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Advances in Computer Assisted Structure Elucidation (CASE)
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Advances in Computer Assisted Structure Elucidation (CASE)

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Computational and Theoretical Chemistry".

Deadline for manuscript submissions: closed (1 October 2023) | Viewed by 15728

Special Issue Editors

Prof. Dr. Mikhail E. Elyashberg

E-Mail Website
Guest Editor
Advanced Chemistry Development, Moscow, Russia
Interests: NMR spectroscopy; IR-Raman spectroscopy; MS spectrometry; cheminformatics; structure elucidation; CASE; expert systems; stereochemistry; analytical chemistry; standardless quantitative spectral analysis
Dr. Jean-Marc Nuzillard

E-Mail Website
Guest Editor
Institute de Chimie Moleculaire de Reims (ICMR-UMR 7312 CNRS), Universite de Reims Champagne Ardenne, Reims, France
Interests: CASE and NMR spectroscopy

Special Issue Information

Dear Colleagues,

Computer-assisted structure elucidation (CASE) as a new scientific direction emerged at the intersection of organic chemistry, molecular spectroscopy, and discrete mathematics back in the 1960s. The approach was aimed for structure elucidation of small organic molecules. Now, CASE-based expert systems (ESs) have matured, and there are several ESs (commercial and of open access) available for identification of new organic compounds and first isolated natural products. The input information for these programs includes the molecular formula and 1D and 2D NMR spectra of unknown products. The structures of a great number of complex natural products have been elucidated and/or revised using such programs. Further ES development is based on synergistic interaction between CASE, new NMR experiments, and methods of computational chemistry which are continuously being improved.

The purpose of this Special Issue is to familiarize the chemical community with advances in CASE development, as well as to show examples of ES application to the structure elucidation of complex organic molecules such as natural products. We encourage and welcome manuscripts (research articles, reviews, and tutorials) devoted to the following topics for CASE:

  • NMR experiments;
  • NMR spectrum processing;
  • Prediction of chemical shifts and coupling constants;
  • CASE applications for structure elucidation, dereplication, and verification;
  • Machine learning;
  • 3D model determination;
  • CASE in chemical education.

Prof. Dr. Mikhail E. Elyashberg
Dr. Jean-Marc Nuzillard
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CASE
  • expert system
  • structure elucidation
  • structure dereplication
  • NMR experiments
  • chemical shift prediction
  • NMR spectra processing

Published Papers (6 papers)

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Research

10 pages, 2764 KiB  
Article
Four New Diterpenoids from the South China Sea Soft Coral Sinularia nanolobata and DFT-Based Structure Elucidation
by Dan-Dan Yu, Lin-Mao Ke, Jiao Liu, Song-Wei Li, Ming-Zhi Su, Li-Gong Yao, Hui Luo and Yue-Wei Guo
Molecules 2023, 28(19), 6892; https://doi.org/10.3390/molecules28196892 - 30 Sep 2023
Viewed by 817
Abstract
Three new cembranoids (1–3) and a new casbanoid (4), along with three known analogues (5–7), have been isolated from the soft coral Sinularia nanolobata collected off Ximao Island. The structures, including the absolute [...] Read more.
Three new cembranoids (1–3) and a new casbanoid (4), along with three known analogues (5–7), have been isolated from the soft coral Sinularia nanolobata collected off Ximao Island. The structures, including the absolute configurations of new compounds, were established using extensive spectroscopic data analysis, time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations, and the comparison with spectroscopic data of known compounds. In the in vitro bioassay, compounds 1 and 5 exhibited moderate cytotoxic activities against human erythroleukemia (HEL) cell lines, with IC50 values of 37.1 and 42.4 μM, respectively. Full article
(This article belongs to the Special Issue Advances in Computer Assisted Structure Elucidation (CASE))
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33 pages, 13706 KiB  
Article
Enhancing Efficiency of Natural Product Structure Revision: Leveraging CASE and DFT over Total Synthesis
by Mikhail Elyashberg, Sriram Tyagarajan, Mihir Mandal and Alexei V. Buevich
Molecules 2023, 28(9), 3796; https://doi.org/10.3390/molecules28093796 - 28 Apr 2023
Cited by 2 | Viewed by 1751
Abstract
Natural products remain one of the major sources of coveted, biologically active compounds. Each isolated compound undergoes biological testing, and its structure is usually established using a set of spectroscopic techniques (NMR, MS, UV-IR, ECD, VCD, etc.). However, the number of erroneously determined [...] Read more.
Natural products remain one of the major sources of coveted, biologically active compounds. Each isolated compound undergoes biological testing, and its structure is usually established using a set of spectroscopic techniques (NMR, MS, UV-IR, ECD, VCD, etc.). However, the number of erroneously determined structures remains noticeable. Structure revisions are very costly, as they usually require extensive use of spectroscopic data, computational chemistry, and total synthesis. The cost is particularly high when a biologically active compound is resynthesized and the product is inactive because its structure is wrong and remains unknown. In this paper, we propose using Computer-Assisted Structure Elucidation (CASE) and Density Functional Theory (DFT) methods as tools for preventive verification of the originally proposed structure, and elucidation of the correct structure if the original structure is deemed to be incorrect. We examined twelve real cases in which structure revisions of natural products were performed using total synthesis, and we showed that in each of these cases, time-consuming total synthesis could have been avoided if CASE and DFT had been applied. In all described cases, the correct structures were established within minutes of using the originally published NMR and MS data, which were sometimes incomplete or had typos. Full article
(This article belongs to the Special Issue Advances in Computer Assisted Structure Elucidation (CASE))
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28 pages, 3655 KiB  
Article
DELTA50: A Highly Accurate Database of Experimental 1H and 13C NMR Chemical Shifts Applied to DFT Benchmarking
by Ryan D. Cohen, Jared S. Wood, Yu-Hong Lam, Alexei V. Buevich, Edward C. Sherer, Mikhail Reibarkh, R. Thomas Williamson and Gary E. Martin
Molecules 2023, 28(6), 2449; https://doi.org/10.3390/molecules28062449 - 7 Mar 2023
Cited by 6 | Viewed by 5877
Abstract
Density functional theory (DFT) benchmark studies of 1H and 13C NMR chemical shifts often yield differing conclusions, likely due to non-optimal test molecules and non-standardized data acquisition. To address this issue, we carefully selected and measured 1H and 13C [...] Read more.
Density functional theory (DFT) benchmark studies of 1H and 13C NMR chemical shifts often yield differing conclusions, likely due to non-optimal test molecules and non-standardized data acquisition. To address this issue, we carefully selected and measured 1H and 13C NMR chemical shifts for 50 structurally diverse small organic molecules containing atoms from only the first two rows of the periodic table. Our NMR dataset, DELTA50, was used to calculate linear scaling factors and to evaluate the accuracy of 73 density functionals, 40 basis sets, 3 solvent models, and 3 gauge-referencing schemes. The best performing DFT methodologies for 1H and 13C NMR chemical shift predictions were WP04/6-311++G(2d,p) and ωB97X-D/def2-SVP, respectively, when combined with the polarizable continuum solvent model (PCM) and gauge-independent atomic orbital (GIAO) method. Geometries should be optimized at the B3LYP-D3/6-311G(d,p) level including the PCM solvent model for the best accuracy. Predictions of 20 organic compounds and natural products from a separate probe set had root-mean-square deviations (RMSD) of 0.07 to 0.19 for 1H and 0.5 to 2.9 for 13C. Maximum deviations were less than 0.5 and 6.5 ppm for 1H and 13C, respectively. Full article
(This article belongs to the Special Issue Advances in Computer Assisted Structure Elucidation (CASE))
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18 pages, 4141 KiB  
Article
NMR-Based Metabolite Profiling and the Application of STOCSY toward the Quality and Authentication Assessment of European EVOOs
by Stavros Beteinakis, Anastasia Papachristodoulou, Peter Kolb, Paul Rösch, Stephan Schwarzinger, Emmanuel Mikros and Maria Halabalaki
Molecules 2023, 28(4), 1738; https://doi.org/10.3390/molecules28041738 - 11 Feb 2023
Cited by 5 | Viewed by 1611
Abstract
Extra virgin olive oil (EVOO) possesses a high-value rank in the food industry, thus making it a common target for adulteration. Hence, several methods have been essentially made available over the years. However, the issue of authentication remains unresolved with national and food [...] Read more.
Extra virgin olive oil (EVOO) possesses a high-value rank in the food industry, thus making it a common target for adulteration. Hence, several methods have been essentially made available over the years. However, the issue of authentication remains unresolved with national and food safety organizations globally struggling to regulate and control its market. Over the course of this study, the aim was to determine the origin of EVOOs suggesting a high-throughput, state-of-the-art method that could be easily adopted. A rapid, NMR-based untargeted metabolite profiling method was applied and complemented by multivariate analysis (MVA) and statistical total correlation spectroscopy (STOCSY). STOCSY is a valuable statistical tool contributing to the biomarker identification process and was employed for the first time in EVOO analysis. Market samples from three Mediterranean countries of Spain, Italy, and Greece, blended samples from these countries, as well as monocultivar samples from Greece were analyzed. The NMR spectra were collected, with the help of chemometrics acting as “fingerprints” leading to the discovery of certain chemical classes and single biomarkers that were related to the classification of the samples into groups based on their origin. Full article
(This article belongs to the Special Issue Advances in Computer Assisted Structure Elucidation (CASE))
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11 pages, 1363 KiB  
Article
Ominoxanthone—The First Xanthone Linearly Fused to a γ-Lactone from Cortinarius ominosus Bidaud Basidiomata. CASE- and DFT-Based Structure Elucidation
by Alice Trac, Célia Issaad, Mehdi A. Beniddir, Jean-Michel Bellanger, Jean-François Gallard, Alexei V. Buevich, Mikhail E. Elyashberg and Pierre Le Pogam
Molecules 2023, 28(4), 1557; https://doi.org/10.3390/molecules28041557 - 6 Feb 2023
Viewed by 1487
Abstract
The UHPLC–HRMS analysis of Cortinarius ominosus basidiomata extract revealed that this mushroom accumulated elevated yields of an unreported specialized metabolite. The molecular formula of this unknown compound, C17H10O8, indicated that a challenging structure elucidation lay ahead, owing [...] Read more.
The UHPLC–HRMS analysis of Cortinarius ominosus basidiomata extract revealed that this mushroom accumulated elevated yields of an unreported specialized metabolite. The molecular formula of this unknown compound, C17H10O8, indicated that a challenging structure elucidation lay ahead, owing to its critically low H/C atom ratio. The structure of this new isolate, namely ominoxanthone (1), could not be solved from the interpretation of the usual set of 1D/2D NMR data that conveyed too limited information to afford a single, unambiguous structure. To remedy this, a Computer-Assisted Structure Elucidation (CASE) workflow was used to rank the different possible structure candidates consistent with our scarce spectroscopic data. DFT-based chemical shift calculations on a limited set of top-ranked structures further ascertained the determined structure for ominoxanthone. Although the determined scaffold of ominoxanthone is unprecedented as a natural product, a plausible biosynthetic scenario involving a precursor known from cortinariaceous sources and classical biogenetic reactions could be proposed. Full article
(This article belongs to the Special Issue Advances in Computer Assisted Structure Elucidation (CASE))
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27 pages, 16915 KiB  
Article
Sherlock—A Free and Open-Source System for the Computer-Assisted Structure Elucidation of Organic Compounds from NMR Data
by Michael Wenk, Jean-Marc Nuzillard and Christoph Steinbeck
Molecules 2023, 28(3), 1448; https://doi.org/10.3390/molecules28031448 - 2 Feb 2023
Cited by 6 | Viewed by 2909
Abstract
The structure elucidation of small organic molecules (<1500 Dalton) through 1D and 2D nuclear magnetic resonance (NMR) data analysis is a potentially challenging, combinatorial problem. This publication presents Sherlock, a free and open-source Computer-Assisted Structure Elucidation (CASE) software where the user controls the [...] Read more.
The structure elucidation of small organic molecules (<1500 Dalton) through 1D and 2D nuclear magnetic resonance (NMR) data analysis is a potentially challenging, combinatorial problem. This publication presents Sherlock, a free and open-source Computer-Assisted Structure Elucidation (CASE) software where the user controls the chain of elementary operations through a versatile graphical user interface, including spectral peak picking, addition of automatically or user-defined structure constraints, structure generation, ranking and display of the solutions. A set of forty-five compounds was selected in order to illustrate the new possibilities offered to organic chemists by Sherlock for improving the reliability and traceability of structure elucidation results. Full article
(This article belongs to the Special Issue Advances in Computer Assisted Structure Elucidation (CASE))
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