Synthesis of 14H-dibenzoxanthenes in green media using Sn(II)/nano silica as an efficient catalyst.

In this project, Sn(II)/nano silica has been prepared using a simple deposition of SnCl2.2.H2O on nano-silica. The prepared catalyst has been used as a green and reusable catalyst for synthesis of 14H-dibenzoxanthenes through a one-pot condensation reaction of ß-naphthol with various aliphatic and aromatic aldehydes. Several xanthene derivatives have been synthesized using ethanol as the solvent, 10 mol percent of the catalyst, at reflux condition, in 3 h, and by 48%-94% yield. The structures of the synthesized derivatives are confirmed by melting point, FT-IR, 13C-NMR, and 1H-NMR analyses. Additionally, the nanocatalyst composition was confirmed by SEM, EDX, FT-IR, and XRD.

Developing a variation of 3D-QSAR/MD method in drug design.

In continuation of the previous reports on a combination of 3D-quantitative structure-activity relationships (QSAR) with computational molecular dynamics (MD) studies, a new variation of 3D-QSAR/MD method has been employed for drug-design as an alternative or supplementary for the typical experimental methods. The presented method is more cost-effective and less time-consuming than the previous methods and avoids several restrictions of experimental methods, such as validity estimation, and predictability. For this purpose, seven inhibitors for bromodomain (BRD)-containing protein, as an important protein in the development of different types of cancer and responsible for oncogenic rearrangements, have been selected to study of their interactions by docking and MD simulations using molecular mechanics/generalized born surface area (MM/GBSA) method. To build the proposed model, a common variant of 3D-QSAR methods, comparative molecular field analysis has been employed using a dataset of 100 MD-extracted ligand conformations and their corresponding MM/GBSA BRD4-binding energies. The results showed excellent predictability of the generated model for both the training set and test groups. Finally, two new inhibitors were selected among total 4000 designed derivatives (generated through evolutionary techniques) using the proposed 3D-QSAR-MD model. The potentials of these inhibitors were assessed by MD simulations, which showed the higher inhibitory of these compounds than the previous inhibitors. Therefore, this method showed high potentials for acceleration of the procedure of drug design and a basis for joining researchers in computational biology and pharmaceutical sciences.

Catalyst-Free Synthesis of Benzofuran Derivatives from Cascade Reactions between Nitroepoxides and Salicylaldehydes.

Different benzofuran derivatives are synthesized via a catalyst-free reaction between nitroepoxides and salicylaldehydes. In the employed methodology, K2CO3 and DMF have been used at 110 °C, and the reactions were completed after 12 h in 33-84% yields. The highest yields were obtained using 3-nitrosalicylaldehyde. Finally, a plausible mechanism was proposed for the reaction, and some evidence was provided for this mechanism such as the detection of released acetate anion (using FTIR) and isolation and structure determination of the critical intermediate.

AMBER Force Field Parameters for Cobalt-Containing Biological Systems: A Systematic Derivation Study.

In the present work, the parameterization of a set of cobalt-containing systems has been performed to create a comprehensive library for bonding parameters of biological Co-containing systems. A standard process for the extraction and validation of parameters was employed, which could be used to create force field parameters for the other metal-containing systems. All protein data banks were searched to extract common chemical groups in bonding with cobalt, and finally, 16 structures were designed to represent the binding model of the chemical moieties with cobalt. The Hessian matrix of each structure was computed at the B3LYP/6-311++G(2d,2p) level of theory and the Seminario method was employed to compute cobalt bond stretching and angle bending parameters. Validation of the derived parameters was performed using structural minimization and molecular dynamics (MD) simulations of four models. Further validation was performed using an extensive MD simulation on carbonic anhydrase II as a common cobalt-containing metalloprotein. The results demonstrated that among models, the bonded model in combination with the RESP charges can produce the most reliable and accurate structural conformations for the metal site of cobalt-containing systems.

Antiproliferative activity of morpholine-based compounds on MCF-7 breast cancer, colon carcinoma C26, and normal fibroblast NIH-3T3 cell lines and study of their binding affinity to calf thymus-DNA and bovine serum albumin.

This report describes the results of a study on the antiproliferative activity of the morpholine-based ligand 1,3-bis(1-morpholinothiocarbonyl)benzene (HL) and its nickel(II) complex (NiL) against human breast cancer cells (MCF-7), colon carcinoma cells (C26), and normal fibroblast NIH-3T3 cells. NiL showed better cytotoxicity on both cancerous cells relative to normal cells in vitro with the highest selective index of 2.22 in MCF-7 cells. The interaction of both compounds with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) was studied using various spectroscopic techniques and analytical methods such as UV - vis titrations, thermal denaturation, circular dichroism, competitive fluorescent intercalator displacement assays, as well as molecular modeling. The fluorescence intensity of the probe molecule increases clearly when HL and NiL are added to the methylene blue (MB)-DNA system. Furthermore, the binding of HL and NiL quenches the BSA fluorescence, revealing a 1:1 interaction with a binding constant of about 105 M-1. Communicated by Ramaswamy H. Sarma.

Molecular dynamics study of biodegradation of azo dyes via their interactions with AzrC azoreductase.

Azo dyes are one of the most important class of dyes, which have been widely used in industries. Because of the environmental pollution of azo dyes, many studies have been performed to study their biodegradation using bacterial systems. In present work, the AzrC of mesophilic gram-positive Bacillus sp. B29 has been considered to study its interaction with five common azo dyes (orange G, acid red 88, Sudan I, orange I, and methyl red). The molecular dynamics simulations have been employed to study the interaction between AzrC and azo dyes. The trajectory was confirmed using root mean square deviation and the root mean square fluctuation analyses. Then, the hydrogen bond and alanine scanning analyses were performed to reveal active site residues. Phe105 (A), Phe125 (B), Phe172 (B), and Pro132 (B) have been found as the most important hydrophobic residues whereas Asn104 (A), Tyr127 (B), and Asn187 (A) have key role in making hydrogen bond. The results of molecular mechanics Poisson-Boltzmann surface area and molecular mechanics generalized Born surface area calculations proved that the hydrophobic azo dyes like Acid red 88 binds more tightly to the AzrC protein. The calculated data suggested MR A 121 (B) I as a potential candidate for improving the AzrC-MR interactions.

New mixed ligand palladium(II) complexes based on the antiepileptic drug sodium valproate and bioactive nitrogen-donor ligands: synthesis, structural characterization, binding interactions with DNA and BSA, in vitro cytotoxicity studies and DFT calculations.

The complexes [Pd(valp)2(imidazole)2] (1), [Pd(valp)2(pyrazine)2] (2) (valp is sodium valproate) have been synthesized and characterized using IR, (1)H NMR, (13)C{(1)H} NMR and UV-Vis spectrometry. The interaction of complexes with CT-DNA has been investigated using spectroscopic tools and viscosity measurement. In each case, the association constant (Kb) was deduced from the absorption spectral study and the number of binding sites (n) and the binding constant (K) were calculated from relevant fluorescence quenching data. As a result, a non-covalent interaction between the metal complex and DNA was suggested, which could be assigned to an intercalative binding. In addition, the interaction of 1 and 2 was ventured with bovine serum albumin (BSA) with the help of absorption and fluorescence spectroscopy measurements. Through these techniques, the apparent association constant (Kapp) and the binding constant (K) could be calculated for each complex. Evaluation of cytotoxic activity of the complexes against four different cancer cell lines proved that the complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate. Moreover, density functional theory (DFT) calculations were employed to provide more evidence about the observed data. The majority of trans isomers were supported not only by energies, but also by the similarity of its calculated IR frequencies, UV adsorptions and NMR chemical shifts to the experimental values.

Barrierless inter and intramolecular proton transfer; a DFT study of tautomerism in microsolvated and protonated systems.

DFT calculations were employed to study tautomers of 2,2-di(pyrimidin-2-yl)acetic acid (DPA) in the gas phase and in the presence of water, methanol, DMSO (microsolvation models), and proton (H(+)). In the gas phase, all three tautomers were in equilibrium with each other (T2 was slightly more favorable); but, in microsolvation with protic solvent, T3 was a major isomer. Moreover, unexpectedly enough, T1 (common form of DPA) was the least stable tautomer in the gas phase, while, in the water (as solvent), T1 was the most stable one. The calculated energy values indicated a very special barrierless tautomeric system between T2 and T3. In the gas phase, ΔG(#) for T2 → T3 was only 0.30 kcal/mol, while it was 56.4 and 44.8 kcal/mol for T2 → T1 and T3 → T1, respectively. Rate constants for conversion of T2 into T3 were high in all cases, and their values in the gas phase and in the presence of water, methanol, DMSO, and proton were 3.6 × 10(12), 3.3 × 10(9), 2.7 × 10(11), 2.3 × 10(12), and 2.3 × 10(12) s(-1), respectively. All types of microsolvation slightly decreased the rate constant of this conversion. The rate constant for conversion of T2 into T1 (1,3-H shift) in the gas phase and in the presence of water, methanol, DMSO, and proton was 3.0 × 10(-29), 2.2 × 10(5), 1.1 × 10(-34), 5.2 × 10(-40), and 4.2 × 10(-26) s(-1), respectively. These values showed that only microsolvation with water strongly increased rate constants of tautomerism for T2 → T1 and this type of tautomerism was impossible in the gas phase or other microsolvation models. Although using water as the solvent enhanced rate constants of all types of tautomeric interconversions, its enhancement was less than that of microsolvation with water.

DFT and MP2 study of low barrier proton transfer in hydrazide schiff base tautomers via water bridges and in the gas.

MP2 and DFT studies were performed on the tautomers of N'-ethylideneacetohydrazide in different environments including gas phase, continuum solvent and microhydrated environment. The ground electronic state structures of the tautomers were optimized at the MP2 and B3LYP levels of theory using 6-311++G(d,p), separately. The optimized geometries of the transition states of different tautomerism processes, which occur through the proton transfer (PT) reaction, were determined using the QST3 approach at the same levels of theory. The same stability order as T1Z[Symbol in text] T2ZE[Symbol: see text] T2ZZ[Symbol in text] T2EE[Symbol in text] T2EZ[Symbol in text] T6[Symbol in text] T4E was found for the tautomers in the gas phase, continuum solvent and microhydrated environment for both B3LYP and MP2 levels of theory. In addition, the variations of the Gibbs free energies of tautomeric processes, the activation Gibbs free energies of the forward and reverse tautomeric processes with the polarity of the solvent (in continuum solvent model) and the number of water molecules (in microhydrated environment) were investigated. It was found that the reverse tautomeric process is more favorable in all considered environments thermodynamically and kinetically. In addition, it was shown that the rate constants of the reverse and forward considered tautomeric processes decrease with the solvent polarity in the continuum solvent model and the process becomes more difficult than the gas phase. The opposite trend is seen in the microhydrated environment.

Investigation of structure, vibrational and NMR spectra of oxycodone and naltrexone: a combined experimental and theoretical study.

In this work, two important opioid antagonists, naltrexone and oxycodone, were prepared from thebaine and were characterized by IR, (1)H NMR and (13)C NMR spectroscopy. Moreover, computational NMR and IR parameters were obtained using density functional theory (DFT) at B3LYP/6-311++G** level of theory. Complete NMR and vibrational assignment were carried out using the observed and calculated spectra. The IR frequencies and NMR chemical shifts, determined experimentally, were compared with those obtained theoretically from DFT calculations, showed good agreements. The RMS errors observed between experimental and calculated data for the IR absorptions are 85 and 105 cm(-1), for the (1)H NMR peaks are 0.87 and 0.17 ppm and for those of (13)C NMR are 5.6 and 5.3 ppm, respectively for naltrexone and oxycodone.

Theoretical investigation of tautomerism in N-hydroxy amidines.

A DFT study with QST3 approach method is used to calculate kinetic, thermodynamic, spectral and structural data of tautomers and transition state structures of some N-hydroxy amidines. All tautomers and transition states are optimized at the B3LYP/6-311++g** and B3LYP/aug-cc-pvtz level, with good agreement in energetic result with energies obtained from CBS-QB3, a complete basis set composite energy method. The result shows that the tautomer a (amide oxime) is more stable than the tautomer b (imino hydroxylamine) as is reported in the literature. In addition, our finding shows that, the energy difference between two tautomers is only in about 4-10 kcal/mol but the barrier energy found in traversing each tautomer to another one is in the range of 33-71 kcal/mol. Therefore, it is impossible to convert these two tautomers to each other at room temperature. Additionally, transition state theory is applied to estimate the barrier energy and reaction rate constants of the hydrogen exchange between tautomers in presence of 1-3 molecules of water. The computed activation barrier shows us that the barrier energy of solvent assisted tautomerism is about 9-20 kcal/mol and lower than simple tautomerism and this water-assisted tautomerism is much faster than simple tautomerism, especially with the assisting two molecules of water.