ABSTRACT
The solvation parameters model was used to develop a series of statistically significant linear free-energy relationship [LFER] associating lipophilicity [expressed as the logarithm of partition coefficients in n-octanol/water system, log P oct] of 25 diverse alkanolamines with their five structural descriptors constituting the general solvation parameters model proposed by Abraham [1989], as V x, the McGowan [1987] characteristic volume R 2, the excess of molar refraction [PI] H, the dipolarity/polarizability, sigma alpha H, the hydrogen-bond acidity, and sigma beta H, the effective hydrogen-bond basicity. A modified set of the fragmental constants for estimation of PI H, sigma alpha H, and sigma beta H, descriptors of individual alkanolamines has been proposed and applied to calculations of LFER by the multivariate regression procedure. Similary, LFER were established for the experimental values of logarithms of reciprocal of the minimal bactericidal concentration [log[1/MBC]] in a series of lysosomotropic alkabikanubes as reported by Sandin et al. [1992]. The calculated LFER model demonstrates that molecular size [V x term] and effective hydrogen-bond acidity [sigma alpha H term] are the most important structural parameters favouring the transport of uncharged forms of alkanolamines through the bacterial cytoplasmic membrane and their accumulation in bacterial cells. The LFER approach was also applied to experimental data relating 14 alkanolamines as the inhibitors of choline uptake into murine L1210 leukemia cells reported by Naujokaitis et al. [1984]. In this case the established LFER shows that the crucial factors which determine the inhibition of choline transport by alkanolamines are specific dispersion interactions [R 2 term], molecular size [V x term] and effective hydrogen-bond basicity [sigma beta H term] that decreases observed inhibition. The results of the studies presented indicate LFER as a suitable method for the pre-selection of the alkanolamines with defined molecular characteristics for the in vivo chemotherapy of lymphocytic leukemia