Ternary complexes of cisplatin with amino acids and nucleobases. The crystal structure of cis-[(NH 3) 2Pt(1-MeC- N3)(Gly-N)](NO 3)·2H 2O

Abstract

Ternary complexes of Pt(II) with the amino acids=amacH, glycine=GlyH, L-alanine=AlaH, L-2-aminobutyric acid=2-AbaH, L-valine=ValH and L-norvaline=nValH and the nucleobases, 1-methylcytosine=1-MeC and 9-methylguanine=9-MeG were prepared in aqueous solutions via two synthetic routes: by reacting the binary complexes, either cis-[(NH 3) 2Pt(amac)](NO 3) with 1-MeC or 9-MeG (route 1)), or the cis-[(NH 3) 2Pt(nucleobase)Cl](NO 3) with the amino acids. Complexes of the following formulae were isolated as solid adducts: cis-[(NH 3) 2Pt(1-MeC)(Gly)](NO 3), cis-[(NH 3) 2Pt(1-MeC)(Ala)](NO 3), cis-[(NH 3) 2Pt(1-MeC)(2-Aba)](NO 3), cis-[(NH 3) 2Pt(1-MeC)(Val)](NO 3), cis-[(NH 3) 2Pt(1-MeC)(nVal)](NO 3) (not obtained analytically pure), cis-[(NH 3) 2Pt(9-MeG)(Gly)](NO 3), cis-[(NH 3) 2Pt(9-MeG)(Ala)](NO 3), cis-[(NH 3) 2Pt(9-MeG)(2-Aba)](NO 3), cis-[(NH 3) 2Pt(9-MeG)(Val)](NO 3) and cis-[(NH 3) 2Pt(9-MeG)(n-Val)](NO 3). These were characterized by elemental analysis, conductivity measurements and IR, Raman and 1H NMR spectra. The results show that the amino acids are monodentate (coordination through NH 2) and their carboxylate groups are deprotonated. The nucleobases coordinate through N(3) (1-MeC) and N(7) (9-MeG). Hindered rotation was also observed in the case of the ternary complexes with 1-MeC, in D 2O solutions persisting up to 90 °C. A cis-trans isomerization was also taking place in solution, increasing with temperature. A hydrophobic ligand-ligand interaction was detected to take place between the amino acid with aliphatic side chains (starting with 2-Aba), and the nucleobase ring systems, by 1H NMR spectroscopy in aqueous solution, increasing with increasing length of the aliphatic side chain. Finally the crystal structure of the complex cis-[(NH 3) 2Pt(1-MeC)(Gly)](NO 3) was solved by X-ray diffraction: space group P 1 (No. 2), triclinic, a=7.495(3), b=16.388(4), c=6.846(3) Å, α=97.58(3), β=104.86, ⪢ γ=102.05(3)°, V=779.5(6) Å 3, Z=2. A weak Pt interaction with the O(2) of 1-MeC was observed as in other similar cases. No hydrophobic ligand-ligand interactions were found, however, in this complex, as expected.