Spectroscopic evidence of the interaction of titanium(<scp>iv</scp>) coordination complexes with a phosphate head group in phospholipids

Biological membranes are potentially involved in the transport of metal ions, such as Ti(IV), and, sometimes, their associated ligands. Understanding the interactions of Ti(IV) ions and complexes with biological membranes provides a basis for elucidating the action mechanism of titanium anticancer drugs. Herein, we investigated the interactions of two neutral titanium(IV) complexes, <i>viz.</i> [H₂Ti(Cat)₃] (1) and [H₂Ti(Napht)₃] (2), incorporated into DOPC multi-bilayers using ATR-FTIR spectroscopy. Infrared results showed that complexes 1 and 2, when interacting with DOPC multi-bilayers, highly affected the hydration of the lipid phosphate group and its mobility, revealing that the phosphate group is the main group involved in the interactions of complexes 1 and 2 with DOPC phospholipids. NMR studies involving complex 1 and DOPC dissolved in deuterated DMSO solution were performed, and interactions between the Ti complex and DOPC phosphate group could be evidenced. DFT calculations of model complexes were in good agreement with experimental data, and the stability of three model complexes was estimated. On the basis of the obtained data, it can be suggested that the oxygen atom(s) of the phosphato group of the DOPC ligand acted as donor atoms for Ti.