TiO4N2 complexes formed with 1,10-phenanthroline ligands containing a donor-acceptor hydrogen bond site: Synthesis, cytotoxicity and docking experiments

Abstract

The synthesis of five 1,10-phenanthroline-based ligands (ligands A-E), where a pyridinone group is grafted onto a 1,10-phenanthroline backbone through various linkers is described. From these compounds and ligand F (a 2,2′-bipyridine backbone fused with a NH-CO motif), two monomeric octahedral complexes formulated as [Ti(1)2(A)] and [Ti(1)2(F)] (1 is 6,6′-diphenyl-2,2′-biphenolato) are obtained. The X-ray crystal structures attested the formation of hydrogen bonded supramolecular dimers in the solid state for both complexes. Colorimetric cell viability assays (MTT) performed on human gastric adenocarcinoma cells (AGS) have permitted to determine IC50 around 20 μM for phenanthrolines A-C whereas compound F was non-toxic. Owing their insolubility, the cytotoxic activities of the two Ti-complexes were not measured. Docking experiments conducted with [Ti(1)2(A)] and [Ti(1)2(F)] evidenced major clashes within the MST2 kinase binding pocket while the free ligands have a shape fitting with the size of this enzyme pocket.