Substituent effects on reactivity of 3-cinnamoylcoumarins with thiols of biological interest

The Michael addition reactions of the biothiols cysteine, homocysteine, cysteinyl-glycine, gamma -glutamyl-cysteine and glutathione with 3-cinnamoylcoumarin derivatives (ChC1-ChC4) in aqueous solution (30 degree C, ionic strength 0.2 M KCl) were followed fluorimetrically and evaluated kinetically. The study was completed with a theoretical analysis based on the inverse of the Fukui potential (1/ nu sub(f) (r)), which is proposed for the first time as a local softness descriptor. Thus, considering both experimental results and theoretical analysis, the following conclusions can be drawn: (i) the reactivity of the tested probes towards Michael addition increases in the para-substitution sequence: H < OEt < SMe < Br < NO sub(2), and is not correlated with the sigma sub(P) values of the substituents; (ii) in turn, the descriptor proposed here as local softness (1/ nu sub(f) (r)) appears as a promising reactivity index that is able to explain the higher k sub(N) values found for both electron-withdrawing and electron-donating groups; (iii) the nucleophilic reactivity of the biothiols employed increases in the sequence Cys-Gly < Hcy < GSH < Cys < gamma -Glu-Cys; and also finally (iv) we have demonstrated that these probes can be used for fluorimetric thiol determination in SH-SY5Y cells.