Acyl‐Directed ortho‐Borylation of Anilines and C7 Borylation of Indoles using just BBr3

Indoles are privileged heterocycles found in many biologically active pharmaceuticals and natural products. However, the selective functionalization of the benzenoid moiety in indoles in preference to the more reactive pyrrolic unit is a significant challenge. Herein we report that N‐acyl directing groups enable the C7‐selective C?H borylation of indoles using just BBr₃. This transformation shows some functional‐group tolerance and notably proceeds with C6 substituted indoles. The directing group can be readily removed in situ and the products isolated as the pinacol boronate esters. Acyl‐directed electrophilic borylation can be extended to carbazoles and anilines with excellent ortho selectivity. 4‐amino‐indoles are amenable to this process, with acyl group installation and directed electrophilic C?H borylation enabling selective formation of C5‐BPin‐indoles.     

3‐Germyl‐3,3‐di­methyl­propionic acid derivatives

The crystal structures of 3,3‐di­methyl‐3‐(tri­chloro­germyl)­propionic acid, [Ge(C₅H₉O₂)Cl₃], 3,3‐di­methyl‐3‐(tri­phenyl­germyl)­propionic acid, [Ge(C₆H₅)₃(C₅H₉O₂)], and 3,3‐di­methyl‐3‐(tri‐p‐toly­lgermyl)­propionic acid, [Ge(C₇H₇)₃(C₅H₉O₂)], have slightly distorted tetrahedral geometries about the Ge atoms. All the structures form dimers via strong O—H·O hydrogen bonds, resulting in eight‐membered rings that can be best described in terms of graph‐set notation (8).     

catena‐Poly­[[tri‐n‐butyl­tin]‐μ‐N‐(1‐naphthyl)­maleamato]

The crystal structure of catena‐poly­[[tri‐n‐butyl­tin]‐μ‐3‐(1‐naph­thyl­amino­carbonyl)­acrylato‐κ²O¹:O³], [Sn(C₄H₉)₃(C₁₄H₁₀NO₃)]_n, is composed of polymeric chains wherein the metal center exhibits a distorted trigonal‐bipyramidal geometry, with three n‐butyl groups defining the trigonal plane [mean Sn—C 2.133 (7) Å] and the axial positions being occupied by the carboxyl­ate O atoms of two different N‐(1‐naphthyl)­maleamate ligands with inequivalent Sn—O distances [2.167 (4) and 2.457 (4) Å]. The N‐(1‐naphthyl)­maleamate fragment forms an essentially planar seven‐membered ring involving an intramolecular N—H?O hydrogen bond.     

Synthesis and Characterization of Biologically Potent Di‐organotin(IV) Complexes of Mono‐Methyl Glutarate

The synthesis and characterization of some novel compounds of organotin(IV) chlorides with monomethyl glutarate is reported; the ligand molecule appears to be bound to the tin atom through the carbonyl oxygen. The results obtained through ¹H‐¹³C‐¹¹⁹Sn NMR, FT‐IR and ¹¹⁹Sn Mössbauer spectra show that the diorganotin(IV) complexes have hexacoordination with octahedral geometry. Biological screening of the complexes reveals that the diorganotin(IV) complexes show significant activity against all microorganisms.     

Electrostatic Perturbations in the Substrate-Binding Pocket of Taurine/α-Ketoglutarate Dioxygenase Determine its Selectivity

Taurine/α-ketoglutarate dioxygenase is an important enzyme that takes part in the cysteine catabolism process in the human body and selectively hydroxylates taurine at the C¹-position. Recent computational studies showed that in the gas-phase the C²−H bond of taurine is substantially weaker than the C¹−H bond, yet no evidence exists of 2-hydroxytaurine products. To this end, a detailed computational study on the selectivity patterns in TauD was performed. The calculations show that the second-coordination sphere and the protonation states of residues play a major role in guiding the enzyme to the right selectivity. Specifically, a single proton on an active site histidine residue can change the regioselectivity of the reaction through its electrostatic perturbations in the active site and effectively changes the C¹−H and C²−H bond strengths of taurine. This is further emphasized by many polar and hydrogen bonding interactions of the protein cage in TauD with the substrate and the oxidant that weaken the pro-R C¹−H bond and triggers a chemoselective reaction process. The large cluster models reproduce the experimental free energy of activation excellently.     

Synthesis,structural elucidation and biological activities of organotin(IV) derivatives of 4-(2-thienyl)butyric acid

A series of tri- and diorganotin(IV) derivatives of 4-(2-thienyl)butyric acid have been synthesized by the reaction of ligand acid with tri- and diorganotin salts in 1:1 and 2:1 molar ratios, respectively. The synthesized compounds have been confirmed by CHNS elemental analyses, FTIR, multinuclear NMR (¹H and ¹³C) spectroscopy and X-ray diffraction studies. NMR data reveal a 5-coordinate geometry for the triorganotin(IV) derivatives, while 6-coordinate for the diorganotin(IV) derivatives, respectively. The X-ray crystallographic analysis of the compound 2 showed polymeric 5-coordinate trigonal bipyramidal geometry. Antimicrobial studies were also evaluated against different strains of bacteria (Escherichia coli, Klebsiella pneumoniae, Bacillus subtilis and Staphylococcus aureus) and fungi (Mucor species, Aspergillus solani, Helminthosporium oryzae, Aspergillus flavus, Aspergillus niger) to establish the biological significance of these compounds. The synthesized compounds probably work by interfering with the ability of bacteria to form cell walls by keeping unwanted substances from entering their cells and stop the contents of their cells from leaking out due which the bacteria get die. The antifungal activity of some of the tested compound is comparable to that of the standard drug, terbinafine. From their antimicrobial results, it was concluded that they might be used as potential candidate for the generation of new antimicrobial drugs.     

Energy–entropy method using multiscale cell correlation to calculate binding free energies in the SAMPL8 host–guest challenge

Free energy drives a wide range of molecular processes such as solvation, binding, chemical reactions and conformational change. Given the central importance of binding, a wide range of methods exist to calculate it, whether based on scoring functions, machine-learning, classical or electronic structure methods, alchemy, or explicit evaluation of energy and entropy. Here we present a new energy–entropy (EE) method to calculate the host–guest binding free energy directly from molecular dynamics (MD) simulation. Entropy is evaluated using Multiscale Cell Correlation (MCC) which uses force and torque covariance and contacts at two different length scales. The method is tested on a series of seven host–guest complexes in the SAMPL8 (Statistical Assessment of the Modeling of Proteins and Ligands) “Drugs of Abuse” Blind Challenge. The EE-MCC binding free energies are found to agree with experiment with an average error of 0.9 kcal mol^?1. MCC makes clear the origin of the entropy changes, showing that the large loss of positional, orientational, and to a lesser extent conformational entropy of each binding guest is compensated for by a gain in orientational entropy of water released to bulk, combined with smaller decreases in vibrational entropy of the host, guest and contacting water.

     

Morphological and electrical properties of SrTiO_3/TiO_2/SrTiO_3 sandwich structures prepared by plasma sputtering

SrTiO_3(STO) and TiO_2 are insulating materials with large dielectric constants and opposite signs of the quadratic coefficient of voltage(α). Insertion of a TiO_2 thin film between STO layers increases the linearity of the capacitance in response to an applied voltage, to meet the increasing demand of large-capacitance-density dynamic random access memory capacitors. Both STO and TiO_2 suffer from the problem of high leakage current owing to their almost equivalent and low bandgap energies. To overcome this, the thickness of the thin TiO_2 film sandwiched between the STO films was varied. A magnetron sputtering system equipped with radio frequency and direct current power supply was employed for depositing the thin films. Ti N was deposited as the top and bottom metal electrodes to form a metal–insulator metal(MIM) structure,which exhibited a very large linear capacitance density of 21 fF/um~2 that decreased by increasing the thickness of the TiO_2 film. The leakage current decreased with an increase in the thickness of TiO_2, and for a 27-nm-thick film, the measured leakage current was 2.0 × 10~(-10) A. X-ray diffraction and Raman spectroscopy revealed that Ti N, STO, and TiO_2 films are crystalline and TiO_2 has a dominant anatese phase structure.     

Synthesis of stannic(IV) complexes: Their structural elucidation in solid and solution state and antimicrobial activity

A series of organotin(IV) thiocarboxylates have been synthesized with the general formula R₂SnL₂ and R₃SnL (R = Ph₂(I), Me₃(II), n‐Bu₃(III), Ph₃(IV), Cy₃(V), Me₂(VI), n‐Bu₂(VII), and L = piperidine‐1‐thiocarboxylic acid) in anhydrous toluene under the reflux conditions. The complexes were characterized by microanalysis, IR, ¹H and ¹³C NMR, mass spectrometry, and XRD. NMR data revealed that thiocarboxylic acid acts as bidentate, and complexes exhibit the four‐coordinated geometry in solution state. In solid state, diorganotin complexes exhibit the hexa‐coordinated geometry whereas the triorganotin(IV) compounds show the five‐coordinated geometry. These complexes were also tested for their antimicrobial activity along with the ligand against different animals, plant pathogens, and Artemia salina. All complexes with few exceptions show high activity as compared to the ligand. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:664–674, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20380