Lee Griffiths

Towards the automatic analysis of 1H NMR spectra

A method was developed to yield automatically accurate chemical shifts from peak‐pick tables of proton spectra. Not only does this allow the rapid comparison of proton spectra obtained at any external magnetic field strength with spectral databases or calculated chemical shifts, but it also allows the facile building of proton chemical shift databases. The extraction of chemical shifts was successful in many situations of multiplet overlap and second‐order coupling. Scalar couplings were also extracted fairly successfully, although the performance was compromised at lower external magnetic field strength and in spectra displaying second‐order couplings. Copyright

1H NMR spectra. Part 30: 1H chemical shifts in amides and the magnetic anisotropy, electric field and steric effects of the amide group†

The 1H spectra of 37 amides in CDCl3 solvent were analysed and the chemical shifts obtained. The molecular geometries and conformational analysis of these amides were considered in detail. The NMR spectral assignments are of interest, e.g. the assignments of the formamide NH2 protons reverse in going from CDCl3 to more polar solvents. The substituent chemical shifts of the amide group in both aliphatic and aromatic amides were analysed using an approach based on neural network data for near (≤3 bonds removed) protons and the electric field, magnetic anisotropy, steric and for aromatic systems π effects of the amide group for more distant protons. The electric field is calculated from the partial atomic charges on the N.C═O atoms of the amide group. The magnetic anisotropy of the carbonyl group was reproduced with the asymmetric magnetic anisotropy acting at the midpoint of the carbonyl bond. The values of the anisotropies Δχparl and Δχperp were for the aliphatic amides 10.53 and −23.67 (×10−6u2009Å3/molecule) and for the aromatic amides 2.12 and −10.43 (×10−6u2009Å3/molecule). The nitrogen anisotropy was 7.62 (×10−6u2009Å3/molecule). These values are compared with previous literature values. The 1H chemical shifts were calculated from the semi‐empirical approach and also by gauge‐independent atomic orbital calculations with the density functional theory method and B3LYP/6–31G++ (d,p) basis set. The semi‐empirical approach gave good agreement with root mean square error of 0.081u2009ppm for the data set of 280 entries. The gauge‐independent atomic orbital approach was generally acceptable, but significant errors (ca. 1u2009ppm) were found for the NH and CHO protons and also for some other protons. Copyright

1H chemical shifts in NMR. Part 27: proton chemical shifts in sulfoxides and sulfones and the magnetic anisotropy, electric field and steric effects of the SO bond†

The 1H chemical shifts of a series of sulfoxide and sulfone compounds in CDCl3 solvent were obtained from experiment and the literature. These included dialkyl sulfoxides and sulfones (R2SO/R2SO2, R = Me, Et, Pr, n‐Bu), the cyclic compounds tetramethylene sulfoxide/sulfone, pentamethylene sulfoxide/sulfone and the aromatic compounds p‐tolylmethylsulfoxide, dibenzothiopheneoxide/dioxide, E‐9‐phenanthrylmethylsulfoxide and (E) (Z)‐1‐methylsulfinyl‐2‐methylnaphthalene. The spectra of the pentamethylene SO and SO2 compounds were obtained at −70 °C to obtain the spectra from the separate conformers (SO) and from the noninverting ring (SO2). This allowed the determination of the substituent chemical shifts (SCS) of the SO and SO2 functional groups, which were analyzed in terms of the SO bond electric field, magnetic anisotropy and steric effect for long‐range protons together with a model (CHARGE8d) for the calculation of the two and three bond effects. After parameterization, the overall root mean square (RMS) error (observed‐calculated) for a dataset of 354 1H chemical shifts was 0.11 ppm. The anisotropy of the SO bond was found to be very small, supporting the dominant single bond S+uf8ffO− character of this bond. Copyright

Towards the automatic analysis of NMR spectra: Part 7. Assignment of 1H by employing both 1H and 1H/13C correlation spectra

A reliable method of automatically assigning one‐dimensional proton spectra is described. The method relies on the alignment of the proton spectrum with an associated heteronuclear single‐quantum coherence (HSQC) spectrum, transferring the stoichiometry and couplings to the HSQC. The HSQC spectrum is then assigned using a linear assignment procedure in which a fitness function incorporating 1H chemical shifts, 1H couplings and 13C shifts are employed. The method uniquely employs a sequential procedure in which only correlations of like stoichiometry are assigned at the same time. Copyright

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 (1–2u2009ppm) for the NH protons but smaller and negative (−0.1 to −0.2u2009ppm) 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.

Proton chemical shifts in NMR. Part 14. Proton chemical shifts, ring currents and π electron effects in condensed aromatic hydrocarbons and substituted benzenes

The proton resonance spectra of a variety of condensed aromatic compounds including benzene, naphthalene, anthracene, phenanthrene, pyrene, acenaphthylene and triphenylene were obtained in dilute CDCl3 solution. Comparison of the proton chemical shifts obtained with previous literature data for CCl4 solution shows small but significant differences. A previous model (CHARGE6) for calculating the proton chemical shifts of aliphatic compounds was extended to aromatic compounds. This was achieved by including an automatic identification of both five- and six-membered aromatic rings based on atomic connectivities plus a dipole calculation of the aromatic ring current. The ring current intensity in the molecules was calculated by two alternative methods. a) The ring current intensity in the individual benzenoid rings was a function of the number of adjoining rings and b) the molecular ring current was proportional to the molecular area divided by the molecular perimeter. This, plus the inclusion of deshielding steric effects for the crowded protons in these molecules, gave a good account of the observed chemical shifts. The model was also applied successfully to the non-alternant hydrocarbons of fulvene and acenaphthylene and to the aliphatic protons near to and above the benzene ring in tricyclophane and [10]cyclophane.The Huckel calculation of the π electron densities in CHARGE6 was used to calculate the π electron densities in substituted benzenes. The π-inductive effect was used to simulate the effect of CX3 groups (Xxa0=xa0H, Me, F) on the benzene ring. These together with the long range effects of the substituent groups identified previously allowed a precise calculation of the SCS of a variety of substituents on all the benzene ring protons.The model gives the first accurate calculation of the proton chemical shifts of condensed aromatic compounds and of the proton SCS in the benzene ring. For the data set of 55 proton chemical shifts spanning 3 ppm the rms error of the observed vs. calculated shifts was ca. 0.1 ppm. The model also allows the interpretation of the shifts in terms of the separate interactions calculated in the programme, i.e. nπ electron densities and steric, anisotropic and electric field effects. Previous correlations of the proton SCS with π electron densities and substituent parameters are shown to be over simplified. The relative proportions of these different interactions are very different for each substituent and for each ring proton. np

NMR pulsed field gradient characterization of the behavior of water in gels and emulsions containing cetostearyl alcohol and cetrimide

Abstract The refocused three pulse stimulated echo NMR experiment has been used to investigate the behavior of water in gels and emulsions containing cetostearyl alcohol and cetrimide. A restricted diffusion model was found to be inadequate to explain the data. Instead, the data fitted a bimodal diffusion model, confirming the results of several other techniques.

OPTIMIZATION OF LIQUID CHROMATOGRAPHY-NMR SPECTROSCOPY. II-SATURATION AND FLOW IN ON-FLOW LIQUID CHROMATOGRAPHY-NMR SPECTROSCOPY

The effects of pulse interval and flow on relaxation and signal‐to‐noise ratio in an on‐flow liquid chromatography (LC)–NMR experiment were investigated theoretically. The results led to a procedure for the optimization of on‐flow LC–NMR experiments.

NMR diffusion measurements using refocused three-pulse stimulated echoes

Abstract A modification to the three-pulse stimulated-echo pulse sequence for measuring high-resolution resf-diffusion coefficients, which substantially minimizes phase distortions and other spectral artifacts, is proposed. The new pulse sequence is shown to yield accurate self-diffusion coefficients.

Automatic Analysis of NMR Spectra

Abstract Automatic spectral processing, spectral analysis, spectral prediction and structural confirmation/elucidation have been reviewed. 13 C and two-dimensional spectra have been included, but particular emphasis has been placed on one-dimensional 1 H spectra of small to medium-sized molecules. This is highly pertinent to the explosion in flow NMR currently taking place, which supports multiple parallel synthesis and combinatorial chemistry.