Structure-based predictions of H NMR chemical shifts of sesquiterpene lactones using neural networks

In this work the prediction of ¹H NMR chemical shifts of CH_n protons of sesquiterpene lactones by means of neural networks is described. This method is based on the incorporation of experimental chemical shifts of protons of sesquiterpene lactones as additional memory of an associative neural network system previously trained with chemical shifts of other organic compounds. One advantage of this method is its ability to distinguish between CH₂ diastereotopic protons belonging to rigid substructures since stereochemistry is considered. This is achieved via the automatic conversion of the 2D structure diagram into a 3D molecular structure. The predicted ¹H NMR chemical shifts of the sesquiterpene lactones showed a high level of accuracy. This is the first report on a fully automatic proton assignment of structures of sesquiterpene lactones of an accuracy that allows its use in structure elucidation.     

Substituent effects on 33S NMR chemical shifts in sulphones

The ³³S NMR spectra of some selected sulphones demonstrate additive substituent-induced chemical shift (SCS) effects. In dimethyl sulphone (1), replacement of a methyl group by a vinyl or a phenyl group causes an SCS effect of ?7 to ?8.5 ppm or ?4 to ?5 ppm, respectively. The ³³S chemical shift in 1 is also sensitive to substitution of methyl protons. The ß-substituent effect for methyl and phenyl groups is in the range +7 to +8 ppm and +5.5 to +6 ppm, respectively.     

Substituent effects on 15N and 13C NMR chemical shifts of 3-phenylisoxazoles: a theoretical and spectroscopic study

The synthesis and assignment of 15N and 13C NMR signals of the isoxazole ring in a series of para-substituted 3-phenyl derivatives are reported. DFT calculations of 15N and 13C chemical shifts are presented and compared to observed values. Substituent effects are interpreted in terms of the Hammett correlation and calculated bond orders.     

Orientational effect of aryl groups on 77Se NMR chemical shifts: experimental and theoretical investigations

The orientational effect of p-YC6H4 (Ar) on delta(Se) is elucidated for ArSeR, based on experimental and theoretical investigations. The effect is examined in the cases in which Se--CR in ArSeR is either in the Ar plane (pl) or is perpendicular to the plane (pd). 9-(Arylselanyl)anthracenes (1) and 1-(arylselanyl)anthraquionones (2) are employed to establish the effect in pl and pd, respectively. Large upfield shifts are observed for Y=NMe2, OMe, and Me, and large downfield shifts for Y=COOEt, CN, and NO2 in 1, relative to Y=H, as is expected. Large upfield shifts are brought by Y=NMe2, OMe, Me, F, Cl, and Br, and downfield shifts by Y=CN and NO2 in 2, relative to Y=H, with a negligible shift by Y=COOEt. Absolute magnetic shielding tensors of Se (sigma(Se)) are calculated for ArSeR (R=H, Me, and Ph), assuming pl and pd, based on the DFT-GIAO method. Observed characters are well explained by the total sigma(Se). Paramagnetic terms (sigmap(Se)) are governed by (sigmap(Se)xx+sigmap(Se)yy), in which the direction of np(Se) (constructed by 4pz(Se)) is set to the z axis. The main interaction in pl is the np(Se)-pi(C6H4)-pz(Y) type. The Y dependence in pl occurs through admixtures of 4pz(Se) in pi(SeC6H4Y) and pi*(SeC6H4Y), modified by the conjugation, with 4px(Se) and 4py(Se) in sigma(CSeX) and sigma*(CSeX) (X=H or C) under a magnetic field. The main interaction in pd is the sigma(CSeX)-pi(C6H4)-px(Y) type, in which Se-X is nearly on the x axis. The Y dependence in pd mainly arises from admixtures of 4pz(Se) in np(Se) with 4px(Se) and 4py(Se) in modified sigma*(CSeX), since np(Se) is filled with electrons. It is demonstrated that the effect of Y on sigmap(Se) in the pl conformation is the same regardless of whether Y is an electron-donor or electron-acceptor, whereas for pd conformations the effect is greater when Y is an electron donor, as observed in 1 and 2, respectively. Contributions of each molecular orbital and each transition on sigmap(Se) are evaluated, which enables us to recognize and visualize the effect clearly.     

Substituent effects on the P NMR chemical shifts of arylphosphorothionates

Six tris(aryloxy)phosphorothionates substituted in the para position of the aromatic rings were synthesized and studied by ³¹P NMR, X-ray diffraction techniques and ab initio calculations at a RHF/6-31G** level of theory, in order to find the main structural factors associated with the δ³¹P in these compounds. As the electron-withdrawing (EW) ability of the substituents was increased, an ‘abnormal’ shielding effect on δ³¹P of the arylphosphorothionates was observed. The analyses of the geometrical properties obtained through both experimental and theoretical methods showed that a propeller-type conformation is preferred for the arylphosphorothionates, except in the case of the tris(O-4-methylphenyl)phosphorothionate, since one of the aromatic rings is not rotated in the same direction as the other two in the solid state. The main features associated with the δ³¹P NMR of compounds 1-6 were a decrease of the averaged O-P-O angle and mainly the shortening of the PS bond length, which is consistent with an increase of the thiophosphoryl bond order as δ³¹P values go upfield. On the other hand, comparison of the experimental and calculated bond lengths and bond angles involving α bonded atoms to phosphorus of the six compounds suggested that stereoelectronic interactions of the type n_πO-σ*_PS, n_πO-σ*_P-OAr and n_πS-σ*_P-OAr could be present in the arylphosphorothionates 1-6.     

Quantum-chemical calculations of NMR chemical shifts of organic molecules: VIII. Solvation effects on 15N NMR chemical shifts of nitrogen-containing heterocycles

Effect of solvation on the accuracy of DFT quantum-chemical calculations of ¹⁵N NMR chemical shifts of pyrrole, N-methylpyrrole, and pyridine was studied. The use of continuum model is sufficient to obtain consistent theoretical σ_N values for weakly polar aprotic solvents, whereas solvation effects in strongly polar and protic solvents should be taken into account in the explicit form.     

A survey of wave function effects on theoretical calculation of gas phase F NMR chemical shifts using factorial design

The wave functions for calculating gas phase ¹⁹F chemical shifts were optimally selected using the factorial design as a multivariate technique. The effects of electron correlation, triple-ξ valance shell, diffuse function, and polarization function on calculated ¹⁹F chemical shifts were discussed. It is shown that of the four factors, electron correlation and the polarization functions affect the results significantly. B3LYP/6-31 + G(df,p) wave functions have been proposed as the best and the most efficient level of theory for calculating ¹⁹F chemical shifts. An additional series of fluoro compounds were used as a test set and their predicted ¹⁹F chemical shifts values confirmed the validity of the approaches.     

Quantum-chemical calculation of NMR chemical shifts of organic molecules: III. Intramolecular coordination effects on the 31P NMR chemical shifts of phosphorylated N-vinylazoles

Theoretical and experimental studies on magnetic shielding of the phosphorus nucleus in trichloro-[2-(1H-pyrazol-1-yl)ethenyl]phosphonium hexachlorophosphate(V) and 1,1,1,1-tetrachloro-1H-1λ⁶-pyrazolo-[1,2-a][1,2,3]diazaphosphol-8-ium-1-ide showed that intramolecular coordination of the phosphorus atom in the chlorophosphonium group to the nitrogen atom in the pyrazole ring leads to upfield shift of the phosphorus signal (to δ_P 170 ppm) and that the contribution of the spin-orbital contribution to the ³¹P chemical shift reaches 15%. Relativistic effects and effects of the medium are determining in the theoretical calculation of ³¹P NMR chemical shifts.     

Silylanions: inversion barriers and NMR chemical shifts

Alpha-substituent effects on inversion barriers and NMR chemical shifts have been studied on a set of silyl anions, [X(3-n)Y(n)Si](-) (X, Y=H, CH(3), and SiH(3)). The MP2/6-31+G* optimized structures show a pattern of increasing inversion barriers with augmenting numbers of methyl substituents. The highest barrier of 48.5 kcalmol(-1) is obtained for the (CH(3))(3)Si(-) ion. The silyl group displays the opposite effect by decreasing the inversion barrier to a minimum of 16.3 kcalmol(-1) in (SiH(3))(3)Si(-). The influence of counterions on these barriers is probed by addition of a lithium or potassium cation. In most cases, a decrease of the energy barriers with respect to the bare anions is observed. The (29)Si NMR chemical shifts calculated at the IGLO-DFT and GIAO-MP2 level of theory are also analyzed in view of the substituents and counterions.     

Thermal effects and vibrational corrections to transition metal NMR chemical shifts

Both zero-point and classical thermal effects on the chemical shift of transition metals have been calculated at appropriate levels of density functional theory for a number of complexes of titanium, vanadium, manganese and iron. The zero-point effects were computed by applying a perturbational approach, whereas classical thermal effects were probed by Car-Parrinello molecular dynamics simulations. The systematic investigation shows that both procedures lead to a deshielding of the magnetic shielding constants evaluated at the GIAO-B3 LYP level, which in general also leads to a downfield shift in the relative chemical shifts, delta. The effect is small for the titanium and vanadium complexes, where it is typically on the order of a few dozen ppm, and is larger for the manganese and iron complexes, where it can amount to several hundred ppm. Zero-point corrections are usually smaller than the classical thermal effect. The pronounced downfield shift is due to the sensitivity of the shielding of the metal centre with regard to the metal-ligand bond length, which increase upon vibrational averaging. Both applied methods improve the accuracy of the chemical shifts in some cases, but not in general.     

Theoretical studies on NMR chemical shifts in azacubanes

Successive substitution of CH groups of cubane (CH)(8), by isoelectronic nitrogen atoms leads to a class of energy-rich azacubanes (CH)(8-alpha)N(alpha) (with alpha=1-8). In the present work, we systematically investigate how substitution of nitrogen in a cubanoid influence deshielding of carbon and manifest in the chemical shift in NMR spectra calculated using the second order M?ller-Plesset (MP2) perturbation level of theory. PMR spectra predict a large downshift of delta(H)=7.9 ppm in heptaazacubane owing to the more number of nitrogen and the stronger C-H...N interactions. These chemical shifts are explained by the net atomic charges derived from the population analysis based on Hirshfeld partitioning scheme.     

Silicon-29 NMR. Solvent effects on chemical shifts of silanols and silylamines

The ²⁹Si NMR spectra of six silanols and four silylamines were examined in several solvents of varying electron pair donor ability. A linear correlation was found between the silanol silicon-29 chemical shift and solvent donor ability. The silylamines were considerably less sensitive to solvent. The effect is attributed to hydrogen bonding between the hydroxyl proton of the silanol and an electron pair of the solvent.     

An NMR, IR and theoretical investigation of (1)H chemical shifts and hydrogen bonding in phenols

The change in (1)H NMR chemical shifts upon hydrogen bonding was investigated using both experimental and theoretical methods. The (1)H NMR spectra of a number of phenols were recorded in CDCl(3) and DMSO solvents. For phenol, 2- and 4-cyanophenol and 2-nitrophenol the OH chemical shifts were measured as a function of concentration in CDCl(3). The plots were all linear with concentration, the gradients varying from 0.940 (phenol) to 7.85 (4-cyanophenol) ppm/M because of competing inter- and intramolecular hydrogen bonding. Ab initio calculations of a model acetone/phenol system showed that the OH shielding was linear with the H...O=C distance (R) for R < 2.1 A with a shielding coefficient of - 7.8 ppm/A and proportional to cos(2)phi where phi is the H...O=C--C dihedral angle. Other geometrical parameters had little effect. It was also found that the nuclear shielding profile is unrelated to the hydrogen bonding energy profile. The dependence of the OH chemical shift on the pi density on the oxygen atom was determined as ca 40 ppm/pi electron. This factor is similar to that for NH but four times the value for sp(2) hybridized carbon atoms. The introduction of these effects into the CHARGE programme allowed the calculation of the (1)H chemical shifts of the compounds studied. The CHARGE calculations were compared with those from the ACD database and from GIAO calculations. The CHARGE calculations were more accurate than other calculations both when all the shifts were considered and also when the OH shifts were excluded. The calculations from the ACD and GIAO approaches were reasonable when the OH shifts were excluded but not as good when all the shifts were considered. The poor treatment of the OH shifts in the GIAO calculations is very likely due to the lack of explicit solvent effects in these calculations.     

Quantum-chemical calculations of NMR chemical shifts of organic molecules: XIV. Solvation effects in calculations of chemical shifts in 13C NMR spectra of chlorine-containing compounds

Analysis of precision factors in calculations of ¹³C NMR chemical shifts in the series of saturated and unsaturated organochlorine compounds was performed in the framework of the method of electron density functional theory GIAO-DFT-KT3/pcS-2 in the gas phase and with accounting for solvent effect by the polarized continuum model IEF-PCM. The accounting for solvation effects in calculations of ¹³C NMR chemical shifts within the framework of the IEF-PCM model is not fundamental for organochlorine compounds, yet it considerably improves the precision of calculations up to 2.5 ppm.     

Orbital interactions and their effects on 13C NMR chemical shifts for 4,6-disubstituted-2,2-dimethyl-1,3-dioxanes. A theoretical study

A theoretical study is employed to describe the orbital interactions involved in the conformers' stability, the energies for the stereoelectronic interactions, and the corresponding effects of these interactions on the molecular structure (bond lengths) for cis- and trans-4,6-disubstituted-2,2-dimethyl-1,3-dioxanes. For cis-4,6-disubstituted-2,2-dimethyl-1,3-dioxanes, two LPO --> sigma*C(2)-Me(8) interactions are extremely important and the energies involved in these interactions are in the range 6.81-7.58 kcal mol(-1) for the LP(O)(1) --> sigma*C(2)-Me(8) and 7.58-7.71 kcal mol(-1) for the LP(O)(3) --> sigma*C(2)-Me(8) interaction. These two LP(O) --> sigma*C(2)-Me(8) interactions cause an upfield shift, indicating an increased shielding (increased electron density) of the ketal carbon C(2) as well as the axial Me(8) group in the chair conformation. These LP(O) --> sigma*C(2)-Me(8) hyperconjugative anomeric type interactions can explain the 13C NMR chemical shifts at 19 ppm for the axial methyl group "Me(8)" and 98.5 ppm for the ketal carbon "C(2)". The observed results for the trans derivatives showed that for compounds 2a-c (R = -CN, -C[triple bond]CH, and -CHO, respectively) the chair conformation is predominant, whereas for 2d,f-h [-CH3, -Ph, -C6H4(p-NO2), -C6H4(p-OCH3), respectively] the twist-boat is the most stable compound and for 2e [-C(CH3)3] is the only form.     

Substituent effects in the 13C NMR chemical shifts of alpha-mono-substituted acetonitriles

13C chemical shifts empirical calculations, through a very simple additivity relationship, for the alpha-methylene carbon of some alpha-mono-substituted acetonitriles, Y-CH(2)-CN (Y=H, F, Cl, Br, I, OMe, OEt, SMe, SEt, NMe(2), NEt(2), Me and Et), lead to similar, or even better, results in comparison to the reported values obtained through Quantum Mechanics methods. The observed deviations, for some substituents, are very similar for both approaches. This divergence between experimental and calculated, either empirically or theoretically, values are smaller than for the corresponding acetones, amides, acetic acids and methyl esters, which had been named non-additivity effects (or intramolecular interaction chemical shifts, ICS) and attributed to some orbital interactions. Here, these orbital interactions do not seem to be the main reason for the non-additivity effects in the empirical calculations, which must be due solely to the magnetic anisotropy of the heavy atom present in the substituent. These deviations, which were also observed in the theoretical calculations, were attributed in that case to the non-inclusion of relativistic effects and spin-orbit coupling in the Hamiltonian. Some divergence is also observed for the cyano carbon chemical shifts, probably due to the same reasons.     

Theoretical study on metal NMR chemical shifts: Germanium compounds

Germanium chemical shifts were studied theoretically by the ab initio molecular orbital method. The compounds studied were GeMe_4?xCl_x and GeMe_4?xH_x(x = 0–4). The calculated values of the germanium chemical shifts agreed well with the available experimental values. The germanium chemical shift is due to the p-electron mechanism that reflects the ligand electronic effect on the p-p* excitation term in the second-order paramagnetic term. For GeMe_4?xH_x, the chemical shift is almost linear to the number of the ligand, x. On the other hand, a U-shaped dependence is predicted for the chemical shifts of the GeMe_4?xCl_x series and is shown to be caused by the strong and nonadditive electron-withdrawing ability of the Cl ligand. The diamagnetic contribution is relatively small for the chemical shift and is determined solely by a structural factor. © 1994 John Wiley & Sons, Inc.