Preliminary anti-cancer photodynamic therapeutic in vitro studies with mixed-metal binuclear ruthenium(ii)-vanadium(iv) complexes

Alvin A. Holder, Patrick Taylor, Anthony R. Magnusen, Erick T. Moffett, Kyle Meyer, Yiling Hong, Stuart E. Ramsdale, Michelle Gordon, Javelyn Stubbs, Luke A. Seymour, Dhiraj Acharya, Ralph T. Weber, Paul F. Smith, G. Charles Dismukes, Ping Ji, Laura Menocal, Fengwei Bai, Jennie L. Williams, Donald M. Cropek, William L. Jarrett

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Abstract

We report the synthesis and characterisation of mixed-metal binuclear ruthenium(ii)-vanadium(iv) complexes, which were used as potential photodynamic therapeutic agents for melanoma cell growth inhibition. The novel complexes, [Ru(pbt)2(phen2DTT)](PF6)2·1. 5H2O 1 (where phen2DTT = 1,4-bis(1,10-phenanthrolin-5- ylsulfanyl)butane-2,3-diol and pbt = 2-(2′-pyridyl)benzothiazole) and [Ru(pbt)2(tpphz)](PF6)2·3H2O 2 (where tpphz = tetrapyrido[3,2-a:2′,3′-c:3′′, 2′′-h:2′′′,3′′′-j]phenazine) were synthesised and characterised. Compound 1 was reacted with [VO(sal-l-tryp)(H2O)] (where sal-l-tryp = N-salicylidene-l- tryptophanate) to produce [Ru(pbt)2(phen2DTT)VO(sal-l- tryp)](PF6)2·5H2O 4; while [VO(sal-l-tryp)(H2O)] was reacted with compound 2 to produce [Ru(pbt)2(tpphz)VO(sal-l-tryp)](PF6)2· 6H2O 3. All complexes were characterised by elemental analysis, HRMS, ESI MS, UV-visible absorption, ESR spectroscopy, and cyclic voltammetry, where appropriate. In vitro cell toxicity studies (with the 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay) via dark and light reaction conditions were carried out with sodium diaqua-4,4′, 4′′,4′′′ tetrasulfophthalocyaninecobaltate(ii) (Na4[Co(tspc)(H2O)2]), [VO(sal-l-tryp)(phen)] ·H2O, and the chloride salts of complexes 3 and 4. Such studies involved A431, human epidermoid carcinoma cells; human amelanotic malignant melanoma cells; and HFF, non-cancerous human skin fibroblast cells. Both chloride salts of complexes 3 and 4 were found to be more toxic to melanoma cells than to non-cancerous fibroblast cells, and preferentially led to apoptosis of the melanoma cells over non-cancerous skin cells. The anti-cancer property of the chloride salts of complexes 3 and 4 was further enhanced when treated cells were exposed to light, while no such effect was observed on non-cancerous skin fibroblast cells. ESR and 51V NMR spectroscopic studies were also used to assess the stability of the chloride salts of complexes 3 and 4 in aqueous media at pH 7.19. This research illustrates the potential for using mixed-metal binuclear ruthenium(ii)-vanadium(iv) complexes to fight skin cancer.

Original languageEnglish
Pages (from-to)11881-11899
Number of pages19
JournalDalton Transactions
Volume42
Issue number33
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Inorganic Chemistry

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    Holder, A. A., Taylor, P., Magnusen, A. R., Moffett, E. T., Meyer, K., Hong, Y., Ramsdale, S. E., Gordon, M., Stubbs, J., Seymour, L. A., Acharya, D., Weber, R. T., Smith, P. F., Dismukes, G. C., Ji, P., Menocal, L., Bai, F., Williams, J. L., Cropek, D. M., & Jarrett, W. L. (2013). Preliminary anti-cancer photodynamic therapeutic in vitro studies with mixed-metal binuclear ruthenium(ii)-vanadium(iv) complexes. Dalton Transactions, 42(33), 11881-11899. https://doi.org/10.1039/c3dt50547b