THE SOURCE FOR THE DIFFERENCE BETWEEN SULFHYDRYL AND HYDROXYL ANIONS IN THEIR NUCLEOPHILIC-ADDITION REACTION TO A CARBONYL GROUP - A DFT APPROACH

Ab initio calculations show that sulfhydryl anion has a significantly lower potential than the hydroxide anion for stabilizing the products of its attack on carbonyl moieties - the tetrahedral complexes (TC). I n this paper we analyze the factors that contribute to this phenomenon . Quantum mechanical MO ab initio calculations were used for studies o f two reaction series, one for the attack of hydroxyl and one for the attack of sulfhydryl anion on different carbonyl compounds and their a nalogs. All of the anionic TCs formed by HS. are characterized by high er charge transfer, but are significantly less stable than the relevan t TC of HO.. To explain the phenomenon we used a simple qualitative mo del based on Density Functional Theory (DFT). The crucial role of the occupied valence MOs is demonstrated in the process of electronegativi ty equalization between the donor and acceptor fragments in the final TC product. The sulfhydryl anion has significantly lower potential to stabilize TC products in comparison with the hydroxide anion because o f the larger extent of electron back-donation from the electrophile's HOMO(A) to the nucleophile's LUMO(D). This electron back-donation thus reduces the stability of the anionic TC in the case of HS. and may ac count for the calculational results. Applications of this work to enzy me reactions help in understanding the differences in mechanisms of se rine and cysteine proteases and may be used to guide the design of inh ibitors for these enzymes. In perspective, the back-donation phenomeno n discussed here may be applied to the study of electron transfer proc esses involving oxidation-reduction enzymes.