Solid-State ¹⁷O NMR Investigation of the Carbonyl Oxygen Electric-Field-Gradient Tensor and Chemical Shielding Tensor in Amides

Abstract

We have presented a systematic experimental and theoretical investigation of the carbonyl oxygen electric-field-gradient (EFG) tensor and chemical shielding (CS) tensor in crystalline amides. Three 17 O-labled secondary amides, R 1 C[ 17 O]-NHR 2 , have been synthesized: benzanilide (1), N-methylbenzamide (2), and acetanilide (3). Analysis of 17 O magic-angle spinning (MAS) and stationary NMR spectra yields not only the magnitude but also the orientation of the carbonyl 17 O EFG and CS tensors. For compounds 1-3, the carbonyl 17 O quadrupolar coupling constant (QCC) and the span of the chemical shift tensor are found to be in the range of 8.5-8.97 MHz and 560-630 ppm, respectively. The largest 17 O EFG component lies in the amide plane and is perpendicular to the CdO bond, whereas the smallest component is perpendicular to the N-Cd O plane. For the carbonyl 17 O CS tensor, the principal component with the largest shielding, δ 33 , is perpendicular to the amide plane, and the tensor component corresponding to the least shielding, δ 11 , is in the amide plane approximately 20°off the direction of the CdO bond. Extensive quantum chemical calculations using density functional theory (DFT) have been performed for both isolated and hydrogen-bonded molecules of compounds 1-3. The calculated carbonyl 17 O EFG and CS tensors from the latter molecular models are in reasonably good agreement with the experimental values. In particular, the B3LYP/D95** EFG calculations overestimate the carbonyl 17 O QCC by approximately 0.5 MHz. The B3LYP/D95**/GIAO shielding calculations yield a linear correlation between the calculated and experimental data (slope ) 1.125 and R 2 ) 0.9952). The quantum chemical calculations indicated that the intermolecular CdO‚‚‚H-N hydrogen-bonding interactions play an important role in determining the carbonyl oxygen EFG and CS tensors for an amide functional group.

Peptide 17O Chemical Shielding and Electric Field Gradient Tensors

“…For example, model calculations in a methylacetamide:formamide dimer 8 showed that as r(O‚‚‚N) increases, δ 11 and δ 22 move downfield and δ 33 moves upfield. With r(O‚‚‚N) distances of 2.777 (GGV) and 2.926 Å (AGG), the NMR data, Table 2, is consistent with this trend.…”

“…These tensor orientations are in excellent agreement with orientations reported for non-peptide amides that were arrived at using a combination of powder NMR experiments and DFT calculations. 8 The NMR parameters most sensitive to structure are the CS and QC principal components. Thus, reliable powder sample experiments for obtaining these are inherently more general and less arduous since single crystals and a large number of spectra are not required.…”

“…This is very close to the calculated molecular orientations reported for benzamide, benzanilide, N-methylbenazamide, and acetanilide. 8,10 The central residue tensor span in the more strongly H-bonded GGV (δ span ) 549 ( 8 ppm) is significantly smaller than in AGG (δ span ) 606 ( 8 ppm), indicating the effects of intermolecular interactions, which are modeled by DFT calculations of isolated molecules and trimers. The latter contain direct and indirect H-bonded neighbors in the crystal lattice and predict principal axis orientations within 7°of experiment and CS principal components with an rmsd of 16 ppm.…”

“…Isotropic chemical shifts (δ iso ), quadrupolar coupling constants ( ), and the asymmetry parameters (η) were reported in this study, i.e., a subset of the 11 parameters that describe the full CS and QC tensors. Previously, Wu and co-workers 8 reported complete CS and QC tensors in non-peptide amides. They used DFT calculations to set initial estimates for extracting these parameters from powder data, and ultimately the absolute molecular orientations were inferred from the calculations.…”

Solid‐State 17O NMR Spectroscopy of Large Protein–Ligand Complexes

“…In the spectral simulations, we used the Euler angles a = 08, b = 808, and g = 308 to describe the relative orientation between the quadrupole-coupling tensor and the chemicalshift tensor [18] for all four oxygen sites, on the basis of the computational results reported by Wong et al for oxalatemetal complexes. [19] Quite remarkably, the solid-state 17 [17] which suggests that this protein-ligand complex adopts essentially the same structure in the two phases.…”