Preliminary Anti-Cancer Photodynamic Therapeutic In Vitro Studies With Mixed-Metal Binuclear Ruthenium(II)-Vanadium(IV) Complexes

Alvin A. Holder, University of Southern Mississippi
Patrick Taylor, University of Southern Mississippi
Anthony R. Magnusen, University of Southern Mississippi
Erick T. Moffett, University of Southern Mississippi
Kyle Meyer, University of Dayton
Yiling Hong, University of Dayton
Stuart E. Ramsdale, University of Southern Mississippi
Michelle Gordon, University of Southern Mississippi
Javelyn Stubbs, University of Southern Mississippi
Luke A. Seymour, University of Southern Mississippi
Dhiraj Acharya, University of Southern Mississippi
Ralph T. Weber, EPR Division Bruker BioSpin
Paul F. Smith, Rutgers University
G. Charles Dismukes, Rutgers University
Ping Ji, Stony Brook University
Laura Menocal, Stony Brook University
Fengwei Bai, University of Southern Mississippi
Jennie L. Williams, Stony Brook University
Donald M. Cropek, U.S. Army Corps of Engineers
William L. Jarrett, University of Southern Mississippi


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)(phen(2)DTT)](PF6)(2)center dot 1.5H(2)O 1 (where phen(2)DTT = 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)center dot 3H(2)O 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)(phen(2)DTT)VO(sal-L-tryp)](PF6)(2)center dot 5H(2)O 4; while [VO(sal-L-tryp)(H2O)] was reacted with compound 2 to produce [Ru(pbt)(2)(tpphz)VO(sal-L-tryp)](PF6)(2)center dot 6H(2)O 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) (Na-4[Co(tspc)(H2O)(2)]), [VO(sal-L-tryp)(phen)]center dot 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 V-51 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.