2 and [Cu2{Si(SiMe3)3}2BrLi(thf)3] Fig. 9 shows the cuprate anion. The Li(thf)4 cation has been omitted for clarity. To the best of our knowledge it is the first structurally characterized lithium silylcuprate. The silicon atom is in quite an unusual bonding situation. The central Si(1) is bonded to the three trimethylsilyl groups and to two copper atoms leading to five-coordinated silicon m2-bridging for silyl groups is very rare,25 although it is well documented for alkyl and aryl bridging carbons.The two Si–Cu bonds are equally long (234.8 and 233.4 pm). The bridged Cu(1)–Cu(2a) bond is with 240.3 pm by far the shortest of the Cu–Cu distances and 25 pm shorter than the others in the complex. So the almost equilateral triangle SiCu2 can be described in terms of a threecenter two-electron bond. In contrast to [Li(thf)4][Cu5Cl4{Si(SiMe3)3}2] [Cu2{Si- (SiMe3)3}2BrLi(thf)3]23b is a contact ion pair. It contains two differently bound (Me3Si)3Si groups and an additional LiBr equivalent. The tris(trimethylsilyl)silyl group around Si(1) is coordinated side on to a very short Cu(1)–Cu(2) bond again leading to a five-coordinated central Si(1) atom. The Cu(1)– Cu(2) distance is 236.9 pm and more than 3 pm shorter than in the last complex.In this example the three-center two-electron bond does not form an equilateral triangle. While the Si(1)– Cu(2) bond is 228.3 pm long the Si(1)–Cu(1) bond is more than 12 pm longer (240.6 pm). The shortest Si–Cu bond is that of the terminally-bound tris(trimethylsilyl)silyl group around Si(2) and Cu(1) (226.6 pm). Cu(2) is coordinated by a (thf)3LiBr group. 3LiBr In view of the Li–Br and Cu–Br bond length the (thf) group could be considered as the leaving group in this complex. When reacted further Cu2{Si(SiMe3)3}2 might be the product. However in the light of the growing importance of lithium cuprates as in situ synthetic tools in organic reactions certainly more structural information of this reactive species is required to elucidate reaction mechanistics and to design new synthetic concepts.Apparently the m2-bridging of a short Cu–Cu distance is not limited to carbon. Further experiments to isolate other intermediates in the reactions of copper(i) halides as well as to elucidate the final products are underway. 4.3 Lithium aluminum hydrides While butyllithium discussed in section 4.1 is a frequently used deprotonating reagent lithium aluminum hydride LiAlH4 is a versatile reducing and hydrogenating reagent in both inorganic and organic synthesis. Although more than 60 functional groups are known to react with LiAlH4 very little is known of the reactive species involved in these syntheses. N�oth and coworkers investigated the reaction of aliphatic secondary amines with LiAlH4 by 7Li and 27Al NMR spectroscopy from solution and determined the structure of [(Pri 2N)4AlLi·2thf]26 and [(Pri- 2N)3AlHLi]H.26 We reported the isolation of two intermediates in the following reaction (Scheme 2).27 1/2[(Me3Si)2NAlH3Li•2Et2O]2 HN(SiMe3)2 + LiAlH4 +HN(SiMe3)2 –H2 +2HN(SiMe3)2 [(Me3Si)2N]2AlH2Li•2Et2O [(Me3Si)2N]3Al + LiN(SiMe3)2 –2H2 Scheme 2 The isolation of products along this reaction pathway shows that the overall reaction to form the trisubstituted aluminum compound Al[N(SiMe3)2]3 28 proceeds stepwise. The reactive mono-substituted complex [(Me3Si)2NAlH3Li·(OEt2)2]2 and 3Si)2N]2AlH2Li·(OEt2)2 can be isolated. the disubstituted [(Me Lithium aluminum hydride was reacted in diethyl ether with di(trimethylsilyl)amine.The reaction mixture was stirred at room temperature for 24 hours. After filtering crystals of [(Me3Si)2NAlH3Li·2Et2O]2 are obtained after 3 days at 235 °C. These crystals directly mounted from mother-liquor at ca. 250 °C have been investigated by single crystal structure analysis. At approximately 230 °C the colorless crystals start to effervesce like champagne and turn into a white insoluble powder. We assume they lose hydrogen. [(Me3Si)2NAl- H3·2Et2O]2 (Fig. 10 left) is a dimer in the solid state. The aluminum in the central eight-membered Al2H4Li2-ring is coordinated by three hydride atoms and one N(SiMe3) ligand. The lithium atoms form two bridges between the two (Me3- Si)2NAlH3 units via Li–H contacts. Each of them is also coordinated by two diethyl ether molecules.The average Li–H distance in [(Me3Si)2NAlH3Li·2Et2O]2 is 177.7 pm and therefore significantly shorter than in solid LiH (204.0 pm)29 or even in AlH of [(Me 4Li (188–216 pm).30 The very similar dimeric structures 2PhSi)3CAlH3Li·2thf]2,31 [Mes*AlH3Li·2thf]2 32 and Fig. 10 The structures of the lithium aluminum hydrides [Ph3C6H2AlH3Li·2Et2O]2 32 prove that this structural type is not limited to amido aluminum complexes. 3)2 to LiAlH4 in diethyl ether and Addition of HN(SiMe subsequent refluxing for 3 hours and stirring for 12 hours at room temperature leads to the formation of the disubstituted complex [{(Me3Si)2N}2AlH2Li·2Et2O]. Crystals were grown in good yield at 218 °C. Under these conditions the reaction is stopped after the substitution of the second equivalent of di(trimethylsilyl)amine rather than going on to the trisubstituted product Al[N(SiMe3)2]3.Crystals of [{(Me3Si)2N}2Al- H2Li·2Et2O] were mounted on the diffractometer at ca. 210 °C and started to effervesce above +5 °C. They lose hydrogen as well. Fig. 10 right shows that the structure of [{(Me3 Si)2N}2AlH2Li·2Et2O] in the solid state is monomeric. The most striking feature is the central AlH2Li four-membered kiteshaped ring where the lithium atom bridges the two aluminumbonded hydride atoms. The structure of [Li{N- (But)CH(But)CH2N(But)}AlH2]4 33 resembles this structural feature within an Al2H6Li4 twelve-membered ring. In contrast to the C(m-H)2Li bonding situation discussed earlier this interaction seems to be chemical bonding.The hydride atoms in the Al(m-H)2Li four-membered ring differ from the hydrogen atoms in the C(m-H)2Li ring being negatively charged and thus attractive to the positively charged lithium atom. This coordination is even present in solution and can be verified by a NMR experiment. The bond angles show that [{(Me3Si)2N}2Al- H2Li·2Et2O] forms a rather strained structure. The average H–Al–H bond angle in the monomer (94.3°) is 12.9° smaller than in the dimer (107.2°). The average H–Li–H angle in [{(Me3Si)2N}2AlH2Li·2Et2O] (73.6°) is as much as 33.8° smaller than in [(Me3Si)2NAlH3Li·2Et2O]2 (107.4°). The intramolecular bridging of the lithium atom leads to a longer LiH distance (av.193.3 pm; cf. 177.7 pm in [(Me3- Si)2NAlH3Li·2Et2O]2) which is comparable to the distance in AlH4Li. The hydride atoms are forced close together in the transannular distance of 233.1 pm. Despite this steric strain the molecule does not dissociate in 3Si)2N}2Al- 2Li.2Et2O] shows a 1J(Li,H) coupling constant of 10.5 Hz LiH coupling solution. The 7Li NMR spectrum of [{(Me H (Fig. 11). This is in good agreement with J constances in lithium organics.34 In [{(Me3Si)2N}2AlH2Li·2Et2O] the 7Li–1H coupling is only resolvable in the temperature window of 230 °C to 270 °C. Outside this window the triplet structure of the signal is lost at higher temperatures as a result of exchange and at lower temperatures probably by 7Li quadruple effects and rising viscosity of the solution.The coupling could not be verified in the 1H NMR experiment because the hydride signals are too broad. Furthermore the 1JLiH coupling could not be observed in [(Me3Si)2NAlH3Li·2Et2O]2 at any temperature between room temperature and 2120 °C in [2H]8toluene. It is fluctional in solution. This fluctionality could consist in a monomer–dimer equilibrium superposed in a m1 and/or m2 and/or m3 hydride bridging exchange. A recent report of Roesky and coworkers on reactions of primary and secondary amines with LiAlH4 and Na(AlHEt3) and the isolation and structural determination of related intermediates proves,35 that our knowledge for describing and 177 Chemical Society Reviews 1998 volume 27 constant 1J Fig.11 Experimental 7Li NMR spectra of [{(Me3Si)2N}2AlH2Li·2Et2O] at various temperatures. The chemical shift at 250 °C is 0.4 the coupling (Li,H) 10.5 Hz. predicting reaction pathways in this area of chemistry is not by any means satisfactory. To extend our understanding a great deal of structural work on intermediates is still required. With the latest progress in cryo crystal structure analysis and in the area detector technology this seems feasible. 5 Conclusion The last pages have demonstrated that the cryogenic single crystal structure analysis has been successfully developed and used to gain structural information on reaction intermediates and reactive metal organic systems. The classical structure analysis very well established for thermodynamically stable compounds can readily be extended by cryogenic techniques to work on metastable compounds as well.Some examples may have shown that although the structure analysis plays the leading r�ole complementary analytical information is required to elucidate phenomena in solution or in the solid state. Spectroscopic data are still needed for the comprehensive description of a chemical system. Once the structure has been determined it should not only be noted for deposition at a data base but it should also promote new original ideas and synthetic concepts towards making target molecules. Mutual learning by chemists and crystallographers will give a tremendous impetus to all fields of chemistry and alkali metal chemistry and this will be a particularly flourishing area of research.6 Acknowledgements In particular I thank Professor G. M. Sheldrick for the excellent working conditions and his constant interest even in nonprotein molecules. The enthusiasm of all diploma and PhD students over the years is acknowledged. T. Kottke developed the device for low temperature crystal mounting. Parts of his and A. Heines work are presented here. I thank them for their days at the bench and their nights at the diffractometer. The expertise of the workshop of the Anorganisch Chemisches Institut der Universit�at G�ottingen was essential to the success of this work. J. Haupt H. Dehnhardt B. Jones D. Laudenbach G. Ramm D. Hesse and W. Berg realized more than once the squaring of the circle.G. Elter and W. Zolke have been easy to approach even with extreme NMR ideas. M. Haase Bruker axs X-ray systems Karlsruhe kindly supported the work. The project was financed by the Deutsche Forschungsgemeinschaft Chemical Society Reviews 1998 volume 27 178 Fonds der Chemischen Industrie and the Stiftung Volkswagenwerk. 7 References 1 (a) R. Rudman Low Temperature X-Ray Diffraction Apparatus and Techniques Plenum New York 1976; (b) M. Veith and W. Frank 2 For a review see E. F. Garman and T. R. Schneider J. Appl. 3 H. D. Bellamy R. P Phizackerley S. M. Soltis and H. Hope J. Appl. 4 M. Veith and H. B�arnighausen Acta Crystallogr. Sect. B 1974 30 5 D. Seebach R. Amstutz T. Laube W. B. Schweizer and J. D. Dunitz Chem. Rev. 1988 88 81. Crystallogr.1997 30 211 and references therein. Crystallogr. 1994 27 967 and references therein 1806. J. Am. Chem. Soc. 1985 107 5403. 6 R. Boese and D. Bl�aser J. Appl. Crystallogr. 1989 22 394. 7 See for example A. Simon W. Br�amer B. Hillenk�otter and H.-J. Kullmann Z. Anorg. Allg. Chem. 1976 419 253. 8 D. Brodalla D. Mootz R. Boese and W. Osswald J. Appl. Crystallogr. 1985 18 316. 9 See for example M. B�uhl H. F. Schaefer III P. v. R. Schleyer and R. Boese Angew. Chem. 1993 105 1265; Angew. Chem. Int. Ed. Engl. 1993 32 1154. 10 See for example A. J. Blake S. Cradock E. A. V. Ebsworth and K. C. Franklin Angew. Chem. 1990 102 87; Angew. Chem. Int. Ed. Engl. 1990 29 76. 11 H. Hope Acta Crystallogr. Sect. B.,1988 44 22. 12 T. Kottke and D.Stalke J. Appl. Crystallogr. 1993 26 615. 13 T. Kottke D. Stalke J. Appl. Crystallogr. 1996 29 465. 14 Lithium Chemistry eds. A.-M. Sapse and P. v. R. Schleyer John Wiley and Sons New York 1994. 15 W. Schlenk and J. Holtz Ber. Dtsch. Chem. Ges. 1917 50 262. 16 T. Kottke and D. Stalke Angew. Chem. 1993 105 619; Angew. Chem. Int. Ed. Engl. 1993 32 580. 17 J. Hulliger Angew. Chem. 1994 106 151; Angew. Chem. Int. Ed. Engl. 1994 33 143. 18 For a review see E. Weis Angew. Chem. 1993 105 1565; Angew. Chem. Int. Ed. Engl. 1993 32 1501. 19 H. Gilman and C. L. Smith J. Organomet. Chem. 1968 14 91. 20 K. W. Klinkhammer Chem. Eur. J. 1997 3 1418 and references therein. 21 B. H. Lipshutz and S. Sengupta Org. React. 1992 41 153. 22 See for example P. Pyykk�o Chem. Rev. 1997 97 597. 23 (a) A. Heine and D. Stalke Angew. Chem. 1993 105 90 Angew. Chem. Int. Ed. Engl. 1993 32 121; (b) A. Heine R. Herbst-Irmer and D. Stalke J. Chem. Soc. Chem. Commun. 1993 1729. 24 A. Heine R. Herbst-Irmer G. M. Sheldrick and D. Stalke Inorg. Chem. 1993 32 2694. 25 J. C. Calabrese and L. F. Dahl J. Am. Chem. Soc. 1971 6042. 26 S. B�ock H. N�oth and P. Rahm Z. Naturforsch. B 1988 43 53. 27 A. Heine and D. Stalke Angew. Chem. 1992 104 941; Angew. Chem. Int. Ed. Engl. 1992 31 854. 28 J. Pump E. G. Rochow and U. Wannagat Angew. Chem. 1963 8 375; Angew. Chem. Int. Ed. Engl. 1963 2 264. 29 E. Zintl and A. Harder Z. Phys. Chem. B 1935 28 478. 30 N. Sklar and B. Post Inorg. Chem. 1969 6 669. 31 C. Eaborn I. B. Gorrell P. B. Hichcock J. D. Smith and K. Tavakkoli Organometallics 1994 13 4143. 32 R. J. Wehmschulte J. J. Ellison K. Ruhlandt-Senge and P. P. Power Inorg. Chem. 1994 33 6300. 33 M. G. Gardener S. M. Lawrence and C. L. Raston Inorg. Chem. 1995 34 4652. 34 H.-E. Mons H. G�unther and A. Maercker Chem. Ber. 1993 126 2747. 35 M. L. Montero H. Wessel H. W. Roesky M. Teichert and I. Us�on Angew. Chem. 1997 109 644; Angew. Chem. Int. Ed. Engl. 1997 36 629. Received 3rd July 1997 Accepted 2nd Feb

ISSN:0306-0012    

DOI:10.1039/a827171z

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Recent development of zinc-fluorophores Eiichi Kimura† and Tohru Koike Department of Medicinal Chemistry School of Medicine Hiroshima University Minami-ku Hiroshima 734-8551 Japan Zinc-fluorophores have recently been attracting much interest in biological and environmental applications. How to detect selectively trace Zn2+ with efficient signal transduction is the central problem. Following carbonic anhydrasebased biosensors with fluorescent aromatic sulfonamides a chemosensor Zinquin is now extensively used to study the role of intracellular Zn2+ in cellular biology. New types of zinc-fluorophores zinc-finger peptides attached with fluorescent dyes and a dansylamide-pendant macrocyclic polyamine have been developed in 1996. The principles properties and limitations of these are discussed.1 Introduction to fluorescent indicators Quantitative analysis of trace metal ions with a selective analytical reagent has become extremely important for environmental and biological applications.1 Remarkable development of fluorescent indicators has been made for biologically important divalent metal ions in particular Ca2+ and Mg2+ with several selective fluorophores such as Fura-2 (1) Quin-2 (2) and Mag-indo-1 (3).2,3 d The criteria for these sensors are (i) stability (ii) metal selectivity (iii) metal affinity (iv) signal transduction (v) fluorescent signaling (vi) kinetically rapid sensitization (vii) ease of delivery to target systems and (viii) availability. For measurement of the dynamic mechanism of intracellular Ca2+ the typical concentration in resting cells is 50–200 nm and the intracellular physiological range is 10 nm–10 mm.Therefore as for metal affinity Ca2+-selective biosensors should possess a K (dissociation constant) near the median concentration (ca. 10–6 m). When a normal median concentration (given above) gives a 50% signal one could most effectively detect both concentration increases and concentration decreases. Fura-2 and Quin-2 in this regard are quite appropriate probes for the measurement † E-mail ekimura@ipc.hiroshima-u.ac.jp Eiichi Kimura obtained his BSc and MSc from the University of Tokyo and his PhD from the University of North Carolina under Professor James P. Collman in 1967. After postdoctoral years at Syntex and Chicago University he became an associate professor at Hiroshima University in 1970 where he is presently a professor.His research interests include the supramolecular chemistry of macrocyclic polyamines and their use in molecular recognition and as zinc-enzyme models. He was given the 2nd Izatt- Christensen award for macrocyclic chemistry in 1992. Tohru Koike Eiichi Kimura N ydrase Hydropho Environm O2S –NH Zn2+ N N NH HN N Em 468n Ex 320 n NH of intracellular Ca2+ concentrations.3 As for the desirable fluorescent signaling properties these are (a) intense fluorescence (b) excitation wavelengths exceeding 340 nm (to pass through glass microscope objectives and minimize UV-induced cell damage) with a wavelength corresponding to available laser sources and (c) emission wavelengths should shift by > 80 nm before and after complexation so that ratiometric titration can be utilized (for quantification) rather than mere intensity changes.Fura-2 for example fits these criteria. 2 History of classical zinc-fluorophores The zinc(ii) ion has been recognized as an important cation in biological systems (e.g. influencing DNA synthesis apoptosis gene expression and protein structure and function).4 The zinc(ii) ion is also implicated in the formation of amyloid plaques during the onset of Alzheimer’s disease. The relative concentration of free Zn2+ within biological cells varies from about 1 nm in the cytoplasm of many cells to about 1 mm in some vesicles.Clearly a mechanism must be available for moving Zn2+ ions into complexing sites and for pumping it to elevated concentrations that allow triggering mechanisms to operate as with Ca2+. The need for useful zinc-fluorophores to quantify trace Zn2+ ions is becoming more acute. The first zinc-fluorophore TSQ (4)5 was used as an histochemical stain for Zn2+ in various tissue sections of the brain heart and some other tissues. This stain was the only useful Zn2+-specific fluorophore that worked in the presence of physiological concentrations of Ca2+ and Mg2+. The complex of TSQ with free Zn2+ apparently has a stoichiometry of 2 1 TSQ/ Zn2+ but a 1 1 complex may equilibrate with protein-bound Zn2+. These TSQ-Zn2+ complexes were not fully identified nor fully characterized because of their complex structures and their stability constants were not determined.The fluorescence intensity (i.e. quantum yield) of the complex(es) varies with the media. Accordingly TSQ was far from an ideal fluorophore for the quantitative analysis of Zn2+. Tohru Koike was born in Hiroshima in 1959. After receiving his PhD in 1986 from Hiroshima University under the direction of Professor Eiichi Kimura he became an associate professor at Hiroshima University. His research interest is bioinorganic chemistry. He has been inventing new macrocyclic polyamines to disclose the intrinsic properties of Zn2+ in metalloproteins. 179 Chemical Society Reviews 1998 volume 27 COO– H3CO O COO– N N O COO– N COO– H3C O N O N COO– O COO– COO– N H3C COO– COO– 2 1 Quin-2 Fula-2 Kd(Ca2+) 60 nM Em 495 nm Ex 333 nm Kd(Ca2+) 145 nM Em 505 nm Ex 335 nm COO– COO– N COO– O 3 Mag-indo-1 NH Kd(Mg2+) 2.7 mM Em 417 nm Ex 330 nm COO– Whilst the TSQ-Zn2+ complexes were still chemically to be characterized a modified TSQ Zinquin 5 was developed and extensively used for cellular physiological studies by Zalewsky’s group.6,7 This was the first probe to visualize intracellular Zn2+ ions in living cells.An ester group is incorporated in 5 so that after the neutral lipophilic probe permeates into the cell the ester is hydrolyzed by intracellular esterases to become a carboxylate anionic form 6 and therefore be retained for a long time within the cell (see Scheme 1).Thus Zinquin became the first practical zinc-fluorophore to be used to determine the role of Zn2+ in the regulation of cell growth. Zinquin 5 can monitor loosely bound labile intracellular Zn2+ (not tightly bound Zn2+ in zinc-enzymes or zinc-finger proteins) by fluorescence video image analysis or fluorometric spectroscopy. The importance of cellular Zn2+ distribution in the process of apoptosis was first revealed by Zinquin for in zincrich cells such as hepatocytes and pancreatic islet b-cells the fluorescence is very intense. By fluorometric titration Zinquin was found to form both 1 1 and 2 1 complexes with Zn2+ with binding constants of 7.0 3 106 m21 and 11.7 3 106 m21 at pH 7.4.6 However the structure of these complexes was not determined but on the basis of our following findings 7 is a reasonable formula for the 1 1 complex where the sulfonamide is deprotonated.It is certain however that the stability constants are not big enough to permit interaction of Zinquin with the tightly bound (Kd << 1 nm) Zn2+ in metalloenzymes or zinc-finger proteins. The H3CO N HN TSQ Em 495nm Ex 334 nm CH3 SO2 4 Chemical Society Reviews 1998 volume 27 180 COO– COOEt O O Intracellular Esterases N NH N NH O2S O2S CH3 CH3 H3C H3C 5 Zinquin – H+ COO– N O2S 6 + Zn2+ O N– Zn2+ CH3 etc. H3C 7 1:1 Complex Em 490nm Ex 370 nm Scheme 1 intracellular Zn2+ chelator N,N,NA,NA-tetrakis(2-pyridylmethyl) ethylendiamine (TPEN) which has a much higher affinity towards Zn2+ can mask the Zn2+-dependent Zinquin’s fluorescence.6 Very weak fluorescence (at 490 nm) of a 2 mm solution of Zinquin at pH 7.4 was increased at subnanomolar concentrations of free Zn2+ and was fully saturated at 1 mm Zn2+.5 Fluorescence was enhanced 20-fold by 1 mm Zn2+.None of the other biologically relevant metal ions (Ca2+ Mg2+ Cu2+ Fe2+ Fe3+ Mn2+ Co2+ etc.) affected the Zn2+- dependent fluorescence of Zinquin. However when it comes to quantitative analysis of Zn2+ either in living cells or in other environments Zinquin is still far from satisfactory due to the mixed complexes it forms with varying fluorescence intensity.3 Development of new zinc-fluorophores In 1940 Mann and Keilin reported the discovery that sulfonamides inhibit zinc-containing carbonic anhydrase (CA).8 Chen and Kernohan showed that bovine erythrocyte carbonic anhydrase interacts with equimolar dansylamide 8 to form a highly fluorescent complex 9 with a dissociation constant Kd of 2.5 3 1027 m at pH 7.4.9 For reference the Kd value for Zn2+ binding to apoCA is 4 3 10212 m. The fluorescence of free dansylamide in water has an emission peak at 580 nm with a quantum yield of only 5.5% but the CA-bound dansylamide shifted the emission maximum to 468 nm with a much higher quantum yield of 84% (excited at 326 nm). The large emission blue shift is rationalized by a well shielded and extremely hydrophobic binding site and in addition by the sulfonamide group losing a proton (to form SO2NH2) upon binding to CA (see Scheme 2).Thus dansylamide may serve as a good candidate for a fluorescent probe for CA or Zn2+ in the presence of apoCA. The pKa value of the free SO2NH2 group is 9.8 either in the ground state or in the excited state. Mere deprotonation of the free SO2NH2 group (in the absence of CA) shifted the emission peak from 580 to 540 nm and the quantum yield from 5.5% to 8.5%. These chemical principles were adopted to a CA-based fiber optic zinc-biosensor developed by Thompson and Jones in 1993.10 The concentration of Zn2+ ion is proportional to the ratio of fluorescence intensities (at 460/560 nm) at 10–1000 nm (with 1 mm apoCA and 10 mm dansylamide in pH 7.4 HEPES buffer).A special advantage with the CA-dansylamide system N Carbonic Anhydrase O2S –NH pH 7.4 O2S NH2 Zn2+ N 8 HN N Dansylamide Em 580nm Ex 320 nm Scheme 2 is that a large wavelength shift in fluorescence with or without Zn2+ in CA permits the ratio of emission at two different wavelengths to be correlated with the analytical level. This linear range interestingly corresponds to the zinc(ii) concentration range in the ocean. A fiber optic sensor constructed using this approach however showed the zinc-detection limit to be reduced by tenfold. For practical application to the measurment of environmental Zn2+ (e.g. in sea water) a problem is the reversibility.The dissociation rate of Zn2+ from CA is ca. 1028 s21 which is too slow to take continuous data. Another serious problem was fiber attenuation. Back in 1988 chelation-enhanced fluorescence (CHEF) was reported by Czarnik et al. with 9,10-bis(2,5-dimethyl-2,5-diazahexyl) anthracene 10 for Zn2+ in CH3CN.11 In 1990 10 was N N N N 10 N Zn2+ NH HN NH 12 extended to macrocyclic system 11.12,13 A large CHEF effect by Zn2+ (14.4-fold) and Cd2+ (nine-fold) was observed with 11 (n = 2) at pH 10 in aqueous solution where the metal-free ligand is almost entirely a monoprotonated species. In fluorescence titration of 11 (n = 2) (10 mm) with Zn2+ (0–20 mm) in pH 12 buffer (highly alkaline) where 11 (n = 2) is unprotonated the emission maximum at 416 nm (excited at 335 nm) increases linearly until almost 1 1 complexation (to 12).The reason why such a high pH was employed was to avoid the intrinsic competition between H+ and Zn2+ for 11 at lower pHs. The protonation(s) and metal complexation at the macrocyclic polyamine moiety commonly inhibit the quenching process by free nitrogen atoms e.g. the protonated ligand 11 (n = 2)·2H+ at pH 7 showed almost 120-fold larger fluorescence intensity N Hydrophobic Environment N NH Em 468nm Ex 320 nm NH 9 N NH n 11 n = 1–5 than that of the free ligand 11 (n = 2) at pH 12. Thus 11 (n = 2) can not be a practical zinc-fluorophore under normal pH conditions. A conceptually new zinc-fluorophore 13 was designed in 1996 by Imperiali et al.14 A peptide 13 containing a zinc-finger motif (a strong Zn2+-binding site Cys2/His2)15 attached to a N O2S NH YQ CQY CEKR ADSSNLKT HIKTK HS CH3CONH NH2 NH O 2/ HO O O N N+ O COO– SO3 – N Lissamine (L) O O SO2 HN 13 dansylamide residue was synthesized (i) for selective and efficient Zn2+-binding (Kd = 1.4 3 10210 m at pH 7)16 and (ii) to create a hydrophobic environment around the encapsulated dansylamide residue upon its Zn2+ complexation.The addition of Zn2+ (0.1–1 mm) to the peptide 13 (1.4 mm) in pH 7 HEPES buffer resulted in a linearly increased emission peak at 475 nm (excited at 333 nm). In the absence of Zn2+ the emission maximum was 560 nm. The presence of 0.5 M Na+ 50 mm Mg2+ and 100 mm Co2+ did not interfere in the Zn2+ analysis.The design presented here consists of a synthetic polypeptide (25 amino acids) template and covalently attached fluorescent reporter dansylamide that is sensitive to any metal-induced conformational changes of the supporting framework yet remote from the Zn2+-binding site. The enhanced emission is mostly due to the reporter being placed in a hydrophobic environment. Problems with the zinc-finger motif in addition to its synthetic availability were its susceptibility to air oxidation of the cysteine residues and to redox active metal ions such as Cu2+. This was despite its high affinity for Zn2+ ions. In application to the reductive environment of some cells this may not be problematic however in aerobic oxidative environmental analysis this zinc-fluorophore may not be suitable.An oxidatively robust peptidyl zinc-fluorophore was later synthesized by making the peptide substitution from Cys2/His2 to Cys/His3 at the Zn2+-binding site.16 However the zinc affinity dropped (Kd = 3 3 1029 m at pH 7) and the fluorescence response to Zn2+ became too small to be useful as a sensitive zinc-fluorophore. Another modification from Cys His2 to Cys/Asp/His2 yielded a zinc sensor with enhanced oxidative stability but with further weakened affinity (Kd = 6.5 3 1028 m at pH 7) although this one is responsive to a submicromolar to micromolar concentration of Zn2+ in the presence of redox active Cu2+ and Fe2+. Another type of zinc-fluorophore 14 having a zinc-finger motif (Cys2/His2) was designed in 1996 by Berg et al.17 The peptide was attached with two fluorescent dyes fluorescein (F) 14 Fluorescein (F) ATK CPE CGKSFSQ C SDLVK HQRT HTG COO– as the energy donor and lissamine (L) as the acceptor to visualize zinc binding.In the absence of Zn2+ ion the peptide is unfolded as shown for Imperiali’s peptides and the dyes are Chemical Society Reviews 1998 volume 27 181 relatively far apart (i.e. small intramolecular energy transfer occurs between F and L). Upon Zn2+-binding to the Cys2/His2 site the peptide folds to bring the two fluorophores closer together increasing the amount of intramolecular energy transfer. The Zn2+-binding to 14 (3.7 mm) at pH 7.1 was monitored by increasing fluorescence (ca.2.3-fold) at 596 nm (excitation at 430 nm) with an increase in [Zn2+] which provides the 1 1 and 2 1 peptide to Zn2+ complex formation. The complexation had to be carried out under a reductive atmosphere of 95% N2/5% H2 to avoid peptide oxidation however. 4 A novel biomimetic zinc-fluorophore While engaged in elucidation of the roles of Zn2+ ions in zinc enzymes [in particular carbonic anhydrase (CA)] by means of macrocyclic polyamine complexes {e.g. 15 with 1,5,9-triazacyclododecane ([12]aneN3) and 16 with 1,4,7,10-tetraazacyclododecane (cyclen)},18–23 we have discovered intrinsic acid properties of the Zn2+ ion. One of the most outstanding properties is a strong affinity for aromatic sulfonamides,21 as illustrated by the formation of the strong bonds between Zn2+ and deprotonated sulfonamide N2 anions at physiological pH.Thus for the first time a chemical model 15c was presented to account for aromatic sulfonamide anions being good ligands for Zn2+ ion at the active center of CA making them strong inhibitors (see Scheme 2). The zinc enzyme models 15 and 16 also form stable 1 1 complexes with deprotonated weak acids such as thymine derivatives (16c) and barbital (16d) in neutral aqueous solution,24 which result from the Zn2+-bound OH2 species generated with pKa values of 7.3 (for 15a to 15b + H+) and 7.9 (for 16a to 16b + H+)18 acting as bases to dissociate the X X Zn2+ HN Zn2+ NH NH HN NH HN NH O N– c; X = 16a; X = OH2 b; X = OH– O O 15a; X = OH2 b; X = OH– c; X = NR S O N H – R N– O d; X = O NH O acidic protons.The resulting conjugate bases strongly bind to Zn2+ which compensate for the unfavorable deprotonations at neutral pH. We further demonstrated that tosylamidopropyl[ 12]aneN3 17 yields a very stable four-coordinate tetrahedral zinc(ii) complex 18 under physiological pH (see Scheme 3) where the aromatic sulfonamide N2 anion strongly CH3 CH3 O O S O O S –N HN + Zn2+ Zn2+ –3H+ N H N N HN pH ~7 2H+ NH NH 18 17 Tosylamidopropyl[12]aneN3 Scheme 3 binds to a Zn2+ ion from the fourth coordination site. On the basis of these basic studies on a CA-model a dansylamide- Chemical Society Reviews 1998 volume 27 182 pendant macrocyclic tetraamine (dansylamidoethylcyclen) 1925 was designed for a new type of selective and efficient zincfluorophore 20.The reason why we initially adopted the macrocyclic tetraamine (L) is because it forms a much more stable Zn2+ complex (K = [ZnL]/[Zn2+][L] = 1015.3 m21)26 than [12]aneN3 (K = 108.4 m21)18 in H2O at 25 °C. 4.1 Synthesis of dansylamidoethylcyclen Dansylamidoethylcyclen 19 was initially synthesized according to Scheme 4,25 but recently a more convenient synthetic route has been developed as shown in Scheme 5 which is used commercially.27An X-ray crystal structure of the Zn2+ complex 20 confirmed the 5-coordinate disordered square-pyramid structure with a short Zn2+-sulfonamide N2 bonding (1.97 Å).25 O S O NH N NH HN NH HN O NH N HN 4.2 Zinc(ii) affinity of dansylamidoethylcyclen The zinc(ii) complexation equilibria were determined by potentiometric pH titration of dansylamidoethylcyclen 19 in the presence of an equimolar amount of Zn2+ at 25 °C with I = 0.10 (NaNO3).The complexation constant for 19 (HL) (K = [20]/[L2][Zn2+]) was establised to be 1020.8 m21. The dissociation constants Kd at pH 7.8 were calculated from the complexation constants as summarized with reference values in Table 1. It is of interest to note that the Kd values are adjustable within physiological pH (e.g. 1.4 3 10210 m at pH 7.0 to 5.5 3 10213 m at pH 7.8) for the new biomimetic zinc-fluorophore 19. As the pH is raised the K 20 d value for 19 becomes smaller than the HN N BH3•THF HN N NH HN 19 Dansylamidoethylcyclen HN H2N Zn2+ i) dansyl chloride K2CO3 ii) NaClO4 in H2O pH 7 20•ClO4 – N N O S O -N HN Zn2+ N NH HN O O O BrCH2CN NH HN NH in MeOH CN in THF i) Amberlite IRA-400 NH HN ii) Zn(ClO4)2 in EtOH 5HCl 2ClO4 – NH2 i) 5 equiv.EDTA 19•5HCl ii) 6 M HCl Scheme 4 N HN Boc Boc N N + N O2S Cl Boc N O2S NH NH HCl aq in MeOH N Boc N N Boc Cyclen Boc = tert-butoxycarbonyl KI/K2CO3 in CH3CN [12]aneN3 1.031024 19•5HCl Zinquin (1 1 complex)a 1.431027 N 4.4310211 a Boc Scheme 5 Table 1 Comparison of dissociation constants Kd (M) ( = [Zn2+][zinc(ii) complex]/[free ligand]) at 25 °C and pH 7.8 19 5.5310213 Calculated using the 1 1 complexation constant (at pH 7.4) given in ref.6. Kd values for the zinc-finger consensus peptides (e.g. 5.7 3 10212 m at pH 7.0).15 The distribution of various species in solution is shown as a function of pH at [total Zn2+] = [total ligand] = 1 mm in Fig. 1 for 19. Most remarkably 19 (almost in HL·2H+ form 1 mm) sequesters nearly 100% of trace Zn2+ (1 mm) in the form of stoichiometric ZnL 20 at physiological pH of 7.8. Such a strong affinity to Zn2+ is one of the most characteristic properties of the new macrocyclic ligand [in comparison to Zinquin 5 and anthracene-pendant cyclen 11 (n = 2)] and will be very useful for quantifying trace amounts of Zn2+ in environmental and biological systems.4.3 Fluorescent signalling behaviour of dansylamidoethylcyclen In principle a direct signal transduction linked with Zn2+ sensing is straightforward and should be more desirable than indirect ones (such as the metal-induced conformational changes).15,16 Thus the use of dansylamide for both Zn2+ recognition and fluorescence signaling would make a simpler and side-effects-free probe. Despite similar UV excitation spectra the fluorescence emission spectra vary dramatically for protonated ligand 19·2H+ (HL·2H+) at pH 7.8 deprotonated ligand (L2) at pH 12.8 Zn2+ complex 20 (ZnL) at pH 7.8 and Cu2+ complex with 19 (CuL) at pH 7.8 (see Fig. 2).25 While the non-metallated dansylamide deprotonation of HL·2H+ to L2 without Zn2+ at high pH brought about only ca.20% increase in the emission intensity the dansylamide deprotonation with Zn2+ at pH 7.8 increased the emission intensity by 4.9-fold at 540 nm and ten-fold at 490 nm. In contrast the dansylamide Fig. 1. Distribution diagram for the zinc(ii) species in 1 mm 19/1 mm Zn2+ system as a function of pH at 25 °C where ZnHL is a monoprotonated species of 20. Fig. 2 UV absorption spectra at 25 °C and pH 7.3 (10 mm HEPES) with I = 0.1 (NaNO3) (a) 0.1 mm 19·2H+ (HL·2H+) lmax = 330 nm; (b) 0.1 mm 20 (ZnL) lmax = 323 nm; (c) 0.1 mm copper(ii) complex of 19 (CuL) lmax = 305 nm. Fluorescence spectra by 330 nm excitation at 25 °C with I = 0.1 (NaNO3); (d) 10 mm HL·2H+ at pH 7.8 (10 mm EPPS buffer) lmax = 582 nm; (e) 10 mm L2 at pH 12.8 lmax = 578 nm; (f) 10 mm ZnL at pH 7.8 (10 mm EPPS buffer) lmax = 540 nm.10 mm CuL has no fluorescence under the same conditions. deprotonation with Cu2+ completely quenched the fluorescence. The fluorescence maximum of HL·2H+ (582 nm) at neutral pH blue-shifted upon zinc(ii) complexation (ZnL) to 540 nm. A greater fluorescence blue shift (580 nm to 468 nm) and intensity enhancement (15.3-fold in quantum yield excited at 320 nm) were reported for the dansylamide complexation with carbonic anhydrase (CA),9 which were accounted for by the hydrophobic environment and the deprotonation of dansylamide on Zn2+ at the active center of CA. In support of this explanation the fluorescence maximum (540 nm) of 20 in H2O moved toward shorter wavelength in organic solvents with higher quantum yields 502 nm in MeOH and 490 nm in CH3CN.25,27 4.4 Evaluation of the zinc sensitivity of dansylamidoethylcyclen The fluorescence changes of 19 (5 mm) with various metal ions (5 mm) at pH 7.3 (HEPES buffer) and 25 °C are summarized in Fig.3.25,28 The addition of various concentrations of Zn2+ ion (0–10 mm) resulted in increased emission upon excitation at 330 nm as shown in Fig. 4. The response (at 528 nm) was linear between 0.1 and 5 mm until it reached a 1 1 [19]/[Zn2+] ratio and then became a plateau. These responses indicate that the increase in fluorescence is stoichiometric due totally to the 1 1 ZnL formation and moreover ZnL is so stable that even at 183 Chemical Society Reviews 1998 volume 27 Fig.3 Comparison of the relative fluorescence intensity of 5 mm 19 in the presence of various additives at 25 °C and pH 7.3 (1 mm HEPES) with I = 0.1 (NaNO3). The data marked with * were collected without the supporting electrolyte. nanomolar concentrations it does not dissociate which is in good agreement with the results obtained by the potentiometric pH titration (see the pH distribution curve in Fig. 1). The Zn2+- dependent fluorescence was unaffected by the presence of an excess amount of Zn2+. On the other hand Cu2+ ion linearly diminished the fluorescence emission until complete quenching at [19]/[Cu2+] = 1 (see Fig. 4). Other fluorescence-quenching metal ions (paramagnetic Co2+ easily reducible Hg2+ Pb2+) that tend to bind fairly stongly with cyclen also caused minor intramolecular quenching although the effects were not so drastic as Cu2+.Cu2+ ion forms the most stable five-coordinate complex CuL (K = [CuL]/[Cu2+][L–] > 1030 m21 at 25 °C),25 which account for the most dramatic effect by Cu2+. When the binding to cyclen is not strong (in aqueous solution) as demonstrated by Fe2+ Fe3+ Mn2+ or Mg2+ there was no effect on the fluorescence. The fluorescence intensity of 5 mm ZnL 20 was practically unaffected by the presence of physiological concentrations ( > 103-fold) of Na+ K+ Ca2+ or Mg2+ at pH 7.3. Fig. 4 Fluorescence emission response (at 528 nm) of 5 mm 19 to increasing levels of Zn2+ or Cu2+ at 25 °C and pH 7.3 (1 mm HEPES) with I = 0.1 (NaNO3).The interference of Cu2+ in the fluorescence response of 20 by Cu2+ could be prevented by using bovine serum albumin (BSA) which specifically masked Cu2+.28 The mixture of [Zn2+] = [Cu2+] = [19] = 5 mm at pH 7.3 showed no fluorescence. However with an increasing amount of BSA the fluorescence increased due to 20 and at [BSA] = 50 mm the original intensity (without Cu2+) was regained (see Fig. 4). Chemical Society Reviews 1998 volume 27 184 5 Future perspectives on zinc-fluorophores Currently the macrocyclic polyamine attached with a dansylamide-pendant 19 seems to offer the most useful prototype for practical zinc-fluorophores with the various criteria described in the introduction (i) the ligands are easy to make and very robust; (ii) the affinity for Zn2+ is extremely high catching trace Zn2+ in nanomolar concentrations at physiological pH; (iii) the Zn2+ selectivity in fluorescence sensing is very high and the zinc-fluorescence perturbing metal ions are limited (e.g.Hg2+ Pb2+); (iv) the most interfering metal Cu2+ can be masked by use of BSA. Further studies to be made for biological applications are (i) kinetic aspects (e.g. how fast is the Zn2+ sensitization) (ii) delivery into cells and how long it remains responsive to intracellular Zn2+ and (iii) improvement in the fluorescence efficiency. It is anticipated that these problems may be solved by appropriate modification of the relatively simple macrocyclic structure. 6 References 1 A. W. Czarnik Chem.Biol. 1995 2 423. 2 G. Grynkiewicz M. Poenie and R. Y. Ysien J. Biol. Chem. 1985 260 3440. 3 R. P. Haugland Handbook of Fluorescent Probes and Research Chemicals ed. by M. T. Z. Spence Molecular Probes Eugene 6th edn. 4 J. J. Fra�usto da Silva and R. J. P. Williams The Biological Chemistry of 5 C. J. Frederickson E. J. Kasarskis D. Ringo and R. E. Frederickson J. 6 P. D. Zalewski I. J. Forbes and W. H. Betts Biochem. J. 1993 296 7 P. D. Zalewski I. J. Forbes R. F. Seamark R. Borlinghaus W. H. Betts 1996 p. 503. the Elements Clarendon Press Oxford 1991 p. 302. Neurosci. Methods 1987 20 91. 403. S. F. Lincoln and A. D. Ward Chem. Biol. 1994 3 153. 8 T. Mann and D. Keilin Nature 1940 146 164. 9 R. F. Chen and J. C. Kernohan J. Biol. Chem. 1967 247 5813.10 R. B. Thompson and E. R. Jones Anal. Chem. 1993 65 730. 11 M. H. Huston K. W. Haider and A. W. Czarnik J. Am. Chem. Soc. 1988 110 4460. 12 E. U. Akkaya M. H. Huston and A. W. Czarnik J. Am. Chem. Soc. 1990 112 3590. 13 A. W. Czarnik Acc. Chem. Res. 1994 27 302. 14 G. K. Walkup and B. Imperiali J. Am. Chem. Soc. 1996 118 3053. 15 B. A. Krizek D. L. Merkle and J. M. Berg Inorg. Chem. 1993 32 937. 16 G. K. Walkup and B. Imperiali J. Am. Chem. Soc. 1997 119 3443. 17 H. A. Godwin and J. M. Berg J. Am. Chem. Soc. 1996 118 6514. 18 E. Kimura T. Shiota T. Koike M. Shiro and M. Kodama J. Am. Chem. Soc. 1990 112 5805. 19 T. Koike and E. Kimura J. Am. Chem. Soc. 1991 113 8935. 20 E. Kimura T. Koike M. Shionoya and M. Shiro Chem. Lett. 1992 787. 21 T. Koike E. Kimura I. Nakamura Y. Hashimoto and M. Shiro J. Am. Chem. Soc. 1992 114 7338. 22 X. Zhang R. van Eldik T. Koike and E. Kimura Inorg. Chem. 1993 32 5749. 23 T. Koike M. Takamura and E. Kimura J. Am. Chem. Soc. 1994 116 8443. 24 T. Koike M. Takashige E. Kimura H. Fujioka and M. Shiro Chem. Eur. J. 1996 2 617. 25 T. Koike T. Watanabe S. Aoki E. Kimura and M. Shiro J. Am. Chem. Soc. 1996 118 12696. The fluorescence is so sensitive that extreme care to exclude contamination should be exercised in preparing the analytical solution (e.g. our experience showed that for the supporting electrolyte optical grade purity was needed for micromolar fluorometric analysis). 26 T. Koike S. Kajitani I. Nakamura E. Kimura and M. Shiro J. Am. Chem. Soc. 1995 117 1210. 27 K. Takesako Dojin News 1998 86 18. Dansylamidoethylcyclen 19·5HCl is commercially available from Funakoshi Ltd. (http:/ /www.funakoshi.co.jp/) and Dojindo (http://www.dojindo.co.jp/) in Japan. 28 E. Kimura S. Afr. J. Chem. 1997 50 in press. Received 2nd July 1997 Accepted 29th January 19

ISSN:0306-0012    

DOI:10.1039/a827179z

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Isolation and characterisation of stereoisomers in di- and tri-nuclear complexes F. Richard Keene School of Biomedical and Molecular Sciences James Cook University of North Queensland Townsville Queensland 4811 Australia A number of synthetic methodologies have recently been developed for polymetallic supramolecular assemblies commonly without consideration of the stereochemistry of the component octahedral metal centres. This review discusses stereochemical aspects of ligand-bridged di- and tri-nuclear complexes with an emphasis on those involving ruthenium( II) octahedral metal centres coordinated to bidentate N-heterocyclic ligands. It examines recent studies devoted to the isolation of individual stereoisomers of such complexes using both stereoselective synthetic procedures through precursors with pre-determined chiralities and/or chromatographic techniques.The characterisation of the stereoisomers is also addressed. 1 Introduction In recent years a number of synthetic methodologies have been developed1 for polymetallic supramolecular assemblies which may have considerable potential as the basis of materials designed for use in photochemical molecular devices.2 Because of their favourable photophysical and redox characteristics,3 d6 transition metal centres (e.g. RuII OsII ReI) coordinated to polypyridyl ligands have been of particular interest as the building blocks for such assemblies. However in contrast to the development of molecular assemblies in organic chemistry where there was a prior understanding of the nature of the tetrahedral carbon atom the present advances in inorganic supramolecules have taken place without suitable methodologies to control the stereochemistry at the component octahedral metal centres.This is particularly true where bidentate ligands are involved. However such ligands are important as they extend the three-dimensionality of resultant polynuclear species whereas the involvement of tridentate ligands tends to impose chain-like characteristics on the structures. The stereochemical factor should be of considerable importance as the spatial relationship of the components influences the nature of intramolecular electron and energy transfer processes within the assemblies.4–7 Additionally the Richard Keene graduated from the University of Adelaide and subsequently undertook postdoctoral work at the Australian National University and the University of North Carolina at Chapel Hill.On his return to Australia he was appointed to James Cook University of North Queensland in Townsville in 1978. He has published in a number of areas of coordination chemistry but his present research interests relate primarily to the stereochemistry of polymetallic supramolecular assemblies and its effects on their physical properties. NMR spectra of the oligomeric assemblies are complicated and are different for each stereoisomer (other than enantiomers) consequently since isolated complexes have generally been isomeric mixtures characterisation by this technique has been extremely difficult because the spectra were not interpretable.Crystals appropriate for structural studies of such assemblies are notoriously difficult to obtain. 2 Isomers of dinuclear complexes 2.1 Diastereoisomers Ligand-bridged dinuclear species represent the simplest examples of the assemblies. Where the individual centres are tris(bidentate) in nature each may inherently possess right- or left-handed chirality (designated D or L respectively). In principle a dinuclear species may therefore exist in two diastereoisomeric forms—DD/LL or DL/LD—and where the bridge is relatively rigid stereoisomerism has a profound effect on shape and on the electronic interactions within the molecule. In cases where the bridge is not rigid and there is free rotation within the link between the two metal centres the differences may not be so significant and such species are not considered in any detail in this review.Terminal Ligands N N bpy (2,2'-bipyridine) CH3 H3C CH3 H3C N N Me4bpy (4,4',5,5'-tetramethyl-2,2'-bipyridine) The most fundamental example of the genre is [{M(pp)2}2(m- BL)]n+ [where pp is a symmetrical bidentate ligand (C2v point group symmetry) such as 2,2A-bipyridine (bpy) and BL is a symmetrical (C2v) bridging ligand such as 2,2A-bipyrimidine bpm]. In this case there are three possible stereoisomers—two diastereoisomers [meso (point group symmetry C2h) and rac (point group symmetry D2)] with the latter comprising two enantiomeric forms (Fig.1). The terminal bidentate polypyridyl ligands ‘above’ and ‘below’ the plane of the bridging ligand bear a significantly different relationship in the rac and meso diastereoisomers. For the complexes where the axes of the ‘bites’ of the two bidentate ligating moieties of the bridge (BL) are linear (e.g. bpm) or have a stepped-parallel relationship (e.g. 2,5-dpp or apy) the terminal polypyridyl ligands ‘above’ and ‘below’ the plane of the bridging ligand are approximately parallel in the rac (DD/ LL) form [Fig. 2(B)] whereas they are orthogonal in the meso (DL/LD) stereoisomer [Fig. 2(A)].8–10 Fig. 2 shows the view Chemical Society Reviews 1998 volume 27 CH3 H3C N N Me2bpy (4,4'-dimethyl-2,2'-bipyridine) N N phen (1,10-phenanthroline) 185 Bridging Ligands R N N N N N N N N R R = H apy [azobis(2-pyridine)] R = CH3 mapy [azobis(4-methyl-2-pyridine)] N N N N bpm (2,2'-bipyrimidine) N N N N N N N N 2,5-dpp [2,5-bis(2-pyridyl)pyrazine] N N 2,3-dpp [2,3-bis(2-pyridyl)pyrazine] N N N Fig.2 CHEM3D representations of the meso (LD; A) and rac (DD; B) diastereoisomers of [{Ru(bpy)2}2(m-bpm)]4+ (hydrogen atoms are omitted for clarity) N HAT (1,4,5,8,9,12-hexaazatriphenylene) N N N 4,6-dppm [4,6-bis(2-pyridyl)pyrimidine] N N N N N– N There are limited examples of complexes in the above categories where individual stereoisomers have actually been separated. Hua and von Zelewsky9,11 utilised the complexes [Ru(phen)2(py)2]2+ and [Ru(bpy)2(py)2]2+ [conveniently resolved by conventional diastereoisomer formation using the chiral arsenyl-(+)-tartrate and O,OA-dibenzoyltartrate anions respectively] which they established to undergo stereoretentive substitution of the two monodentate pyridine ligands.These chiral precursors were used to synthesise the dinuclear species bpt– [3,5-bis(2-pyridyl)-1,2,4-triazolate anion] 2. M M M M M Fig. 3 CHEM3D representations of diastereoisomers of [{Ru(bpy)2}2(m- HAT)]4+ (A) rac (DD; point group symmetry C2) and (B) meso (LD; point {LL} rac {LD} group symmetry Cs) dpq [2,3-bis(2-pyridyl)quinoxaline] from above the bridging ligand (bpm) in the complex [{Ru- (bpy)2}2(m-bpm)]4+. On the other hand if the relationship of the axes of the two ‘bites’ are angular (e.g.the ‘unsymmetrical’ bridging ligands 2,3-dpp 4,6-dppm HAT) the above description is reversed with the terminal rings above the plane of the bridge being more appropriately described as approximately parallel and orthogonal for the meso [Fig. 3(B)] and rac [Fig. 3(A)] diastereoisomers (respectively) in the complex [{Ru(bpy)2}2(m-HAT)]4+. When each metal centre of the dinuclear species has two equivalent ligands but the two metal centres are no longer identical as in the homometallic case [{M(pp)2}{M(ppA)2}(m- BL)]n+ (pp ­ ppA) or the heterometallic cases [{M(pp)2}{MA(pp)2}(m-BL)]n+ and [{M(pp)2}{MA(ppA)2}(m- BL)]n+ then the DL and LD forms will constitute an enantiomeric pair.In all three systems the point group symmetries of both diastereoisomers will be C M 186 meso {LD} Fig. 1 Stereoisomeric forms of [{M(pp)2}2(m-BL)]n+ Chemical Society Reviews 1998 volume 27 [{Ru(pp)2}2(m-BL)]4+ [pp = bpy or phen; BL = bridging ligands 2,2-bipyrimidine (bpm) 2,5-bis(2-pyridyl)pyrazine (2,5-dpp) or 4,6-bis(2-pyridyl)pyrimidine (4,6-dppm)] with predetermined stereochemistry (i.e. DL DD or LL). The methodology has also been used for analogous dinuclear complexes involving the bridging ligands 2,3-bis(2-pyridyl)- pyrazine (2,3-dpp) and its fused analogue pyrazino[2,3-f]- [4,7]phenanthroline (ppz).12 In studies in our own laboratory we established the use of chiral [Ru(pp)2(CO)2]2+ as a precursor for the syntheses of individual stereoisomers of the dinuclear complex [{Ru- (phen)2}{Ru(Me4bpy)2}(m-bpm)]4+.13 We have also extended the technique of Hua and von Zelewsky9,11 by the utilisation of resolved hetereoleptic bis(pyridine) species {[Ru(pp)(ppA)- (py)2]2+ to obtain individual stereoisomers of [{Ru(phen)- (Me4bpy)}2(m-bpm)]4+.14 Importantly we have also used cation exchange chromatographic methods to separate the diastereoisomers of the dinuclear species [{Ru(bpy)2}{Ru(phen)2}(m-bpm)]4+ [{Ru- (bpy)2}{Ru(phen)2}{m-(2,3-dpp)}]4+ [{Ru(phen)2}{Ru(Me4- bpy)2}(m-bpm)]4+ [{Ru(bpy)2}{Ru(Me4bpy)2}(m-bpm)]4+ [{Ru(phen)2}{Os(bpy)2}(m-bpm)]4+ and [{Ru(Me4bpy)2}- {Os(bpy)2}(m-bpm)]4+,8 [{Ru(bpy)2)}2(m-apy)]4+ [{Ru(Me2- bpy)2}2(m-apy)]4+ [{Ru(bpy)2}2(m-mapy)]4+ [{Ru(Me2- bpy)2}2(m-mapy)]4+ and [{Ru(bpy)2}{Ru(Me2bpy)2}- (m-mapy)]4+.4 The combination of these stereoselective synthetic techniques and chromatographic procedures provides a significant advance in the access to stereoisomeric forms of dinuclear complexes and oligomers of higher nuclearity.We have used such methodologies to isolate all stereoisomers of the dinuclear species [{Ru(bpy)2}2(m-HAT)]4+ (Fig. 3) and [{Ru(phen)2}2(m- HAT)]4+,6 and [{Ru(bpy)2}{Ru(phen)2}(m-HAT)]4+:15 examples of studies of trinuclear species are given below. There have been a number of other approaches to the isolation of individual stereoisomeric forms of ligand-bridged dinuclear species. von Zelewsky and co-workers have reported the use of ligands (‘chiragens’) which impose a particular stereochemistry on the monomer precursors (‘stereospecificity’).16,17 N N (CH2) n Chiragen[ n] { n = 0,3–7} N N Chiragen[m–xyl] A number of studies have reported utilising condensation reactions of chiral monomers containing the 1,10-phenanthroline-5,6-dione ligand e.g. [Ru(phen)2(1,10-phenanthroline- 5,6-dione)]2+,18 as the precursor to form bridged complexes of predetermined stereochemistry.19–22 Tor and co-workers23 have reported the use of the Hua and von Zelewsky precursor D/L-[Ru(phen)2(py)2]2+ to produce N N N N N N Super Chiragen[0] N N 2}(m-bpy)]3+ have been synthesised. chiral complexes of functionalised phen ligands,9,11 which may be subsequently linked to form individually the DD LL and DL stereoisomers of an alkyne-bridged dinuclear species.These researchers also reported the use of analogous methods to obtain the LLL and DLD diastereoisomers of trinuclear species.23 There are no reports of the isolation of the individual diastereoisomers of dinuclear species involving ‘unsymmetrical’ bridging ligands although there are examples—such as the case involving 3,5-bis(2-pyridyl)-1,2,4-triazolate anion (bpt2)—where the coordination isomers of the complex24 [{Ru(bpy)2}{Ru(phen)2}(m-bpt)]3+ and25 [{Ru(bpy)2}- {Os(bpy) In almost all the dinuclear systems listed above where separation of diastereoisomeric forms was achieved (or the two forms quantified in a mixture) the ratios of their proportions were close to 1 1.One notable exception is the species [{Ru(bpy)2}2(m-mapy)]4+ where the meso rac ratio was 3.8 1.4 In the mapy bridging ligand the two bidentate ‘bites’ have a stepped-parallel relationship and the offset position of the metal centres places the ‘above plane’ ligands almost coplanar in the DD/LL (rac) isomer (Fig. 4). The preference for the meso diastereoisomer may arise from steric factors as examination of models reveals possible inter-ligand interactions within the rac form. Fig. 4 CHEM3D representations of the (A) meso (DL) and (B) rac (DD) diastereoisomeric forms of [{Ru(Me2bpy)2}2(m-mapy)]4+ (ref. 4) 2.2 Enantiomers The chromatographic technique may also be used to chirally resolve the enantiomers that comprise the rac diastereoisomer in these species as reported for the complexes [{Ru(bpy)2}2(m- 187 Chemical Society Reviews 1998 volume 27 2}3(m-HAT)]6+,6 [{Rubpm)] 4+,10 [{Ru(pp)2}2(m-HAT)]4+ (pp = bpy phen)6 and [{Ru(bpy)2}{Ru(phen)2}(m-HAT)]4+.15 The chromatographic resolution of the DDD and LLL forms has also been achieved for the trinuclear species [{Ru(pp) (bpy)2}2{Os(bpy)2}(m-HAT)]6+ and [{Ru(phen)2}{Ru- (bpy)2}{Ru(Me2bpy)2}(m-HAT)]6+.15 2.3 Geometrical isomers The presence of more varied combinations of terminal ligands —and the use of unsymmetrical terminal and bridging ligands—leads to situations of increasing complexity.If the metal centres are identical but contain two different terminal ligands {e.g. [{Ru(pp)(ppA)}2(m-BL)]n+} then there will still be two diastereoisomeric forms with each now having two geometrical isomers (cis and trans) as shown in Fig.5. Ru Ru Ru Ru cis {Cs} trans {Ci} meso{LD (º DL)} Ru Ru Ru Ru trans {C2} cis {C2} rac {LL (º DD)} Fig. 5 Schematic representation of the geometrical isomers of the 2(m-BL)]n+ (C2 axes are diastereoisomeric forms of [{Ru(pp)(ppA)} shown)14 For the dinuclear complex [{Ru(phen)(Me4bpy)}2(m- HAT)]4+ the diastereoisomeric forms [meso (DL) and rac (DD/LL)] were either separated by cation exchange chromatography or the individual forms (DL DD and LL) synthesised stereoselectively by reaction of appropriate chirally resolved forms of [{Ru(phen)(Me4bpy)}2(py)2]2+ and [{Ru- (phen)(Me4bpy)}(bpm)]2+.14 Each diastereoisomer was chromatographically separated into its two geometrical forms which were readily assigned by NMR techniques on the basis of symmetry.The final scenario in this series of dinuclear complexes involving symmetrical bridging ligands is the situation in which there are unsymmetrical terminal ligands coordinated to the metal centres involved. For example with a bidentate ligand A–B then each Ru(A–B)2(BL) moiety may exist in three geometric forms (each of which may be chiral)—accordingly there will be six geometrical forms of each of the two diastereoisomers. Isolation of all forms would indeed be a challenge! 2.4 Conformational isomers It is also noted that in cases where there is some limited movement within the ligand bridge conformational isomerism may also be observed.In dinuclear complexes involving 2,3-bis(2-pyridyl)pyrazine as the bridge the steric interaction of the two protons attached at the 3-positions of the respective pyridine rings imposes non-planarity on the two a,aA-diimine coordinating moieties. This effect has been described in a monomeric complex of a closely related analogue 2,3-bis(2- pyridyl)quinoxaline (dpq).26 In our 1H NMR characterisation of the two diastereoisomers of the dinuclear complex [{Ru(bpy)2}{Ru(phen)2}{m- (2,3-dpp)}]4+,8,27 a broadening of some of the resonances was observed in the aromatic region of the spectra of the two isomers at room temperature. On raising the temperature a sharpening of Chemical Society Reviews 1998 volume 27 188 the resonances occurred whereas at low temperatures the resonances not only sharpened but both spectra became considerably more complex (Fig.6). It is apparent that in these Fig. 6 1H NMR spectra (aromatic region; 300 MHz; [2H6]acetone solvent) of diastereoisomers of [{Ru(bpy)2}{Ru(phen)2}{m-(2,3-dpp)]}4+ at different temperatures (A) meso at 45 (top) 10 210 250 °C (bottom); (B) rac at 45 (top) 25 250 °C (bottom) cases there are conformational isomers which interconvert at room temperature on a time-scale comparable to that of the NMR experiment. At higher temperatures the interconversion becomes more rapid so that the spectrum for each diastereoisomer corresponds to an average conformation. At low temperatures separate spectra are observed for the two conformations.For this bridging ligand the two conformations can be assumed to correspond to the two possible skew dispositions of the two a,aA-diimine ligating moieties either side of the mutually planar arrangement (Fig. 7). Because of this skew relationship the two conformations of the 2,3-dpp ligand are chiral so that the conformers are in fact diastereoisomeric! Fig. 7 Conformations of the 2,3-dpp ligand. (Absolute configurations are based on the orientation of the two skew lines37 generated by the two coordinating N–N moieties.) It is interesting that in the meso diastereoisomer the two conformers are in approximately equal proportions whereas in the rac form they appear in a ca. 4 1 ratio perhaps as a consequence of steric interactions. 3 Isomers of trinuclear complexes There are a very limited number of examples of the isolation of stereoisomeric trinuclear complexes.Two diastereoisomers of an alkyne-bridged trinuclear species have been isolated by Tor and co-workers using chiral precursors as described earlier.23 Lehn and co-workers have also reported the isolation of the homochiral forms (DDD and LLL) of two trinuclear complexes, 28 using the appropriate chiral form of [Ru- (phen)2(py)2]2+ as precursor,9,11 and individual diastereoisomeric forms of trinuclear complexes have been obtained which involve a ‘chiragen’ bridging ligand {chiragen[bpy]}.17 Our own methodologies (outlined above) may be extended to higher oligonuclear species. For example the ligand 1,4,5,8,9,12-hexaazatriphenylene (HAT) may bridge between three metal centres and we have used a combination of the stereoselective synthetic techniques and chromatographic procedures to isolate the stereoisomeric forms of the homometallic trinuclear complexes [{Ru(bpy)2}3(m-HAT)]6+ and [{Ru- (phen)2}3(m-HAT)]6+ (Fig.8).6 The techniques may be applied to realise all the stereoisomers of the heterometallic trinuclear species [{Ru(bpy)2}2{Os(bpy)2}(m-HAT)]6+ (Fig. 9),15,29 and the diastereoisomeric forms of homometallic heteroleptic trinuclear species [{Ru(phen)2}{Ru(bpy)2}{Ru(Me2bpy)2}(m- HAT)]6+.15 In the chromatographic procedures (discussed below) the separation of diastereoisomers of the various systems is observed to be more efficient than the separation of enantiomeric forms of the diastereoisomers.Accordingly the reaction of one stereoisomeric form of a dinuclear species (e.g. DD-[{Ru(pp)2}2(m-HAT)]4+) with rac-[Ru(pp)2Cl2] results in Fig. 8 CHEM3D representation of (A) heterochiral (D2L) and (B) homochiral D3 (·L3)} diastereoisomeric forms of [{Ru(bpy)2}3(m- HAT)]6+6 the diastereoisomeric mixture DDD/DDL which may readily be separated. To give an example of the methodology the scheme in Fig. 10 shows the sequence used for the isolation of the stereoisomers of the heterometallic trinuclear species [{Ru(bpy)2}2{Os(bpy)2}(m-HAT)]6+.15,29 The general strategy can be extended to the isolation of stereoisomers of other oligonuclear assemblies involving different terminal and bridging ligands. 4 NMR characterisation of stereoisomers As noted above the NMR spectra of the oligomeric assemblies are complex and they are different for each diastereoisomer/ geometrical isomer.Until the isolation of individual stereoisomeric forms of such species the influence on the spectra of electronic effects and magnetic anisotropic interactions between the various terminal and bridging ligands had not been elucidated. For a number of ligand-bridged dinuclear4,6,9,15 and trinuclear species,6,15 detailed NMR studies and assignment of individual proton resonances have been undertaken allowing an assessment of such factors. To illustrate the point an example is taken of two trinuclear complexes—viz. the homometallic homoleptic complex [{Ru- (bpy)2}3(m-HAT)]6+ and its heterometallic analogue [{Ru- 189 Chemical Society Reviews 1998 volume 27 Fig.9 CHEM3D representations of the diastereoisomeric forms of [{Ru(bpy)2}2{Os(bpy)2}(m-HAT)]6+; DDDA/LLLA (A) DDLA/LLDA (B) and LDLA/DLDA (C). {Hydrogen atoms omitted for clarity; bpy rings about Os centre are darkened to allow identification.}15,29 L- (or D-)-[Ru(bpy)2(CO)2]2+ + 0.5 HAT LL [Os(bpy)2Cl2] DD [{Ru(bpy)2}2(m-HAT)]4+ [Os(bpy)2Cl2] [{Ru(bpy) rac- (DD/LL) meso- (DL) 2}2(m-HAT)]4+ Fig. 10 Synthetic scheme for stereoisomers of [{Ru(bpy)2}2{Os(bpy)2}(m- HAT)]6+. (Chromatographic procedures are indicated by single arrows synthetic procedures by double arrows and the prime denotes chirality which refers to the osmium centre.)15,29 (bpy)2}2{Os(bpy)2}(m-HAT)]6+.The two diastereoisomers of the Ru3 species (Fig. 8) have the point group symmetries D3 (homochiral D3/L3) and C2 (heterochiral D2L/L2D),6 which give rise to different numbers of inequivalent proton resonances in the 1H NMR spectra. Full assignment of these signals and determination of the relative connectivities can be made using 1H-COSY NOE-difference spectra and selective decoupling experiments. In particular the resonances of the H6 (bpy) Chemical Society Reviews 1998 volume 27 DLD' + DLL' [{Ru(bpy)2}2{Os(bpy)2}(m-HAT)]6+ 190 LLD' LLD' + LLL' LLL' DDL' DDD' + DDL' DDD' protons (compared with the H3 protons for example) show marked differences in chemical shifts depending upon the environment.Since the proton in the H6 position points directly towards the aromatic ring of an adjacent ligand (bpy or HAT) the relative degrees of ring anisotropy (current) experienced will vary considerably. Such effects allow in conjuction with NOE-difference spectra the assignment of the positioning of the pyridine rings relative to one another. The connectivity within the rings is established by 1H-COSY spectra. (The assignments are described in detail in the literature for the analogous phen species but the bpy complexes have been similarly characterised6). For the three diastereoisomeric forms of the analogous heterometallic complex [{Ru(bpy)2}2{Os(bpy)2}(m-HAT)]6+ (Fig. 9) the point group symmetries are lowered as the metal centres are no longer identical {viz.both the DDDA/LLLA [Fig. 9(A)] and DDLA/LLDA [Fig. 9(B)] diastereoisomers possess C2 symmetry and the DLLA/LDDA [Fig. 9(C)] possesses C1}.15,29 The spectra are consequently more complex than those of the homonuclear species to the extent that coincidental equivalences of certain resonances may render assignment of the chemical shifts to individual proton environments ambiguous. Nevetheless by use of 1H NMR spectroscopic techniques mentioned earlier as well as 1H-NOESY and 1H-TOCSY experiments in combination with the symmetry differences and comparisons with the known assignments for the homometallic analogues a definitive characterisation of the diastereoisomers may be made.15 These procedures have been extended to the characterisation by NMR techniques of the four diastereoisomers of the homometallic heteroleptic trinuclear species [{Ru(bpy)2}{Ru(Me2bpy)2}{Ru(phen)2}(m-HAT)]6+,15 for each of which there are 54 magnetically non-equivalent proton resonances! The 1H NMR spectra of this sequence of homochiral trinuclear species (DDD-Ru3 -Ru2Os and -RuRuARuAA) are presented in Fig.11 to show the increasing complexity as the symmetry is lowered. Fig. 11 1H NMR spectra (aromatic region; 300 MHz; [2H6]acetone solvent) of the D3-diastereoisomeric forms of (A) [{Ru(bpy)2}3{m- HAT}]6+ (B) [{Ru(bpy)2}2{Os(bpy)2}{m-HAT}]6+ and (C) [{Ru(bpy)2}{Ru(Me2- bpy)2}{Ru(phen)2}{m-HAT}]6+.15,29 Undoubtedly the availability of data from detailed investigations of this type the accessibility of higher field NMR facilities and the development of improved high-resolution NMR techniques will allow the characterisation of stereoisomers of higher nucleate assemblies to become routine.5 Chromatographic techniques In our studies the use of cation exchange chromatography (with SP Sephadex C-25 as the support) has been a significant factor in the isolation of individual stereoisomers (geometrical isomers diastereoisomers and enantiomers) of mono- and polynuclear ruthenium complexes with bidentate a,aA-diimine ligands. Using a wide range of organic and aliphatic counter-anions in the aqueous eluents it is apparent that the rate of passage down the column for any cation is profoundly influenced by the anion present. Certain anions are particularly effective including aromatic anions such as 4-toluate toluene-4-sulfonate O,OAdibenzoyl-l-tartrate and di-4-toluoyl-l-tartrate and longer chain aliphatic carboxylates such as hexanoate and octanoate.30 The observation is consistent with a second-sphere association of the eluent anion with the cations effectively reducing the overall charge of the cation and resulting in its increased elution rate.10 Furthermore in cases where there are stereoisomeric forms of the cations differential associations with the anion may result in their separation:30 geometrical isomers31,32 and enantiomers6,13,14 of mononuclear complexes as well as diastereoisomers enantiomers and geometrical isomers of diand tri-nuclear species.4,6,8,15,29 A detailed 1H NMR titration study has provided an interesting insight into the nature of these associations.As an example the perturbations of the resonances of the cation host [{(Me2bpy)2Ru}2(m-bpm)]4+ were measured as a function of the addition of sodium salts of various anions (guest) in D2O solution.30 In the majority of titration curves a distinct change at 4 equivalents of the anion indicated a stoichiometry of 1 4 as would be expected on the basis of electrostatic attraction. The perturbations (Dd in ppm) observed for the bpm-H4/6 Me2bpy-H3 and Me2bpy-H6A protons of the diastereoisomers of the dinuclear species after the addition of ten equivalents of the respective anions are shown in Fig. 12.30 The shifts observed for the two different diastereoisomers are similar although smaller for the rac form.The most striking observation is that the aliphatic anions all induced downfield shifts in the protons of the dinuclear complex while the shifts were upfield for the aromatic anions under the same conditions. The approach of a negative charge had been observed previously to cause downfield shifts in the 1H NMR spectrum of a complex cation as a result of second sphere interactions,34 in accordance with the present results for the aliphatic anions. The antithetic effect of the aromatic anions indicates that ring current (anisotropic) interactions of the anions on the protons of the associated complex resulting in upfield shifts are more significant. The presence of substituents at the ortho-position(s) to the carboxylate group in the aromatic anions 2-toluate and mesitoate led to great reductions in the shifts implying that the aromatic interaction is being blocked and the H2/6 protons of the aromatic anion play an important role in the association which suggests that the association relies on an edge-to-face p-stacking.33 The effects showed little dependence on the basicity of the carboxylate but as the chain length of the aliphatic anions increased greater shifts were observed by implication there were larger associations as a consequence of the geometry and hydrophobicity of the anion relative to the complex cation.Fig. 12 The relative 1H NMR signal (500 MHz) perturbations observed on the protons bpm-H4/6 (a; hatched) Me2bpy-H3 (b; open) and Me2bpy-H6A (c; filled) respectively for meso- and rac-[{(Me2bpy)2Ru}2(m-bpm)]Cl4 on the addition of 10 equiv.of the organic anions (D2O solvent; 30 °C).30 eluted first. As discussed earlier in this review the spatial relationship of the terminal ligands in ligand-bridged dinuclear There is some correlation between the magnitude of the shifts and the rate of passage down the column which is not entirely unexpected as the former is undoubtedly influenced by the strength of the association. It is an interesting observation that in all the dinuclear cases studied the meso diastereoisomer was 191 Chemical Society Reviews 1998 volume 27 complexes is dependent on the relative orientation of the ‘bites’ of the two bidentate ligating groups. However a perusal of the [{Ru(bpy)2}2(m-bpm)]4+ (Fig.2) and [{Ru(bpy)2}2(m-HAT)]4+ complexes (Fig. 3) reveals that the meso form in both cases has a cleft into which the associating anion may enter despite the linear and angular relationship (respectively) of the ligating moieties of the bridging ligand in the two cases. The determination of association constants of the various anions with the stereoisomers of the dinuclear species is rendered difficult by the 4 1 stoichiometric ratio of anion to cation. However similar anion interactions may be expected with the simpler mononuclear species such as [Ru(Me2bpy)3]2+ and to assess the magnitude of these associations a series of titrations were carried out with this complex against the same series of anions.The titration curves obtained indicated a 2 1 stoichiometry and the magnitudes of the perturbations were similar to those observed for the dinuclear species.30 The stability constants for the association of the first (kstab1) anion with the mononuclear target were typically ca. 100 dm3 mol21 for the anions identified as showing a strong interaction with the cations.30 While these values are small they are nevertheless significant especially in aqueous solution where the polarity of the solvent effectively negates the electrostatic attractions. While an intimate understanding of the nature of these associations allows a much more efficient application of the technique to the chromatogrpahic separation of stereoisomers of mononuclear and oligonuclear assemblies the connotations extend beyond the chromatographic process.For example the interaction of metal complexes with biological molecules (such as polynucleotides) is of considerable interest as metal centres have potential as sensitisers in sequencing and in site-specific cleavage processes.35.36 The nature of such interactions is not always well understood but there are undoubtedly aspects of p-stacking hydrophobicity and the chirality of the metal complex which influence intercalative and specific groove binding. The chromatographic separation of stereoisomers of mono- and oligo-nuclear species therefore offers not only a significantly larger stereochemical array of complexes as targets for such investigations but also a means of interpreting the fundamental nature of the interaction itself.These aspects are currently under study. 6 Consequences of stereoisomerism on physical properties of ligand-bridged oligomeric complexes There are a number of consequences of the isolation of the stereoisomers of mono- and oligo-nuclear complexes of the above types given their potential in the development of new materials for photochemical molecular devices.2 In terms of identification each diastereoisomeric or geometrical form of a complex will have its own distinctive NMR spectrum so that the spectral characteristics of an isomeric mixture are of minimal use in structural elucidation particularly for higher nucleate assemblies. For such mixtures bulk characteristics such as nuclearity (from mass spectral measurements) or spectral properties (which will be averages of the stereoisomeric mixture) are accessible but contain no intimate structural information.The isolation of the individual stereoisomers has allowed not only structural assignment but also a general assessment of the factors contributing to the various physical characteristics. More importantly there are spatial consequences on physical properties in these assemblies:7 the dependence of such fundamental features as intramolecular energy and electron transfer processes on the stereochemical relationship of components in a polymetallic supramolecular structure may well be an essential factor in the design of new materials. We have recently reported three examples where differences have been observed in the spectral electrochemical and photophysical properties of stereoisomers in mononuclear5,32 and dinuclear/trinuclear assemblies.4,6,7 Chemical Society Reviews 1998 volume 27 192 The first of these examples involves mononuclear complexes and although such species have not been the subject of this review the results are salient to the present discussion. A comparative study of the photophysics5 of the four separate geometric isomers (one trans and three cis30) of the chromophore-quencher triad [Ru(Me2bpy)(bpyCH2PTZ)- (bpyCH2MV2+)]4+ {bpyCH2PTZ = 10-[(4A-methyl- 2,2A-bipyridin-4-yl)methyl]phenothiazine and bpyCH2MV2+ = 1-[(4A-methyl-2,2A-bipyridin-4-yl)methyl]-1A-methyl-4,4Abipyridinediium cation} has shown that following metal-toligand charge transfer (MLCT) excitation by laser flash photolysis the redox charge-separated states [RuII(Me2bpy)- (bpyCH2PTZ·+)(bpyCH2MV·+)]4+ are formed rapidly ( < 5 ns).While the driving force for the back electron transfer process from -MV+ to -PTZ+ is the same in every case the rates are different for the four isomers and kET varies from 4.5 3 106 to 8.7 3 106 s21 in acetonitrile solution at 25 °C. The second example involves a series of dinuclear complexes [{Ru(pp)2}2(m-BL)]2+ incorporating an a-azodiimine (such as apy and mapy) as the bridge and bpy or Me2bpy as the terminal ligands.4 The meso and rac diastereoisomeric forms of such species (Fig. 4) have been separated electronic spectral and electrochemical studies indicate there are differences in intermetal communication between the diastereoisomeric forms.The third example involves the meso and rac diastereoisomers of the dinuclear complexes [{Ru(pp)2}2(m-HAT)]4+ (Fig. 3) and the homochiral (D3/L3) and heterochiral (D2L/L2D) diastereoisomers of the trinuclear complexes [{Ru(pp)2}3(m- HAT)]6+ (Fig. 8) where pp = bpy or phen.8 Emission studies of all the dinuclear species at room temperature indicate the relative luminescence quantum yields and the emission lifetimes significantly decrease for the meso compared with the rac diastereoisomers. While no significant differences were detected at room temperature in the diastereoisomeric forms of the trinuclear compounds in a glass at low temperature (80 K) the luminescence lifetimes of the heterochiral diastereoisomer were slightly shorter than those of the homochiral form.8 While there are a limited number of examples of such studies of physical characteristics as a function of the stereochemical identity at this stage the factors controlling such differences are not yet understood and their elucidation constitutes a significant challenge in supramolecular chemistry in the immediate future.The development of techniques such as those described in this review to realise separate stereoisomers in a wide variety of assemblies provides the means of addressing this important problem. 7 Acknowledgements I wish to acknowledge the considerable talent and insights of a number of my postgraduate students and postdoctoral associates whose input has maintained our efforts—in particular I thank Dr Todd Rutherford Dr Nick Fletcher Mr Laurie Kelso Mr Brad Patterson and Mr Dave Reitsma.Drs Nick Fletcher Todd Rutherford and Brett Yeomans are also thanked for constructive comments on this manuscript. Our work in this area is supported by the Australian Research Council. 8 References 1V. Balzani A. Juris M. Venturi S. Campagna and S. Serroni Chem. Rev. 1996 96 759; and references cited therein. 2 V. Balzani and F. Scandola Supramolecular Photochemistry Ellis Horwood Chichester 1991. 3 A. Juris S. Barigelletti S. Campagna V. Balzani P. Belser and A. von Zelewsky Coord. Chem. Rev. 1988 84 85; and references cited 4 L. S. Kelso D. A.Reitsma and F. R. Keene Inorg. Chem. 1996 35 5 J. A. Treadway P. Chen T. J. Rutherford F. R. Keene and T. J. Meyer 6 T. J. Rutherford O. Van Gijte A. Kirsch-De Mesmaeker and F. R. therein. 5144. J. Phys. Chem. A 1997 101 6824. Keene Inorg. Chem. 1997 36 4465. 7 F. R. Keene Coord. Chem. Rev. 1997 166 121; and references cited therein. 8 D. A. Reitsma and F. R. Keene J. Chem. Soc. Dalton Trans. 1993 2859. 9 X. Hua and A. von Zelewsky Inorg. Chem. 1995 34 5791. 10 N. C. Fletcher P. C. Junk D. A. Reitsma and F. R. Keene J. Chem. Soc. Dalton Trans. 1998 133. 11 X. Hua and A. von Zelewsky Inorg. Chem. 1991 30 3796. 12 O. Morgan S. Wang S.-A. Bae R. J. Morgan A. D. Baker T. C. Strekas and R. Engel J. Chem. Soc. Dalton Trans. 1997 3773. 13 T.J. Rutherford M. G. Quagliotto and F. R. Keene Inorg. Chem. 1995 34 3857. 14 B. T. Patterson and F. R. Keene Inorg. Chem. 1998 37 645 15 T. J. Rutherford and F. R. Keene J. Chem. Soc. Dalton Trans. 1998 1155. 16 H.-R. M�urner P. Belser and A. von Zelewsky J. Am. Chem. Soc. 1996 118 7989. 17 N. C. Fletcher F. R. Keene H. Viebrock and A. von Zelewsky Inorg. Chem. 1997 36 1113. 18 C. Hiort P. Lincoln and B. Nord�en J. Am. Chem. Soc. 1993 115 3448. 19 P. Lincoln and B. Nord�en Chem. Commun. 1996 2145. 20 K. W�arnmark J. A. Thomas O. Heyke and J.-M. Lehn Chem. Commun. 1996 701. 21 F. M. MacDonnell and S. Bodige Inorg. Chem. 1996 35 5758. 22 S. Bodige A. S. Torres D. J. Maloney D. Tate G. R. Kinsel A. K. Walker and F. M. MacDonnell J. Am.Chem. Soc. 1997 119 10 364. 23 D. Tzalis and Y. Tor J. Am. Chem. Soc. 1997 119 852. 24 H. P. Hughes D. Martin S. Bell J. J. McGarvey and J. G. Vos Inorg. Chem. 1993 32 4402. 25 L. De Cola F. Barigelletti V. Balzani R. Hage J. G. Haasnoot J. Reedijk and J. G. Vos Chem. Phys. Lett. 1991 178 491. 26 D. P. Rillema D. G. Taghdiri D. S. Jones C. D. Keller L. A. Worl T. J. Meyer and H. A. Levy Inorg. Chem. 1987 26 578. 27 D. A. Reitsma PhD thesis in preparation James Cook University Townsville Australia. 28 K. W�arnmark O. Heyke J. A. Thomas and J.-M. Lehn Chem Commun 1996 2603. 29 T. J. Rutherford and F. R. Keene Inorg. Chem. 1997 36 3580. 30 N. C. Fletcher F. R. Keene and D. A. Reitsma Presented at IC98 the National Conference of the Division of Inorganic Chemistry RACI Wollongong 1998; Abstract p. 83. 31 T. J. Rutherford D. A. Reitsma and F. R. Keene J. Chem. Soc. Dalton Trans. 1994 3659. 32 T. J. Rutherford and F. R. Keene Inorg. Chem. 1997 36 2872. 33 C. A. Hunter and J. K. M. Sanders J. Am. Chem. Soc. 1990 112 5525. 34 P. D. Beer Chem. Commun. 1996 689. 35 A. Kirsch-de Mesmaeker J.-P. Lecomte and J. M. Kelly Photoreactions of metal complexes with DNA especially those involving a primary photo-electron transfer in Electron Transfer II; ed. J. Mattay Springer- Verlag Berlin 1996 and references cited therein. 36 A. M. Pyle and J. K. Barton Prog. Inorg. Chem. 1990 38 413; and references cited therein. 37 A. von Zelewsky Stereochemistry of Coordination Compounds Wiley Chichester 1995; and references cited therein. Received 4th June 1997 Accepted 22nd December 1997 193 Chemical Society Reviews 1998

ISSN:0306-0012    

DOI:10.1039/a827185z

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Template self-assembly of polyiodide networks Alexander J. Blake,a Francesco A. Devillanova,b Robert O. Gould,c Wan-Sheung Li,a Vito Lippolis,a Simon Parsons,c Christian Radekc and Martin Schr�oder*a 09124 Cagliari Italy c Department of Chemistry The University of Edinburgh Edinburgh UK EH9 3JJ A range of metal thioether macrocyclic complexes has been used as templating agents in the preparation of extended multi-dimensional polyiodide arrays. A selection of unusual Alexander J. Blake received both his BSc and PhD degrees in Chemistry from Aberdeen University where he was first introduced to crystal structure determination. Following a period of postdoctoral work at Exeter University he moved to the Chemistry Department at the University of Edinburgh in 1982 initially to develop new methods for the study of lowmelting compounds by single crystal X-ray diffraction.From 1985 he took over responsibility for the running of the Department’s Crystal Structure Service as a Staff Crystallographer. He has been a Co-Editor of Acta Crystallographica since 1995 and in August of that year moved to the Chemistry Department of the University of Nottingham where he is currently a Research Officer and the Manager of the Crystal Structure Service. Research interests include supramolecular structure and the exploitation of low-temperature techniques for crystallographic data collection. Francesco A. Devillanova graduated in Chemistry at the University of Bari in 1964. In the same year he moved to the University of Modena as temporary Professor of General and Inorganic Chemistry.In 1972 he moved to the University of Cagliari where in 1980 he was appointed to the Chair of Inorganic Chemistry. His scientific interests focus on sulfur and selenium chemistry and on the donor–acceptor interaction between chalcogen donors and transition metal ions halogens and interhalogens. Robert O. Gould was an undergraduate at Williams College Williamstown Mass and gained his PhD from Queen’s College Dundee (University of St. Andrews) under the supervision of Dr R. F. Jameson in 1963. He was appointed to the staff in the Chemistry Department University of Edinburgh in 1962 and was subsequently promoted to lecturer (1964) Senior Lecturer (1985) and Reader (1997). His research interests are primarily in the study of complexes by X-ray diffraction and to improving methods of crystal structure determination.Wan-Sheung Li gained both her BSc and PhD degrees at the University of North London. The latter under the supervision of Professor Mary McPartlin was devoted to the study of homoand hetero-nuclear metal–metal bonded complexes. In early 1996 she took up a postdoctoral position in the Department of Chemistry of the University of Nottingham where she was a Department of Chemistry The University of Nottingham Nottingham UK NG7 2RD b Dipartmento di Chimica e Tecnologie Inorganiche e Metallorganiche University of Cagliari Via Ospedale 72 and intriguing polyiodides is described and the role played by the size shape and charge of the metal macrocyclic complex discussed.involved in the running of the Departmental Crystal Structure Service. In January 1998 she took up a position in the Computational Chemistry Group within the Institute of Chemistry Academia Sinica Taipei Taiwan. Vito Lippolis graduated in Chemistry in 1991 at the University of Pisa and in the same year gained a Diploma in Chemistry at the ‘Scuola Normale Superiore’ of Pisa. In 1992 he was appointed permanent researcher in Inorganic Chemistry at the University of Cagliari. He is currently a 2nd year PhD student at the University of Nottingham under the supervision of Professor Martin Schr�oder. Simon Parsons gained a BSc Degree in 1987 from the University of Durham and PhD in Chemistry in 1991 from the University of New Brunswick Canada under the supervision of J.Passmore. After postdoctoral research at the University of Oxford (with A. J. Downs) he was appointed to a postdoctoral position in crystallography at the University of Edinburgh in 1993. In 1995 he was appointed Staff Crystallographer in the same Department. Christian Radek gained his first degree (1990) from the Ruhr- University Bochum and carried out his Diplom-arbeit with Professor Karl Wieghardt. He was awarded his PhD from the University of Edinburgh under the supervision of Professor Martin Schr�oder in 1995 and is currently studying for a degree in Economics at the Hogeschool van Utrecht. Martin Schr�oder gained a BSc Degree in Chemistry from the University of Sheffield in 1975 and a PhD in Inorganic Chemistry from Imperial College London under the supervision of W.P. Griffith in 1978. After postdoctoral research at the ETH Z�urich (with A. Eschenmoser) and Cambridge (with J. Lewis) he was appointed in 1982 to a Demonstratorship in Inorganic Chemistry at the University of Edinburgh. He was subsequently promoted in Edinburgh to lecturer reader and in 1994 to a personal chair in Inorganic Chemistry. In 1995 he was appointed to the Chair and Head of Inorganic Chemistry at the University of Nottingham. He has been awarded the Corday Morgan Medal and Prize of the Royal Society of Chemistry and a Royal Society of Edinburgh Support Research Fellowship. 195 Chemical Society Reviews 1998 volume 27 1 Introduction It is well known that the heavier halogens can form oligomeric catenated cations and anions.1 Since I2 exhibits the highest tendency to form stable catenated anionic species,1 the synthesis and structural characterisation of polyiodides continue to be an active area of investigation.Recent interest in this aspect of the chemistry of I2 comes from its use as an acceptor in the synthesis of mixed-valence donor–acceptor materials which exhibit unusual electrical behavior.2 The resulting polyiodide species fit favourably in the crystal lattice of these materials by occupying one-dimensional channels within stacks of partially oxidized donor molecules. 32 I4 22 Numerous examples of small polyiodides such as I and I52 have been reported but relatively few extended and very extended discrete oligomeric anionic polyiodides such as I72,3–7 I8 22,8–11 I92,12 I10 42,13 I12 22,14,15 I16 22,15 I16 42,16 I22 42,17 and I29 3218 have been characterised structurally.Although these higher polyiodides can all be described on the basis of crystallographic structural data and spectroscopic studies19 as a combination of perturbed (slightly elongated) I2 molecules [I–I = 2.75–2.80 Å] with long-range interactions to I32 and I2 ions [I···I = 3.4–3.6 Å] their geometrical features can be very different. ‘Z’ and ‘S’-shaped chains have been found for I8 228 and I16 4216 units respectively; a ‘T’-bonding motif has been observed for I9212 whereas for I72 different arrangements from a twisted ladder in N-methyl-g-picolinium heptaiodide20 to a trigonal pyramidal shape in the iodonium salt [(N-methylbenzothiazole-2(3H)-thione)2I]I7,5 have been reported.Thus variation of the counter-cation leads to variation in counter-anion structures. Some of these polyiodides are present in the crystal lattice as discrete aggregates but they frequently tend to form polymeric one-dimensional chain structures or infinite three-or two-dimensional networks15,21–24 in which the identification of the basic polyiodide unit becomes arbitrary. In these cases the polyiodide arrays form ‘unusual supramolecular inorganic matrices’ (ref. 25 in ref. 15) and are better described as aggregates of I2 I2 and I32 entities held together by I···I bonding interactions of varying strengths from rather strong [ca.3.4 Å] to fairly weak [ca. 4.1 Å]. Some authors have recognised the nature (shape size and charge) of the cation as playing a crucial role on the structural and geometrical features of the associated polyiodide species. For example small cations in the crystal lattice tend to be associated wtric I32 ions whereas larger cations seem to induce a symmetrical shape.25 It is commonly accepted that large anions are stabilised best by large cations and Mertes et al.9,26 recognised the use of bulky metal macrocyclic complexes for the stabilization of unusual extended polyiodide species. They expected that the steric properties of the chosen aza-macrocyclic ligand would be more important than the nature of the metal ion in determining the nature of polyiodide ion.Indeed macrocyclic thioether complexes seem to be ideal reaction partners in the preparation of oligomeric anionic polyiodides since they are relatively chemically inert and their size shape and charge can be fine-tuned by changing either the metal ion or the thioether ligand. Furthermore thioether macrocycles are known as free ligands to form a range of charge-transfer (CT) adducts with I2.27 We describe in this review the synthesis and structures of a selection of unique polyiodide arrays using thioether macrocycle complexes28 as templating agents. For some of these structures it has been found necessary to consider I···I nonbonding contacts of lengths similar to the sum of the van der Waals radii for I2 [4.3 Å] in order to allow adequate description of the polyiodide lattice.The discussion has been organised into two sections. The first dealing with structural results has been divided into several subsections according to the chemical formula of the starting template metal macrocyclic complex used for the formation of the polyiodide array. In the second section an overview will be given of the information obtainable Chemical Society Reviews 1998 volume 27 196 from the use of the FT-Raman spectroscopy in the characterisation of polyiodide species; finally this background will be used to interpret the FT-Raman spectra of the polyiodides described. 2 Structural characterisation 2.1 [Ag([15]aneS5)]BF4 ([15]aneS5 = 1,4,7,10,13-pentathiacyclopentadecane) The co-ordination chemistry of AgI with [15]aneS5 has already attracted some attention because of the predicted stereochemical mismatch between the co-ordination preferences of the AgI ion (octahedral or tetrahedral) and the macrocycle (five coordinate).The structure of the [Ag([15]aneS5)]+ cation has been found to be dependent upon the nature of the counter-anion29 and we thought that this structural flexibility might be a useful attribute in a templating agent for polyiodide anions. S S S S S S S S S S S S S S [18]aneS6 [9]aneS3 [15]aneS5 H S S N S S S S S N S H [16]aneS4 [18]aneN2S4 O O O O O [15]aneO5 2.1.1 [Ag2([15]aneS5)2]I12 Reaction of [Ag([15]aneS5)](BF4) (prepared in situ from [15]aneS5 and AgBF4) with three molar equivalents of I2 in MeCN and slow evaporation of the solvent affords dark red plates.An X-ray crystal structure determination shows30 the asymmetric unit to consist of two independent [Ag([15]aneS5)]+ cations and a discrete I12 22 polyiodide anion interacting with each other through Ag–I bonds the two cations being located on the same side of the polyiodide anion (Fig. 1). The AgI ions are four co-ordinate with a very distorted tetrahedral geometry. Only three of the five potential S-donor atoms of the macrocyclic ligand are co-ordinated to each AgI ion [Ag–S = 2.593(6)–2.783(6) Å] and the fourth co-ordination site is occupied by an I2 ion [Ag–I = 2.781(3) 2.830(3) Å]. Fig. 1 View of [Ag([15]aneS5)]2I12.The asymmetric unit consists of two independent [Ag([15]aneS5)]+ cations and a discrete I12 22 polyiodide anion. The I12 22 polyiodide anion can be viewed as an almost linear I4 22 unit interacting at each of its termini with two di-iodine molecules to give an overall twisted ‘H’ configuration (Fig. 1) (the twisting angle between the two peripheral I2···I2···I2 fragments is ca. 40.3°). The I4 22 unit is built up from one diiodine molecule and two I2 and consequently the overall I12 22 polyiodide is best described as [2I2·5I2]. The I–I bond distances in the perturbed I2 molecules [2.755(2)–2.770(2) Å] are longer than that in I2 in the vapour [2.667(2) Å] or in the solid state [2.715(6) Å].19 This elongation is attributable to donation of electron density from I2 to the s*-antibonding LUMO of the I2 molecules with I2···I–I contacts ranging from 3.242(2) to 3.563(2) Å.2I12,14 I12 22 polyiodides are quite rare in the literature with only four examples being reported [K(Crypt-2.2.2)] (Me2Ph2N)2I12,15 [Cu(dafone)3]I12 (dafone = 4,5-diazafluoren-9-one),31 and (MePh3P)4I22.17 In these compounds the I12 22 polyiodides are crystallographically centrosymmetric and consist of two pentaiodide groups bridged through their central I2 by di-iodine molecules [I52···I2 = 3.360(2)–3.481(2) Å]; in the last compound two further end-on interacting pentaiodides [I52···I2 = 3.667(2) Å] give rise to an overall discrete I22 42 ion. In [Ag2([15]aneS5)2]I12 an extended three-dimensional superstructure is built up via a network of additional I···S interactions with the terminal iodine atoms [I(1) I(2) I(3) and I(4) in Fig.2] Fig. 2 View of [Ag2([15]aneS5)2]I12. I···S interactions link adjacent asymmetric units. I(1)···S(1) = 2.987(6) I(2)···S(2) = 3.131(6) I(3)···S(3) = 3.056(6) I(4)···S(4) = 3.498(6) Å. of each I2 unit interacting with one S-donor atom of four adjacent [Ag([15]aneS5)]+ cations. These interactions involve sulfur atoms unco-ordinated to AgI [I···S = 2.987(6)–3.131(6) Å] and sulfur atoms already bound to the metal ion [I···S = 3.498(6) Å] and generate spirals of I12 22 and [Ag([15]aneS5)]+ ions which alternate through the crystal lattice along the (001) direction with a distorted square projection in the (110) plane (Fig.3). 2.2 [Ag([18]aneS6)]BF4 [Ag([9]aneS3)2]BF4 ([18]aneS6 = 1,4,7,10,13,16-hexathiacyclooctadecane [9]aneS3 = 1,4,7-trithiacyclononane) Our postulate that the shape and the charge of the cation might play the main role in the assembly of the polyiodide anions led us to investigate [Ag([18]aneS6)]+ and [Ag([9]aneS3)2]+ as potential templates. The charge on these cations is the same as for [Ag([15]aneS5)]+ but the shape is very different with [Ag([18]aneS6)]+ and [Ag([9]aneS3)2]+ regarded as essentially spherical. Furthermore these AgI cations are octahedral and therefore co-ordinatively saturated with no further co-ordination sites available for I2 ions. The structures of the [Ag([18]aneS6)]+ and [Ag([9]aneS3)2]+ cations have been Fig.3 View of [Ag([15]aneS5)]2I12. Alternating I12 22 anions and [Ag([15]aneS5)]+ cations spiral along the (001) direction reported previously28 and show the AgI ion to have trigonally distorted octahedral co-ordination geometries. Reaction of [Ag([18]aneS6)]BF4 with three molar equivalents of I2 in CHCl3–MeNO2 (8 5 v/v) affords after the evaporation of the solvent in vacuo a dark-blue powder presumed to be [Ag([18]aneS6)]I5. Re-crystallisation of this product from MeCN and EtOH gives deep red crystals of [Ag([18]aneS6)]I7 and brown crystals of [Ag([18]aneS6)]I3 respectively. [Ag([18]aneS6)]I3 can also be prepared by metathesis of [Ag([18]aneS6)]BF4 with Bu4NI3 while addition of two molar equivalents of I2 to [Ag([18]aneS6)]I3 affords [Ag([18]aneS6)]I7 in high yield.Likewise the reaction of [Ag([9]aneS3)2]BF4 with I2 in MeCN affords [Ag([9]- aneS3)2]I5 crystals of which have been isolated by slow evaporation of the solvent. 2.2.1 [Ag([18]aneS6)]I7 The single crystal structure of [Ag([18]aneS [Ag([18]aneS polymeric polyiodide matrix of I 6)]I7 32 shows the 6)]+ cations embedded in a three-dimensional 72 anions (Fig. 4). The overall Fig. 4 View of {[Ag([18]aneS6)]I7}H structure of the [I72]H network can best be described as a distorted cube in which I2 ions occupy the lattice points of a primitive rhombohedral lattice with one slightly elongated I2 molecule [I–I = 2.7519(14) Å] placed along each edge bridging two I2 ions [I2···I2 = 3.3564(15) Å]. Each cube edge in this unique three-dimensional network (Fig.5) consists therefore of an I2···I–I···I2 arrangement and each I2 interacts with six molecules of I2 with a local D3d symmetry. None of the previously reported I72 polyiodide species exhibit a comparable cube-like structure. Before 1991 only two structurally characterised heptaiodide ions namely [NEt4]I7 23 and [(py)2I]I7 24 were known. Both of these show threedimensional networks of symmetrical I32 anions and I2 197 Chemical Society Reviews 1998 volume 27 Fig. 5 View of one cube-like array in {[Ag([18]aneS6)]I7}H 52·I2] molecules and are best described as adducts of the type [I32·(I2)2]. In 1992 Poli et al. reported4 the crystal structure of [PPh4]I7 as the first example of a discrete I72 ion but the presence of a significantly asymmetric I32 unit [I–I = 2.814(1) 3.07(1) Å] means that the [I32·(I2)2] description cannot be ruled out.The same might be said of the trigonal pyramidal heptaiodides in EtPh3PI7 and Bipy·HI7 reported by Tebbe et al.,21,22 the latter being better described perhaps as [I rather than [I32·(I2)2] or [I2·(I2)3] because of the pattern in the bonding-interactions between the central I2 and the three perturbed di-iodine molecules [I2···I2 = 3.089(3) 3.094(4) 3.440(4) Å]. In 1993 Devillanova et al. reported5 the first example of an I72 ion—in [(N-methylbenzothiazole -2(3H)-thione)2I]I7—which is a genuine [I2·(I2)3] adduct. This has approximate C3v symmetry and I–I distances within the 2 three perturbed I2 molecules ranging from 2.746(1) to 2.771(1) Å; the three I2···I interactions lie in the range 3.237(1)–3.260(1) Å.Only three other I72 ions with the same trigonal pyramidal geometry are known. In (Hpy)2I7I3,3 [Cu(OETTP)]I7 6 and [(H3O+·18-crown-6)]I7 7 one of the three I2···I2 interactions is either much longer or much shorter than the other two with a distance in the range 3.154(9) to 3.354(3) Å. These I72 anions can still be described as [I2·(I2)3] adducts but with approximate Cs symmetry. The I72 anions in (Hpy)2I7I3,3 and [(H3O+·18-crown-6)]I7,7 like the one in [(N-methylbenzothiazole-2(3H)-thione)2I]I7 5 are characterised by head-to-tail long-range interactions [3.426(3)–3.545(13) Å] of the I2 of one I72 unit with an I2 molecule of the next to give infinite one-dimensional chains.6)]+ cation in the The template effect of the [Ag([18]aneS formation of the unique cubic [I72]H structure may be rationalised by comparing the diagonals of the cube of iodines with the spacing of the S3 triangles making up the faces of the distorted co-ordination octahedron around AgI. The diagonal along the threefold axis of the cation is 11.850 Å while the other diagonals are 17.635 Å. The thickness of the cation may be estimated as the separation of the S3 triangles [2.48 Å] plus twice the van der Waals radius of the sulfur [1.85 Å] giving 6.18 Å. Its mean diameter may be considered as twice the mean distance of the carbon atoms from the threefold axis [3.55 Å] plus twice the van der Waals radius of carbon [1.50 Å] giving 72]H 10.10 Å.Therefore the [Ag([18]aneS6)]+ cations fit very well into the cubic second-sphere polyiodide framework. Conceptually therefore the formation of the cube-like [I matrix may be regarded as a second-sphere template reaction around a central metal-complex cation. 2.2.2 [Ag([18]aneS6)]I3 The structure of this complex shows [Ag([18]aneS6)]+ cations and symmetrical I32 ions [I–I 2.9137(3) Å] in the crystal Chemical Society Reviews 1998 volume 27 198 lattice.32 Fig. 6 shows parallel stacks of macrocycle complexes and I32 ions. This I32 salt may be considered a structural precursor to [Ag([18]aneS6)]I7 via the addition of two equivalents of I2 to [Ag([18]aneS6)]I3. Thus addition of I2 to [Ag([18]aneS6)]I3 converts a one-dimensional (1D) lattice of I32 to 2D and 3D lattices of I52 and I72 respectively.Unfortunately we have thus far been unable to crystallise the I52 salt of [Ag([18]aneS6)]+ due to its relative instability. Fig. 6 The single crystal structure of [Ag([18]aneS6)]I3; packing diagram in the (110) plane It is important to note the different structural modifications of the [Ag([18]aneS6)]+ cation observed in [Ag([18]aneS6)]PF6 [Ag([18]aneS6)]I7 and [Ag([18]aneS6)]I3. In all three cases the macrocyclic cation adopts a trigonally compressed octahedral geometry with S–Ag–S chelate angles of about 80° and nonchelate angles of about 100°. However in the I72 salt all the Ag–S distances are equivalent [2.754(2) Å] while the PF shows a tetragonal compression [Ag–S 2.753(4) Å]28 and the I 62 salt ax = 2.697(5) Ag–Seq = 32 salt a tetragonal elongation [Ag–Sax = 2.8007(10) Ag–Seq = 2.7255(7) Å].32 The cation is therefore able to modify its shape slightly thereby perhaps offering different templating effects to the polyiodide anion.3)2]I5 2.2.3 [Ag([9]aneS Although the [Ag([9]aneS3)2]+ cation has potentially the same shape dimensions and charge as [Ag([18]aneS6)]+ it does not show the same template effect under the same reaction conditions as above it forms an I52 salt rather than a cube-like [I72]H polyiodide array.30 The crystal structure shows [Ag([9]aneS3)2]+ cations and discrete V-shaped pentaiodide units. The cation shows very similar structural features to those already reported in other salts28 with two molecules of [9]aneS3 bound facially to the AgI metal centre conferring a distorted octahedral arrangement of six sulfur atoms.Each I52 unit is best described as an [I2·(I2)2] adduct [I–I = 2.7898(9) I2···I = 3.1118(9) Å I2···I2···I2 84.61(4)°] which is located on a plane perpendicular to the approximate threefold axis of the cation. The terminal atoms of each I52 unit interact weakly with one sulfur atom in each of two adjacent cations [I···S = 3.618(2) Å] so that a sinusoidal polymeric succession of cations and I52 ions develop along the (110) direction (Fig. 7). Each chain alternates with its inversion mate such that the chains pack efficiently. The chains themselves may be regarded as being disposed in phase even though their constituent anions and cations have been interchanged.2.3 [M([16]aneS4)](PF6)2 (M = Pd Pt) ([16]aneS4 = 1,5,9,13-tetrathiacyclohexadecane) In our attempts to synthesise unusual polyiodide arrays by using metal macrocycle complexes as template agents we have always obtained the metathesis product whenever Bun 4NI3 was used as starting material. In this way [M([9]aneS3)2](I3)2 (M = Ni Co Pd) [Pd([12]aneS4](I3)2 [Pd([15]aneN4)](I3)2 and [Ni([15]aneN4)(MeCN)2](I3)2 have all been synthesised and structurally characterised.33 All of these complexes show but with the cations and anions interchanged. Fig. 7 View of [Ag([9]aneS3)2]I5. Adjacent chains are related through inversions centres and may be regarded as being in phase with each other isolated I32 anions in the crystal lattice.However in the case of [M([16]aneS4)](PF6)2 (M = Pd Pt) the reaction with Bun 4NI3 in MeCN afforded unexpected products on slow evaporation of the solvent. These are isostructural and contain the binuclear cations [([16]aneS4)M–I–M([16]aneS4)]3+ (M = Pd Pt) involving a highly unusual linear M–I–M moiety in which an I2 bridges two MII centres symmetrically (Fig. 8).34 The M–I Pd([16]aneS4)]3+ cation template Fig. 8 View of 14-membered polyiodide belt at the [([16]aneS4)Pd–I– distances are relatively long [3.135(3) for Pd and 3.194(2) Å for Pt] so the I2 anion may be regarded as being trapped inside a pseudo cavity formed by two [M([16]aneS4)]2+ cations with the linear M–I–M bridge being imposed by the steric bulk of the tetrathioether crown.The [16]aneS4 ligand is bound via all four S-donors to the MII centres which are formally five co-ordinate in each cation. The M–S distances in [([16]aneS4)M– I–M([16]aneS4)]3+ lie in the range 2.300(10)–2.315(9) Å (Pd) and 2.332(3)–2.339(3) Å (Pt) and are slightly elongated compared to those of the parent [Pd([16]aneS4)]2+ and [Pt([16]aneS4)]2+ cations.28,35 The PdII and PtII centres lie 0.352 and 0.306 Å respectively out of the least-squares mean plane of their S4 donor sets in the direction of the bridging I2 ion. Interestingly this displacement is into the methylene manifold of the macrocycle the opposite to that observed for [Pd([16]aneS4)]2+ and [Pt([16]aneS4)]2+.28,35 The same counter-polyanion structure is present in both PdII and PtII complex crystal structures.The basic units of the polyiodide array are a I2 a distorted L-shaped I52 fragment which can be described either as [I2·(I2)2] or as [I32·I2] and a highly asymmetric I32 moiety. In fact choosing the first description the I–I bond distances in the two perturbed I2 molecules [I(1)–I(2) I(4)–I(5)] are 2.798(2) and 2.836(2) Å whereas the associated I2···I2 bond lengths are 3.409(2) [I(2)–I(3)] and 3.044(2) Å [I(3)–I(4)] respectively. The I2–I(3)– I2 angle is approximately 90° as normally found in discrete L-shaped I52 units. The I52 units are connected to each other through contacts of 3.806(2) Å between two perturbed I2 molecules to form planar zig-zag polymeric chains (Fig. 9); two of these chains flank a row of cations and are linked by pairs of bond-interactions [I(5)···I(6) = 3.285(2) Å] between an iodide [I(6)] and two terminal iodine atoms from two I52 units.Considering the reasonably short I2···I52 bond lengths an Fig. 9 View of [([16]aneS4)Pd–I–Pd([16]aneS4)]3+·I11 32 showing the 14-membered polyiodide rings fused to give an infinite polycyclic ribbon. Starred atoms identify the basic I11 32 unit. I(1)–I(2) = 2.798(2) I(2)– I(3) = 3.409(2) I(3)–I(4) = 3.044(2) I(4)–I(5) = 2.836(2) I(5)– I(6) = 3.285(2) Å. overall and unique I11 32 can be identified as a basic unit of the resulting polyiodide array (Fig. 9). An infinite polycyclic ribbon is therefore built up of 14-membered polyhalide rings sharing three iodine atoms.Each ring measures 9.657 by 12.640 Å (diagonal length 16.383 Å) and surrounds a binuclear metal cation with the M–I–M bridging I2 placed exactly at its centre (Figs. 8 and 9). Therefore the central complex cation may be regarded as acting as a template for the synthesis of this unique cyclic polyhalide array in which the binuclear complex cation sits. 2.4 [Pd2Cl2([18]aneN2S4)](PF6)2 ([18]aneN2S4 = 1,4,10,13-tetrathia-7,16-diazacyclooctadecane) On the basis of the results obtained with [M([16]aneS4)](PF6)2 (M = Pd Pt) the binuclear complex [Pd2Cl2([18]- aneN2S4)](PF6)2 having the same overall charge but different shape was treated with Bun 4NI3 in MeCN solution. After several days two different crystal morphologies black facetted prisms and brown elongated plates were obtained and X-ray diffraction studies undertaken to determine their structure.2.4.1 [Pd2Cl2([18]aneN2S4)]1.5I5(I3)2 For the black prisms the asymmetric unit consists of one I52 and two I32 ions and 1.5 [Pd2Cl2([18]aneN2S4)]2+ dications.36 The structure of the cations is similar to that in the corresponding PF62 salt.37 The PdII ions are each co-ordinated to one Nand two S-donor atoms with a Cl2 ligand completing the square planar co-ordination. The two co-ordination planes lie parallel to each other but the overall binuclear dication adopts a stepped conformation in order to minimise steric interactions. Interestingly the dications are linked by an extensive network of hydrogen bonds between the (N)H and Cl atoms to form infinite chains in the crystal lattice [N···Cl = 3.254(14)–3.356(12) (N)H···Cl = 2.57 Å].The intra-cation Pd···Pd distances are 4.055(2) and 4.155(2) Å while the Pd–Pd distances between adjacent cations are significantly shorter [3.449(2) 3.463(2) Å] (Fig. 10). Fig. 10 View of cation in [Pd2Cl2([18]aneN2S4)]1.5I5(I3)2 The infinite chains of binuclear dications are embedded into a unique polyiodide matrix whose fundamental units are one L-shaped I52 ion consisting of an asymmetric I32 [I(1)–I(2) = 2.845(2) I(2)–I(3) = 3.045(2) Å < I(1)–I(2)–I(3) = 179.69(9)°] and a di-iodine molecule [I(10)–I(11) = 2.775(3) Å] linked by I(3)–I(10) = 3.349(2) Å and forming an I(2)–I(3)– 199 Chemical Society Reviews 1998 volume 27 I(10) angle of 90.00(6)° and two slightly asymmetric I32 ions [I(4)–I(5) = 2.904(2) I(5)–I(6) = 2.959(2) Å I(4)–I(5)–I(6) = 176.47(6)°; I(7)–I(8) = 2.948(2) I(8)–I(9) = 2.929(2) Å I(7)–I(8)–I(9) = 171.58(5)°].The I32 ions including those belonging to the I52 units lie on parallel planes and form unprecedented continuous planar two-dimensional layers. Each layer [Fig. 11(a)] consists of alternating fused ribbons of 14-membered and 24-membered rings with contacts among the Fig. 11 (a) View of polyanion in [Pd2Cl2([18]aneN2S4)]1.5I5(I3)2 showing two-dimensional layers comprising linked I32 anions form alternating fused ribbons of 14-membered and 24-membered rings. I(1)–I(2) = 2.845(2) I(2)–I(3) = 3.045(2) I(4)–I(5) = 2.904(2) I(5)–I(6) = 2.959(2) I(7)–I(8) = 2.948(2) I(8)–I(9) = 2.929(2) I(10)–I(11) = 2.775(3) I(3)–I(10) = 3.349(2) I(3)···I(6) = 4.217(2) I(3)···I(7) = 4.184(2) I(6)···I(7) = 4.006(2) I(1)···I(9i) = 3.812(2) I(4)···I(4ii) = 4.017(2) I(9)···I(9iii) = 3.758(2) I(6)···I(11iv) = 3.579(2) Å.Symmetry operations i = x 2 1 y 2 1 1 + z; ii = 1 2 x 1 2 y 1 2 z; iii = 2 2 x 1 2 y 2z; iv = 2 2 x 2y 1 2 z. (b) Alternate view of polyanion in [Pd2Cl2([18]aneN2S4)]1.5I5(I3)2. The poly-I32 layers are linked by di-iodine bridges which link two 14-membered rings through a 24-membered ring. Open circles identify the basic I8 22 unit. Chemical Society Reviews 1998 volume 27 200 I32 ranging from 3.758(2) to 4.217(2) Å. Pairs of parallel I2 molecules [I2···I2 = 4.257(2) Å] from two symmetry-related I52 fragments lie orthogonal to the two-dimensional layers and connect two of these by passing through the centres of the 24-membered rings of a third layer located in between them [Fig.11(a) and (b)]. The connection of two alternating layers takes place through an I52···I32 interaction of 3.573(2) Å so that an overall I8 22 [shown as open circles in Fig. 11(b)] can be envisaged as the yarn interlocking the infinite two-dimensional poly-I32 sheets. The 24-membered rings of each layer measure ca. 25.31 3 13.31 Å the dimensions of each half [ca. 12.65 3 13.31 Å] are similar to those of the 14-membered rings [ca. 12.18 314.73 Å] resulting in channels along the body diagonal of the unit cell. These channels are occupied by the chains of hydrogen-bonded binuclear complexes described above (Fig.10) to give a pseudo-rotaxane structure (Fig. 12) and it appears that it is these chains rather than the individual dication which act as the template for the polyiodide architecture.36 Fig. 12 View of overall structure of [Pd2Cl2([18]aneN2S4)]1.5I5(I3)2. Chains of [Pd2Cl2([18]aneN2S4)]2+ dications occupy channels in the threedimensional polyiodide network in [Pd2Cl2([18]aneN2S4)]1.5I5(I3)2. 2.4.2 [Pd2Cl2([18]aneN2S4)](I3)2 The elongated plates obtained from the same reaction above give a much simpler structure even although the complex cation is the same.33 The asymmetric unit consists of half of a 2Cl2([18]- 2S4)]1.5I5(I3)2 but it does not generate infinite poly-cation [Pd2Cl2([18]aneN2S4)]2+ cation and one slightly asymmetric I32 anion [I(1)–I(2) = 2.8649(6) I(2)–I(3) = 2.9889(5) Å < I(1)–I(2)–I(3) = 174.55(2)°].The geometry of the dinuclear PdII complex is similar to that observed in [Pd aneN chains through hydrogen-bonding. Instead the I32 ions form polymeric sinusoidal chains in the crystal lattice via head-to-tail I32···I32 interactions of 4.0236(6) Å. These chains propagate along the (100) direction and are linked together by dinuclear Pd complex units via Pd···I contacts of 3.5429(6) Å [Fig. 13(a) (b)]. As shown in Fig. 13(a) the dications are arranged in an alternating side-to-side arrangement along the poly-I32 chains giving rise to infinite two-dimensional undulating layers [Fig. 13(b)]. 5)5]I12 {[M([16]aneS2)]2I}(I5)2I (M = Pd Pt) and 2.5 [RhCl2([16]aneS4)]PF6 The RhIII complex [RhCl2[16]aneS4]+ allowed variation of both the overall charge of the metal cation and its shape compared to the above PdII and PtII complexes.In fact the presence of the two co-ordinated chloride ligands gives an overall ellipsoidal shape to the [RhCl2([16]aneS4)]+ cation and furthermore does not allow interactions between the metal centre and I2 or I2. Such interactions are observed in the structures of [Ag2([15]- aneS [Pd2Cl2([18]aneN2S4)](I3)2 described above and may play an important role in the overall organization of these polyiodide arrays. The reaction of [RhCl2([16]aneS4)]PF6 with three molar 2 in MeCN solution afforded dark crystalline equivalents of I blocks after slow evaporation of the solvent.A structure determination showed the compound to have the formulation [RhCl2([16]aneS4)]I5I2.33 As for its parent PF62 complex,28 the RhIII ion has a distorted octahedral geometry being bound to all 52 four S-donors of the thioether macrocycle in an equatorial plane and to two chloride ligands in trans-axial positions [Rh–S = 2.352(4)–2.361(4) Rh–Cl = 2.330(3) Å]. The [RhCl2([16]aneS4)]+ cations are encapsulated within a threedimensional polymeric polyiodide matrix made up of I52 anions and slightly elongated I2 molecules [I(6)–I(7) = 2.732(2) Å]. The I52 ions consist of an asymmetric I32 [I(3)–I(4) = 2.962(2) I(4)–I(5) = 2.884(2) Å < I(3)–I(4)–I(5) 175.18(5)°] and a di-iodine molecule [I(1)–I(2) 2.752(2) Å] linked by I(2)–I(3) [3.172(2) Å] and forming an angle I(2)–I(3)–I(4) of 103.01(5)° (Figs.14 and 15). Puckered anionic layers can be identified within the polyiodide network in the crystal lattice. They are composed of I32 from the I52 fragments and the I(6)–I(7) di-iodine molecules to form 4- 10- and 12-membered polyiodide rings through I···I interactions of 3.336(2)–4.133(2) Å (Fig. 14). These two-dimensional infinite sheets stack along the (001) direction such that the 10-membered rings in one layer lie approximately above and below the 12-membered rings of the adjacent layers. The I(1)–I(2) molecules from the I fragments link consecutive anionic layers through I···I bridging interactions of 4.106(2) Å to form very irregular cages (Fig. 15). The four vertical edges of each cage are made up of four bridging I2 units whereas the upper and lower faces each consists of one four- and one ten-membered ring.The cages have dimensions ca. 11.14 3 9.09 3 8.03 Å and the guest [RhCl2([16]aneS4)]+ cation is located centrally within this cavity. 2.6 [K([15]aneO5)2]I ([15]aneO5 = 1,4,7,10,13-pentaoxacyclopentadecane) In order to determine whether other types of metal macrocyclic complexes could have the same templating effect on the selfassembly of polyiodide arrays we treated the potassium complex [K([15]aneO5)2]I with an excess of I2 in MeCN. After a few days dark crystals were obtained by slow evaporation of the solvent. The crystal structure determination established the formulation [K([15]aneO5)2]I9.36 Within the cation two molecules of the crown ether sandwich one K+ ion within a ten coordinate environment with K–O bond distances in the range 2.62(2)–3.21(2) Å.These cations are embedded into a threedimensional polyiodide matrix made up of nona-iodide units (Fig. 16). Each I92 ion can be described as an [I32·(I2)3] chargetransfer complex with the three perturbed I2 molecules showing intermolecular distances ranging from 2.716(3) to 2.740(4) Å and interacting with the slightly asymmetric I32 [I(7)–I(8) = 2.874(3) I(8)–I(9) = 2.978(3) Å < I(7)–I(8)–I(9) = 178.2(1)°] through bonding contacts of 3.396(4)–3.503(4) Å. Two of the three I2 molecules [I(5)–I(6) and I(3)–I(4)] and the I32 ion [I(7)–I(8)–I(9)] lie approximately in the same plane whereas the third I2 molecule [I(1)–I(2)] is perpendicular to it [ < I(1)–I(9)–I(8) = 92.4 < I(1)–I(9)–I(3) = 97.6°].This configuration for the I92 polyiodide ions allows them to form a three-dimensional network of puckered cube-like cages through I···I interactions of 3.732(4)–4.074(4) Å (Fig. 17). Each cage measures 9.658 3 9.521 3 9.959 Å the diagonals across are 17.371 and 17.393 Å and the [K([15]crownO5)2]+ cations lie almost at the centre of the cages. This polyiodide array is surprisingly similar to the ideal cubic polyiodide network in [Ag([18]aneS6)]I7 the main difference being the extra I2 molecule of the I92 ion located in the middle of the lower face of each cage reflecting the different topologies of the AgI and KI complexes (Fig. 5 and 17).There is therefore a clear link between the templating of I72 vs. I92 anions. The puckered cube-like cages are arranged in a centred lattice and in projection along the crystallographic (100) axis each cage can be seen to lie above the midpoint of four cages in the layer below. Furthermore it is clear that the concept of self-assembly of polyiodide arrays is not restricted to transition metal thioether and aza macrocyclic complexes but can in principle be extended to any complex cationic system. 201 Chemical Society Reviews 1998 volume 27 Fig. 13 (a) View of [Pd2Cl2([18]aneN2S4)](I3)2 showing polymeric sinusoidal chains of I32 ions cross-linked by [Pd2Cl2([18]aneN2S4)]2+ dications I(1)–I(2) = 2.8649(6) I(2)–I(3) = 2.9889(5) Å. (b) View of [Pd2Cl2([18]aneN2S4)](I3)2 projection onto the (011) plane.Fig. 14 View of polyanion in [RhCl2([16]aneS4)]I5I2 showing the puckered anionic layer within the polyiodide network sharing 4- 10- and 12-membered rings I(5)···I(7i) = 3.336(2) I(5)···I(7ii) = 4.133(2) I(3)···I(3iii) = 3.871(2) Å. i = 2x 1 2 y 2z; ii = x 2 1 + y z; iii = 1 2 x 1 2 y 2z. Chemical Society Reviews 1998 volume 27 202 3 FT-Raman spectroscopy When dissolved in solvents such as CHCl3 CH2Cl2 CCl4 and heptane I2 normally interacts with molecules (D) containing Group V and Group VI donor elements (N P O S Se) to give charge-transfer (CT) complexes via an acid–base equilibrium reaction.38 In the solid state a variety of products is observed (D·I2 C–T complexes D·nI2 C–T complexes hypervalent compounds characterised by the I–D–I group iodonium salts polyiodides and mixed-valence compounds) depending upon the nature of the donor atom the solvent and the reaction molar ratio.5,38 This great variability of products calls for other techniques for their identification; this is particularly necessary when X-ray crystal structure determination is not available.Raman spectroscopy has been used widely for this purpose and it provides a simple way to obtain qualitative information on the nature of iodine in the crystal lattice. Fig. 15 View of [RhCl2([16]aneS4)]I5I2 showing the puckered polyiodide cages enclosing the metal cations I(1)–I(2) = 2.752(2) I(2)–I(3) = 3.172(2) I(1)···I(7iv) = 4.106(2) I(3)–I(4) = 2.962(2) I(4)–I(5) = 2.884(2) I(3)···I(6) = 3.776(2) I(6)–I(7) = 2.732(2) Å iv = 1/2 + x 1/2 2 y 1/2 + z Fig.16 View of [K([15]aneO5)2]I9 along the crystallographic c axis In the past resonance Raman (RR) spectroscopy has been widely employed and the assignment of typical spectra to polyiodides have been generally made on model compounds which had been previously structurally characterized by X-ray diffraction.19 However RR uses visible laser excitation sources which may induce fluorescence sample pyrolysis or photoreactions so that spurious peaks can appear in the spectrum.19 This is a real possibility for polyiodides which absorb strongly in the visible region (where RR laser sources emit) and those with and the formation of I high iodine content are potentially prone to decomposition to give I2 I2 and I32 as final products.19 This decomposition causes changes in the Raman spectrum due to elimination of I2 32 which may be incorrectly assigned to the starting polyiodide material.Recently introduced Fourier transform Raman spectrometers use a near-infrared laser excitation source and thereby reduce or eliminate the above problems so that the resulting spectra can be more confidently attributed to the starting compound.19 Fig. 17 View of one polyiodide cage in [K([15]crownO5)2]I9 I(1)–I(2) = 2.740(4) I(3)–I(4) = 2.716(3) I(5)–I(6) = 2.728(4) I(7)–I(8) = 2.874(3) I(8)–I(9) = 2.978(3) I(1)···I(9) = 3.503(4) I(3)···I(9) = 3.396(4) I(7)···I(6) = 3.346(4) Å 3.1 Neutral charge-transfer complexes The n(I–I) Raman band at 180 cm21 for I2 in the solid state [d(I–I) = 2.715 Å] is expected to move to lower frequencies when I2 interacts with donor molecules to form CT-adducts.Donation of electron density occurs from a non-bonding orbital on the donor atom into the LUMO of the I2 molecule as this LUMO is an antibonding s* orbital lying along the interatomic axis the net bond order decreases and a longer bond distance is observed within the perturbed I2 molecule. The lowering of the FT-Raman frequencies n(I–I) upon formation of CT complex occurs for all the adducts in which the I2 unit can be considered a perturbed diatomic molecule (weak or medium-weak complexes) irrespective of the nature of the donor atom. In this case a linear relationship has been found to exist between the FTRaman frequencies n(I–I) and the d(I–I) bond distances.39 In order to differentiate weak or medium-weak adducts from strong complexes a useful criterion is based on the value of the I–I bond order (n) calculated as a function of the I–I bond lengthening according to the equation d = do 2 clogn (d and do are the I–I bond distances in co-ordinated and free I2 respectively and c = 0.85 Å is an empirical constant).39 For values of n higher than 0.6 the I2 moiety in the CT complexes may be considered a perturbed diatomic molecule and a band in the range 180–150 cm21 is expected in the FT-Raman spectrum.This hypothesis is supported by the observation that polyiodides which may be described as weak or medium-weak adducts of the type I2·(I2)n give very similar FT-Raman spectra and the recorded frequencies fit the linear correlation n(I–I) versus d(I–I).19 When the interaction between a donor molecule and I2 is strong (0.4 < n < 0.6) as in the case of adducts with selenium-containing molecules or in symmetric triiodide only by describing the D–I–I vibrating group as a three-body system is it possible to predict and/or assign the FT-Raman spectrum.19 3.2 Triiodides and other higher polyiodide species In the linear and symmetric I32 anion the Raman-active symmetric stretch (n1) occurs near 110 cm21 while the antisymmetric stretch (n3) and the bending deformation (n2) are only infrared-active. The latter two may also become Ramanactive if a distortion of the I32 occurs in which case they are normally found near 130 (n3) and 70 cm21 (n2) having medium and medium-weak intensities respectively.19,39 For highly asymmetric I32 ions [I2·I2] as found in neutral CT adducts the FT-Raman spectrum shows only one strong band in the range 180–150 cm21 indicative of a perturbed I2 molecule.39 203 Chemical Society Reviews 1998 volume 27 On the basis of structural determinations all the higher 52 to I16 42) may be regarded as weak polyiodide species (from I or medium-weak adducts of the type [I2·(I2)n] or [I32·(I2)n].Consequently the corresponding FT-Raman spectra will show peaks due to perturbed di-iodine molecules for [I2·(I systems and characteristic peaks due to both perturbed diiodine molecules and symmetric or slightly asymmetric I32 ions for polyiodides describable as [I32·(I2)n].39 It is therefore evident that except for symmetric I32 cases the Raman technique is unable to distinguish between the different types of polyiodides or to discriminate unambiguously between the polyiodides and the neutral adducts.However it can give valuable information on the extent of the lengthening of the I–I bond whether or not it has been produced by interaction with a neutral donor or an ion. FT Raman spectroscopy cannot give any structural information on the nature of an extended polyiodide matrix as the technique cannot elucidate the Table 1 Structural and Raman parameters for some representative polyiodides and for the polyiodides arrays synthesised by using metal macrocycle complexes as templating agents Polyiodide anion I32 (very asymm.) I52 (bent) I52 (bent) I72 I16 42 I12 22 I52 I72 I52 I52 + I32 I32 I52 + I2 I92 131 w 109 w a For polyiodides not described herein see refs 19 and 39.b Note br = broad s = strong m = medium w = weak br = broad. c The I–I bond order (n) e has been calculated using the equation d = do-clogn (do = 2.67 Å c = 0.85) ref. 19. d (EtNH2)dtl = 3,5-bis(ethylamino)-1,2-dithiolylium. moH = morpholinium. f modtc = morpholinecarbodithioato. g bntSeMe = N-methylbenzothiazole-2(3H)-selone. h mo2ttl = 3,5-bis(N-morpholinio)- 1,2,3-trithiolate. Chemical Society Reviews 1998 volume 27 204 Compounda [(EtNH2)dtl]I3 d [moH]I5 e [Mn(modtc)3]I5 f [bntSeMe)2I]I7 g [mo2ttl]2I16 h [Ag2([15]aneS5)2]I12 [Ag([9]aneS3)2]I5 [Ag([18]aneS6)]I7 [(M([16]aneS4))2I](I5)I (M = Pd Pt) [Pd2Cl2([18]aneN2S4)]1.5I5(I3)2 [Pd2Cl2([18]aneN2S4)](I3)2 [RhCl2[16]aneS4)]I5I2 [K([15]aneO5)2]I9 2)n] structure beyond the basic polyiodide unit in terms of combinations of I2 I2 and I32 fragments.In Table 1 the I–I distances the bond orders and the proposed combinations of I2 I2 and slightly asymmetric I32 are collected for some polyiodides reported in the literature19,39 as well as for the polyiodides described herein. For every compound the recorded FT-Raman spectrum is in accordance with the structural features of the basic polyiodide unit as given in the last column on the right. Further information may be extracted from the FT Raman spectrum of [Ag([18]aneS6)]I7 in which each I2 interacts with six I2 molecules arranged in D3d symmetry.Because all six I2 molecules have the same I–I bond distance only one band should be present in the FT Raman spectrum below 180 cm21. However the stretching vibrations of the six individual I2 units can combine and in D3d symmetry give rise to two Raman-active normal modes of A1g + Eg types. The 179 and 165 cm21 bands can therefore be assigned to A1g Raman data (cm21)b 167 s 164 s 135 m 106 mw 165 s 143 s 175.2 m 157.4 s 174 s 139 m 112 mw 161 ms 172 br s 162 s 151 s 179 m 165 s 157 s 149 m 168 w 147 w 138 w 108 s 130 s 108 w 172 s 126 w 107 w 180 br s Bond orderc X-Ray d(I–I)/Å 0.82 0.28 0.74 0.58 0.44 0.80–0.81 0.68–0.65 0.30–0.38 0.25–0.23 0.81 0.77 0.76 0.83 0.60 0.44 0.65 0.39 0.79 0.79 0.78 0.77 0.76 0.72 0.30 0.80 0.16 0.71 0.64 0.14 0.36 0.75 0.62 0.36 0.16 0.53(0.50) 0.46(0.47) 0.59 0.42 0.85 0.80 0.45 0.56 0.88 0.85 0.83 0.58 0.43 2.714 3.141 2.783 2.872 2.973 2.750–2.759 2.810–2.827 3.117–3.031 3.186–3.216 2.746 2.766 2.771 2.741 2.858 2.976 2.827 3.018 2.755 2.756 2.760 2.768 2.770 2.790 3.112 2.752 3.357 2.798 2.836 3.409 3.044 2.775 2.847 3.045 3.349 2.904(2.929) 2.959(2.948) 2.865 2.989 2.732 2.752 2.962 2.884 2.716 2.728 2.740 2.874 2.978 Comments I2·I2 I2 I32 (asymm.) I2·2I2 I2·3I2 (C3v symm.) I2 I32 (asymm.) I2·I2 2I2·5I2 I2·2I2 (C2v symm.) I2·3I2 (D3d symm.) I2·2I2 I2·2I2 I32 (sl.asymm.) I32 (asymm.) I2 + I32·I2 I32 (asymm.) I2 I32 (asymm.) g modes respectively. It is important to note that the 2 and E Raman spectrum of [Ag([18]aneS6)]I7 is very similar to that recorded for [(butSeMe)2I]I7 in which the I72 unit has an approximate C3v symmetry describable as [I2·(I2)3]. In the C3v point group the stretching vibrations of the three individual I molecules combine to give normal modes of A1 + E type.A slight distortion of the symmetry from C3v to Cs may redistribute the contribution of the individual I2 groups the shorter I2 unit giving a greater contribution to the higher frequency band and the longer I2 units to the lower frequency band.5 Similarly the case of the I52 ion with a C2v symmetry in [Ag([9]aneS3)2]I5 can be tackled; the vibrations of the two individual I2 units combine to give normal modes of the A1 + B2 types. A lowering of the symmetry due to different bond distances for the two perturbed I2 units will increase the energy of the higher and lower the energy of the lower energy stretch. 32 The extended interactions in the crystal lattice can play an important role in determining the intensities of the FT-Raman bands.Indeed quite surprisingly in the Raman spectrum of [Pd2Cl2([18]aneN2S4)]1.5I5(I3)2 a lower intensity is found for the peaks due to the perturbed I2 molecules compared to the intensity of the peak assigned to the symmetric stretch of the I units at 108 cm21. The FT Raman spectra have also been recorded after mixing solutions of the metal complex and diiodine for several hours. The presence of only the broad peak at around 208 cm21 due to I2 in solution clearly indicates that the template effect of the metal macrocyclic complexes takes place during the crystallization process. 4 Conclusions Although extended oligomeric anionic polyiodides are a well established aspect of the chemistry of I2 no attempts have been made previously to control their geometrical features by tuning the size shape and charge of the cation partner.On the grounds that large anions tend to be stabilised by large cations we thought that thioether macrocyclic complexes could be useful templating agents for extented polyiodide arrays they are relatively inert species and their size shape and charge can be varied readily through changes of the metal ion the macrocyclic crown and co-ligands. The results presented in this review clearly show our aim partially fulfilled. Undoubtedly the shape of the cation plays the major role on the overall templating effect. For example essentially spherical cations such as [Ag([18]aneS6)]+ and [K([15]aneO5)2]+ appear to be good template agents for cage-like polyiodide arrays.However longrange S···I and metal···I contacts can tip the balance and lead to different geometrical motifs in the resulting polyiodide arrays. The synthetic approach also has its own importance; the use of an excess of I2 instead of preformed I32 or I52 salts is recommended in the first instance with the preferred polyiodide nuclearity being formed by self-assembly. Once the preferred nuclearity is known high yielding routes can be developed by the use of preformed I32 or I52 salts and titration with I2. The use of thioether macrocyclic and related protected complexes appears to be a promising way to template-synthesize extended polyiodide matrices and to control their geometrical features. Moreover these results suggest that shape-selectivity can be achieved via template synthesis of for example helicate polyanions at helicate metal-complexes and related hosts.5 Acknowledgements We thank the EPSRC and the University of Nottingham for support. Figures 4 5 12 and 16 have been reproduced with permission. 6 References 1 K.-F. Tebbe in Polyhalogen cations and Polyhalide Anions. Homoatomic Rings Chains and Macromolecules of Main-Group Elements ed. A. L. Rheingold Elsevier Amsterdam 1977 p. 551. 2 J. R. Ferraro and J. M. Williams in Introduction to Synthetic Electrical Conductors Academic Press New York 1987. 3 T. L. Hendixson M. A. ter Horst and R. A. Jacobson Acta Crystallogr. Sect. C 1991 47 2141. 4 R. Poli J. C. Gordon R. K. Khanna and P. E. Fanwick Inorg. Chem. 1992 31 3165.5 F. Demartin P. Deplano F. A. Devillanova F. Isaia V. Lippolis and G. Verani Inorg. Chem. 1993 32 3694. 6 M. W. Renner K. M. Barkigia Y. Zhang C. J. Medforth K. M. Smith and J. Fajer J. Am. Chem. Soc. 1994 116 8582. 7 P. C. Junk L. R. MacGillivray M. T. May K. D. Robinson and J. L. Atwood Inorg. Chem. 1995 34 5395. 8 P. K. Hon T. C. W. Mak and J. Trotter Inorg. Chem. 1979 18 2916. 9 A. J. Jircitano M. C. Colton and K. B. Mertes Inorg. Chem. 1981 20 890. 10 U. Behrens H. J. Breunig M. Denker and K. H. Ebert Angew. Chem. Int. Ed. Engl. 1994 33 987. 11 K.-F. Tebbe M. El Essawi and S. Abd El Khalik Z. Naturforsch. Teil B 1995 50 1429 and references therein. 12 W. J. James R. J. Hach D. French and E. R. Rundle Acta Crystallogr. 1955 8 814.13 F. Bigoli F. Demartin P. Deplano F. A. Devillanova F. Isaia V. Lippolis M. L Mercuri M. A. Pellinghelli and E. F. Trogu Inorg. Chem. 1996 35 3195. 14 K.-F. Tebbe and A. Kavoosian Z. Naturforsch. Teil B 1993 48 438. 15 K.-F. Tebbe and T. Gilles Z. Anorg. Allg. Chem. 1996 622 138. 16 F. Bigoli M. A. Pellinghelli G. Crisponi P. Deplano and E. F. Trogu J. Chem. Soc. Dalton Trans. 1985 1349. 17 K.-F. Tebbe and T. Farida Z. Naturforsch. Teil B 1995 50 1440. 18 K.-F. Tebbe and R. Buchem Angew. Chem. Int. Ed. Engl. 1997 36 1345. 19 P. Deplano F. A. Devillanova J. R. Ferraro M. L. Mercuri V. Lippolis and E. F. Trogu Appl. Spectrosc. 1994 48 1236 and refs. therein. 20 F. H. Herbstein G. M. Reisner and W. Schwotzer J. Inclusion Phenom.1985 3 173. 21 K.-F. Tebbe and T. Farida Z. Naturforsch. Teil B 1995 50 1685. 22 K.-F. Tebbe and M. Bittner Z. Anorg. Allg. Chem. 1995 621 218. 23 E. E. Havinga and E. H. Wiebenga Acta Crystallogr. 1958 11 733. 24 O. Hassel and H. Hope Acta Chem. Scand. 1961 15 407. 25 J. C. Slater Acta Crystallogr. 1959 12 197. 26 A. J. Jircitano and K. B. Mertes Inorg. Chem. 1983 22 1828. 27 A. J. Blake F. Cristiani F. A. Devillanova A. Garau L. M. Gilby R. O. Gould F. Isaia V. Lippolis S. Parsons C. Radek and M. Schr�oder J. Chem. Soc. Dalton Trans. 1997 1337 and references therein. 28 A. J. Blake and M. Schr�oder Adv. Inorg. Chem. 1990 35 1 and references therein. 29 A. J. Blake D. Collison R. O. Gould G. Reid and M. Schr�oder J. Chem. Soc. Dalton Trans. 1993 521. 30 A. J. Blake R. O. Gould W.-S. Li V. Lippolis S. Parsons C. Radek and M. Schr�oder Inorg. Chem. submitted. 31 S. Menon and M. V. Rajasekharan Inorg. Chem. 1997 36 4983. 32 A. J. Blake R. O. Gould S. Parsons C. Radek and M. Schr�oderhem. Int. Ed. Engl. 1995 34 2374. 33 A. J. Blake W.-S. Li V. Lippolis S. Parsons and M. Schr�oder Acta Crystallogr. Sect C. 1998 54 299 and papers in the press. 34 A. J. Blake V. Lippolis S. Parsons and M. Schr�oder Chem. Commun. 1996 2207. 35 A. J. Blake M. J. Bywater R. D. Crofts A. M. Gibson G. Reid and M. Schr�oder J. Chem. Soc. Dalton Trans. 1996 2979. 36 A. J. Blake W.-S. Li V. Lippolis S. Parsons C. Radek and M. Schr�oder Angew. Chem. 1998 37 293. 37 A. J. Blake G. Reid and M. Schr�oder J. Chem. Soc. Dalton Trans. 1990 3363. 38 F. Demartin F. A. Devillanova F. Isaia V. Lippolis and G. Verani Inorg. Chim. Acta 1997 255 203 and references therein. 39 P. Deplano F. A. Devillanova J. R. Ferraro F. Isaia V. Lippolis and M. L. Mercuri J. Appl. Spectrosc. 1992 11 1625 and references therein. Received 19th June 1997 Accepted 5th January 1998 205 Chemical Society Reviews 1998

ISSN:0306-0012    

DOI:10.1039/a827195z

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Tropic acid ester biosynthesis in Datura stramonium and related species David O’Hagana and Richard J. Robinsb a Department of Chemistry University of Durham Science Laboratories South Road Durham UK DH1 31E b etabolismes CNRS UPRES-A 6006 Universit Laboratoire d’Analyse Isotopique et Electrochimique de M� e de � Nantes D�epartement de Chimie 2 rue de la Houssiniere 44072 Nantes cedex 03 France The origin of the tropic acid ester moiety found in some of the tropane alkaloids but particularly in hyoscyamine and scopolamine has been a subject of discussion and investigation in biosynthesis for many years. Recently it has been shown in Datura stramonium root cultures that hyoscyamine arises by isomerisation of the tropane alkaloid littorine. The mechanism of this isomerisation process is not obvious and in this review we present our recent results and current thinking on this process.1 Introduction In the last few years new experimental evidence has forced a reevaluation of the biosynthesis of the tropate ester moiety of the tropane alkaloids hyoscyamine and scopolamine. Robert Me N Me N O O O O O 1' 3' 2' OH OH scopolamine hyoscyamine David O’Hagan was born in Glasgow in 1961. He was an undergraduate at the University of Glasgow (1982) and carried out his doctoral research (1985) on antibiotic biosynthesis at the University of Southampton with Professor John A Robinson. After a postdoctoral year with Professor Heinz G Floss (Ohio State University) he took up a position at the University of Durham where he is now a Senior Lecturer.His main research interests are in the biosynthesis of secondary metabolites and in bio-organic fluorine chemistry. Richard J. Robins David O’Hagan CD3 N O O um OH hyoscyamine Robinson recognised in 19281 that the tropate ester is an isomer of the phenylpropionoid skeleton a structural motif common in plant alkaloids and other plant metabolites such as the flavanoids. The phenylpropionoid moiety derives from (S)-phenylalanine and Robinson later (1955) proposed2 that tropic acid may originate by a rearrangement of the phenylpropanoid skeleton. In a definitive experiment twenty years later (Scheme 1) Leete demonstrated3 in Datura innoxia plants that (R,S)- phenyl[1,3-13C2]alanine was indeed incorporated intact into the tropate moiety of hyoscyamine.Importantly this experiment demonstrated an intramolecular rearrangement where the two isotopes became contiguous in the resultant tropate. Thus the origin of the tropate ester from phenylalanine was established. A number of intriguing questions remained however concerning this conversion. Although phenylalanine is a good precursor the true substrate for the rearrangement and the stereochemistry remained ill-defined until recently. The rearrangement belongs to a small class of enzyme-mediated carbon skeletal isomerisations and the mechanism of these enzymes has attracted wide interest. The rearrangement has a RO O O D. innoxia O– plants OH NH3 + ( RS)-phenyl[1,3-13C2] alanine Scheme 1 Richard J.Robins read Biochemistry at the University of Oxford (1971–75) and carried out doctoral work on the digestive processes of carnivorous plants with Dr B. E. Juniper University of Oxford. After a post-doctoral study of the mechanism of amino acid absorption with Professor D. D. Davies (University of East Anglia) he joined (1981) the AFRC Institute of Food Research to study the biosynthesis and control of secondary product formation in plant tissue cultures. In 1995 he moved to Nantes to become Director of the CNRS Unit of Isotopic and Electrochemical Studies of Metabolism. His current research interests include the biosynthesis of secondary metabolites and the use of natural-abundance isotopic techniques to study metabolism.207 Chemical Society Reviews 1998 volume 27 superficial similarity to those mediated by some co-enzyme B12-dependant mutases however the process does not appear to be B12-dependent. 2 Plants and transformed roots of Datura stramonium Much of the recent work on the biosynthetic origin of tropic acid has exploited transformed root cultures as experimental material. These cultures are generated by infecting the lightlydamaged surface of sterile leaf or stem from tropic acidproducing plants such as D. stramonium with a suspension of the pathogenic bacterium Agrobacterium rhizogenes. The bacterium inserts into the plant cells a short section of DNA (the Ri-DNA) which stimulates cell division to cause root formation.The emergent roots can be removed treated with antibiotic to kill the remaining bacteria and cultured in perpetuity in a sterile liquid medium. A small part of the culture is transferred to fresh medium every two or three weeks (see ref 4 for a review of the properties of these cultures). Figure 1 This system offers many advantages over the use of whole plants; * large amounts of genetically identical material can be generated. * the roots grow at a constant rate. * the experiment is conducted under asceptic conditions. * precursors can readily be added and their absorption by the tissue monitored directly and multiple additions can be made. * experiments can be conducted on small amounts of material allowing considerable savings on the quantity of isotopically labelled precursor required.* very high specific incorporations can be obtained rendering analysis by GCMS and NMR relatively straightforward. Chemical Society Reviews 1998 volume 27 208 Figure 2 Root cultures are not however suitable for all studies. In D. stramonium plants scopolamine is a major product in the leaves yet only traces of this alkaloid are recovered from root cultures. In other species however such as Hyoscyamus muticus or a Brugmansia hybrid scopolamine accumulates in the root cultures as a major alkaloid. A key requirement for using root cultures is that this tissue must be the site of biosynthesis in the plant. For example terpenes in Mentha species are made in leaf glands and shoot cultures5 are required in this case.3 The role of (R)-phenyllactate (S)-Phenylalanine is efficiently incorporated into the tropate ester moiety of hyoscyamine.3 Other experiments6 with 14C-labelled phenylpyruvate and phenyllactate indicated that all of these compounds become similarly incorporated into the tropate ester moiety of the alklaloids. This observation is readily rationalised if these compounds interconvert in vivo. The importance of phenyllactic acid as an intermediate was confirmed by feeding (R,S)-phenyl[1,3-13C2]lactate to D. stramonium transformed root cultures7 or plants.8 High incorporation was obtained and the observed spin-spin coupling of the two 13C nuclei in the extracted hyoscyamine7 and scopolamine8 confirmed both the intramolecular rearrangement shown by Leete3 and the putative role of phenyllactic acid in the formation of hyoscyamine.It remained therefore to identify the most direct precursor of the three. In an effort to resolve this issue we studied the incorporation of deuterium from (R,S)-[2-13C 2H]phenyllactate. If phenyllactate is oxidised to phenylpyruvate then the deuterium atom will be lost prior to incorporation into tropic acid. If however phenyllactate is utilised directly then the deuterium atom will be retained. An initial feeding experiment supplementing D. stramonium root cultures with (R,S)phenyl[2-13C,2H]alanine resulted9a in a substantial retention of deuterium isotope attached to carbon-13 (17%) at C-3A of the tropate ester moiety of hyoscyamine.In a further experiment9b resolved (R)- and (S)-phenyl[2-13C 2H]- alanines were added to D. stramonium cultures. Feeding the (R)-isomer resulted in hyoscyamine showing retention of the dual 13C-2H isotopes (28.9%) indicating that the bond had remained intact during the biosynthesis. For the (S)-isomer there was a significant 13C-enrichment but all of the deuterium was lost indicating that this bond had been broken during hyoscyamine formation. These results demonstrate that (R)- and not (S)-phenyllais the stereoisomer used during the biosynthesis. (S)-Phenyllactate must be converted to the 13 (R)-isomer presumably via phenylpyruvate prior to incorporation into tropic acid. The experiment also established that the C-2 hydrogen atom of (R)-phenyllactate is retained during the rearrangement.Experiments using (R)- and (S)-phenyl[1,3- 2]lactates fed to whole plants10 have also indicated on the C basis of differential incorporation levels that only the (R)- isomer is the precursor of hyoscyamine and scopolamine. 4 Stereochemistry of the rearrangement During the rearrangement of phenyllactate to tropate two bonds are broken and two are formed. In a given reaction bonds are normally broken/formed with either retention or inversion of configuration. A recent stereochemical analysis11 on tropate biosynthesis has revealed that both of the bonds are broken/ formed with inversion of configuration. O O– NH3 + ( S)-phenylalanine O O– O –D phenylpyruvate –D O O– D OH ( R)-phenyl[2-13C]lactate ( R)-phenyl[2-13C 2H]lactate RO O D OH 13C - 2H-labelled tropate Scheme 2 Firstly radiolabelled phenyl[2-3H]lactate was incubated with D.stramonium root cultures.11a The resultant hyoscyamine retained tritium at the 3-pro-S position of the tropate ester. This conclusion was drawn after diluting the isolated hyoscyamine with ‘cold’ unlabelled alkaloid and converting the carbon atom carrying the tritium into a chiral methyl group by introduction of deuterium in a stereospecific manner. The strategy is shown in Scheme 3. Oxidation of 2-phenylpropanol carrying the chiral methyl group generated a sample of chiral acetic acid. Although O O– OH D ( S)-phenyl[2-13C 2H]lactate O O– H OH RO O H OH 13C - labelled tropate cold carrier was added such that sufficient material could be manipulated through the derivatisation protocol it is important to note that all of the molecules carrying tritium had come through the biosynthetic experiment and that only these molecules give rise to chiral acetic acid.Enzymatic assay of the resultant chiral acetic acid indicated that the methyl group had an R-configuration (98% ee). Thus by deduction the tritium must have occupied the 3-pro-S site in the hyoscyamine isolated after the biosynthetic experiment. In view of the fact that (R)- and not (S)-phenyllactate is utilised then it was concluded that there is an overall inversion of configuration at this centre during the rearrangement.Me N O D. stramonium O O– O OH T T OH 50 mgs isolated of 1 500 mgs cold carrier Ba(OH) CH2N2 2 Mesyl Cl MeO MeO O O DMAP T T O-SO2Me OH 78% LiAlD4 stereochemical inversion D HO D O H KIO4 H HO T T KMnO4 D D 82% 16%, (98%ee) ( R)-acetic acid 6.0 mCi mmol Scheme 3 The stereochemistry at the other migration terminus was established after feeding experiments with (2R,3R)- and (2R,3S)-phenyl[3-2H]lactates. In the event only deuterium from 3-pro-S (2R)-phenyllactate was retained. However this deuterium –carbon bond had become configurationally inverted in the resultant hyoscyamine. In the complementary experiment the 3-pro-R hydrogen was lost during the rearrangement.With this information we concluded that the bond breaking/forming at this carbon atom proceeds with an inversion of configuration. The overall stereochemical course of the rearrangement is summarised in Scheme 4 inversion of configuration occurring at both migration termini. This study has corrected a previous stereochemical analysis12 of this system in plants and supported an even earlier study by Haslam13 who also showed an inversion of configuration at C-2 of the tropate ester. 209 Chemical Society Reviews 1998 volume 27 inversion RO O O HS HS HR H* OR OH H* HO inversion HR Scheme 4 5 Substrate for the rearrangement process The above experiments proved a clearly defined role for (R)- phenyllactate in the biosynthesis of the tropate ester moiety.However the true substrate for the putative isomerase is not free (R)-phenyllactate. It is poignant that the co-produced alkaloid littorine the tropine ester of (R)-phenyllactate is found widely in tropane-alkaloid forming species. So clearly (R)-phenyllactate can couple to tropine in D. stramonium raising the possibility that littorine is the substrate for the enzyme. Indirect evidence to support this conclusion was obtained from experiments7 in which added unlabelled tropic acid failed to diminish the incorporation of label from (R,S)- phenyl[1,3-13C2]lactate. Thus free tropic acid was found unlikely to be an intermediate of hyoscyamine formation. Similarly 14C-tropic acid was found14 to be a very poor precursor for hyoscyamine compared with 14C-phenylalanine in root cultures of Duboisia leichhardtii.The role of littorine as a direct precursor of hyoscyamine was established in an experiment14 using littorine isotopically labelled in both the tropane ring and the tropate ester moiety. This study demonstrated unequivocally that littorine can rearrange in vivo to hyoscyamine. The precursor littorine was labelled by incorporating three 2H nuclei in the N-methyl of the tropine moiety and two 13C nuclei in the phenyllactoyl moiety (Scheme 5). A specific incorporation into hyoscyamine of between 4.5 and 6.5% of the quintuply-labelled molecule was measured by GCMS analysis. Some hydrolysis of littorine occurred resulting in labelling of both tropine (at the M + 3 ion) and phenlylactate methyl ester (at the M + 2 ion).From the percent isotopic excess in these products it could be estimated however that a route involving hydrolysis of the ester followed by reincorporation could only account for about 0.2% isotopic excess in the isolated hyoscyamine. Furthermore neither added cold tropine nor phenyllactate diluted the percent isotopic incorporation. Confirmation that the rearrangement is intramolecular was shown by NMR the isolated hyoscyamine showing a high level of 13C spin-spin coupling due to the adjacent enriched nuclei at the C-1A and C-2A positions. Thus after many years of speculation the substrate for the isomerisation is now established as the tropane alkaloid littorine. CD3 CD3 N N O O O D.stramonium O OH OH hyoscyamine littorine Scheme 5 6 Some ideas on the mechanism of rearrangement There is a superficial similarity between co-enzyme B12 processes and the rearrangement of littorine to hyoscyamine. However in the related co-enzyme B12 processes a vicinal Chemical Society Reviews 1998 volume 27 210 interchange process is apparent. This is illustrated typically for (R)-methylmalonyl-CoA mutase15 in Scheme 6 where the thioester carboxylate migrates to the vicinal carbon and the hydrogen that is removed from this carbon is relocated at the O SCoA SCoA methylmalony-CoA mutase co-enzyme B12 O H O– H O– 1,2-vicinal interchange O O succinyl-CoA R-methylmalonyl-CoA Scheme 6 original carboxy site.It had been reported12 that the hydrogen at C-3 (of phenyllactate) which is removed during the process was relocated at the C-3A position of hyoscyamine. This conclusion was drawn after a 3H/14C labelling study and the observation of an apparent vicinal interchange process clearly implied a role for co-enzyme B12 in the rearrangement process. However our stable isotope study11b did not reveal any evidence for a vicinal interchange process i.e. the 3-pro-R hydrogen of littorine is not relocated at the 3-pro-R site of hyoscyamine. This observation and the apparent lack of coenzyme B12 in plants lays to rest the putative involvement of this co-factor. In many plant systems iron-oxo species operate to generate radicals.For example Sankawa has shown16 that the isoflavone synthase of Pueraria lobata cell cultures is a cytochrome P450-mediated reaction as illustrated in Scheme 7. An important OH Fe(V)=O OH Fe(IV)-OH HO O O HO O O OH HO O O HO Fe(IV)-OH Fe(III) • oxygen rebound O O OH OH 2,7,4'-trihydroxyflavanone –H2O dehydratase O HO O OH daidzein Scheme 7 • rearrangement observation in that system is the ‘oxygen rebound’ process where it is proposed that the rearranged radical is quenched by an hydroxyl radical from Fe(iv)-OH to generate 2,7,4A-trihydroxyisoflavone. In cell free extracts this intermediate was isolable and the new hydroxy group was labelled from 18O2. A dehydratase then acts to generate the isoflavanone daidzein.We have recently demonstrated that the P-450 inhibitor chlotrimazole appears to inhibit the conversion of littorine to O O– HO D D. stramonium Me N Me N D. stramonium O O O 25-29% loss D O oxygen-18 HO D OH littorine hyoscyamine 71-75% retention Scheme 8 hyoscyamine17 in roots of D. stramonium. So it became relevant to explore the possibility of an oxygen rebound process operating in the rearrangement of littorine to hyoscyamine. Our most recent results18 utilising (R,S)-phenyl[2-2H,18O]lactate have shed some light on this issue but do not provide convincing evidence for an oxygen rebound process operating during the rearrangement of littorine to hyoscyamine. After supplementing D. stramonium cultures with (R,S)-phenyl[2- 2H,18O]lactate as shown in Scheme 8 GCMS analysis demonstrated that both littorine and hyoscyamine had enriched M + 3 ions showing that the oxygen-18 and deuterium atoms were both incorporated but to different extents in each of the metabolites.The relative ratio of M + 1 (2H only) to M + 3 (18O + 2H) in the molecular ions of hyoscyamine and littorine demonstrated that ~ 71–75% of the oxygen-18 was retained and recriprocally that ~ 25–29% of the oxygen-18 was lost during the conversion from littorine to hyoscyamine. This can be accounted for by several mechanistic possibilities as illustrated in Schemes 9 10 and 12. A process initiated by iron-oxo abstraction of hydrogen will generate a substrate radical. Rearrangement to a product radical followed by oxygen rebound in the classical manner [Scheme 9 and process (a) Scheme 10] would then generate an aldehyde hydrate as an intermediate.If this is the case then the collapse of this hydrate to an aldehyde prior to reduction by a dehydrogenase may be partially stereospecific as only ~ 25–29% of the original C-2A oxygen of littorine is lost or fully stereospecific forwarding retention of the labelled oxygen with loss of isotope occurring by exchange of the aldehyde oxygen with the aqueous medium prior to reduction. A non-ster- 2 1 Fe(V)=O CO2R • CO2R isomerisation HO Fe(IV)-OH Fe(IV)-OH Scheme 9 • OH O eospecific process would lead to 50% loss and this is not observed. An alternative explanation [Scheme 9 and process (b) Scheme 10] invokes disproportionation of the putative Fe(iv)- OH intermediate and the product radical to generate an aldehyde directly.Such a conclusion has been discussed in a P-450 mediated oxidation operating during oestrogen biosynthesis19,20 where a similar level (80%) of oxygen-18 retention was observed in the oxidation of a primary alcohol to an aldehyde as shown in Scheme 11. Again the high retention of oxygen-18 here either requires a collapse of a diol hydrate (generated after oxygen rebound) or disproportionation. In the latter case the ~ 20% loss of oxygen- 18 can be accounted for by some exchange of the aldehyde carbonyl with the aqueous medium. In the light of the high level of retention of oxygen-18 in going from littorine to hyoscyamine and also in the case in Scheme 11 the oxygen rebound process perhaps appears less likely than disproportionation as it requires both systems to display the same stereoselectivity and to favour retention of the original C–O bond.Alternatively a two electron oxidation of littorine to generate a carbocation as illustrated in Scheme 12 offers an appealing mechanism. The generation of carbocations in iron-oxo systems is not judged so common but such intermediates are implicated for example during the biosynthesis of prostacylin and thromboxane, 21 in two closely related heme-thiolate enzymes. Also carbocations have been recently implicated22 in the generation of minor side products in reactions of mechanistic probes in P-450 enzyme hydroxylations.Scheme 12 illustrates a two electron oxidation of littorine 1 to a substrate carbocation. Rearrangement and the collapse of the product carbocation to an aldehyde would not require oxygen loss and is consistent with the experimental observation with labelled oxygen if accompanied by some exchange at the aldehyde level. An attractive feature here is that the substrate oxygen • OH Fe(IV)-OH a HO OH Fe(III) rebound H H + disproport- • OH O Fe(IV)-OH b Fe(III) H2O ionation H H Scheme 10 HO O P-450 80% retention oxygen-18 O O Scheme 11 CO2R dehydrogenase Fe(III) + H2O O disproportionation CO2R OH Fe(III) OH oxygen rebound 211 Chemical Society Reviews 1998 volume 27 CO2R dehydrogenase O 1 H2O Fe(V)=O (two electron oxidation) CO2R + + HO OH O Fe(III) + –OH Fe(III) + –OH Scheme 12 + cation ring opening + OMe OMe • • radical ring opening OMe OMe Scheme 13 2 CO2R isomerisation benzylic carbocation is predicted to rearrange to the more stable product carbocation,22,23 an oxonium ion.This is most clearly illustrated by the methylcyclopropane ring opening reactions of Newcomb23 shown in Scheme 13 which show a common cyclopropane ring being opened under radical and carbocation conditions. The stabilising substituents are aryl and oxygen and the system closely models the putative intermediates in the littorine to hyoscyamine rearrangement. It was demonstrated that the methylcyclopropane carbocation opens towards oxygen in the same direction as the rearrangement of littorine to hyoscyamine whereas the methylcyclopropane radical opens towards the aryl ring the opposite direction to the rearrangement.So such models suggest a carbocation process. In conclusion our working hypothesis proposes the involvement of two enzymes (mutase + dehydrogenase). The experimental evidence is consistent with an iron-oxo mutase perhaps a heme-thiolate in view of the inhibition by the P-450 inhibitor chlotrimazole17 and an analogy with carbocation generating heme-thiolate enzymes however the mechanism of the rearrangement remains elusive and must await further evaluation and in particular enzyme isolation. More generally little is known of the enzymes implicated on this biosynthetic pathway.Earlier claims made in the literature for enzyme activities that convert phenylalanine to phenylpyruvate and that esterify tropine with free tropic acid (see ref 24 for a review) have proved dubious. A transaminase for phenylalanine reported25 from Hyoscyamus albus transformed roots shows only weak activity and poor kinetic properties. Despite the efforts of several laboratories the conversion of phenylpyruvate to phenyllactate in vitro has not been demonstrated. Similarly the putative CoA-thioligase for phenyllactate and phenyllactoyl-CoA tropine acyltransferase activities have both proved ellusive. Yet these studies have used tissues from Chemical Society Reviews 1998 volume 27 212 7 Acknowledgements We are grateful to all of our co-authors but particularly to Dr Nicola C.J. E. Chesters and to Professor Heinz G. Floss Dr Jack G. Woolley and Dr Nicholas J. Walton for their contributions to the project. We also thank the CIBA foundation for an ACE award. which other enzymes,24 notably hyoscyamine 6b-hydroxylase,26 have been readily extracted and purified. A clear definition in vitro of these activities is required to confirm that the pathway of tropic acid biosynthesis proposed on the evidence of chemical labelling is indeed that which functions in planta. Received 9th January 1998 Accepted 16th January 1998 8 References 1 R. Robinson Proceedings of the University of Durham Philosophical Society 1927–1932 8 14.2 R. Robinson Structural Relations of Natural Products Clarendon Press Oxford 1955. 3 E. Leete N. Kowanko and R. A. Newmark J. Am. Chem. Soc. 1975 97 6826. 4 M. J. C. Rhodes R. J. Robins J. D. Hamill A. J. Parr M. G. Hilton and N. J. Walton in Secondary Products from Plant Tissue Culture eds. B. V. Charlwood and M. J. C. Rhodes Oxford University Press Oxford 5 A. Spencer J. D. Hamill and M. J. C. Rhodes Phytochemistry 1993 32 6 M. Ansarin and J. G. Woolley (a) Phytochemistry 1993 32 1183; (b) 7 R. J. Robins J. G. Woolley M. Ansarin J. Eagles and B. J. Goodfellow 1990 Proc. Phytochem. Soc. Europe 30 201. 911. J. Nat. Prod. 1993 56 1211. Planta 1994 194 86. 8 M. Ansarin and J. G. Woolley Phytochemistry 1994 35 935. 9 (a) N.C. J. E. Chesters D. O’Hagan and R. J. Robins J. Chem. Soc. Perkin Trans. 1 1994 1159; (b) N. C. J. E. Chesters D. O’Hagan and R. J. Robins J. Chem. Soc. Chem. Commun. 1995 127. 10 M. Ansarin and J. G. Woolley J. Chem. Soc. Perkin Trans. 1 1995 487. 11 (a) N. C. J. E. Chesters D. O’Hagan R. J. Robins A. Kastelle and H. G. Floss J. Chem. Soc. Chem. Commun. 1995 129; (b) N. C. J. E. Chesters K. Walker D. O’Hagan and H. G. Floss J. Am. Chem. Soc. 1996 118 925. 12 (a) E. Leete Can. J. Chem. 1987 65 226; (b) E. Leete J. Am. Chem. Soc. 1984 106 7271. 13 V. R. Platt C. T. Opie and E. Haslam Phytochemistry 1984 23 2211. 14 R. J. Robins P. Bachmann and J. G. Woolley J. Chem. Soc. Perkin Trans. 1 1994 615. 15 J. Retey in B12 Biochemistry and Medicine ed. D. Dolphin Wiley 1982 2 357. 16 (a) T. Hakamatsuka M. F. Hashim Y. Ebizuka and U. Sankawa Tetrahedron 1991 47 5969; (b) M. F. Hashim T. Hakamatsuka Y. Ebizuka and U. Sankawa FEBS Lett. 1990 271 219. 17 I. Zabetakis R. Edwards J. T. G. Hamilton and D. O’Hagan Plant Cell Rep. 1998 in press. 18 C. W Wong J. T. G. Hamilton D. O’Hagan and R. J. Robins Chem. Commun. 1998 in the press. 19 M. Akhtar M. R. Calder D. L. Corina and J. N. Wright Biochem. J 1982 201 569. 20 M. Akhtar and J. N. Wright Nat. Prod. Rep. 1991 8 527. 21 V. Ullrich and R. Brugger Angew. Chem. Int. Ed. Eng. 1994 33 1911. 22 M. Newcomb M. H. Le Tadic-Biadatti D. L. Chestney E. S. Roberts and P. F. Hollenberg J. Am. Chem. Soc. 1995 117 12085. 23 M. Newcomb and D. L. Chetney J. Am. Chem. Soc. 1994 116 9753. 24 R. J. Robins and N. J. Walton in The Alkaloids ed. G. A. Cordell Academic Press Orlando 1993 44 115. 25 K. Doerk Disertation zur Doktorgrades Universit�at D�usseldorf 1993 pp. 187. 26 T. Hashimoto and Y. Yamada Eur. J. Biochem. 1987 164

ISSN:0306-0012    

DOI:10.1039/a827207z

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Dielectric parameters relevant to microwave dielectric heating a Microwave Consultants Ltd. Woodford Essex UK E18 2EL b Department of Chemistry Imperial College of Science Technology and Medicine South Kensington London UK SW7 2AY Microwave dielectric heating is rapidly becoming an established procedure in synthetic chemistry. This review summarises the basic theory underlying microwave dielectric heating and collates the dielectric data for a wide range of organic solvents which are commmonly used in microwave syntheses. The loss tangents of the solvents which may be related to the ability of the solvent to absorb energy in a microwave cavity depend on the relaxation times of the Camelia Gabriel is founder and Director of Microwave Consultants Ltd. Her main research interests are concerned with the interaction of electromagnetic radiation with materials and their application in industry.Other special interests include the biological effects of electromagnetic radiation and their implications in terms of health and the safety of people. She is active in National and European committees on safe exposure to electromagnetic fields. Camelia Gabriel Edward H. Grant Sami Gabriel Sami Gabriel is an engineer in the field of Electromagnetics and Information Technology. He has carried out post-graduate research at King’s College London and Imperial College on the dielectric properties of organic and inorganic materials. He is involved in the development and implementation of a national materials database holding dielectric data on organic and inorganic materials.His commercial interests include the development of di- Camelia Gabriel,a Sami Gabriel,a Edward H. Grant,a,b Ben S. J. Halsteadb and D. Michael P. Mingosb* molecules. These relaxation times depend critically on the nature of the functional groups and the volume of the molecule. Functional groups capable of hydrogen bonding have a particularly strong influence on the relaxation times. The relaxation times of solvents decrease as the temperature of the solvent is increased. Loss tangent data at different microwave frequencies are also presented and discussed. electric measurement software and field monitoring of nonionising radiation and its implications on health and safety.Edward Grant was born in Croydon in 1931 and educated at Selhurst Grammar School and King’s College London. He obtained his PhD at the Middlesex Hospital Medical School where he worked on the dielectric properties of biological materials an area in which he is still currently active. He has been Professor (now Emeritus) of Physics in the University of London since 1974 and was Head of the Physics Department at King’s College just prior to retirement. He has spent 18 months at Imperial College working with Professor D. M. P. Mingos and is now Principal Scientific Consultant to Microwave Consultants Limited (MCL). Ben Halstead was born in Rainham Kent. He graduated from Hull University in 1994 and is currently researching dielectric heating effects in inorganic synthesis at Imperial College.Michael Mingos was born in Basrah Iraq in 1944 and was an undergraduate at UMIST. After a DPhil at Sussex University he did postdoctoral work at Northwestern University. He is currently the Sir Edward Frankland BP Professor of Inorganic Chemistry at Imperial College of Science Technology and Medicine. Ben S. J. Halstead D. Michael P. Mingos 213 Chemical Society Reviews 1998 volume 27 1 Introduction Microwave dielectric heating is a well established procedure not only for the domestic preparation of meals but also it is widely used industrially for the processing of food and industrial materials. Microwave applications have been designed for the volumetric heating of rubber wood paper and agricultural products and for the inclusion of waste materials into glasses.1 The classic work of von Hippel and his co-workers2 in the early 1950s provided a sound theoretical basis for these technological developments and his group provided an important database of dielectric properties on common substances foodstuffs and materials.3 This database has been expanded upon as the technological need arose and more recently a considerable effort has been directed towards the measurement of the dielectric properties of biological materials.4,5 This was prompted in part by a need to provide fundamental data which would underpin the public and scientific discussions concerning the health hazards6 which may arise from the interaction of electromagnetic radiation in the microwave and radio frequency ranges with biological tissues and the widespread use of electromagnetic radiation in various medical diagnostic and therapeutic procedures.The dielectric analysis of pharmaceutical materials has increased in importance in recent years and Craig has written a timely book summarising the theoretical and practical aspects of these studies.7 More recently microwave dielectric heating has attracted the attention of chemists.8 Initially the reduced time scales of chemical reactions which were performed in microwave cavities were attributed to a specific ‘microwave effect’ however more detailed reaction rate measurements have established that in general chemical reactions which occur under microwave conditions are governed by the same fundamental principles of thermodynamics and kinetics as reactions which occur under conventional conditions.9,10 A recent Chemical Society Review has given a balanced acount of these developments.11 Microwave dielectric heating has the following advantages compared to conventional heating for chemical conversions.(1) The introduction of microwave energy into a chemical reaction which has at least one component which is capable of coupling strongly with microwaves can lead to much higher heating rates than those which are achieved conventionally. (2) The microwave energy is introduced into the chemical reactor remotely and therefore there is no direct contact between the energy source and the reacting chemicals.This when combined with (1) above may lead to a significantly different temperature profile for the reaction and may lead to an alternative distribution of chemical products from a reaction. (3) Chemicals and the containment materials for chemical reactions do not interact equally with the commonly used microwave frequencies for dielectric heating and consequently selective heating may be achieved. Specifically the containment materials for a chemical reaction may be chosen in such a way that the microwave energy passes through the walls of the vessel and heats only the reactants. The very high temperatures which result when metal powders are exposed to microwave fields have been used to create ‘hot spots’ which accelerate the reactions of the metals with gases other inorganic solids and organic substrates.12 (4) These selective interactions mean that microwave dielectric heating is an ideal method for accelerating chemical reactions under increased pressure conditions.Using quite simple apparatus based either on transparent plastics e.g. Teflon or glass it is possible to increase the temperature of a reaction in common organic solvents up to 100 °C above the conventional boiling point of the solvent. For example ethanol has a conventional boiling point of 79 °C microwave dielectric heating in a closed vessel can rapidly lead to temperatures of 164 °C and a pressure of 12 atmospheres. This higher Chemical Society Reviews 1998 volume 27 214 temperature leads to a thousand-fold acceleration of the reaction rate for reactions which are studied in this solvent.13 The advantages outlined above have been exploited by chemists extensively during the last ten years and to date more than 300 papers have been published describing the applications of microwave dielectric heating to chemical problems.14 However much of the work has been empirical and qualitative.The theoretical basis of microwave dielectric heating remains poorly understood by many chemists and although the database of dielectric properties initiated by von Hippel and extended by others2 contains much information about materials and foodstuffs the data for commonly available organic solvents used for chemical reactions are not readily available to the chemical community.The recent developments in dielectric measuring techniques using wideband swept frequency instrumentation have made it relatively easy to obtain the required dielectric data in order to interpret the heating characteristics of a wide range of chemicals.15 This review has the following specific aims 1. To provide a basic introduction to dielectric theory which will enable chemists to understand at a molecular level the fundamental nature of the phenomenon which results in the heating of solutions in microwave fields. 2. To provide an interpretation of the relaxation times associated with the rotational behaviour of homologous series of solvents and account for their relative abilities to couple with microwave radiation. 3.To consider the consequences of having mixtures of solvents and salts dissolved in the solvents. 4. To define the relationships between the dielectric properties of the materials and their heating rates in commonly encountered situations. 5. To provide a database of dielectric parameters for organic solvents which are used in synthetic organic and inorganic chemistry.15–17 2 Fundamental theory5,16,17 A dielectric material is one which contains either permanent or induced dipoles which when placed between two electrodes acts as a capacitor i.e. the material allows charge to be stored and no dc conductivity is observed between the plates. The polarisation of dielectrics arises from the finite displacement of charges or rotation of dipoles in an electric field and should not be confused with conduction which results from translational motion of the charges when the electric field is applied.At the molecular level polarisation involves either the distortion of the distribution of the electron cloud within a molecule or the physical rotation of molecular dipoles. The latter are particularly significant in the context of microwave dielectric heating. The permittivity of a material e is a property which describes the charge storing ability of that substance irrespective of the sample’s dimensions. The dielectric constant or relative permittivity is the permittivity of the material relative to that of free space and Table 1 gives some representative values. It is Table 1 Value of relative permittivity (dielectric constant) at 20 °C for some common solventsa Dielectric constant (e Solvent S) 2.3 2.2 4.8 21.4 25.7 33.7 80.4 Benzene Carbon tetrachloride Chloroform Acetoneb Ethanolb Methanolb Waterb a Data have been taken from reference 7.b For those polar compounds eA is frequency dependent and the values given in the Table refer to the static value eS. noteworthy that compounds which have large permanent dipole moments also have large dielectric constants because the dielectric polarisation depends primarily on the ability of their dipoles to reorientate in an applied electric field. In the gas and liquid phases the molecules rotate so rapidly that they are normally able to respond to field reverses occurring at 106 times a second or higher but in the solid state the molecular rotations are generally restricted and therefore reorientation in an electric field does not generally contribute to the dielectric constant.If the electric field component is reversed much more rapidly e.g. at 1012 times per second even the smallest molecules are no longer able to rotate a significant amount before the electric field is reversed and the permittivity necessarily falls. Such rapid field reversals are of course produced when the material is exposed to electromagnetic radiation. The permittivity of the material is therefore frequency dependent and for a polar liquid generally shows a marked decrease as the frequency of the electromagnetic radiation increases from 106 (radio frequencies) to 1012 Hz (infrared frequencies).The precise frequency at which this falls reflects the frequency of the rotations within the molecule which in turn depends on the size of the molecule and the intermolecular forces which it experiences in solution. For polar molecules with molecular weights less than a few hundred this relaxation process occurs in the microwave region i.e. in the frequency range 300 MHz–300 GHz. The re-orientation of the dipoles and displacement of charge is equivalent to an electric currrent known as the Maxwell displacement current and named after the author of electromagnetic theory. For an ideal dielectric there is no lag between the orientation of the molecules and the variations of the alternating voltage the displacement current is 90° out-of-phase with the oscillating electric field as shown in Fig.1. The Fig. 1 Application of a sinusoidal electric field to liquid ideal dielectric (top) and the out-of-phase diplacement current which is induced (bottom) relevant phase diagram shown in Fig. 2(a) shows that for a dielectric material where the molecules can keep pace with the field changes no heating occurs. There is no component of the current in-phase with the electric field i.e. the product E 3 I is zero because of the 90° phase lag between the field and the current. If the frequency of the electromagnetic radiation is pushed up into the microwave region ( ~ 109 Hz) the rotations of the polar molecules in the liquid begin to lag behind the electric field oscillations.The resulting phase displacement d shown in Fig 2(b) acquires a component I 3 sind in phase with the electric field and so resistive heating occurs in the medium—this is described as dielectric loss and causes energy to be absorbed from the electric field. Since the dipoles are unable to follow the Fig. 2 Phase diagrams for (a) an ideal dielectric where the energy is transmitted without loss; (b) where there is a phase displacement d) and the current acquires a component I 3 sind in-phase with the voltage and consequently there is a dissipation of energy. In (c) the relationship between e* eA and eB is illustrated; tand = eB/eA. higher frequency electric field oscillations the permittivity falls at the higher frequency and the substance behaves increasingly like a non-polar material.At frequencies for which the loss angle (d) differs significantly from 90° the liquid has a dual role. It functions both as a dielectric and as a conductor. Since sind is an in-phase current component it gives the total relative permittivity a complex character. (1) * (2) e* = eA2jeB where eA is the real part of the relative permittivity (the dielectric constant) and eB is the loss factor which reflects the conductance of the material. In the phase diagram [Fig 2(c)] eB/eA = tand and tand is described as the energy dissipation factor or loss tangent which for low values of tand provides a convenient parameter for comparing the efficiency of conversion of microwave energy into thermal energy within the dielectric for materials with comparable eA.Athough tand is a helpful parameter for comparing the heating rates of a series of compounds with similar chemical and physical characteristics more complex expressions which take into account the complexity of the electric field pattern the heat capacity of the compound and its density are required in order to calculate these heating rates reliably. The frequency dependence of eA and eB and their magnitudes control the extent to which a substance is able to couple with microwave radiation and are therefore fundamental parameters for interpreting the dielectric heating phenomenon. For a polar liquid with a single relaxation time the complex permittivity can be expressed by the following equation due to Debye s ¥ ¥ e - e 1+ jwt e = e + where t is the relaxation time and es and eH are the values of permittivity at frequencies << t21 and >> t21 respectively.Chemical Society Reviews 1998 volume 27 215 Using Eqn (1) and separating into real and imaginary parts leads to s • (3) • w ¥ (4) e - e e ¢ = e + 1+ 2t2 s e (e - e )wt 1+w2t2 e (5) ¢¢ = The relaxation time t has the following significance. The application of a static electric field to a solution containing polar molecules will have the effect of aligning the molecules in the direction of the external field. If the field is switched off the molecules do not immediately adopt random orientations.The relaxation time is a measure of the time taken to achieve this randomised state. The maximum value of eB occurs when eA reaches half of its declining value between es (the permittivity in a static field) and H (the permittivity at frequencies much greater than the inverse of t). The angular frequency of the electromagnetic radiation w = 2pn and t = 1/wo where wo is the angular frequency at which eB is a maximum. The maximum in tand occurs at slightly higher frequencies than the maximum in eB since eB/ eA = tand. For a spherical molecule of radius r rotating in a viscous continuum the relaxation time may be interpreted using the following expression also due to Debye t = 4pr3h/kT which emphasises the importance of the volume of the molecule 4/3pr3 and the viscosity h of the medium.The latter like the relaxation time is strongly related to the intermolecular forces. For example when liquid water freezes the loss of rotational freedom has a dramatic effect on the relaxation time increasing it by approximately 106. The relaxation time is temperature dependent and since it is related to the rate constant k for the relaxation process an Arrhenius type analysis may be used to calculate the enthalpy and entropy of the relaxation process. For liquid water DH‡ (enthalpy of activation) is 18 kJ mol21 which corresponds roughly to the energy required to break one hydrogen bond. For ice the equivalent value is 55 kJ mol21 thereby suggesting that three hydrogen bonds are involved.Since the water molecules in ice form four hydrogen bonds with neighbouring molecules this observation is consistent with what would be expected for a rotation process which retains one hydrogen bond. The water molecules in liquid water clearly retain some of the structure of ice and it is perhaps better to think of water either as a series of clusters of water molecules which interact with each other or as a statistical assembly of water molecules forming different numbers of hydrogen bonds. As a consequence of the former the relaxation process in the microwave region corresponds to cooperative rotational movements of molecules within the clusters and between the clusters. Whereas in the latter it is an average relaxation time resulting from the different bonding arrangements adopted in the liquid.It should be emphasised that the interaction between the microwave radiation and the polar solvent which occurs when the frequency of the radiation approximately matches the frequency of the rotational relaxation processes is not a quantum mechanical resonance phenomenon. Transitions between quantised rotational bands are not involved and the energy transfer is not a property of a specific molecule but the result of a collective phenomenon involving the bulk. In the Debye interpretation the heat is generated by frictional forces occurring between the polar molecule whose rotational velocity has been increased by the coupling with the microwave radiation and neighbouring molecules.A more chemical view of the process would involve the increase in the translational energy of neighbouring molecules induced by the more rapid rotation of the central molecule which acts like a bat or paddle Chemical Society Reviews 1998 volume 27 216 knocking away neighbouring molecules as a result of its faster rotation. In the liquid phase the molecules experience many different environments both spatially and as a function of time but mathematically the dispersion can often be expressed in terms of a single average relaxation time (Eqns. 2 and 3 ). However the dispersion region is spread out over at least two decades and consequently dielectric heating is a broad band phenomenon and rapid energy transfer occurs even when the frequency of the microwaves and the relaxation frequency are not perfectly matched.Studies on the relaxation properties of mixtures of solvents have provided some interesting insights into the volumes implicated by the Debye expression and the nature of the mixing process. If the solvents are chemically similar and mix well at the molecular level then the mixture will often exhibit a single relaxation time at an average position which reflects the molar ratios of the two components. However if the solvents do not mix well at the molecular level e.g. alcohols and bromides and alcohols and ethers then two distinct relaxation times are observed and they do not differ greatly from those of the pure solvents. This suggests that the molecules do not experience average environments but form aggregates which are microassemblies of like molecules.Therefore the relaxation times resemble those of the pure solvents and the relaxation volumes are significantly larger than the molecular volumes indicating that the relaxation processes are occurring within an aggregate of molecules.17 3 Aqueous systems The dielectric properties of water and aqueous solutions are clearly relevant to the primary applications of microwave dielectric heating in domestic and commericial applications and consequently the available data and their interpretation are reasonably well documented. In this section a brief survey will be given of the dielectric properties of water and aqueous solutions including biological materials.The subject has been treated comprehensively recently by Craig.7 The permittivity/frequency graph for pure water at 20 °C is illustrated in Fig. 3 and the graphs are well reproduced using Eqns. (2) and (3). At 20 °C the relaxation time for water is 9 3 1012 s i.e. it has a relaxation frequency of ca. 18 GHz. Fig. 3 The variation of eA and eB with frequency for water at 20 °C Therefore the most effective conversion of microwave energy into thermal energy will occur in this frequency region. In practice the majority of commercial and domestic microwave appliances function at 2.45 GHz (this corresponds to a relaxation time of 65 ps) which is displaced from this maximum and the implications of this difference are discussed further below. The structure of water is influenced when ionic salts are dissolved in it and the relaxation time decreases at low concentrations and then increases.It has been proposed that the presence of the ions causes a structure breaking process to occur in water. Those water molecules which are coordinated to the ions are rotationally fixed but those which are not coordinated do not experience such strong intermolecular hydrogen bonding effects and consequently in this freer state they have lower relaxation times.7 At higher concentrations the effects are reversed and the relaxation frequency of water in concentrated salt solutions is higher than that of pure water presumably due to a greater ordering of the water molecules when a large number of ions are present.At frequencies in excess of around 100 GHz contributions from resonance absorption due to intermolecular vibrations are observed.19 This extra dispersion region explains why for water the permittivity at the high frequency limit of the Debye dispersion is greater than that at optical frequencies. 3.1 Water–alcohol and water–carbohydrates mixtures Alcohols and carbohydrates are likely to be highly miscible with water and may be viewed as organic radicals with pendant hydroxy groups and in solution their molecules are able to form intermolecular hydrogen bonds with each other or with neighbouring water molecules. They form an interactive mixture characterised by a main dispersion with parameters that vary continuously between those of the components.20 The dispersion may however be broader than that predicted by the Debye expression and may be better described by for example s (6) • e - e 1+ ( • (1-a) • e = e + • jwt) This equation is empirical in its derivation and is known as the Cole–Cole model in which a is a distribution parameter acting on the relaxation time such that 1 > a ! 0 which for a = 0 reverts to the Debye equation.Implicit in this analysis of interactive mixtures is the fact that some of the water in the system is affected by the presence of the organic molecule and may well be referred to as bound water. The broadening of the dispersion is however mathematically equivalent to multiple Debye dispersions spanning a distribution of relaxation times.Another model which is useful for describing the frequency dependence of some sugars and alcohols is due to Davidson and Cole21 and is given by s (7) e - e 1+ ( jwt)b e = e + which for b = 1 reverts to the Debye equation. The Cole– Davidson model is useful for describing those situations where a skewed distribution of relaxation times is present. 3.2 Aqueous protein solution5 A protein molecule typically has a molecular weight several orders of magnitude greater than that of water. Consequently the dielectric dispersion region for a protein occurs at frequencies well below those observed for pure water. For a moderate sized globular protein such as haemoglobin the relaxation frequency is in the 1–10 MHz region as distinct from around 20 GHz for the water component (Fig.4). For low protein concentrations the bulk of the water will be relatively unaffected by the presence of the protein and two well defined dispersion regions are observed.22–25 In Fig. 4 the water relaxation region is shown as the g dispersion and that of the protein the b dispersion according to convention. At higher concentrations a significant amount of the water is influenced by the protein and is described as bound water. Because of the stronger intermolecular forces arising from the influence of the protein bound water exhibits Fig. 4 Schematic illustration of the dielectric spectrum of an aqueous protein solution its dielectric dispersion at frequencies less than free water; typically an order of magnitude is involved.The bound water dispersion occurs as a small extra dispersion between the b and g dispersions. Grant et al.5 have established a linear relationship between the relaxation time of water and the molecular weight of 20 biological molecules with molecular weights up to 68 000 (haemoglobin) which suggests that the size of the molecule is the predominant influence. 3.3 Ionic solutions The dielectric properties of ionic solutions have been described by Hasted26 and Craig.7 A typical example is shown in Fig. 5 where the dielectric dispersion curves for three concentrations Fig. 5 Experimental values of the permittivity and total loss factor for KCl solutions with differing concentrations of potassium chloride in water are shown.For an aqueous solution of ions there are two processes leading to energy absorption and therefore dielectric heating. These are ionic drift which gives rise to Joule heating and dipolar relaxation due to the relaxation of the water molecules. The conductivity of these loss processes may be represented by si and sd respectively iB and edB. The and the correspondiing loss factors are e relationship between eB and s is (8) eB = s/we (9) 0 = (sd + si)/we0 and consequently Eqn. (1) may be written e* = eA2jA(eBd + si/we0) As the concentration increases the contribution of eiB predominates over eBd and consequently the value of eB increases with decreasing frequency (Fig. 5). From a chemical point of view this means that the introduction of ions into a solution leads to a marked increase in dielectric heating rates.217 Chemical Society Reviews 1998 volume 27 3.4 Organic compounds Although the relaxation times of a range of organic molecules have been discussed at some length16,17 the dielectric properties at frequencies which are relevant to microwave dielectric heating are less available. In this review we have collected together these data. In addition the dielectric data for a wide range of organic compounds which are of interest as potential solvents for microwave dielectric heating have been remeasured recently in our laboratories15 and the important features of the data are discussed below. The dielectric properties of the compounds were measured at a range of frequencies from 300 kHz to 20 GHz and at a fixed temperature of 20 °C.The temperature dependence of the dielectric properties of many of the compounds were also measured and are discussed below. The static permittivity and the relaxation times were obtained by curve fitting the experimental data to the Cole–Cole model [Eqn. (6)] with eH = 3 this being the average value for the compounds studied. In fact the fitted values of es and t are not particularly sensitive to the value of eH. The analysis also showed that a?0 i.e. the dielectric behaviour of the compounds was represented to a good approximation by the Debye Eqns. (3) and (4). 3.5 Alcohols Alcohols are able to form hydrogen bonds in much the same way as water albeit to a lesser extent and therefore their dielectric properties bear many similarities to those of water.The aliphatic alcohols also have dipole moments which are similar to those of water. Table 2 summarises the relaxation Table 2 Relaxation times (at 20 °C) and dielectric properties of aliphatic alcohols compared with H2O moment Viscosity millipoise Debye Compound Loss tangent at 2.45 GHz Relaxation Dipole time t /ps 10.1 5.45 10.8 20 17.7 22.7 1.84 1.70 1.69 1.68 1.66 1.66 33.5 1.80 1.67 9.04 51.5 170 332 237 538 562 644 792 976 322 169 170 277 188 H2Oa MeOH EtOH Propan-1-ol Propan-2-ol Butan-1-ol Butan-2-ol 2-Methylpropan-1-ol Pentan-1-ol Hexan-1-ol Pent-4-en-1-ol Pent-3-en-2-ol 3-Methyl but-2-en-1-ol trans-Hex-2-en-1-ol Benzyl alcohol a 0.123 0.659 0.941 0.757 0.799 0.571 0.447 0.522 0.427 0.344 0.669 0.720 0.846 0.571 0.667 1.84 refers to the dipole moment in the vapour phase—in the liquid state it is appreciably higher (ca.2.5 D). times of alcohols as a function of chain length and isomer type. As the chain length of the alcohols increases the relaxation time becomes longer. The results fit in well with those anticipated from the Debye expression [Eqn. (5)] and Fig. 6 shows an approximately linear relationship between the relaxation time and the product of the calculated molecular volume and the viscosity. Therefore it can be reasonably assumed that with the exception of benzyl alcohol it is the restricted rotation of the whole molecule which is giving rise to the relaxation process which occurs in the microwave region.The data in Table 2 also suggest that the relaxation time is not greatly influenced by the position of the OH group in the molecule since isomeric alcohols e.g. the isomeric propanols and butanols have similar relaxation times. The data in Table 2 do however indicate a significant decrease in the relaxation times when the hydrocarbon chain contains a double bond or a phenyl ring adjacent to the CH2OH fragment. It is possible that in these more rigid Chemical Society Reviews 1998 volume 27 218 Fig. 6 Plot of relaxation time t vs 4/3pr3 for a number of alcohols.The specific points may be identified by their relaxations times which are given in Table 2. The anomalous position of the point for benzyl alcohol is particularly noteworthy. molecules a more localised rotational process is being observed at these frequencies and this aspect is discussed in more detail below. The slope of the line in Fig. 6 gives t/Vh = 2.4 3 10221 J21. For a rigid sphere rotating in a continuum the slope should be 3/kT which at 20 °C is equal to 0.74 3 10221 J21 according to the Debye Eqn. (5) which highlights the limitations of the Debye analysis and the assumption that molecules behave as rigid hard spheres. There have been a number of attempts to build into the Debye equation parameters which take into account the varying shapes of molecules their tendency to aggregate and the directional nature of hydrogen bonding interactions.5,17 Although the relaxation times are important in influencing heating rates the breadth of the eB against frequency curves is also important and Fig.7 illustrates the dielectric spectra for water and aliphatic alcohols in the range 108–1011 Hz. The value of the dielectric increment (es 2 eH) is related by the Kirkwood equation28 to the correlation factor g which takes into account the highly directional nature of the hydrogen bonds the dipole moment of the molecule (m) and the number of molecules in a unit volume (n). s (10) gnm2 2e kT 0 e g S e 2.94 3.04 3.07 3.43 32.8 24.6 19.5 15.8 = e + MeOH EtOH Propan-1-ol Pentan-1-ol a See also reference 7 page 60.• For water the g parameter expression is around 2.5 and increases as the chain length increases. Some representative values are given in Table 3. As the molecules become more complex the Table 3 Values of static permittivity (eS) and Kirkwood correlation factor g for some non-aqueous solvents.a T/°C 20 20 20 20 complexity of the rotational relaxation increases and the permittivity-curves reflect the superposition of an increasing number of relaxation processes within the molecules and between molecules as a result of self association. The standard microwave frequency for dielectric heating of 2.45 GHz corresponds to a relaxation time of 65 ps. Therefore the alcohols listed in Table 2 which have relaxation times of 51.5–800 ps have relaxation properties which enable them to couple effectively with this fixed microwave frequency and have therefore proved to be effective solvents for dielectric heating.14 The loss tangents given in Table 2 for alcohols are in fact significantly larger than that of water itself.The more detailed relationships between loss tangents and heating rates will be discussed in a subsequent section. Fig. 7 Dielectric spectra for water and a range of alcohols 4 Nitriles esters ketones and chlorohydrocarbons The relaxation times for a series of nitriles are given in Table 4 together with some of the relevant loss tangents at 2.45 GHz. The weaker hydrogen bonding in these compounds leads to much shorter relaxation times (4–68 ps) and for the earlier members of the homologous series much smaller loss tangents than the aliphatic alcohols discussed previously.The relaxation times of the nitriles are much less sensitive to the increase in the hydrocarbon chain length than those noted above for alcohols. Presumably the increased volume and the viscosity have a cancelling effect. The loss tangents for the more commonly used nitriles are comparable with water and therefore the aliphatic nitriles may be used effectively as solvents in microwave cavities. The relaxation time for benzonitrile a common solvent for coordination and organometallic chemistry more closely matches that of the fixed frequency microwave source commonly used in cavities and this is reflected in the larger loss tangent.The loss tangents of the longer chain nitriles are similar to that for benzonitrile. The relaxation times given in Table 4 for some esters and ketones are similar to those for nitriles and clearly indicate the absence of strong hydrogen bonding and the importance of increasing molecular volume. The halogeneated aliphatic compounds listed in Table 4 also exhibit similar and short relaxation times (4–15 ps). It is noteworthy that the relaxation times for these molecules are almost independent of the halogen and occur in a relatively narrow range. Tetrahydrofuran and nitromethane have relatively short relaxation times but the relaxation time for DMF is comparable to those for nitriles.Formic acid and acetic acid have long relaxation times because of the strong hydrogen bonding associated with the carboxylic acid groups and the large loss tangent of formic acid at 2.45 GHz is particularly noteworthy. 5 Aromatic compounds Table 5 summarises the relaxation times and loss tangents of a series of mono-substituted benzene derivatives. The chloro- bromo- and iodo-derivatives have very similar dipole moments and the relaxation time increases progressively as the volume of the substituent increases. The relaxation times of nitrobenzene and benzonitrile are longer and their loss tangents suggest that Table 4 Relaxation times of some nitriles esters carboxylic acids ketones and chlorohydrocarbons. (Literature data in italics) Compound Nitriles CH3CN CH2NCHCN CH3CHNCHCN CH3CH2CH2CN (CH3)2CHCN CH3(CH2)3CN CH3(CH2)4CN CH3(CH2)6CN CH3(CH2)8CN CH3(CH2)9CN PhCN Esters CH3CO2Et CH3CO2C16H31 C17H35CO2C10H21 Acids HCO2H CH3CO2H Ketones CH3COCH3 CH3COCH2CH3 (CH3)2CHCOCH2CH3 Chlorinated hydrocarbons CHCl3 CH2Cl2 CH2ClCH2Cl CHCl2CH2Cl CH3CCl3 (CH3)2CCl2 (CH3)3CCl 3CBr (CH) thf C4H8O CH3NO2 HCONH2 HCONH(CH3) HCON(CH3)2 (CH3)2SO a D.Bertolini M. Cassetori G. Salvetti E. Tombarit and S. Veronesi Rev. Sci. Instrum. 1990 61 450. b S. N. Helambe M. P. Lokhande A. C. Kumbharkhane and S. C. Mehrotra Pramana 1995 45 19. c See refs. 16 17 and also C. Clemett and M. Davies Trans. Farad. Soc. 1962 58 1705.d U. Kaatze K. Menzel and R. Pottel J. Phys. Chem. 1991 95 324. e J. K. Vij T. Grochulski A. Kocot and F.Hufnagel Mol. Phys. 1991 72 353. f A. C. Kumbharkhane S. N. Helambe M. P. Lokhande S. Doraiswamy and S. C. Mehrotra Pramana 1996 46 91. g J. Goulon J. L. Rival J. W. F. Gleming J. Chamberlain and G. W. Chantry Chem. Phys. Lett. 1973 18 211. h J. K. Vij F. Hufnagel and T. Grochulksi J. Mol. Liq. 1991 49 1. i S. M. Puranik A. C. Kumbharkhane and S. C. Mehrotra Ind. J. Chem. A 1993 32 613. j U. Kaatze and V. L�unnecke-Gabel J. Mol. Liq. 1991 48 45. Chemical Society Reviews 1998 volume 27 Relaxation time t/ps 4.47 (20 °C) 3.21 (25 °C) 3.4 (25 °C) 5.91 (20 °C) 10.8 (20 °C) 8.9 (25 °C) 7.92 (20 °C) 12.9 (20 °C) 13.0 (25 °C) 17.4 (25 °C) 31.4 (25 °C) 67.5 (25 °C) 64.6 (25 °C) 33.5 (20 °C) 4.41 (20 °C) 3.66 (40 °C) 13.3 (35 °C) 30.8 (40 °C) 76.7 (25 °C) 177.4 (25 °C) 3.54 (20 °C) 3.22 (20 °C) 3.40 (25 °C) 5.90 (20 °C) 11.3 (20 °C) 8.94 (20 °C) 7.20 (25 °C) 3.12 (20 °C) 2.07 (20 °C) 11.14 (20 °C) 15.18 (20 °C) 5.9 (20 °C) 6.4 (20 °C) 4.8 (20 °C) 6.7 (20 °C) 3.49 (20 °C) 4.0 (25 °C) 4.51 (20 °C) 128 37.3 (25 °C) 38.3 (25 °C) (25 °C) 122.9 (25 °C) 13.05 (20 °C) 10.2 (25 °C) 20.5 (25 °C) 23.1 (25 °C) Loss tangent at 2.45 GHz Ref.0.062 a b 0.052 0.049 0.082 0.149 b 0.119 0.107 0.167 b b b b b 0.172 0.215 0.343 0.527 0.500 0.459 0.059 c c c d d 0.722 0.174 0.054 e f 0.045 0.045 0.079 0.143 0.091 g 0.058 0.042 h 0.027 0.127 0.181 c c c c 0.047 f 0.030 0.064 a i 0.561 0.524 a i 1.610 0.161 i a 0.142 0.825 j 219 Table 5 Relaxation times and dielectric properties of simple aromatic compounds Dipole moment Debye Loss tangent at 2.45 GHz Relaxation time t/ps Compound 1.69 1.70 1.70 4.22 4.68 2.84 0.101 0.138 0.157 0.589 0.459 0.337 12.9 18.0 27.3 43.7 33.5 25.8 Chlorobenzene Bromobenzene Iodobenzene Nitrobenzene Benzonitrile Benzaldehyde they are very effective solvents for microwave dielectric heating at the commonly used frequency.The intermolecular forces between molecules containing these substituents are probably larger because of the larger dipole moments associated with them and this is probably the primary reason for the longer relaxation times. 6 Polyalcohols20 Table 6 provides some comparative data on a series of alcohols which have several OH groups attached to the carbon backbone. These compounds are able to hydrogen bond very extensively and this is refcted in their very high viscosities which in turn correlate with a long relaxation time. The high loss tangents associated with these solvents are particularly noteworthy and it is surprising that they have not been more widely used as solvents for synthetic procedures based on microwave dielectric heating.It was previously noted that the activation energy for the relaxation process in water was around 15–20 kJ mol21. For simple aliphatic alcohols the corresponding value is in the range 16–23 kJ mol21 and in these polyalcohols where the extent of hydrogen bonding is very extensive and their viscosities are high then it rises to 50–130 kJ mol21. 7 Intramolecular rotations Although the relaxation process in the microwave region is generally associated with rotation of the whole molecule there are some important exceptions. From the analysis above it is clear that as the molecular mass of the compound becomes larger as the relaxation time increases and particularly for those solvents where hydrogen bonding is significant.However for large relatively rigid molecules with pendant substituents it is possible to observe more localised rotational processes. A functional group e.g. OH or NH2 attached to a large molecule Table 6 Relaxation times and dielectric properties of glycols Relaxation time t/ps Compound 170 112.87 Ethanol Ethyleneglycol 104.6 (25 °C) 1.17 (25 °C) 1.30 340 760 1,3-Propanediol 1,4-Butanediol 1,5-pentanediol 1,7-Heptanediol 2-Methoxyethanol 0.783 1150 0.456 1950 0.206 33.55 0.410 23.7 (35 °C) 0.282 31.6 (35 °C) 0.301 36.6 (35 °C) 0.276 1215.6 26.1 (35 °C) 0.310 35.5 (35 °C) 0.325 43.6 (35 °C) 0.303 2-Ethoxyethanol 2-Butoxyethanol Glycerol Di(ethylene glycol) methyl ether Di(ethylene glycol) ethyl ether Di(ethylene glycol) butyl ether a A.C. Kumbharkhane S. M. Puranik and S. C. Mehrotra J. Sol. Chem. 1991 21 201. b F. Wang R. Pottel and U. Kaatze J. Phys. Chem. 1997 101 922. c H. D. Purohit and R. J. Sengwa J. Mol. Liq. 1990 47 53. t = 10 ps Fig. 8 Possible localised relaxation process for Ph3COH ing rigid phenyl groups bond rotations are observed e.g. benzyl alcohol has a relaxation time of only 188 ps whereas its molecular volume would suggest a relaxation time for complete molecular rotation of more than 1000 ps. The anomalous behaviour of benzylalcohol compared to other alcohols is clearly visible in Fig. 6. Davies and Meakins17 were able to discern simultaneously the localised and molecular rotations in tri-tert-butylphenol (in decalin) and the relevant dielectric spectrum is illustrated in Fig.9. It is signifcant from the data in Table 2 that those compounds with CH2OH groups adjacent to either a double bond or a phenyl ring have relaxation times of 170–270 ps which suggests a localised rotation of the CH2OH group. The very different relaxation frequencies of the isomeric pentenols are particularly noteworthy in this regard. Primary amines anchored to large molecules also show relaxation frequencies which are inconsistent with the rotation of the whole molecule and it has been proposed that it is not a local rotation but an inversion at the nitrogen atom which is responsible. Table 7 summarises the data on three amines. The series of ortho- meta- and para-methoxy amino-benzenes is particularly interesting since they all show a relaxation time of 25–30 ps which can be associated with inversion of the NH groups but the ortho-isomer shows in addition a second and longer relaxation process at 105 ps which presumably is associated with the occurrence of intramolecular hydrogen bonding between the NH2 and the methoxy group.It is tempting for a chemist to give a chemical significance to these localised rotations and speculate that microwave dielectric heating of molecules containing these groups may result in an enhancement of reaction rates specifically at these groups. However it should be recalled that the dielectric heating Chemical Society Reviews 1998 volume 27 220 behaves as if it were anchored to an immobile raft and its localised rotations may be observed in the microwave region.For example triphenylchloromethane and triphenylhydroxymethane have very different relaxation frequencies and it has been proposed that in the latter case the relaxation time of 10 ps is associated with a rotation of the O–H bond relative to the triphenylmethyl fragment (Fig. 8). In many compounds contain- H Cl O C C Ph Ph Ph Ph Ph Ph 2 Loss tangent at 2.45 GHz Ref. 1.26 1.35 a b b b b c c c t = 62 ps Viscosity/ millipoise 10.8 1.36 9450 0.651 c c c Fig. 9 Dielectric absorption of tri-tert-butylphenol in decalin ( 0.76 m) at 20 °C (adapted from M. Davies and R. Meakins J.Chem. Phys. 1957 26 1584). Table 7 Structure and dielectric parameters of three methoxybenzylamines Relaxation time/ps S 25.4 28.1 and 105 29.2 p-Methoxy o-Methoxy m-Methoxy (11) (12) e 7.2 7.2 7.4 process involves the rapid energy transfer from these groups to neighbouring molecules and it is not possible to store the energy in a specific part of the molecule. 8 More specific aspects of microwave dielectric heating The previous section has qualitatively alluded to the relationship between the dielectric heating rates and tand and this section attempts to define these realationships more precisely. An excellent detailed account of this aspect has been given in the book by Metaxas and Meredith,29 and more recent developments have been documented by Dibben and Metaxas.30 The efficiency of conversion of microwave energy into thermal energy depends upon both the dielectric and thermal properties of the material. The fundamental relationship is P = sýEý2 = (we0eB)ýEý2 = (we0eA tand)ýEý2 where P stands for power dissipation per unit volume in a material of conductivity s. The electric field in the sample is E and w is the angular frequency. Substituting for the conductivity from eqns (4) and (8) gives P in terms of the Debye parameters as 2 2 s 0 • (13) E P 1 = s = 2 we e we e D ¢tand E = (14) e (e - e )w t +w2t 2 Assuming negligible heat loss and diffusion the rate of heating or temperature rise DT in a time interval t can be expressed as 2 E rC 2 0 0 ¢¢ E rC DT t T t rC = where r is the density and C the specific heat capacity.In practice the field strength is dictated by the characteristic shape and dimensions of the cavity and the field strength in the material is neither known nor constant. Moreover the value of E is itself strongly dependent upon the dielectric properties of the material. Therefore a rigorous numerical analysis is necessary in order to establish the distribution of electric field in the cavity and within the sample. This situation has been dealt with by Dibben and Metaxas.30 In summary the following general points may be made 1. Non-polar solvents which have no permanent dipole moment have no relaxation processes in the microwave region and are therefore transparent to microwaves.Whilst this means that they are ineffective as solvents for microwave dielectric heating experiments they may be used as coolants for removing excess heat from a microwave cavity. 2. Polar solvents which have a permanent dipole moment do have relaxation processes in the microwave region and are therefore suitable candidates as solvents for microwave dielectric heating experiments. The data provided in previous sections have given some guidance concerning their relaxation times and loss tangents. It is perhaps worth re-emphasising that even when the relaxation time is one or two orders of magnitude different from that which corresponds to the microwave frequency operating in the cavity then the solvent is still capable of acting as an effective medium for dielectric heating because its loss tangent is sufficiently large.Indeed the loss tangent of water at 2.45 GHz is only 0.1 and yet the heating rates are sufficiently high for this frequency to be used as the basis of an enormous food processing industry. Therefore solvents with tand greater than 0.1 are good bets for microwave dielectric heating experiments. 3. The relaxation time of a solvent depends on the temperature and decreases as the temperature is increased i.e. the larger translational motions of the molecules enable them to randomise their position more quickly when the electric field is switched off. Therefore if an organic solvent has a relaxation time greater than around 65 ps (i.e.corresponding to 2.45 GHz) it will have a loss tangent which increases with temperature. Therefore as the temperature increases as a result of microwave dielectric heating then the loss tangent increases and the solvent converts more of the microwave energy into thermal energy. The heating rate therefore rises. The resulting phenomenon is described as thermal runaway. The analysis of relaxation times provided in the previous section has indicated that the majority of organic solvents have relaxation times greater than 65 ps (in some cases it is larger than 1000 ps) and therefore it is not surprising that many organic solvents superheat in a microwave cavity. The extent and origins of this phenomenon have been discussed by Baghurst and Mingos.31 It is not uncommon for organic solvents to exhibit boiling points some 10–20 °C higher than their conventional boiling points in a microwave cavity.These raised boiling points have a number of implications regarding the relative rates of reaction under conventional and microwave conditions. Fig. 10 and Tables 8 and 9 give some data concerning the variations of the dielectric properties of some alcohols as a function of temperature and illustrate the conclusions developed above. Low molecular weight polar organic molecules e.g. MeOH and CH3CN are rare instances where the relaxation times are very short and where raising the temperature leads to a reduction in loss tangents. For methanol ethanol and n-butanol the relaxation frequency varies from < 2.45 GHz at the low temperature end to > 2.45 GHz at the highest temperature reported (Table 9) therefore thermal runaway effects may diminish as the boiling point is approached.4. The addition of small amounts of a polar solvent with a large loss tangent usually leads to high heating rates for the whole mixture. The energy transfer between the polar molecules which are coupling with the microwaves and the majority non-polar solvent is rapid and therefore this provides an effective mechanism for introducing non-polar solvents as 221 Chemical Society Reviews 1998 volume 27 Table 9 Relaxation times and frequencies and dielectric properties at 2.45 GHz of ethanol and butan-1-ol as a function of temperature T/°C 10 20 30 40 50 60 70 80 90 100 110 Fig.10 Variation of the dielectric properties as a function of temperature Table 8 Relaxation times and dielectric properties at 2.45 GHz of propan- 1-ol and methanol as a function of temperature Methanol Propanol T/°C t/ps t/ps eB eB eA 884 548 442 1.34 1.65 2.08 2.59 3.41 11.01 133.6 109.0 96.4 62.6 52.0 40.8 34.4 28.8 26.6 12.59 14.25 16.46 15.32 11.77 12.52 10.43 8.62 6.10 14.75 17.85 20.90 22.63 20.06 24.49 24.19 23.95 19.42 220 210 0 10 20 30 40 50 60 microwave radiation results in a decrease in the loss tangent but for hexan-1-ol and glycerol which have much longer relaxation times a much larger loss target is observed at 433.9 MHz.Therefore for some solvents with high relaxation times there may be an advantage to using some of the alternative microwave frequencies which have been designated for dielectric heating. In summary it may be appreciated that the relaxation times of molecules have a profound influence on the dielectric parameters which influence the rate of heating in a microwave cavity. The relaxation times may involve the whole molecule or a functional group anchored to a large molecule and they depend on the intermolecular forces between the molecules and the size of the molecule. It is hoped the ready access to the data presented in this review will lead to the design of microwave heating experiments which are based more soundly on the relevant dielectric parameters.9 Acknowledgements BP plc are thanked for endowing D. M. P. Mingos’ chair the EPSRC for financial support and CEM for generously providing equipment. Hexan-1-ol Methanol Frequency Tan d Tan d eB eB eA eA eA 0.70 0.90 3.62 2.25 1.17 8.00 9.30 5.16 3.96 3.43 0.011 0.014 0.130 0.265 0.665 0.40 0.50 4.44 8.49 14.6 35.1 35.0 34.2 32.1 21.9 0.001 0.001 0.022 0.045 0.122 78.3 78.4 78.5 78.6 77.4 13.56 MHz 27.12 MHz 433.9 MHz 900 MHz 2.45 GHz eA 6.33 6.94 6.97 6.87 7.94 17.97 coupling agents into a microwave cavity (see Fig. 11 for example).5. The addition of salts to solvents increases their conductivities and has a dramatic influence on their heating rates. 6. Generally the rate of the rise in temperature of an elemental volume is related to the heat input eBýEý2 but the heat is conducted away at a rate which depends upon the thermal diffusivity and the temperature gradient in the sample. An equilibrium temperature is reached when these two terms are equal. Multimode cavities are particularly susceptible to cause thermal runaway in samples which have high loss tangents because of their standing wave characteristics. 7. Table 10 summarises some loss tangent data for some organic solvents as a function of frequency. Clearly for water methanol and nitrobenzene changing the frequency of the Table 10 Loss tangent data for some common solvents as a function of frequency Water eB 0.10 0.10 1.70 3.51 9.48 Chemical Society Reviews 1998 volume 27 222 Butan-1-ol fr GHz Ethanol fr GHz t/ps t/ps eB eB eA eA 7.05 5.81 7.49 6.46 8.05 7.06 8.95 7.39 10.11 7.28 11.15 6.76 11.71 6.35 0.59 0.80 1.19 1.53 2.03 2.88 3.26 1.16 1.45 1.80 2.22 2.63 2.88 2.92 2.67 2.28 1.77 1.33 4.22 3.52 3.55 3.71 4.04 4.47 5.03 5.50 5.75 5.83 5.73 269.8 199.0 0.38 133.8 0.43 104.0 0.69 78.4 0.93 55.2 1.32 48.8 1.97 2.81 3.90 5.35 6.50 419.0 370.2 230.8 171.1 120.6 80.8 56.6 40.8 29.8 24.4 Fig.11 Variation in heating rates for a CHCl3–CCl4 mixture Glycerol Nitrobenzene Tan d Tan d Tan d eB eB eA eA 0.20 0.40 3.98 0.006 0.011 0.113 7.73 0.229 0.584 35.1 35.2 35.3 33.7 25.2 0.087 0.197 0.866 0.759 0.540 3.70 8.30 9.87 6.39 3.42 42.5 42.1 11.4 8.41 6.33 0.088 0.097 0.702 0.568 0.341 14.7 10 References 1 R. Dayani Molecular Magic with Microwaves Chem. Eng. News 1997 Feb 10th 26. 2 A. R. von Hippel Dielectric Materials and Applications MIT Press Cambridge Mass. USA 1954. 3 A. R. von Hippel Dielectric and Waves MIT Press Massachusetts Institute of Technology Cambridge Mass USA 1954. 4 C. Gabriel S. Gabriel and E. Courtout Phys. Med. Biol. 1996 41 2231.5 E. H. Grant R. J. Sheppard and G. P. South Dielectric Behaviour of Biological Molecules in Solution Clarendon Press Oxford UK 1978. 6 E. H. Grant IEE Proc. ptA 1981 128 602. 7 D. Q. M. Craig Dielectric Analysis of Pharmaceucitical Systems Taylor and Francis London UK 1995. 8 H. M. Kingston and S. J. Haswell Microwave Enhanced Chemistry American Chemical Society Washington DC USA 1997. 9 R. Lauvert A. Laporterie J. Dubac J. Berlan S. Lefeuvre and M. Auchay J. Org. Chem. 1992 57 7099 and references therein. 10 R. D. Raner C. R. Strauss F. Vyskoc and L. Mokbel J. Org. Chem. 1993 58 950. 11 S. A. Galema Chem. Soc. Rev. 1997 26 233. 12 D. M. P. Mingos and A. G. Whittaker J. Chem. Soc. Dalton Trans. 1992 2751. 13 D. R. Baghurst and D. M. P. Mingos Chem. Soc. Rev. 1991 20 1. 14 G. Majetich and K. Wheless ref. 8 p 455; D. R. Baghurst and D. M. P. Mingos ref. 8 p. 523. 15 The data given in the Tables represent a combination of literature data (see particularly references 7 16 and 17 for general compilations and the Tables for specific references) and recent redeterminations in our laboratories using the methods described in C. Gabriel T. Y. A. Chan and E. H. Grant Phys. Med. Biol. 1994 34 2183. 16 N. E. Hill W. E. Vaughan A. H. Price and M. Davies Dielectric Properties and Molecular Behaviour van Nostrand New York 1969. 17 M. Davies Some Electrical and Optical Aspects of Molecular Behaviour Commonwealth and International Library of Science Technology and Liberal Studies Pergamon Press Oxford 1962. 18 H. J. Liebe G. A. Hufford and T. Manabe Int. J. Infrared Millimetre Waves 1991 12 659. 19 A. Stogryn IEEE Transaction on microwave theory and techniques 1971 19 733. 20 J. B. Bateman and C. Gabriel J. Chem. Soc. Faraday Trans. 2 1987 83 355. 21 D. W. Davidson and R. H. Cole J. Chem. Phys. 1951 19 1484; K. S. Cole and R. H. Cole J. Chem. Phys. 1941 9 341. 22 S. E. Keefe and E. H. Grant Phys. Med. Biol. 1974 19 201. 23 E. H. Grant J. Mol. Biol. 1966 19 133. 24 E. H. Grant G. P. South S. Takashima and H. Ichimura Biochem. J. 1971 122 691. 25 E. H. Grant R. J. Sheppard G. L. Mills and J. Slack Lancet 1972 159. 26 J. B. Hasted Aqueous Dielectrics Chapman and Hall London UK 1973. 27 B. P. Jordan R. J. Sheppard and E. H. Grant J. Appl. Phys. 1972 11 675. 28 J. G. Kirkwood J. Chem. Phys. 1939 7 911. 29 A. C. Metaxas and R. J. Meredith Industrial Microwave Heating Peter Peregrinces Institution of Electrical Engineers Exeter 1982. 30 D. R. Baghurst and D. M. P. Mingos J. Chem. Soc. Chem. Commun. 1992 674. 31 D. C. Dibben and A. C. Metaxas J. Microwave Power 1994 29 242. Received 26th January 1998 Accepted 12th February 1998 223 Chemical Society Reviews 1998 volume 27

ISSN:0306-0012    

DOI:10.1039/a827213z

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

p-Block metallocenes the other side of the coin Michael A. Beswick Julie S. Palmer and Dominic S. Wright*† Chemistry Department University of Cambridge Lensfield Road Cambridge UK CB2 1EW Although transition metal metallocenes {such as ferrocene [(C5H5)2Fe]} have been a cornerstone in the development of modern organometallic chemistry and continue to be a focus for chemical and structural studies in comparison the chemistry of the main group metal counterparts has remained relatively undeveloped. The recent resurgence of interest in p-block (Groups 13–15) metallocenes in particular has given fresh insights into the structural preferences bonding requirements and reactivity of these under-publicised species which in many ways represent ‘the other side of the coin’.The more varied (ionic and covalent) character of the metal-ligand bonds and the less restricted electronic requirements of p-block metals leads to greater structural diversity and radically different reactivity than is found for the transition metal relatives. This short review focuses on the remarkable range of p-block complexes that has so far been uncovered and attempts to unravel some of the electronic and structural trends in these species. 1 A difference in understanding Since they were first synthesised in the mid to late 1950s transition metal metallocenes containing cyclopentadienide and related ligands (C5H52 Cp) p-bonded to the metals have played a central role in the development of modern organometallic chemistry.1,2 The predominantly covalent metal–ligand † E-mail DSW1000@cus.cam.ac.uk Dr Michael A.Beswick was born in Warrington Cheshire in 1964. He obtained his first degree at Hatfield Polytechnic in 1990 and his PhD at Cambridge University in 1992 under the supervision of Professor the Lord Lewis. After a period of research as a Royal Society Fellow at the University of Murcia in Spain with Professor J. Vicente he returned to Cambridge where he is now a postdoctoral researcher in inorganic chemistry on a Leverhulme Fellowship. His principal interests concern cluster and cage compounds of transition and main group metals. Julie S. Palmer Michael A. Beswick bonding in these species can be explained in simple terms as resulting from the high electronegativity of transition metals.However more detailed examination shows that the metal– ligand interactions in these species involve a complicated covalent bonding situation resulting from a combination of donation of electron density from the ligand to the metal and ‘back-donation’ from the metal to the ligand. This bonding pattern is qualitatively similar to that occurring in transition metal carbonyl compounds such as [Fe(CO)5] and is dependent on the key involvement of the metal d orbitals. The importance of covalency in these species and of the involvement of the metal d orbitals is stressed by the rigid electronic requirements of simple metallocenes such as ferrocene [Cp2Fe] (Fig. 1) in which a total of eighteen electrons (5e from each Cp ligand 8e from Fe) corresponds to the filling of the nine bonding molecular orbitals available and promotes greatest electronic stability (the so-called ‘18 electron rule’).The chemistry of transition metal metallocenes is a mature area in which the reactivity and bonding is well-understood.1,2 Fig. 1 Structure of Ferrocene Julie S. Palmer was born in Bridgend Mid Glamorgan in 1974. She obtained her first degree at the University of Bath in 1996 and is currently studying for her PhD in inorganic chemistry at Cambridge University at Gonville and Caius College. Dr Dominic S. Wright was born in Gosport Hampshire in 1964. He obtained his first degree at Strathclyde University in 1986 and his PhD in Cambridge in 1989 under the supervision of Dr R. Snaith.After a college research fellowship with Gonville and Caius College Cambridge he was appointed to his current position as a lecturer in inorganic chemistry at Cambridge University. He was the recipient of the 1993 RSC Meldola Medal. Current research interests include synthetic and structural studies of the p block metal metallocene compounds metallacyclic p block metal ligand systems and heterometallic complexes containing novel metal-based ligand arrangements. Dominic S. Wright 225 Chemical Society Reviews 1998 volume 27 Although main group metallocenes have been known for as long as their transition metal counterparts studies to date have largely focused on the structures adopted by the neutral species in the solid state and comparatively few investigations have focused on the chemistry of these compounds in their own right.3 In contrast to the transition metal compounds only limited theoretical studies have so far been undertaken on the main group species.The more varied (generally more ionic) character of the metal–ligand bonding and the minimal involvement of higher energy metal d orbitals leads to less restricted electronic demands of the metals and to greater structural diversity than is found in the transition metal counterparts.3 These bonding characteristics have made general structural trends difficult to discern and in many cases reduce ideas of electron counting to little more than formalisms. In particular where ionic bonding is dominant such as in metallocenes formed by the majority of s-block elements (Group 1 Li–Cs; Group 2 Mg–Ba) the relationship between hapticity of the cyclopentadienide ligand and the number of electrons supplied to the metal [e.g.h3-Cp (3e) h5-Cp (5e) (Fig. 2)] should not always be taken literally. Rather in main group metallocenes the coordination of p-bonded Cp ligands is electronically flexible and generally weak. Fig. 2 Bonding of Cp to a metal (M) in (a) h5-mode and (b) an h3-mode As a consequence of the contraction in atomic radii across the d-block the p-block metals which follow have similar electronegativities to transition metals and there is as a result a significantly higher percentage of covalent character in the metal–Cp bonding than is present in s-block metallocenes.This greater covalency has a profound impact on the structural and bonding patterns adopted. The character of p-block metallocenes (Group 13 Al–Tl; Group Ge–Pb; Group 15 As–Bi) can in many ways be seen to combine the distinctive structural features found in the s-block with those typical of d-block compounds. This review focuses on the major structural classes of p-block metallocenes on the nature of the bonding in these species and on the ways by which structural and chemical modification can be achieved. The principal aims are to highlight the fundamental characteristics of these species and to make some sense of the diverse range of structures observed. 2 Reactivity patterns Metallocenes of p-block elements exhibit very different reactivity to the transition metal analogues.3 In contrast to the transition metal metallocenes both the Cp ligands and the metal centres in main group complexes prove to be highly reactive and ligand exchange reactions and reactions involving a change in the oxidation state of the metal centres are particularly characteristic.The most marked difference with transition metal metallocenes is the far greater lability of the Cp rings resulting from weaker metal–ligand interactions and the greater polarity of the metal–Cp bond. 2.1 Reactions at the metals 2.1.1 Nucleophilic addition reactions These can occur where weak nucleophiles are added to p-block metallocenes.4 An example of this type is the reaction of Cp2Mg with stannocene (Cp2Sn) resulting in the coordination of the Cp2 anion to the SnII centre [eqn.(1)]. This reaction is discussed in detail in section 3.2. (1) Cp2 + [Cp2Sn]?[Cp3Sn]2 Chemical Society Reviews 1998 volume 27 226 2.1.2 Oxidative addition reactions These are common in transition metal complexes of various types particularly within catalytic cycles.2 As the name suggests these reactions involve an increase in the oxidation state and coordination number of the metal. This type of reaction is highly dependent on the relative stabilities of the oxidation states involved. For p-block elements there are two potentially stable oxidation states corresponding to the use of the valence s and p electrons (the ‘n oxidation state’) or the use of only the p electrons and with the retention of a non-bonding lone pair (the ‘n 2 2 oxidation state’).Elements at the top of a p-block group prefer the n oxidation state whereas those at the bottom prefer the n 2 2 (commonly known as the ‘inert-pair effect’). This situation is largely the result of the increased stabilisation of the s orbitals as one descends the group the main reason for which is a complex quantum mechanical effect which occurs in atoms with large nuclei (so-called ‘relativistic effects’5). The reaction between Cp2Sn and MeI is an example of oxidative addition in which the SnII centre is oxidised to SnIV with an increase in the coordination number of the metal [eqn. (2)].6 This outcome can be compared to the same reaction with Cp2Pb in which the PbII centre is retained as a result of the greater stability of the lower oxidation state [eqn.(3)]. 2Sn]?[Cp2Sn(Me)I] MeI + [Cp (2) 2Pb]?[CpPbI] + CpMe MeI + [Cp (3) Recently the metallocenes [MeCpGaI]7 and [MeCpAlI]8 (MeCp = C5Me5) have been prepared. Owing to the much greater stability of the higher +3 oxidation state at the top of Group 13 these species are exceptionally reactive. Oxidative addition reactions with elements such as sulfur selenium and phosphorus and reactions with transition metal–metal bonds are known,8 e.g. eqn. (4). (4) 4[MeCpAl] + 4S?[MeCpAlS]4 MeCp MeCp Al S Al S S Al MeCp S Al MeCp 2.1.3 Lewis base characteristics Lewis base characteristics of the metal lone pair in the n 2 2 oxidation state metallocenes tend to be limited as a result of the stabilisation of the non-bonding pair of electrons which is buried in the atomic structure of the metals and not particularly accessible.The lone pair can however be donated to transition metals e.g. eqn. (5). Cp –CO .(5) 2[Cp (CO) 2Sn] + [Fe2(CO)9] 4Fe Cp Sn Fe(CO)4 Sn Cp Cp 2.2 Ligand reactivity 2.2.1 Protolytic cleavage Protolytic cleavage of the Cp–metal bonds in p-block metallocenes results from acid–base reactions with stronger organic and inorganic acids,9 e.g. eqn. (6). HX + [Cp2Sn]?[CpSnX] + CpH (6) This characteristic can be associated with the greater ionic character of the metald+–Cpd2 interactions in p-block metallocenes and is in marked contrast to the greater stability of transition metal–Cp bonding.2.2.2 C–H Bond activation C–H bond activation of the Cp ligand can be achieved by reactions with strong bases.10 This mode of reaction is more common in transition metal metallocenes and can be used to functionalise metal-bonded Cp rings e.g. eqn. (7). Lewis base (7) [Cp2Sn] + BunLi ——? [(C5H4Li)CpSn] + BunH 2.2.3 Equilibration and nucleophilic substitution reactions These are particularly common in p-block metallocenes. Equilibration involves facile ligand exchange between two complexes [eqn. (8)].11 Nucleophilic substitution results from the interaction with stronger nucleophiles [eqn. (9)].12 (8) [Cp2Sn] + [SnCl2]?2[CpSnCl] 2[Cp2Sn] + 2[LiNNC(NMe2)2]? (9) [CpSn{m-NNC(NMe2)2}]2 + 2[CpLi] NMe2 Me2N C N Sn Cp Sn Cp N C NMe Me 2 2N 3 Structural patterns Fig.3 MO diagram for [CpIn] monomer Fig. 4 MO diagram for linear [Cp2M] and the effect of px–lone-pair mixing 3.1 ‘Islands’ of electronic stability In view of the relatively high degree of covalent character of the p-block metallocenes compared to those of the s-block one might expect that like transition metal complexes the total number of metal and ligand electrons will become important in the filling of bonding molecular orbitals and that certain electronic configurations may be particularly favoured on the grounds of electronic stability. A further similarity with transition metal complexes is that p-bonding of the Cp ligands only normally occurs where the oxidation state of the p-block element is low.For p-block elements this is the ‘lone-pair’ oxidation state involving only the use of p electrons and retention of a non-bonding lone pair. However unlike transition metals the Cp–metal interactions do not involve d orbitals and adherence to the 18 electron rule should not be expected.3 Although formally adhering to the octet rule the electronic structure of monomeric CpIn (occurring in the gas phase) is best understood by a molecular orbital (MO) description in which the eight electrons (formally 5e from Cp 3e from In) are accommodated within four molecular orbitals arising from the overlap of the two lowest lying p MOs of the Cp ring [in phase (y1) and out of phase (y2)] with two sp and two p orbitals of In.3 This arrangement gives three filled bonding MOs and one nonbonding MO in which the metal lone pair resides (Fig.3). The unusual ‘bent’ (or angular) sandwich structure of Cp2Sn in the gas phase underlines the importance of the MO treatment in rationalising the behaviour of Group 14 metallocenes.13 In a linear arrangement only six bonding MOs result from the combination of the metal s and p orbitals with y1 and y2 with the lone pair residing in an antibonding MO. The accommodation of all fourteen electrons is achieved by mixing the metal s orbital with the px atomic orbital lowering the energy of the lone pair (Fig. 4). The tendency towards a more linear advanced as for the Group 13 and 14 complexes. However in the neutral Group 15 complexes the tendency for Cp ligands to p-bond appears to be significantly less than for elements of Groups 13 and 14,3 possibly as a result of the higher electronegativity of these elements and their consequently lower metallic character.It is noteworthy in this respect that as Group 15 is descended (the elements becoming more metallic) there is an increased ability to p-bond. Spectroscopic studies of 3As suggest that the Cp rings are s-bonded (giving an 8e Cp octet) whereas rapid interconversion between an 8e s-bonded (‘ferrocene-like’) arrangement going from Cp2Sn to MeCp2Sn and PhCp2Sn (PhCp = C5Ph5) is partly accounted for by steric congestion but also results from the higher energy of the lone pair orbitals in MeCp2Sn and PhCp2Sn which are not sufficiently stabilised by s/px orbital mixing to strongly favour the bent arrangement.3 Unfortunately the level of theory for the Group 15 metallocenes (Cp3E; E = As–Bi) is not anywhere near as structure and a 20e p-bonded arrangement occurs for Cp3Sb in 227 Chemical Society Reviews 1998 volume 27 solution.Two modifications of Cp3Bi an 8e s-structure and a 20e p-structure have been identified. From the point of view of understanding the range of metallocenes which can be prepared it is of value to regard the formal electron counts of the neutral (‘parent’) p-bonded complexes of Groups 13 [CpE (8e)] 14 [Cp2E (14e)] and 15 [Cp3E (20e)] as representing ‘islands’ of electronic stability.14 A range of mononuclear cationic and anionic p complexes can be derived from the parent metallocenes by the formal addition or removal of Cp2 ligands generating charged complexes which are isoelectronic with a parent complex of a neighbouring Group (8e 14e or 20e) (Fig.5). It should be noted that this simple relationship does not define all known metallocene derivatives and other complexes whose formal electron counts do not adhere to this scheme are known (e.g. CpSnCl 10e). Fig. 5 Isoelectronic relationships of some anionic and cationic metallocenes 3.2 Isoelectronic cations and anions The isoelectronic guidelines depicted in Fig. 5 give various targets for chemical study. In the case of anionic complexes the idea of the addition of Cp2 to a parent metallocene is not simply a formalism but works in practice.The reaction of Cp2Mg with CpTl in the presence of the Lewis base donor PMDETA [(Me2NCH2CH2)2NMe] produces [CpMg·PMDETA]+[ Cp2Tl]2,14 containing a thallocene anion which is isoelectronic with 14e Cp2Sn (Fig. 6). Like Cp2Sn a bent sandwich arrangement is found in the thallocene anion. However theoretical investigations of the stabilty of the bent versus the linear geometry reveal that the energy difference between these conformers is very small. The reason for this is most easily appreciated by the view of the electron density ‘surface’ of the [Cp2Tl]2 anion in which an essential spherical lone pair orbital is localised on the Tl atom. Clearly there is insufficent s/px mixing to make the bent arrangement significantly favoured and the lone pair orbital therefore has largely s character.This finding has a broader significance to the electronic structures and stabilities of all 14e systems of this type. As one descends a Group in the p-block the valence s orbital becomes increasingly stabilised with respect to the p as a result of relativistic effects. This factor is apparent in the electronic structure and arrangement of [Cp2Tl]2 since the low A further feature of the [Cp energy of the s orbital makes s/px mixing less favourable. Some hint of the general nature of this observation is given by the more angular arrangement of Cp2Sn (125°) than Cp2Pb (143°)3 in the gas phase and this is confirmed by theoretical calculations of Cp2E (E = Ge–Pb) which show that the lone-pair orbital becomes progressively less stable and the difference in energy between the bent and linear conformations becomes almost insignificant as Group 14 is descended.4 2Tl]2 anion is the asymmetry of the bonding of the two Cp rings seen in the noticeable constriction of the electron density linking one of these ligands Chemical Society Reviews 1998 volume 27 228 Fig.6 Structure of [CpMg·PMDETA]+[CpTl]2 to Tl. This suggests that in electronic terms the anion can be described as a ‘close-contact’ complex between Cp2 and CpTl ([CpTl–Cp]2). In fact the character of this and related systems is highly dependent on the situation and coordination of the cation. In [CpTl(m-Cp)Li·PMDETA] (Fig. 7) the presence of an ion-contact between the Li+ cation (which competes for the electron density of the bridging m-Cp ligand) weakens the Tl– (m-Cp) interaction and has a profound effect on the charge distribution of the [Cp2Tl]2 unit (now best regarded as a ‘loosecontact’ complex between CpTl and CpLi).14 Fig.7 Structure of [CpTl(m-Cp)Li·PMDETA] The same general features seen in the [Cp also apparent in formally 20e complexes containing [Cp 2Tl]2 system are 3E]2 (E = Sn Pb) anions. The reactions of Cp2E with CpNa or Cp2Mg give ion-separated or ion-paired complexes depending on the cation and the extent of its Lewis base solvation.4 In [Mg(thf)6]2+[Cp3E2]2 2E(m-Cp)Na·PMDETA] and [Cp p-bonded ‘paddle-wheel’ arrangements of the three Cp ligands surrounding the Group 14 metals result in almost trigonal planar metal geometries (Fig.8). This arrangement is extremely unusual for stannate or plumbate anions s-bonded organometallic anions of this type (such as 8e [Ph3E]215) conforming to Fig. 8 (a) Structure of [Mg(thf)6]2+[Cp3E2]2 and (b) [Cp2E(m- Cp)Na·PMDETA] 2Sn and CpNa·PMDETA.4 the VSEPR model and having pyramidal metal geometries. The p-bonding of Cp to the SnII and PbII centres in [Cp3E]2 clearly overwhelms conventional octet considerations and their effects on structure. However the switch from an h5-Cp bonding mode in [Cp2E(m-Cp)Na·PMDETA] to an h3-mode in [Mg(thf)6]2+[Cp3E2]2 and the less planar geometry of the Group 14 metal centres in the ion-separated [Cp3E]2 anions can be viewed as resulting from a shift towards partial sp3 hybridisation.4 As with complexes containing [Cp2Tl]2 anions the nature of [Cp3E]2 anions is highly dependent on potential competition with cations and spectroscopic and theoretical studies illustrate that the Sn environment in [Cp2Sn(m- Cp)Na·PMDETA] is electronically similar to that in Cp2Sn.This complex is therefore best considered as a ‘loose-contact’ type complex between Cp Cationic complexes were the earliest examples which portrayed an underlying isoelectronic relationship in p-block metallocenes. Perhaps the most well known example is the 8e [(MeCp)Sn]+ cation (Fig. 9) isoelectronic with the neutral Group 13 metallocene units of CpTl or CpIn.3 This cation is the product of the reaction of (MeCp)2Sn with the acid HBF4 resulting in the formal loss of Cp2 as CpH.The formation of adducts of this cation with various Lewis base donors is also known.3 A second representative of this class is the 14e [(MeCp)2As]+ cation (Fig. 10) generated by the reaction of [(MeCp)2AsF] with SbF5.3 Like the isoelectronic neutral metallocene units of Group 14 in the gas phase a bent sandwich arrangement occurs for the [(MeCp)2As]+ cation in the solid state. The use of the more sterically demanding MeCp ligand in these cationic species is required for their stabilisation. A more recent development is illustrated by the synthesis and structure of the 12e [(MeCp)2Al]+ cation (Fig. 11).8 This species is prepared by the disproportionation reaction of the AlI complex [(MeCp)Al] with AlCl3 and is formally isoelectronic with s-block metallocenes such as Cp2Mg and [Cp2Li]2.3,16 Fig.9 Structure of the [(MeCp)Sn]+ cation Fig. 10 Structure of the [(MeCp)2As]+ cation Fig. 11 Structure of the [(MeCp)2Al]+ cation Like these complexes a linear (‘ferrocene-like’) sandwich structure is found for the [(MeCp)2Al]+ cation in the solid state; the reasons for which can be seen by returning to the MO diagram for Cp2Sn shown in Fig. 4. Unlike the 14e Group 14 metallocenes deformation of the structure into a bent conformation is not necessary in a 12e system since an additional bonding orbital is not required. The considerable interest in Al cations of this type has been generated by the discovery that the less sterically shielded [Cp2Al]+ cation is effective in alkene polymerisation.17 3.3 Fragmentation and control of the metallocene lattice So far the discussion of the structures formed by p-block metallocenes has been confined to the consideration of isoelectronic relationships in simple mononuclear complexes.However although all the known neutral metallocene complexes are monomeric in the gas phase many are in fact associated into polymeric or molecular arrangements in the solid state.3 The simplest metallocenes containing unsubstituted Cp ligands often form polymeric strand structures in which the molecular units are linked by metal–(m-Cp)–metal interactions. The structures of CpTl and CpIn [Fig. 12(a)] and of the orthorhombic form of Cp2Pb [Fig. 12(b)] adopt this structural pattern.3 The tendency for Cp2Pb to polymerise in this manner is unique in Group 14 and probably stems from the more 229 Chemical Society Reviews 1998 volume 27 Fig.12 Structures of (a) [CpE] (E = In Tl) and (b) [Cp2Pb] electropositive nature of Pb. This arrangement can be compared to the structure of Cp2Sn,3 which retains its monomeric nature in the solid state. As is illustrated by the dissociation of these polymeric structures into monomers in the gas phase and in solution the association of the molecular units is weak. What is surprising is that such association should occur at all in these species bearing in mind the presence of metal lone pairs which would normally suggest donor rather than acceptor character. The reasons for the weak acceptor properties arise from the low energy of the lone pair orbitals which have considerable s-character and are buried in the atomic structure of the metals.decker sandwich anions shown in Fig. 14. These species are the next homologues of the mononuclear [Cp2Tl]2 and [Cp3Pb]2 anions discussed previously. The inherent weakness of the association of the metallocene units means that lattice energy considerations dominate the Using the formal electron count of the metals as a basis for the interpretation of structural trends is of far less value in these polymeric systems. However one observation is that the metal environments within the strand structures of CpE (E = In Tl) and Cp2Pb resemble those present in mononuclear [Cp2Tl]214 and [Cp3Pb]24 anions (Figs. 7 and 8 respectively) which can be regarded as representing discrete fragments of the polymeric lattices of the neutral metallocenes.It is of interest to imagine whether ‘extended’ anions can be prepared corresponding to larger segments of these polymeric arrangements. The syntheses of such species is in fact accomplished very easily by reacting CpTl or Cp2Pb with alkali metal cyclopentadienides in the presence of cyclic polyethers (so-called crown ethers). These Lewis base ligands contain molecular cavities which are highly specific for the complexation of alkali metal cations of a particular size [e.g. 12-crown-4 and 15-crown-5 (Fig. 13)]. The [Cp choice of extended anions which are formed. This subtle influence is best seen in [Li(12-crown-4)2 +]2· 5Pb2]2[Cp9Pb4]2 (Fig.15) in which the formation of two Fig. 13 Structures of 12-crown-4 and 15-crown-5 Fig. 14 Structures of (a) [Cp3Tl2]– and (b) [Cp5Pb2]2 Fig. 15 Structure of [Li(12-crown-4)2 +]2·[Cp5Pb2]2[Cp9Pb4]2 sandwich cations [Li(12-crown-4)2]+ and [K(15-crown-5)2]+ are particularly stable18 and the effect of their formation in these reactions is to separate the alkali metal cation and the metallocene anion thus preventing competition for Cp electron density and encouraging the growth of larger anion chains. The 2]+·[Cp3Tl2]214 structures of [Li(12-crown-4) and [K(15-crown-5)2]+·[Cp5Pb2]219 contain the dinuclear triple- Chemical Society Reviews 1998 volume 27 230 different homologous anions (as opposed for example to the isomeric alternative of two identical [Cp7Pb3]2 anions) is probably due to effective packing in the crystalline lattice.14 Chemical fragmentation of the extended lattice of a p-block metallocene is one way by which modification of these systems can be achieved.However there are some more obvious expressions of the weakness in the association of the molecular units in these species. In particular dramatic changes in the structural pattern found in the Group 13 complexes occur upon increasing the substitution of the Cp rings. In contrast to the polymeric arrangement found for CpIn in the solid state the structures of MeCpIn20 and MeCpGa7 are composed of discrete metal octahedra in which the metal centres are linked by weak interactions [Fig. 16(a)].Such metal···metal interactions are reasonably common in compounds of TlI and InI in general and are present within the structures of CpIn and CpTl linking the polymeric stands togther. Increasing the steric bulk of the substituents present on the Cp rings tends to drive the structures towards smaller molecular arrangements an example of which is [BzCpIn] [BzCpNC5(CH2Ph)5] in which extensive metal- ···metal interactions are precluded by the steric demands and metal shielding of the ligand. The structure is that of a loosely Fig. 16 Structures of (a) [MeCpE] (ENIn Ga) and (b) [BzCpIn] linked dimer in which two molecular units are joined by only one In···In interaction [Fig. 16(b)].21 Although InI and TlI complexes have been known for many years the synthesis of stable organometallic complexes of GaI and AlI has only been made possible recently.Previously AlICl was thought to occur only in the gas phase at low pressure. However careful experimental work revealed that this lowoxidation state salt which is the key starting material for organo-AlI compounds can be isolated in a metastable form.8 The structure of [MeCpAl] is particularly intriguing being composed of an Al–Al bonded Al4 tetrahedron (Fig. 17).8 Like Fig. 17 Structures of [MeCpAl]4 other +1 oxidation state complexes discussed above these metal–metal interactions appear to defy simple bonding interpretations. They are commonly described as ‘closed-shell’ dispersive interactions and can only really be explained by detailed quantum mechanical treatments.22 Quantum mechanical calculations and spectroscopic studies of [MeCpAl]4 give good agreement of about 150 kJ mol21 for the association energy of the cluster (i.e.very weakly associated). A more recent development has been the realisation that the choice of solvent from which the metallocene is crystallised may affect the structure adopted.23 If crystals of Cp2Pb are grown by sublimation from the vapour then the orthorhombic form is obtained which has the polymeric zig-zag structure shown in Fig. 12(b). If the orthorhombic form is crystallised from toluene then the major product is the inclusion compound [{Cp2Pb}3·toluene]H having a similar structure to the orthorhombic form but now with an undulating sinusoidal arrangement of the polymer chain [Fig.18(a)]. The minor product of recrystallisation is a new hexagonal phase of plumbocene in which six Cp2Pb units are linked together into a cyclic doughnut [Fig. 18(b)]. A similar structural pattern has been found for the TlI complex [(1,3-Me3Si)2CpTl]6 in the solid state.24 4 Perspectives on the future and closing remarks The amazing structural diversity of main group metallocenes and the variety of bonding patterns they adopt make their study extremely exciting. There is still great scope for novel chemical and structural investigations of these systems and in particular for more extensive theoretical calculations probing the factors responsible for electronic and thermodynamic stabilisation. This review has used simple chemical concepts of design and structural modification in an attempt to provide a broader picture of the underlying trends in these species.These concepts are obviously far from complete and as new species emerge one important area will be the further refinement of existing structural models and the development of new structural concepts. New synthetic challenges are already apparent in the investigation of unusual highly reactive low-oxidation state p 231 Chemical Society Reviews 1998 volume 27 Fig. 18 Structures of (a) [{Cp2Pb}3·toluene] and (b) the hexagonal form of [Cp2Pb] complexes such as [MeCpAl]. There will undoubtedly be increased activity in this area in future. In addition engineering the crystal lattices of metallocene complexes and the preparation of new cationic and anionic multi-decker sandwich and cage arrangements provide a large area of interest which is still under development.5 References 1 C. Elschenbroich and A. Saltzer Organometallics 1st edn. VCH Weinheim 1988 and references therein. 2 J. P. Collman and L. S. Hegedus Principles and Applications of Organotransition Metal Chemistry 1st edn. Oxford University Press 1980 and references therein. 3 P. Jutzi Adv. Organomet. Chem. 1986 26 217. 4 D. R. Armstrong M. G. Davidson M. J. Duer D. Moncrieff C. A. Russell C. Stourton D. Stalke A. Steiner and D. S. Wright Organometallics. 1997 16 3340 and references therein. Chemical Society Reviews 1998 volume 27 232 5 P. Pyykk�o and J.-P. Desclaux Acc.Chem. Res. 1979 12 276 and references therein. 6 K. D. Bos E. J. Bulten and J. G. Noltes J. Organomet. Chem. 1975 99 397. 7 D. Loos E. Baum A. Ecker H. Schn�ockel and A. J. Downs Angew. Chem. 1997 109 894; Angew. Chem. Int. Ed. Engl. 1997 36 860 and references therein. 8 C. Dohmeier D. Loos and H. Schn�ockel Angew. Chem. 1996 108 141; Angew. Chem. Int. Ed. Engl. 1996 35 129 and references 9 See for example A. B. Cornwell and P. G. Harrison J. Chem. Soc. therein. Dalton Trans. 1975 1722. C3. 895. 10 E. J. Bulten and H. A. Budding J. Organomet. Chem. 1978 157 11 D. H. Harris and M. F. Lappert J. Chem. Soc. Chem. Commun. 1974 12 P. Jutzi and B. Hielscher Organometallics 1986 5 2511. 13 J. Alml�of L. Fernholt K. Færgri Jr. A. Haaland B. E. R. Schilling R. Seip and øl Acta Chem. Scand. Ser. A 1983 37 131. 14 M. A. Paver C. A. Russell and D. S. Wright Angew. Chem. 1995 107 1677; Angew. Chem. Int. Ed. Engl. 1995 34 1545. 15 See for example T. Birchall and J. A. Vetrone J. Chem. Soc. Chem. Commun. 1988 877. 16 S. Harder and H. Prosenc Angew. Chem. 1994 106 1830; Angew. Chem. Int. Ed. Engl. 1994 33 1744. 17 M. Bochmann and D. M. Dawson Angew. Chem. 1996 108 2371; Angew. Chem. Int. Ed. Engl. 1996 35 2226. 18 N. S. Poonia and A. V. Bajaj Chem. Rev. 1979 79 389. 19 M. A. Beswick C. N. Harmer C. A. Russell and D. S. Wright unpublished results. 20 O. T. Beachley Jr. M. R. Churchill J. C. Fettinger J. C. Pazik and L. Victoriano J. Am. Chem. Soc. 1986 108 4666. 21 H. Schumann C. Janiak F. G�orlitz J. Loebel and A. Dietrich J. Organomet. Chem. 1989 363 243. 22 R. Ahlrichs M. Ehrig and H. Horn Chem. Phys. Lett. 1991 183 227. 23 M. A. Beswick C. Lopez-Casideo M. A. Paver P. R. Raithby C. A. Russell A. Steiner and D. S. Wright J. Chem. Soc. Chem Commun. 1997 109. 24 S. Harvey C. L. Raston B. W. Skelton A. H. White M. F. Lappert and G. Srivastava J. Organomet. Chem. 1987 326 789. Received 28th November 1997 Accepted 8th January 19

ISSN:0306-0012    

DOI:10.1039/a827225z

出版商:RSC    

年代:1998

数据来源: RSC