Predictive Models for Kinetic Parameters of Cycloaddition Reactions

Abstract

This paper reports SVR (Support Vector Regression) and GTM (Generative Topographic Mapping) modeling of three kinetic properties of cycloaddition reactions: rate constant (logk), activation energy (Ea) and pre-exponential factor (logA). A data set of 1849 reactions, comprising (4+2), (3+2) and (2+2) cycloadditions (CA) were studied in different solvents and at different temperatures. The reactions were encoded by the ISIDA fragment descriptors generated for Condensed Graph of Reaction (CGR). For a given reaction, a CGR condenses structures of all the reactants and products into one single molecular graph, described both by conventional chemical bonds and "dynamical" bonds characterizing chemical transformations. Different scenarios of logk assessment were exploited: direct modeling, application of the Arrhenius equation and temperature-scaled GTM landscapes. The logk models with optimal cross-validated statistics (Q =0.78-0.94 RMSE=0.45-0.86) have been challenged to predict rates for the external test set of 200 reactions, comprising both reactions that were not present in the training set, and training set transformations performed under different reaction conditions. The models are freely available on our web-server: http://cimm.kpfu.ru/models.

ReactionCode: a new versatile format for searching, analysis, classification, transform, and encoding/decoding of reactions

“…6 + 1 (is a center and bond broken) 7 9 8 + 1 (is a center and bond made) 9 10 6 + 4 (bond is both broken and its order changes) A 11 10 + 1 (is a center, bond broken and order changes) B 12 8 + 4 (bond is both made and its order changes) C 13 12 + 1 (is a center, bond made and order changes) D Table S7: Bond change status encoding -1 will be increased to 0 10 will be reduced to 4 11 will be reduced to 5 12 will be reduced to 8 13 will be reduced to 9…”

“…Stored in an SD File, it is mainly employed for machine learning applications, similarity search, and classification. [13,6] Unfortunately, this format cannot be employed as-is and all analysis methods using it are based on molecular graph coloration and molecular fragment generated from the CGR [19,6,17,9]. Next to the CGR format, three multi-layer formats considering the reaction center and the neighbor atoms have been developed by J.L.…”

ReactionCode: Format for Reaction Searching, Analysis, Classification, Transform, and Encoding/Decoding

“…6 + 1 (is a center and bond broken) 7 9 8 + 1 (is a center and bond made) 9 10 6 + 4 (bond is both broken and its order changes) A 11 10 + 1 (is a center, bond broken and order changes) B 12 8 + 4 (bond is both made and its order changes) C 13 12 + 1 (is a center, bond made and order changes) D Table S7: Bond change status encoding -1 will be increased to 0 10 will be reduced to 4 11 will be reduced to 5 12 will be reduced to 8 13 will be reduced to 9…”

ReactionCode: a new versatile format for searching, analysis, classification, transform, and encoding/decoding of reactions

“…The carbon atom with an atom code in orange has a higher priority because the oxygen atom in layer n+2 has a higher rank than the n+2 carbon atom (008 > 006). 19 G 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 H 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 I 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 J 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 K 81 82 83 84 85 86 87 88 89 90 91 92 93 6 + 1 (is a center and bond broken) 7 9 8 + 1 (is a center and bond made) 9 10 6 + 4 (bond is both broken and its order changes) A 11 10 + 1 (is a center, bond broken and order changes) B 12 8 + 4 (bond is both made and its order changes) C 13 12 + 1 (is a center, bond made and order changes) D Table S7: Bond change status encoding -1 will be increased to 0 10 will be reduced to 4 11 will be reduced to 5 12 will be reduced to 8 13 will be reduced to 9 23 Table S8: Atom symbol encoding…”

“…However, this format cannot be used directly for, e.g., string-based comparisons of reactions. Indeed, all analysis methods using it are based on molecular graph coloration and molecular fragment generated from the CGR [21,6,18,10]. Next to the CGR format, three multi-layer formats considering the reaction center and the neighbor atoms have been developed by J.L.…”