ROLE OF THE CENTRAL THIOL IN DETERMINING RATES OF THE THIOL-DISULFIDE INTERCHANGE REACTION

Ellman's reagent, 5,5ʹ-dithiobis(2-nitrobenzoic acid) (1, ESSE) in dilute aqueous solution, reacts with excess 3-mercaptopropanol to form HOCH2CH2CH2SSE followed by a slower second reaction giving the symmetrical disulfide and a second mole of ES-. In this study, we report the rates of reaction of a variety of aliphatic and aromatic thiol anions with HOCH2CH2CH2SSE which were measured by rapidly mixing the thiol with the mixed disulfide immediately after it was formed. The Br0nsted type plot for this reaction shows a βnuc of about 0.58 for either aromatic or aliphatic thiol anions. The aromatic thiol anions were more reactive for their basicity by a factor of about 6 than aliphatic thiols. Exactly the same behavior has been observed for ESSE and HOCH2CH2CH2SSE, indicating that the cause of the split structure reactivity correlation cannot be a favorable aryl-aryl interaction between attacking and central thiols. The previously proposed explanation based on hard-soft acid-base theory is therefore supported. Inductively withdrawing groups on the central thiol increase the rate with βCT≈ -0.3. The rates of reaction with ES as the central thiol are slower than predicted by extrapolation of data for aliphatic central thiols, probably because of the effect of the negative charge on ES. © 1979, American Chemical Society. All rights reserved.