Synthesis, Structural Characterization, Solution Chemistry, and Preliminary Biological Studies of the Ruthenium(III) Complexes [TzH][trans-RuCl₄(Tz)₂] and [TzH][trans-RuCl₄(DMSO)(Tz)]·(DMSO), the Thiazole Analogues of Antitumor ICR and NAMI-A

Abstract

Two ruthenium(III) complexes bearing the thiazole ligand, namely, thiazolium (bisthiazole) tetrachlororuthenate (I, TzICR) and thiazolium (thiazole, DMSO) tetrachlororuthenate (II, TzNAMI) were prepared and characterized. The crystal structures of both complexes were solved by X-ray diffraction methods and found to match closely those of the corresponding imidazole complexes. The behavior in aqueous solution of bothTzICR and TzNAMI was analyzed spectroscopically. The time-dependent spectrophotometric profiles resemble closely those of the related ICR and NAMI-A anticancer compounds, respectively. It is observed that replacement of imidazole with thiazole, a less basic ligand, produces a significant decrease of the ligand exchange rates in the case of the NAMI-like compound. The main electrochemical features of these ruthenium(III) thiazole complexes were determined and compared to those of ICR and NAMI-A. Moreover, some preliminary data were obtained on their biological properties. Notably, both complexes exhibit higher reactivity toward serum albumin than toward calf thymus DNA; cytotoxicity is negligible in line with expectations. A more extensive characterization of the pharmacological properties in vivo is presently in progress.

Ruthenium Complexes as Anticancer Agents

“…As in the case of platinum complexes, interaction of Ru complexes with DNA is assumed to be responsible for antitumor activity, although other additional or supplementary mechanisms are possible as well [31][32][33][34][35][36][37][38].…”

Synthesis, structural characteristics, DNA binding properties and cytotoxicity studies of a series of Ru(III) complexes

“…Since the discovery of antitumor and antimetastatic properties of KP1019 and NAMI-A, many complexes with similar structures have been synthesized [10,38,39], but halo-Ru(III) complexes with bidentate ligands screened for antitumor activity are still scarce. Recently, we have reported the differences in biological properties between two Ru(III) complexes, namely mer-[RuCl 3 (CH 3 CN)(dpq)] and mer-[RuCl 3 (dmso)(dpq)] (dpq = dipyrido[3,2-f:2 0 ,3 0 -h]quinoxaline) [40].…”

Trans–cis–cis-[RuCl2(DMSO)2(2-amino-5-methyl-thiazole)2], (PMRu52), a novel ruthenium(II) compound acting as a strong inhibitor of cathepsin B

“…Ru-Cl and Ru-S distances in I are almost identical (see Table 2) to those of the starting material, cis-[Ru(II)Cl 2 (DMSO) 4 ], (III) [10], when taking into account the standard deviations. On the other hand, it is noteworthy that the Ru-N distances in I, with a mean value of 2.175(3)Å, are significantly longer than the corresponding ones in PMRU20 (L = 2-amino-thiazole) [30] and TzICR (L = Thiazole) [31], the mean value of the latter being 2.101(9)Å in both cases; this finding is in agreement with the strong transinfluence of the DMSO ligand. 10 Interestingly, the Ru _ Cl, Ru _ S and Ru _ N distances for (I) are almost equal, when considering the standard deviations, to the respective bond distances reported by Ales- …”