Understanding the ancillary ligand effect on luminescent cyclometalated Ir(III) complex as a reporter for 2-acetylaminofluorene DNA(AAF-dG) adduct.

Mutagenic agents such as aromatic amines undergo metabolic activation and produce DNA adducts at C8 position of guanine bases. N-2-acetylaminofluorene (AAF) generates different mutational outcomes when placed at G1, G2, and G3 of a NarI sequence (-G1G2CG3CC/T-). These outcomes are dictated by the conformations adopted by these adducts. Detection of such lesions is of considerable interest owing to their hazardous effects. Here, we report the synthesis of three cyclometalated [Ir(L)2dppz]+ complexes (L = 2-phenylpyridine (ppy) 1; benzo[h]quinoline (bhq) 2; 2-phenylquinoline (pq) 3; dppz = dipyrido[3,2-a:2',3'-c]phenazine) and their interaction with AAF adducted NarI DNA. Remarkably, complexes 1 and 2 displayed dominant 3LC transition characteristic of polar environment despite binding to the adducted sites. On the other hand, complex 3 binds to NarI sequences and behaves as a luminescent reporter for AAF-modified DNA. The results reported here emphasize that molecular light switching phenomenon can be stimulated by switching ancillary ligands and might act as potential probes for covalent-DNA defects.

Structural insights into the recognition of DNA defects by small molecules.

Studies on the binding interaction of small molecules and nucleic acids have been explored for their biological applications. With excellent photophysical/chemical properties, numerous metal complexes have been studied as structural probes for nucleic acids. The recognition of DNA defects is of high importance due to their association with various types of cancers. Small molecules that target DNA defects in a specific and selective manner offer a new avenue for developing novel drugs and diagnostic tools. Transition metal complexes have been studied as probes for abasic sites and DNA/RNA mismatches. By changing the ligand structure or metal center, the probing efficiency of the metal complexes varies towards the defects. In this perspective, we have discussed mainly the structural requirement of metal complexes as probes for abasic sites, mismatches, and covalent DNA adducts, followed by the challenges and future directions.