Open AccessThe Use of Atomic Charges and Orbital Energies as Hydrogen‐bonding‐donor Parameters for QSAR Studies: Comparison of MNDO, AM1 and PM3 Methods
Author(s) -
GHAFOURIAN TARAVAT,
DEARDEN JOHN C.
Publication year - 2000
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/0022357001774435
Subject(s) - mndo , homo/lumo , mulliken population analysis , chemistry , hydrogen bond , quantitative structure–activity relationship , computational chemistry , molecular orbital , hydrogen atom , molecule , stereochemistry , organic chemistry , density functional theory , alkyl
Hydrogen‐bonding, important in drug‐receptor interactions, also determines the solubility and partitioning of drugs between phases. It is, therefore, important to incorporate the effects of hydrogen‐bonding in studies of quantitative structure‐activity relationships (QSAR). In this study the atomic charge on the most positively charged hydrogen atom in a molecule and the energy of the lowest unoccupied molecular orbital (LUMO) have been used as a measure of hydrogen‐bond‐donor capacity. For several hydrogen‐bonding acids the Mulliken atomic charges and the energy of the LUMO produced by use of three semi‐empirical methods, AM1, PM3 and MNDO, and MNDO electrostatic‐potential‐derived atomic charges, have been compared in correlations with solvatochromic hydrogen‐bonding acidity (σα 2 H ). Atomic charges and LUMO energies, particularly those calculated by use of the AM1 and MNDO methods, were found to correlate well with σα 2 H . They were also found to be good models of hydrogen‐bonding in QSAR correlations.