IMIDAZOLE HYPOTHESIS 235 



They say : 



"If structure A alone represented the normal state of oxyhemoglobin the 

 acidity * of the NH group of the imidazole ring would be very low, since 



the structure / N — H is characteristic of amines (such as dimethylamine) 



which are basic rather than acidic. If structure B represented the normal 



state, the group would be rather strongly acidic; the group + N — H in the 



pyridinium cation, for example, has pK^ =5.1. With resonance between 

 structures A and B, the group should be somewhat less acidic than the 

 pyridinium cation. This is observed for imidazole derivatives of this type; 

 thus the observed value" {296^) of pK for the .V-methylimidazolium cation 

 is 7.35. For the imidazolium ion itself the observed value of pK, 6.95, 

 becomes 7.25 when corrected by the amount of log 2 to correct for the 

 presence of two equivalent ionizable hydrogen atoms; and the imidazolium 

 group in the histidine cation {1053) has pK = 6.04, which becomes 6.34 on 

 correction, the change from the imidazolium value being attributable to 

 interaction with the charges in the ionized amino and carboxyl groups of 

 the amino acid. Some variation in substituted imidazoles is to be expected 

 also because of the difference in electronegativity of the attached groups. 

 We would predict on the basis of our postulate about the structure of oxy- 

 hemoglobin that pls.2 for this substance should lie in the region near 7; the 

 observed value 6.80 is in satisfactory agreement with this prediction." 



Coryell and Pauling discuss the change in bond type on oxygenation 

 as follows: 



"Structures A and B for oxyhemoglobin are seen to be closely similar, 

 (they are equivalent in the imidazolium ion), and hence they contribute 

 nearly equally to the normal state of the molecule. The decrease from large 

 contribution of a structure of the type of structure B (pyridinium ion) to a 

 contribution of about 50 per cent is accompanied by an increase in pK by 

 about 2 units. Now in ferrohemoglobin itself structure B' makes a still 

 smaller contribution than 50 per cent, because this structure, with separated 

 electric charges, is less stable than structure A' , in which the nitrogen atoms 

 have their normal co valence; hence it is predicted with certainty that the 

 change of bond type for the iron atom accompanying removal of the oxygen 

 molecule must be accompanied by a decrease in the acidity of the attached imi- 

 dazole group. A quantitative prediction of the magnitude of the expected 

 change in pK2 from oxyhemoglobin to ferrohemoglobin cannot be made at 

 present; but the observed change from 6.80 to 7.81 is reasonable in the light 

 of the above discussion." 



* The dissociation referred to is not that of a secondary amine as base: 

 H + + \ NH -^ N NH2, but the dissociation as acid :\nH-^ \ N: + H''" 



