Evaluating electronic structure methods for accurate calculation of ¹⁹F chemical shifts in fluorinated amino acids

Abstract

The ability of electronic structure methods (11 density functionals, HF, and MP2 calculations; two basis sets and two solvation models) to accurately calculate the 19F chemical shifts of 31 structures of fluorinated amino acids and analogues with known experimental 19F NMR spectra has been evaluated. For this task, BH and HLYP, ωB97X, and Hartree-Fock with scaling factors (provided within) are most accurate. Additionally, the accuracy of methods to calculate relative changes in fluorine shielding across 23 sets of structural variants, such as zwitterionic amino acids vs. side chains only, was also determined. This latter criterion may be a better indicator of reliable methods for the ultimate goal of assigning and interpreting chemical shifts of fluorinated amino acids in proteins. It was found that MP2 and M062X calculations most accurately assess changes in shielding among analogues. These results serve as a guide for computational developments to calculate 19F chemical shifts in biomolecular environments.

Extended Benchmark Set of Main-Group Nuclear Shielding Constants and NMR Chemical Shifts and Its Use to Evaluate Modern DFT Methods

“…Interestingly, two LHs and the cMN15-L CDFT meta-GGA compete with DSD-PBEP86 for the second place (the DH has, however, the smallest max. AE), and a number of further functionals from rungs 3 and 4 perform reasonably well too (including the BHLYP GH advocated before for 19 F shifts − ). Finally, the small subset of third-period nuclei 31 P and 33 S is intermediate with regard to static correlation.…”

A computational and experimental study of the fragmentation of l-leucine, l-isoleucine and l-allo-isoleucine under collision-induced dissociation tandem mass spectrometry

“…B3PW91 was chosen due to its successful performance in previously published studies, where it out performs B3LYP. [23][24][25] The basis set chosen was 6-311++G (d,p) based on its consistent results obtained within our own research and in a few relevant studies. [26][27][28] All structures were minimised prior to any frequency calculations.…”

Predicting 19F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase–Inhibitor Complex

“…Nonetheless, the calculations differed from the measurements by between one and more than 20 ppm even after improving predictions by linear regression to experimental data. Another study benchmarked different levels of quantum‐chemical methods for fluorinated amino acids in implicit solvent, achieving at best a mean absolute error of 2.68 ppm with respect to the experiment . Despite the impressive progress in the field, this is not sufficient to explain subtle differences in experimental spectra.…”