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Empirical methods for computing molecular partition coefficients. I. Upon the need to model the specific hydration of polar groups in fragment‐based approaches
Author(s) -
Richards Nigel G. J.,
Williams Philip B.,
Tute Michael S.
Publication year - 1991
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560400727
Subject(s) - parametrization (atmospheric modeling) , solvation , chemistry , molecule , fragment (logic) , polar , computation , hydrogen bond , computational chemistry , solvent , molecular dynamics , thermodynamics , chemical physics , physics , mathematics , algorithm , organic chemistry , quantum mechanics , radiative transfer
An empirical approach for the computation of log P for flexible molecules has been developed. This approach is based upon the use of fragmental parameters for obtaining the free energy of solvation of a given molecular conformation in both water and octan‐1‐ol. Two parametrization methods have been investigated, and the quality of the fragment parameters obtained assessed by computation of log P values for a number of compounds which can only adopt a single conformation. Comparison of these calculated log P values with experimental measurements revealed that simple empirical models which assume a linear relationship of transfer free energy and fragment solvent accessible area do not adequately represent the interaction of polar fragments with water molecules. In the second parametrization method, therefore, a novel step function was introduced, based upon physical models of the specific hydration of polar fragments able to participate in hydrogen bonding, by water molecules. Fragment parameters derived by the second approach gave excellent agreement between calculated and experimental log P values for rigid molecules containing several classes of functional group.