Most efforts to enhance selectivity have relied on the technique of affinity modification in which an electrophile is attached to a DNA-binding ligand. Our laboratory has developed a series of quinone methide precursors that are easily attached to DNA binding ligands and triggered for reaction under the alternative control of reduction and near-UV irradiation. In this case, the reactive intermediate exists only proximal to the desired target. Conformation specific oxidation and arylation of nucleic acids by transition metals. Transition metal complexes have recently received great attention in the field of nucleic acids because of their role in carcinogenesis, chemotherapy and structural studies.
Nickel compounds are particularly interesting because of their diverse biological activity.
To date, research has revealed that square planar complexes promote the oxidative degradation of guanine residues in DNA and RNA through a non-diffusible, two electron process. Related complexes react to form a covalent bond between guanine and a macrocyclic ligand under oxidizing conditions. These derivatives have similar specificity for guanines containing highly exposed N7 groups.