<html> <head> </head> <body> Molcode QSAR for abiotic degradation in air (NO3 radical reaction of volatile organic compounds) </body> </html> <html> <head> </head> <body> </body> </html> <html> <head> </head> <body> 17.02.2010 </body> </html> <html> <head> </head> <body> </body> </html> <html> <head> </head> <body> </body> </html> <html> <head> </head> <body> 16.02.2010 </body> </html> <html> <head> </head> <body> Software is proprietary but model training and test sets provided. Algorithm provided. </body> </html> <html> <head> </head> <body> None to date </body> </html> <html> <head> </head> <body> Not applicable - environmental fate parameter </body> </html> <html> <head> </head> <body> Rate constant for NO3 radical reaction (degradation). The dominant chemical process of chemicals in the gasphase is their reaction with OH radicals, NO3 radicals and ozone. </body> </html> <html> <head> </head> <body> cm3 s-1 molecule-1 </body> </html> <html> <head> </head> <body> -logK (NO3) (original rate constants were transformed into log scale and multiplied by -1 to reduce data range and obtain positive values) </body> </html> <html> <head> </head> <body> The selected data are for reactions at 25 °C and 1 atm. The gas-phase reaction rate constants of NO3 radical and organic chemicals have been directly measured. </body> </html> <html> <head> </head> <body> Original experimental data were collected from ref 1. Statistics (for -logK(NO3): max value: 17.5 min value: 9.41 standard deviation: 2.20 skewness: -0.305 </body> </html> <html> <head> </head> <body> QSAR </body> </html> <html> <head> </head> <body> -logK (NO3) = -7.355 +9.660E-002*HASA-2 (AM1) (all) -2.070*HOMO energy (AM1) +12.005*Relative number of aromatic bonds </body> </html> <html> <head> </head> <body> Initial pool of ~1000 descriptors for each structure calculated. Stepwise descriptor selection was applied to reduce the pool based on a set of statistical selection rules. For one-parameter equations: Fisher criterion and R2 over threshold, variance and t-test value over threshold, intercorrelation with another descriptor not over threshold). Two parameter correlations developed from previously reduced pool, the statistical selection applied: intercorrelation coefficient below threshold, significant correlation with endpoint, in terms of correlation coefficient and t-test. Stepwise trial of additional descriptors not significantly correlated to any already in the model. See refs 2-3. </body> </html> <html> <head> </head> <body> 1D, 2D, and 3D theoretical calculations. Descriptors derived from mol files. Quantum chemical descriptors from AM1 calculations. Model developed by using multilinear regression using ordinary least squares. </body> </html> <html> <head> </head> <body> 27.67 ( 83 chemicals / 3 descriptors) </body> </html> <html> <head> </head> <body> Applicability domain based on training set: a) by chemical identity: Diverse set of Volatile Organic Compounds (alphatic and aromatic hydrocarbons, alcohols, amines, halogenated compounds, etc) b) by descriptor value range: The model is suitable for compounds that have the descriptors in the following minimal-maximal range: HASA-2 (AM1) (all): 0 - 24.9 HOMO energy (AM1): -11.6 - -8.02 Relative number of aromatic bonds: 0 - 0.400 </body> </html> <html> <head> </head> <body> By chemical identity - compounds must be similar to traing set compounds in terms of functionality. By descriptor value range: range of descriptor values similar to training set with ±30% confidence. Descriptor values must fall between maximal and minimal descriptor values of training set ±30%. </body> </html> <html> <head> </head> <body> See 5.1 </body> </html> <html> <head> </head> <body> 83 data points: 0 negative values; 83 positive values Original source dataset of 114 compounds split into training and testing sets - sorted by experimental value, each 4th structure subjected to testing set, others to training set </body> </html> <html> <head> </head> <body> No more than specified in 3.5 </body> </html> <html> <head> </head> <body> R2 = 0.914 (Correlation coefficient) s2 = 0.661 (Standard error of the estimate) F = 256.8 (Fisher function) </body> </html> <html> <head> </head> <body> R2CV = 0.905 </body> </html> <html> <head> </head> <body> R2CVMO = 0.904 ((80% : 20% , training : testing) </body> </html> <html> <head> </head> <body> </body> </html> <html> <head> </head> <body> </body> </html> <html> <head> </head> <body> ABC analysis (2:1 training : prediction) on sorted (in increased order of endpoint value) data divided into 3 subsets (A;B;C). Training set formed with 2/3 of the compounds (set A+B, A+C, B+C) and validation set consisted of 1/3 of the compounds (C, B, A). average R2 (fitting) = 0.916; average R2 (prediction) = 0.899 </body> </html> <html> <head> </head> <body> 27 data points: 0 negative values; 27 positive values </body> </html> <html> <head> </head> <body> Original source dataset split into testing and training. From the original source data, sorted by endpoint value, each 4th was subjected to the test set. </body> </html> <html> <head> </head> <body> R2 = 0.908 (Coefficient of determination) </body> </html> <html> <head> </head> <body> All are in range of applicability domain: HASA-2 (AM1) (all): 0 - 11.1 HOMO energy (AM1): -11.8 - -8.75 Relative number of aromatic bonds: 0 - 0.286 </body> </html> <html> <head> </head> <body> The validation coefficient of determination (R2) is close to the coefficients derived by internal validation (R2CV and R2CVMO). </body> </html> <html> <head> </head> <body> The descriptor "HASA-2 (AM1) (all)" represents the capability of hydrogen acceptor bonding relatively to the total surface area. "HOMO energy (AM1)" is an indicator of the nucleophilicity of the molecule - reactive molecules have relatively higher HOMO energy. "Relative number of aromatic bonds" is represening a (relative) count of aromaticity which differentiates these compounds from aliphatic ones. The descriptors in the model are presenting important molecular properties related to H-abstraction. For most compounds, H-abstraction is known to be the predominant pathway for reactions with NO3 radicals. As HOMO energy has a negative sign in the equation, the larger the energy the faster the reaction. Strong hydrogen bond acceptor type compounds as well as aromatic compounds have smaller rate constants, as indicated by the negative signs in the equation. </body> </html> <html> <head> </head> <body> A posteriori mechanistic interpretation, consistent with published scientific interpretations of experiments. </body> </html> <html> <head> </head> <body> Most published studies and models (see ref 4-5) indicate that the HOMO energy is the most important factor detrmining the rate constants for gas phase reactions with NO3 radicals. Other descriptors depend on the training set used but usually add corrections for structural variations (e.g. aromatics) or heteroatoms. </body> </html> <html> <head> </head> <body> </body> </html> Molcode, abiotic degradation in air, NO3 radical reaction, volatile organic compounds