7-Azaindole-3-carboxylic acid and its Pt(II) and Pd(II) complexes: Crystal structure of the ligand, vibrational spectra, DFT calculations and in vitro antiproliferative activity

Abstract

The crystal and molecular structure of 7-azaindole-3-carboxylic acid (7AI3CAH2) has been determined by a single-crystal X-ray diffraction analysis (space group Pca21, a = 14.247(3), b = 5.1983(10), c = 9.871(2) Å, V = 731.0(2) Å3, Z = 4). The crystal structure consists of chains of the 7AI3CAH2 molecules, arranged into ribbons and connected via intermolecular O–H⋯N and N–H⋯O hydrogen bonds. The IR and Raman spectra of 7AI3CAH2 and its deuterated derivative were recorded in the solid state. The DFT calculations at the B3LYP/6–311++G(d,p) level were performed for four conformers of the 7AI3CAH2 monomer as well as for the dimer and trimer, which included intermolecular H-bonding motifs. The analogous calculations were carried out for the deuterated derivative (7AI3CAD2). The optimized structural parameters and the calculated vibrational spectra of trimer reproduce the experiment very well. In addition, new complexes of 7AI3CAH2 with Pt(II) and Pd(II) were prepared and studied by infrared and Raman spectroscopy. The geometry optimizations and vibrational frequency calculations were conducted for two possible (cis and trans) isomers of [MCl2(7AI3CAH2)2] (where M = Pt(II) or Pd(II)) using the B3LYP method with the 6–311++G(d,p)/LanL2DZ basis sets. The combined experimental and theoretical vibrational spectroscopic studies have shown that in the solid state the platinum(II) complex exists as the cis isomer (cis-[PtCl2(7AI3CAH2)2]), whereas the palladium(II) complex has the trans conformation (trans-[PdCl2(7AI3CAH2)2]). In both isomers, two pyridine nitrogen atoms of the 7AI3CAH2 ligands and two chloride ligands are coordinated to the central Pt(II) or Pd(II) atoms in a square-planar arrangement. The carboxylic and NH groups of 7AI3CAH2 are not bonded by metal ions. Detailed vibrational assignments for 7AI3CAH2 and its Pt(II) and Pd(II) complexes have been made on the basis of the calculated potential energy distributions (PEDs). The in vitro antiproliferative activities of cis-[PtCl2(7AI3CAH2)2] and trans-[PdCl2(7AI3CAH2)2] were studied on two human cancer cell lines (T47D and A549). As follows from the obtained IC50 values, the trans-[PdCl2(7AI3CAH2)2] complex exhibits cytotoxicity against T47D cell line, which is comparable to that of cisplatin.