Sulfhydryl reactants

Further examination of the results indicated that by invocation of Pearson s Hard-Soft Acid-Base (HSAB) theory (57), the results are consistent with experimental observation. According to Pearson s theory, which has been generalized to include nucleophiles (bases) and electrophiles (acids), interactions between hard reactants are proposed to be dependent on coulombic attraction. The combination of soft reactants, however, is thought to be due to overlap of the lowest unoccupied molecular orbital (LUMO) of the electrophile and the highest occupied molecular orbital (HOMO) of the nucleophile, the so-called frontier molecular orbitals. It was found that, compared to all other positions in the quinone methide, the alpha carbon had the greatest LUMO electron density. It appears, therefore, that the frontier molecular orbital interactions are overriding the unfavorable coulombic conditions. This interpretation also supports the preferential reaction of the sulfhydryl ion over the hydroxide ion in kraft pulping. In comparison to the hydroxide ion, the sulfhydryl is relatively soft, and in Pearson s theory, soft reactants will bond preferentially to soft reactants, while hard acids will favorably combine with hard bases. Since the alpha position is the softest in the entire molecule, as evidenced by the LUMO density, the softer sulfhydryl ion would be more likely to attack this position than the hydroxide. 

Additional examples of type d (Scheme 5.1) bifunctional reactants are provided by the alkaline-earth metal ion complexes of lariat ethers 8-10, bearing a sulfhydryl side arm, instead ofthe phenolic hydroxyl of a calixcrown [23,24]. Here the acyl-receiving and acyl-releasing unit, like in papain and ficin, is a sulfhydryl group. 

Let us consider the mechanism of glyceraldehyde 3-phosphate dehydrogenase in detail (Figure 16.8). In step 1, the aldehyde substrate reacts with the sulfhydryl group of cysteine 149 on the enzyme to form a hemithioacetal. Step 2 is the transfer of a hydride ion to a molecule of NAD + that is tightly bound to the enzyme and is adjacent to the cysteine residue. This reaction is favored by the deprotonation of the hemithioacetal by histidine 176. The products of this reaction are the reduced coenzyme NADH and a thioester intermediate. This thioester intermediate has a free energy close to that of the reactants. In step 3, orthophosphate attacks the thioester to form 1,3-BPG and free the cysteine residue. This displacement occurs only after the NADH formed from the aldehyde oxidation has left the enzyme and been replaced by a second NAD+. The positive charge on the NAD+ may help polarize the thioester intermediate to facilitate the attack by orthophosphate. 

Actual compound formation also occurs between the dehydroascorhic acid and GSH reactants, though little attention has been paid to this condensation. Complexes of dehydroascorhic acid with one molecule of either GSH or thioglycolic acid were formed by Drake et al. (D19) in acetic acid solutions. Disappearance of iodine-titrable -SH groups and appearance of a new levorotatory material indicated the complex formation. This continued until an equilibrium was reached in about one hour at 0°C. At equilibrium more than half the dehydroascorhic acid was complexed. Remarkably little reduction of dehydroascorhic by the sulfhydryl compound occurred, since this reaction becomes significant only at neutral pH s. The complex is probably a thiosemiacetal, similar to... 

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