Oxidative Addition of the Dithiobis(formamidinium) Cation to Platinum(II) Chloro Am(m)ine Compounds:  Studies on Structure, Spectroscopic Properties, Reactivity, and Cytotoxicity of a New Class of Platinum(IV) Complexes ExhibitingS-Thiourea Coordination

Abstract

The oxidative addition of the salt [{SC(NMe(2))(2)}(2)]Cl(2).2H(2)O (1), the disulfide-like dimerized form of 1,1,3,3-tetramethylthiourea (tmtu), to Pt(II) chloro am(m)ine compounds is described. Oxidation of the [PtCl(3)(NH(3))](-) anion with 1 in methanol yields cis-[PtCl(4)(NH(3))L] (2; L = tmtu) as the result of the trans addition of one tmtu and one chloro ligand. The same mode of oxidation is found in reactions of 1 with [PtCl(dien)](+) (dien = diethylenetriamine) and trans-[PtCl(2)(NH(3))(2)]. In these cases, however, the oxidation is followed by (light-independent) cis,trans isomerizations, giving trans,mer-[PtCl(2)(dien)L]Cl(2) (4) and fac-[PtCl(3)(NH(3))(2)L]Cl.0.5MeOH (6), respectively. The single-crystal X-ray structures of 2 and trans,mer-[PtCl(2)(dien)L](BF(4))(2) (4a) have been determined. 2: monoclinic, space group P2(1)/n, a = 6.280(1) Å, b = 13.221(3) Å, c = 16.575(2) Å, beta = 96.45(1) degrees, Z = 4. 4a: monoclinic, space group C2/m, a = 21.093(5) Å, b = 8.9411(9) Å, c = 14.208(2) Å, beta = 124.65(2) degrees, Z = 4. The tmtu ligands are S-bound. In 2 a pronounced trans influence of the S-donor ligand on the Pt-Cl bond (2.370(1) Å) trans to sulfur is observed. The unusual acidity of the Pt(IV) complexes exhibiting tmtu coordination trans to chloride is attributed to hydrolysis of the labilized Pt-Cl(trans) bond, which is supported by ion sensitive electrode measurements. An upfield shift of the (195)Pt resonances is found on changing the ligand combination from NCl(4)S (2) to N(3)Cl(2)S (4). This order correlates with the trans influences of the ligands: tmtu > am(m)ine > chloride. The cytotoxicity of 2 and 6 in L1210 cell lines is reported and discussed in terms of a possible mechanism of action of the compounds invivo. It is suggested that tmtu may act as a lipophilic carrier ligand and therefore enhance the cellular uptake of the new potential Pt(IV) drugs.

Synthetic Methods for the Preparation of Platinum Anticancer Complexes

“…292 Notably, the tetrafluoroborate salt of the dithiobis(formamidinium) cation does not give any oxidation products, thus highlighting the important role of the coordinating chloride counterion in facilitating the oxidative addition. 291,292 Bromine, like chlorine, also oxidizes diamine platinum(II) complexes, generally forming trans dibromido complexes (Scheme 21). 293 The bromine oxidation of several dichlorido platinum(II) complexes, however, failed to give the expected trans dibromido products; instead, a mixture of complexes with different ratios of chloride and bromide ligands was obtained.…”

Synthesis of diorganoplatinum(IV) complexes by the S S bond cleavage with platinum(II) complexes

“…The route to bis(thiolato) complexes is valuable since such platinum(IV) complexes may be important in catalysis [4,5] or medicinal chemistry [6,7]. The bis(-thiolato)Pt(IV) products of the reaction of complex [PtR 2 (NN)] with MeSSMe contained only the thermodynamic isomers in which SMe groups are trans to each other, as was confirmed by DFT calculations.…”

Crystal structure of N,N′-(1,6-hexamethylene)-bis(benzoylthiourea), C22H26N4O2S2

“…Thioureaand its derivatives, especially acylthiourea,are extensivelystudied because of their biologicalactivities such asherbicides, insecticides, plant-growth regulators,antifungaland pharmacodynamics [1][2][3][4]. Some thioureasare organic reaction catalyst in the metal-catalyzed asymmetric reduction of carbonyl compounds and carbonylativecyclization of o -hydroxyarylacetylenes [5,6].…”