Biophysical Characterization of Membrane Interactions of 3-Hydroxy-4-Pyridinone Vanadium Complexes: Insights for Antidiabetic Applications

The development of metallopharmaceuticals for diabetes treatment has garnered increasing attention due to its insulin-mimetic properties, particularly in vanadium complexes. In this study, we report the biophysical evaluation of a series of 3-hydroxy-4-pyridinone (3,4-HPO) vanadium complexes, designed to improve lipophilicity and biological cytocompatibility. Dynamic light scattering (DLS) was used to get insight on the size of the liposomes and Differential Scanning Calorimetry (DSC) was employed to investigate the interaction of these complexes with model biological membranes made from dimyristoylphosphatidylcholine (DMPC) unilamellar liposomes. The thermotropic phase behavior of the lipid bilayers was analyzed in the presence of vanadium complexes. The results reveal that the alkyl chain length of the 3,4-HPO ligands modulates membrane interaction of the respective vanadium compounds, with specific complexes inducing significant shifts in the lipid phase transition temperature (Tm), suggesting alterations in membrane fluidity and packing. These findings provide valuable insight into the membrane affinity of vanadium-based drug candidates and support their potential as next-generation antidiabetic agents.