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Synthesis and characterization of ruthenium maltolato, sulfoxide, and nitroimidazole complexes as potential anticancer agents

University of British Columbia

The anticancer properties of Ru sulfoxide and imidazole complexes, including cis-RuCl₂(DMSO)₃(DMSO), trans-RuCl₂(DMSO)₄, and [trans-Ru(Im)(DMSO)Cl₄]⁻ have previously been studied by other groups (DMSO and DMSO = S-bonded and O-bonded dimethylsulfoxide, respectively; Im = imidazole). This thesis work concerns the use of Ru maltolato complexes in this regard; maltol (3-hydroxy-2-methyl-4-pyranone), being a non-toxic, water-soluble food additive, is suitable for biological use. [diagrams not included] Several Ru[sup II] bis(maltolato) and bis(ethylmaltolato) complexes with ancillary monodentate and bidentate sulfoxide ligands (DMSO, TMSO, and BESE) have been synthesized and well characterized, as well as a Ru[sup II] BESE-metronidazole complex, RuCl₂(BESE)(metro)₂ (TMSO = tetramethylenesulfoxide, BESE = 1,2- bis(ethylsulfinyl)ethane, metro = metronidazole). Some Ru[sup III] maltolato complexes have also been synthesized in order to compare their anticancer activities to those of related Ru[sup II] complexes. The Ru complexes were characterized by a variety of spectroscopic techniques, including NMR, UV-vis, IR, and MS; elemental analysis and solution conductivity data were also collected. Cyclic voltammetry was used to determine the reduction potentials of various Ru complexes. X-ray crystallographic structures were determined for cis-Ru(ma)₂(S,R-BESE), trans-RuCl₂(R,R-BESE)(metro)₂, and trans- [Ru(ma)₂(metro)₂](CF₃S0₃) (ma = maltolato). The sulfoxide ligands are exclusively S-bonded as observed in the IR and ¹H NMR spectra, and in the first two X-ray structures. Of the complexes tested, Ru(ma)₃ and Ru(etma)₃ (etma = ethylmaltolato) exhibit the best anticancer activities against human breast cancer cells (MDA435/LCC6) in the in vitro MTT assay (a colorimetric determination of cancer cell viability), in terms of the lowest IC₅₀ values of 150 and 80 μM, respectively, IC₅₀ being the drug concentration that kills 50 % of the cancer cells relative to the control. The Ru[sup II] maltolato-sulfoxide complexes also showed some anticancer activities, with Ru(etma)₂(DMSO)₂ being the most potent (IC₅₀ = 470 μM). The ethylmaltolato complexes are generally more effective than the corresponding maltolato complexes. Further anticancer testing of Ru maltolato complexes is encouraged from these preliminary results.

Thesis/Dissertation

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2009-10-05

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http://hdl.handle.net/2429/13641

Chemistry

University of British Columbia

UBCV

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