Ru(II)/diphenylphosphine/pyridine-6-thiolate complexes induce S-180 cell apoptosis through intrinsic mitochondrial pathway involving inhibition of Bcl-2 and p53/Bax activation.

The aim of this work was the synthesis, characterization, and cytotoxicity evaluation of three new Ru(II) complexes with a general formula [Ru(Spy)(bipy)(P-P)]PF6 [Spy = pyridine-6-thiolate; bipy = 2,2'-bipyridine; P-P = 1,2-bis(diphenylphosphine)ethane (1); 1,3-bis(diphenylphosphine) propane (2); and 1,1'-bis(diphenylphosphino)ferrocene] (4). Complex (3) with the 1,4-bis(diphenylphosphine)butane ligand, already known from the literature, was also synthesized, to be better studied here. The cytotoxicities of the complexes toward two kinds of cancerous cells (K562 and S-180 cells) were evaluated and compared to normal cells (L-929 and PBMC) by MTT assay. The complex [Ru(Spy)(bipy)(dppb)]PF6 (3) was selected to study both the cellular and molecular mechanisms underlying its promising anticancer action in S-180 cells. The results obtained from this study indicated that complex (3) induces cell cycle arrest in the G0/G1 phase in S-180 cells associated with a decrease in the number of cells in S phase. After 24 and 48 h of exposure to complex (3), the cell viability decreased when compared to the negative control. Complex (3) does not appear to be involved in the DNA damage, but induced changes in the mitochondrial membrane potential in S-180 cells. Furthermore, there was also an increase in the gene expression of Bax, Caspase 9, and Tp53. According to our results, complex (3) induces cell apoptosis through p53/Bax-dependent intrinsic pathway and suppresses the expression of active antiapoptotic Bcl-2 protein.

A three-dimensional metal-organic polymer: poly[bis(µ2-pyrimidine-2-thiolato-κ4N¹,S:S,N³)lead(II)].

The title compound, [Pb(C4H3N2S)2]n, was prepared by the reaction of [Pb(OAc)2]·3H2O (OAc is acetate) with pyrimidine-2-thione in the presence of triethylamine in methanol. In the crystal structure, the Pb(II) atom has an N4S4 coordination environment with four ligands coordinated by N- and S-donor atoms. This compound shows that the pyrimidine-2-thiolate anion can lead to a three-dimensional network when the coordination number of the metal ion can be higher than 6, as is the case with the Pb(II) ion. This compound presents only covalent bonds, showing that despite the possibility of the hemidirected geometries of Pb(II), the eight-coordinated ion does not allow the formation of an isolated molecular structure with pyrimidine-2-thiolate as the ligand.