Charge transfer in trans-combretastatins

Abstract The non-toxic trans isomer of combretastatin-A4 can be photoisomerised in physiological conditions to cis -CA4, a potential anticancer drug. Absorption at wavelengths with high tissue penetration can be achieved by functionalization with substituents influencing the degree of charge-transfer (CT) of the S 1 state, in which the isomerisation occurs. We present a TDDFT study of the excited state properties of a series of substituted combretastatins with various degrees of CT character. Increasing the CT character determines a redshift of absorption and an intensity enhancement, but it disfavours the isomerisation. An appropriate choice of substituents is therefore required to achieve optimal isomerisation conditions.