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A tremendous research on Poly (ADP-ribose) polymerase (PARP) pertaining to cancer and ischemia is in very rapid progress. PARP's are a specific class of enzymes that repairs the damaged DNA. Recent findings suggest also that PARP-1 is the most abundantly expressed nuclear enzyme which involves in various therapeutic areas like inflammation, stroke, cardiac ischemia, cancer and diabetes. The current review describes the overview on clinical candidates of PARP1 and its current status in clinical trials. This paper also covers identification of potent PARP1 inhibitors using structure and ligand based pharmacophore models. Finally 36 potential hits were identified from the virtual screening of pharmacophore models and screened for PARP1 activity. 15 actives were identified as potent PARP1 inhibitors and further optimization of these analogues are in progress.

Bacillus anthracis is a causative organism of anthrax. The main reason to use anthrax as a bioweapon is the combination of the spore's durability and the lethal toxaemia of the vegetative stage. In anthrax infection, lethal factor (LF) is playing crucial role in causing cell death, by inhibiting pathways that rely on this kinase family. The combination of vaccine and antibiotics is preferred as an effective treatment for this target. Till date, no small molecule inhibitor is identified as a drug on the target. In this study, we have performed pharmacophore modeling and docking studies to identify a novel small molecule inhibitor to target the Anthrax LF. The best pharmacophore model is used to screen approximately 2M drug-like small molecule database and yielded 2543 hits. Docking studies of the pharmacophore hits on to the active site of Anthrax LF resulted 120 structurally diverse hits. Out of 120 hits, based on synthetic feasibility, 17 hits are selected for further synthesis and pharmacological screening. In due course, we will publish the updated results.

Structure and ligand based pharmacophore modeling and docking studies carried out using diversified set of c-Jun N-terminal kinase-3 (JNK3) inhibitors are presented in this paper. Ligand based pharmacophore model (LBPM) was developed for 106 inhibitors of JNK3 using a training set of 21 compounds to reveal structural and chemical features necessary for these molecules to inhibit JNK3. Hypo1 consisted of two hydrogen bond acceptors (HBA), one hydrogen bond donor (HBD), and a hydrophobic (HY) feature with a correlation coefficient (r2) of 0.950. This pharmacophore model was validated using test set containing 85 inhibitors and had a good r2 of 0.846. All the molecules were docked using Glide software and interestingly, all the docked conformations showed hydrogen bond interactions with important hinge region amino acids (Gln155 and Met149) and these interactions were compared with Hypo1 features. The results of ligand based pharmacophore model (LBPM) and docking studies are validated each other. The structure based pharmacophore model (SBPM) studies have identified additional features, two hydrogen bond donors and one hydrogen bond acceptor. The combination of these methodologies is useful in designing ideal pharmacophore which provides a powerful tool for the discovery of novel and selective JNK3 inhibitors.

Consensus virtual screening models were generated and validated utilizing a set of known human epidermal growth factor receptor-2 (HER2) inhibitors and modeled HER2 active and inactive state structures. The virtual screening models were successfully employed to discover a set of structurally diverse compounds with growth inhibitory activity against HER2-overexpressing SKBR3 breast cancer cell line. A search of a 3D database containing 350000 small-molecules using the consensus models retrieved 531 potential hits. Of the 531 hits, 57 were selected for testing in SKBR3 cells on the basis of structural novelty and desirable drug-like properties. Seven compounds inhibited growth of SKBR3 cells with IC50 values

Rhombohedral Nasicon type materials of composition Ag3–2xTax Al2–x(PO4)3 (x = 0.6, 0.7,0.8, 0.9, 1.0, 1.1,1.2, 1.3 and 1.4) have been prepared and characterized by powder XRD and IR. All these compositions are found to be isomorphous with NbTiP3O12, lithium and sodium analogues of same Nasicon framework. The unit cell parameters were derived from powder XRD. All the compounds show characteristic PO4 vibrational bands. DC conductivity measurements were carried out in the temperature range 300–650 K. The activation energies for conduction were deduced from the Arrhenius plots and are in the range 0.42–0.71 eV. Among the series investigated, Ag0.8Ta1.1Al0.9P3O12 exhibits the highest conductivity, σ ≈ 5.01 × 10–3 S cm–1 at 350 °C (Ea = 0.55 eV). (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Thromboxane A2receptor antagonists have attracted much attention in recent times in the design of new agents that could be active against diseases such as thrombosis, asthma and myocardial ischemia. 3D-QSAR studies have been performed on a series of [[1-aryl(or benzyl)-1-(benzenesulphonamido)methyl] phenyl] alkanoic acid derivatives by using the receptor surface analysis (RSA) method. The RSA analysis was carried out on 31 analogues of which 25 were used in the training set and the rest considered for the test set. This study produced reasonably good predictive models with good cross-validated and conventionalr2values in both the models.

3D-QSAR studies using MFA and RSA methods were performed on a series of 39MMP-13 inhibitors. Model developed by MFA method has a r(2)(cv) (cross-validated) of 0.616 while its r(2) (conventional) value is 0.822. For the RSA model r(2)(cv) and r(2) are 0.681 and 0.847, respectively. Both the models indicate good internal as well as external predictive abilities. These models provide crucial information about the field descriptors for the design of potential inhibitors of MMP-13.

A new approach has been proposed for the ab initio crystal structure prediction of small organic molecules. This exercise forms a part of the recent blind test on crystal structure prediction condu...

Aromatic aldehydes undergo cross-aldol condensation with ketones in the presence of KF-Al2O3 under microwave irradiation in solvent-free conditions to afford the corresponding α,α′-bis(benzylidene) alkanones in high yields. *IICT Communication No. 4420.

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.

Anthrax Lethal Factor (LF) is a zinc-dependent metalloprotease, one of the virulence factor of anthrax infection. Three forms of the anthrax infection have been identified: cutaneous (through skin), gastrointestinal (through alimentary tract), and pulmonary (by inhalation of spores). Anthrax toxin is composed of protective antigen (PA), lethal factor (LF), and edema factor (EF). Protective antigen mediates the entry of Lethal Factor/Edema Factor into the cytosol of host cells. Lethal factor (LF) inactivates mitogen-activated protein kinase kinase inducing cell death, and EF is an adenylyl cyclase impairing host defenses. In the past few years, extensive studies are undertaken to design inhibitors targeting LF. The current review focuses on the small molecule inhibitors targeting LF activity and its structure activity relationships (SAR).

Fibroblast growth factor receptor 1 (FGFR1) a tyrosine kinase receptor, plays important roles in angiogenesis, embryonic development, cell proliferation, cell differentiation, and wound healing. The FGFR isoforms and their receptors (FGFRs) considered as a potential targets and under intense research to design potential anticancer agents. Fibroblast growth factors (FGF’s) and its growth factor receptors (FGFR) plays vital role in one of the critical pathway in monitoring angiogenesis. In the current study, quantitative pharmacophore models were generated and validated using known FGFR1 inhibitors. The pharmacophore models were generated using a set of 28 compounds (training). The top pharmacophore model was selected and validated using a set of 126 compounds (test set) and also using external validation. The validated pharmacophore was considered as a virtual screening query to screen a database of 400,000 virtual molecules and pharmacophore model retrieved 2800 hits. The retrieved hits were subsequently filtered based on the fit value. The selected hits were subjected for docking studies to observe the binding modes of the retrieved hits and also to reduce the false positives. One of the potential hits (thiazole-2-amine derivative) was selected based the pharmacophore fit value, dock score, and synthetic feasibility. A few analogues of the thiazole-2-amine derivative were synthesized. These compounds were screened for FGFR1 activity and anti-proliferative studies. The top active compound showed 56.87% inhibition of FGFR1 activity at 50 µM and also showed good cellular activity. Further optimization of thiazole-2-amine derivatives is in progress.

The recent discovery of a second, inducible isoform of cyclooxygenase, COX-2, has stimulated the search for highly selective non-steroidal anti-inflammatory drugs (NSAIDs). These NSAIDs have the ability to treat pain and inflammation caused by arthritis with less risk of gastrointestinal or renal toxicity. We report here the results of 3D-quantitative structure–activity relationship and docking studies, performed on a series of 3,4-diaryloxazolones. Comparative moleculer field analysis studies provided a good model with cross-validated and conventional r2 values of 0.688 and 0.969 respectively for 24 analogues in the training set with six components. Docking studies with both COX-1 and COX-2 indicate good selectivity for COX-2. The binding energies between COX-2 and some of the most active oxazolones are comparable to those of celecoxib or rofecoxib. These compounds adopt similar orientations and form similar sets of hydrogen bonds involving the sulfonyl group of the ligand and His 90, Leu 352, Ser 353, Arg 513, Phe 518 and Ser 530 residues of the receptor. Copyright © 2001 John Wiley & Sons, Ltd.

There are more organic compounds with an even number of carbon atoms than with an odd number. This disparity could result mainly from the methods used in synthetic chemistry to build large molecules from smaller ones. Samples of C 28 , C 47 and C 48 compounds have been examined in this context.

Solid state bromination of a number of substituted phenol, aniline and nitro aromatic compounds with N-bromosuccinimide yields exclusively the nuclear brominated products. Reactivity in the solid state depends on the reaction time, temperature and nature of the substituent on the substrate. The reaction apparently proceeds by an electrophilic aromatic substitution pathway. Molecular orbital and reaction free energy calculations also support such a view. Thermal analysis and video microscopic observation reveal the nature of the solid state reaction. Crystallinity is required for the reactivity and product selectivity. Product yield decreases with loss of selectivity when the reaction is carried out in a melt or in solution. Unlike the topochemical solid state reactions wherein molecular packing is more important than the intrinsic reactivity, these reactions demonstrate the importance of both these factors.

N-Bromosuccinimide reacts with aromatic aldehydes in the solid state to yield exclusively nuclear brominated products while a similar reaction in the solution phase produces a number of products under varied conditions. The reactivity and regioselectivity have been studied in terms of the energies of HOMO, HOMO–LUMO difference, reaction free energy, reaction conditions and crystal packing. Single crystal X-ray structural analysis of 3,4-dihydroxybenzaldehyde has been carried out. Crystal packing energies of some of the reactive and unreactive benzaldehydes indicate the importance of molecular bromine diffusion in the solid state.

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 © 2000 John Wiley & Sons, Ltd.

The conformational space of 1,4,7-trioxacyclononane (9-crown-3) was studied using Conflex-AMBER and ab initio calculations at the density functional level of theory (DFT). The Conflex-AMBER calcula...

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.

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 and yields where zeolite HY (ca. 7.6 A pore diameter) yields mainly the linear chain dimer and no cyclic products.

Aromatic aldehydes undergo cross-aldol condensation with ketones in the presence of KF-Al2O3 under microwave irradiation in solvent-free conditions to afford the corresponding α,α′-bis(benzylidene) alkanones in high yields. *IICT Communication No. 4420.

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 molecular and crystal structure of 2,5-dibenzylidenecyclopent-3-ene-1-one has been studied in detail to explain the formation of a non-topochemical pseudo-mirror-symmetric dimer upon photoirradiation. Packing energy calculations, analysis of the thermal motion, and lattice energy calculations are employed to analyse and understand the observed dimerization reaction, crystal structure, and crystal properties.

In the crystal structure of the title compound, 2C5H5N4O+·SO42−, N—H...O hydrogen bonds assemble the molecules into a two-dimensional network structure parallel to the cb plane. The S atom of the sulfate ion lies on a special position on a twofold axis.

Using geometrical inferences from known crystal structures of aromatic hydrocarbons, some novel orthorhombic crystal structures are proposed for naphthalene, anthracene and biphenyl. Their packing energies and relative stabilities are discussed.

The 99m Tc d,l-HM-PAO complex has been shown to be an effective complex for cerebral perfusion imaging. Fractional crystallizations of the crude HM-PAO reduction product yield several fractions of varying crystallinity and isomeric purity. The presence of these mixed fractions greatly hinders the efficient separation of d,l and meso diastereomers and lowers the overall yield of the d,l isomer. The measurement of the respective melting points does not reveal accurately the composition of these fractions as regards the degree of meso impurity. Therefore these fractions have been identified and characterized by mass spectroscopy, optical and scanning electron microscopy, differential scanning calorimetry, NMR spectroscopy, and powder X-ray diffraction. Single crystals of pure d,l-HM-PAO (m.p. 129.8°C) have been isolated as well as pure meso HM-PAO (m.p. 144°C). A lower melting point fraction (117–118°C) is present in large amounts. This is a mixture of d,l and meso HM-PAO diastereomers and contains a significant amount of amorphous phase. We propose that this amorphous phase is derived from inefficient dissolution of meso HM-PAO in the crude reduction reaction mixture. This results in mixed meso-d,l fractions which thereafter are very difficult to separate. These observations regarding amorphous and crystalline phases in isomeric mixtures have general implications regarding ligands used in the preparation of radiopharmaceuticals, specifically 99m Tc complexes as brain imaging agents, where stereochemical purity invariably plays significant role.

We have performed a ligand coordinate analysis to monitor the movement of the inhibitor SC-558 from the active site of the COX-2 protein to the exterior using molecular dynamics techniques. This study provides an insight into the intermolecular interactions formed by the ligand during this journey. The published crystal structure of COX-2 with SC-558 in the active site (1cx2) was taken, and the ligand was moved incrementally in 13 steps. At each of these points on the path, exhaustive minimization and dynamics calculations were performed. The role of water was found to be important in these computations. An average structure was obtained from 250 conformations at each point and minimized. At each point on the path, the 10 lowest-energy conformations were also selected; a consideration of the average and lowest conformations provides fine details on the consistency of specific and strong interactions, and also on the geometry of the ligand. The movement of the ligand through the protein may be divided into three stages that are distinguished from each other because of energy and geometry discontinuities in both the ligand and the protein. The first of these covers the region between the active site and the point at 5.8 A from it. The second, which covers the distance between 8.2 and 10.0 A and is associated with maximum energetic and structural instability, is of critical importance. The third stage covers the distance between 10.5 A and the exterior and represents a stage of increasing hydration and expulsion of the ligand from the protein. Our results provide a confirmation for the existence of a shallow cavity near the protein surface in which the ligand is bound reversibly. By examining the residues that show maximum mobility, one obtains an idea of the gating mechanism that governs the entry and exit of the protein into or from the deep pocket that contains the active site. We note, however, that the variation of the root-mean-square deviation of all residues begins to increase almost as soon as the ligand leaves the active site, and even before there are any changes in the gate inter-residue distances. This loosening of the protein even before the gate opens might be a part of the enthalpy-entropy balance that accompanies the ligand's passage through the protein. Our results provide an energy profile of the ligand during its entry/exit into/from the protein and can, in principle, enable one to assess the residence time, which in turn may be associated or indirectly correlated with adverse cardiovascular side effects of nonsteroidal anti-inflammatory drugs. We believe that similar analyses for other selected COX-2-specific inhibitors will provide a measure (or prediction) of possible toxicity effects.

Virtual Screening (VS) is a computational technique that allows selection and ranking of possible hits from a library of compounds. We have carried out VS on 128 selected EGFR kinase inhibitors with GOLD and LigandFit. From the experimental crystal structure of the erlotinib-EGFR complex, three key hydrogen bonds were identified as responsible for anchoring the ligand in the active site. These are of the N-H...N, O(w)-H...N, and C-H...O types. Failure to include the hydrogen-bonded water molecule that forms the O(w)-H...N bond leads to incorrect results. Of the three interactions, the C-H...O formed by an activated C-H group is the best conserved. On the basis of the efficacy of these hydrogen bonds, the poses were classified into one of three categories: close, shifted, and misoriented. In the VS context, all three interactions need to be modeled correctly so that correct poses and affinities are obtained, and this happens in ligands of the close variety. Cross scoring wherein the poses from one software are input into another for scoring and consensus scoring wherein the scores from various software packages are weighted are also helpful in obtaining better agreements.

Thromboxane A(2) receptor antagonists have attracted much attention in recent times in the design of new agents that could be active against diseases such as thrombosis, asthma and myocardial ischemia. 3D-QSAR studies have been performed on a series of [[1-aryl(or benzyl)-1-(benzenesulphonamido)methyl] phenyl] alkanoic acid derivatives by using the receptor surface analysis (RSA) method. The RSA analysis was carried out on 31 analogues of which 25 were used in the training set and the rest considered for the test set. This study produced reasonably good predictive models with good cross-validated and conventional r(2) values in both the models.

Three-dimensional quantitative structure–activity relationship (3D-QSAR) models were developed for 100 anilinoquinazolines, inhibiting epidermal growth factor receptor (EGFR) kinase. The studies included molecular field analysis (MFA) and receptor surface analysis (RSA). The cross-validated r 2 ( r 2 cv ) values are 0.81 and 0.79 for MFA and RSA, respectively. The predictive ability of these models was validated by 28 test set molecules. The results of the best QSAR model were further compared with structure-based investigations using docking studies with the crystal structure of EGFR kinase domain. The results helped to understand the nature of substituents at the 6- and 7-positions, thereby providing new guidelines for the design of novel inhibitors.

Comparative molecular field analysis and comparative molecular similarity indices analysis were performed on 114 analogues of 1,2-diarylimidazole to optimize their cyclooxygenase-2 (COX-2) selective antiinflammatory activities. These studies produced models with high correlation coefficients and good predictive abilities. Docking studies were also carried out wherein these analogues were docked into the active sites of both COX-1 and COX-2 to analyze the receptor ligand interactions that confer selectivity for COX-2. The most active molecule in the series (53) adopts an orientation similar to that of SC-558 (4-[5-(4-bromophenyl)-3-trifluoromethyl-1H-1-pyrozolyl]-1-benzenesulfonamide) inside the COX-2 active site while the least active molecule (101) optimizes in a different orientation. In the active site, there are some strong hydrogen-bonding interactions observed between residues His90, Arg513, and Phe518 and the ligands. Additionally, a correlation of the quantitative structure-activity relationship data and the docking results is found to validate each other and suggests the importance of the binding step in overall drug action.

Utilising the preferential adoption of hydroxy–cyano hydrogen bond over the hydroxy–hydroxy hydrogen bond in molecular crystals, the crystal structure of 4′-cyano-2,6-dimethyl-4-hydroxyazobenzene is designed into an acentric space group.

Tetrakis(4-nitrophenyl)methane is a new host material with considerable structural adaptability over a range of solvents. The crystal structures of 14 of these solvates have been determined and classified into three groups. The diamondoid group, wherein the host molecules form a 2-fold interpenetrated diamondoid network structure, is unprecedented in that network connections are made exclusively with weak C-H...O and pi...pi interactions. This group consists of the solvates of THF, dioxane, nitrobenzene, 4-bromoanisole, anisole, phenetole, p-xylene, and chlorobenzene. The rhombohedral group, which is characterized by specific host.guest interactions of the C-H...O and halogen...O2N type, consists of the solvates of CHCl3 and CHBr3 and somewhat surprisingly DMF, which shows an unusual 3-fold disorder mimicking in part the shape and size of the haloform molecules though not their orientation. The third group comprises solvent-rich solvates of the host with mesitylene, collidine, and o-xylene with quite different crystal structures. The THF solvate was found to lose solvent over limited temperature ranges transforming reversibly from the diamondoid structure to the rhombohedral structure. A mechanism for this process is outlined. Material from which solvent has been removed by heating was also found to resolvate upon soaking in appropriate solvents. In summary, the title compound forms a host network that is partially robust and in part flexible. It is possible that this fluxional nature of the host network derives from the weakness of the connecting interactions.

N-Bromosuccinimide reacts with aromatic aldehydes in the solid state to yield exclusively nuclear brominated products while a similar reaction in the solution phase produces a number of products under varied conditions. The reactivity and regioselectivity have been studied in terms of the energies of HOMO, HOMO–LUMO difference, reaction free energy, reaction conditions and crystal packing. Single crystal X-ray structural analysis of 3,4-dihydroxybenzaldehyde has been carried out. Crystal packing energies of some of the reactive and unreactive benzaldehydes indicate the importance of molecular bromine diffusion in the solid state.

Solid state bromination of a number of substituted phenol, aniline and nitro aromatic compounds with N-bromosuccinimide yields exclusively the nuclear brominated products. Reactivity in the solid state depends on the reaction time, temperature and nature of the substituent on the substrate. The reaction apparently proceeds by an electrophilic aromatic substitution pathway. Molecular orbital and reaction free energy calculations also support such a view. Thermal analysis and video microscopic observation reveal the nature of the solid state reaction. Crystallinity is required for the reactivity and product selectivity. Product yield decreases with loss of selectivity when the reaction is carried out in a melt or in solution. Unlike the topochemical solid state reactions wherein molecular packing is more important than the intrinsic reactivity, these reactions demonstrate the importance of both these factors.

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.

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 and yields where zeolite HY (ca. 7.6 A pore diameter) yields mainly the linear chain dimer and no cyclic products.

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.

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