Multiple Intramolecular Hydrogen Bonding in Large Biomolecules: DFT Calculations and Deuterium Isotope Effects on 13C Chemical Shifts as a Tool in Structural Studies

Abstract

Large biomolecules often have multiple intramolecular hydrogen bonds. In the cases where these interact, it requires special tools to disentangle the patterns. Such a tool could be deuterium isotope effects on chemical shifts. The use of theoretical calculations is an indispensable tool in such studies. The present paper illustrates how DFT calculations of chemical shifts and deuterium isotope effects on chemical shifts in combination with measurements of these effects can establish the complex intramolecular hydrogen bond patterns of rifampicin as an example) The structures were calculated using DFT theoretical calculations, performed with the Gaussian 16 software. The geometries were optimized using the B3LYP functional and the Pople basis set 6-31G(d) and the solvent (DMSO) was taken into account in the PCM approach. Besides the 6-31G(d) basis set, the 6-31 G(d,p) and the 6-3111G(d,p) basis sets were also tested. The nuclear shieldings were calculated using the GIAO approach. Deuteriation was simulated by shortening the X-H bond lengths by 0.01 Å.

The Synergy between Nuclear Magnetic Resonance and Density Functional Theory Calculations

“…Rifamycin is a complex multi-hydrogen-bonded system [ 36 ] (see Figure 15 ). Its geometries were optimized using the B3LYP functional with the Pople basis set 6-31G(d) [ 37 ] and the solvent (DMSO) was taken into account in the PCM approach in the calculations of 13 C chemical shifts.…”