The logarithm of the partition coefficient (log P) of low-molecular-weight organic compounds is a physicochemical parameter used extensively in structure-biological activity studies to model interactions of the compounds with nonpolar phases in vitro and in vivo. The partition coefficient can be determined between water and a number of nonpolar solvents. The most common nonpolar solvent is 1-octanol, but solvents such as benzene, carbon tetrachloride, and chloroform are frequently used as models for the nonpolar phases. The functional relationship between chemical structure and partitioning is not well-understood. In this paper, partition coefficient data for 50 solutes in six nonpolar solvent systems are analyzed by using principal components analysis. The objective of the work is to explore the relationship between solute structure and partitioning behavior for simple organic compounds. Two structural factors are found to be important, with the isotropic surface area being the most important. The isotropic surface area can be used to estimate log P in some solvents and as an independent variable in quantitative structure-activity relationships (QSAR). This is illustrated by estimating the rate of epidermal diffusion of steroids.

The relationship between chemical structure of a solute and the logarithm of its partition coefficient (log P) between the aqueous and a nonpolar phase is poorly understood. We have recently shown that the variation in log P data for 50 low molecular‐weight organic solutes in 6 aqueous‐non‐polar solvents is a function of two structural features. The main feature accounts for ≈︁60% of the variation in the log P data, and is uniformly weighted in all 6 nonpolar solvent systems. This suggests that it is related to the aqueous solution properties of the solute. The first feature is termed the isotropic surface area, or the surface area associated with the nonpolar portion of the solute when the solute is considered to be a hydrated complex. The hydrated solute complex is termed a supermolecule with waters of hydration occupying hydrogen bonding sites on the functional groups of the solute. Empirical rules for formation of the super molecule are discussed. In this report the analysis is extended to log P data for 72 solutes in the 6 nonpolar solvent systems. The results of the analysis are essentially unchanged for this more extended data set and the second factor is tentatively identified. The second structural feature accounted for ≈︁35% of the variation in the log P data was not equally weighted in all solvents and is difficult to interpret structurally.

A new approach based on computation of the molecular surface interactions (MSI) to estimate several physical properties of pure organic substances is described. MSI are derived from molecular structural data and consist of total molecular surface area, electrostatic molecular surface interactions, and a hydrogen bonding term. This new approach estimates the critical temperature and the molar critical volume of pure organic substances with molecular weights in the range of 40-500 a.u.. In addition, the following properties can be calculated: the critical pressure, the boiling temperature, the molar volume in liquid state at normal pressure and temperature. The method can be used to predict physical properties of compounds having flexible or rigid, symmetric or asymmetric, polar or nonpolar molecular structures, and compounds with or without hydrogen bonding groups.

The effect of polarization functions for ab initio molecular orbital calculations at the 3-21G* level has been studied for disiloxane. Calculated molecular geometry, dipole moment, and the linearization barrier variation were analyzed for different uncontracted polarization functions. It was concluded that variation of the polarization function on oxygen has only a minor influence on the molecular properties of disiloxane, but its presence is required to obtain a bent geometry for the disiloxane bond. The calculated molecular properties of disiloxane are greatly influenced when the polarization function on silicon is varied. Two different values (0.3 and 0.9) for the exponent of the silicon polarization function provide results comparable to the experimental values for disiloxane. The only significant differences between the results obtained from ab initio calculations using the two polarization functions are in net atomic charges. The uncontracted polarization function of silicon with a value of 0.3 for its exponent is transferable to other organosilicon compounds. Calculated molecular geometries of flexible or rigid structures are in very good agreement with the experimental values.

Molecular structures of 26 organosilicon compounds have been optimized using ab initio calculations at the 3-21G* (modified) level. From these optimized structures, the internal coordinates have been deformed and the variation of the total molecular energy has been studied. Parameters for stretching and bending deformations are reported herein. The bending potential for the Si-0-Si bond which has an unusual flexibility is also included. Nonbonding interactions are described in terms of steric and electrostatic potentials. For systems which do not include bond resonance effects, torsional behavior is well described by steric potentials with van der Waals radii 20% larger than the previous values and simple electrostatic potential (monopole-monopole) with net atomic charges obtained from ab initio or Extended Huckel Theory calculations. The nonbonding potentials, as defined in this study, have an advantage in that they allow for the computation of torsional barriers without torsional potentials, in the case of single bonds where no additional electronic effects interfere. As an example, it is shown that no torsional potentials are necessary to estimate the torsional barriers in the case of ethane. The newly defined potentials are used to study the torsional barrier in hexamethyldisiloxane and the conformation of octamethylcyclotetrasiloxane (DJ. The most stable calculated conformation of D4, coincides with the experimentally determined structure. This study shows that the most stable conformation is determined by the steric repulsion of methyl groups.