H. M. KALCKAR 



How, then, is the removal of hydrogen ions (which must pre- 

 cede the electron removal) accomplished in biological systems at neu- 

 tral reactions? In trying to answer this question one may refer to a 

 fact which has been particularly emphasized by Pauling (9), namely, 

 that the high dissociation constant of carboxyl hydroxyl is mainly attrib- 

 uted to the higher mesomeric stability of the symmetric carboxylate 



ion, — C , as compared with the asymmetric carboxyl group, 



\o- 



— C . Suppose that an alcohol group bound to a specific enzyme 



\0H 

 were able to undergo intermolecular mesomerism with two or more 

 other alcohol groups, provided that it existed in the ionized form. This 

 would imply that such an alcohol group showed greater tendency to 

 release hydrogen ions when forming a substrate-enzyme complex with 

 the specific dehydrogenase than when in free solution. If one imagines 

 two alcohol molecules brought together in close vicinity by the specific 

 enzyme protein, one sees immediately that the dissociation of a hydro- 

 gen ion from one of the alcohol groups would give rise to the formation 

 of a hydrogen bond (formula XI). Since a hydrogen bond is a struc- 

 tural feature with a certain degree of stability, it means that the 

 addition product would have a fair chance of existence. Now the way is 

 paved for the first oxidation step, i. e., the removal of one electron from 

 one of the alcohol groups. If the other alcohol group simultaneously 

 gives up its hydrogen ion, an ideal opportunity for forming a three- 

 electron bond has been created (formula XII). The free radical, 

 although possessing a certain degree of stability due to the existence of 

 the mesomeric three-electron bond, is nevertheless a labile configura- 

 tion, which tends to expel a second hydrogen ion and electron. 

 H ^ H H H 



K:'6:'6::^=z ^ :0:'C:R ^r.n - ^ on-R 



H H H H 



: H+ : ; H+ : +e 



XI XII 



Waelsch (11) has suggested the possibility that the alcohol group 

 of the substrate may form a mesomeric complex with certain hydroxy 



238 



