Modification of platinum(II) antitumor complexes with sulfur ligands.: 1.: Synthesis, structure, and spectroscopic properties of cationic complexes of the types [PtCl(diamine)(L)]NO3 and [{PtCl(diamine)}2(L-L)1(NO3)2 (L = Monofunctional thiourea derivative;: L-L = bifunctional thiourea derivative)

A new class of mono-and dinuclear platinum(II) complexes is described that derives from the cisplatin analogues (Pt(en)Cl-2] and [Pt(dach)Cl-2] (en = 1,2-ethanediamine, dach = racemic trans-1,2-cyclohexanediamine). The selective substitution of one chloro ligand in these species by 1,1,3,3-tetramethylthiourea (tmtu), which requires abstraction of chloride with silver salt in DMF, gives [PtCl(en)(tmtu)]NO3 (1) and [PtCl(dach)(tmtu)]NO3 (2). Similarly, reactions employing the novel bifunctional thiourea derivatives C2H4(NMeCSNMe2)(2) (3) and C6H12-(NMeCSNMe2)(2) (4) yield the dinuclear complexes [{Pt(en)Cl}(2)(mu-3-S,S')](NO3)(2) (5) and [{Pt(en)Cl}(2)(mu-4-S,S')]-(NO3)(2) . 0.5EtOH (6), respectively. The compounds were characterized by H-1, C-13, and Pt-195 Nh IR spectroscopy, elemental analyses, and IR data, Pt-195 chemical shifts in the -2895 to -2929 ppm region confirm the mixed-donor [PtN2ClS] coordination for 1, 2, 5, and 6 and thiourea-S coordination in all cases, The single-crystal X-ray structures of 2-4 have been determined. 2: monoclinic, space group P2(1)/n, a = 10.804 Angstrom, b = 16.221 Angstrom, c = 21.789 Angstrom, beta = 102.16(1)degrees, Z = 8. 3: monoclinic, space group P2(1)/n, a = 12.787(2) Angstrom, b = 6.250(1) Angstrom, c = 17.777(3) Angstrom, beta = 98.21(1)degrees, Z = 4. 4: monoclinic, space group P2(1)/n, a = 11.097(3) Angstrom, b = 13.717 Angstrom, c = 11.925 Angstrom, beta = 97.61(2)degrees, Z = 4. The Pt-S distance in 2 (2.285(2) Angstrom, mean) is in accordance with the magnitude of shielding found for the Pt-195 core and suggests weak pi-acceptor properties of tmtu. The bifunctional thiourea derivatives 3 and 4 adopt highly elongated conformations in the solid state where the sulfur atoms and the n-(CH2)(n), (n = 2, 6) linkers are Z-oriented. Force field calculations on 3 and 1 imply that the Z-form should be the prefer-red conformer for the thiourea groups in solution, H-1 NMR spectra indicate a dynamic equilibrium of different rotamers due to low barriers of rotation within the thiourea moieties in free and coordinated 3 and 4. It is suggested that the steric and electronic effects of the peralkylated thiourea derivatives in 1, 2, 5, and 6 may modulate the affinity of the complexes for biomolecules.