Computed electrostatic potentials and average local ionization energies on the molecular surfaces of some tetracyclines

Abstract

ABSTRACT:The electrostatic potentials and average local ionization energies computed on the molecular surfaces of four tetracyclines have been investigated with the objective of identifying common features as well as subtle differences that may be related to their biological activities. The four are the parent molecule tetracycline, chlortetracycline, oxytetracycline, and doxycyline. The calculations were carried out at the HF/STO-3G * //STO-3G * level. Our electrostatic potential results show that each molecule has a large negative region that extends along its lower portion, consistent with its ability to complex Ca 2+ and Mg 2+ ions. Although the surface electrostatic potentials of the four tetracyclines show many similarities, our statistical measure of local polarity allows us to label doxycycline as the one with the lowest degree of local polarity, consistent with its longer half-life in vivo. The regions in the tetracyclines with the most reactive electrons are the amide nitrogen lone pairs and certain carbons of the outermost rings.

Combined experimental and computational modeling studies on 4‐[(2‐hydroxy‐3‐methylbenzylidene) amino]‐1,5‐dimethyl‐2‐phenyl‐1,2‐dihydro‐3H‐pyrazol‐3‐one

“…The MEP is best suited for identifying sites for intra-and intermolecular interactions [77]. When an intramolecular interaction takes place, the electrostatic potential of the negative atom becomes less negative and the positive region on the other atom becomes less positive [77,78]. For the MEP surface in the studied molecule, the weak negative region associated with N1 atom and also the weak positive region by the nearby H1 atom are indicative of an intramolecular (N1ÁÁÁH1AO1) hydrogen bonding [78].…”

Molecular surface electrostatic potentials in relation to noncovalent interactions in biological systems

“…Detailed discussions are presented in the respective papers [59,60]. What we wish to emphasize here is the marked similarity of the internal charge separations, as measured by , within each series of molecules: it is between 10.00 and 12.78 for most of the anticonvulsants, and between 12.38 and 13.94 for the tetracyclines.…”

“…(8) were 19 anticonvulsants [59] and 4 tetracyclines [60]. The anticonvulsants are of various chemical types, which act upon different convulsive disorders [61 -63]; most can be viewed as derivatives of five-, six-, and seven-membered heterocyclic rings, generally having ureide and/or amide linkages.…”

A theoretical approach to the nucleophilic behavior of benzofused thieno[3,2-b]furans using DFT and HF based reactivity descriptors

“…Murray and Politzer et al [41][42][43][44] have discussed the properties of the local ionization energy in detail. It is clear that it describes the donor properties of the molecule directly.…”