Compensating for variation in 1JCH coupling constants in HSQC spectra acquired on small organic molecules

The HSQC sequence provides a sensitive way of determining the ¹³C chemical shift of protonated carbons. It uses INEPT elements for magnetization transfer, which can only be optimized for one value of ¹J_CH, but small organic molecules contain a wide range of ¹J_CH values. One popular method of compensating for ¹J_CH variation is to incorporate adiabatic pulses into the INEPT elements. This article shows that this method fails for a significant subset of functional groups. It also shows that the effects of this failure can be reduced by avoiding refocusing delays and by using a J‐compensated excitation element. Copyright © 2010 John Wiley & Sons, Ltd.     

Simulation of 2D H homo- and H-C heteronuclear NMR spectra of organic molecules by DFT calculations of spin-spin coupling constants and H and C-chemical shifts

Simulation of 2D ¹H homo- and ¹H-¹³C heteronuclear NMR spectra of organic molecules are here suggested as a tool in the structure elucidation of organic compounds. DFT calculations of ¹H and ¹³C chemical shifts are performed on a sample compound, the ethyl ester of the exo-2-norbornanecarbamic acid, with the mPW1PW91 method using the 6-31G(d) basis set, following a full optimization of the geometry. Homo and heteronuclear spin-spin coupling constants are also calculated, providing full prediction of the common 2D ¹H-¹H COSY, 2D ¹H-¹³C HSQC, and 2D ¹H-¹³C HMBC.     

Analysis of 1H NMR spectra of fluorene and azafluorenes: Long-range coupling constants

Analyses of the ¹H NMR spectra of fluorene, 2-nitrofluorene, 1-azafluorene, 2-azafluorene, 4-azafluorene, 7-nitro-4-azafluorene and 1,4-diazafuorene have been carried out using computer calculations and homo double resonance techniques. The relative signs and magnitude of the ⁴J, ⁵J and ⁶J long-range coupling constants of the 9-CH₂ group protons with the pyridine and phenylene ring protons have been measured by five- and six-spin calculations. It was established that the presence of substituents and the N heteroatom has only a very weak effect on the values and signs of these coupling constants. The usual alternating signs of long-range coupling constants involving π-electron systems were confirmed, giving negative signs for even and positive signs for odd numbers of bonds separating the coupling protons.     

Complete prediction of the 1H NMR spectrum of organic molecules by DFT calculations of chemical shifts and spin-spin coupling constants

1H NMR chemical shifts and coupling constants for several aromatic and aliphatic organic molecules have been calculated with DFT methods. In some test cases (furan, o-dichlorobenzene and n-butyl chloride) the performance of several functionals and basis sets has been analyzed, and the various contributions to spin-spin coupling (Fermi-contact, diamagnetic and paramagnetic spin-orbit) have been evaluated. The latter two components cancel each other, so that the calculation of the contact term only is sufficient for an accurate evaluation of proton-proton couplings. Such calculated values are used to simulate the 1H NMR spectra of organic molecules with complicated spin systems (e.g. naphthalene, o-bromochlorobenzene), obtaining a generally very good agreement with experimental spectra with no prior knowledge of the involved parameters.     

Quantum-chemical calculations of NMR chemical shifts of organic molecules: X. Dynamic equilibrium effects in the 29Si NMR spectra of silacycloalkanes

Dynamic equilibria related to change of the coordination number of the silicon atom in bis[N-(dimethylamino) imidato-N′,O]silacycloalkanes in solution were studied by theoretical calculations and experimental measurement of the ²⁹Si NMR chemical shifts. Silacyclopentane derivatives were found to exist in solution as mixtures of species with six- and five-coordinate silicon atoms, and silacyclohexane derivatives, as mixtures of five- and four-coordinate silicon compounds.     

Quantum-chemical calculations of NMR chemical shifts of organic molecules: VII. Intramolecular coordination effect in the 29Si NMR spectra of siletanes

The effects of intramolecular N→Si coordination and electronic and conformational factors on the chemical shift of ²⁹Si nucleus in silacyclobutane (siletane) derivatives were studied by quantum-chemical methods. Intramolecular coordination induces upfield shift of the ²⁹Si resonance on the average by 50 ppm when the coordination number of the silicon atom increases by unity. The state of conformational equilibrium of siletane derivatives critically affects the accuracy of δ_Si predictions.     

Measurement of 1H-1H residual dipolar coupling constants for structural studies of medium size molecules.

Residual dipolar coupling constants (RDCs) are being increasingly applied to elucidate the configuration and conformation of small organic molecules, peptides and oligosaccharides. In this paper we describe a set of robust 1D NMR methods for accurate and precise measurement of proton-proton RDCs of small and medium size molecules. The performance of these techniques is not impeded by the presence of overlapping and broad (1)H multiplets that are typically observed for such molecules in weakly aligned media. The use of these techniques provides access to a large pool of proton-proton RDCs opening new avenues for the solution structure elucidation of medium size molecules by NMR. The techniques are illustrated on the determination of the alignment tensor of the reducing monosaccharide ring of cellobiose and the determination of the relative configuration of sodium cholate.     

A simple method for measuring long-range 1H-13C coupling constants in organic molecules

This study presents a simple method for measuring long-range heteronuclear coupling constants between protons and proton-bearing carbons. The approach involves recording two conventional 1D-TOCSY experiments in which the offset of the selective proton pulse is set on the low- and high-frequency 13C satellites of an isolated proton signal, Hi. Long-range heteronuclear coupling values between the 13Ci bonded to Hi and the protons Hj,k...n that belong to the same spin system were easily determined from the relative displacement of the relayed Hj,k...n signals in the satellite-selective TOCSY spectra. The sense of the displacement indicated the sign of the coupling constants.     

Calculations of 1H NMR coupling constants for conformational studies of isomeric pentofuranosyl nucleosides

The SCF FPT method in the INDO approximation of molecular orbital theory is employed for calculations of ¹H NMR cisoidal coupling constants in model compounds. Obtained results are used for finding conformational states of α-xylo-, β-lyxo-, and α-2′-deoxyribonucleosides in solution.     

A two-stage approach to automatic determination of 1H NMR coupling constants

(1)H NMR scalar coupling constants are a rich source of information on molecular structure, but their extraction from spectra can be less than straightforward. Previous approaches to J extraction include methods proposed by Hoye, Golotvin, and the 'modified J-doubling' method. Here we describe the ACCA method, currently implemented in the NMR package MestReC, which allows a high degree of automation in the extraction of coupling patterns even in the case of complex multiplets with sublinewidth splitting. The new approach is illustrated by application to strychnine, for which it has detected previously unreported couplings.     

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.     

Quantum-chemical calculations of chemical shifts in NMR spectra of organic molecules: V. Stereochemical structure of unsaturated phosphonic acids dichlorides from 31P NMR spectral data

The stereochemical structure of unsaturated phosphonic acids dichlorides containing fragments C=C-POCl₂ and C=N-POCl₂ was investigated by ³¹P NMR spectroscopy and quantum chemistry. Starting from the experimental measurement and theoretical calculation of ³¹P NMR chemical shifts configurations were assigned and the conformational composition of compounds under study was determined.     

Vicinal 1H-1H NMR coupling constants from density functional theory as reliable tools for stereochemical analysis of highly flexible multichiral center molecules

A protocol for stereochemical analysis, based on the systematic comparison between theoretical and experimental vicinal (1)H-(1)H NMR coupling constants, was developed and applied to a series of flexible compounds (1-8) derived from the 6-heptenyl-5,6-dihydro-2H-pyran-2-one framework. The method included a broad conformational search, followed by geometry optimization at the DFT B3LYP/DGDZVP level, calculation of the vibrational frequencies, thermochemical parameters, magnetic shielding tensors, and the total NMR spin-spin coupling constants. Three scaling factors, depending on the carbon atom hybridizations, were found for the (1)H-C-C-(1)H vicinal coupling constants: f((sp3)-(sp3)) = 0.910, f((sp3)-(sp2)) = 0.929, and f((sp2)-(sp2))= 0.977. A remarkable correlation between the theoretical (J(pre)) and experimental (1)H-(1)H NMR (J(exp)) coupling constants for spicigerolide (1), a cytotoxic natural product, and some of its synthetic stereoisomers (2-4) demonstrated the predictive value of this approach for the stereochemical assignment of highly flexible compounds containing multiple chiral centers. The stereochemistry of two natural 6-heptenyl-5,6-dihydro-2H-pyran-2-ones (14 and 15) containing diverse functional groups in the heptenyl side chain was also analyzed by application of this combined theoretical and experimental approach, confirming its reliability. Additionally, a geometrical analysis for the conformations of 1-8 revealed that weak hydrogen bonds substantially guide the conformational behavior of the tetraacyloxy-6-heptenyl-2H-pyran-2-ones.     

Observation and interpretation of HH coupling in 1H187Os satellite NMR spectra

The single hydride resonance observed for each of the compounds H₃Os₃(CO)₉CX (X = OMe, Br, H) has one set of ¹⁸⁷Os satellites which are further split into doublets by HH coupling. The implications of this observation for structural assignments based on ¹⁸⁷Os satellites are discussed.     

17O NMR: 2J(17O1H) coupling constants by line shape analysis

Two bond spin-spin coupling constants ²J(¹⁷O¹H) are determined for the oxygen in ether, aldehyde, acid, ester and amide groups by line shape analysis of the corresponding ¹⁷O NMR spectra.     

1H and 13C chemical shifts and coupling constants of lupane. Application of two-dimensional NMR techniques

2D NMR techniques (J-resolved ¹³C, ¹³C? ¹³C correlated, ¹H? ¹³C correlated) were used to gather more chemical shift and coupling information on the pentacyclic triterpene, lupane. They confirm and complete ¹³C assignments made earlier, and corroborate the constitution and major configurational details of lupane. Lupane is a parent compound and spectral reference in the study of sedimental demethylated triterpenes.