On the Stability of Oxyhaemoglobin 



101 



behaviour of alkyl isocyanides (St. George and Pauling, 1951; Lein and 

 Pauling, 1956), imidazole and pyridine toward haem and haemoglobin 

 respectively. Perhaps even more striking is the reaction of cyanide ion with 

 haem and haemoglobin. The cyanide ion is isoelectronic with the carbon 

 monoxide molecule. It has been mentioned above that haemoglobin binds 

 carbon monoxide slightly more strongly than free haem does. But the 

 observed affinity of haemoglobin for cyanide ion is, on the contrary, very 

 much smaller than that of free haem, corresponding to a ratio of about 



Wavelength, A 



5700 5500 5300 5700 5500 5300 5700 5500 5300 



Fig. 2. Spectra and structural diagrams of a high polystyrene-content film at 

 various stages of the experiment. Curve I, spectrum of the film saturated with 

 carbon monoxide; Curve II, spectrum of the active form of the film; Curve III, 

 spectrum of the same film after thermal denaturation. The schematic diagram 

 under each curve represents the structure of the active centre at the corresponding 

 stage of the experiment. 



1:10^ in the formation constants of the respective complexes (Callaghan, 

 1949; Stitt and Coryell, 1939). Since the cyanide ion and the carbon 

 monoxide molecule have almost identical size and shape, the observed con- 

 trasting behaviour of haemoglobin and free haem toward carbon monoxide 

 and cyanide ion respectively cannot be explained in terms of simple steric 

 factors. But if it is assumed that the combining site in haemoglobin is 

 covered with hydrophobic structural elements of the globin, then the free 

 energy of formation of the cyanide complex should be greater than that for an 

 exposed haem by an amount equal to the electrical work required to bring the 

 charged cyanide ion from an environment of higher to one of lower dielectric 

 constant. If the average dielectric constant of the surroundings of the 

 combining site in haemoglobin is considerably lower than that for free haem, 

 this work could be sufficient to account for the difference in the formation 

 constants of the two cyanide complexes. 



