Effect of linker length on DNA-binding affinity, cross-linking efficiency and cytotoxicity of C8-linked pyrrolobenzodiazepine dimers

An efficient synthesis of a homologous series of C8-linked pyrrolobenzodiazepine dimers is reported; compounds with an odd number of methylenes (n= 3 or 5) in the linker show a higher affinity for DNA, enhanced cross-linking efficiency, and are more cytotoxic compared with compounds with either n= 4 or 6.