LIPOIC ACID HYPOTHESIS 1699 



as photosynthesis is going on, thus preventing it from catalyzing the oxida- 

 tion process. (Another way to state the same fact is to say that the com- 

 petition between the photochemical and the thermal supply of H atoms to 

 the oxidizing catalyst is won by the former in practically every case.) 

 Specifically, Calvin (19522) suggested that this catalyst is lipoic acid (LA), 

 which is needed, in accord with scheme 36.1, as hydrogen acceptor for the 

 conversion of pyruvate into "active acetyl ' ' (acety 1-CoA) . This suggestion 

 formed part of a hypothesis ascribing to lipoid acid a key role in photosyn- 

 thesis (Calvin 1952^; Calvin and Barltrop 1952; Barltrop, Hayes and 

 Calvin 1954). This compound, whose presence in green plants and blue- 

 green algae has been demonstrated by Cayle, Holt, and Punnett (1953), 

 contains a ring of three carbon and two sulfur atoms. Calvin et al. sug- 

 gested that this ring is under such a strain that it can be opened, and lipoic 

 acid thus converted into a biradical (a dithiyl) by an energy quantum of 

 ~40 kcal (i. e., by a single photon of red light), although the standard value 

 for the energy of a S— S bond is (according to Pauling's tables) > 60 kcal. 



Calvin and Barltrop (1952) argued that the shift of the absorption peak 

 in the series: straight-chain disulfide - 4,8-thioctic acid - 5,8-thioctic acid 

 - 6,8-thioctic (lipoic) acid, from 250 to 330 mju, indicates that the dissocia- 

 tion energy of the ground state is decreased, from the open chain to the 

 five-membered ring, by someting like 10,000 cm.-^, or ~20 kcal. How- 

 ever, this estimate is based on the assumption of an approximately un- 

 changed energy of the excited state — while it seems more likely that the 

 latter changes even more strongly than the former. 



From stereochemical considerations, Barltrop, Hayes, and Calvin 

 (1954) estimated a strain of about 10 kcal/mole in the 5-membered ring. 



Postulating that the strain in the five-membered ring is sufficient to 

 reduce the S— S dissociation energy to below 40 kcal, Barltrop and Calvin 

 suggested that the photochemical formation of the dithiyl biradical: 



-S— 



-S— 

 is followed by a dark reaction with water: 



(36.14, <4 > ^_ 



/— S— /— SH 



(36.15) < + H2O 



V_s_ " \— SOH 



The addition product was assumed to dismute, liberating O2 (perhaps 

 with H2O2 as intermediate) : 



(36.16) 2 < > < + < I + H2O + V2O2 



\— SOH \— SH \— S 



