Lipoic acid ring strain

The special properties of lipoic acid arise from the ring strain experienced by oxidized lipoic acid. The closed ring form is approximately 20 kj higher in energy than the open-chain form, and this results in a strong negative reduction potential of about —0.30 V. The oxidized form readily oxidizes cyanides to isothiocyanates and sulfhydryl groups to mixed disulfides. 

The most striking chemical property of lipoic acid is the presence of ring strain of 17-25 kj mol 1 in the cyclic disulfide. Because of this, thiol groups and cyanide ions react readily with oxidized lipoic acid to give mixed disulfides (Eq. 15-32a) and isothiocyanates (Eq. 15-32b), respectively. 

Another result of the ring strain is that the reduction potential E° (pH 7, 25°C), is -0.30 V, almost the same as that of reduced NAD (-0.32V). Thus, reoxidation of reduced lipoic acid amide by NAD+ is thermodynamically feasible. Yet another property attributed to the ring strain in lipoic acid is the presence of an absorption maximum at 333 nm. 

Dithiolanes are very reactive because of ring strain. 1,2-Dithiolane polymerizes at room temperature. Nevertheless, about 20 1,2-dithiolanes are found in nature. Among them, a-lipoic acid (6,8-disul-fanyloctanoic acid) is of great biological importance. The crystalline compound was isolated for the first time in 1951 from the liver of cattle. 

Torsion about the dihedral angle of the sulfur-sulfur bond can also affect the reactivity. If the sulfur-sulfur bond is placed in a strained ring system, the reactivity increases. Calvin and Barltrop (1952) and Barltrop et al. (1954) have suggested that lipoic acid with its strained suKur-sulfur bond... 

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