Tag Archives: Nuclear magnetic resonance

Our Contributions to the Literature Regarding Computer-Assisted Structure Elucidation

When writing a publication how many of us conduct complete literature searches? For those of us who do not have access to Scifinder how are we finding our literature? Probably through Google Scholar? When I write a paper I admit that some of my searches may be less than complete but I do try and stay informed in regards to what is going on in my domain. VERY occasionally I get feedback from reviewers pointing me to references that they feel I either ignored or was unaware of. Many times they are co-authored by the reviewer themselves…and it is pretty easy to figure out who the reviewers are ūüôā

Today I received an email in my inbox about the latest article in the Journal of Cheminformatics.¬†It is¬†OMG: Open Molecule Generator. The article is¬†here.¬†¬†The abstract opens with “Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, ¬†Open ¬†Molecule ¬†Generator ¬†(OMG), ¬†which ¬†for ¬†a ¬†given ¬†elemental ¬†composition produces ¬†all ¬†non-isomorphic ¬†chemical ¬†structures ¬†that ¬†match ¬†that ¬†elemental ¬†composition.”

Having been involved with Computer-Assisted Structure Elucidation for many years, having co-authored a book about it (here) and probably the definitive review article from the past 5 years (here) I would have assumed that our work would have been referenced. I was surprised to see that our work was not referenced while other CASE systems were. Articles we’ve issued over the past few years are below. I’ve gathered them here to point the authors to in case they want to reference any of them and missed them in the literatire search.

I am taking advantage of the fact that I can leave comments on the provisional manuscript¬†here¬†(what a great capability!!!) and will let them know about this list. it would be good to compare the performance of the OMG with the structure generator under ACD/Structure Elucidator sometime….


1) M.E. Elyashberg, K.A. Blinov and A.J. Williams, Computer-aided Molecular Structure Elucidation on the Basis of 1D and 2D NMR Spectra, Applied Magnetic Resonance, (May 2000)

2) K.A. Blinov, M.E. Elyashberg, S.G. Molodtsov, A.J. Williams and E.R. Martirosian, An Expert System for Automated Structure Elucidation Utilizing 1H-1H, 13C-1H, and 15N-1H 2D NMR correlations, Fresenius J. Anal. Chem., 369, 709 (2001)

3) G.E. Martin, C.E. Hadden, D.J. Russell, B.D. Kaluzny, J.E. Guido, W.K. Duholke, B.A. Stiemsma, T.J. Thamann, R.C. Crouch, K.A. Blinov, M.E. Elyashberg, E.R. Martirosian, S.G. Molodtsov, A.J. Williams, P.L. Schiff, Jr., Identification of Degradants of a Complex Alkaloid Using NMR Cryoprobe Technology and ACD/Structure Elucidator, J. Heterocyclic Chem. 39, 1241 (2002)

4) M.E. Elyashberg, K.A. Blinov, A.J. Williams, E.R. Martirosian, S.G. Molodtsov, Application of a New Expert System for the Structure Elucidation of Natural Products from the 1D and 2D NMR Data, J. Nat. Prod., 65, 693 (2002)

5) G . E. Martin, C .E. Hadden, D. J. Russell, B. D. Kaluzny, J. E. Guido, W. K. Duholke, B. A. Stiemsma, T. J. Thamann, R. C. Crouch, K. A. Blinov, M. E. Elyashberg, E. R. Martirosian, S. G. Molodotsov, A. J. Williams, and P. L. Schiff, Jr., Identification of Degradants of a Complex Alkaloid Using NMR Cryoprobe Technology and ACD/Structure Elucidator, J. Heterocyclic Chem., 39 1241-1250 (2002).

6) K. A. Blinov, D. Carlson, M. E. Elyashberg, G. E. Martin, E. R. Martirosian, S. Molodtsov, and A. J. Williams, Computer-Assisted Structure Elucidation of Natural Products with Limited 2D NMR Data: Applications of the StrucEluc System, Magn. Reson. Chem., 41, 359-372 (2003).

7) G. E. Martin, D. J. Russell, K. A. Blinov, M. E. Elyashberg and A. J. Williams, Applications and Advances in Cryogenic NMR Probes & Computer-Assisted Structure Elucidation. Ann. Magn. Reson., 2, 1-31 (2003)

8)¬†K. Blinov, M. Elyashberg, E. R. Martirosian, S. G. Molodtsov,¬†A. J. Williams, M. H. M. Sharaf, P. L. Schiff, Jr., R. C. Crouch, G. E. Martin, C. E. Hadden, and J. E. Guido, ‚ÄúQuindolinocryptotackieine: The Elucidation of a Novel Indoloquinoline Alkaloid Structure through the Use of Computer-Assisted Structure Elucidation and 2D-NMR,‚Ä̬†Magn. Reson. Chem.,¬†41, 577-584 (2003).

9) M. E. Elyashberg, K. A. Blinov, E. R. Martirosian, S. G. Molodtsov,¬†A. J. Williams, and G. E. Martin, Automated Structure Elucidation ‚Äď The Benefits of a Symbiotic Relationship between the Spectroscopist and the Expert System,¬†J. Heterocyclic Chem.,¬†40, 1017-1029 (2003).

10) M. E. Elyashberg, K. A. Blinov, A. J. Williams, S. G. Molodtsov, G. E. Martin, and E. R. Martirosian, Structure Elucidator: A Versatile Expert System for Molecular Structure Elucidation from 1D and 2D NMR Data and Molecular Fragments, J. Chem. Inf. Comput. Sci. 44, 771-792 (2004).

11) S. G. Molodtsov, M. E. Elyashberg, K. A. Blinov, A. J. Williams, E. E. Martirosian, G. E. Martin, and B. Lefebvre. Structure Elucidation from 2D NMR Spectra Using the StrucEluc Expert System: Detection and Removal of Contradictions in the Data. J. Chem. Inf. Comp. Sci., 44, 1737-1751 (2004)

12) G. J. Sharman, I. C. Jones, M. P. Parnell, M. C. Willis, M. F. Mahon, D. V. Carlson, A. J. Williams, M. E. Elyashberg, K. A. Blinov, S. G. Molodtsov. Automated structure elucidation of two products in a reaction of an a,b-unsaturated pyruvate. Magn. Reson. Chem. 42, 567 (2004)

13) Y. D. Smurnyy, M. E. Elyashberg, K. A. Blinov,  B. A. Lefebvre, G. E. Martin, and A. J. Williams, Computer-Aided Determination of Relative Stereochemistry and 3D Models of Complex Organic Molecules from 2D NMR Spectra, Tetrahedron, 61, 9980-9989 (2005).

14) M. E. Elyashberg, K. A. Blinov, A. J. Williams, S. G. Molodtsov, and G. E. Martin, Are Deterministic Expert Systems for Computer-Assisted Structure Elucidation Obsolete? J. Chem. Inf. Model. 46, 1643-1656 (2006).

15) M. E. Elyashberg, K. A. Blinov, S. G. Molodtsov, A. J. Williams, and G. E. Martin, Fuzzy Structure Generation: An Efficient New Tool for Computer-Aided Structure Elucidation (CASE), J. Chem. Inf. Model., 47, 1053-1066 (2007). 10.1021/ci600528g

16) M. E. Elyashberg, A. J. Williams, and G. E. Martin. Computer-Assisted Structure Verification and Elucidation Tools In NMR-Based Structure Elucidation. Review article. Progress in NMR Spectroscopy (2007) 10.1016/j.pnmrs.2007.04.003 

17) Y. D. Smurnyy, K. A. Blinov, T. S. Churanova, M. E. Elyashberg, and A. J. Williams. Toward More Reliable 13C and 1H Chemical Shift Prediction: A Systematic Comparison of Neural-Network and Least-Squares Regression Based Approaches, J. Chem. Inf. Model.  48, 128-134, (2008)

18) M. E. Elyashberg,¬†A. J. Williams, D. C. Lankin, G. E. Martin, J. Porco, W. F. Reynolds, and C. Singleton, Applying Computer-Assisted Structure Elucidation Algorithms for the Purpose of Structure Validation ‚Äď Revising the NMR Assignments of Hexacyclinol,¬†J. Nat. Prod.,¬†71, 581-588 (2008).

19) M.E. Elyashberg, K.A. Blinov and A.J. Williams, A Systematic Approach for the Generation and Verification of Structural Hypotheses. Magn. Reson. Chem. 47, 371-389, (2009)

20) M. E. Elyashberg, A. J. Williams, and K.A. Blinov, The Application of Empirical Methods of 13C NMR Chemical Shift Prediction as a Filter for Determining Possible Relative Stereochemistry. Magn. Reson. Chem. 47, 333-341 (2009)

21) Y. D. Smurnyy, K. A. Blinov, T. S. Churanova, M. E. Elyashberg, and A. J. Williams. Development of a fast and accurate method of 13C NMR chemical shift prediction. Chemometrics and Intelligent Laboratory Systems, 97(1), 91-97, (2009)

22) M. E. Elyashberg, A. J. Williams and K. A. Blinov, Structural revisions of natural products by Computer Assisted Structure Elucidation (CASE) Systems, Nat. Prod. Rep., 2010, DOI: 10.1039/c002332a

23) Blind trials of computer-assisted structure elucidation software, Journal of cheminformatics 4 (1), 5, A Moser, ME Elyashberg, AJ Williams, KA Blinov, JC DiMartino

24) ¬†Elucidating ‚Äėundecipherable‚Äôchemical structures using computer‚Äźassisted structure elucidation approaches, Mikhail Elyashberg, Kirill Blinov, Sergey Molodtsov, Antony Williams,¬† ¬†Magnetic Resonance in Chemistry,¬†50(1), ¬†22‚Äď27, ¬†2012¬†DOI:¬†10.1002/mrc.2849

BOOK: Contemporary Computer Assisted Approaches to Molecular Structure Elucidation by Kirill Blinov, Mikhail Elyashberg and Antony J. Williams, Royal Society of Chemistry




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Our book published Contemporary Computer-Assisted Approaches to Molecular Structure Elucidation

Almost two years of work, a collaboration and friendship developed over many years of my tenure at Advanced Chemistry Development¬†(with Mikhail Elyashberg and Kirill Blinov),¬†a story about a decade of work to develop what we believe is the world’s premier Computer Assisted Structure Elucidation software, and multiple iterations later, our book is now at the printers.

Our Book COver

Our book is “Contemporary Computer-Assisted Approaches to Molecular Structure Elucidation” and is already listed on Amazon here.

“Computer Assisted Structure Elucidation (CASE) systems are powerful software applications capable of outperforming human data interpretation in terms of both speed and reliability. They combine software algorithms with tools for molecular structure elucidation using spectroscopic data. This book describes the principles on which CASE systems are based and concisely explains the algorithmic concepts behind the programs. It puts the technique in the context of its origins and describes the challenges that have been overcome to produce modern CASE systems. It uses the authors’ software development experience to discuss the present state-of-the-art and explains how the synergistic marrying of man and machine can provide superior results. Readers will gain a firm grounding in the fundamentals of CASE, an understanding of the challenges associated with algorithms, and an appreciation of the technologies underlying NMR prediction and structure verification. Scientists who have never used CASE systems before will find all the information necessary to master this new and very effective approach. Those with some experience will benefit from details on the latest developments.”

I willingly admit I’m glad it’s over…it feels great to have it finished, great to know its at the printers and good to know that we have likely written the definitive volume in this area for the time being. Now time to let my eyes recover before getting back to writing two more volumes about NMR applied to Natural Products, to be released next year all being well!



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Three Articles Published Online in One Week

During my career I have had the opportunity to work with some of the best scientists. During my >10 year tenure at ACD/Labs I directly managed the NMR product line for a number of years and was involved with the development of both the NMR prediction and Computer Assisted Structure Elucidation software. Over the past couple of years since leaving ACD/Labs I have continued to co-author articles with two of my ex-colleagues, and still friends, Kirill Blinov and Mikhail Elyashberg. Three of these articles were released in one work. If you are interested in NMR prediction and CASE systems you might find these articles interesting.

The application of empirical methods of 13C NMR chemical shift prediction as a filter for determining possible relative stereochemistry

Mikhail E. Elyashberg, Kirill A. Blinov, Antony J. Williams
Published Online: Feb 10 2009 8:59AM

DOI: 10.1002/mrc.2396

The reliable determination of stereocenters contained within chemical structures usually requires utilization of NMR data, chemical derivatization, molecular modeling, quantum-mechanical calculations and, if available, X-ray analysis. In this article we show that the number of stereoisomers which need to be thoroughly verified can be significantly reduced using NMR chemical shift calculations for the full stereoisomer set of possibilities using a fragmental approach based on HOSE codes. The applicability of this suggested method is illustrated using a series of complex chemical structures.

A systematic approach for the generation and verification of structural hypotheses

Mikhail Elyashberg, Kirill Blinov, Antony Williams
Published Online: Feb 5 2009 4:33AM

DOI: 10.1002/mrc.2397

In this article we show that the most rational manner by which to create structural hypotheses is by the application of an expert system capable of deducing all potential structures consistent with the experimental spectral data. Empirical or quantum-mechanical (QM) NMR prediction methods are compared. It is shown that when an expert system is used the best structure(s) can be distinguished using either incremental or neural net (NN)-based NMR prediction algorithms.

Development of a fast and accurate method of 13C NMR chemical shift prediction

Available online 11 February 2009
Kirill A. Blinov, Yegor D. Smurnyy, Tatiana S. Churanova, Mikhail E. Elyashberg, Antony J. Williams


In this article we describe a fast and accurate method of 13C NMR chemical shift prediction. The high speed of chemical shift calculation described is achieved using a simple structure description scheme based on individual atoms rather than functional groups. The systematic choice of an appropriate encoding scheme and the usage of partial least squares regression on a large training set has resulted in a robust and fast algorithm. The approach provides accuracy comparable with other well known approaches but demonstrates accelerated calculation speeds of up to a thousand times faster.

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Posted by on February 27, 2009 in Uncategorized


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