As the knowledge of the predominant molecular structure of antioxidant and anticancer flavonoid rutin in solution is very important for understanding the mechanism of action, a quantum chemical investigation of plausible rutin structures including solvent effects is of relevance. In this work, DFT calculations were performed to find possible minimum energy structures for the rutin molecule. 1H NMR chemical shift DFT calculations were carried out in DMSO solution using the polarizable continuum model (PCM) to simulate the solvent effect. Analysis of the experimental and theoretical 1H NMR chemical shift profiles offers a powerful fingerprint criterion to determine the predominant molecular structure in solution. Therefore, our aim is to find the best match between experimental (in DMSO-d) and theoretical (PCM-DMSO) 1H NMR spectrum profiles. Among 34 optimized structures located on the potential energy surface, we found that structure 32, with a B-ring deviated 30° from a planar configuration (geometry usually assumed for polyphenols), showed an almost perfect agreement with experimental the 1H NMR pattern when compared to the corresponding fully optimized planar geometry. This structure is also predicted as the global minimum based on room-temperature Gibbs free energy calculations in solution and, therefore, should be experimentally observed. This is new and valuable structural information regarding structure-activity relationship studies, and such information is hard to obtain by experimentalists without the aid of the X-ray diffraction technique.

https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/open.201800209

Structural Determination of Antioxidant and Anticancer Flavonoid Rutin in Solution through DFT Calculations of 1H NMR Chemical Shifts.

Introduction: 8-hydroxyquinoline derivatives and their complexes with transition metals are the subject of many studies due to their anticancer, anti-inflammatory, anti-infective, and antidiabetic activities.Areas covered: Within this article, the authors review the synthesis and current applications of metal-8-hydroxyquinoline complexes in drug design with a critical overview of the latest advancements in the field.Expert opinion: Metal-8-hydroxyquinoline complexes are especially interesting because of their simple synthesis procedures and possible applications in modern medicine. The complexation between transition metal ions and 8-hydroxyquinoline or its derivatives is achieved via their O and N atoms. The main problem with their application is lipophilicity. This particular property has an impact on their solubility, biological activity, transport through the cell membrane, construction of the complex with a receptor, and development of drugs. Furthermore, in the treatment of neurodegenerative diseases and brain cancers, the passage of the complexes through the blood-brain barrier can only be ensured through novel drug design.

Drug design strategies with metal-hydroxyquinoline complexes.

The onset of Alzheimer's disease (AD) is caused by amyloid-β (Aβ) aggregation. Elevated levels of metals, specifically copper, zinc, iron, and aluminum, accumulate in senile Aβ; plaque deposits, disrupting normal brain homeostasis and cognitive functions. In this investigation, we studied the potential of several molecular and graphene oxide chelators to be used for future AD research and chelation therapy. To understand the interactions between selected metals (Cu, Zn, Fe, and Al), the Aβ peptide, and various potential metal chelating compounds, we implemented the density functional theory (DFT) method to calculate the binding energies of each metal–molecule complex. The binding energy of each metal–chelator complex was compared with that of the metal–Aβ compound to determine the chelation potential of the selected chelator. The potential chelating agents studied were 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INNHQ), 8-hydroxyquinoline-2-carboxaldehyde 2-furoyl hydrazone (HQFUH), quercetin, and graphene oxide (GO). Our calculated binding energies revealed that the HQFUH molecule holds direct ability to chelate copper, zinc, iron, and aluminum. In addition, the GO complex with a 12.5% oxygen concentration demonstrates aluminum chelation ability. Our results demonstrate that HQFUH and GO can be used in future AD drug development research and therapy to target toxic metal–Aβ interactions and reduce Aβ aggregation.

Potential molecular and graphene oxide chelators to dissolve amyloid-β plaques in Alzheimer's disease: a density functional theory study.

Electronic investigation of the effect of substituents on the SOD mimic activity of copper (II) complexes with 8-hydroxyquinoline-derived ligands.

The Zn(II) complex, dichloro[N-hydroxy-1,1-di(2-pyridinyl)methanimine]zinc(II), was synthesized from the reaction between ZnCl2 and di-2-pyridylketone oxime. The structural and spectral characterizations were performed by using single crystal X-ray diffraction, FT-IR, Laser-Raman, NMR and UV–Vis spectroscopic techniques. To support experimental evidences, computational results were obtained with the DFT/B3LYP method using the 6-311++G(d,p)+LanL2DZ mixed basis set. Theoretical analyses of some structural and spectroscopic results of effects of intermolecular Cl···H interactions in the crystal packing of the Zn(II) complex were investigated with the mentioned computational level. The non-bonding interactions in the experimental crystal packing of the complex were examined by Hirshfeld surface analysis. The HOMO and LUMO analyses were used for investigation of electronic transitions obtained with UV–Vis spectroscopy. NBO analyses were used to investigate the hyperconjugation interactions between dono...

Jader B. Calixto

Papers

Synthesis and structural characterization of a 8-hydroxyquinoline derivative coordinated to Zn(II)