Photo-induced DNA cleavage activity and remarkable photocytotoxicity of lanthanide(iii) complexes of a polypyridyl ligand

Abstract

Lanthanide(III) complexes [Ln(pyphen)(acac)₂(NO₃)] (1, 2), [Ln(pydppz)(acac)₂(NO₃)] (3, 4) and [La(pydppz)(anacac)₂(NO₃)] (5), where Ln is La(III) (in 1, 3, 5) and Gd(III) (in 2, 4), pyphen is 6-(2-pyridyl)-1,10-phenanthroline, pydppz is 6-(2-pyridyl)-dipyrido[3,2-a:2′,3′-c]phenazine, anacac is anthracenylacetylacetonate and acac is acetylacetonate, were prepared, characterized and their DNA photocleavage activity and photocytotoxicity studied. The crystal structure of complex 2 displays a GdO₆N₃ coordination. The pydppz complexes 3–5 show an electronic spectral band at ∼390 nm in DMF. The La(III) complexes are diamagnetic, while the Gd(III) complexes are paramagnetic with seven unpaired electrons. The molar conductivity data suggest 1 : 1 electrolytic nature of the complexes in aqueous DMF. They are avid binders to calf thymus DNA giving K_b in the range of 5.4 × 10⁴–1.2 × 10⁶ M⁻¹. Complexes 3–5 efficiently cleave supercoiled DNA to its nicked circular form in UV-A light of 365 nm via formation of singlet oxygen (¹O₂) and hydroxyl radical (HO˙) species. Complexes 3–5 also exhibit significant photocytotoxic effect in HeLa cancer cells giving respective IC₅₀ value of 0.16(±0.01), 0.15(±0.01) and 0.26±(0.02) μM in UV-A light of 365 nm, while they are less toxic in dark with an IC₅₀ value of >3 μM. The presence of an additional pyridyl group makes the pydppz complexes more photocytotoxic than their dppz analogues. FACS analysis of the HeLa cells treated with complex 4 shows apoptosis as the major pathway of cell death. Nuclear localization of complex 5 having an anthracenyl moiety as a fluorophore is evidenced from the confocal microscopic studies.