Spectroscopic, kinetic, and mechanistic study of a new mode of coordination of indole derivatives to platinum(II) and palladium(II) ions in complexes

Binding of tryptophan residue to intrinsic metal ions in proteins is unknow n, and very little is known about the coordinating abilities of indole. Ind ole-3-acetamide displaces the solvent ligands from cis-[Pt(en)(sol)(2)](2+) , in which sol is acetone or H2O, in acetone solution and forms the complex cis-[Pt(en)(indole-3-acetamide)](2+) (3) of spiro structure, in which the new bidentate ligand coordinates to the Pt(II) atom via the C(3) atom of th e indolyl group and the amide oxygen atom. This structure is supported by H -1, C-13, N-15, and Pt-195 NMR spectra and by UV, IR, and mass spectra. Mol ecular mechanical simulations by Hyperchem and CHARMM methods give consiste nt structural models; the latter is optimized by density-functional quantum chemical calculations. Dipeptide-like molecules N-(3-indolylacetyl)-L-amin o acid in which amino acid is alanine, leucine, isoleucine, valine, asparti c acid, or phenylalanine also displace the solvent ligands in acetone solut ion and form complexes cis-[Pt(en) N-(3-indolylacetyl)-L-amino acid)](2+) ( 6), which structurally resemble 3 but exist as two diastereomers, detected by H-1 NMR spectroscopy. The bulkier the amino acid moiety, the slower the coordination of these dipeptide-like ligands to the Pt(TI) atom. The indoly l group does not coordinate as a unidentate ligand; a second donor atom is necessary for bidentate coordination of this atom and the indolyl C(3) atom . The solvent-displacement reaction is of first and zeroth orders with resp ect to indole-3-acetamide and cis-[Pt(en)(sol)(2)](2+), respectively. A mec hanism consisting of initial unidentate coordination of the ligand via the amide oxygen atom followed by closing of the spiro ring is supported by H-1 NMR data, the kinetic effects of acid and water, and the activation parame ters for the displacement reaction. In the case of N-(3-indolylacetyl)-L-ph enylalanine, the bulkiest of the entering ligands, the reaction is of first order with respect to both reactants. The bidentate indole-3-acetamide lig and in 3 is readily displaced by (CH3)(2)SO and 2-methylimidazole, but not by CNO-, CH3COO-, and CH3CN. Complexes cis-[Pd(en)(sol)(2)](2+) and cis-[Pd (dtco)(sol)(2)](2+) react with indole-3-acetamide more rapidly than their P t(II) analogues do and yield complexes similar to 3. This study augments ou r recent discovery of selective, hydrolytic cleavage of tryptophan-containi ng peptides by Pd(II) and Pt(II) complexes.