Voltammetric analysis of lipophilicity of benzodiazepine derivatives at the water ∣ 1,2-dichloroethane interface

The transfer of benzodiazepine derivatives (diazepam, bromazepam, alprazolam, oxazepam, nitrazepam, clonazepam, chlordiazepoxide, flunitrazepam, midazolam and lorazepam) across the water ∣ 1,2-dichloroethane interface was studied using cyclic voltammetry. The partition coefficients of ionic species of benzodiazepines, log PXH+, were calculated from the transfer potentials measured at pH<pKa. These values were compared with the partition coefficient of neutral species, log PX. The difference between log PXH+ and log PX was related to the degree of charge delocalization, which depends markedly on the presence of electron acceptor substituents in the molecule. These electron acceptor groups, in turn, affect the biological activity of these drugs. The results indicated that the difference Δlog PXH+=log PXH+−log PX can be used in structure–activity correlations as it takes into account the effects of substituents on the main positions within the molecule.