The relationship between 19F chemical shifts and calculated electron densities in perfluorinated annulenes

Ab initio calculations for a series of perfluorinated annulenes suggest that there is a linear correlation between the total charge density at fluorine and the fluorine chemical shift. The STO-3G basis set overestimates the degree of pi-electron donation by fluorine.     

NMR studies in the heterocyclic series. XVIII—Carbon-13 NMR study of azolium salts. Attempted correlation of chemical shifts with calculated charge densities

The carbon-13 chemical shifts and the ¹J(CH) coupling constants for 18 azolium salts (di-N-methyl-pyrazolium, -indazolium, -benzimidazolium and -benzotriazolium iodides) have been determined and assigned. The chemical shifts are discussed as a function of substituent effects, positive charge introduction and total electronic density (calculated by the CNDO/2 method). The general problem of correlations between chemical shifts and total charge densities in azoles is discussed. A statistical approach shows that these correlations are of poor quality.     

Local protein backbone folds determined by calculated NMR chemical shifts

NMR chemical shifts (CSs: δN(NH), δC(α), δC(β), δC', δH(NH), and δH(α)) were computed for the amino acid backbone conformers (α(L), β(L), γ(L), δ(L), ε(L), α(D), γ(D), δ(D), and ε(D) [Perczel et al., J Am Chem Soc 1991, 113, 6256]) modeled by oligoalanine structures. Topological differences of the extended fold were investigated on single β-strands, hairpins with type I and II β-turns, as well as double- and triple-stranded β-sheet models. The so-called "capping effect" was analyzed: residues at the termini of a homoconformer sequence unit usually have different CSs than the central residues of an adequately long homoconformer model. In heteroconformer sequences capping effect ruins the direct applicability of several chemical shift types (δH(NH), δC', and δN(NH)) for backbone structure determination of the parent residue. Experimental δH(α), δC(α), and δC(β) values retrieved from protein database are in good agreement with the relevant computed data in the case of the common backbone conformers (α(L), β(L), γ(L), and ε(L)), even though neighboring residue effects were not accounted for. Experimental and computed ΔδH(α)-ΔδC(α), ΔδH(α)-ΔδC(β), and ΔδC(α)-ΔδC(β) maps give qualitatively the same picture, that is, the positions of the backbone conformers relative to each other are very similar. This indicates that the H(α), C(α), and C(β) chemical shifts of alanine depend considerably on the backbone fold of the parent residue also in proteins. We provide tabulated CSs of the chiral amino acids that may predict the various structures of the residues.     

51V NMR chemical shifts calculated from QM/MM models of vanadium chloroperoxidase

(51)V NMR chemical shifts calculated from QM/MM-optimized (QM=quantum mechanical; MM=molecular mechanical) models of vanadium-dependent chloroperoxidase (VCPO) are presented. An extensive number of protonation states for the vanadium cofactor (active site of the protein) and a number of probable positional isomers for each of the protonation states are considered. The size of the QM region is increased incrementally to observe the convergence behavior of the (51)V NMR chemical shifts. A total of 40 models are assessed by comparison to experimental solid-state (51)V NMR results recently reported in the literature. Isotropic chemical shifts are found to be a poor indicator of the protonation state; however, anisotropic chemical shifts and the nuclear quadrupole tensors appear to be sensitive to changes in the proton environment of the vanadium nuclei. This detailed investigation of the (51)V NMR chemical shifts computed from QM/MM models provides further evidence that the ground state is either a triply protonated (one axial water and one equatorial hydroxyl group) or a doubly protonated vanadate moiety in VCPO. Particular attention is given to the electrostatic and geometric effects of the protein environment. This is the first study to compute anisotropic NMR chemical shifts from QM/MM models of an active metalloprotein for direct comparison with solid-state MAS NMR data. This theoretical approach enhances the potential use of experimental solid-state NMR spectroscopy for the structural determination of metalloproteins.     

Additivity model study of EHT electron densities in some fluoro- and aza-substituted naphthalenes

It has been shown that a simple additivity model can be used quite successfully to predict EHT electron densities in a series of fluoro- and aza-substituted naphthalenes. The predicted electrondensities have been used to obtain good estimates of ¹H NMR chemical shifts in a series of aza-naphthalenes.     

Estimating electron spectrial densities for NMR relaxation calculations

Electron spectral densities J_S+S?(ω) have an incorrect temperature dependence when estimated by Fourier transforming an assumed relationship

, where the electron Zeeman energy is

is a transverse decay rate. Improved answers follow from the fluctuation-dissipation theorem.     

The relationship between 19F substituent chemical shifts and electron densities: meta- and para-substituted benzoyl fluorides

The ¹⁹F substituent chemical shifts (SCS) of meta- and para-benzoyl fluorides are found to correlate well with substituent parameters using the dual substituent parameter (DSP) equation, indicating that they reflect electronic perturbations induced by the substituent. The direction of the SCS values is such that donating substituents cause upfield shifts whilst acceptors cause downfield shifts. STO-3G calculations indicate that substituents induce only very small changes in π-electron density about the fluorine atom, but that these changes correlate reasonably well with the observed SCS values. For the para series, the slope of the relationship between δq and ¹⁹F SCS is 5000 ppm/electron, indicating the great sensitivity of the flourine atom to small changes in electron density.     

Regression formulas for density functional theory calculated 1H and 13C NMR chemical shifts in toluene-d8

This study aimed at investigating the performance of a series of basis sets, density functional theory (DFT) functionals, and the IEF-PCM solvation model in the accurate calculation of (1)H and (13)C NMR chemical shifts in toluene-d(8). We demonstrated that, on a test set of 37 organic species with various functional moieties, linear scaling significantly improved the calculated shifts and was necessary to obtain more accurate results. Inclusion of a solvation model produced larger deviations from the experimental data as compared to the gas-phase calculations. Moreover, we did not find any evidence that very large basis sets were necessary to reproduce the experimental NMR data. Ultimately, we recommend the use of the BMK functional. For the (1)H shifts the use of the 6-311G(d) basis set gave linearly scaled mean unsigned (MU) and root-mean-square (rms) errors of 0.15 ppm and 0.21 ppm, respectively. For the calculation of the (13)C chemical shifts the 6-31G(d) basis set produced MUE of 1.82 ppm and RMSE of 3.29 ppm.     

Oxygen-17 NMR chemical shifts of esters

The ¹⁷O NMR spectra of some esters are discussed and are correlated with ¹³C NMR chemical shift and IR carbonyl streching band data.     

Ab initio calculations of NMR chemical shifts

The nuclear magnetic resonance chemical shift is one of the most powerful properties available for structure determination at the molecular level. A review of advances made in the ab initio calculation of chemical shielding during the past five years is presented. Specifically, progress in the areas including the effects of an unpaired electron, electron correlation, and relativistic effects into ab initio chemical shielding calculations, the tensor nature of the chemical shift, and intramolecular and intermolecular effects on the chemical shift will be covered.     

Scaling factors for carbon NMR chemical shifts obtained from DFT B3LYP calculations

A linear scaling of the calculated chemical shifts is used in order to improve the accuracy of the DFT predicted ¹³C NMR chemical shifts. The widely applied method of GIAO B3LYP/6-311+G(2d,p) using the B3LYP/6-31G(d) optimized geometries is chosen, which allows cost-effective calculations of the ¹³C chemical shifts in the molecular systems with 100 and more atoms. A set of 27 ¹³C NMR chemical shifts determined experimentally for 22 simple molecules with various functional groups is used in order to determine scaling factors for reproducing experimentally measured values of ¹³C chemical shifts. The results show that the use of a simple relationship (δ_scalc = 0.95 δ_calc + 0.30, where δ_calc and δ_scalc are the calculated and the linearly scaled values of the ¹³C chemical shifts, respectively) allows to achieve a three-fold improvement in mean absolute deviations for 27 chemical shifts considered. To test the universal applicability of the scaling factors derived, we have used complex organic molecules such as taxol and a steroid to demonstrate the significantly improved accuracy of the DFT predicted chemical shifts. This approach also outperforms the recently recommended usage of the Hartree-Fock optimized geometries for the GIAO B3LYP/6-311+G(2d,p) calculations of the ¹³C chemical shifts.     

Carbon-13 NMR chemical shifts in some substituted 1,2,4-triazol-3-ones

Carbon-13 NMR data for 15 substituted 1,2,4-triazol-3-ones are presented and discussed with regard to enolization in the neutral molecules. The coupling constant and chemical shift data show that the proton at N-2 is not exchanging rapidly in the DMSO-d₆ solvent. Using D₂O? OD^? as a solvent, it is found that the C-3 and C-5 resonances are shifted downfield by nearly the same amount, suggesting that the proton at N-4 is being removed. Enolization in the neutral molecules does not occur to any significant extent.     

On the relativistic theory of NMR chemical shifts

A relativistic analogue to Ramsey's theory of NMR chemical shifts is formulated. Four-component spinor one-electron wavefunctions and relativistic magnetic hamiltonians are used. In contrast to the third-order Pauli approximation theory of Nakagawa et al., the main relativistic effects are then included in the usual second-order theory.     

Density-functional computation of 53Cr NMR chemical shifts

53Cr chemical shifts of CrO4(2-), Cr2O7(2-), CrO3X-, CrO2X2(X = F, Cl), and Cr(CO)5L (L = CO, PF3, CHNH2, CMeNMe2) are computed, using geometries optimized with the gradient-corrected BP86 density functional, at the gauge-including atomic orbitals (GIAO)-, BPW91-, and B3LYP levels. For this set of compounds, substituent effects on delta(53Cr) are better described with the pure BPW91 functional than with B3LYP, in contrast to most other transition-metal chemical shifts studied so far. For selected cases, 53Cr NMR line widths can be rationalized in terms of electric field gradients (EFGs) computed with the BPW91 functional, but in general other factors such as molecular correlation times appear to be dominating. 53Cr chemical shifts and EFGs are predicted for CrO3, Cr(C6H6)2, Cr(C6H6)CO3, and, with reduced reliability, for Cr2(mu2-O2CH)4.     

Spatial localization of ligand binding sites from electron current density surfaces calculated from NMR chemical shift perturbations

Rapid, accurate structure determination of protein-ligand complexes is an essential component in structure-based drug design. We have developed a method that uses NMR protein chemical shift perturbations to spatially localize a ligand when it is complexed with a protein. Chemical shift perturbations on the protein arise primarily from the close proximity of electron current density from the ligand. In our approach the location of the center of the electron current density for a ligand aromatic ring was approximated by a point-dipole, and dot densities were used to represent ligand positions that are allowed by the experimental data. The dot density is increased in the region of space that is consistent for the most data. A surface can be formed in regions of the highest dot density that correlates to the center of the ligand aromatic ring. These surfaces allow for the rapid evaluation of ligand binding, which is demonstrated on a model system and on real data from HCV NS3 protease and HCV NS3 helicase, where the location of ligand binding can be compared to that obtained from difference electron density from X-ray crystallography.     

Utility of calculated 13C NMR chemical shifts in differentiating conformational isomers: a study of metal-complexed and uncomplexed bispidines

Calculated 13C NMR chemical shifts were key to assigning the structures of the conformational forms of complexed and uncomplexed bispidine derivatives.     

15N NMR chemical shifts for the identification of dipyrrolic structures

A variety of dipyrromethanes and dipyrromethenes have been prepared, and their 15N NMR chemical shifts have been measured by two-dimensional correlation to 1H NMR signals. The nitrogen atoms in five examples of dipyrromethanes consistently exhibit chemical shifts around -231 ppm, relative to nitromethane. Seven examples of hydrobromide salts of meso-unsubstituted dipyrromethenes consistently display 15N chemical shifts around -210 ppm, while their corresponding zinc(II) complexes exhibit chemical shifts around -170 ppm. The presence of electron-withdrawing substituents on one of the pyrrolic rings of dipyrromethenes affects the chemical shifts of both of the nitrogen nuclei in the molecule. Boron difluoride complexes of meso-unsubstituted dipyrromethenes display 15N chemical shifts around -190 ppm. Two examples of free-base dipyrromethenes bearing substituents at the meso-position exhibit 15N chemical shifts at approximately -156 ppm, and for the zinc complexes of these compounds at -162 ppm. One-bond nitrogen-hydrogen coupling constants, when measurable, were consistently in the range of -96 Hz. Since the measured 15N chemical shifts have such a high regularity correlated to structure, they can be used as diagnostic indications for identifying the structure of dipyrrolic compounds.     

DFT-GIAO calculations of 19F NMR chemical shifts for perfluoro compounds

The (19)F NMR shieldings for 53 kinds of perfluoro compounds were calculated by the B3LYP-GIAO method using the 6-31G(d), 6-31+G(d), 6-31G(d,p), 6-31++G(d,p), 6-311G(d,p), 6-311++G(d,p), 6-311G(2d,2p), 6-311++G(2d,2p), 6-311++G(2df,2p), 6-311++G(3d,2p), and 6-311++G(3df,2p) basis sets. The diffuse functions markedly reduce the difference between the calculated and experimental chemical shifts. The calculations using the 6-31++G(d,p) basis set give the chemical shifts within 10 ppm deviations from experimental values except for the fluorine nuclei attached to an oxygen atom, a four- and a six-coordinated sulfur atom, and FC(CF(3))(2) attached to a sulfur atom.