ON THE NATURE OF HEMOPROTEIN REACTIONS 



ferrous state complexes are formed preferentially with neutral 

 molecules, e.g., O2 and CO, and in the ferric state with singly 

 charged anionic ligands, e.g., CN~, F~, and Ng (30,32). 

 There has been scarcely any need to question its general validity, 

 although there are exceptions, for example, nitric oxide and 

 cyanide combine with both ferri- and ferro-hemoglobin. 



The justification for such a hypothesis has received little 

 attention. Two of the four pyrollic nitrogen atoms of the 

 porphyrin ring are negatively charged, and so, provided that 

 the atom in the amino acid residue to which the iron is attached 

 does not itself carry a charge, the iron atom in the ferrous state 

 is uncharged, and in the ferric state carries a charge of +1. 

 Thus if complex formation was in accord with the hypothesis, 

 both ferrous and ferric complexes would be neutral, and this 

 could be regarded as the required condition for the most stable 

 complex. Furthermore, if the bonding was covalent through 

 d^sp^ hybridization, as it is in many of the complexes (28), and 

 there were in addition double bonds utilizing otherwise un- 

 shared d electrons of the iron atom, then the iron atom itself 

 could become neutral. Recent considerations of the stability 

 of aquated ions, ammonia complexes, cyanide complexes, and 

 oxy-acids of the transition elements, suggest that this particular 

 charge distribution is the most favorable (35). 



There are good thermochemical reasons why this should 

 be so. A large amount of energy, given by the ionization 

 potential, is required to produce an ion by the expulsion of an 

 electron. In forming coordinate links of the covalent type an 

 ion regains electrons, and, depending upon the extent to which 

 this happens, the resultant charge may become zero or even 

 negative. The energy release accompanying the decrease in 

 charge is taken up in endothermic steps necessary for bond 

 formation, the balance appearing as the heat of reaction. The 

 nearer the charge to zero the larger the energy release, which, 

 other factors being equal, would favor an exothermic heat of 

 reaction, and thus a favorable free-energy change. 



Considerations of the entropy changes associated with 



343 



