Azithromycin (AZM) is a well-known macrolide-type antibiotic that has been used in the treatment of infections and inflammations. Knowledge of the predominant molecular structure in solution is a prerequisite for...

In the present study, we benchmark computational protocols for predicting Co-59 NMR chemical shift. Quantum mechanical calculations based on density functional theory were used, in conjunction with our NMR-DKH basis sets for all atoms, including Co, which were developed in the present study. The best protocol included the geometry optimization at BLYP/def2-SVP/def2-SVP/IEF-PCM(UFF) and shielding constant calculation at GIAO-LC-ωPBE/NMR-DKH/IEF-PCM(UFF). This computational scheme was applied to a set of 34 Co(III) complexes, in which, Co-59 NMR chemical shift ranges from +1162 ppm to +15,100 ppm, and these were obtained in distinct solvents (water and organic solvents). The resulting mean absolute deviation (MAD), mean relative deviation (MRD), and coefficient of determination (R2) were 158 ppm, 3.0%, and 0.9966, respectively, suggesting an excellent alternative for studying Co-59 NMR.

The cobalt-59 nucleus is an NMR active nucleus with the nuclear spin I = 7/2 and has a natural abundance of 100 %. It is an important nucleus because it has ease of detectable NMR signals both liquid and solid-state. The Co-59 NMR chemical shift range is one of the largest known in NMR spectroscopy, spanning some 18,000 ppm or more. However, Co-59 NMR is an extremely sensitive technique to external factors such as pressure, temperature, and others. Therefore, predicting Co-59 NMR chemical shift might be useful to assist experimentalists in the structural characterization. In the present study, we propose a new NMR-DKH basis set for Co atom to predict NMR chemical shift in Co complexes. Besides, we proposed a computational protocol (Functional DFT/Co basis set/Ligands basis set) for the prediction of the structure and, later, for the prediction of the Co-59 NMR chemical shift using 6 Co complexes as model systems. The results show that the computational protocol (NMR/structure) GIAO-B3LYP/NMR-DKH/IEF-PCM(UFF)//CAM-B3LYP/LANL2DZ/jorge-DZP/IEF-PCM(UFF) presents a mean relative deviation (DRM) of 1.48% for the structure, a mean absolute deviation (MAD) of 101 ppm and a DRM of 1.2% for the Co-59 chemical shift. Finally, the protocol was corrected by a linear regression model giving a MAD and MRD of 57 ppm and 0.7%, respectively.