11 12 M. B. Hursthouse and S. Neidle MULTAN procedure. It seems that these methods have the attraction of relative simplicity and do actually solve difficult structures.' Of especial interest to the non-theoretical crystallographer is an analysis of a number of 'failures' of crystal- structure analysis;' it is apparent that exercise of a non 'black-box' mentality in the application of the direct methods computer programs available can often pay dividends in the solution of such structures. Some even small structures are it seems inherently impossible to solve by simple approaches. A procedure to over- come these problems has been suggested,' which 'should be able routinely to solve structures with 100 atoms' 2 Electron Density Distribution More papers have described the determination of electron density distributions in molecules.X-N maps for sulphamic acid using X-ray and ncutron data collected at 78 K show strong bond populations in all bonds with peaks in the S-N and S-0 bonds similar to peaks in bonds between first row atoms only." Broad peaks for the lone pairs on oxygen atoms suggest a situation intermediate between sp and sp2 hybridization and the absence of any build-up of electron density in the H.-O bonds supports the idea of an electrostatic model. For the molecule of ['H12]-2,5- dimethylhex-3-yne-2,5-diol the deformation density maxima are 0.58 and 0.36 e A-3 for the triple and single C-C bonds but only 0.09 for the C-0 single bonds." In the molecule of tetraphenylbutatriene the central C=C bond length is 1.260A in contrast to the outer bonds whose lengths are 1.348 A.12aThe defor- mation densities in the butadiene skeleton show that the .rr-lobes in adjacent C=C bonds are mutually perpendicular.The deformation densities in allene carboxyl and amide groups have also been determined for a complex between allenedicar- boxylic acid and acetamide.126 In the molecule of sym -dibenzo-cyclo-octa-13-diene-3,7-diyne (l),the electron density around the centre of the triple bond is asymmetric with a sIight accumulation of charge inside the ring. l3 3 Molecular Conformations The incorporation of potential energy calculations into structural studies is also attracting more and more attention. One of the main problems in this kind of work is the reliability and suitability of the interatomic potential functions used in the calculations and attempts are being made to determine these experimentally.An example of this approach is the calculation of such functions via an analysis of ' P. Main Actu Cryst. 1978 A34 31. L. Lessinger Acta Cryst. 1976 A32 538. M. M. Woolfson Acta Cryst. 1977 A33 219. lo J. W. Bats P. Coppens. and T. F. Koetzle Actu Cryst. 1977 B33 37. '' R. B. Helmhold and A. Vos. Acta Cryst. 1977 A33 456. (a)Z. Berkovitch-Yellin and L. Leiserowitz Acta Cryst. 1977 B33 3657; (b)Z. Berkovitch-Yellin,L. Leiserowitz and F. Nader ibid. p. 3670. l3 R. Destro T. Pilati and M. Simonetta. Acfa Crysf.. 1977 B33 447. Physical Methods-Part (ii) X-Ray Crystallography crystal lattice vibrational frequencies in some hydrocarbons.l4 Applications of potential energy calculations have been described for the system l-ethyl-l-methyl- 4-piperidinium perchlorate where deformations of some interbond angles in the cation have been correlated with particular van der Waals' and for the adrenaline In this latter case the conformation of the molecule found in some structures does not correspond to a minimum in the free-molecule con- formational energy map and it has been shown that the lattice energy compensates for the loss in conformation energy. Structure analyses of some polyphenyls have also raised some interesting conformational points. At room temperature the crystal structure of p-terphenyl apparently contains only one molecule per asym- metric unit in which some of the atoms show very large thermal motion.On cooling two of the unit cell edges double up to give a superstructure where the end rings of the molecule are stabilized into one of the two potential wells associated with each C-C single bond.I7" Similar effects are found for p-quaterphenyl"' and biphenyl. 17' A topic in many ways related to the study of molecular conformation is that of the geometry of strained molecules particularly those containing ring systems. Classic examples of strained aromatic molecules are the cyclophanes and studies of meta-I' and para-cyclophane derivatives have been described. In the centrosym- metric quadruple-layered cyclophane (2),19the two outer benzene rings are boat- shaped and the inner rings adopt a novel twist shape.(21 In the crowded fulvalene l-methyl-2-(9'-fluorenylidene)-1,2-dihydropyridine,*' the twist about the linkage bond is 35.7' indicating a significant contribution from the form (3). Other examples of strained-ring molecules which show bond lengthening and/or angle strain are the A-C'-C stereoisomer of dodecahydro- trypticene,*' the triterpene oxide companulin (4),22 and 6,9-diaza-5,10-l4 T. L. Starr and D. E. Williams Acta Cryst. 1977 A33 771. Is W. Fedeli F. Mama E. Giglio C. Quagliata and N. Scarcelli Actu Cryst. 1976 B32 878. 16 J. Caillet P. Claveni and B. Pullmann Acru Crysf.,1976 B32 2740. l7 (a) J. L. Baudoir Y. Delugeard and H. Caillean Acta Cryst. 1976 B32 150; (6)Y.Delugeard J. Desucher and J. L. Baudoir ibid..p. 702;(c) G. P. Charbonneau and Y. Delugeard ibid.,p. 1420. 18 Y. Kai N. Yasuoka and N. Kasai Actu Cryst. 1971 B33 754. H Mizuno K. Nishiguchi T. Toyoda T. Otsubo S. Misurni and N. Morimoto Acta Crysr. 1977 B33 329. 2o H. L. Arnmon Acru Cryst. 1976 B32 2693. 21 A. Albinati J. Briickner and G. Allegra Actu Crysf. 1977.B33 229. '' F. Mo Acra Cryst. 1977.B33 641. M. B. Hursthouse and S. Neidle dioxotricyclo[7,3,0,0'.6]dodecane (5) a molecule designed to contain non-planar amide In the overcrowded but planar tetramethylcytoxine molecule (6) Me ,Me Yd the steric strain arising out of the retention of the sp2 geometry for the dimethyl- amino nitrogen atom and the Me...Me clash is taken up by the spreading of the angles at N-4 C-4 and C-5.24 In our last Report we mentioned three papers which described the correlation of crystal structure of some carboxylic acids with their reaction with amines and ammonia and another example of this has been given.In the structures of (S)-(+)-2,2-diphenylcyclopropanecarboxylicacid and (R)-( +)-2,2-diphenyl-1-methylcyclopropanecarboxylicacid the crystal packing particularly the closed environment of the polar groups explains the observed ditropic attack by NH3 gas on single In a similar study26 the crystal structure analyses of dimethyl rneso-(2R,3S,4R,5S)-and rneso-(2R,3R,4S,5S)- a,a'-dimethyl-P,P'-dibromoadipate have assisted in the interpretation of the reac- tion of single crystals of the two compounds with gaseous NH3and amines to yield the corresponding diesters of (E,E)-and (E,Z)-butadiene by double dehy- drobromination.In both cases the reaction is topochemically controlled in that the configurations of the products correlate directly with the conformation of the starting molecules in their crystals. Other examples of this very interesting kind of study are the solid-state dehydration of 2-hydroxy-2-(P-benzoy~-~-phenyl-hydrazy1)indane- 1,3-dione [(7a) +(7b)],*' where compound (7a) also appears to be the first example of the type of intermediate found in reactions of carbonyl 23 S. E. Ealick and R. Vander Helm Acru Crysf..1977 B33 76. 24 J. K. Dattaguysta W. Saenger K. Bolewska and I. Kulakowska Act0 Cryst. 1977 B33 85. 25 C. C. Chiang C.-T. Lin A. H.-J. Wand D. Y. Cuttin and I. C. Paul.J. Amer. Chem. Soc. 1977 99 6303. 26 D. Rabinovich and Z. Shakked Acru Cryst. 1977 B33 809. 27 S. A. Puckett I. C. Paul and D. Y. Curtin J. Amer. Chem. Soc. 1976.98 787 2371. Physical Methods-Part (ii)X-Ray Crystallography compounds with arylhydrazines and related compounds and the conversion in the solid state of the yellow form of 2-(4’-methoxypheny1)- 1,4-benzoquinone into the red form.28 In this latter reaction the process begins at a limited number of nucleation sites in the crystal and spreads by migration in well-defined fronts and the colours of the two forms correlate with the different types of packing adopted particularly in relation to intermolecular .rr-interactions. Peptide-containing antibiotics continue to be of major structural interest partly on account of their interesting conformational and hydrogen-bonding properties.[Phe4 Va16]antamanide is a synthetic analogue of the cyclic decapeptide antamanide that possesses biological activity in respect of ion selectivity. It appears to have a novel type of (5 -+ 1)NH...O=C hydrogen bond.29 An X-ray study of a degradation product has finally confirmed the structure of the complex antibiotic vancomycin (8);30 suggestions have been made for a possible binding mode to peptides terminating in the residues D-alanyl-D-alanine a crucial process in its biological action. An a-helical conformation has been observed31 for the amide units in the crystal structure of N-acetylactinobolin. 28 G. R. Desirajin I. C. Paul and D. Y. Curtin J.Amer. Chem. Soc. 1977 99. 1594. 29 I. L. Karle,J. Amer. Chem. SOC.,1977,99 5152. 30 G. M. Sheldrick P. G. Jones 0. Kennard D. H. Williams and G. A. Smith Nufure 1978,271 223 31 R. B. Von Dreele Actu Cryst. 1976 B32 2852. 16 M. B. Hursthouse and S. Neidle The linear tetrapyrrole bilirub has a compact conformation in the solid state which is stabilized by intramolecular hydrogen bonds,’ a feature shown by both indepen- dent molecules in the asymmetric unit. This structure is not dissimilar to that of a biladiene analogue (9)32-both have the two planar pyrromethane groups hinged together at right angles. Me Me Me Me Me (9) The remarkable crystal structure of anhydrous cholesterol contains eight independent molecules in the asymmetric unit,33 a total of 224 non-hydrogen atoms.Although the skeletal frameworks are all the same there are considerable variations in the tail conformations. The packing of molecules in the crystal lattice differs from that in cholesterol m~nohydrate,~~ which has a bilayer-type structure with the rings almost parallel to one another. An X-ray analysis of 3B-acetoxy-17aa-(2-acetoxyethoxy)- 17a 17ao- dimethyl -D-homoandrost-5 -en -176-01 (10) has disproved the notion of isolating rotamers that have restricted rotation about the steroidal C-17-C-20 bond.35 The structure of prostaglandin FZa(11) has two OCH,CH ,OAc OH (10) (1 1) independent molecules in the asymmetric unit both have the side-chains aligned roughly A model for the biological recognition by prostaglandin recep- tors has been suggested on the basis of this structure which explains much of the binding data.The structures of a number of nucleic acid constituents have been reported some of which are notable for their broader biological significance and interest. A new pattern of hydrogen-bonding has been observed in the structure of 5-nitro-6-rnethylura~il,~~ which has adjacent bases perpendicular to one another in contrast 32 G. Struckmeier U. Thewalt and J. Engel J.C.S. Chem. Comm. 1976 963 ” H. S. Shieh L. G. Hoard and C. E. Nordman Nature 1977,267 287. 34 B. M. Craven Narure 1976,260 727. 35 Y. Osawa T. Makino and C. M. Weeks J.C.S. Chem. Comm. 1976,990. ” D. A. Langs M. Erman and G. T. DeTitta Science 1977 197 1003. ’’ R.Parthasarathy and T. Srikrishnan Acta Cryst. 1977 B33 1749. Physical Methods-Part (ii) X-Ray Crystallography to the normal parallel arrangements. The structures of the hypermodified nucleosides t6A and g6A (the former occurs in the anticodon loop of tRNA) have conformational alterations in this loop that depend on the codon being read. The interactions of drugs with nucleic acids have been investigated via the structures of several model systems such as ethidium-dinu~leoside~~*~~ and 9-aminoacridine-dinucleoside41complexes and an extrapolation from these models to the polymers has been attempted.42 The crystal of a proflavine-dinucleoside phosphate (CpG) has however cast some doubt on the general validity of these conclusions; in particular the conformational changes induced in the miniature double helix can be related to even small alterations in the base pair geome try.44 38 R.Parthasarathy J. M. Ohrt and G. B. Chheda Biochemistry 1977 16,4999. 39 C.C.Tsai S. C. Jain and H. M. Sobell J. Mol. Biob 1977 144 301. 40 S. C.Jain C. C. Tsai and H. M. Sobell I.Mol. Biol.. 1977 144 317. T. D.Sakore S. C. Jain C. C. Tsai and H. M. Sobell Proc. Nut. Acad. Sci. U.S.A.,1977,74 188. 41 42 H. M.Sobell C. C. Tsai S. C. Jain and S. G. Gilbert J. Mol. Biol. 1977 114,'333. 43 S. Neidle A. Achari G. L. Taylor H. M. Berman H. L. Carrell J. P. Glusker and W. C. Stallings Nature 1977 269 304. 44 H.M.Berman S. Neidle and R. K. Stodola Proc. Nut. Acad. Sci. U.S.A. 1978,75 828.