KINETICS OF SUBCELLULAR-DISTRIBUTION OF MULTIPLY IONIZABLE COMPOUNDS - A MATHEMATICAL-DESCRIPTION AND ITS USE IN QSAR

An explicit mathematical model describing the distribution and, in som e cases, also biological activity of anthropogenic chemicals capable o f multiple ionization in biological systems during the elimination per iod has been constructed. The biological system is represented by a ca tenary chain of alternating aqueous phases (with proteins and other ma cromolecular and low-molecular-weight cell constituents) and membranes . Pseudo-equilibrium distribution of the compounds before the start of elimination is a key assumption which has led to a substantial simpli fication of the mathematical description. Substitution of the model pa rameters by their appropriate relations to physicochemical properties of the compounds (the reference partition coefficients and dissociatio n constants) converts the model to the quantitative structure-activity relationship. The resulting expression satisfactorily describes the p ublished data on growth inhibitory activity of phenol derivatives, aga inst the ciliate Tetrahymena pyriformis, as a function of their hydrop hobicity and acidity. The model can be used in drug design for descrip tion of the distribution of compounds in biological test systems or in environmental sciences to predict the fate of anthropogenic chemicals in ecological systems.