Theoretical prediction of the spin-spin coupling constants between an axis and macrocycle of a rotaxane

The indirect nuclear spin-spin coupling constants between nuclei belonging to the axis and to the macrocycle of three structurally related rotaxanes have been calculated by means of density functional theory. It has been shown that the through-space axis-macrocycle proton-proton coupling constants can be as large as 0.4-0.5 Hz and therefore of measurable values. The largest through-space axis-macrocycle carbon-proton and nitrogen-proton coupling constants are 0.2-0.3 Hz. Visualization of coupling pathways by means of the coupling energy density method indicates that the larger proton-proton couplings are indeed transmitted through the space between the coupled nuclei. Thus, it seems that measurement of such couplings should be possible and that indirect spin-spin couplings can be actually transmitted through-space, with no covalent or hydrogen bonds between the coupled nuclei.     

On the capriciousness of the FCCF Karplus curve

Numerous well-behaved Karplus curves correlating dihedral angle (phi) and NMR coupling constants (3JXY) exist for X-C-Z-Y fragments with X or Y = H, C, F, and P. Absent is the enigmatic F-C-C-F moiety. By calculating the four Ramsey contributions to 3JFF for F-CH2-CH2-F, a pleasing phi/3JFF curve with both positive and negative regions arises. Unlike the H-C-C-H curve, F-C-C-F is PSO vs FC dominated. The latter and the F lone electron pairs cause both the negative J values and the substituent-induced J-leveling effect.     

Self-consistent Karplus parametrization of 3J couplings depending on the polypeptide side-chain torsion chi1.

Recently proposed self-consistent 3J coupling analysis (Schmidt, J. M.; Blümel, M.; L?hr, F.; Rüterjans, H. J. Biomol. NMR 1999, 14, 1-12) has been carried out to calibrate Karplus parameters constituting the empirical dependence of 3J coupling constants on the chi1 dihedral angle in amino acid side chains. The procedure involves simultaneous least-squares optimization of six sets of three Karplus coefficients related to all six 3J coupling types accessible in 15N,13C-labeled proteins. A simple concept of fundamental and incremental component couplings is proposed to account for substituent effects, eventually yielding amino acid topology-specific Karplus parameters. The method is exemplified with recombinant Desulfovibrio vulgaris flavodoxin (147 amino acids, 16 kDa) with reference to a total of 749 experimental 3JHalpha,Hbeta, 3JN',Hbeta, 3JC',Hbeta, 3JHalpha,Cgamma, 3JN',Cgamma, and 3JC',Cgamma coupling constants. Unlike other parametrizations, the present method does not make reference to X-ray coordinates, so that the Karplus coefficients obtained are not influenced by differences between solution and crystal states. Cross validation using X-ray torsion angles demonstrates the improvement relative to previous parametrizations. The Karplus coefficients derived are applicable to other proteins, too. Parameter refinement also yields a series of chi1 torsion angles, providing valuable constraints for protein structure determination, as well as optional parameters of local angular mobility in the contexts of Gaussian random fluctuation or a three-site jump model. The procedure permits automatic stereospecific assignments of Hbeta and Cgamma chemical shifts. The majority of the flavodoxin side-chain conformations agrees with high-resolution X-ray structures of the protein. Marked deviations between NMR and X-ray datasets are attributed to different rotameric states due to crystal-packing effects and to conformational equilibria between multiple chi1 rotamers.     

Non‐empirical calculations of NMR indirect carbon–carbon coupling constants: 1. Three‐membered rings

The carbon–carbon indirect nuclear spin–spin coupling constants in cyclopropane, aziridine and oxirane were investigated by means of ab initio calculations at the RPA, SOPPA and DFT/B3LYP levels. We found that the carbon–carbon couplings are by far dominated by the Fermi contact term. Our best SOPPA and DFT results are in a very good agreement with each other and with the experimental values, whereas calculations at the RPA level of theory strongly overestimate the carbon–carbon couplings. Significant differences in the basis set dependence of the calculated carbon–carbon coupling constants obtained with either wavefunction method, RPA or SOPPA, or the density functional method, DFT/B3LYP, are observed. The SOPPA results depend much more strongly on the quality of the basis set than the results of DFT/B3LYP calculations. The medium‐sized core‐valence basis sets cc‐pCVTZ and even cc‐pCVDZ were found to perform fairly well at the SOPPA level for the one‐bond carbon–carbon couplings investigated here. Copyright © 2002 John Wiley & Sons, Ltd.     

Difluorobenzenes revisited: an experimental and theoretical study of spin–spin coupling constants for 1,2‐, 1,3‐, and 1,4‐difluorobenzene

The experimental spin–spin coupling constants (SSCCs) for 1,3‐ and 1,4‐difluorobenzene have been determined anew, and found to be consistent with previously determined values. SSCCs for 1,2‐, 1,3‐, and 1,4‐difluorobenzene have been analyzed by comparing them with the coupling constants computed using the second‐order polarization propagator approximation (SOPPA) and the equation‐of‐motion coupled cluster singles and doubles method (EOM‐CCSD). Eighty experimental values have been analyzed using SOPPA calculations, and a subset of 40 values using both SOPPA and EOM‐CCSD approaches. One‐bond coupling constants ¹J(C? C) and ¹J(C? F) are better described by EOM‐CCSD, whereas one‐bond ¹J(C? H) values are better described by SOPPA. An empirical equation is presented which allows for the prediction of unknown coupling constants from computed SOPPA values. A similar approach may prove useful for predicting coupling constants in larger systems. Copyright © 2009 John Wiley & Sons, Ltd.     

Non-empirical calculations of NMR indirect carbon-carbon coupling constants. Part 6: propellanes

A full set of carbon-carbon coupling constants have been calculated at the SOPPA level in the series of six most representative propellanes. Special attention was focused on spin-spin couplings involving both bridgehead carbons, and these data were rationalized in terms of the multipath coupling mechanism and hybridization effects. Many unknown couplings in the propellane frameworks were predicted with high reliability.     

Through-space spin-spin coupling in van der Waals dimers and CH/pi interacting systems. An ab initio and DFT study

The through-space J(HH) and J(CH) spin-spin coupling constants of model van der Waals dimers (involving methane, ethylene, and benzene), and of selected compounds showing the CH/pi interaction, have been investigated by means of DFT and ab initio calculations. In the range of intermolecular separations for which the interaction is stabilizing, weak couplings (0.1-0.3 Hz) are predicted for J(CH), while the corresponding J(HH) couplings are much smaller. The relative contributions (Fermi-contact, spin-orbit, and spin-dipole) are strongly dependent on the geometry of the dimers and on the distance; the non-negligible values of J(CH) for pi systems stem largely from an incomplete cancellation of spin-orbit terms. The results obtained for the larger molecules, that is, acetonitrile@calix[4]arene 5, the imine 6, and the aryl ester 7 are consistent with those on the model dimers. For 7, the occurrence of a through-space mechanism for the transmission of coupling is established by examining trends in the magnitude of couplings as a function of the number of intervening covalent bonds.     

Correlated calculations of indirect nuclear spin-spin coupling constants using second-order polarization propagator approximations: SOPPA and SOPPA(CCSD)

We present correlated calculations of the indirect nuclear spin-spin coupling constants of HD, HF, H₂O, CH₄, C₂H₂, BH, AlH, CO and N₂ at the level of the second-order polarization propagator approximation (SOPPA) and the second-order polarization propagator approximation with coupled-cluster singles and doubles amplitudes – SOPPA(CCSD). Attention is given to the effect of the so-called W ₄ term, which has not been included in previous SOPPA spin-spin coupling constant studies of these molecules. Large sets of Gaussian basis functions, optimized for the calculation of indirect nuclear spin-spin coupling constants, were used instead of the in general rather small basis sets used in previous studies. We find that for nearly all couplings the SOPPA(CCSD) method performs better than SOPPA. Received: 6 July 1998 / Accepted: 8 September 1998 / Published online: 23 November 1998     

Non-empirical calculations of NMR indirect carbon-carbon coupling constants. Part 8--monocycloalkanes

Carbon-carbon and carbon-hydrogen spin-spin coupling constants were calculated in the series of the first six monocycloalkanes using SOPPA and SOPPA(CCSD) methods, and very good agreement with the available experimental data was achieved, with the latter method showing slightly better results in most cases, at least in those involving calculations of J(C,C). Benchmark calculations of all possible 21 coupling constants J(C,C), J(C,H) and J(H,H) in chair cyclohexane revealed the importance of using the appropriate level of theory and adequate quality of the basis sets. Many unknown couplings in this series were predicted with high confidence and several interesting structural trends (hybridization effects, multipath coupling transmission mechanisms, hyperconjugative interactions) were elucidated and are discussed based on the present calculations of spin-spin couplings.     

DFT and NMR studies of 2JCOH, 3JHCOH, and 3JCCOH spin-couplings in saccharides: C-O torsional bias and H-bonding in aqueous solution

Density functional theory (DFT) has been used to investigate the structural dependencies of NMR spin-coupling constants (J-couplings) involving the exchangeable hydroxyl protons of saccharides. 3JHCOH, 3JCCOH, and 2JCOH values were calculated at different positions in model aldopyranosyl rings as a function of one or more torsion angles, and results support the use of a generalized Karplus equation to treat 3JHCOH involving the non-anomeric OH groups. The presence of O5 appended to the H1-C1-O1-H coupling pathway introduces asymmetry in 3JH1,O1H Karplus curves due to internal electronegative substituent effects on the gauche couplings, thus requiring separate equations to treat this coupling. 3JCCOH values depend not only on the C-C-O-H torsion angle but also on the orientation of terminal substituents on the coupled carbon, similar to 3JCOCC studied previously (Bose et al., J. Am. Chem. Soc. 1998, 120, 11158-11173). "In-plane" oxygen increased 3JCCOH by approximately 3-4 Hz, whereas "in-plane" carbon gave more modest enhancements ( approximately 1 Hz). Three Karplus equations were derived for non-anomeric 3JCCOH based on the nature and orientation of substituents on the coupled carbon. Like 3JH1,O1H, 3JC2,O1H is also subject to internal electronegative substituent effects on the gauche couplings, thus necessitating separate equations to treat this coupling. 2JCOH values were found not to be useful probes of C-O torsions as a result of their nonsystematic dependence on these torsions. Experimental measurements of 3JHCOH and 3JCCOH in doubly 13C-labeled methyl beta-lactoside 20 and its constituent 13C-labeled methyl aldopyranosides in H2O/acetone-d6 at -20 degrees C showed that some C-O torsion angles are influenced by molecular context and do not experience complete rotational averaging in solution. A strong bias in the H3-C3-O3-H torsion angle in the Glc residue of 20 favoring a gauche conformation suggests the presence of inter-residue H-bonding between O3HGlc and O5Gal. Quantitative analysis of 3JHCOH and 3JCCOH values in 20 indicates that approximately 85% of the forms in solution have geometries consistent with H-bonding. These results suggest that H-bonding between adjacent and/or remote residues may play a role in dictating preferred glycosidic bond conformation in simple and complex oligosaccharides in aqueous solution.     

Assignment of cis-Epoxides and Crystal Structure of cis-4-Nitro-N-（7-oxabicyclo[4.1.0]hept-2-yl）benzamide

1 INTRODUCTION The success of strategies for total synthesis con-tinues to depend on high levels of stereoselectivityobserved in substrate-directed diastereoselective re-actions[1]. In this context, one of the most widelyused processes is diastereoselective epoxidation ofcyclic alkenes with allylic O- and N-directing group,which is very useful in building stereodefined syn-thetic blocks[2, 3] .However, in some circumstances,the assignment of resulting epoxides is not straight-forward[4～8…     

Stereochemical behavior of 77Se‐1H spin‐spin coupling constants in pyrazolyl‐1,3‐diselenanes and 1,2‐diselenolane

Conformational study of five derivatives of 2‐(pyrazol‐4‐yl)‐1,3‐diselenane together with related 1,2‐diselenolane in respect to the stereochemical trends of geminal and vicinal ⁷⁷Se‐¹H spin‐spin coupling constants has been carried out by means of high‐level theoretical calculations in combination with experiment. The marked dihedral angle dependences for both types of couplings accounted for the lone pair effect in the case of geminal coupling constants and the Karplus‐type relationship for vicinal couplings have been established, which is of major importance for the stereochemical analysis of saturated selenium containing heterocycles. Copyright © 2012 John Wiley & Sons, Ltd.     

Non-empirical calculations of NMR indirect carbon-carbon coupling constants. Part 12--aliphatic and alicyclic oximes

One-bond carbon-carbon coupling constants were calculated in a series of nine aliphatic and alicyclic oximes at the SOPPA (second-order polarization propagator approach) level in good agreement with the available experimental data, and several unknown couplings were predicted with high reliability. The experimental difference between J(C,C) of the corresponding carbon-carbon bonds in cis and trans orientations to the nitrogen lone pair is very well reproduced at the SOPPA level, and this provides an additional tool in the configurational assignment at the C=N bond in oximes and related systems.     

A proton magnetic resonance study of the conformation of the seven-membered ring in benzocycloheptene

The computer analysis of the PMR spectra of several partially deuterated benzocycloheptene derivatives at ?120° provides values for all the coupling constants about the C₃? C₄ bond. An interpretaion using the Karplus equation shows unambiguously that the seven-membered ring exists as a chair conformation. The relationship between the coupling constants determined shows that the form of the Karplus equation established empirically for cyclohexane is applicable to this seven-membered ring. A comparison of coupling constants shows that the benzocycloheptene chair is more puckered than the cyclohexane chair.     

Benchmark calculations of 29Si–1H spin–spin coupling constants across double bond

Benchmark calculations of geminal and vicinal ²⁹Si–¹H spin–spin coupling constants across double bond in three reference alkenylsilanes have been carried out at both DFT and SOPPA levels in comparison with experiment. At the former, four density functionals, B3LYP, B3PW91, PBE0 and KT3, were tested in combination with five representative basis sets. At the latter, three main SOPPA‐based methods, SOPPA, SOPPA(CC2) and SOPPA(CCSD), were examined in combination with the same series of basis sets. On the whole, the wavefunction methods showed much better results as compared to DFT, with the most efficient combination of SOPPA/cc‐pVTZ‐su2 characterized by a mean absolute error of only 0.4 Hz calculated for a set of nine coupling constants in three compounds with a sample span of around 40 Hz. Copyright © 2012 John Wiley & Sons, Ltd.     

Exchange coupling mediated through-bonds and through-space in conformationally constrained polyradical scaffolds: calix[4]arene nitroxide tetraradicals and diradical

Calix[4]arenes constrained to the 1,3-alternate conformation and functionalized at the upper rim with four and two tert-butylnitroxides have been synthesized and characterized by X-ray crystallography, magnetic resonance (EPR and (1)H NMR) spectroscopy, and magnetic studies. The 1,3-alternate nitroxide tetraradical and diradical provide unique polyradical scaffolds for dissection of the through-bond and through-space intramolecular exchange couplings. In addition, detailed magnetic studies of the previously reported calix[4]arene nitroxide tetraradical, which possesses cone conformation in solution, reveal conformational dependence of exchange coupling. Through-bond coupling between the adjacent nitroxide radicals is mediated by the nitroxide-m-phenylene-CH(2)-m-phenylene-nitroxide coupling pathway, and through-space coupling is found between the diagonal nitroxide radicals at the conformationally constrained N...N distance of 5-6 A. Magnetic studies of the calix[4]arene polyradical scaffolds in frozen solutions show that the through-bond exchange coupling in the 1,3-alternate calix[4]arene tetraradical is antiferromagnetic, while that in cone calix[4]arene tetraradical is ferromagnetic. The through-space exchange couplings are antiferromagnetic in both cone and 1,3-alternate calix[4]arene tetraradical, as well as in the 1,3-alternate calix[4]arene diradical. The exchange coupling constants (|J/k|) are of the order of 1 K.     

Phosphorus-31 Fluorine-19 N.M.R. Through-Space Coupling

Abstract

Through-space coupling, which may be observed when NMR active nuclei are close in space, is additive to any through-bond coupling. The magnitude of the coupling via the through-space mechanism varies according to the element, its valency and the distance between the coupled atoms-independently of the number of bonds separating the coupled atoms. The couplings between carbon-bound fluorine and phosphorus (in its three valent three coordinate state) have been studied using a series of 0-(trifluoromethyl)phenylphosphanes (1). The phosphorusfluorine coupling is lowest (29. 6Hz) for the primary phosphine (1, Y = H). It is 43 Ha for the diethylamino derivative (1, R = Et₂N), rising to 53–56 Ha when Y is phenyl, heteroaromatic, alkyl and ethoxy groups, and then to 63 and 68 Hz for the phenoxy and fluoro derivatives. The PF coupling is largest (85–88 Hz) for the dichloro and dibromo compounds. The coupling constants are zero or close to aero for the corresponding salts, oxides and sulphides. The changes in the magnitude of the phoaphane couplings are discussed in terms of conformational and electronic influences on a through-space spin-spin coupling mechanism.     

Non-empirical calculations of NMR indirect carbon-carbon coupling constants. Part 11--saturated carbocycles: a reference data set and a practical guide to structural elucidation

Carbon-carbon spin-spin coupling constants, J(C,C), calculated at the SOPPA level for 50 mono-, bi- and polycycloalkanes in 10 previous papers are put in order and discussed on unified grounds. Basic structural trends of J(C,C) established in the original publications are summarized and briefly outlined for the representative series. Many unknown couplings are predicted with high reliability, and this provides a good reference data set and a practical guide to the structural elucidation of saturated carbocycles by means of J(C,C) coupling constants.     

Communication: Accurate determination of side-chain torsion angle χ1 in proteins: phenylalanine residues

Quantitative side-chain torsion angle χ(1) determinations of phenylalanine residues in Desulfovibrio vulgaris flavodoxin are carried out using exclusively the correlation between the experimental vicinal coupling constants and theoretically determined Karplus equations. Karplus coefficients for nine vicinal coupling related with the torsion angle χ(1) were calculated using the B3LYP functional and basis sets of different size. Optimized χ(1) angles are in outstanding agreement with those previously reported by employing x ray and NMR measurements.     

Benchmarking NMR indirect nuclear spin-spin coupling constants: SOPPA, SOPPA(CC2), and SOPPA(CCSD) versus CCSD

Accurate calculations of NMR indirect nuclear spin-spin coupling constants require especially optimized basis sets and correlated wave function methods such as CCSD or SOPPA(CCSD). Both methods scale as N(6), where N is the number of orbitals, which prevents routine applications to molecules with more than 10-15 nonhydrogen atoms. We have therefore developed a modification of the SOPPA(CCSD) method in which the CCSD singles and doubles amplitudes are replaced by CC2 singles and doubles amplitudes. This new method, called SOPPA(CC2), scales only as N(5), like the original SOPPA-method. The performance of the SOPPA(CC2) method for the calculation of indirect nuclear spin-spin coupling constants is compared to SOPPA and SOPPA(CCSD) employing a set of benchmark molecules. We also investigate the basis set dependence by employing three different basis sets optimized for spin-spin coupling constants, namely the HuzIV-su4, ccJ-pVTZ, and ccJ-pVQZ basis sets. The results of the corresponding CCSD calculations are used as a theoretical reference.