Structure–reactivity relationship in Diels–Alder reactions obtained using the condensed reaction graph approach

By the structural representation of a chemical reaction in the form of a condensed graph a model allowing the prediction of rate constants (logk) of Diels–Alder reactions performed in different solvents and at different temperatures is constructed for the first time. The model demonstrates good agreement between the predicted and experimental logk values: the mean squared error is less than 0.75 log units. Erroneous predictions correspond to reactions in which reagents contain rarely occurring structural fragments. The model is available for users at https://cimm.kpfu.ru/predictor/.

[1]  Gilles Marcou,et al.  An Evolutionary Optimizer of libsvm Models , 2014 .

[2]  Igor I. Baskin,et al.  Development of “structure-property” models in nucleophilic substitution reactions involving azides , 2014, Journal of Structural Chemistry.

[3]  Alexander J. Smola,et al.  Support Vector Regression Machines , 1996, NIPS.

[4]  Joseph M. Fox,et al.  Tetrazine ligation: fast bioconjugation based on inverse-electron-demand Diels-Alder reactivity. , 2008, Journal of the American Chemical Society.

[5]  Alexandre Varnek,et al.  Substructural fragments: an universal language to encode reactions, molecular and supramolecular structures , 2005, J. Comput. Aided Mol. Des..

[6]  C. Bertozzi,et al.  From Mechanism to Mouse: A Tale of Two Bioorthogonal Reactions , 2011, Accounts of chemical research.

[7]  Timur I. Madzhidov,et al.  Structure–reactivity relationship in bimolecular elimination reactions based on the condensed graph of a reaction , 2015, Journal of Structural Chemistry.

[8]  Javier Catalán,et al.  A Generalized Solvent Acidity Scale: The Solvatochromism of o-tert-Butylstilbazolium Betaine Dye and Its Homomorph o,o′-Di-tert-butylstilbazolium Betaine Dye† , 1997 .

[9]  Dragos Horvath,et al.  Models for Identification of Erroneous Atom-to-Atom Mapping of Reactions Performed by Automated Algorithms , 2012, J. Chem. Inf. Model..

[10]  Dragos Horvath,et al.  Expert System for Predicting Reaction Conditions: The Michael Reaction Case , 2015, J. Chem. Inf. Model..

[11]  H. Kolb,et al.  The growing impact of click chemistry on drug discovery. , 2003, Drug discovery today.

[12]  Igor I. Baskin,et al.  Prediction of the preferable mechanism of nucleophilic substitution at saturated carbon atom and prognosis of SN1 rate constants by means of QSPR , 2011 .

[13]  V. A. Palyulin,et al.  Prediction of rate constants of SN2 reactions by the multicomponent QSPR method , 2011 .

[14]  Gilles Marcou,et al.  Mining Chemical Reactions Using Neighborhood Behavior and Condensed Graphs of Reactions Approaches , 2012, J. Chem. Inf. Model..

[15]  Igor I. Baskin,et al.  Structure-reactivity relationships in terms of the condensed graphs of reactions , 2014, Russian Journal of Organic Chemistry.

[16]  Nicolas Lachiche,et al.  A Representation to Apply Usual Data Mining Techniques to Chemical reactions - Illustration on the Rate Constant of SN2 reactions in water , 2011, Int. J. Artif. Intell. Tools.

[17]  Javier Catalán,et al.  Progress towards a generalized solvent polarity scale: The solvatochromism of 2‐(dimethylamino)‐7‐nitrofluorene and its homomorph 2‐fluoro‐7‐nitrofluorene , 1995 .

[18]  M. G. Finn,et al.  Click Chemistry: Diverse Chemical Function from a Few Good Reactions. , 2001, Angewandte Chemie.

[19]  R. Taft,et al.  The solvatochromic comparison method. I. The .beta.-scale of solvent hydrogen-bond acceptor (HBA) basicities , 1976 .

[20]  Igor I. Baskin,et al.  Quantitative structure–conditions–property relationship studies. Neural network modelling of the acid hydrolysis of esters , 2002 .

[21]  Markus Hartenfeller,et al.  A Collection of Robust Organic Synthesis Reactions for In Silico Molecule Design , 2011, J. Chem. Inf. Model..

[22]  J. Pezacki,et al.  Strain-promoted cycloadditions involving nitrones and alkynes--rapid tunable reactions for bioorthogonal labeling. , 2014, Current opinion in chemical biology.

[23]  Igor V. Tetko,et al.  Critical Assessment of QSAR Models of Environmental Toxicity against Tetrahymena pyriformis: Focusing on Applicability Domain and Overfitting by Variable Selection , 2008, J. Chem. Inf. Model..

[24]  L. Pan,et al.  Recent advances in bioorthogonal reactions for site-specific protein labeling and engineering , 2015 .

[25]  Javier Catalán,et al.  A Generalized Solvent Basicity Scale: The Solvatochromism of 5‐Nitroindoline and Its Homomorph 1‐Methyl‐5‐nitroindoline , 1996 .

[26]  R. Taft,et al.  The solvatochromic comparison method. 2. The .alpha.-scale of solvent hydrogen-bond donor (HBD) acidities , 1976 .