An overview of Helium-3 NMR: Recent developments and applications.

The present review is focused on experimental and theoretical methods together with applications of helium NMR in chemistry and biochemistry. It comprises two main sections, the first dealing with standardization and instrumentation for 3He NMR spectroscopy and the second dealing with its practical applications, mainly those in general and organic chemistry with a special emphasis on the rapidly developing and exciting area of fullerenes encapsulating helium atoms. Several general applications of 3He NMR spectroscopy in physical chemistry and biomedicine are also briefly discussed.

17 O nuclear magnetic resonance: Recent advances and applications.

The present review is focused on the most recent achievements in the application of liquid phase 17 O nuclear magnetic resonance (NMR) to inorganic, organic, and biochemical molecules focusing on their structure, conformations, and (bio)chemical behavior. The review is composed of four basic parts, namely, (1) simple molecules; (2) water and hydrogen bonding; (3) metal oxides, clusters, and complexes; and (4) biological molecules. Experimental 17 O NMR chemical shifts are thoroughly tabulated. They span a range of as much as almost 650 ppm (from -35.6 to +610.0 ppm) for inorganic and organic molecules, whereas this range is much wider for biological species being of about 1350 ppm (from -12 to +1332 ppm), and in the case of hemoproteins and heme-model compounds, isotropic chemical shifts of up to 2500 ppm were observed. The general prospects and caveats in the modern development of the liquid phase 17 O NMR in chemistry and biochemistry are critically discussed and briefly outlined in view of their future applications.

Structural applications of the isotropic liquid-phase deuterium nuclear magnetic resonance.

Present review is focused on recent experimental and computational advances of the liquid-phase deuterium nuclear magnetic resonance (NMR). Nowadays, isotropic liquid-phase 2 H NMR became one of the most important instruments for the identification and certification of organic compounds of biological interest together with natural products and biosynthetic molecules. Of special interest are the 2 H NMR biochemical and microbiological applications. This review consists of three main parts. The first part deals with the practical applications of 2 H NMR to organic compounds of biological interest. The second part is connected with natural products and biosynthetic molecules, while the third part exemplifies and outlines 2 H NMR advances in biochemistry and microbiology.

Stereochemical Study of the Super Large Tetrakis Alkaloid Alasmontamine A by Means of an Advanced Computational NMR.

1H and 13C NMR chemical shifts of the tetrakis monoterpene indole alkaloid alasmontamine A, with a molecular formula of C84H91N8O12, have been calculated within the DFT framework. Six minimum energy conformers of this alkaloid were identified, and three key configurations that contribute to its NMR shielding constants were established. Several ambiguities in the reported assignment of the NMR chemical shifts of alasmontamine A have been resolved.

Computational studies of [1]benzothieno[2,3-c]naphtho[1,2-f]quinoline.

Early NMR studies of several heterohelicenes containing an annular nitrogen atom and a thiophene ring in their structure suggested the possibility of the lengthening of the carbon-carbon bonds in the interior of the helical turn of the molecule based on the progressive more shielded nature of 13 C resonances toward the center of the helical turn. Computational chemistry capabilities when those NMR studies were performed were primitive in comparison to what is now possible. We now report the optimized geometry and a comparison of the calculated versus observed 1 H and 13 C NMR chemical shift assignments for [1]benzothieno[2,3-c]naphtho[1,2-f]quinoline that confirms these suspicions.

Computational 19 F NMR of trifluoromethyl derivatives of alkenes, pyrimidines, and indenes.

The 19 F NMR chemical shifts of 13 trifluoromethyl derivatives of alkenes, pyrimidines, and indenes were calculated at the DFT level using the BhandHLYP, BHandH, PBE, PBE0, O3LYP, B3LYP, KT2, and KT3 functionals in combination with the pcS-2 basis set. Best result was documented for the BHandHLYP functional: The mean absolute error (MAE) of 0.66 ppm for the scaled values was achieved for the range of about 20 ppm. Solvent, vibrational, and relativistic corrections were found to be rather small, especially when taken in combination, generally demonstrating a slight decrease in the difference between calculated and experimental fluorine chemical shifts. As a measure of the practical importance of these compounds, one should recall that the growing number of life science products that contain trifluoromethyl groups provides a continuing driving force for the development of an effective methodology that enables both regio- and stereoselective introduction of trifluoromethyl groups into both aliphatic and aromatic systems.

Tritium NMR: A compilation of data and a practical guide.

The present review is focused on experimental methods and structural applications of tritium NMR. It consists of five parts covering accordingly, introduction, brief overview, early (based on the papers appearing before 2000), more recent (based on the papers appeared in the interim of 2000 to 2015), and recent (based on the papers that appeared after 2015) reports. A special interest in this review is focused on practical aspects of tritium NMR spectroscopy, which is thoroughly illustrated by its numerous applications in chemistry and biochemistry.

Recent advances in the liquid-phase 6,7 Li nuclear magnetic resonance.

The present review is focused on experimental methods and structural applications, including computational aspects, of classical lithium liquid-phase nuclear magnetic resonance (NMR). It consists of four parts covering accordingly a brief overview, early experimental reports (papers of up to about 2015) and more recent (papers appearing in the interim of about 2015 until 2022) results, together with very few but highly prospective computational results.

Computational NMR of carbohydrates: 1. Glucopyranoses.

A high-level calculation of 1 H and 13 C NMR chemical shifts of α- and ß-d-glucopyranoses is carried out at the DFT level with taking into account their conformational composition to reveal the most effective computational protocols. A number of dedicated DFT functionals in combination with Jensen's pcS-n (n = 0-4) family of basis sets were applied to evaluate the most reliable combination. It was found that BHandHLYP/pcS-2 provided the most accurate and reliable computational protocol. Based on the performed calculations, the established computational protocol is generally recommended for the calculation of 1 H and 13 C NMR chemical shifts of a wide series of carbohydrates.

The Development of Pharmacophore Models for the Search of New Natural Inhibitors of SARS-CoV-2 Spike RBD-ACE2 Binding Interface.

To date, some succeeding variants of SARS-CoV-2 have become more contagious. This virus is known to enter human cells by binding the receptor-binding domain (RBD) of spike protein with the angiotensin-converting enzyme 2 (ACE2), the latter being a membrane protein that regulates the renin-angiotensin system. Since the host cell receptor plays a critical role in viral entry, inhibition of the RBD-ACE2 complex is a promising strategy for preventing COVID-19 infection. In the present communication, we propose and utilize an approach based on the generation of a complex of pharmacophore models and subsequent Induced Fit Docking (IFD) to identify potential inhibitors of the main binding sites of the Omicron SARS-CoV-2 RBD(S1)-ACE2 complex (PDB ID: 7T9L) among a number of natural products of various types and origins. Several natural compounds have been found to provide a high affinity for the receptor of interest. It is expected that the present results will stimulate further research aimed at the development of specialized drugs against this virus.

Four-Component Relativistic Calculations of NMR Shielding Constants of the Transition Metal Complexes-Part 2: Nitrogen-Coordinated Complexes of Cobalt.

Both four-component relativistic and nonrelativistic computations within the GIAO-DFT(PBE0) formalism have been carried out for 15N and 59Co NMR shielding constants and chemical shifts of a number of the nitrogen-coordinated complexes of cobalt. It was found that the total values of the calculated nitrogen chemical shifts of considered cobalt complexes span over a range of more than 580 ppm, varying from -452 to +136 ppm. At that, the relativistic corrections to nitrogen shielding constants and chemical shifts were demonstrated to be substantial, changing accordingly from ca. -19 to +74 ppm and from -68 to +25 ppm. Solvent effects on 15N shielding constants and chemical shifts were shown to have contributions no less important than the relativistic effects, namely from -35 to +63 ppm and from -74 to +23 ppm, respectively. Cobalt shielding constants and chemical shifts were found to vary in the ranges of, accordingly, -20,157 to -11,373 ppm and from +3781 to +13,811. The relativistic effects are of major importance in the cobalt shielding constants, resulting in about 4% for the shielding-type contributions, while solvent corrections to cobalt shielding constants appeared to be of less significance, providing corrections of about 1.4% to the gas phase values.

Computational 199 Hg NMR.

Theoretical background and fundamental results dealing with the computation of mercury chemical shifts and spin-spin coupling constants are reviewed with a special emphasis on their stereochemical behavior and applications.

Stereochemical dependence of substituent γ-effects in the 19 F NMR shielding constants.

The substituent α-, ß-, and γ-effects of the elements of the second and third periods on 19 F NMR chemical shifts are evaluated including the establishment of stereochemical dependence of γ-effect, the latter particularly important in stereochemical studies of fluorine-containing compounds. Benchmark calculations performed for a series of 32 simple inorganic fluorine-containing molecules demonstrated a markedly good correlation between calculated and experimental fluorine chemical shifts characterized by a mean absolute error of 22.5 ppm in the range of about 900 ppm, which corresponds to a 2.5% error in the percentage terms.

Fluorine spin-spin coupling constants of pentafluorobenzene revisited at the ab initio correlated levels.

All possible spin-spin coupling constants, 19 F-19 F, 19 F-13 C, and 19 F-1 H, of pentafluorobenzene were calculated at five different levels of theory, HF, DFT, SOPPA (CCSD), CCSD, and the SOPPA (CCSD)-based composite scheme with taking into account solvent, vibrational, relativistic, and correlation corrections. Most corrections were next to negligible for the long-range couplings but quite essential for the one-bond carbon-fluorine coupling constants. Hartree-Fock calculations were found to be entirely unreliable, while DFT results were comparable in accuracy with the data obtained using the wave function-based methods.

Combined Computational NMR and Molecular Docking Scrutiny of Potential Natural SARS-CoV-2 Mpro Inhibitors.

In continuation of the search for potential drugs that inhibit the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in this work, a combined approach based on the modeling of NMR chemical shifts and molecular docking is suggested to identify the possible suppressors of the main protease of this virus among a number of natural products of diverse nature. Primarily, with the aid of an artificial neural network, the problem of the reliable determination of the stereochemical structure of a number of studied compounds was solved. Complementary to the main goal of this study, theoretical modeling of NMR spectral parameters made it feasible to perform a number of signal reassignments together with introducing some missing NMR data. Finally, molecular docking formalism was applied to the analysis of several natural products that could be chosen as prospective candidates for the role of potential inhibitors of the main protease. The results of this study are believed to assist in further research aimed at the development of specific drugs based on the natural products against COVID-19.

Computational 1 H and 13 C NMR in structural and stereochemical studies.

Present review outlines the advances and perspectives of computational 1 H and 13 C NMR applied to the stereochemical studies of inorganic, organic, and bioorganic compounds, involving in particular natural products, carbohydrates, and carbonium ions. The first part of the review briefly outlines theoretical background of the modern computational methods applied to the calculation of chemical shifts and spin-spin coupling constants at the DFT and the non-empirical levels. The second part of the review deals with the achievements of the computational 1 H and 13 C NMR in the stereochemical investigation of a variety of inorganic, organic, and bioorganic compounds, providing in an abridged form the material partly discussed by the author in a series of parent reviews. Major attention is focused herewith on the publications of the recent years, which were not reviewed elsewhere.

Computational NMR of natural products: On the way to super large molecules exemplified with alasmontamine A.

1 H and 13 C nuclear magnetic resonance (NMR) chemical shifts of a tetrakis monoterpene indole alkaloid alasmontamine A with a molecular formula of C84 H91 N8 O12 have been calculated at the PBE0/pcSseg-2//pcseg-2 level of theory on M06-2X/aug-cc-pVDZ geometry. In the course of the preliminary conformational search, six true minimum energy conformers were identified that can contribute to the actual conformation of this huge alkaloid. Calculated chemical shifts generally demonstrated a good agreement with available experimental data characterized with a corrected mean absolute error of 0.10 ppm for the range of about 7 ppm for protons and 1.1 ppm for the range of about 160 ppm for carbons.

Four-component relativistic calculations of NMR shielding constants of the transition metal complexes. Part 1: Pentaammines of cobalt, rhodium, and iridium.

The nonrelativistic and four-component fully relativistic calculations of 1 H, 15 N, 59 Co, 103 Rh, and 193 Ir shielding constants of pentaammineaquacomplexes of cobalt(III), rhodium(III), and iridium(III) were carried out at the density functional theory (DFT) level of theory. The noticeable deshielding relativistic corrections were observed for nitrogen shielding constants (chemical shifts), whereas those corrections were found to be negligible for protons. For the transition metals cobalt, rhodium, and iridium, relativistic corrections to their nuclear magnetic resonance (NMR) shielding constants were found to be rather small for cobalt and rhodium (some 5-10%), whereas they are essentially larger for iridium (up to 70%).

Computational NMR of charged systems.

This review covers NMR computational aspects of charged systems-carbocations, heterocations, and heteroanions, which were extensively studied in a number of laboratories worldwide, first of all, at the Loker Hydrocarbon Research Institute in California directed for several decades by a distinguished scientist, the Nobel laureate George Andrew Olah. The first part of the review briefly outlines computational background of the modern theoretical methods applied to the calculation of chemical shifts and spin-spin coupling constants at the DFT and the non-empirical levels. The second part of the review deals with the historical results, advances, and perspectives of the computational NMR of classical carbocations like methyl cation, CH3+ , and protonated methane, CH5+ , together with their numerous homologs and derivatives. The third and the forth parts of this survey are focused on the NMR computational aspects of accordingly, heterocations and heteroanions, the organic and inorganic ions with a charge localized mainly on heteroatoms like boron, oxygen, nitrogen, and heavier elements.

Simple and Versatile Scheme for the Stereochemical Identification of Natural Products and Diverse Organic Compounds with Multiple Asymmetric Centers.

A simple and versatile scheme of stereochemical identification of the stereochemically rich natural products and organic compounds with multiple asymmetric centers is proposed based on a detailed parsing of calculated 1H and 13C NMR chemical shifts in combination with their DP4+ analysis, as exemplified for three natural products: sungucine, physalin D, and anabsinthin. Performed benchmark calculations of the considered diastereomers provided very good agreement with their known experimental stereochemical structures.