Synthesis, characterization, Hirshfeld surface analysis, antioxidant and selective ß-glucuronidase inhibitory studies of transition metal complexes of hydrazide based Schiff base ligand.

The synthesis of N'-[(4-hydroxy-3-methoxyphenyl)methylidene] 2-aminobenzohydrazide (H-AHMB) was performed by condensing O-vanillin with 2-aminobenzohydrazide and was characterized by FTIR, high resolution ESI(+) mass spectral analysis, 1H and 13C-NMR. The compound H-AHMB was crystallized in orthorhombic Pbca space group and studied for single crystal diffraction analysis. Hirshfeld surface analysis was also carried out for identifying short interatomic interactions. The major interactions H…H, O…H and C…H cover the Hirshfeld surface of H-AHMB. The metal complexes [M(AHMB)n] where M = Co(II), Ni(II), Cu(II) and Zn(II) were prepared from metal chlorides and H-AHMB ligand. The bonding was unambigously assigned using FTIR and UV/vis analysis. The synthesized ligand H-AHMB and its metal complexes were studied for ß-glucuronidase enzyme inhibition. Surprisingly the metal complexes were found more active than the parent ligand and even the standard drug. Zn-AHMB shown IC50 = 17.3 ± 0.68 µM compared to IC50 = 45.75 ± 2.16 µM shown by D-saccharic acid-1,4-lactone used as standard. The better activity by Zn-AHMB implying zinc based metallodrug for the treatment of diseases associated with ß-glucuronidase enzyme. The DPPH radical scavenging activities were also studied for all the synthesized compounds. The Co-AHMB complex with IC50 = 98.2 ± 1.78 µM was the only candidate to scavenge the DPPH free radicals.

Computational investigation of N2O adsorption and dissociation on the silicon-embedded graphene catalyst: A density functional theory perspective.

One of the encouraging processes to protect the environment is the catalytic conversion of N2O and other harmful greenhouse gases. Employing heteroatom dopants into the Graphene structure for this conversion is an attractive technique owing to its relatively low price and the very low destructive impacts. DFT was applied to explore fundamental and principal reactions of N2O adsorption and dissociation over the Silicon-embedded Graphene catalyst to contribute to the search for green catalysts in the conversion of toxic gases into less harmful ones. Forming a surface peroxy group O22-, N2O bond cleavage and oxygen atom transfer were theoretically investigated. It is found that the N2O molecule requires +0.52, +0.88 and + 0.4 eV of activation energies through mentioned three reactions, respectively, to adsorb and decompose to N2 and O2. The parallel, lying-atop-011 and flat were stable forms with adsorption energies of -0.20 (-4.65), -0.19 (-4.53) and -0.18 (-4.46) and -0.19 eV (-4.53 kcal/mol), respectively. The achieved outcomes reveal that Silicon-embedded Graphene has a high potential to be used as a more efficient and green catalyst for the catalytic conversion of the air polluting gases in comparison to the Selenium-doped Graphene, Fe+, Manganese-embedded Graphene and Magnesium oxide (MgO) catalysts.

Computational study of the unimolecular and bimolecular decomposition mechanisms of propylamine.

A detailed computational study of the dehydrogenation reaction of trans-propylamine (trans-PA) in the gas phase has been performed using density functional method (DFT) and CBS-QB3 calculations. Different mechanistic pathways were studied for the reaction of n-propylamine. Both thermodynamic functions and activation parameters were calculated for all investigated pathways. Most of the dehydrogenation reaction mechanisms occur in a concerted step transition state as an exothermic process. The mechanisms for pathways A and B comprise two key-steps: H2 eliminated from PA leading to the formation of allylamine that undergoes an unimolecular dissociation in the second step of the mechanism. Among these pathways, the formation of ethyl cyanide and H2 is the most significant one (pathway B), both kinetically and thermodynamically, with an energy barrier of 416 kJ mol-1. The individual mechanisms for the pathways from C to N involve the dehydrogenation reaction of PA via hydrogen ion, ammonia ion and methyl cation. The formation of α-propylamine cation and NH3 (pathway E) is the most favorable reaction with an activation barrier of 1 kJ mol-1. This pathway has the lowest activation energy calculated of all proposed pathways.

Design, Synthesis and Qualitative Structure Activity Relationship Evaluations of Quinoline-Based Bisarylimidazoles as Antibacterial Motifs.

BACKGROUND: The emergence of drug-resistant bacteria in clinical practice has propelled a concerted effort to find new classes of antibiotics that will circumvent current modes of resistance. We previously described a set of imidazopyridine antibacterial leads that contain a core composed of benzimidazole and a central phthalic acid linker. These compounds showed potent antibacterial properties against a wide range of Gram-positive and Gram-negative bacteria. In this respect, we conducted a systematic exploration of new disubstituted imidazole functionalities on quinoline 4-position as the central linker, to determine the factors that direct the potent antibacterial activity. We found that some of the newly synthesized compounds possessed more potent activity compared to currently available medications. The newly synthesized compounds were screened against several clinical isolates and Staphylococcus aureus, including the methicillinresistant (MRSA) and the methicillin-sensitive (MSAA). METHODS: The goal of this work is to undertake rigorous testing of new hybrid scaffolds of quinoline flanked by diaryl imidazoles and their structure-activity against a range of bacterial strains. Described herein is the account of the modification of the central linker region, the imidazole functionality, and substituents at the 4-position of the quinoline, and their effect on the antibacterial potency of the resulting derivatives. Our efforts here have been driven by previous reports on the applications of Pfitzinger cyclization protocol. This complexity-generating reaction transforms a relatively simple substrate, into a more complex products with the potential for diversification via functionalization of the resultant acid. RESULTS: We identified compounds that possess potent and broad-spectrum antibacterial activities against clinical isolates and drug resistant strains. Structure-Activity relationships of these compounds were further explored to determine the crucial structural features needed to enhance their antibacterial activity. In this respect, it was found that, hydrophobic and electron-withdrawing moieties, such as halogens, were required on each end of the isoquinoline-based bisaryl imidazole hybrid motifs to produce broad-spectrum activity against the tested strains. Thus, molecules containing halophenyl or pyridyl arms were found more potent than molecules containing thiophene and/or electron-releasing groups on the phenyl arms, which showed much less antibacterial activity against the tested strains. CONCLUSION: In summary, 4-(4,5-diphenyl-1H-imidazol-2-yl)-2-phenylquinoline systems can be assembled efficiently through the Pfitzinger ring expansion- condensation strategy. This approach appears to hold considerable synthetic utility. The particular value of such a synthetic route resides on the conciseness and efficiency through which imidazo-quinoline construction can be synthesized from structurally simple and accessible acetophenone precursors.

Assessment of standard force field models against high-quality ab initio potential curves for prototypes of pi-pi, CH/pi, and SH/pi interactions.

Several popular force fields, namely, CHARMM, AMBER, OPLS-AA, and MM3, have been tested for their ability to reproduce highly accurate quantum mechanical potential energy curves for noncovalent interactions in the benzene dimer, the benzene-CH(4) complex, and the benzene-H(2)S complex. All of the force fields are semi-quantitatively correct, but none of them is consistently reliable quantitatively. Re-optimization of Lennard-Jones parameters and symmetry-adapted perturbation theory analysis for the benzene dimer suggests that better agreement cannot be expected unless more flexible functional forms (particularly for the electrostatic contributions) are employed for the empirical force fields.

High-accuracy quantum mechanical studies of pi-pi interactions in benzene dimers.

Although supramolecular chemistry and noncovalent interactions are playing an increasingly important role in modern chemical research, a detailed understanding of prototype noncovalent interactions remains lacking. In particular, pi-pi interactions, which are ubiquitous in biological systems, are not fully understood in terms of their strength, geometrical dependence, substituent effects, or fundamental physical nature. However, state-of-the-art quantum chemical methods are beginning to provide answers to these questions. Coupled-cluster theory through perturbative triple excitations in conjunction with large basis sets and extrapolations to the complete basis set limit have provided definitive results for the binding energy of several configurations of the benzene dimer, and benchmark-quality ab initio potential curves are being used to calibrate new density functional and force-field models for pi-pi interactions. Studies of substituted benzene dimers indicate flaws in the conventional wisdom about substituent effects in pi-pi interactions. Three-body and four-body interactions in benzene clusters have also been examined.

Aliphatic C-H/pi interactions: Methane-benzene, methane-phenol, and methane-indole complexes.

Noncovalent C-H/pi interactions are prevalent in biochemistry and are important in molecular recognition. In this work, we present potential energy curves for methane-benzene, methane-phenol, and methane-indole complexes as prototypes for interactions between C-H bonds and the aromatic components of phenylalanine, tyrosine, and tryptophan. Second-order perturbation theory (MP2) is used in conjunction with the aug-cc-pVDZ and aug-cc-pVTZ basis sets to determine the counterpoise-corrected interaction energy for selected complex configurations. Using corrections for higher-order electron correlation determined with coupled-cluster theory through perturbative triples [CCSD(T)] in the aug-cc-pVDZ basis set, we estimate, through an additive approximation, results at the very accurate CCSD(T)/aug-cc-pVTZ level of theory. Symmetry-adapted perturbation theory (SAPT) is employed to determine the physically significant components of the total interaction energy for each complex.

The effect of multiple substituents on sandwich and T-shaped pi-pi interactions.

Sandwich and T-shaped configurations of substituted benzene dimers were studied by second-order perturbation theory to determine how substituents tune pi-pi interactions. Remarkably, multiple substituents have an additive effect on the binding energy of sandwich dimers, except in some cases when substituents are aligned on top of each other. The energetics of substituted T-shaped configurations are more complex, but nevertheless a simple model that accounts for electrostatic and dispersion interactions (and direct contacts between substituents on one ring and hydrogen atoms on the other), provides a good match to the quantum mechanical results. These results provide insight into the manner by which substituents csan be utilized in supramolecular design.

Substituent effects in pi-pi interactions: sandwich and T-shaped configurations.

Sandwich and T-shaped configurations of benzene dimer, benzene-phenol, benzene-toluene, benzene-fluorobenzene, and benzene-benzonitrile are studied by coupled-cluster theory to elucidate how substituents tune pi-pi interactions. All substituted sandwich dimers bind more strongly than benzene dimer, whereas the T-shaped configurations bind more or less favorably depending on the substituent. Symmetry-adapted perturbation theory (SAPT) indicates that electrostatic, dispersion, induction, and exchange-repulsion contributions are all significant to the overall binding energies, and all but induction are important in determining relative energies. Models of pi-pi interactions based solely on electrostatics, such as the Hunter-Sanders rules, do not seem capable of explaining the energetic ordering of the dimers considered.

Estimates of the ab initio limit for pi-pi interactions: the benzene dimer.

State-of-the-art electronic structure methods have been applied to the simplest prototype of aromatic pi-pi interactions, the benzene dimer. By comparison to results with a large aug-cc-pVTZ basis set, we demonstrate that more modest basis sets such as aug-cc-pVDZ are sufficient for geometry optimizations of intermolecular parameters at the second-order Møller-Plesset perturbation theory (MP2) level. However, basis sets even larger than aug-cc-pVTZ are important for accurate binding energies. The complete basis set MP2 binding energies, estimated by explicitly correlated MP2-R12/A techniques, are significantly larger in magnitude than previous estimates. When corrected for higher-order correlation effects via coupled cluster with singles, doubles, and perturbative triples [CCSD(T)], the binding energies D(e) (D(0)) for the sandwich, T-shaped, and parallel-displaced configurations are found to be 1.8 (2.0), 2.7 (2.4), and 2.8 (2.7) kcal mol(-1), respectively.