Extracting spin system parameters from 1D high resolution 1H-NMR spectra can be an intricate task requiring sophisticate methods. With a few exceptions methods to perform such a total line shape analysis commonly rely on local optimization techniques which for increasing complexity of the underlying spin system tend to reveal local solutions. In this work we propose a full Bayesian modeling approach based on a quantum mechanical model of the spin system. The Bayesian formalism provides a global optimization strategy which allows to efficiently include prior knowledge about the spin system or to incorporate additional constraints concerning the parameters of interest. The proposed algorithm has been tested on synthetic and real 1D 1H-NMR data for various spin systems with increasing complexity. The results show that the Bayesian algorithm provides accurate estimates even for complex spectra with many overlapping regions, and that it can cope with symmetry induced local minima. By providing an unbiased estimate of the model evidence the proposed algorithm furthermore offers a way to discriminate between different spin system candidates.

β-lactams are a chemically diverse group of molecules with a wide range of biological activities. Having recently observed curious trends in 2JHH coupling values in studies on this structural class, we sought to obtain a more comprehensive understanding of these diagnostic NMR parameters, specifically interrogating 1JCH, 2JCH, and 2JHH, to differentiate 3- and 4-monosubstituted β-lactams. Further investigation using computational chemistry methods was employed to explore the geometric and electronic origins for the observed and calculated differences between the two substitution patterns.

Nuclear magnetic resonance (NMR) is a valuable tool for determining the structures of molecules and probing their dynamics. A longstanding problem facing both small-molecule and macromolecular NMR is overlapped signals in crowded spectra. To address this, we have developed a method that extracts peak features by fitting analytically derived models of NMR lineshapes. The approach takes into account the effects of truncation, apodization, and the resulting artifacts, while avoiding systematic errors that have affected other models. Even severely overlapped peaks, beyond the point of coalescence, can be distinguished in both simulated and experimental data. We show that the method can measure unresolved backbone scalar couplings directly from a 2D proton-nitrogen spectrum of a de novo designed mini protein. The algorithm is implemented in the FitNMR open-source R package and can be used to analyze nearly any type of single or multidimensional data from small molecules or biomolecules.

A novel G-SERF-PSYCHE-TOCSY (gradient encoded selective refocusing in pure shift yielded by chirp excitation version of total correlation spectroscopy) NMR pulse scheme has been proposed, which produces TOCSY chemical shift correlations, on one hand, and scalar coupling values for the spins scalarly coupled to irradiated resonances, by showing them as doublets along the indirect dimension, on the other. Therefore, recording such an experiment, for a group of spins with overlapping chemical shifts, in organic molecules can adequately provide scalar coupling information in a G-SERF manner along the indirect dimensions, and they can be assigned to particular spin pairs. Such COSY chemical shift correlations (which appear as doublets for the scalarly coupled spins) can be readily discriminated from the TOCSY peaks (which do not show such splitting) in the G-SERF-PSYCHE-TOCSY spectrum.

MSpin-JCoupling is a modular program for the prediction of scalar couplings using a large variety of Karplus relationships. The program was specially designed for small molecule analysis and can be run in graphical or command-line mode. The architecture of the program is highly modular, and new equations can be rapidly implemented, through a complete C++ programming interface, and deployed as run-time loadable plugins.

This study explores the feasibility of using a combination of experimental and theoretical 1-bond 13 C─13 C scalar couplings (1 JCC ) to establish structure in organic compounds, including unknowns. Historically, n JCC and n JCH studies have emphasized 2 and 3-bond couplings, yet 1 JCC couplings exhibit significantly larger variations. Moreover, recent improvements in experimental measurement and data processing methods have made 1 JCC data more available. Herein, an approach is evaluated in which a collection of theoretical structures is created from a partial nuclear magnetic resonance structural characterization. Computed 1 JCC values are compared to experimental data to identify candidates giving the best agreement. This process requires knowledge of the error in theoretical methods, thus the B3LYP, B3PW91, and PBE0 functionals are evaluated by comparing to 27 experimental values from INADEQUATE. Respective errors of ±1.2, ±3.8, and ±2.3 Hz are observed. An initial test of this methodology involves the natural product 5-methylmellein. In this case, only a single candidate matches experimental data with high statistical confidence. This analysis establishes the intramolecular hydrogen-bonding arrangement, ring heteroatom identity, and conformation at one position. This approach is then extended to hydroheptelidic acid, a natural product not fully characterized in prior studies. The experimental/theoretical approach proposed herein identifies a single best-fit structure from among 26 candidates and establishes, for the first time, 1 configuration and 3 conformations to complete the characterization. These results suggest that accurate and complete structural characterizations of many moderately sized organic structures (<800 Da) may be possible using only 1 JCC data.

An intramolecular bifurcated H-bond from the axial HO-2 group to the axial F-4 atom and to the O5 atom of α-D-hexopyranosides in apolar solvents is evidenced in (1)H NMR spectra. The H-accepting properties of the F atom are modulated by the orientation of the O-substituent at the C3 atom and by an additional F atom at the C4 atom.