Jagarlapudi A. R. P. Sarma

3-D QSAR studies on new dibenzyltin(IV) anticancer agents by comparative molecular field analysis (CoMFA)

Dibenzyltin(IV)dichloride and dibenzyltin(IV)diisothiocyanate derivatives with N,S-donor ligands show significant cytotoxic activities against human cancer cell lines, and are well compared to analogous dialkyltin(IV) derivatives. CoMFA models were generated for the first time for these organotin derivatives using the cytotoxic activities (against two human tumor cell lines, MCF-7, a mammary carcinoma and WiDr, a colon carcinoma) of 21 complexes. High r(2) and r(2)(cv) values for both CoMFA models indicate good predictive power for the models.

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.

Crystal engineering and solid state chemistry of some β-nitrostyrenes

The unusual solid state photodimerisation of (E)-β-nitrostyrene to yield ‘topochemical’ and ‘non-topochemical’ cyclobutanes is accounted for by its disordered, photoreactive crystal structure which is monoclinic, P21/c, Z= 4, a= 8.097(6)A, b= 5.768(5)A, c= 18.647(2)A, β= 117.71(5)°. This structure permits a trans→cis isomerisation which facilitates the formation of the anomalous product. However, 4-methyl-β-nitrostyrene which has a very similar disordered structure is photostable in the solid state since the potentially ‘reactive’ double bonds are beyond the topochemical threshold. C–H ⋯ O and C–H ⋯ Cl interactions are important to the exclusion of Cl ⋯ Cl interactions in the layered structure of the 4-chloro derivative, but this nitrostyrene forms mixed crystals with the 4-methyl compound in the disordered structure of the latter showing that the role of the Cl atom in the 4-chloro derivative is at best marginal. In contrast, the higher Cl stoichiometry in the 2,4-dichloro analogue results in a layered, photoreactive β-structure characterised by Cl ⋯ Cl and C–H ⋯ O interactions. The structures of three layered alkoxy-β-nitrostyrenes are very similar to each other and are held by strong, directional C–H ⋯ O contacts. The 4-methoxy compound has a photostable crystal structure while the 3,4-methylenedioxy and 3,4-dimethoxy crystals appear to be capable of topochemical 2 + 2 cycloaddition. However, only the latter is photoreactive because of optimal double-bond-to-double-bond overlap in the crystal. The 4-bromo derivative is distinct from the 4-chloro compound and there are two molecules in the asymmetric unit because of conflicting packing requirements of the C–H ⋯ O and Br ⋯ O interactions. A survey of 84 intermolecular Br ⋯ O contacts retrieved from 39 nitro-bromo crystal structures has revealed that at least some of these arise due to halogen polarisability. Atomic motion analysis in this crystal structure indicates the importance of lateral C–H ⋯ O interactions.

The novel 1 : 1 donor–acceptor complex, 3,4-dimethoxycinnamic acid–2,4-dinitrocinnamic acid. Crystal engineering, structure, and anomalous lack of solid-state topochemical reactivity

Donor–acceptor interactions have been exploited to engineer a crystal structure of a 1 : 1 molecular complex (2a) of the title acids (1a) and (1d), where solid-state topochemical 2 + 2 photoaddition to yield pseudo-symmetrical cyclobutanes is permitted. Orange crystals of (2a) are triclinic, P, a= 8.857(5), b= 13.872(8), c= 8.578(4)A, α= 101.41(4), β= 100.98(4), γ= 95.98(4)°, Z= 2, R= 0.054 on 1 315 non-zero reflections. The crystal structure consists of interleaving donor and acceptor molecules in the stack with two unequal separations of 3.80 and 4.97 A with the former overlap relating ‘potentially reactive’ double bonds. Contrary to expectation, complex (2a) is photostable. This inertness is shared by several other aromatic nitro compounds and some mechanistic possibilities are discussed. A classification of solid-state 2 + 2 cycloaddition reactions is attempted on the basis of how far topochemical predictions match with observed photochemical behaviour.

Design of an SHG-active crystal, 4-iodo-4′-nitrobiphenyl: the role of supramolecular synthons

The crystal structure of 4-iodo-4′-nitrobiphenyl has been determined with packing calculations and the presence of polar and parallel iodo···nitro supramolecular synthons leads to non-centrosymmetry and measurable SHG activity

Selective nitration of aromatic compounds by solid acid catalysts

High activity and para-selectivity in the nitration of aromatic compounds is achieved by a high density of acidic sites and ready formation of the para-isomer in the pores of zeolite beta with low Si/Al ratio as revealed by molecular modeling studies.

C–H ⋯ O interactions and the adoption of 4 Å short-axis crystal structures by oxygenated aromatic compounds

Oxygen atoms, pendant as substituents or occurring within the ring systems of planar aromatic molecules, have a pronounced tendency to direct crystallisation patterns of such compounds to the β-structure, characterised by a 4 A short axis. They seem to perform this function by stabilising a critical number of hydrogen atoms, covalently bonded to carbon, through short and directionally specific intermolecular C–H ⋯ O hydrogen bonds. Consequently, the number of ‘free’ hydrogen atoms which contribute to crystal stabilisation through non-β steering C ⋯ H interactions is reduced. Both these factors result in the formation of C–H ⋯ O stabilised two-dimensional entities such as sheets and ribbons. Such entities may be stacked at 4 A translational separation to generate the entire structure. These concepts are illustrated for some methylenedioxy and alkoxy aromatic systems, quinones, and heterocycles. However, both intra- and inter-sheet C–H ⋯ O interactions may sometimes be present and the unusual crystal structure of 7-acetoxycoumarin (5) shows how a significantly non-planar molecule may still adopt the β-structure if it is particularly well suited for the formation of C–H ⋯ O bonds. Yet 4-acetoxycinnamic acid (6), the crystal structure of which was determined in this work and which has almost the same C:H:O ratio as (5), adopts a non-β structure because the number of oxygen atoms available for C–H ⋯ O bond formation is greatly reduced. The crucial role of the number of such ‘available’ oxygen atoms and ‘H-bonded’ and ‘free’(C–)H atoms vis-a-vis the carbon content is exemplified by the β-steering behaviour of oxygen in some large fused-ring quinones and heterocycles. These trends may also be extended to nitrogen and sulphur heterocycles.

Crystal engineering via Cl ⋯ Cl non-bonded interactions. The novel 2 : 1 complex, 6-chloro-3,4-(methylenedioxy)cinnamic acid–2,4-dichlorocinnamic acid. Topochemical conversion into an unsymmetrical cyclobutane and kinetics of the reaction

Two chloro-subsitituted cinnamic acids have been induced to co-crystallise as a molecular complex which is converted, at different rates, into an unsymmetrical and two symmetrical cyclobutanes during solid-state topochemical 2 + 2 photoaddition.

Melting-points of the meta- and para-isomers of anisylpinacolone

The generally higher melting-point of a para-disubstituted benzene relative to the corresponding meta-isomer has been ascribed to the fact that, being more symmetrical, it can pack more tightly. Exceptionally, it was observed that whereas m-anisylpinacolone melts at 58.0 °C, the para-isomer melts lower at 39.5 °C. In this work we have attempted to understand this apparent anomaly. The crystal structures of both isomers were determined and the packing analysed. Energy calculations of the static structures and molecular dynamics (MD) simulations at temperatures just below the respective melting-points were performed. The structure analyses indicate that the intermolecular contacts are comparably weak in the two cases, and do not appear to be the direct cause of the melting-point difference. Thermal motion analysis, packing energies and MD simulations on minicrystals indicate the importance of both enthalpic and entropic factors in the melting behaviour of the two isomers. The higher melting point of the meta-isomer could originate from both a smaller ΔSf and higher ΔHf relative to the para-isomer. Copyright

A novel, shape-selective, zeolite-catalyzed synthesis of calix(4) pyrroles

Porosity and acidity of molecular sieve Al-MCM-41 (ca. 30 A pore diameter) plays a crucial role in the synthesis of novel calix(4)pyrroles; for the first time, Al-MCM-41 has been used as a solid acid catalyst to produce a number of calix(4)pyrroles with good selectivity ad yields where zeolite HY (ca. 7.6 A pore diameter) yields mainly the linear chain dimer and no cyclic products.