A quantitative approach to polar organic reactivity

A method is presented which allows one to predict toxic effects which are triggered by the formation of covalent bonds between electron-deficient (electrophilic) compounds and biological electron-rich (nucleophilic) targets, as proteins or nucleic acids. It is based on our comprehensive nucleophilicity and electrophilicity scales, which we constructed as an aid for the planning of organic syntheses. For the construction of these scales, rate constants for the reactions of benzhydrylium ions (aryl2CH(+)) and structurally related quinone methides with nucleophiles have been measured and correlated by the equation lg k(20 °C) = sN(E + N), which yields absolute rate constants k (L mol(-1) s(-1)) from one parameter for electrophiles (the electrophilicity E) and two for nucleophiles (the nucleophilicity parameter N and the susceptibility sN). A freely accessible database (http://www.cup.uni-muenchen.de/oc/mayr/DBintro.html) is described, which presently comprises data for 1000 nucleophiles and 260 electrophiles and provides links to the original literature reports. The kinetic scales are complemented by a thermodynamic counterpart, which enables one to calculate association constants K (L mol(-1)) of electrophiles with nucleophiles from the empirical Lewis acidity parameters LA and Lewis basicity parameters LB by the equation lg K (20°C) = LA + LB.