Calculations of ¹³C NMR chemical shifts and F–C coupling constants of ciprofloxacin

Abstract

Ciprofloxacin is a widely used fluoroquinolone antibiotic. In this work, a comprehensive evaluation of MP2 and DFT with different functionals and basis sets was carried out to select the most suitable level of theory for the study of the NMR properties of ciprofloxacin. Their relative predictive capabilities were evaluated comparing the theoretically predicted and experimental spectral data. Our computational results indicated that in contrast to the solid state, the molecule of ciprofloxacin does not exist as a zwitterion in gaseous state. The results of the calculations of the chemical shifts most close to the experimental were obtained with B3LYP/aug‐cc‐pVDZ. The F–C coupling constants were calculated systematically with different DFT methods and several basis sets. In general, the calculations of the coupling constants with the BHandH computational method including the applied in this work 6‐311++G**, EPRII, and EPRIII basis sets showed a good reproducibility of the experimental values of the coupling constants.

Structural parameters of the interaction between ciprofloxacin and human topoisomerase-II β enzyme: toward new 19F NMR Chemical Shift probes

“…The first point to highlight is the high similarity between the experimental value and the theoretical value obtained for CPX in the CPX:explicit water system. The low Δδ value indicates that the method and the level of theory selected are very accurate for this type of calculation [49]. Secondly, it is observed that the value obtained in the calculation using the implicit solvation model, CPX:implicit water, is very far from the experimental value.…”

“…All 19 F NMR shielding constants calculations of this step were performed using GAUSSIAN 09 software package [59] at DFT level with the B3LYP functional and Dunning basis set [60] with diffuse function [61,62] aug-cc-pVDZ, by applying gauge-including atomic orbital (GIAO) method [63]. These levels of theory selected were based on previous parametrization studies performed on NMR calculations [64] for the CPX molecule [49]. Calculations were made for CPX in the selected frames of two MD systems using the ONIOM model [65].…”

“…The main advantages include its high sensitivity, very low background signal, the scarce natural occurrence of fluorinated compounds and the high magnetic moment, the last results in a 19 F NMR sensitivity similar to that of 1 H [94]. The fluorinated compound chosen for this work is a widely marketed and prescribed antibiotic drug in the world [49,95], which means that CPX is safe for in vivo use and that much information related to its pharmacodynamics and pharmacokinetics are already well known [96][97][98]. The repositioning drug strategy, which consists in proposing new uses for existing drugs [99], is a growing field of research, because the implementation of already known compounds for new applications considerably saves a lot of time and resources related to the studies of bioavailability, toxicity and implementation of these compounds [100][101][102].…”

“…Computational methods have been widely employed to predict spectroscopic properties of various compounds for various purposes [48][49][50]. In fact, theoretical methods offer a fast, efficient and practical way to investigate changes in the NMR properties of different compounds, which can be caused by several factors, such as changes in the chemical environment or structure of the molecule, caused by interactions with biological macromolecules [29,51].…”

Structural Parameters of the Interaction between Ciprofloxacin and Human Topoisomerase-II β Enzyme: Toward New 19F NMR Chemical Shift Probes

“…Computational methods have been widely employed to predict the spectroscopic properties of different compounds for various purposes [48][49][50]. Theoretical methods offer a fast, efficient and practical way to investigate changes in the NMR properties of different compounds, which can be caused by several factors, such as changes in the chemical environment or structure of the molecule that can occur due to interactions with biological macromolecules [29,51].…”