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

Hussain, Akhtar and Gadadhar, Sudarshan and Goswami, Tridib K and Karande, Anjali A and Chakravarty, Akhil R (2012) Photo-induced DNA cleavage activity and remarkable photocytotoxicity of lanthanide(III) complexes of a polypyridyl ligand. In: Dalton Transactions (2003), 41 (3). pp. 885-895.

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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 similar to 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 x 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 (O-1(2)) and hydroxyl radical (HO center dot) 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) mu M in UV-A light of 365 nm, while they are less toxic in dark with an IC50 value of >3 mu M. 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.

Item Type: Journal Article
Publication: Dalton Transactions (2003)
Publisher: Royal Society of Chemistry
Additional Information: Copyright of this article belongs to Royal Society of Chemistry.
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited: 27 Feb 2012 12:21
Last Modified: 27 Feb 2012 12:21
URI: http://eprints.iisc.ac.in/id/eprint/43681

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