Steering non-centrosymmetry into the third dimension: crystal engineering of an octupolar nonlinear optical crystal

The ability of CH3 groups to form helical chains of C-H…∏ interactions with phenyl rings leads to polar stacking of trigonal octupolar networks in a substituted triazine, and therefore to three-dimensional non-centrosymmetry

Supramolecular equivalence of halogen, ethynyl and hydroxy groups. A comparison of the crystal structures of some 4-substituted anilines

Chloro, bromo and ethynyl substituents play exactly the same role in the crystal structures of the corresponding 4-substituted anilines and this is related to their similar polarisations. The iodo derivative is, however, distinct and this may be related to its greater size

Five new pseudopolymorphs of sym-trinitrobenzene

1,3,5-Trinitrobenzene (TNB) was recrystallized from about 30 solvents and five mixed solvents in around 50 experiments to yield five new solvates. All the solvates lose their solvent readily, and special precautions were required to determine their crystal structures. In all cases, the solvents that gave solvates are electron-rich aromatics leading to the conjecture that ∏ ···∏ donor-acceptor stacking interactions are important. This was confirmed from the crystal structures. Additionally, these structures are composed of hexagonal sheets in which TNB and solvent molecules are linked with weak C-H···O hydrogen bonds. The benzene solvate contains an unusual finite TNB motif not hitherto seen. The toluene and chlorobenzene solvates are not isostructural, and C-H···Cl interactions in the latter are unusually short and linear, accounting thereby for the failure of chloro-methyl structural exchange. The m-xylene and mesitylene solvates are similar to the toluene solvate. This study indicates that the use of terms such as solvate, pseudopolymorph, donor-acceptor complex, and molecular complex is a subjective matter, and also that a better definition for the term pseudopolymorph may be needed, especially because it occurs frequently in the pharmaceutical literature

Stereoelectronic effects of substituent groups in the solid state. Crystal chemistry of some cubanecarboxylic and phenylpropiolic acids

A series of 4-substituted cubanecarboxylic acids and phenylpropiolic acids have been studied with the aim of elucidating steric and electronic factors exerted by the 4-substituent in the formation of the dimer, or alternatively, the rare syn-anti catemer patterns in their respective crystal structures. It is shown that catemer formation depends critically on the ability of a proximal C-H group to form a supportive C-H···O bond. In turn, this means that the C-H group must be sufficiently activated toward hydrogen bond formation. Such activation is inherent to the cubyl group but must be present additionally from a suitable electron withdrawing group in the phenylpropiolic acids. In any event, while C-H activation is necessary for catemer formation it is not sufficient. The substituent group that is present in the 4-position must also be sufficiently bulky so as to form a close packed array that is compatible with the catemer geometry. These trends are justified by the crystal structures of the 12 acids in the two families wherein the 4-substituent group is H, F, Cl, Br, I, and CH3. Our results indicate that electronic and steric effects of functional groups may be distinguished in the solid state, in that the formation of either a dimer or catemer may be rationalized on the basis of these effects

Steroidal aromatase inhibitors : Model receptor surfaces and 3D QSAR^†

1054-1062Receptor surfaces have been generated with a training set of 50 steroids active against cytochrome P450 enzyme, aromatase, using the Drug Discovery Workbench (Cerius2). A combination of van der Waals-electrostatic and Wyvill-partial- charge force fields together with overlay of 17- and 13-atoms of the steroid ligand resulted in four different receptor surface models. These models have high conventional and cross-validated r2, q2 values (> 0.8) for 50 training set molecules with the four components, vdW-17A, vdW-13A, Wsc-17A, Wsc-13A. Binding energies of six synthetic 2-oxasteroid analogues are evaluated with receptor surfaces and their biological activity predicted through 3D QSAR. Ligand-receptor binding is examined in relation to (1) van der Waals vs. Wyvill force fields, (2) 17- vs. 13-atoms overlay, (3) conformation of the 2-oxasteroid. Our computations show that replacement of C2-methylene group with an O-atom in the A-ring of androgens (2-oxasteroids) is accommodated during recognition by the receptor

Halogen trimer-mediated hexagonal host framework of 2,4,6-tris(4-halophenoxy)-1,3,5-triazine. Supramolecular isomerism from hexagonal channel (X = Cl, Br) to cage structure (X = I)

The hexagonal layer structure of host atoms in chloro, bromo, and iodo derivatives of 2,4,6-tris(4-halophenoxy)-1,3,5-triazine, X-POT, is stabilized by a cyclic and cooperative halogen trimer (X···X) synthon. The X···X distance is ~3.5 Å in isostructural channel inclusion adducts of Cl-POT and Br-POT, whereas I···I is ~3.8 Å in cage structures of I-POT with aromatic and hydrophobic guests. X-ray crystal structures of I-POT with mesitylene, collidine, tribromomesitylene, triiodomesitylene, hexachlorobenzene, hexafluorobenzene, 1-methylnaphthalene, CH2Cl2, CH2Br2, and CH2I2 guests in R3 space group are reported. Host molecules are fully ordered in these isostructural clathrates, whereas guest atoms are disordered except for C6Cl6 and C6F6. The guest molecule resides in a penta-decker sandwich surrounded by double layers of iodo trimer and triazine ring. Supramolecular isomerism from channel to cage framework and the persistent crystallization of trigonal X-POT molecules in high-symmetry host networks (space groups P63/m, P63, R3) are discussed in crystal engineering terms: halogen trimer synthon, C3i-Piedfort unit, weak C-H···O/N interactions, changes in size/polarizability of halogen atom, and CSDSymmetry statistics. Br-POT crystallizes in a channel or cage lattice depending on the guest species. Guest release from the cage framework occurs at a higher temperature compared to the channel structure in thermal gravimetric analysis, suggesting applications in organic zeolites. This study illustrates several aspects of crystal engineering from the understanding of intermolecular interactions to the design of crystal structures and their utility as functional solids

Proton transfer and N⁽⁺⁾-H···S^(-) hydrogen bonds in the crystal structure of 4-aminothiophenol

4-Aminothiophenol exists as 4-ammonio-1-benzenethiolate in the solid and liquid state. The crystal structure is characterised by a tetrahedral β -As type network which is the driving force for the proton transfer

Hexagonal nanoporous host structures based on 2,4,6-tris-4-(halo-phenoxy)-1,3,5-triazines (halo=chloro, bromo)

Based on our earlier observation that para-halogenated phenoxy triazines self-assemble as hexagonal nanoporous frameworks, this study deals with the inclusion of structurally related guest species in the one-dimensional channels of the title host compounds. A systematic analysis of six isomorphous, X-ray crystal structures (space group P63/m) provides valuable information of wide-ranging implications in host-guest chemistry: (1) construction of a host lattice with weak intermolecular interactions; (2) correlation of guest-size and host-channel area with order/disorder in the host; (3) role of molecular symmetry and multi-point hydrogen bond recognition for ordered guest species; (4) unusual structural behaviour and properties of guests constrained in a narrow channel. Lastly, a ternary adduct crystal shows an intricate hydrogen bonding network in the polar space group R3c with a super-cell of c=63.67 Å

Structural variations and polymorphism of some derivatives of 6-amino-2-phenylsulfonylimino- 1,2-dihydropyridine

Following up from a study of polymorphism in the title compound, 6-amino-2-phenylsulfonylimino-1,2-dihydropyridine, 12 phenyl-substituted derivatives were examined for polymorphism by recrystallization from a large number of solvents. The title compound contains hydrogen bond donor (D) and acceptor sites (A) located in a AADD juxtapositioning. Two structural families that differ in their use of the AADD hydrogen bond functionality may be identified. Methyl and chloro substitution in the ortho position or fluoro substitution in the para position leads to a catemer motif, which is related to the kinetic form of the title molecule. Meta Substitution by methyl and larger substituents in the para position block this structural option. While meta-methyl and para-chloro substitution lead to unique structures, two polymorphs of the para-methyl-substituted derivative could be crystallized and these adopt the dimer arrangement. With the larger bromo, iodo, methoxy, and trifluoromethyl substituents in the para position, dimers arranged into interconnected layers are obtained. These dimer structures are reminiscent of the thermodynamic form of the title compound. It is noteworthy that the majority of derivatives of the title compound fail to show polymorphic behavior, and this shows that our understanding of polymorphism is still far from complete

Three-Dimensional Quantitative Structural Activity Relationship (3D-QSAR) Studies of Some 1,5-Diarylpyrazoles: Analogue Based Design of Selective Cyclooxygenase-2 Inhibitors

Selective cyclooxygenase inhibitors have attracted much attention in recent times in the design of new non-steroidal anti-inflammatory drugs (NSAID). 3D-QSAR studies have been performed on a series of 1,5-diarylpyrazoles that act as selective cyclooxygenase-2 (COX-2) inhibitors, using three different methods: comparative molecular field analysis (CoMFA) with partial least squares (PLS) fit; molecular field analysis (MFA) and; receptor surface analysis (RSA) with genetic function algorithms (GFA). The analyses were carried out on 30 analogues of which 25 were used in the training set and the rest considered for the test set. These studies produced reasonably good predictive models with high cross-validated and conventional r2 values in all the three cases