On the Use of 1H and 13C 1D NMR Spectra as QSPR Descriptors

Recently, 1D NMR and IR spectra have been proposed as descriptors containing 3D information. And, as such, said to be suitable for making QSAR and QSPR models where 3D molecular geometries matter, for example, in binding affinities. This paper presents a study on the predictive power of 1D NMR spectra-based QSPR models using simulated proton and carbon 1D NMR spectra. It shows that the spectra-based models are outperformed by models based on theoretical molecular descriptors and that spectra-based models are not easy to interpret. We therefore conclude that the use of such NMR spectra offers no added value.

[1]  R. Cramer,et al.  Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. , 1988, Journal of the American Chemical Society.

[2]  C. Steinbeck,et al.  Recent developments of the chemistry development kit (CDK) - an open-source java library for chemo- and bioinformatics. , 2006, Current pharmaceutical design.

[3]  Johann Gasteiger,et al.  Prediction of Aqueous Solubility of Organic Compounds Based on a 3D Structure Representation , 2003, J. Chem. Inf. Comput. Sci..

[4]  Vimukta Sharma,et al.  Novel estimation of lipophilicity using 13C NMR chemical shifts as molecular descriptor. , 2005, Bioorganic & medicinal chemistry letters.

[5]  Dan A. Buzatu,et al.  Comparative Structural Connectivity Spectra Analysis (CoSCoSA) Models of Steroid Binding to the Corticosteroid Binding Globulin , 2002, J. Chem. Inf. Comput. Sci..

[6]  Jon G. Wilkes,et al.  Use of 13C NMR Spectrometric Data To Produce a Predictive Model of Estrogen Receptor Binding Activity , 2001, J. Chem. Inf. Comput. Sci..

[7]  A. Tropsha,et al.  Beware of q2! , 2002, Journal of molecular graphics & modelling.

[8]  Laura K. Schnackenberg,et al.  Whole-Molecule Calculation of Log P Based on Molar Volume, Hydrogen Bonds, and Simulated 13C NMR Spectra , 2005, J. Chem. Inf. Model..

[9]  Alessandro Giuliani,et al.  Infrared Spectra Information and Their Correlation with QSAR Descriptors , 1999, J. Chem. Inf. Comput. Sci..

[10]  Nello Cristianini,et al.  An introduction to Support Vector Machines , 2000 .

[11]  Roberto Todeschini,et al.  Handbook of Molecular Descriptors , 2002 .

[12]  Peter C. Jurs,et al.  Prediction of the Normal Boiling Points of Organic Compounds from Molecular Structures with a Computational Neural Network Model. , 2000 .

[13]  Egon L. Willighagen,et al.  The Chemistry Development Kit (CDK): An Open-Source Java Library for Chemo-and Bioinformatics , 2003, J. Chem. Inf. Comput. Sci..

[14]  David J. Livingstone.  The Characterization of Chemical Structures Using Molecular Properties. A Survey , 2000 .

[15]  B. Kowalski,et al.  Partial least-squares regression: a tutorial , 1986 .

[16]  Alessandro Giuliani,et al.  Infrared Spectra as Chemical Descriptors for QSAR Models , 2001, J. Chem. Inf. Comput. Sci..

[17]  Jon G. Wilkes,et al.  Developing 13C NMR quantitative spectrometric data-activity relationship (QSDAR) models of steroid binding to the corticosteroid binding globulin , 2001, J. Comput. Aided Mol. Des..

[18]  Jon G. Wilkes,et al.  Models of Polychlorinated Dibenzodioxins, Dibenzofurans, and Biphenyls Binding Affinity to the Aryl Hydrocarbon Receptor Developed Using 13C NMR Data , 2001, J. Chem. Inf. Comput. Sci..

[19]  J C Lindon,et al.  Nuclear magnetic resonance (NMR) and quantitative structure–activity relationship (QSAR) studies on the transacylation reactivity of model 1β-O-acyl glucuronides. II: QSAR modelling of the reaction using both computational and experimental NMR parameters , 2004, Xenobiotica; the fate of foreign compounds in biological systems.

[20]  A. Tropsha,et al.  Beware of q 2 , 2002 .

[21]  Arja Asikainen,et al.  Spectroscopic QSAR Methods and Self-Organizing Molecular Field Analysis for Relating Molecular Structure and Estrogenic Activity , 2003, J. Chem. Inf. Comput. Sci..

[22]  Elaine Holmes,et al.  Prediction of anti-plasmodial activity of Artemisia annua extracts: application of 1H NMR spectroscopy and chemometrics. , 2004, Journal of pharmaceutical and biomedical analysis.

[23]  Dan A. Buzatu,et al.  Combining NMR spectral and structural data to form models of polychlorinated dibenzodioxins, dibenzofurans, and biphenyls binding to the AhR , 2002, J. Comput. Aided Mol. Des..

[24]  Peter C. Jurs,et al.  Prediction of the Normal Boiling Points of Organic Compounds from Molecular Structures with a Computational Neural Network Model , 1999, J. Chem. Inf. Comput. Sci..

[25]  M. Cronin,et al.  Pitfalls in QSAR , 2003 .

[26]  Trevor Hastie,et al.  The Elements of Statistical Learning , 2001 .