title: Photo-induced DNA cleavage activity and remarkable photocytotoxicity of lanthanide(III) complexes of a polypyridyl ligand.
abstract: Lanthanide(III) complexes [Ln(pyphen)(acac)(2)(NO(3))] (1, 2), [Ln(pydppz)(acac)(2)(NO(3))] (3, 4) and [La(pydppz)(anacac)(2)(NO(3))] (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 GdO(6)N(3) 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 × 10(4)-1.2 × 10(6) 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 ((1)O(2)) and hydroxyl radical (HO˙) species. Complexes 3-5 also exhibit significant photocytotoxic effect in HeLa cancer cells giving respective IC(50) 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 IC(50) 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.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, 560 012, India.
authors.forename: Akhtar
authors.initials: A
authors.lastname: Hussain
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Gadadhar
authors.forename: Tridib K
authors.initials: TK
authors.lastname: Goswami
authors.forename: Anjali A
authors.initials: AA
authors.lastname: Karande
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D053837:DNA Cleavage / Q000528:radiation effects*; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D028581:Lanthanoid Series Elements / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008027:Light; D015394:Molecular Structure; D010777:Photochemistry / Q000379:methods*
chemical_list: D028581:Lanthanoid Series Elements; D008024:Ligands; D004247:DNA