Thiamine Derivatives of Disulfide Type. VIII. The Exchange Reaction between Thiamine Propyl Disulfide and the Various Thiols

The exchange reactions between TPD and polyfunctional thiols such as glutathione, 2-aminoethylmercaptan, 2-hydroxyethylmercaptan and 2-carboxyethylmercaptan were examined under an anaerobic condition. The following conclusions were drawn from the results presented. From an analysis of the pH-rate profile of the reactions between TPD and thiols containing the amino group in a molecule, the reaction was revealed as the combination of the following three reactions through the pH range of 3 to 12, HB1SSPr + NH3+RS-→HB1S- + NH3+RSSPr B1SSPr + NH3+RS-→B1S- + NH3+RSSPr B1SSPr + NH2RS-→B1S- + NH2RSSPr where HB1SSPr is the protonated form of TPD, NH3+RS- is the protonated amino-thiol anion, HB1S- is the protonated thiamine and NH3+RSSPr is the protonated amino-alkyl propyl disulfide. On the other hand, in the reaction between TPD and thiol, 2-hydroxyethylmercaptan, the following two reaction equations were presented through the experimental pH range of 3.5 to 12.0. HB1SSPr + RS-→HB1S + RSSPr B1SSPr + RS-→B1S + RSSPr The second order rate constants of individual reactions were determined. The activation energies of these reactions obtained were about 10 kcal mole-1, and the values of activation entropies were 5 to 24 cal mole-1 deg-1. These second order rate constants were correlated with the pKa values of the thiol group with Bronsted equation, log k=αpKa + C, with a resultant very large α value. From this relationship, it may be concluded that these thiols are an extremely good nucleophile to the disulfide bond and especially to protonated TPD.