ACS Publications. Most Trusted. Most Cited. Most Read
My Activity

Figure 1Loading Img

Prediction of 1H NMR Coupling Constants with Associative Neural Networks Trained for Chemical Shifts

View Author Information
REQUIMTE and CQFB, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
Cite this: J. Chem. Inf. Model. 2007, 47, 6, 2089–2097
Publication Date (Web):October 23, 2007
Copyright © 2007 American Chemical Society

    Article Views





    Read OnlinePDF (127 KB)
    Supporting Info (3)»


    Abstract Image

    Fast accurate predictions of 1H NMR spectra of organic compounds play an important role in structure validation, automatic structure elucidation, or calibration of chemometric methods. The SPINUS program is a feed-forward neural network (FFNN) system developed over the last 8 years for the prediction of 1H NMR properties from the molecular structure. It was trained using a series of empirical proton descriptors. Ensembles of FFNNs were incorporated into Associative Neural Networks (ASNN), which correct a prediction on the basis of the observed errors for the k nearest neighbors in an additional memory. Here we show a procedure to estimate coupling constants with the ASNNs trained for chemical shiftsa second memory is linked consisting of coupled protons and their experimental coupling constants. An ASNN finds the pairs of coupled protons most similar to a query, and these are used to estimate coupling constants. Using a diverse general data set of 618 coupling constants, mean absolute errors of 0.6−0.8 Hz could be achieved in different experiments. A Web interface for 1H NMR full-spectrum prediction is available at


     Corresponding author phone:  (+351) 21 2948300; fax:  (+351) 21 2948550; e-mail:  [email protected].

    Supporting Information Available

    Jump To

    Initial pool of proton descriptors, selected descriptors used as input to the final neural networks, and spectroscopic data for compound 1. This material is available free of charge via the Internet at

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system:

    Cited By

    This article is cited by 56 publications.

    1. Sara E. Johnson, Taylor A. Bell, Joseph K. West. Cp2TiCl2: Synthesis, Characterization, Modeling and Catalysis. Journal of Chemical Education 2022, 99 (5) , 2121-2128.
    2. Qingyuan Zheng, Mick D. Mantle, Andrew J. Sederman, Timothy A. Baart, Constant M. Guédon, Lynn F. Gladden. In Situ Characterization of Mixtures of Linear and Branched Hydrocarbons Confined within Porous Media Using 2D DQF-COSY NMR Spectroscopy. Analytical Chemistry 2022, 94 (7) , 3135-3141.
    3. J. J. Wylde, G. N. Taylor, K. S. Sorbie, W. N. Samaniego, B. N. Allan. Oxazolidine-Based H2S and Mercaptan Scavengers: Uncovering the Myths. Energy & Fuels 2021, 35 (16) , 12993-13010.
    4. Renan P. O. Costa, Lucas F. Lucena, Lorena Mara A. Silva, Guilherme Julião Zocolo, Chonny Herrera-Acevedo, Luciana Scotti, Fernando Batista Da-Costa, Nikita Ionov, Vladimir Poroikov, Eugene N. Muratov, Marcus T. Scotti. The SistematX Web Portal of Natural Products: An Update. Journal of Chemical Information and Modeling 2021, 61 (6) , 2516-2522.
    5. Seokho Kang, Youngchun Kwon, Dongseon Lee, Youn-Suk Choi. Predictive Modeling of NMR Chemical Shifts without Using Atomic-Level Annotations. Journal of Chemical Information and Modeling 2020, 60 (8) , 3765-3769.
    6. Liliya Vugmeyster, Dan Fai Au, Dmitry Ostrovsky, Dillon Ray Lee Rickertsen, Scott M. Reed. Dynamics of Serine-8 Side-Chain in Amyloid-β Fibrils and Fluorenylmethyloxycarbonyl Serine Amino Acid, Investigated by Solid-State Deuteron NMR. The Journal of Physical Chemistry B 2020, 124 (23) , 4723-4731.
    7. Youngchun Kwon, Dongseon Lee, Youn-Suk Choi, Myeonginn Kang, Seokho Kang. Neural Message Passing for NMR Chemical Shift Prediction. Journal of Chemical Information and Modeling 2020, 60 (4) , 2024-2030.
    8. Linsen Li, Antony A. Okumu, Sheri Nolan, Anthony English, Sandip Vibhute, Yanran Lu, Katherine Hervert-Thomas, Justin T. Seffernick, Lovette Azap, Serena L. Cole, D. Shinabarger, Laura M. Koeth, Steffen Lindert, Jack C. Yalowich, Daniel J. Wozniak, Mark J. Mitton-Fry. 1,3-Dioxane-Linked Bacterial Topoisomerase Inhibitors with Enhanced Antibacterial Activity and Reduced hERG Inhibition. ACS Infectious Diseases 2019, 5 (7) , 1115-1128.
    9. Ian Ronningen, Michelle Miller, Youlin Xia, Devin G. Peterson. Identification and Validation of Sensory-Active Compounds from Data-Driven Research: A Flavoromics Approach. Journal of Agricultural and Food Chemistry 2018, 66 (10) , 2473-2479.
    10. Hesam Dashti, William M. Westler, Marco Tonelli, Jonathan R. Wedell, John L. Markley, and Hamid R. Eghbalnia . Spin System Modeling of Nuclear Magnetic Resonance Spectra for Applications in Metabolomics and Small Molecule Screening. Analytical Chemistry 2017, 89 (22) , 12201-12208.
    11. Leah Chibwe, Ivan A. Titaley, Eunha Hoh, and Staci L. Massey Simonich . Integrated Framework for Identifying Toxic Transformation Products in Complex Environmental Mixtures. Environmental Science & Technology Letters 2017, 4 (2) , 32-43.
    12. Philipp Rovedo, Stephan Knecht, Tim Bäumlisberger, Anna Lena Cremer, Simon B. Duckett, Ryan E. Mewis, Gary G. R. Green, Michael Burns, Peter J. Rayner, Dieter Leibfritz, Jan G. Korvink, Jürgen Hennig, Gerhard Pütz, Dominik von Elverfeldt, and Jan-Bernd Hövener . Molecular MRI in the Earth’s Magnetic Field Using Continuous Hyperpolarization of a Biomolecule in Water. The Journal of Physical Chemistry B 2016, 120 (25) , 5670-5677.
    13. Juuso Lehtivarjo, Matthias Niemitz, and Samuli-Petrus Korhonen . Universal J-Coupling Prediction. Journal of Chemical Information and Modeling 2014, 54 (3) , 810-817.
    14. Farkhondeh Ooshall, Saeed Jamehbozorgi, Reza Golbedaghi, Licínia L.G. Justino, Keyvan Mirzaei Feshalame, Mozhdeh Liyaghati-Delshad, Hossein Anaraki-Ardakani, Babak Jaleh, Rui Fausto. Synthesis, characterization and sensing mechanism of a novel fluorescence probe for Fe(III) in semi-aqueous solution based on a Schiff base hexadentate receptor. Inorganica Chimica Acta 2023, 558 , 121761.
    15. Per‐Anders Hansen, Silje Holm Sørensen, Nicolas Desbois, Claude P. Gros, Ola Nilsen. Perylenes, Porphyrins, and Other Large Dye Molecules for Molecular Layer Deposition. Advanced Materials Interfaces 2023, 3
    16. Sebastian Mihai, Denisa Elena Dumitrescu, Antoanela Popescu, Iuliana Stoicescu, Nadia Matroud, Ana-Mădălina Răducanu, Magdalena Mititelu. Semperivium Ruthenicum Koch Extract-Loaded Bio-Adhesive Formulation: A Novel Oral Antioxidant Delivery System for Oxidative Stress Reduction. Pharmaceuticals 2023, 16 (8) , 1110.
    17. Milan N. Chhaganlal, Jarl Underhaug, Svein A. Mjøs. Evaluation of NMR predictors for accuracy and ability to reveal trends in 1 H NMR spectra of fatty acids. Magnetic Resonance in Chemistry 2023, 61 (5) , 318-332.
    18. Davide Candoli, Ilija K. Nikolov, Lucas Z. Brito, Stephen Carr, Samuele Sanna, Vesna F. Mitrović. PULSEE: A software for the quantum simulation of an extensive set of magnetic resonance observables. Computer Physics Communications 2023, 284 , 108598.
    19. Guilherme Baumgarten, Morgan Madec, Duc-Vinh Nguyen, Lucas Werling, Joris Pascal, Chunchesh Malangi Gajendramurthy, Philippe Bertani, Jean-Pierre Djukic, Luc Hebrard. Assessment of the Impact of Static Field Inhomogeneity on the Performance of Miniaturized NMR Devices. IEEE Transactions on Magnetics 2023, 59 (2) , 1-6.
    20. Angus E. McMillan, Wilson W. X. Wu, Paula L. Nichols, Benedikt M. Wanner, Jeffrey W. Bode. A vending machine for drug-like molecules – automated synthesis of virtual screening hits. Chemical Science 2022, 13 (48) , 14292-14299.
    21. Eric Jonas, Stefan Kuhn, Nils Schlörer. Prediction of chemical shift in NMR: A review. Magnetic Resonance in Chemistry 2022, 60 (11) , 1021-1031.
    22. Markus Fischer, Benedikt Schwarze, Nikola Ristic, Holger A. Scheidt. Predicting 2H NMR acyl chain order parameters with graph neural networks. Computational Biology and Chemistry 2022, 100 , 107750.
    23. Reza Golbedaghi, Gulce Ogruc Ildiz, Reza Azadbakht, Rui Fausto. A new tetramine bis(2-naphthol)-derivative fluorescent chemosensor for aluminum ion (Al3+). Journal of Molecular Structure 2022, 1250 , 131775.
    24. Gulce Ogruc Ildiz, Andreia M. Tabanez, António Nunes, José P.L. Roque, Licínia L.G. Justino, M. Luísa Ramos, Rui Fausto. Molecular structure, spectroscopy and photochemistry of alprazolam. Journal of Molecular Structure 2022, 1247 , 131295.
    25. Reza Golbedaghi, Licínia L.G. Justino, Farkhondeh Ooshall, Saeeid Jamehbozorgi, Mehdi Abdolmaleki, Rui Fausto. A new Schiff base ligand as a fluorescence probe for Cu(II) detection in semi-aqueous solution: synthesis, characterization, fluorescence and mechanistic insight. Inorganica Chimica Acta 2021, 528 , 120623.
    26. Jia Fang, Linyuan Hu, Jianfeng Dong, Haowei Li, Hui Wang, Huafen Zhao, Yao Zhang, Min Liu. Predicting scalar coupling constants by graph angle-attention neural network. Scientific Reports 2021, 11 (1)
    27. Federico Riu, Luca Sanna, Roberta Ibba, Sandra Piras, Valentina Bordoni, M. Andrea Scorciapino, Michele Lai, Simona Sestito, Luigi Bagella, Antonio Carta. A comprehensive assessment of a new series of 5′,6′-difluorobenzotriazole-acrylonitrile derivatives as microtubule targeting agents (MTAs). European Journal of Medicinal Chemistry 2021, 222 , 113590.
    28. V. Nivetha, V. Ragavendran, V. Santhanam, B. Logeswaran, S. Kaleeswaran. Experimental and computational insights into the synthesis and characterization of a novel Schiff base ligand 2, 2′-[(1z, 14e)-2, 5, 8,11,14-pentaazapentadeca-1, 14-diene-diyl] diphenol. CSI Transactions on ICT 2021, 9 (1) , 71-81.
    29. Connor W. Coley, Natalie S. Eyke, Klavs F. Jensen. Autonome Entdeckung in den chemischen Wissenschaften, Teil I: Fortschritt. Angewandte Chemie 2020, 132 (51) , 23054-23091.
    30. Connor W. Coley, Natalie S. Eyke, Klavs F. Jensen. Autonomous Discovery in the Chemical Sciences Part I: Progress. Angewandte Chemie International Edition 2020, 59 (51) , 22858-22893.
    31. Will Gerrard, Lars A. Bratholm, Martin J. Packer, Adrian J. Mulholland, David R. Glowacki, Craig P. Butts. IMPRESSION – prediction of NMR parameters for 3-dimensional chemical structures using machine learning with near quantum chemical accuracy. Chemical Science 2020, 11 (2) , 508-515.
    32. Cameron Robertson, Robert A. Lucas, Adam Le Gresley. Scope and limitations of nuclear magnetic resonance techniques for characterisation and quantitation of vitamin D in complex mixtures. Skin Research and Technology 2020, 26 (1) , 112-120.
    33. Sébastien Campagne, Sarah Boigner, Simon Rüdisser, Ahmed Moursy, Laurent Gillioz, Anna Knörlein, Jonathan Hall, Hasane Ratni, Antoine Cléry, Frédéric H.-T. Allain. Structural basis of a small molecule targeting RNA for a specific splicing correction. Nature Chemical Biology 2019, 15 (12) , 1191-1198.
    34. Marilia Valli, Helena Mannochio Russo, Alan Cesar Pilon, Meri Emili Ferreira Pinto, Nathalia B. Dias, Rafael Teixeira Freire, Ian Castro-Gamboa, Vanderlan da Silva Bolzani. Computational methods for NMR and MS for structure elucidation I: software for basic NMR. Physical Sciences Reviews 2019, 4 (10)
    35. Elisa Ruhland, Caroline Bund, Hassiba Outilaft, Martial Piotto, Izzie‐Jacques Namer. A metabolic database for biomedical studies of biopsy specimens by high‐resolution magic angle spinning nuclear MR: a qualitative and quantitative tool. Magnetic Resonance in Medicine 2019, 82 (1) , 62-83.
    36. V. Ragavendran, S. Muthunatesan, V. Santhanam, Biljana Arsic. Synthesis and characterization of cinnamylidene acetone – A study on tuning of band gap by vibrational spectroscopic tools. Journal of Molecular Structure 2019, 1184 , 593-603.
    37. Vanthana Jeyasingh, Kumaresan Murugesan, Sudha Lakshminarayanan, Selvapalam Narayanan, Lakshminarayanan Piramuthu, I.V. Muthu Vijayan Enoch, Mosae Selvakumar Paulraj. Tuning the recognition properties of urea based receptor towards cyanide in aqueous medium: Effect of fluorine substitution on strength and selectivity of the anion receptor. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2019, 215 , 233-243.
    38. Andrei Filippov, Shubhankar Bhattacharyya, Faiz Ullah Shah. CO2 absorption and ion mobility in aqueous choline-based ionic liquids. Journal of Molecular Liquids 2019, 276 , 748-752.
    39. James B. McAlpine, Shao-Nong Chen, Andrei Kutateladze, John B. MacMillan, Giovanni Appendino, Andersson Barison, Mehdi A. Beniddir, Maique W. Biavatti, Stefan Bluml, Asmaa Boufridi, Mark S. Butler, Robert J. Capon, Young H. Choi, David Coppage, Phillip Crews, Michael T. Crimmins, Marie Csete, Pradeep Dewapriya, Joseph M. Egan, Mary J. Garson, Grégory Genta-Jouve, William H. Gerwick, Harald Gross, Mary Kay Harper, Precilia Hermanto, James M. Hook, Luke Hunter, Damien Jeannerat, Nai-Yun Ji, Tyler A. Johnson, David G. I. Kingston, Hiroyuki Koshino, Hsiau-Wei Lee, Guy Lewin, Jie Li, Roger G. Linington, Miaomiao Liu, Kerry L. McPhail, Tadeusz F. Molinski, Bradley S. Moore, Joo-Won Nam, Ram P. Neupane, Matthias Niemitz, Jean-Marc Nuzillard, Nicholas H. Oberlies, Fernanda M. M. Ocampos, Guohui Pan, Ronald J. Quinn, D. Sai Reddy, Jean-Hugues Renault, José Rivera-Chávez, Wolfgang Robien, Carla M. Saunders, Thomas J. Schmidt, Christoph Seger, Ben Shen, Christoph Steinbeck, Hermann Stuppner, Sonja Sturm, Orazio Taglialatela-Scafati, Dean J. Tantillo, Robert Verpoorte, Bin-Gui Wang, Craig M. Williams, Philip G. Williams, Julien Wist, Jian-Min Yue, Chen Zhang, Zhengren Xu, Charlotte Simmler, David C. Lankin, Jonathan Bisson, Guido F. Pauli. The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research. Natural Product Reports 2019, 36 (1) , 35-107.
    40. John L. Markley, Hesam Dashti, Jonathan R. Wedell, William M. Westler, Hamid R. Eghbalnia. Tools for Enhanced NMR-Based Metabolomics Analysis. 2019, 413-427.
    41. Joao Aires de Sousa. Structure–Spectrum Correlations and Computer‐Assisted Structure Elucidation. 2018, 133-163.
    42. Thomas Vosegaard. Fast simulations of multidimensional NMR spectra of proteins and peptides. Magnetic Resonance in Chemistry 2018, 56 (6) , 438-448.
    43. Luc Patiny, Michaël Zasso, Daniel Kostro, Andrés Bernal, Andrés M. Castillo, Alejandro Bolaños, Miguel A. Asencio, Norman Pellet, Matthew Todd, Nils Schloerer, Stefan Kuhn, Elaine Holmes, Sacha Javor, Julien Wist. The C6H6 NMR repository: An integral solution to control the flow of your data from the magnet to the public. Magnetic Resonance in Chemistry 2018, 56 (6) , 520-528.
    44. Luc Patiny, Alejandro Bolaños, Andrés M. Castillo, Andrés Bernal, Julien Wist. Teaching NMR spectra analysis with Magnetic Resonance in Chemistry 2018, 56 (6) , 529-534.
    45. Francisco-Jose Santiago-Medina, Antonio Pizzi, Maria Basso, Luc Delmotte, Alain Celzard. Polycondensation Resins by Flavonoid Tannins Reaction with Amines. Polymers 2017, 9 (12) , 37.
    46. Sumona Sarkar, Carli Moorehead, Katsiaryna Prudnikova, Caroline L. Schauer, Lynn S. Penn, Michele Marcolongo. Synthesis of macromolecular mimics of small leucine-rich proteoglycans with a poly(ethylene glycol) core and chondroitin sulphate bristles. Carbohydrate Polymers 2017, 166 , 338-347.
    47. Andrés M. Castillo, Andrés Bernal, Reiner Dieden, Luc Patiny, Julien Wist. “Ask Ernö”: a self-learning tool for assignment and prediction of nuclear magnetic resonance spectra. Journal of Cheminformatics 2016, 8 (1)
    48. Andrés M. Castillo, Andrés Bernal, Luc Patiny, Julien Wist. Fully automatic assignment of small molecules' NMR spectra without relying on chemical shift predictions. Magnetic Resonance in Chemistry 2015, 53 (8) , 603-611.
    49. Susana P. Gaudêncio, Florbela Pereira. Dereplication: racing to speed up the natural products discovery process. Natural Product Reports 2015, 32 (6) , 779-810.
    50. Yang Li. Structural revision of glabramycins B and C, antibiotics from the fungus Neosartorya glabra by DFT calculations of NMR chemical shifts and coupling constants. RSC Advances 2015, 5 (46) , 36858-36864.
    51. Andrés M Castillo, Andrés Bernal, Luc Patiny, Julien Wist. A new method for the comparison of 1H NMR predictors based on tree-similarity of spectra. Journal of Cheminformatics 2014, 6 (1)
    52. Andrés Mauricio Castillo, Lalita Uribe, Luc Patiny, Julien Wist. Fast and shift-insensitive similarity comparisons of NMR using a tree-representation of spectra. Chemometrics and Intelligent Laboratory Systems 2013, 127 , 1-6.
    53. Jarosław Jaźwiński. Theoretical aspects of indirect spin-spin couplings. 2012, 119-147.
    54. Andrés M. Castillo, Luc Patiny, Julien Wist. Fast and accurate algorithm for the simulation of NMR spectra of large spin systems. Journal of Magnetic Resonance 2011, 209 (2) , 123-130.
    55. Riina Aav, Tõnis Pehk, Sven Tamp, Toomas Tamm, Marina Kudrjašova, Omar Parve, Margus Lopp. Theoretical prediction and assignment of vicinal 1 H– 1 H coupling constants of diastereomeric 3‐alkoxy‐6,7‐epoxy‐2‐oxabicyclo[3.3.0]octanes. Magnetic Resonance in Chemistry 2011, 49 (2) , 76-82.
    56. Mark Edgar. Physical methods and techniques : NMR spectroscopy. Annual Reports Section "B" (Organic Chemistry) 2008, 104 , 312.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Your Mendeley pairing has expired. Please reconnect