Partition coefficients and capacity factors of some nucleoside analogues

The AIDS epidemic has brought into focus the development of antiviral agents, of which nucleoside analogues are an important class. The single most important physico-chemical property of a chemotherapeutic agent is its hydrophobicity. This paper reports the hydrophobicity, determined as log partition coefficient (P) by the shake-flask method, of 25 nucleoside analogues. The capacity factors (k') of these analogues were also obtained by reversed-phase liquid chromatography. There is a very strong linear correlation between the log P and the log k' values of all the nucleoside analogues, indicating that hydrophobicity of nucleosides can be determined by liquid chromatography. Examination of the P data indicates that an empirical mathematical relationship exists between the partition coefficient value and the molecular structure of the nucleoside analogues. A table of constants and an equation is proposed to estimate the P of nucleoside analogues.