Towards Accurate Predictions of Proton NMR Spectroscopic Parameters in Molecular Solids

Abstract

The factors contributing to the accuracy of quantum‐chemical calculations for the prediction of proton NMR chemical shifts in molecular solids are systematically investigated. Proton chemical shifts of six solid amino acids with hydrogen atoms in various bonding environments (CH, CH2, CH3, OH, SH and NH3) were determined experimentally using ultra‐fast magic‐angle spinning and proton‐detected 2D NMR experiments. The standard DFT method commonly used for the calculations of NMR parameters of solids is shown to provide chemical shifts that deviate from experiment by up to 1.5 ppm. The effects of the computational level (hybrid DFT functional, coupled‐cluster calculation, inclusion of relativistic spin‐orbit coupling) are thoroughly discussed. The effect of molecular dynamics and nuclear quantum effects are investigated using path‐integral molecular dynamics (PIMD) simulations. It is demonstrated that the accuracy of the calculated proton chemical shifts is significantly better when these effects are included in the calculations.

High Level Electronic Structure Calculation of Molecular Solid-State NMR Shielding Constants

“… b Maximum error and the corresponding hydrogen atom. c GIPAW values from the work of Dračínský et al 18 …”

“… a Experimental values from ref ( 18 ). b Values calculated using the scheme described in Section 2.2 with pcSseg-3 and pcSseg-2 basis sets for QM1 and QM2, respectively.…”

“… 15 , 16 , 5 , 17 Recently, Dračínský et al presented a study on the molecular crystals of six amino acids using MP2 or CCSD corrections on PBE GIPAW results. 18 These corrections were obtained by calculating the isolated single amino acid molecules at a higher level of theory. However, the main improvement of their results was found when they included vibrational effects via the use of path-integral molecular dynamics (PIMD).…”

“…Thus, as a proof of concept and first benchmark, we have decided to study the same amino acid molecular crystals that Dračínský et al have studied and use their experimental results. 18 However, we use nonperiodic methods with embedding as this allows us to apply methods developed for molecular systems. Namely, we use the domain-based local pair natural orbital (DLPNO) approximation as this has been shown to provide high accuracy and allows sufficiently large systems to be treated in the QM region.…”

Analyzing Discrepancies in Chemical-Shift Predictions of Solid Pyridinium Fumarates

“…We have recently investigated the factors contributing to the accuracy of the chemicalshift predictions of hydrogen nuclei in molecular solids and observed that the GGAcalculated proton chemical shifts deviated up to 1.5 ppm from the experiment, with the largest deviation observed for a hydrogen atom attached to sulfur, which has been explained by the neglect of relativistic effects in the calculations [21]. Furthermore, when hydrogen atoms are involved in strong hydrogen bonds, nuclear quantum effects (NQEs), such as proton delocalization and tunneling, may become important for the predictions of nuclear shielding [22][23][24][25].…”