Computational studies of 13C NMR chemical shifts of saccharides

Abstract

The ¹³C NMR chemical shifts for α-D-lyxofuranose, α-D-lyxopyranose ¹C₄, α-D-lyxopyranose ⁴C₁, α-D-glucopyranose ⁴C₁, and α-D-glucofuranose have been studied at ab initio and density-functional theory levels using TZVP quality basis set. The methods were tested by calculating the nuclear magnetic shieldings for tetramethylsilane (TMS) at different levels of theory using large basis sets. Test calculations on the monosaccharides showed B3LYP(TZVP) and BP86(TZVP) to be cost-efficient levels of theory for calculation of NMR chemical shifts of carbohydrates. The accuracy of the molecular structures and chemical shifts calculated at the B3LYP(TZVP) level is comparable to those obtained at the MP2(TZVP) level. Solvent effects were considered by surrounding the saccharides by water molecules and also by employing a continuum solvent model. None of the applied methods to consider solvent effects was successful. The B3LYP(TZVP) and MP2(TZVP) ¹³C NMR chemical shift calculations yielded without solvent and rovibrational corrections an average deviation of 5.4 ppm and 5.0 ppm between calculated and measured shifts. A closer agreement between calculated and measured chemical shifts can be obtained by using a reference compound that is structurally reminiscent of saccharides such as neat methanol. An accurate shielding reference for carbohydrates can be constructed by adding an empirical constant shift to the calculated chemical shifts, deduced from comparisons of B3LYP(TZVP) or BP86(TZVP) and measured chemical shifts of monosaccharides. The systematic deviation of about 3 ppm for O¹H chemical shifts can be designed to hydrogen bonding, whereas solvent effects on the ¹H NMR chemical shifts of C¹H were found to be small. At the B3LYP(TZVP) level, the barrier for the torsional motion of the hydroxyl group at C₆ in α-D-glucofuranose was calculated to 7.5 kcal mol⁻¹. The torsional displacement was found to introduce large changes of up to 10 ppm to the ¹³C NMR chemical shifts yielding uncertainties of about ±2 ppm in the chemical shifts.