ABSTRACT
The theoretical charge density study for the gas phase of anti-leprosy drug Dapsone has been carried out in the light of the theory of atoms in molecules using density functional theory employing B3LYP(6-311G++(d, p) hybrid functional completed with dispersion corrections. The Hirshfeld surface analysis as well as fingerprint plots has been utilized to visualize and quantify the intermolecular contacts present in the molecule. The topological properties such as electron density and its Laplacian, delocalization index have been elucidated to throw light into the chemical bonding and atomic and molecular details. The electron localization function has been used to visualize and deduce information on the lone pair and the subshells of the Cl atom. The electrostatic potential visualizes the positive and negative electrostatic potential regions which are susceptible to nucleophilic and electrophilic attack. On the whole, this study provides an exact mechanism, interaction, and topological and electrostatic properties of the drug through theoretical insights which all will be a platform for our further investigation of the interaction between dapsone and dihydropteroate synthase (DHPS).
Subject(s)
Dapsone/chemistry , Dihydropteroate Synthase/antagonists & inhibitors , Models, Molecular , Bacterial Proteins/antagonists & inhibitors , Computational Chemistry , Dapsone/pharmacology , Hydrogen Bonding , Leprostatic Agents/chemistry , Leprostatic Agents/pharmacology , Molecular Docking Simulation , Mycobacterium leprae/enzymology , Static ElectricityABSTRACT
Three benzenedithiolate-bridged diiron hexacarbonyl complexes (2, 3 and 4) with different functional groups were designed and synthesized. In addition, a well-defined benzenedithiolate-bridged complex without any functional groups, 5, was employed for comparison. Electrochemical investigations using five different acids showed that the first reduction potential of the complexes shifted positively in acidic media. This potential shift is attributed to a PCET (Proton-Coupled Electron Transfer) reaction and depends on the acid strength. When an acid is too weak (pKa ≥ 24 in this case), no potential shift is observed. Moreover, increasing the acid strength does not lead always to a linear trend in the potential shift for all of the complexes due to kinetic resistance during proton transfer for some of the complexes. The presence of a pendant basic group (2) can ease such kinetic resistance, and the linear trend holds valid up to pKa 1.8, whereas for the rest of the complexes (3-5), which do not bear an internal basic group, the correlation between the potential shift and the acid strength levels off after a certain pKa value (12). Alternatively, when the acid is strong enough to provide sufficient proton, further increases in the acid strength do not improve the potential shift and the kinetic resistance for a proton to cross the solvated layer becomes dominant.
