Physico-chemical characterization of cyclic nucleotides by reversed-phase high-performance liquid chromatography: II. Quantitative determination of hydrophobicity

Abstract

Retention data for 42 adenosine 3′,5′-monophosphate derivatives were measured in a reversed-phase high-performance liquid chromatographic (RPLC) system. Using methanol—water and methanol—phosphate buffer as the mobile phase, the relationship between the volume fraction or organic modifier, φ, and the logarithm of the capacity factor, log k′, can be adequately described by a linear regression equation. The resulting log k w values, obtained by extrapolation of retention to φ = 0, are correlated with other physico-chemical solute properties that are commonly used to described quantitatively the hydrophobic nature of solutes. The results indicate that the retention behaviour of complex molecular structures, including ionic, hydrogen bonding and hydrophobic functions, is only moderately described by the standard Hansch π substituent constant, although the underlying distribution mechanism of both RPLC and a true liquid—liquid system is the solvophobic effect. This additionally demonstrated by the strong dependence of log k w on the molecular volume of the substituents. It is concluded that, rather than attempt to establish correlations between RPLC retention data and distribution coefficients, log k w values can be used directly as descriptors of a solute's hydrophobicity and may therefore be used in studies of quantitative structure—activity relationships for cyclic nucleotides.