The 1H and 13C NMR chemical shifts of Strychnos alkaloids revisited at the DFT level

The density functional theory calculation of ¹H and ¹³C NMR chemical shifts in a series of ten 10 classically known Strychnos alkaloids with a strychnine skeleton was performed at the PBE0/pcSseg-2//pcseg-2 level. It was found that calculated ¹H and ¹³C NMR chemical shifts provided a markedly good correlation with experiment characterized by a mean absolute error of 0.08 ppm in the range of 7 ppm for protons and 1.67 ppm in the range of 150 ppm for carbons, so that a mean absolute percentage error was as small as ~1% in both cases.     

Stereochemical dependence of substituent γ-effects in the 19F NMR shielding constants

The substituent α-, β-, and γ-effects of the elements of the second and third periods on ¹⁹F NMR chemical shifts are evaluated including the establishment of stereochemical dependence of γ-effect, the latter particularly important in stereochemical studies of fluorine-containing compounds. Benchmark calculations performed for a series of 32 simple inorganic fluorine-containing molecules demonstrated a markedly good correlation between calculated and experimental fluorine chemical shifts characterized by a mean absolute error of 22.5 ppm in the range of about 900 ppm, which corresponds to a 2.5% error in the percentage terms.     

1H and 13C NMR spectra of Strychnos alkaloids: Selected NMR updates

The PBE0/pcSseg-2//pcseg-2 calculations of ¹H and ¹³C NMR chemical shifts were performed for a classical series of 12 Strychnos alkaloids (except for the earlier studied parent strychnine), namely akuammicine, isostrychnine, rosibiline, tsilanine, spermostrychnine, diaboline, cyclostrychnine, henningsamide, strychnosilidine, strychnobrasiline, holstiine, and icajine. It was found that the calculated ¹H and ¹³C NMR chemical shifts show markedly good correlations with available experimental data, as characterized by a mean absolute error of 0.22 ppm for the range of 8 ppm for protons and 1.97 ppm for the range of 180 ppm for carbons. Complementarily, the present results provide essential NMR update and fill a gap in the NMR data of this distinguished group of vitally important natural products.     

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.     

13C-NMR-Spektren isomerer Diazaphenanthrene

The ¹³C chemical shifts of eleven isomeric diazaphenathrenes (1.5-? 1.10-, 2.7-, 4.5-? 4.7-, and 5.6-DAP) have been determined and iteratively assigned by means of comparison with suitable model compounds. The data obtained (132 points) were used to test the relationship between ¹³C chemical shifts and HMO charge densities. The best correlation with a standard deviation S(E) = 4.8 ppm was found for the chemical shifts, relative to phenanthrene, of tertiary carbons. The different slopes for correlations of tertiary and quarternary carbons (275–300 vs 540–550 ppm/electron) are most probably due to different ΔE values for both types of carbons.     

Versuche zur Berechnung der chemischen Verschiebung von 1H, 13C und 19F Atomen in Aliphaten,Olefinen und Acetylenen

An attempt was made to predict the chemical shifts of ¹H, ¹³C and ¹⁹F atoms based on SCF LCGO MO calculations. The expectation value 〈1/R〉 as a measure for the diamagnetism was calculated exactly, the paramagnetism approximated by 〈1/R³〉 and values of the charge density bond order matrix. The influence of the neighbouring atoms was calculated point by point by the electron-density p(r) estimated by a spherical screening function. The terms permit one to calculate the ¹H and ¹³C chemical shifts in fluoroacetylene, fluoroethylene and fluoroethane by a linear relationship with a standard deviation of 0.39 ppm for ¹H and 1.6 ppm for ¹³C. The ¹⁹F chemical shifts were calculated directly by assuming σ_dia: σ_para = 1:10.     

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.     

On the accuracy of the GIAO‐DFT calculation of 15N NMR chemical shifts of the nitrogen‐containing heterocycles – a gateway to better agreement with experiment at lower computational cost

The main factors affecting the accuracy and computational cost of the gauge‐independent atomic orbital density functional theory (GIAO‐DFT) calculation of ¹⁵N NMR chemical shifts in the representative series of key nitrogen‐containing heterocycles – azoles and azines – have been systematically analyzed. In the calculation of ¹⁵N NMR chemical shifts, the best result has been achieved with the KT3 functional used in combination with Jensen's pcS‐3 basis set (GIAO‐DFT‐KT3/pcS‐3) resulting in the value of mean absolute error as small as 5 ppm for a range exceeding 270 ppm in a benchmark series of 23 compounds with an overall number of 41 different ¹⁵N NMR chemical shifts. Another essential finding is that basically, the application of the locally dense basis set approach is justified in the calculation of ¹⁵N NMR chemical shifts within the 3–4 ppm error that results in a dramatic decrease in computational cost. Based on the present data, we recommend GIAO‐DFT‐KT3/pcS‐3//pc‐2 as one of the most effective locally dense basis set schemes for the calculation of ¹⁵N NMR chemical shifts. Copyright © 2014 John Wiley & Sons, Ltd.     

Molecular conformations at the cellulose–water interface

¹³C-NMR chemical shifts were measured for C-4 and C-6 in a collection of eight crystalline glucoses and glucosides. The influence of the hydroxymethyl conformation was greater at C-4 than at C-6, with mean chemical shifts for gauche–trans molecules displaced 3.1 ppm (C-4) and 2.5 ppm (C-6) relative to gauche–gauche molecules. This information was used to interpret ¹³C-NMR spectra of crystalline celluloses. Chemical shifts for C-4 in the crystallite cores of celluloses I and II differed by just 0.2 ppm, but the corresponding chemical shifts for well-ordered crystallite surfaces differed by 3.0 ppm. The separation between crystallite-surface signals was attributed to different hydroxymethyl conformations at the cellulose–water interface, i.e., gauche–gauche and gauche–trans on crystallites of cellulose I and cellulose II, respectively. A broad C-4 signal in the spectrum of cellulose II indicated gauche–gauche conformations in disordered cellulose. Chemical shifts for C-6 were consistent with these conformations.     

1H NMR spectra. Part 29§: proton chemical shifts and couplings in esters—the conformational analysis of methyl γ‐butyrolactones

The ¹H NMR spectra of 35 cyclic and acyclic esters are analysed to give the ¹H chemical shifts and couplings. The substituent chemical shifts of the ester group were analysed using three‐bond (γ) effects for near protons and the electric field, magnetic anisotropy and steric effect of the ester group for more distant protons. The electric field is calculated from the partial atomic charges on the O?C = O atoms, and the asymmetric magnetic anisotropy of the carbonyl group acts at the midpoint of the C = O bond. The values of the anisotropies Δχ_parl and Δχ_perp were for the aliphatic esters 10.35 and ?18.84 and for the conjugated esters 7.33 and ?15.75 (×10^?6 ų/molecule). The oxygen steric coefficients found were 104.4 (aliphatic C = O), 45.5 (aromatic C = O) and 16.0 (C–O) (×10^?6 Å⁶/molecule). After parameterisation, the overall RMS error for the data set of 280 entries was 0.079 ppm. The strongly coupled ¹H NMR spectra of the 2‐methyl, 3‐methyl and 4‐methyl γ‐butyrolactones were analysed and the methyl conformational equilibrium obtained from the observed couplings. The observed versus calculated density functional theory (DFT) ΔG(ax‐eq) was 1.0 (1.01), 0.34 (0.54) and 0.65 (0.71) kcal/mol res. The shielding effect of a methyl cis to a proton in the five‐membered lactone rings is ?0.40 ±0.05 ppm and deshielding trans effect 0.12 ±0.05 ppm, which is common to both five and six membered rings. The cis/trans isomerism in the vinyl esters methyl acrylate, crotonate and methacrylate and methyl furoate was examined using the ¹H chemical shifts. The calculated shifts of both the cis and trans isomers were in good agreement with the observed shifts. Copyright © 2012 John Wiley & Sons, Ltd.     

Sur le calcul a priori des déplacements chimiques de 1H et de 19F

We propose a new method for calculating ¹H and ¹⁹F chemical shifts in saturated organic compounds. Results show that the shifts are a balance of several contributions and allow an evaluation of these effects: a diamagnetic contribution d(—?) proportional to the net charge ? of the electronic environment of the nucleus considered and paramagnetic contributions p_X of each of substituents, constant attached to the substituent X in any molecule. For both nuclei, d values were deduced from a theoretical calculation of the screen in the free atom. This method, using a restricted number of parameters obtained from experiment, lead to the observed chemical shifts with a mean accuracy of ± 0,32 ppm for ¹H and ± 11 ppm for ¹⁹F. Therefore this method gives a simple quantitative relation between chemical shift and structure from which precise indications about the origin of the contributions from neighbouring electronic surroundings can be obtained.     

Nitrogen-15 magnetic resonance spectroscopy XVI—natural-abundance spectra of aromatic amines

The ¹⁵N chemical shifts of aniline, the toluidines, xylidines, and several halogen and oxygen substituted anilines have been measured at the natural abundance level of ¹⁵N. Substituent parameters obtained by multiple regression analysis show that the methyl group induces comparable upfield shifts at the ortho and para positions (2·37 and 2·55 ppm/methyl, respectively) and a small (0·77 ppm/methyl) upfield shift at the meta position. The chemical shifts correlate reasonably well with ¹⁹F shifts of similarly substituted fluorobenzenes, with C-1 of the anilines themselves and with Hammett sigma values. While the shifts of C-methyl substituted anilines do not correlate with the methyl resonances of corresponding polymethylbenzenes, those of the halo- and alkoxyanilines show a reasonable parallelism with corresponding ¹³C-methyl shifts. The results are interpreted in terms of possible modes of transmission of electron density in an alternating and additive manner through the sigma framework.     

Quantum-chemical calculations of NMR chemical shifts of organic molecules: XV. Relativistic calculations of <Superscript>29</Superscript>Si NMR chemical shifts of silanes

Calculations of ²⁹Si NMR chemical shifts of 68 silanes possessing various substituents, in particular, with heavy halogens attached to silicon atom, were carried out applying an efficient calculation scheme of locally dense basis set in the framework of the electron density functional theory utilizing the Keal–Tozer functional combined with relativistic Dyall basis sets on a four-component relativistic level. The main factors of calculation accuracy of silicon chemical shifts were analyzed including the relativistic effects, environmental impact, and vibrational corrections. The mean absolute calculation error for the studied compounds series accounting for all mentioned factors was 14.0 ppm for the nonrelativistic calculation and 6.7 ppm for the four-component relativistic calculation at the range of silicon chemical shifts variation of ~250 ppm.     

DFT computational schemes for 1H and 13C NMR chemical shifts of natural products,exemplified by strychnine

A number of computational schemes based on different Density Functional Theory (DFT) functionals in combination with a number of basis sets were tested in the calculation of ¹H and ¹³C NMR chemical shifts of strychnine, as a typical representative of the vitally important natural products, and used as a challenging benchmark and a rigorous test for such calculations. It was found that the most accurate computational scheme, as compared with experiment, was PBE0/pcSseg-4//pcseg-3 characterized by a mean absolute error of 0.07 ppm for the range of about 7 ppm for ¹H NMR chemical shifts and that of only 1.13 ppm for ¹³C NMR chemical shifts spread over the range of about 150 ppm. For more practical purposes, including investigation of larger molecules from this series, a much more economical computational scheme, PBE0/pcSseg-2//pcseg-2, characterized by almost the same accuracy and much less computational demand, was recommended.     

Natural abundance 17O NMR spectroscopy of heterocyclic N-oxides and Di N-oxides. Structural effects

The ¹⁷O chemical shift data for a series of azine N-oxides, diazine N-oxides and di-N-oxides at natural abundance are reported. Isomeric methyl substituted quinoline N-oxides exhibited chemical shifts which are interpreted in terms of electronic and compressional effects. The ¹⁷O chemical shift for 8-methylquinoline N-oxide (370 ppm) is deshielded by 25 ppm more than predicted, based upon electronic considerations. The ¹⁷O chemical shift for the N-oxide of 8-hydroxyquinoline (289 ppm) is substantially shielded as a result of intramolecular hydrogen bonding. The relative ¹⁷O chemical shifts for diazine N-oxides of pyrazine, pyridazine and pyrimidine follow predictions based on back donation considerations. Because of solubility limitations, spectra of only two N,N′-dioxides were obtained. The chemical shift of benzopyrazine di N-oxide in acetonitrile was shielded by 18 ppm compared to that of its mono N-oxide.     

Towards the versatile DFT and MP2 computational schemes for 31P NMR chemical shifts taking into account relativistic corrections

The main factors affecting the accuracy and computational cost of the calculation of ³¹P NMR chemical shifts in the representative series of organophosphorous compounds are examined at the density functional theory (DFT) and second‐order Møller–Plesset perturbation theory (MP2) levels. At the DFT level, the best functionals for the calculation of ³¹P NMR chemical shifts are those of Keal and Tozer, KT2 and KT3. Both at the DFT and MP2 levels, the most reliable basis sets are those of Jensen, pcS‐2 or larger, and those of Pople, 6‐311G(d,p) or larger. The reliable basis sets of Dunning's family are those of at least penta‐zeta quality that precludes their practical consideration. An encouraging finding is that basically, the locally dense basis set approach resulting in a dramatic decrease in computational cost is justified in the calculation of ³¹P NMR chemical shifts within the 1–2‐ppm error. Relativistic corrections to ³¹P NMR absolute shielding constants are of major importance reaching about 20–30 ppm (ca 7%) improving (not worsening!) the agreement of calculation with experiment. Further better agreement with the experiment by 1–2 ppm can be obtained by taking into account solvent effects within the integral equation formalism polarizable continuum model solvation scheme. We recommend the GIAO‐DFT‐KT2/pcS‐3//pcS‐2 scheme with relativistic corrections and solvent effects taken into account as the most versatile computational scheme for the calculation of ³¹P NMR chemical shifts characterized by a mean absolute error of ca 9 ppm in the range of 550 ppm. Copyright © 2014 John Wiley & Sons, Ltd.     

Computational NMR of natural products: On the way to super large molecules exemplified with alasmontamine A

¹H and ¹³C nuclear magnetic resonance (NMR) chemical shifts of a tetrakis monoterpene indole alkaloid alasmontamine A with a molecular formula of C₈₄H₉₁N₈O₁₂ have been calculated at the PBE0/pcSseg-2//pcseg-2 level of theory on M06-2X/aug-cc-pVDZ geometry. In the course of the preliminary conformational search, six true minimum energy conformers were identified that can contribute to the actual conformation of this huge alkaloid. Calculated chemical shifts generally demonstrated a good agreement with available experimental data characterized with a corrected mean absolute error of 0.10 ppm for the range of about 7 ppm for protons and 1.1 ppm for the range of about 160 ppm for carbons.     

Are there reliable DFT approaches for 13C NMR chemical shift predictions of fullerene C60 derivatives?

The relationships between experimental and theoretical ¹³C NMR chemical shifts of a pristine fullerene C₆₀, monoadducts from [2 + n] cycloaddition (n = 1–3), and one [2 + 1] bis‐adduct are systematically analyzed for the first time by using diverse quantum‐chemical levels of theory. These levels involved B3LYP, B3PW91, B97‐2, mPW1PW91, PBE1PBE, and X3LYP hybrid functionals combined with 3‐21G, 6‐31G, 6‐31G(d), 6‐31G(d,p), 6‐31G(d,2p), LanL2DZ, and SDDAll basis sets. X3LYP/6‐31G approach is determined to have the lowest deviations from the ¹³C NMR experimental data compared to the other methods for all the fullerene compounds (mean absolute error value is 0.856 ppm and root mean squared error value is 1.197 ppm). The highest deviations are characteristic for α (sp² C2/C5/C8/C10) and β (sp² C6/C7/C11/C12) carbon atoms relative to a functionalization site and for those (sp³ C1/C9) directly attached with a side fragment in the [2 + n] monoadducts (n = 1–3). A probable reason of such deviation is that the approaches do not take into account a contribution of paramagnetic ring currents to ¹³C NMR chemical shifts. The results will be useful in design of novel fullerene derivatives and in performing unambiguous ¹³C NMR chemical shift assignments with modern quantum chemistry calculations.     

Konformationsuntersuchungen mit Hilfe der 13C-NMR-Spektroskopie. III. 13C-NMR-spektroskopische Verschiebungen durch sterisch gehinderte Methylgruppen

The ¹³C NMR chemical shifts of some cyclohexane derivatives containing 1,3-diaxial methyl groups are assigned. The resonance signals of the methyl carbon atoms 1 and 3 in these compounds are shifted on average by 4.5 ppm to lower field (δ-effect). The ring carbon atoms 1 and 3 also show shifts to lower field, averaging 0.7 ppm (γ-effect). In open-chain hydrocarbons, analogous shift effects are observed when the investigated compounds have the geometry of the g^Pg^M conformer of n-pentane.