MD Simulations to Calculate NMR Relaxation Parameters of Vanadium(IV) Complexes: A Promising Diagnostic Tool for Cancer and Alzheimer's Disease.

Early phase diagnosis of human diseases has still been a challenge in the medicinal field, and one of the efficient non-invasive techniques that is vastly used for this purpose is magnetic resonance imaging (MRI). MRI is able to detect a wide range of diseases and conditions, including nervous system disorders and cancer, and uses the principles of NMR relaxation to generate detailed internal images of the body. For such investigation, different metal complexes have been studied as potential MRI contrast agents. With this in mind, this work aims to investigate two systems containing the vanadium complexes [VO(metf)2 ]·H2 O (VC1) and [VO(bpy)2 Cl]+ (VC2), being metformin and bipyridine ligands of the respective complexes, with the biological targets AMPK and ULK1. These biomolecules are involved in the progression of Alzheimer's disease and triple-negative breast cancer, respectively, and may act as promising spectroscopic probes for detection of these diseases. To initially evaluate the behavior of the studied ligands within the aforementioned protein active sites and aqueous environment, four classical molecular dynamics (MD) simulations including VC1 + H2 O (1), VC2 + H2 O (2), VC1 + AMPK + H2 O (3), and VC2 + ULK1 + H2 O (4) were performed. From this, it was obtained that for both systems containing VCs and water only, the theoretical calculations implied a higher efficiency when compared with DOTAREM , a famous commercially available contrast agent for MRI. This result is maintained when evaluating the system containing VC1 + AMPK + H2 O. Nevertheless, for the system VC2 + ULK1 + H2 O, there was observed a decrease in the vanadium complex efficiency due to the presence of a relevant steric hindrance. Despite that, due to the nature of the interaction between VC2 and ULK1, and the nature of its ligands, the study gives an insight that some modifications on VC2 structure might improve its efficiency as an MRI probe.