PROPENSITIES OF AMINO ACID RESIDUES IN PROTEINS FOR DIFFERENT REGIONS OF THE RAMACHANDRAN MAP

Using a dataset of 1164 crystal structures of largely non-homologous proteins defined at a resolution of 1.5 angstrom or better, we have investigated the (phi,psi) preferences of 20 residue types by considering the residues which occur in loops. Propensities of residue types to occur in the loops with (phi,psi) values in the aa region of the Ramachandran map has a poor correlation coefficient of 0.48 to the Chou-Fasman propensities of the residue types to occur in the a-helical segments. However the correlation coefficient between propensities of residues in loops to adopt beta conformations and those in beta-sheet is much higher (0.95). These observations suggest that a-helix formation is well influenced by the local amino acid sequence while intrinsic preference of residue types for beta-sheet plays a major role in the formation of beta-sheet. The main chain polar groups of residues in loops, that can affect the (phi,psi) values, can be involved in intra-molecular hydrogen bonding. Therefore we investigated further by considering subset of residues in loops with low (0 to 2) number of intra-molecular hydrogen bonds per residue involving main chain polar atoms. For this subset, the correlation coefficients between propensities for alpha-helix and alpha(R) region and between beta-sheet and beta-region are 0.26 and 0.64 respectively. This reiterates higher intrinsic tendency of beta-region favouring residues to adopt beta-sheet than alpha(R) region favouring residues to adopt alpha-helical structure.

CHLORAL HYDRATE AS A WATER CARRIER FOR THE EFFICIENT DEPROTECTION OF ACETALS, DITHIOACETALS, AND TETRAHYDROPYRANYL ETHERS IN ORGANIC SOLVENTS

The efficient deprotection of several acetals, dithioacetals, and tetrahydropyranyl (THP) ethers under ambient conditions, using chloral hydrate in hexane, is described. Excellent yields were realized for a wide range of both aliphatic and aromatic substrates. The method is characterized by mild conditions (room temperatures or below), simple workup, and the ready availability of chloral hydrate. High chemoselectivity was also observed in the deprotection, acetonides, esters, and amides being unaffected under the reaction conditions. Products were generally purified chromatographically and identified spectrally. These results constitute a novel addition to current methodology involving a widely employed deprotection tactic in organic synthesis. It seems likely that the mechanism of the reaction involves adsorption of the substrate on the surface of the sparingly soluble chloral hydrate.

Role of Vertex Index in Substructure Identification and Activity Prediction: A Study on Antitubercular Activity of a Series of Acid Alkyl Ester Derivatives

Tuberculosis (TB) is a life threatening disease caused due to infection from Mycobacterium tuberculosis (Mtb). That most of the TB strains have become resistant to various existing drugs, development of effective novel drug candidates to combat this disease is a need of the day. In spite of intensive research world-wide, the success rate of discovering a new anti-TB drug is very poor. Therefore, novel drug discovery methods have to be tried. We have used a rule based computational method that utilizes a vertex index, named `distance exponent index (D-x)' (taken x = -4 here) for predicting anti-TB activity of a series of acid alkyl ester derivatives. The method is meant to identify activity related substructures from a series a compounds and predict activity of a compound on that basis. The high degree of successful prediction in the present study suggests that the said method may be useful in discovering effective anti-TB compound. It is also apparent that substructural approaches may be leveraged for wide purposes in computer-aided drug design.

Ferrocenyl-L-amino acid copper(II) complexes showing remarkable photo-induced anticancer activity in visible light

Ferrocene-conjugated copper(II) complexes Cu(Fc-aa)(aip)](ClO4) (1-3) and (Cu(Fc-aa)(pyip)](ClO4) (4-6) of L-amino acid reduced Schiff bases (Fc-aa), 2-(9-anthryl)-1H-imidazo4,5-f]1,10]phenanthroline (aip) and 2-(1-pyrenyl)-1H-imidazo4,5-f] 1,10]phenanthroline (pyip), where Fc-aa is ferrocenylmethyl-L-tyrosine (Fc-Tyr in 1, 4), ferrocenylmethyl-L-tryptophan (Fc-Trp in 2, 5) and ferrocenylmethyl-L-methionine (Fc-Met in 3, 6), were prepared and characterized, and their photocytotoxicity was studied (Fc = ferrocenyl moiety). Phenyl analogues, viz. (Cu(Ph-Met)(aip)](ClO4) (7) and (Cu(Ph-Met)(pyip)](ClO4) (8), were prepared and used as control compounds. The bis-imidazophenanthroline copper(II) complexes, viz. (Cu(aip)(2)(NO3)](NO3) (9) and Cu(pyip)(2)(NO3)](NO3) (10), were also prepared and used as controls. Complexes 1-6 having a redox inactive cooper(II) center showed the Fc(+)-Fc redox couple at similar to 0.5 V vs. SCE in DMF-0.1 mol (Bu4N)-N-n](ClO4). The copper(II)-based d-d band was observed near 600 nm in DMF-Tris-HCl buffer (1 :1 v/v). The ferrocenyl complexes showed low dark toxicity, but remarkably high photocytotoxicity in human cervical HeLa and human breast adenocarcinoma MCF-7 cancer cells giving an excellent photo-dynamic effect while their phenyl analogues were inactive. The photo-exposure caused significant morphological changes in the cancer cells when compared to the non-irradiated ones. The photophysical processes were rationalized from the theoretical studies. Fluorescence microscopic images showed 3 and 6 localizing predominantly in the endoplasmic reticulum (ER) of the cancer cells, thus minimizing any undesirable effects involving nuclear DNA.

Zoledronic acid in combination with alfacalcidol has additive effects on trabecular microarchitecture and mechanical properties in osteopenic ovariectomized rats

We conducted the present study to investigate the therapeutic effects of the antiresorptive agent zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF), in a rat model of postmenopausal osteoporosis. Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age. Twelve weeks post surgery, rats were randomized into six groups: (1) sham + vehicle, (2) OVX + vehicle, (3) OVX + ZOL (100 mu g/kg, i.v. single dose), (4) OVX + ZOL (50 mu g/kg, i.v. single dose), (5) OVX + ALF (0.5 mu g/kg, oral gauge daily) and (6) OVX + ZOL (50 mu g/kg, i.v. single dose) + ALF (0.5 mu g/kg, oral gauge daily) for 12 weeks. After treatment, we evaluated the mechanical properties of the lumbar vertebra and femoral mid-shaft. Femurs were also tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the combination treatment of ZOL and ALF was more effective than each administered as a monotherapy. Moreover, combination therapy using ZOL and ALF preserved the trabecular micro-architecture and cortical bone porosity. Furthermore, the combination treatment of ZOL and ALF corrected the decrease in serum calcium and increase in serum alkaline phosphatase and the tartarate-resistant acid phosphatase level better than single-drug therapy using ZOL or ALF in OVX rats. In addition, the combination treatment of ZOL and ALF corrected the increase in urine calcium, phosphorous and creatinine levels better than single-drug therapy using ZOL or ALF in OVX rats. These data suggest that the combination treatment of ZOL and ALF has a therapeutic advantage over each monotherapy for the treatment of osteoporosis.

Calculation of three-phase methane-ethane binary clathrate hydrate phase equilibrium from Monte Carlo molecular simulations

Methane and ethane are the simplest hydrocarbon molecules that can form clathrate hydrates. Previous studies have reported methods for calculating the three-phase equilibrium using Monte Carlo simulation methods in systems with a single component in the gas phase. Here we extend those methods to a binary gas mixture of methane and ethane. Methane-ethane system is an interesting one in that the pure components form sII clathrate hydrate whereas a binary mixture of the two can form the sII clathrate. The phase equilibria computed from Monte Carlo simulations show a good agreement with experimental data and are also able to predict the sI-sII structural transition in the clathrate hydrate. This is attributed to the quality of the TIP4P/Ice and TRaPPE models used in the simulations. (C) 2014 Elsevier B.V. All rights reserved.

Reduced graphene oxide-supported nickel oxide catalyst with improved CO tolerance for formic acid electrooxidation

The superior catalytic activity along with improved CO tolerance for formic acid electro-oxidation has been demonstrated on a NiO-decorated reduced graphene oxide (rGO) catalyst. The cyclic voltammetry response of rGO-NiO/Pt catalyst elucidates improved CO tolerance and follows direct oxidation pathway. It is probably due to the beneficial effect of residual oxygen groups on rGO support which is supported by FT-IR spectrum. A strong interaction of rGO support with NiO nanoparticles facilitates the removal of CO from the catalyst surface. The chronoamperometric response indicates a higher catalytic activity and stability of rGO-NiO/Pt catalyst than the NiO/Pt and unmodified Pt electrode catalyst for a prolonged time of continuous oxidation of formic acid. Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

Stepwise Crystallization: Illustrative Examples of the Use of Metalloligands Cu-6(mna)(6)](6-) and (Ag-6(Hmna)(2)(mna)(4)](4-) (H(2)mna=2-Mercapto Nicotinic Acid) in the Formation of Heterometallic Two- and Three-Dimensional Assemblies with brucite, pcu, and sql Topologies

Three new inorganic coordination polymers, {Mn(H2O)(6)]-Mn-2(H2O)(6)](Cu-6(mna)(6)]center dot 6H(2)O}, 1, {Mn-4(OH)(2)(H2O)(10)] (Cu-6(mna)6]center dot 8H(2)O}, 2, and {Mn-2(H2O)(5)]Ag-6(Hmna)(2)(mna)(4)]center dot 20H(2)O}, 3, have been synthesized at room temperature through a sequential crystallization route. In addition, we have also prepared and characterized the molecular precursor Cu-6(Hmna)(6)]. Compounds 1 and 3 have a two-dimensional structure, whereas 2 has a three-dimensional structure. The formation of 2 has been achieved by minor modification in the synthetic composition, suggesting the subtle relationship between the reactant composition and the structure. The hexanudear copper and silver duster cores have Cu center dot center dot center dot Cu and Ag center dot center dot center dot Ag distances close to the sum of the van der Waals radii of Cu1+ and Ag1+, respectively. The connectivity between Cu-6(mna)(6)](6-) cluster units and Mn2+ ions gives rise to a brucite related layer in 1 and a pcu-net in 2. The Ag-6(Hmna)(2)(mna)(4)](4-) cluster in 3, on the other hand, forms a sql-net with Mn2+. Compound 1 exhibits an interesting and reversible hydrochromic behavior, changing from pale yellow to red, on heating at 70 degrees C or treatment under a vacuum. Electron paramagnetic resonance studies indicate no change in the valence states, suggesting the color change could be due to changes in the coordination environment only. The magnetic studies indicate weak antiferromagnetic behavior. Proton conductivity studies indicate moderate proton migrations in 1 and 3. The present study dearly establishes sequential crystallization as an important pathway for the synthesis of heterometallic coordination polymers.

Iminodiacetic acid functionalized polypyrrole modified electrode as Pb(II) sensor: Synthesis and DPASV studies

An electrochemical lead ion sensor has been developed by modification of carbon paste electrode (CPE) using polypyrrole functionalized with iminodiacetic acid (IDA-PPy) containing carboxyl group. The electrochemical response of Pb2+ ion on the IDA-PPy modified CPE has been evaluated and the controling parameters have been optimized using differential pulse anodic stripping voltammetry (DPASV). The IDA-PPy modified CPE shows a linear correlation for Pb2+ concentrations in the range of 1 x 10(-6) to 5 x 10(-9) M and the lower detection limit of Pb2+ has been found to be 9.6 x 10(-9) M concentration. Other tested metal ions, namely Cu2+, Cd2+, Co2+, Hg2+, Ni2+ and Zn2+, do not exhibit any voltammetric stripping response below 1 x 10(-7) M concentration. However, the Pb2+ response is affected in the presence of molar equivalents or higher concentrations of Cu2+, Cd2+ and Co2+ ions in binary systems with Pb2+, consequent to their ability to bind with iminodiacetic acid, while Hg2+, Ni2+ and Zn2+ do not interfere at all. A good correlation has been observed between the lead concentrations as analyzed by DPASV using IDA-PPy modified CPE and atomic absorption spectrophotometry for a lead containing industrial effluent sample. (C) 2014 Elsevier Ltd. All rights reserved.

Polymorphism in cocrystals of urea:4,4 `-bipyridine and salicylic acid:4,4 `-bipyridine

Polymorphic cocrystals of urea:4,4'-bipyridine and salicylic acid: 4,4'-bipyridine were obtained by crystallization from different solvents. The urea tape is a rare phenomenon in cocrystals but it is consistent in urea:4,4'-bipyridine polymorphic cocrystals. The polymorph obtained from MeCN has symmetrical N-H...N hydrogen bond distances on either side of the urea tape. However, the other form obtained from MeOH has unsymmetrical N-H...N hydrogen bond lengths. In the polymorphic cocrystals of salicylic acid:4,4'-bipyridine, the basic supramolecular synthon acid-pyridine is the same but the 3D packing is different. Both the polymorphic pairs of cocrystals come under the category of packing polymorphs. All polymorphs were characterized by single-crystal X-ray diffraction (SCXRD), PXRD, DSC, FT-IR and HSM. N-H...N and the acid-pyridine supramolecular synthons were insulated by FT-IR vibrational spectroscopy.

beta gamma-fused turn structures in sugar amino acid (SAA) containing cyclic tetrapeptides with alpha 3 delta architecture

The current manuscript describes conformational analysis of 15-membered cyclic tetrapeptides (CTPs), with alpha 3 delta architecture, containing sugar amino acids (SAA) having variation in the stereocenter at C5 carbon. Conformational analyses of both the series, in protected and deprotected forms, were carried out in DMSO-d(6) using various NMR techniques, supported by restrained MD calculations. It was intriguing to notice that the alpha 3 delta macrocycles got stabilized by both 10-membered beta-turn as well as a seven-membered gamma-turn, fused within the same macrocycle. The presence of fused sub-structures within a 15-membered macrocycle is rare to see. Also, the stereocenter variation at C5 did not affect the fused turn structures and exhibited similar conformations in both the series. The design becomes highly advantageous as fused reverse turn structures are occurring in the cyclic structure with minimalistic size macrocycle and this can be applied to develop suitable pharmacophores in the drug development process. (C) 2014 Elsevier Ltd. All rights reserved.

N-Alkyl derivative of 1,9-pyrazoloanthrone as a sensor for picric acid

The N-alkyl derivative of 1,9-pyrazoloanthrone has been synthesized, characterized and evaluated as a potent sensor for picric acid.

Remarkable isomer-selective gelation of aromatic solvents by a polymorph of a urea-linked bile acid-amino acid conjugate

We report an unusual, isomer-selective gelation of aromatic solvents by a polymorph of a urea-linked bile acid-amino acid conjugate. The gelator showed selectivity towards gelation of 1,2-disubstituted aromatic solvents.

A fluorescent organic cage for picric acid detection

Dynamic covalent imine chemistry has been utilized to synthesize a fluorescent 3+2] self-assembled nanoscopic organic cage. The fluorescent nature of the reduced analogue of the cage was further exploited for the highly selective detection of the explosive picric acid (PA).