NMR applied to investigate coordination compounds towards biological challenges

Studies about coordination compounds using Nuclear Magnetic Resonance (NMR) has been gaining importance, due to the possibility of remarkable applications such as the design of more specific contrast agents (CAs), novel antioxidant candidates and for describing binding-target mechanisms towards biological macromolecules, among them DNA and acetylcholinesterase (AChE), allowing the designing of novel drug candidates with more effective diagnostic and treatment of some biological disorders, including cancer and Alzheimer. In this lecture, three cases studies regarding the research of metal complexes by NMR spectroscopy towards biological challenges will be addressed. The first one, concerns the NMR study by Fast Field Cycling (FFC) relaxometer approach of two novel Gd(III)-complexes derivatives functionalized with short (C2 and C4) n-alkyl acid functions, aiming the design of dedicated molecular probes for a precoce cancer diagnosis using Magnetic Resonance Imaging (MRI) tomographs. The second one regards the comprehension at atomic level about the interplay between electronic and steric effects for a novel Mg(II)-complex antioxidant candidate. The results point out that the small size of the Mg(II) ions facilitates the spatial steric repulsion between the ligands, promoting an interconversion between two conformational chemical arrangements (octahedral and tetrahedral) as confirmed by Mass Spectrometry (MS) and Density Functional Theory (DFT) calculations, and firstly proved by High Resolution (HR)-NMR approaches (1H and DOSY). Finally, the third addresses a novel Ru(II)-complex, cis-[Ru(bpy)2(EtPy)2]2+ (RuEtPy), bpy=2,2’-bipyridine and EtPy= 4,2-Ethylamino-pyridine), as a potential AChE inhibitor. HR-NMR and relaxometric outcomes point out that this novel candidate have a comparable interaction in comparison to traditional human (h)-AChE inhibitors, such as tacrine and donepezil. These results point out that the 4,2-Ethylamino-Pyridine group is spatially closer to h-AChE surface chemical arrangement than 2,2’-bipyridine counterpart, exerting an efficient intermolecular interaction, with a low dissociation constant (KD ≈ 55 μM), probing that 4,2-Ethylamino-pyridine motif plays a key role in the inhibitory action, putting light on the chemical reasons for the inhibitory features associated to this drug candidate, meaningfully contributing to the obtention of promising candidates for the Alzheimer disease (AD) treatment.