Structural analysis of trypanosomal sirtuin: an insight for selective drug design

The infectious disease burden imposed by trypanosomatidae family continues to create burden in countries that are least equipped to bring new medicines to the clinic. For sickness caused by this family of parasites (African trypanosomiasis, Chagas disease, and leishmaniasis) no vaccines are available, and currently available drugs suffer from insufficient efficacy, excessive toxicity, and steady loss of effectiveness due to resistance. Availability of the genome sequence of pathogens of this family offers a unique avenue for the identification of novel common drug targets for all three pathogens. Sirtuin family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases are remarkably conserved throughout evolution from archaebacteria to eukaryotes and plays an important role in trypanosomatidae biology and virulence. In order to gain insight for selective drug design, three-dimensional (3D) models of L. major, L. infantum, T. brucie, and T. cruzi sirtuin were constructed by homology modeling and compared with human sirtuin. The molecular electrostatic potentials and cavity depth analysis of these models suggest that the inhibitor binding catalytic domain has various minor structural differences in the active site of trypanosomal and human sirtuin, regardless of sequence similarity. These studies have implications for designing effective strategies to identify inhibitors that can be developed as novel broad-spectrum antitrypanosomal drugs.     

Synthesis of Polylactide: Effect of Dispersion of the Initiator

The ring opening polymerization of L-lactide was studied in bulk using stannous octoate as initiator. In some experiments, triphenylphosphine, a Lewis base was also used as co-initiator. The polymerization was carried out at 130°C up to 29 h. The monomer was used after recrystallizing three times with dry toluene. Experiments were carried out using a wide range of monomer to initiator ratio. The averages and distributions of molar masses of resulting PLA have been determined by means of size exclusion chromatography, SEC. It is shown that the (mode, process) procedure of dispersion of the catalyst in polymerization system affects the molar mass distribution of the product as is evidenced by the bimodality or even trimodality observed in the SEC chromatograms.     

Insights into the photophysics,protonation and Cu2+ ion coordination behaviour of anthracene-9,10-dione-based chemosensors

Carboxylic acid–diamine-based Cu²⁺ chromogenic sensors (3 and 4) exhibited colour switching from red to blue with good sensitivity and selectivity towards Cu²⁺ among other physiologically important alkali, alkaline earth and heavy metal ions. This colour-switching phenomenon arises due to selective deprotonation of aryl amine NH by Cu²⁺. Significantly, chemosensor 3 (λ_max 492 nm) shows multiple modes of complexation towards Cu²⁺. It is very much evident from the appearance of blue colour (λ_max 615 nm) at pH >7.0 and yellow colour (λ_max 465 nm) at pH < 4.0. In addition, chemosensor 3 exhibits a unique logic gate system that involves ‘INHIBIT’ and ‘TRANSFER’ logic gates.     

The explicit interactions of five-membered saturated heterocyclics containing one and two heteroatoms with single water molecule

In this article, the hydrogen bonding interaction between saturated five-membered heterocyclic molecules and water has been investigated. Molecular orbital and density functional theory methods have been used to evaluate the stabilization energies associated with the adduct formation between heterocyclic molecules and water. The hydrogen bond acceptor ability of O, S, Se, and N as members of five-membered ring has been analyzed. The effect of the presence of second heteroatom N in the ring on the hydrogen bond interaction has also been evaluated. Atoms in molecules theory calculations were carried out to characterize the hydrogen bond through the changes in electron density and Laplacian of electron density. A natural energy decomposition analysis and natural bond orbital analysis is also performed to understand the nature of hydrogen bonding interaction in monohydrated five-membered heterocyclic adducts.     

Quantum chemical investigation on the influence of amino substitution on proton affinity of oxazolidin-2-one

The scenarios of preferred protonation sites and the absolute gas-phase proton affinities of C5- and N4-amino derivatives of oxazolidinone (OXA) molecules possessing two oxygen and two nitrogen atoms, are studied to investigate the effect of substitution of amino group on geometry, electronic structure, and proton affinities of these molecules. The natural bond orbital analysis is invoked to obtain the second-order delocalization energies, occupations of lone pairs, charge distribution, and bond orders to rationalize the obtained results. Our findings reveal a strong nucleophilicity of O1 site in C5-amino and N4-amino-substituted OXA isomers just as in un-substituted OXA. The substituent nitrogen in N4-amino-substituted OXA has comparable electrophilicity to O1 site while lesser than acyl oxygen and higher than nitrogen of OXA ring in C5-amino-substituted OXA. The PA values of C5- and N4-amino-substituted OXA isomers span in the range 172.06–205.77 kcal mol^?1 (at CBS-Q). The PA values for the potential sites increase in the range 1.96–27.08 kcal mol^?1 as a result of the amino substitution at C5 and N4 in orientation (b) while exceptionally they decrease by 0.57–2.95 kcal mol^?1 as a result of the amino substitution at N4 in orientation (a). The results for the order of PA values of potential sites have been supported by molecular electrostatic potential maps. Our findings indicate that the factors such as geometrical rearrangements, variations in atomic charge densities and electron delocalization, effect of substituent, intramolecular hydrogen bonding, and electronic changes direct the relative stabilities and proton affinities of N, C5-substituted amino OXA isomers.     

Metal and Non-metal Based Catalysts for Oxidation of Organic Compounds

The oxidation of organic compounds is of extreme importance in synthetic chemistry. The catalysts provide high selectivity towards the oxidation products employing with the oxidants. This review is not intended to give a complete survey of all oxidation catalysis reactions by different catalysts but rather to give a summary of some important catalytic oxidation reactions by different metal and non-metal based catalysts.     

Synthesis of five-membered N-heterocycles using silver metal

The heterocyclic chemistry field has been revolutionized using transition metal catalyst in recent years. Various research groups have focused on the development of general protocols to achieve better functional group compatibilities and greater levels of molecular complexity under mild reaction conditions using easily available starting substrates. These methods afford many advantages as compared to alternative pathways involved in the synthesis of heterocyclic compounds. In this review article, we have concentrated on the synthesis of nitrogen-containing five-membered heterocylces in the presence of silver catalyst.