NMR chemical shifts of xenon in mixed aprotic solvents: A probe of liquid structure

The chemical shift of elemental xenon is extremely sensitive to the environment. In aprotic solvents, the presence of xenon has little effect on the solvent structure, and preferential solvation is not observed in any mixed solvent system. Consequently, xenon shifts can reveal the presence of short range order in certain liquids. Chemical shift data are presented for several model systems, including mixtures of different alkanes, alkanes with benzene, alkanes with acetone, and carbon tetrachloride with dimethylformamide (DMF). In certain cases, the xenon shift is strongly non-linear with composition. This effect arises from a specific interaction between the two solvents in the CCl₄-DMF system, while it reflects short range liquid order in the acetone-alkane systems. This effect is also apparent in the deviation of the densities of the acetone-alkane mixtures from ideality.     

Calculating nuclear magnetic resonance chemical shifts in solvated systems

The nuclear magnetic resonance (NMR) chemical shift is extremely sensitive to molecular geometry, hydrogen bonding, solvent, temperature, pH, and concentration. Calculated magnetic shielding constants, converted to chemical shifts, can be valuable aids in NMR peak assignment and can also give detailed information about molecular geometry and intermolecular effects. Calculating chemical shifts in solution is complicated by the need to include solvent effects and conformational averaging. Here, we review the current state of NMR chemical shift calculations in solution, beginning with an introduction to the theory of calculating magnetic shielding in general, then covering methods for inclusion of solvent effects and conformational averaging, and finally discussing examples of applications using calculated chemical shifts to gain detailed structural information.     

13C NMR chemical shifts of some highly-branched acyclic compounds

A study has been made of the ¹³C chemical shifts of a number of acyclic alkanes, alkenes, nitriles and ketones which contain quaternary carbon atoms. Similar data have also been obtained for the series of compounds involved in the synthesis of triisopropylacetic acid. Substituent effects and steric factors in these highly substituted compounds are discussed in relation to the chemical shifts.     

Temperature dependence of the carbon-13 chemical shifts of paraffinic hydrocarbons

A study of several linear and branched alkanes indicates that the temperature dependence of ¹³C chemical shifts is a complex phenomenon in which several non-additive effects may be operative. The chemical shift temperature coefficients dδ/dT do, however, reveal some systematic trends which could be helpful in the assignments of ¹³C resonances. An empirical equation is proposed (akin to that of Grant and Paul for ¹³C chemical shifts) which accurately correlates all the data obtained near ambient temperatures.     

Computational studies of 13C NMR chemical shifts of saccharides

The (13)C NMR chemical shifts for alpha-D-lyxofuranose, alpha-D-lyxopyranose (1)C(4), alpha-D-lyxopyranose (4)C(1), alpha-D-glucopyranose (4)C(1), and alpha-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)(13)C 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 O(1)H chemical shifts can be designed to hydrogen bonding, whereas solvent effects on the (1)H NMR chemical shifts of C(1)H were found to be small. At the B3LYP(TZVP) level, the barrier for the torsional motion of the hydroxyl group at C(6) in alpha-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 (13)C NMR chemical shifts yielding uncertainties of about +/-2 ppm in the chemical shifts.     

Molecular dynamics averaging of Xe chemical shifts in liquids

The Xe nuclear magnetic resonance chemical shift differences that afford the discrimination between various biological environments are of current interest for biosensor applications and medical diagnostic purposes. In many such environments the Xe signal appears close to that in water. We calculate average Xe chemical shifts (relative to the free Xe atom) in solution in eleven liquids: water, isobutane, perfluoro-isobutane, n-butane, n-pentane, neopentane, perfluoroneopentane, n-hexane, n-octane, n-perfluorooctane, and perfluorooctyl bromide. The latter is a liquid used for intravenous Xe delivery. We calculate quantum mechanically the Xe shielding response in Xe-molecule van der Waals complexes, from which calculations we develop Xe (atomic site) interpolating functions that reproduce the ab initio Xe shielding response in the complex. By assuming additivity, these Xe-site shielding functions can be used to calculate the shielding for any configuration of such molecules around Xe. The averaging over configurations is done via molecular dynamics (MD). The simulations were carried out using a MD technique that one of us had developed previously for the simulation of Henry's constants of gases dissolved in liquids. It is based on separating a gaseous compartment in the MD system from the solvent using a semipermeable membrane that is permeable only to the gas molecules. We reproduce the experimental trends in the Xe chemical shifts in n-alkanes with increasing number of carbons and the large chemical shift difference between Xe in water and in perfluorooctyl bromide. We also reproduce the trend for a given solvent of decreasing Xe chemical shift with increasing temperature. We predict chemical shift differences between Xe in alkanes vs their perfluoro counterparts.     

离子性指数、极化效应指数烷烃^13C NMR化学位移的 关系研究

定义了烷烃分子中碳原子的离子性指数(INI)，用离子性指数(INI)、极化效应指数(PEI)及N^i~H(i=αβΥ)结构信息参数研究了烷烃的^13CNMR化学位移模型，结果表明，烷烃^13CNMR化学位移(CS)可用下式来定量描述：CS=194.6156-37.7394(INI)+98.6505(ΣPEI)+27.1630(INI/ΣPEI)-652.9106(ΣPEI/INI)+0.7735N^α~H+2.2468N^β~H-0.1742N^γ~H。用上式估算了304个碳原子的化学位移，平均绝对误差仅为0.77δ，标准差0.9860δ，预测值与实验值非常吻合。     

Temperature effects on 13C n.m.r. chemical shifts of normal alkanes and some line r and branched 1-alkenes

¹³C n.m.r. chemical shifts of a number of 1,1-disubstituted ethylenes are presented. Moreover, effects of changing temperatures on the ¹³C n.m.r. chemical shifts of some of these compounds as well as of three normal alkanes are given. These variations in chemical shifts are attributed to varying amounts of sterically induced shifts in the different conformational equilibria. In addition to the well-known 1,4 interaction between two alkyl groups shielding effects on the carbon atoms of the connecting bonds are also proposed. No definite explanation of this effect is presented at this time. It is further shown that no simple correlations exist between ¹³C n.m.r. chemical shifts and calculated total charge densities at this level. Instead, the experimental results in 1-alkenes are rationalized by assuming a linear dependence of the ¹³C n.m.r. chemical shifts of C-1 and C-2 via rehybridizations on changes in bond angles for small skeletal deformations caused by steric interactions. These changes in geometries, as well as conformational energies in three 1-alkenes, were calculated by means of VFF calculations. Finally. upfield shifts for both C-2 and C-4 are proposed for those conformations of 1-alkenes in which the C-3? C-4 group interacts with the p_z-orbital of C-2.     

Prediction of the 1H and 13C NMR spectra of alpha-D-glucose in water by DFT methods and MD simulations

We have applied computational protocols based on DFT and molecular dynamics simulations to the prediction of the alkyl 1H and 13C chemical shifts of alpha-d-glucose in water. Computed data have been compared with accurate experimental chemical shifts obtained in our laboratory. 13C chemical shifts do not show a marked solvent effect. In contrast, the results for 1H chemical shifts provided by structures optimized in the gas phase are only fair and point out that it is necessary to take into account both the flexibility of the glucose structure and the strong effect exerted by solvent water thereupon. Thus, molecular dynamics simulations were carried out to model both the internal geometry as well as the influence of solvent molecules on the conformational distribution of the solute. Snapshots from the simulation were used as input to DFT NMR calculations with varying degrees of sophistication. The most important factor that affects the accuracy of computed 1H chemical shifts is the solute geometry; the effect of the solvent on the shielding constants can be reasonably accounted for by self-consistent reaction field models without the need of explicitly including solvent molecules in the NMR property calculation.     

1H NMR spectra part 31: 1H chemical shifts of amides in DMSO solvent

The ¹H chemical shifts of 48 amides in DMSO solvent are assigned and presented. The solvent shifts Δδ (DMSO‐CDCl₃) are large (1–2 ppm) for the NH protons but smaller and negative (?0.1 to ?0.2 ppm) for close range protons. A selection of the observed solvent shifts is compared with calculated shifts from the present model and from GIAO calculations. Those for the NH protons agree with both calculations, but other solvent shifts such as Δδ(CHO) are not well reproduced by the GIAO calculations. The ¹H chemical shifts of the amides in DMSO were analysed using a functional approach for near ( ≤ 3 bonds removed) protons and the electric field, magnetic anisotropy and steric effect of the amide group for more distant protons. The chemical shifts of the NH protons of acetanilide and benzamide vary linearly with the π density on the αN and βC atoms, respectively. The C=O anisotropy and steric effect are in general little changed from the values in CDCl₃. The effects of substituents F, Cl, Me on the NH proton shifts are reproduced. The electric field coefficient for the protons in DMSO is 90% of that in CDCl₃. There is no steric effect of the C=O oxygen on the NH proton in an NH…O=C hydrogen bond. The observed deshielding is due to the electric field effect. The calculated chemical shifts agree well with the observed shifts (RMS error of 0.106 ppm for the data set of 257 entries). Copyright © 2014 John Wiley & Sons, Ltd.     

Substituent and solvent effects on the 19F chemical shifts of 3- and 4-XCH2-substituted fluorobenzenes

Substituent effects on the ¹⁹F chemical shifts of a series of 3- and 4-XCH₂-substituted fluorobenzenes have been studied in five different solvents (dimethyl sulphoxide, acetone, chloroform, carbon tetrachloride and benzene). The results show that in both series substituent effects (other than inductive effects) contribute in at least some cases to the overall shifts, but that these showed little solvent dependence. The meta series showed a proportionately greater solvent dependence than the para series, and this is attributed to the greater importance of ‘through solvent’ direct field effects in the former.     

1H chemical shifts in NMR: Part 22-Prediction of the 1H chemical shifts of alcohols, diols and inositols in solution, a conformational and solvation investigation

The (1)H NMR spectra of a number of alcohols, diols and inositols are reported and assigned in CDCl(3), D(2)O and DMSO-d(6) (henceforth DMSO) solutions. These data were used to investigate the effects of the OH group on the (1)H chemical shifts in these molecules and also the effect of changing the solvent. Inspection of the (1)H chemical shifts of those alcohols which were soluble in both CDCl(3) and D(2)O shows that there is no difference in the chemical shifts in the two solvents, provided that the molecules exist in the same conformation in the two solvents. In contrast, DMSO gives rise to significant and specific solvation shifts. The (1)H chemical shifts of these compounds in the three solvents were analysed using the CHARGE model. This model incorporates the electric field, magnetic anisotropy and steric effects of the functional group for long-range protons together with functions for the calculation of the two- and three-bond effects. The long-range effect of the OH group was quantitatively explained without the inclusion of either the C--O bond anisotropy or the C--OH electric field. Differential beta and gamma effects for the 1,2-diol group needed to be included to obtain accurate chemical shift predictions. For DMSO solution the differential solvent shifts were calculated in CHARGE on the basis of a similar model, incorporating two-bond, three-bond and long-range effects. The analyses of the (1)H spectra of the inositols and their derivatives in D(2)O and DMSO solution also gave the ring (1)H,(1)H coupling constants and for DMSO solution the CH--OH couplings and OH chemical shifts. The (1)H,(1)H coupling constants were calculated in the CHARGE program by an extension of the cos(2)phi equation to include the orientation effects of electronegative atoms and the CH--OH couplings by a simple cos(2)phi equation. Comparison of the observed and calculated couplings confirmed the proposed conformations of myo-inositol, chiro-inositol, quebrachitol and allo-inositol. The OH chemical shifts were also calculated in the CHARGE program. Comparison of the observed and calculated OH chemical shifts and CH.OH couplings suggested the existence of intramolecular hydrogen bonding in a myo-inositol derivative.     

MP2 calculation of 77Se NMR chemical shifts taking into account relativistic corrections

The main factors affecting the accuracy and computational cost of the Second‐order Möller‐Plesset perturbation theory (MP2) calculation of ⁷⁷Se NMR chemical shifts (methods and basis sets, relativistic corrections, and solvent effects) are addressed with a special emphasis on relativistic effects. For the latter, paramagnetic contribution (390–466 ppm) dominates over diamagnetic term (192–198 ppm) resulting in a total shielding relativistic correction of about 230–260 ppm (some 15% of the total values of selenium absolute shielding constants). Diamagnetic term is practically constant, while paramagnetic contribution spans over 70–80 ppm. In the ⁷⁷Se NMR chemical shifts scale, relativistic corrections are about 20–30 ppm (some 5% of the total values of selenium chemical shifts). Solvent effects evaluated within the polarizable continuum solvation model are of the same order of magnitude as relativistic corrections (about 5%). For the practical calculations of ⁷⁷Se NMR chemical shifts of the medium‐sized organoselenium compounds, the most efficient computational protocols employing relativistic Dyall's basis sets and taking into account relativistic and solvent corrections are suggested. The best result is characterized by a mean absolute error of 17 ppm for the span of ⁷⁷Se NMR chemical shifts reaching 2500 ppm resulting in a mean absolute percentage error of 0.7%. Copyright © 2015 John Wiley & Sons, Ltd.     

Transmission of the substituent effects in 2-substituted benzimidazoles studied by 1H and 13C nuclear magnetic resonance

The substituent influence on the ¹H and ¹³C NMR chemical shifts in 2-substituted benzimidazoles and their anions and cations has been investigated. The transmission of the electronic effects of substituents from C-2 to C-5 (6) is approximately 20% less effective than that in the opposite direction. The solvent influence on the chemical shifts of protons and transmission effects in the charged forms of 2-substituted benzimidazoles has been studied.     

Solvent effects on 195Pt and 205Tl NMR chemical shifts of the complexes [(NC)5Pt--Tl(CN)n]n- (n=0-3), and [(NC)5Pt--Tl--Pt(CN)5]3- studied by relativistic density functional theory

The 295Pt and 205Tl NMR chemical shifts of the complexes [(NC)5Pt-Tl(CN)n]n- n=0-3, and of the related system [(NC)5Pt--Tl--Pt(CN)5]3- have been computationally investigated. It is demonstrated that based on relativistically optimized geometries, by applying an explicit first solvation shell, an additional implicit solvation model to represent the bulk solvent effects (COSMO model), and a DFT exchange-correlation potential that was specifically designed for the treatment of response properties, that the experimentally observed metal chemical shifts can be calculated with satisfactory accuracy. The metal chemical shifts have been computed by means of a two-component relativistic density functional approach. The effects of electronic spin-orbit coupling were included in all NMR computations. The impact of the choice of the reference, which ideally should not affect the accuracy of the computed chemical shifts, is also demonstrated. Together with recent calculations by us of the Pt and Tl spin-spin coupling constants, all measured metal NMR parameters of these complexes are now computationally determined with sufficient accuracy in order to allow a detailed analysis of the experimental results. In particular, we show that interaction of the complexes with the solvent (water) must be an integral part of such an analysis.     

Solvent effects in NMR spectra induced by benzene in amidoximes—V

Proton chemical shifts as well as solvent shifts induced by benzene in several amidoximes are examined with respect to their configuration and are compared to the solvent shifts induced in benzalanilines. The geometry of the benzene-solute ‘collision-complex’ is also discussed.     

Further conventions for NMR shielding and chemical shifts (IUPAC Recommendations 2008)

IUPAC has published a number of recommendations regarding the reporting of nuclear magnetic resonance (NMR) data, especially chemical shifts. The most recent publication [Pure Appl. Chem. 73, 1795 (2001)] recommended that tetramethylsilane (TMS) serve as a universal reference for reporting the shifts of all nuclides, but it deferred recommendations for several aspects of this subject. This document first examines the extent to which the (1)H shielding in TMS itself is subject to change by variation in temperature, concentration, and solvent. On the basis of recently published results, it has been established that the shielding of TMS in solution [along with that of sodium-3-(trimethylsilyl)propanesulfonate, DSS, often used as a reference for aqueous solutions] varies only slightly with temperature but is subject to solvent perturbations of a few tenths of a part per million (ppm). Recommendations are given for reporting chemical shifts under most routine experimental conditions and for quantifying effects of temperature and solvent variation, including the use of magnetic susceptibility corrections and of magic-angle spinning (MAS). This document provides the first IUPAC recommendations for referencing and reporting chemical shifts in solids, based on high-resolution MAS studies. Procedures are given for relating (13)C NMR chemical shifts in solids to the scales used for high-resolution studies in the liquid phase. The notation and terminology used for describing chemical shift and shielding tensors in solids are reviewed in some detail, and recommendations are given for best practice.     

Résonance magnétique nucléaire de 13C et 17O d'éthers aliphatiques. Effets γ entre les atomes d'oxygène et de carbone

The ¹³C- and ¹⁷O-chemical shifts of 31 aliphatic ethers are measured and discussed. The ¹⁷O-chemical shifts of the ethers ROR′ correlate with chemical shifts for the methylene groups of the corresponding alkanes RCH₂R′. The constant of proportionality can be related to the orbital expansion term 〈r^?3〉_2p. The δ_c for carbon atoms can also be correlated with δ_c for the corresponding alkanes. The origin of the correlation is discussed taking into account the conformational modifications resulting from introduction of an oxygen atom in an alkyl chain.     

Fragment density functional theory calculation of NMR chemical shifts for proteins with implicit solvation

Fragment density functional theory (DFT) calculation of NMR chemical shifts for several proteins (Trp-cage, Pin1 WW domain, the third IgG-binding domain of Protein G (GB3) and human ubiquitin) has been carried out. The present study is based on a recently developed automatic fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach but the solvent effects are included by using the PB (Poisson-Boltzmann) model. Our calculated chemical shifts of (1)H and (13)C for these four proteins are in excellent agreement with experimentally measured values and represent clear improvement over that from the gas phase calculation. However, although the inclusion of the solvent effect also improves the computed chemical shifts of (15)N, the results do not agree with experimental values as well as (1)H and (13)C. Our study also demonstrates that AF-QM/MM calculated results accurately reproduce the separation of α-helical and β-sheet chemical shifts for (13)C(α) atoms in proteins, and using the (1)H chemical shift to discriminate the native structure of proteins from decoys is quite remarkable.     

Prediction of Henry's constants of xenon in cyclo-alkanes from molecular dynamics simulations

Using the molecular dynamics (MD) method, we demonstrate that intermolecular nuclear magnetic resonance (NMR) chemical shifts can be used to evaluate and develop intermolecular potentials for cross-interactions for use in solubility studies. The calculation of chemical shifts in MD is an order of magnitude more efficient than solubilities, which makes it an attractive tool for fine-tuning potential models. We examine the average Xe chemical shifts in cyclo-alkanes over a range of temperatures to develop a suitable potential model for the cross-interactions between Xe and a series of cyclo-alkanes. Our results clearly demonstrate that potential models that show better agreement with experiments for chemical shift, invariably lead to better agreement with experiment for Henry's constant and solubility of gases in solvents.