Application of solute descriptors to chemical and biological phenomena

A new general solvation equation developed by Abraham and Whiting has been investigated and its applicability to a number of very important phenomena has been studied. The general solvation equation is: log SP=c + rR2 + spi;H2 + bSigmabeta;H2 + vVx where SP is the measured solutedependent property, the solute descriptors are R2 an excess molar refraction, piH2 the dipolarity/polarisability, EaH2 and EbetaH2 the effective hydrogen-bond acidity and basicity, and VX the characteristic volume of McGowan and the equation constants relate to the properties under investigation. The equation has successfully been applied to chemical phenomena - high performance liquid chromatographic data (SP = K') - octanol-water and alkane-water partitioning (logSP = logP), as well as Seiler's hydrogen bond descriptor (logSP = DeltalogP). The solute factors that influence these processes have been ascertained. The equation has also been applied to biological phenomena; application of the equation to blood-brain equilibrium distribution measurements (SP = BB) for the first time yields the factors controlling the distribution: logBB(all) = -0.038 + 0.198R2 -0.687pi;H2 -0.715Sigmaalpha;H2+ aSigmaalpha;H2 -0.698Sigmabeta;H2+0.995Vx n=57 p=0.9522 sd=0.197 F=99.2 Similarly application to skin (stratum corneum) permeation (SP = kp) and partition data (SP = Km) leads to an understanding of the exact factors that influence these processes. In the former case the derived equation is: logkp = -5.201 - 0782pi;H2 - 0.408Sigmaalpha;H2- 3.393Sigmabeta;H2 + 2.004Vx n=46 p=0.9757 sd=0.266 F=203.2 Many solutedescriptors used in this work have been obtained by a novel techniques, these are illustrated. In addition, the application of the logPplus approach has been described, whereby the well known octanol-water partition coefficient has been combined with solute descriptors to yield a high quality yet simplified correlative tool.