Using theoretical descriptors in quantitative structure-activity relationships: some toxicological indices

Abstract

The application of computational techniques to medicinal chemistry is growing at a tremendous rate. Quantitative structure-activity relationships (QSAR), which relate biological and toxicological activities to structural features, have been employed widely to correlate structure to activity. A difficulty of this approach has been nonuniformity of parameter sets and the inability to examine contributions across properties and data sets. Linear solvation energy relationships (LSER) developed by Kamlet and Taft circumvent many of the difficulties and successfully utilize a single set of parameters for a wide range of physical, chemical, and biological properties. We have replaced the LSER solvato-chromatic parameters with theoretically determined parameters to permit better a priori prediction of properties. Comparison of the two parameter sets for five biological activities is presented, showing the excellent fit of the theoretically determined parameters.

Probing the Primary Mechanisms Affecting the Environmental Distribution of Estrogen and Androgen Isomers

“…TLSER descriptors have been found to account fairly well for acidity 26 and some toxicological indices. 27 Moreover, it has been found that molecular electrostatic potential (ESP) parameters are good descriptors of octanol/water 28 and noncovalent interactions. 29 In this study, both TLSER descriptors and molecular ESP parameters were computed by the Gaussian 09 program 30 (details in the SI) to probe isomer-specific behaviors of hormone compounds.…”

It Is Important to Compute Intramolecular Hydrogen Bonding in Drug Design?

“…The approaches span from simple indicator methods [287,288] to parametrization approaches using theoretically calculated properties, such as atomic charges [289], molecular electrostatic potential [290], LUMO and HOMO properties [289,291], atom polarizability [292], and superdelocalizability [263,293], to model hydrogen bond strength. However, due to the character of being the property of a group of atoms and the susceptibility to local environments, hydrogen bonds could not be modeled accurately by a general semiempirical or rule-based method because there are many exceptions, such as steric factors, to be accommodated by a finite set of rules.…”

Study of Quantitative Structure–Retention Relationship (QSRR) of Gas Chromatography for Polychlorinated Dibenzothiophenes on Non‐polar Columns

“…In this work, the N PCS includes the number of substituting Cl atoms on the different positions of parent compound and the number of relative position for these Cl atoms. All the symbols used in the paper are defined as follows: the number of the position of Cl substitution is defined as N PCS , the numbers of chlorine atoms at positions 1(9), 2(8), 3 (7), and 4(6) are defined as N 1 (9) , N 2 (8) , N 3 (7) , and N 4(6) , the numbers of occurrences of two Cl atoms in one molecule with relative ortho, meta, and para positions to each other are symbolized as N o , N m , and N p , the total number of substituted Cl atoms is N, respectively.…”