摘要:

DALTON FULL PAPER J. Chem. Soc. Dalton Trans. 1998 Pages 1743–1750 1743 Silver(I) nitrate adducts with bidentate 2- 3- and 4-pyridyl phosphines. Solution 31P and [31P]109Ag] NMR studies of 1 2 complexes and crystal structure of dimeric [{Ag(d2pype)(Ï-d2pype)}2]- [NO3]2?2CH2Cl2 [d2pype 5 1,2-bis(di-2-pyridylphosphino)ethane] Susan J. Berners-Price,*,†,a Richard J. Bowen,a Peta J. Harvey,a Peter C. Healy a and George A. Koutsantonis b a School of Science Griffith University Nathan Brisbane Queensland 4111 Australia b Department of Chemistry University of Western Australia Nedlands Western Australia 6907 Australia The 1 2 complexes of silver(I) nitrate with 1,2-bis(di-n-pyridylphosphino)ethane (dnpype) for n = 2 3 and 4 have been synthesized and solution properties characterized by NMR spectroscopy including variable-temperature one-dimensional 31P-{1H} two-dimensional [31P]31P] COSY and [31P]109Ag] HMQC NMR experiments.The 3-pyridyl (d3pype) and 4-pyridyl (d4pype) complexes exist as bis-chelated monomeric [Ag(d3pype)2]1 and [Ag(d4pype)2]1 while the 2-pyridyl (d2pype) complex forms an equilibrium mixture of monomeric [Ag(d2pype)2]1 dimeric [{Ag(d2pype)2}2]21 and trimeric [{Ag(d2pype)2}3]31 species in which the d2pype ligands co-ordinate in both bridging and chelated modes via the phosphorus atoms. The relative percentages of the species present are dependent on both temperature and solvent. Crystals of the 2-pyridyl complex obtained from CH2Cl2–Et2O solution have been shown by crystal structure determination to be the dimer [{Ag(d2pype)(m-d2pype)}2]- [NO3]2?2CH2Cl2.Each silver ion is co-ordinated by one chelated and two bridging d2pype ligands forming a ten-membered ring in a double boat conformation. The pyridyl nitrogen atoms do not co-ordinate to the silver. The diVerences in solution behaviour of the three systems and the potential significance of these complexes to the antitumour properties of chelated 1 2 silver(I) diphosphine complexes are discussed. Like their gold(I) counterparts certain bis-chelated 1 2 silver(I) diphosphine complexes of the type [Ag(P]P)2]NO3 [where P]P is Ph2P(CH2)2PPh2 (dppe) cis-Ph2PCH]] CHPPh2 (dppey) or Et2P(CH2)2PEt2 (depe)] have been shown to exhibit antitumour activity against i.p P388 leukaemia in mice as well as antifungal and modest antibacterial properties.1,2 Although the mechanism for the cytotoxicity is not known tumour cell mitochondria are likely targets for these large lipophilic cations 3,4 and indeed the complex [Ag(eppe)2]NO3 [where eppe is Ph2P(CH2)2PEt2] exhibits selective primary antimitochondrial activity in yeast.5 However a major diYculty in the clinical use of these compounds is that they target mitochondria in all cells resulting in unacceptably high levels of toxicity.Studies of the antitumour activity of other large lipophilic cations such as bis quaternary ammonium heterocycles 6 and trialkylphosphium salts,7 have demonstrated a relationship between antitumour selectivity and lipophilic–hydrophilic balance and we have adopted the approach in our work on the antitumour properties of [M(P]P)2]1 cations of replacing the phenyl substituents of the diphosphine with pyridyl substituents in order to vary the hydrophilic character of the complexes.8 As part of this work we report here the synthesis and characterization by variabletemperature 31P-{1H} two-dimensional [31P]31P] COSY and [31P]109Ag] HMQC NMR spectroscopy of the solution properties of 1 2 complexes of silver(I) nitrate with the diphosphine ligands 1,2 bis(di-n-pyridylphosphino)ethane (dnpype) for n = 2 3 or 4 together with a single-crystal structure determination of the dimeric complex [{Ag(d2pype)(m-d2pype)}2][NO3]2? 2CH2Cl2.The results show the d3pype and d4pype complexes to exist in solution as monomeric bis-chelated [Ag(d3pype)2]1 and [Ag(d4pype)2]1 whereas the d2pype complex forms equilibrium mixtures of monomeric [Ag(d2pype)2]1 dimeric † E-Mail S.Berners-Price@sct.gu.edu.au [{Ag(d2pype)2}2]21 and trimeric [{Ag(d2pype)2}3]31 in which the d2pype ligands co-ordinate in both bridging and chelated modes with the relative percentages of the species present dependent on temperature and solvent.Experimental Preparation of compounds The dnpype ligands for n = 2 3 and 4 were prepared as described elsewhere.9 [Ag(d2pype)2]NO3. The compound AgNO3 (0.077 g 0.453 mmol) in water (1 cm3) was added with stirring to a suspension of d2pype (0.4 g 0.99 mmol) in acetone (20 cm3) to give a P P N N N N P P N N N N P P N N N N d2pype d3pype d4pype 1744 J. Chem. Soc. Dalton Trans. 1998 Pages 1743–1750 clear solution. After further stirring for 1 h the solvent was allowed to evaporate at room temperature depositing white microcrystalline material (0.83 g 94%) m.p.277–287 8C (Found C 54.0; H 4.5; N 12.9; P 12.6. C44H40AgN9O3P4 requires C 54.2; H 4.1; N 12.9; P 12.7%). FAB mass spectrum m/z 913 (M1 100%). ES mass spectrum m/z 913 [Ag- (d2pype)2]1; 1886 (1%) [{Ag(d2pype)2}2 21 1 NO3 2]1. The material was readily soluble in polar organic solvents but only slightly soluble in water. Needle-like crystals of the solvated dimer {[Ag(d2pype)2]NO3}2?2CH2Cl2 of marginal suitability for crystal structure determination were obtained with considerable diYculty by vapour diVusion of Et2O into a CH2Cl2 solution of the complex. [Ag(d3pype)2]NO3?3H2O. The compound AgNO3 (0.061 g 0.358 mmol) in water (0.4 cm3) was added dropwise to a solution of d3pype (0.303 g 0.75 mmol) in acetone (40 cm3) resulting in the immediate formation of a fine white suspension. The volume of the solvent was concentrated to ca.20 cm3 and the flask cooled overnight at 220 8C. The cold suspension was filtered aVording the complex as a microcrystalline solid (0.2 g 57%) m.p. 230–235 8C (Found C 51.1; H 4.4; N 12.1. C44H46AgN9O6P4 requires C 51.4; H 4.5; N 12.3%). [Ag(d4pype)2]NO3?5H2O. The compound AgNO3 (0.084 g 0.5 mmol) was added as a solid to a suspension of d4pype (0.4 g 1.0 mmol) in tetrahydrofuran (20 cm3). The mixture was stirred overnight and the resultant solid product collected by filtration. The solid was dissolved in methanol and insoluble material filtered oV. The compound precipitated as a white solid on addition of Et2O to the filtrate (0.2 g 41%) m.p. 225– 233 8C (decomp.) (Found C 49.8; H 4.5; N 11.6. C44H50- AgN9O8P4 requires C 49.7; H 4.7; N 11.9%).Both the 3- and 4-pyridyl complexes were found to be highly soluble in water dmso and methanol but insoluble in CH2Cl2. Despite many attempts however crystals of a size suitable for X-ray diVraction studies were not obtained for these two complexes. Spectroscopy Electrospray (ES) mass spectra were recorded in acetonitrile solutions on a Quattro II mass spectrometer with a cone potential of 25 V FAB mass spectra in a mixture of CH2Cl2 and p-nitrobenzyl alcohol on a VG Autospec mass spectrometer (Cs1 ion gun) with an accelerating voltage of 8 kV. Proton 13C and 31P NMR spectra were recorded on either Varian Gemini-200 or UNITY-400 spectrometers and were referenced as indicated in Tables 1–3. Typically 31P-{1H} spectra were recorded with a pulse angle of 458 and a relaxation delay of 2 s.‡ The 31P-{109Ag} NMR spectra were recorded on a Varian UNITY-400 spectrometer equipped with three RF channels and a 5 mm triple resonance 31P[1H/X] probehead with the X-channel tuned to 109Ag at 18.64 MHz.The 908 pulse for 31P was 12.3 ms and for 109Ag 100 ms. Sample spinning was not used. Both one-dimensional 109Ag-edited 31P spectra and twodimensional [31P]109Ag] spectra were recorded using an HMQC sequence. For {[Ag(d2pype)2]NO3}n 1J(109Ag]31P) was optimized at 295 K for n = 1 (266 Hz) and at 243 K for n = 2 (310 Hz); WALTZ-16 modulated 1H decoupling was applied throughout the whole sequence and the 109Ag spins were not decoupled. Two-dimensional spectra were acquired using the Haberkorn–Ruben (hypercomplex) method for quadrature detection in F1. Typically the spectral widths were 2000 and ‡ These pulsing conditions allow a fairly accurate estimate of the relative concentrations of [Ag(d2pype)2]1 and [{Ag(d2pype)2}2]21 by comparison of peak integrals since their 31P resonances have similar T1 values 1.71 ± 0.07 and 1.59 ± 0.03 s respectively as measured by the inversion recovery method for a solution of {[Ag(d2pype)2]NO3}n in CD3OD at 295 K.5690 Hz in the F1 (109Ag) and F2 (31P) dimensions respectively. Thirty-two time increments were used in each of which 32 to 160 transients were added with a 1 s relaxation delay. The 31P chemical shifts were referenced to external 85% H3PO4 (d 0) measured at 295 K and the 109Ag chemical shift reference was external 4 M AgNO3 in D2O. Two-dimensional phase-sensitive 31P homonuclear shift correlated (COSY) spectra were recorded with WALTZ-16 modulated 1H decoupling.The spectral width in F2 was 4068 Hz with 2048 data points. A total of 256 free induction decays were taken in F1 with 28 scans each. The recycle delay was set to 3 s to give a total experiment time of 14 h. Crystallography A unique room-temperature diVractometer data set (T 295 K; 2q–q scan mode monochromatic Mo-Ka radiation l = 0.710 73 Å) was collected for [{Ag(d2pype)(m-d2pype)}2]- [NO3]2?2CH2Cl2 on a colourless crystal with dimensions 0.16 × 0.06 × 0.16 mm yielding 6080 independent reflections within the limit 2qmax = 458; 1438 of these with I > 3s(I) were considered ‘observed’ and used in the large-block leastsquares refinement after Gaussian absorption correction (A*min,max = 1.05 1.12). Crystals of the complex were of marginal quality and the quality of the resulting determination was correspondingly poor.The structure was solved by heavy atom Patterson methods expanded using Fourier techniques and refined by full-matrix least squares on |F|. Limited data supported meaningful anisotropic thermal parameter refinement for Ag P and NO3 moieties only all other atoms being modelled with the isotropic form. Hydrogen atoms were included with x y z Uiso constrained at estimated values. Difference map residues were modelled in terms of CH2Cl2 of solvation (chloride thermal parameters anisotropic). The N atoms of the 2-pyridyl rings were indistinguishable and modelled as disordered C N composites over the pairs of possible sites. Conventional residuals R R9 at convergence were 0.078 0.070 [statistical weights derivative of s2(I ) = s2(Idiff) 1 0.0004s4(Idiff)].Neutral atom complex scattering factors were employed computation using the XTAL 3.2 program system implemented by S. R. Hall.10 Crystal data. C90H84Ag2Cl4N18O6P8 M = 2119.2 monoclinic space group P21/c (C5 2h no. 14) a = 15.869(6) b = 18.315(8) c = 17.369(9) Å b = 112.67(4)8 U = 4658 Å3 Dc (Z=2 dimers) = 1.51 g cm23 F(000) = 2160 mMo = 7.4 cm21. CCDC reference number 186/940. See http://www.rsc.org/suppdata/dt/1998/1743/ for crystallographic files in .cif format. Results and Discussion In previous work we have investigated the solution structures of 1 2 adducts of AgNO3 with the bidentate arylphosphines dppe dppp cis-dppey depe and eppe.11,12 Solution 31P NMR studies of these complexes showed evidence for only monomeric bis-chelated ionic complexes of type [Ag(P]P)2]NO3 with unco-ordinated anion and bidentate phosphine ligands.These complexes have greatly enhanced kinetic and thermodynamic stabilities with respect to similar AgP4 complexes containing monodentate phosphines. In the present study the evidence from 31P 1H and 13C NMR spectra (Tables 1–3) is consistent with a similar structural type for 1 2 adducts of AgNO3 with d3pype and d4pype. In contrast Ag P P P P J. Chem. Soc. Dalton Trans. 1998 Pages 1743–1750 1745 Table 1 Phosphorus-31 and 109Ag NMR parameters for {[Ag(dnpype)2]1}n complexes d(31P) a d(109Ag)b 1J(109Ag]31P) c/Hz Compound {[Ag(d2pype)2]NO3}n n = 1 n = 2 n = 3 {[Ag(d2pype)2]NO3}n n = 1 n = 2 [Ag(d3pype)2]NO3 [Ag(d4pype)2]NO3 Solvent CD3OD D2O CD3OD T/K 243 295 295 295 PA 7.3 3.1 1.0 7.3 3.1 25.5 2.2 PB 12.3 15.9 12.3 PC 6.1 AgX d 1411 1400 1418 1378 AgY d 1417 1397 1395 AgZ 1386 PA 266 218 e 203 f 266 263 PB ca.326 ca. 330 PC ca. 257 a Referenced to external 85% H3PO4 at 295 K. b Referenced to 4 M AgNO3 in D2O estimated error in chemical shifts ±5 ppm. c ±1 Hz for PA and ±10 Hz for PB and PC signals which are complex second-order multiplets. d The 109Ag chemical shifts of the monomer and dimer have diVerent temperature dependencies AgX 20.21 ppm K21; AgY 20.42 ppm K21. e 2J(PA]PB) = 41 Hz. f 2J(PA]PB) = 49 Hz. Table 2 Carbon-13 NMR data for 2- 3- and 4-pyridyl ligands and silver(I) complexes (at ambient temperature) d(13C),a J(C]P)/Hz Compound d2pype b {[Ag(d2pype)2]NO3}n c d3pype [Ag(d3pype)2]NO3 d4pype [Ag(d4pype)2]NO3 Solvent CDCl3 CDCl3 CDCl3 D2O CDCl3 CD3OD D2O C2 162.3 157.4 153.2 (vt) (12.6) 151.5 149.8 150.2 150.3 C3 129.1 (vt) (11) 129.2 132.4 (vt) (9.0) 126.8 126.9 (vt) (8.1) 128.9 (vt) (8.5) 127.9 C4 136.3 136.1 139.8 (vt) (7.3) 141.1 146.3 (vt) (9.9) d 141.7 C5 123.0 124.1 123.7 125.2 126.9 (vt) (8.1) 128.9 (vt) (8.5) 127.9 C6 149.8 149.8 150.3 151.2 149.8 150.2 150.3 CH2 22.1 23.0 22.9 23.5 22.3 23.2 24.0 a Singlet unless otherwise stated.b Assignments based on 13C assignments for the bidentate 2-pyridylphosphine Ph(2py)P(CH2)2PPh(2py).13 c Separate 13C resonances for monomer (n = 1) and dimer (n = 2) are not resolved. d Not resolved. Table 3 Proton NMR data for 2- 3- and 4-pyridyl ligands and silver(I) complexes (at ambient temperature) d(1H) Compound d2pype {[Ag(d2pype)2]NO3}n n = 1 n = 2 d3pype [Ag(d3pype)2]NO3 d4pype [Ag(d4pype)2]NO3 Solvent CD3OD CD3OD CDCl3 D2O D2O CDCl3 CD3OD CD3OD H2 8.59 8.09 8.57 8.58 8.39 8.43 H3 7.43 7.44 7.37 7.35 7.18 7.27 7.32 H4 7.69 7.57 7.43 7.46 7.59 7.18 7.87 H5 7.29 7.30 7.13 7.15 7.27 6.90 7.42 7.18 7.27 7.32 H6 8.56 8.55 8.28 8.19 8.59 8.09 8.47 8.58 8.39 8.43 CH2 * 2.44 (8.7) 2.95 3.12 3.00 2.16 (8.7) 1.81 2.86 2.12 (9.3) 2.19 (9.7) 2.77 * Broad singlet or quasi-triplet [J = 2J(31P]1H) 13J (31P]1H) (Hz) in parentheses where resolved].to the complexes with phenyl-substituted phosphines these complexes are highly soluble in water. The 31P NMR spectra of both complexes consist of two overlapping doublets (intensity ratio 51 49). The 1J(31P]107,109Ag) spin–spin couplings were resolved at ambient temperature and the values (Table 1) are typical of those expected for bis-chelated complexes with tetrahedral AgP4 co-ordination.11,12 The 1H NMR data (Table 3) are consistent also with the formation of simple monomeric species.For bidentate phosphines with (CH2)2 backbones (e.g. dppe) the CH2 protons constitute the AA9 part of an A2XX9A29 spin system as a result of unequal 31P]1H spin–spin coupling to the two P atoms and give rise to a quasi-triplet in which the separation of the outer two peaks corresponds to |2J(31P]1H) 1 3J(31P]1H)|. This pattern is observed for the dnpype ligands (Table 3) and the small downfield co-ordination shift (Dd 0.6–1.0) and broadening of the (CH2)2 resonance to give an unresolved multiplet is characteristic of the behaviour observed previously for bis-chelated gold(I) diphosphine complexes. 14 For [Au(dppe)2]Cl the aromatic protons were shielded with respect to those of the free diphosphine but this was not observed here for [Ag(dnpype)2]NO3 (n = 3 4) where all protons are slightly deshielded (Dd < 0.1) with respect to d3pype or d4pype (Table 3).The 109Ag chemical shifts (Table 1) obtained from [31P]109Ag] HMQC spectra lie within the range observed previously 11,15 for [Ag(dppe)2]NO3 and analogous bis-chelated AgNO3 complexes of bidentate phenylphosphines where the strong deshielding (high frequency end of the known 109Ag shift range) was attributed to the good p-acceptor properties of the bidentate phosphine ligands.11 In contrast with the above results the 31P NMR solution spectra for the 2-pyridyl complex were found to be considerably more complex. Variable-temperature data recorded in CH3OH– CD3OD solution are shown in Fig.1 with chemical shift and coupling constant data in Table 1. At 298 K the spectrum consisted of two overlapped doublets [d 7.3 1J(107,109Ag]31P) 231 266 Hz] and two pairs of broadened multiplets at d 3.1 and 12.3. On cooling the solution the peaks sharpened and the pair 1746 J. Chem. Soc. Dalton Trans. 1998 Pages 1743–1750 of doublets at d 7.3 gradually decreased in intensity while the other resonances increased in intensity. The fine structure of these multiplets was fully resolved at 263 K where a new set of peaks centred at d 1.0 6.1 and 15.9 became visible and increased in intensity with decreasing temperature. As for the 3- and 4-pyridyl complexes the pair of doublets at d 7.3 1J(107,109Ag]31P) ca. 250 Hz is typical for monomeric tetrahedral bis-chelated [Ag(P]P)2]1 complexes with four equivalent P atoms11,12 and is accordingly assigned as the monomeric species [Ag(d2pype)2]1.The multiplets at d 3.1 12.3 are assigned however to the dimeric complex {[Ag(d2pype)2]}2 21 with both chelating and bridging phosphine ligands. Although each silver(I) ion in this dimer has AgP4 co-ordination there are two distinct phosphorus environments for chelated (PA) and bridging (PB) d2pype ligands respectively. The 31P COSY spectrum (Fig. 2) shows cross-peaks between the two multiplets confirming that they are part of the same spin system and the assignment is further substantiated by the [31P]109Ag] HMQC NMR spectrum (Fig. 3) which shows two 31P]109Ag two-dimensional cross-peaks with identical 109Ag chemical shifts (d 1417) consistent with only one type of silver environment (AgY).The high field 31P multiplet (d 3.1) can be assigned to the chelated (PA) environment and the multiplet at d 12.3 to the bridging (PB) environment based on the splitting patterns. Although the spin system is second order the 5J(PA]PB) coupling is expected to be only very small. By recording a 109Ag-edited 31P NMR spectrum Fig. 1 161.9 MHz 31P-{1H} NMR spectra of {[Ag(d2pype)2]NO3}n in CH3OH–30% CH3OD at 298 263 243 and 213 K. The resonances are assigned to the monomeric (m) dimeric (d) and trimeric (t) species {[Ag(d2pype)2]1}n Ag PA PA PB PB Ag PA PA PB PB 2+ (thus removing transitions associated with the 107Ag isotope) the PA multiplet simplified to a pair of virtual triplets from which the values of 1J(31PA]109Ag) and 2J(PA]PB) were obtained (Table 1).The 2J(PA]PB) coupling (41 Hz) corresponds to the coupling of P atoms in the chelated and bridging d2pype ligands across silver and is comparable to that observed for the 2J[P(Ph2)]Ag]P(Et2)] coupling in the tetrahedral silver(I) complex [Ag{Ph2P(CH2)2PEt2}2]NO3 (50 Hz).11 The PB multiplet has a greater complexity as a consequence of couplings to both Ag atoms and the spin system is not readily analysable even in the simplified 109Ag-edited 31P spectrum. However based on the splitting between the two symmetrical halves of the multiplet the 1J(31PB]109Ag) coupling is estimated to be ca. 326 Hz and ca. 50% greater than 1J(31PA]109Ag) despite only small diVerences in the values of the Ag]P bond distances found in the crystal structure (see below).The equilibrium between the monomer and dimer can be represented by equation (1) with equilibrium [Ag(d2pype)2] 1 [Ag(d2pype)2] [{Ag(d2pype)2}2] (1) constant K1 = [{Ag(d2pype)2}2]/[Ag(d2pype)2]2. The relative concentrations of monomer and dimer were determined by comparison of the 31P peak integrals for a solution of [Ag- (d2pype)2]1 in CD3OD (5.0 mM based on [Ag]1).§ Values of K1 were obtained in the temperature range 298–213 K and are presented in Table 4. A plot of ln K1 vs. 1/T gives R2 = 0.98 Fig. 2 Phase-sensitive 31P-{1H} COSY spectrum of the solution of {[Ag(d2pype)2]NO3}n in CH3OH–30% CH3OD at 233 K showing connectivities between the PA and PB multiplets of the dimer (d) and between the PA and PB and PB and PC multiplets of the trimer (t). The cross-peaks shown as inserts are plotted at a lower threshold for clarity § At this concentration the complex remained totally soluble in the temperature range 298 to 213 K.J. Chem. Soc. Dalton Trans. 1998 Pages 1743–1750 1747 for ln K1 = (4893/T) 2 9.232 (Fig. 4) yielding values for DH8 and DS8 of 241 (±2) kJ mol21 and 277 (±5) J K21 mol21 respectively. The peaks at d 1.0 6.1 and 15.9 which first appear in the spectrum at 263 K are assigned to formation of a trimeric cluster [{Ag(d2pype)2}3]31 which has three non-equivalent phosphorus sites and two non-equivalent silver sites. In this cluster the terminal chelated (PA) environment would be expected to be similar to that found in the dimer and the high field multiplet (d 10) has a similar splitting but shifted slightly to low frequency of that of the dimer PA multiplet at d 3.1.The values of Fig. 3 The normal 31P NMR spectrum of a solution of {[Ag- (d2pype)2]NO3}n at 243 K (a) and the [31P]109Ag] HMQC NMR spectrum in CD3OD at the same temperature (b) AgZ PC PC PC PC AgY PA PA PB PB AgY PB PB PA PA 3+ Table 4 Values of ln K1 and ln K2 as a function of temperature for {[Ag(d2pype)2]1}n for total [Ag1] = 5.0 × 1023 mol l21 in CH3OH– CD3OD solution T/K 295 283 273 263 253 243 233 223 213 103 [monomer]/ mol l21 1.16 0.83 0.60 0.43 0.32 0.19 0.085 0.095 0.04 103 [dimer]/ mol l21 1.92 2.09 2.15 2.19 2.12 1.97 1.77 1.66 1.67 103 [trimer]/ mol l21 0.00 0.00 0.03 0.06 0.14 0.29 0.46 0.53 0.54 ln K1 7.26 8.02 8.69 9.38 9.94 10.91 12.38 12.12 13.86 ln K2 —— 3.14 4.15 5.33 6.65 8.01 8.12 9.00 1J(31PA]109Ag) 203 Hz and 2J(PA]PB) 49 Hz obtained from the 109Ag-edited 31P spectrum are slightly lower and higher respectively than for the dimer suggesting a relative weakening of Ag]P bond strength in the chelate and a strengthening of the Ag]P (bridging) bonds with respect to the analogous environment of the dimer.The trimer also has two non-equivalent phosphorus environments for bridging d2pype ligands (PB and PC) co-ordinated to the terminal and central Ag atoms respectively. The broadened multiplet at d 15.9 is assignable to PB based on the chemical shift (which is closest to that of the PB multiplet of the dimer) and the 1J(109Ag]31PB) coupling estimated to be ca. 330 Hz based on the splitting between the two symmetrical halves of the multiplet in the 109Ag-edited 31P spectrum which is similar to that of the dimer.The broadened doublet at d 6.1 is assigned to PC and has similar chemical shift and 1J(109Ag]31P) coupling (ca. 257 Hz) to that of the monomer. These assignments are substantiated by the 31P COSY spectrum of the solution at 233 K (Fig. 2) which shows the expected cross-peaks between the PA and PB multiplets and a second set of cross-peaks between the PB and PC multiplets. No correlation is observed between PA and PC which would require a resolved 5J(P]P) coupling. The trimer contains non-equivalent silver environments for the terminal (AgY) and central (AgZ) silver atoms and therefore two distinct 109Ag chemical shifts are expected in the 109Ag NMR spectrum. These are clearly visible in the [31P]109Ag] HMQC spectrum at 243 K (Fig. 3) with 31P/109Ag cross-peaks for Ag]PA at d 1.0/1397 and Ag]PC at d 6.1/1386.A peak for Ag]PB (expected at 15.9/1397) is not resolved in Fig. 3 presumably because the 31PB multiplet is very broad and signal intensity is lost due to relaxation during the HMQC pulse sequence. The equilibrium between the monomer dimer and trimer is represented by equation (2) with K2 = [{Ag(d2pype)2}3]/ [{Ag(d2pype)2}2][Ag(d2pype)2]. As for the monomer–dimer [{Ag(d2pype)2}2] 1 [Ag(d2pype)2] [{Ag(d2pype)2}3] (2) equilibrium the relative concentrations of the three species are obtainable directly from peak integrals yielding values of K2 as a function of temperature (Table 4). The plot of ln K2 vs. 1/T in the temperature range 233–263 K (Fig. 4) gives R2 = 0.99 for ln K2 = 7504(1/T) 2 24.26 and yields values of DH8 and DS8 of 262 (±2) kJ mol21 and 2200 (±5) J K21 mol21 respectively.Values of K2 determined at 213 and 223 K are significantly lower than predicted and while both broadening and overlap of peaks makes the estimation of K2 at these temperatures less Fig. 4 Plots of ln K1 (a) and ln K2 (b) vs. 1/T for the equilibria obtained from variable-temperature 31P NMR spectra of a solution of {[Ag- (d2pype)2]NO3}n in CD3OD (5.0 mM based on [Ag1]) 1748 J. Chem. Soc. Dalton Trans. 1998 Pages 1743–1750 meaningful the possibility of further aggregation to tetrameric or higher order clusters cannot be discounted. Such clusters would contain a greater number of PC phosphorus sites relative to PA and PB with chemical shifts that would be expected to be similar to and overlap with those of the trimer which would result in a greater intensity of the PC multiplet relative to PA and PB.The observation of a small increase in the relative intensity at 213 K for the PC multiplet is consistent with this. As for the 3- and 4-pyridyl complexes the 109Ag chemical shifts for {[Ag(d2pype)2]1}n occur within the range observed previously for AgP4 complexes of phenyl-substituted diphosphines. 11,15 The 109Ag chemical shifts become more shielded with increase in temperature but the 109Ag environments in the monomer and dimer exhibit diVerent temperature dependencies (Table 1) so that at 295 K the 109Ag shift of the dimer is to lower frequency of the monomer but this situation is reversed at 243 K. For the trimer the 109Ag shifts of both Ag are significantly more shielded than those of the dimer at the same temperature. The presence of an equilibrium mixture of the monomeric and dimeric d2pype species in methanol was not apparent in 13C NMR spectra because separate peaks for monomer and dimer were not resolved (Table 2) but it was evident in the variable-temperature 1H NMR spectra of the system albeit less easily followed than in the 31P spectra due to considerable overlap of resonances.However in the aromatic region the H6 proton of the pyridine ring of 2-pyridylphosphines is strongly deshielded from the remaining aromatic protons 16 and occurs in a clear region of the spectrum. At 298 K all 1H resonances were broadened but multiplet splitting patterns were resolved on cooling to 273 K. For the monomer the H6 resonance could be assigned to a peak at d 8.55 since this decreased in intensity on cooling the solution consistent with the behaviour observed in the 31P NMR spectra.Similarly a pair of peaks of equal intensity at d 8.19 and 8.28 could be assigned to the H6 protons of pyridyl rings in the dimer in non-equivalent chelated and bridged d2pype ligands. By using these resonances as a reference point the other pyridyl 1H resonances of the monomer and dimer could be assigned from observed connectivities in phasesensitive double-quantum filtered 1H COSY spectra. These assignments are in Table 3. Additional resonances appeared in the aromatic region as the solution was cooled which are possibly due to the trimer but the peaks were too broad to allow a complete assignment. The 31P NMR spectra recorded at 295 K for solutions of {[Ag(d2pype)2]NO3}n of equal concentration (10.2 mM based on [Ag1]) in a range of solvents show the relative percentages of the monomer and dimer to be strongly solvent dependent with the concentration of the monomer decreasing from ca.67% in CHCl3 and CH2Cl2 to 19% in methanol and 12% in ethanol while in acetonitrile the dimer was found to be the only species present in the solution with no signal from the monomeric species observed. These data suggest that the [M(P]P)2]1 cations in these systems are not isolated species in solution but interact strongly with solvent such that equilibrium (1) is likely to be more properly represented by equation (1a) or similar 2[M(P]P)2]1X2.solv [{M(P]P)2}2]212X2.solv (1a) with involvement of anion as well as solvent. Within this context the relative stability of the monomeric dimeric and trimeric species will depend not only on the relative stabilities of the isolated cations but also on diVerences in the strength of intermolecular interactions between the anion solvent and cation.While a detailed analysis of the reasons as to underlying cause(s) for the shift of the equilibrium to the left for complexes with dppe d3pype and d4pype ligands and to the right for d2pype requires the collection of further spectroscopic and structural data on complexes with a variety of counter anions in a wider range of solvents it is clear from the present results that the position of the pyridine nitrogen in the ring has a significant eVect on this chemistry. The mechanism of the transition between the monomeric dimeric and trimeric 2-pyridyl species requires the breaking of at least one Ag]P bond for each silver atom and in principle formation of unco-ordinated P atoms.We have shown previously that this mechanism occurs for 1 2 adducts of silver(I) salts with 1,3-bis(diphenylphosphino)propane (dppp) where there is an equilibrium in solution between neutral [AgX(dppp- P,P9)(dppp-P)] and ionic [Ag(dppp-P,P9)2]X with the position of the equilibrium dependent on the nature of the anion X.12 In the present case there is no evidence from the 31P NMR spectra for unco-ordinated P which suggests that the process may involve formation of clusters of monomers for example of the type {[M(P]P)2]1X2[M(P]P)2]1} (observed as minor species in the electrospray mass spectrum) which are then able to rearrange in a concerted fashion to form dimeric or higher order complexes at a rate faster than the NMR timescale.Crystal structure The results of the room-temperature single-crystal X-ray study on crystals obtained from recrystallization of the 1 2 adduct of AgNO3 with d2pype from CH2Cl2–Et2O solution are consistent with the formation of dimeric cations [(d2pype)Ag(m-d2pype)2- Ag(d2pype)]21 unco-ordinated nitrate anions and solvated dichloromethane. Importantly this complex is isomorphous with the methanol solvate of the analogous dppe complex.17 A projection of the cation is shown in Fig. 5 with relevant geometric parameters for the two structures listed in Table 5. The two halves of the cation dimer are related by a centre of crystallographic symmetry with each silver atom co-ordinated Fig. 5 Representative view of the [Ag2(d2pype)4]21 cation of [Ag2- (d2pype)4][NO3]2?2CH2Cl2 Table 5 Geometric parameters (bond lengths in Å angles in 8) for dimeric complexes M]P(A1) M]P(A2) M]P(B1) M]P(B2) Average M]P P(A1)]Ag]P(A2) P(A1)]Ag]P(B1) P(A1)]Ag]P(B2) P(A2)]Ag]P(B1) P(A2)]Ag]P(B2) P(B1)]Ag]P(B2) Ag/d2pype a 2.50(1) 2.521(8) 2.46(1) 2.496(8) 2.49(3) 83.4(3) 125.5(3) 110.3(3) 115.1(3) 120.7(3) 102.6(3) Ag/dppeb 2.597 2.509 2.526 2.550 2.55(4) 84.1 118.0 119.4 118.5 106.4 108.4 Ag/dmpec 2.557(6) 2.491(4) 2.471(4) 2.465(4) 2.50(4) 83.5(2) 114.1(2) 144.4(2) 115.6(2) 117.6(2) 109.6(2) Cu/dmped 2.289(1) 2.293(1) 2.267(1) 2.263(1) 2.28(2) 89.2(1) 116.9(1) 113.2(1) 110.3(1) 115.1(1) 110.7(1) a This work.b Ref. 17. c Ref. 19. d Ref. 18. J. Chem. Soc. Dalton Trans. 1998 Pages 1743–1750 1749 to one bidentate and two bridging d2pype ligands with the bridging ligands and silver atoms forming a ten-membered ring in a double boat conformation.This structural type is rare for Group 11 bidentate phosphine complexes being recorded previously only for [Ag(dppe)2]2- [NO3]2 17 and for [Cu(dmpe)2]2[BF4]2 18 and [Ag(dmpe)2]2- [BPh4]2,19 the majority of reported structures existing as the tetrahedral monomer12,20 or for copper complexes as 2 3 dimers with co-ordinated anion X displacing the second bridging phosphine.21–26 However X-ray crystallographic studies currently in progress show that 1 2 complexes of gold chloride 27 and copper iodide28 with d2pype also crystallize as solvated dimers analogous to the present silver nitrate complex suggesting that the dimeric structural type may be stabilized in the solid state with respect to the monomer by the d2pype ligand.In the present structure the pyridyl groups on the chelating and bridging ligands adopt both approximate edge-face and butterfly wing conformations with acute Ag]P]Cipso]Cortho torsion angles of 16.8 74.78 [P(A1)] 263.5 65.8 [P(A2)] 21.1 282.2 [P(B1)] and 254.9 28.38 [P(B2)]. The bridging pyridyl substituents occupy approximately axial and equatorial positions in the ten-membered ring with the axial groups from adjacent ligands atoms adopting a face-face conformation (Fig. 5). The nitrate group is located in a general lattice position adjacent to the chelating phosphine and forms a weak hydrogen bond with the solvated CH2Cl2 (O ? ? ? H ca. 2.4 Å). The CH2Cl2 molecule lies in proximity to three phenyl rings (A11) (A22) from the chelating ligand and (B11) from the bridging ligand.The Ag]P bond lengths range from 2.46(1) to 2.521(8) Å with an average value of 2.49(3) Å (Table 5). The two Ag]PA distances are marginally shorter than the Ag]PB distances but probably not significantly so given the relatively poor quality of the X-ray data. For comparison the average values of Ag]P for the analogous dppe and dmpe complexes are 2.55(4) and 2.50(4) Å respectively while values for the monomeric tetrahedral complexes [Ag(dppe)2]NO3 20 and [Ag(dppp)2]- SCN12 are 2.52(2) and 2.52(1) Å. Overall the changes in substituent or co-ordination mode from chelating to bridging appear to have only a marginal eVect on the Ag]P bond lengths. The P]Ag]P angles reflect diVerences in chelate versus bridging co-ordination with PB]Ag]PB 102.6(3)8 greater than PA]Ag]PA 83.4(3)8 while the four PA]Ag]PB angles are each greater than the tetrahedral angle ranging from 110.3(3) to 125.5(3)8.Finally we note that the results of this work provide no evidence for the co-ordination of the pyridyl N atoms (either in the solid state or in solution). Previous work on diphenyl- (2-pyridyl)phosphine complexes [PPh2(2py)] with silver chloride have shown that for the dimeric system [{PPh2(2py)}Ag(m- Cl)2{m-PPh2(2py)}Ag{PPh2(2py)}] the two silver atoms have AgCl2P2 and AgCl2PN co-ordination with one of the PPh2(2py) ligands bridging the two Ag atoms in a P N bidentate fashion,29 while for the tetrameric complex [{Ag[PPh2(2py)]Cl}4] no nitrogen co-ordination occurs,30 with the conclusion that pyridine N-co-ordination to silver is only possible when chloro/ phosphorus co-ordination is not suYcient for co-ordinative saturation.It was proposed also 30 that weak donor atoms such as BF4 2 or PF6 2 would favour N-co-ordination. In the present case with the nitrate anion however this is prevented by P P P P M M Cu PA PA PB X Cu PA PA PB X the apparent strong preference of the silver for the AgP4 co-ordination sites through either chelation or bridging co-ordination of the diphosphine ligands. Conclusion The 1 2 complexes AgNO3 with bidentate pyridylphosphine ligands are more hydrophilic than the phenyl-substituted analogues and the degree of hydrophilicity depends critically on the position of the pyridyl N atom. The results presented here are of importance to the interpretation of the antitumour properties of complexes of this type. We have shown here that the association equilibrium between the monomeric and dimeric forms of {[Ag(d2pype)2]1}n is solvent dependent and we have reported elsewhere 3 that 31P NMR signals assignable to both the monomeric and dimeric species were observed for {[Ag(d2pype)2]1}n in blood plasma at 37 8C.Clearly such an association equilibrium must be taken into account when considering the likely speciation of the complex in vivo. The structural results for [{Ag(d2pype)(m-d2pype)}2][NO3]2 show that the solvent is incorporated within the lattice and the 2-pyridyl complex has only limited solubility in water. The location of the pyridyl N atom within the inner core of the cation means that the lipophilic properties of the 2-pyridyl complexes are not likely to vary greatly between the various species.On the other hand the increased hydrophilic character of the monomeric 3-pyridyl and 4-pyridyl complexes is a consequence of the more exposed N atoms. Several classes of lipophilic cations with antimitochondrial antitumour activity have demonstrated a relationship between antitumour selectivity and lipophilic– hydrophilic balance and our preliminary studies show a similar relationship for these silver(I) complexes and for related gold(I) pyridylphosphine complexes when tested against human ovarian cancer cell lines in culture.8 We are currently investigating further the antitumour selectivity of these types of complexes. Acknowledgements We acknowledge support of this work by the Australian Research Council and the Australian National Health & Medical Research Council (R.Douglas Wright Award to S. J. B.-P.) and thank Dr. Rodney Sue for assistance with some of the NMR experiments and Dr. Paul Bowyer Research School of Chemistry Australian National University for recording the electrospray mass spectra. We are grateful also to Associate Professor Allan White Dr. Brian Skelton and Dr. EVendy and the University of Western Australia Crystallographic Centre for recollection of the structural data for [{Ag(d2pype)2}2]- [NO3]2 and expert advice and assistance in the structure determination and thank Dr. Ken Busfield for helpful advice on the thermodynamic data. References 1 S. J. Berners-Price and P. J. Sadler Struct. Bonding (Berlin) 1988 70 27. 2 S. J. Berners-Price R. K. Johnson A. J. Giovenella L. F. Faucette C. K. Mirabelli and P. J. Sadler J. Inorg.Biochem. 1988 33 285. 3 S. J. Berners-Price and P. J. Sadler Coord. Chem. Rev. 1996 151 1. 4 Y. Dong S. J. Berners-Price D. R. Thorburn T. Antalis J. Dickinson T. Hurst L. Qui S. K. Khoo and P. G. Parsons Biochem. Pharmacol. 1997 53 1673. 5 S. J. Berners-Price D. C. Collier M. A. Mazid P. J. Sadler R. E. Sue and D. Wilkie Metal-Based Drugs 1995 2 111. 6 W. A. Denny G. J. Atwell B. C. Baguley and B. F. Cain J. Med. Chem. 1979 22 134. 7 D. C. Rideout T. Calogeropoulou J. S. Jaworski R. J. Dagino and M. R. McCarthy Anti-Cancer Drug Design 1989 4 265. 8 S. J. Berners-Price R. J. Bowen M. J. McKeage P. Galettis L. Ding C. Baguley and W. Brouwer J. Inorg. Biochem. 1997 67 154. 1750 J. Chem. Soc. Dalton Trans. 1998 Pages 1743–1750 9 R. J. Bowen A. C. Garner S. J. Berners-Price I.D. Jenkins and R. E. Sue J. Organomet. Chem. in the press. 10 S. R. Hall H. D. Flack and J. M. Stewart The XTAL 3.2 Reference Manual Universities of Western Australia Geneva and Maryland 1992. 11 S. J. Berners-Price C. Brevard A. Pagelot and P. J. Sadler Inorg. Chem. 1985 24 4278. 12 D. AVandi S. J. Berners-Price EVendy P. J. Harvey P. C. Healy B. E. Ruch and A. H. White J. Chem. Soc. Dalton Trans. 1997 1411. 13 P. H. M. Budzelaar J. H. G. Frijns and A. G. Orpen Organometallics 1990 9 1222. 14 S. J. Berners-Price and P. J. Sadler Inorg. Chem. 1986 25 3822. 15 S. J. Berners-Price P. J. Sadler and C. Brevard Magn. Reson. Chem. 1990 28 145. 16 G. E. GriYn and W. A. Thomas J. Chem. Soc. B 1970 477. 17 H. Yang L. Zheng Y. Xu and Q. Zhang Wuji Huaxue Xuebao 1992 8 65 (Chem. Abstr. 1992 117 212 593e).18 B. Mohr E. E. Brooks N. Rath and E. Deutsch Inorg. Chem. 1991 30 4541. 19 V. Saboonchian G. Wilkinson B. Hussain-Bates and M. B. Hursthouse Polyhedron 1991 10 737. 20 C. S. W. Harker and E. R. T. Tiekink J. Coord. Chem. 1990 21 287. 21 A. P. Gaughan R. F. Ziolo and Z. Dori Inorg. Chem. 1971 10 2776. 22 V. G. Albano P. L. Bellon and G. Ciani J. Chem. Soc. Dalton Trans. 1972 1938. 23 P. Fiaschi C. Floriani M. Pasquali A. Chiesi-Villa and C. Guastini Inorg. Chem. 1986 25 462. 24 E. W. Ainscough E. N. Baker A. G. Bingham A. M. Brodie and C. A. Smith J. Chem. Soc. Dalton Trans. 1989 2167. 25 A. P. Gaughan K. S. Bowman and Z. Dori Inorg. Chem. 1972 11 601. 26 E. W. Ainscough E. N. Baker M. L. Brader A. M. Brodie S. L. Ingham J. M. Walters J. V. Hanna and P. C. Healy J. Chem. Soc. Dalton Trans. 1991 1243. 27 S. J. Berners-Price R. J. Bowen T. W. Hambley and P. C. Healy unpublished work. 28 S. J. Berners-Price R. J. Bowen and P. C. Healy unpublished work. 29 N. W. Alcock P. Moore P. A. Lampe and K. F. Mok J. Chem. Soc. Dalton Trans. 1982 207. 30 Y. Inoguchi B. Milewski-Mahrla D. Neugebauer P. G. Jones and H. Schmidbaur Chem. Ber. 1983 116 1487. Received 19th December 1997; Paper 7/09098F

ISSN:1477-9226    

DOI:10.1039/a709098f

出版商:RSC    

年代:1998

数据来源: RSC