Leonid Borisovich Krivdin

There are many hundreds, if not thousands of original publications and reviews dealing with different aspects of computational NMR applied to structural investigations of inorganic, organic, and bioorganic molecules together with organometallics and metal complexes. In the present review, we introduce a short overview of the most popular computational protocols -- NMR simulations and semiempirical calculations, DFT methods in NMR spectral analysis, and non-empirical NMR calculations. Several dozens of NMR simulative and iterative codes are used in the NMR spectral analysis. At the early stage of development of NMR computations, very popular were semiempirical methods based on complete or partial neglect of differential overlap. Later, very popular became the DFT NMR-based computations because they take into account electron correlation effects via the exchange-correlation potential requiring essentially low computational efforts. However, in the most recent years, NMR calculations are mostly performed based on general Polarization Propagator theory and Coupled Cluster methods. Of all these approaches, SOPPA(CCSD) and pure CCSD schemes turned out to be the most popular and robust methods for calculating NMR parameters.

Members of the broad family of Strychnos alkaloids have been the favorite molecules for the development and evaluation of new NMR methods for many years, including the establishment of the ¹H-¹⁵N two-dimensional NMR methods. The present study is an effort to computationally evaluate the ¹⁵N chemical shift behavior of eight members of this structurally diverse group of indole alkaloids. The molecules range from relatively “simple” strychnine and brucine and their respective N-oxides to molecules as complex as vinorelbine, a synthetic analog used in cancer chemotherapy, and sungucine, a naturally occurring complex dimeric member of the family. The 20 ¹⁵N chemical shifts in this study afforded a CMAE of 2.96 ppm and an RMSD of 3.50 ppm, with the data affording a correlation coefficient, r = 0.997.

Allose, an aldohexose sugar, is a rare natural monosaccharide that occurs in nature in the form of a 6‐O‐cinnamyl glycoside in the leaves of the African shrub Protea rubropilosa . It differs from glucose in the orientation of the hydroxyl group at the C‐3 position, being thus the C‐3 substituted epimer of glucopyranose. In this paper, a detailed theoretical modeling of α ‐ and β ‐D‐alloses was performed, including molecular dynamics (MD) simulations, high‐level geometry optimizations, and GIAO‐DFT NMR studies. Generally, a good correlation between calculated ¹ H and ¹³ C NMR chemical shifts of the conformationally averaged α ‐ and β ‐D‐alloses against experiment was found. Based on the performed calculations, the optimal combination of functionals with basis sets for the geometry optimization (M06‐2X/aug‐pc‐2) and NMR calculations (BHandHLYP/aug‐pcSseg‐2) for carbohydrates was suggested.

The present review provides a brief summary of the most popular statistical protocols applied in the NMR spectral analysis: machine-learning, neural network, computer assisted structure elucidation, and DP4-based probability methods, which produced a real breakthrough in the interpretation of challenging NMR spectra. Those protocols are a broad family of related machine-learning and artificial neural network statistical treatments, the latter being on the cutting edge of modern statistical science providing an alternative to the state-of-the-art multidimensional NMR experiments, which are often combined with quantum chemical calculations at different levels of theory.

Results of the high-level computational study of 12 bisindole alkaloids of the Strychnos-Strychnos type are reported in addition of that of five retuline-like monomers frequently encountered in moieties constituting dimeric alkaloids. Based on the comparison of theoretical and experimental NMR chemical shifts, a detailed conformational survey of these stereochemically rich natural products containing multiple asymmetric centers was performed. Our original methodology is based on searching multiple conformational states, geometry optimization, and high-level NMR calculations at the DFT level. Taking into account all known experimental chemical shifts together with their calculated values in the natural products under study, a correlation estimate of NMR chemical shifts was performed by using statistical descriptors. In general, a good agreement of the performed calculations with experiment was achieved, which is manifested by the Corrected Mean Absolute Error of about 0.2 ppm for ¹H and 1.9 ppm for ¹³C NMR chemical shifts in this series.

The possibilities of reliable determination of spatial structures of natural products based on correlation of high-level calculated and experimental 1H and 13C NMR chemical shifts are considered using the example of four main representatives of the panganensine series, Strychnos-Strychnos type bisindole alkaloids. For isomeric panganensines X and Y, the reassignment of a number of individual NMR signals together with the spectral assignment of experimentally unresolved peaks is suggested, which allows the establishment of the absolute configuration for C-19, the only out-of-ring asymmetric carbon atom.

The present review focuses on the most recent results of a liquid-phase nuclear magnetic resonance (NMR) study of lignin together with the lignin-derived products and related chemicals. Collected and discussed are the recent applications of 1H, 13C and 31P NMR spectroscopy as well as the NMR of less popular nuclei to the structural studies and practical recommendations in this field. Due to the complexity of lignin and the products of its transformation, their NMR spectra consist of a number of overlapping signals belonging to different structural types. In this regard, comprehensive studies of lignin by NMR over the past few decades have revealed characteristic functional groups of lignin and lignin-related products together with the spectral regions in which they resonate. Quantitative NMR spectra of 1H, 13C together and less popular nuclei such as 31P are used to characterize different structural units of lignin (such as guaiacyl, syringil and p-hydroxyphenyl), which provide aromatic and saturated carbons spread over many structural moieties. The bibliography includes 54 references.

It is demonstrated that by using modern computational methods, it is possible to identify potential structural misassignments for even molecules as complex as cryptospirolepine. While methods that rely on anisotropic nuclear magnetic resonance (NMR) methods can also be used to offer a powerful orthogonal means of structure elucidation and verification, the present computational study should be feasible in most chemistry departments with access to sophisticated computational facilities. From the overall correlations calculated against experimental ¹H and ¹³C NMR chemical shifts in the series of thirteen Cryptolepis alkaloids, it follows that, generally, they provide a very high level of correlation. The corrected mean absolute error (CMAE) is found to be at the level of 0.13 and 1.5 ppm for, proton and carbon chemical shifts, respectively, which is only about 2 and 1% of their ranges. Based on the performed calculations, some spectral reassignments are suggested, and a number of missing (unknown) experimental chemical shifts are predicted.