Solubility properties in biological media 9: Prediction of solubility and partition of organic nonelectrolytes in blood and tissues from solvatochromic parameters

Solubilities in and partition among human blood, brain, lung, kidney, muscle, and fat tissue are well correlated by linear solvation energy relationships of the form: XYZ = XYZ_o + mV_I/100 + sπ* + bßm where XYZ is the logarithm of the solubility property, V_I is the intrinsic (van der Waals') molar volume, π* and β are the solvatochromic parameters that measure solute dipolarity/polarizability and hydrogenbond acceptor basicity, respectively, and the subscript m indicates that for self‐associating compounds, the parameter applies to the non‐self‐associated “monomer” solute. The equation for log K(brain—blood) indicates that increasing molar volume favors, whereas increasing dipolarity and hydrogen‐bond acceptor basicity oppose, solute transfer from blood into brain.