PREDICTION OF RATE CONSTANTS FOR METHYL RADICAL ADDITIONS ON VINYL TYPE ALKENES USING PARTIAL LEAST SQUARES

K. Héberger

Institute of Chemistry, Chemical Research Center,
Hungarian Academy of Sciences
H-1525 Budapest, P.O. Box 17, Hungary

Rate constants are good candidates for prediction, however, it is not known, which reactant should be chosen for structure description? Methyl radical was fixed, then, either the alkene or the adduct radical (product) is suitable for structure description.

The reaction can be given as:

CH3. + CH2=CXY ® R-CH2-C.XY

{where CH2=CXY is the vinyl type alkene and R-CH2-C.XY is the adduct radical;
X, Y are substituents: H, Ph, Me, CN, Cl, COOMe, OCOMe, OMe, CHO, etc.}

Structure entry and modeling

Initial 3D modeling of alkenes and adduct radicals was performed using Hyperchem (Hypercube Inc. Waterloo, ON). 3D structure was refined by AM1 (semiempirical MO program). Descriptor generation and reduction Predictor variables (descriptors) were generated using the DRAGON program package (Milano Chemometrics).

Objective (non-supervised) variable selection: Pair-wise correlations were investigated and one of any two descriptors with R > 0.99999 were removed.

From among 200 descriptors 189 (case A) and 181 (case B) remained.

 Principal aim is to build a linear PLS model for prediction purposes. Many descriptors are easy to interpret. We would like to know, which structural feature is responsible for the magnitude of the rate constants.

A set of 20 rate constants was characterized using 189 descriptors:

constitutional {(23) e.g. number of various atoms and bonds, Mw, etc.},

topological {(68) connectivity indices, information content, path counts, Wiener index, etc.},

Weighted Holistic Invariant Molecular (WHIM) descriptors,

empirical descriptors (3).

Conclusions