Effect of electron acceptor groups on partition coefficient of phenothiazine derivatives at the water∣1,2-dichloroethane interface

The transfer of phenothiazine derivatives (promazine, chlorpromazine, triflupromazine, methotrimeprazine, perphenazine and fluphenazine) across the water∣1,2-dichloroethane interface was studied using cyclic voltammetry. The partition coefficients of ionic species of phenothiazines, logPXH+logPXH+, were calculated from the transfer potentials measured at pH < pKa. These values were related with the Hammet parameter of substituents in order to find a dependence with the presence of electron acceptor substituents in the molecule. These electron acceptor groups affect the biological activity of these drugs. The results indicated that logPXH+logPXH+ can be used in structure–activity correlations as it takes into account the effects of substituents on the main positions within the phenothiazine molecule.