Simultaneous hydrogen bonding and π-stacking interactions between flavin/porphyrin host-guest systems

In this Letter, we describe the formation of complexes between flavin and diamidopyridine functionalized porphyrin systems via hydrogen bonding and π-stacking interactions.     

Reversal of Regioselectivity in Asymmetric C−H Bond Annulation with Bromoalkynes under Cobalt Catalysis**

Metal-catalyzed asymmetric C−H bond annulation strategy offers a versatile platform, allowing the construction of complex P-chiral molecules through atom- and step-economical fashion. However, regioselective insertion of π-coupling partner between M−C bond with high enantio-induction remain elusive. Using commercially available Co(II) salt and chiral-Salox ligands, we demonstrate an unusual protocol for the regio-reversal, enantioselective C−H bond annulation of phosphinamide with bromoalkyne through desymmetrization. The reaction proceeds through ligand-assisted enantiodetermining cyclocobaltation followed by regioselective insertion of bromoalkyne between Co−C, subsequent reductive elimination, and halogen exchange with carboxylate resulted in P-stereogenic compounds in excellent ee (up to >99 %). The isolation of cobaltacycle involved in the catalytic cycle and the outcome of control experiments provide support for a plausible mechanism.     

Comparison of experimental and ab initio HF and DFT vibrational spectra of benzimidazole

In this work, we will report a combined experimental and theoretical study on molecular and vibrational structure of benzimidazole. The laser Raman and Fourier transform infrared spectra of benzimidazole were recorded in the solid phase. The equilibrium geometry, harmonic vibrational frequencies, infrared intensities, Raman scattering activities, depolarization ratios and reduced masses were calculated by HF and density functional B3LYP method with the 6-311G(d,p) basis set. The scaled theoretical wavenumbers showed very good agreement with the experimental values. The thermodynamic functions of the title compound were also performed at HF/6-31G(d,p)/6-311G(d,p) and B3LYP/6-31G(d,p)/6-311G(d,p) levels of theory. A detailed interpretations of the infrared and Raman spectra of benzimidazole is reported. The theoretical spectrograms for FT-IR spectra of the title molecule have been constructed.     

Computational identification of novel piperidine derivatives as potential HDM2 inhibitors designed by fragment-based QSAR,molecular docking and molecular dynamics simulations

Tumor suppressor protein p53 maintains integrity of genome and regulates the genes responsible for DNA repair mechanism, apoptosis as well as cell cycle and growth arrest. As with murine double minute 2 (MDM2), the human homolog HDM2 is a principal cellular antagonist of p53. In unstressed cells, cellular levels of p53 and HDM2 are maintained in an autoregulatory manner in which both mutually control cellular levels of each other. About half of the human cancers express wild-type p53 protein that is antagonized by over-expressed HDM2. Restoring p53 function via HDM2 antagonists is a leading therapeutic approach for treating a variety of tumors. In this study, we have developed a novel statistically sound group-based QSAR (GQSAR) model using piperidine-derived compounds that have been validated experimentally to inhibit p53–HDM2 interaction. On the basis of developed GQSAR model, a combinatorial library of molecules was prepared and its activity was predicted. These molecules were then docked to HDM2, and two top-scoring molecules possessing a binding energy of ?6.639 and ?6.305 kcal/mol were selected for further study. These molecules and their binding poses were analyzed further via molecular dynamic simulations. In this study, we report two lead compounds as potent HDM2 inhibitors and also provide an insight into mechanism of interaction of the lead compounds to HDM2 target.

     

Chiral Phosphoric Acid Catalyzed Kinetic Resolution of 2‐Amido Benzyl Alcohols: Asymmetric Synthesis of 4H‐3,1‐Benzoxazines

An efficient method for the asymmetric synthesis of 4H‐3,1‐benzoxazines was developed by kinetic resolution of 2‐amido benzyl alcohols using chiral phosphoric acid catalyzed intramolecular cyclizations. A broad range of benzyl alcohols (both secondary and tertiary alcohols) were kinetically resolved with high selectivities, with an s factor of up to 94. Mechanistic studies were performed to elucidate the mechanism of these reactions, wherein the amide moieties reacted as the electrophiles. Gram‐scale reaction and facile transformations of the chiral products demonstrate the potential of this method in asymmetric synthesis of biologically active chiral heterocycles.     

Homophtalonitrile for Multicomponent Reactions: Syntheses and Optical Properties of o-Cyanophenyl- or Indol-3-yl-Substituted Chromeno[2,3-c]isoquinolin-5-Amines

Malononitrile is a useful reagent for multicomponent reactions with hundreds of methods developed. In this paper, we suggest α-(cyano)-o-tolunitrile (homophtalonitrile) to work as a vinylogous malononitrile. Thus, a organocatalytic pseudo-three-component reaction of homopthalonitrile (2 equiv) and o-hydroxybenzaldehyde, leading to the diastereoselective formation of 5-amino-12H-chromeno[2,3-c]isoquinolin-12-yl)(cyano)methyl)benzonitriles, was discovered. The possibility to employ other nucleophiles was demonstrated for indoles, and a sequential three-component reaction of homophtalonitrile, o-hydroxybenzaldehyde, and (aza)indole, giving 12-(1H-Indol-3-yl)-12H-chromeno[2,3-c]isoquinolin-5-amines, was developed. The photophysical properties of the synthesized compounds have been studied, revealing high fluorescence quantum yields (42–70 %) for indol-3-yl substituted 12H-chromeno[2,3-c]isoquinolin-5-amines and reversible fluorescence quenching under acidic conditions.     

Effect of emulsifiers on surface properties of sucrose by inverse gas chromatography

Inverse gas chromatography (IGC) was employed to characterize the changes in surface properties of sucrose particles coated with either lecithin or polyglycerol polyricinoleate. IGC was performed using polar and non-polar adsorbates at infinite dilution with the sucrose particles as the solid stationary phase. Coating the sugar surface with emulsifiers induced an increase in the lipophilicity of the sugar particles, i.e. a sharp decrease in the acidity of the surface. Yet the two emulsifiers induced a slightly different increase in the surface basicity. It was hypothesized that this observation was due to a difference in the molecular structure of the emulsifiers.     

Adsorption of H2 molecules on B/N-doped defected graphene sheets—a DFT study

Structural Chemistry - Adsorption of hydrogen molecules on the surface of two-dimensional sheets is extremely challenging due to the non-polar nature of the molecules. Though the adsorption occurs...     

Chiral Phosphoric Acid Catalyzed Kinetic Resolution of 2-Amido Benzyl Alcohols: Asymmetric Synthesis of 4H-3,1-Benzoxazines

An efficient method for the asymmetric synthesis of 4H-3,1-benzoxazines was developed by kinetic resolution of 2-amido benzyl alcohols using chiral phosphoric acid catalyzed intramolecular cyclizations. A broad range of benzyl alcohols (both secondary and tertiary alcohols) were kinetically resolved with high selectivities, with an s factor of up to 94. Mechanistic studies were performed to elucidate the mechanism of these reactions, wherein the amide moieties reacted as the electrophiles. Gram-scale reaction and facile transformations of the chiral products demonstrate the potential of this method in asymmetric synthesis of biologically active chiral heterocycles.