Ruthenium Complexes as Catalysts and Chemotherapeutic Agents

Nowadays, there is a growing interest in the development of new ruthenium compounds for C-H activation reactions, alongside the exploration of their potential chemotherapeutic activity. Thus, several Ru based complexes has been synthesis and characterise. The first class of compounds explored belongs to the mono-cationic carbonyl diphosphine Ru (II) complexes of general formula [Ru(X)(CO)(P^P)(phen)]X, where P^P = dppe; (R)-BINAP; (S)-BINAP; (Rac)-BINAP, and X = OAc, OPiv, Cl, I. The behaviour of these compounds in water media and their interaction with reducing agents (NADH; HCOONa) have been studied by NMR techniques. These complexes have been found to be active in catalytic transfer hydrogenation in water / alcohol media for the reduction of aldehydes derived from degradation of biomass and of metabolites, such as pyruvate. The cytotoxic activity of this class of compounds has been evaluated against U87 glioblastoma cancer cell line via MTT assay (72 h). The reactivity of the carbonyl complexes, [Ru(η1-OAc)(CO)(dppe)(phen)]OAc (5) and [Ru(η1-OAc)(CO)((Rac)-BINAP)(phen)]OAc (11Rac), has been explored using thiols (SH; SAc; PhS; BnS; L-cyst). The resulting thiolates complexes have been found to be unstable in air, leading to the catalytic oxidation of the S containing ligand to the corresponding disulphide. The mechanism of action of this class of compounds as chemotherapeutic agents may be related to the catalytic depletion of redox balancing molecules, such as GSH, leading to oxidative stress. The second class of compounds, which has been synthesised and characterised, belongs to the neutral cyclometalated Ru (II) diphosphine complexes of general formula [Ru(C^N)(OAc)(dppb), with C^N = 2-phenylpyridine, benzo[h]quinoline, 1-phenylpyrazole, and 2-phenyloxazoline. These derivatives have been found active both in Oppenauer-type oxidations of alcohols and in the reduction of carbonyl compounds via TH in iso-propanol. The cytotoxic activity of this class of compounds has been evaluated against glioblastoma cancer cells. The third class of compounds, which has been synthesised and characterised, belongs to the mono-cationic cyclometalated Ru (II) diphosphine complexes of general formula [Ru(C^N)(N^N)(dppb)]X, where C^N = 2-phenylpyridine, benzo[h]quinoline; N^N = phen, dppz; and X = OAc, PF6. Preliminary tests on this class of compounds have been carried against glioblastoma cancer cells to evaluate their cytotoxic activity.