Coenzyme A forms high-energy thioester bonds with acyl groups. The energy-rich nature of thioesters, as compared with ordinary esters, is related primarily to resonance stabilization (Figure 14.9). Most esters have two resonance forms (Figure 14.9). Stabilization involves -electron overlap, giving partial double-bond character to the C-O link.

In thioesters, the larger atomic size of S (as compared with O) reduces the -electron overlap between C and S, so that the C=S structure does not contribute significantly to resonance stabilization. As a result, the thioester is destabilized relative to an ester, thus releasing more energy on hydrolysis.

The lack of double-bond character in the C-S bond of acyl-CoAs makes this bond weaker than the corresponding C-O bond in ordinary esters, thus making the thioalkoxide ion, a good leaving group in nucleophilic displacement reactions. Consequently, the acyl group is readily transferred to other metabolites, as occurs in the first reaction of the citric acid cycle (Figure 14.3).