Derivatization of Preformed Platinum N-Heterocyclic Carbene Complexes with Amino Acid and Peptide Ligands and Cytotoxic Activities toward Human Cancer Cells

A simple procedure for the preparation of N-heterocyclic carbene platinum complexes with a nitrogen-based neutral ligand in trans geometry is presented. The lability of a trans pyridine ligand in an N-heterocyclic carbene-Pt(II)-pyridine complex, namely, (3-benzyl-1-methylimidazolylidene)PtI2-pyridine), 2, was probed by a displacement reaction with various nitrogen-based ligands (e.g., amines, hydrazine, amino esters, and peptides) to yield the corresponding complexes, which could be easily isolated by column chromatography. Two representative complexes could be characterized by X-ray crystallographic studies. This strategy allows generating diversity in metallodrug candidates. Preliminary results of the biological effects on various human cancer cells and comparison wih cisplatin are reported.