Red-light photosensitized cleavage of DNA by (l-lysine)(phenanthroline base)copper(ii) complexes

Abstract

Ternary copper(II) complexes [Cu(L-lys)B(ClO₄)](ClO₄) (1–4), where B is a heterocyclic base, viz. 2,2′–bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 3) and dipyrido[3,2-a:2′,3′-c]phenazene (dppz, 4), are prepared and their DNA binding and photo-induced DNA cleavage activity studied (L-lys = L-lysine). Complex 2, structurally characterized by X-ray crystallography, shows a square-pyramidal (4 + 1) coordination geometry in which the N,O-donor L-lysine and N,N-donor heterocyclic base bind at the basal plane and the perchlorate ligand is bonded at the elongated axial site. The crystal structure shows the presence of a pendant cationic amine moiety –(CH₂)₄NH₃⁺ of L-lysine. The one-electron paramagnetic complexes display a d–d band in the range of 598–762 nm in DMF and exhibit cyclic voltammetric response due to Cu(II)/Cu(I) couple in the range of 0.07 to −0.20 V vs. SCE in DMF–Tris-HCl buffer. The complexes having phenanthroline bases display good binding propensity to the calf thymus DNA giving an order: 4 (dppz) > 3 (dpq) > 2 (phen) ≫ 1 (bpy). Control cleavage experiments using pUC19 supercoiled DNA and distamycin suggest major groove binding for the dppz and minor groove binding for the other complexes. Complexes 2–4 show efficient DNA cleavage activity on UV (365 nm) or visible light (694 nm ruby laser) irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. The amino acid L-lysine bound to the metal shows photosensitizing effect at red light, while the heterocyclic bases are primarily DNA groove binders. The dpq and dppz ligands display red light-induced photosensitizing effects in copper-bound form.