102 Discussion 



The present hypothesis only requires the immediate environment of the 

 combining site in haemoglobin or myoglobin to have a low dielectric constant ; 

 it is generally non-committal regarding the other side of the haem plane 

 except that there should be a strong ligand, presumably an imidazole group, 

 snugly co-ordinated to the Fe++-ion of the haem. 



SUMMARY 



(1) The existing physico-chemical data on haemoglobin and haem are 

 examined, and a hypothetical structure for the combining sites in haemo- 

 globin is proposed to account for the stability of oxyhaemoglobin. 



(2) A synthetic model is made which oxygenates reversibly, is stable in the 

 presence of water, and can be 'denatured' and reactivated by proper treat- 

 ments. 



(3) A molecular interpretation of the properties of this synthetic model is 

 suggested, and its implication on the haemoglobin problem is discussed. 



Acknowledgement 



This work was supported in part by a grant (USPHS-RG-4483) from the 

 Division of Research Grants, U.S. Public Health Service. 



REFERENCES 



Barron, E. S. G. (1937). J. biol. Chem. 121, 285. 



Callaghan, J. p. (1949). Hematin Compounds and Bile Pigments, Lemberg, R. & Legge, 



J. W., p. 189. Interscience, New York. 

 Lein, a. & Pauling, L. (1956). Proc. nat. Acad. Sci. Wash. 42, 51. 

 Havemann, R. (1943). Biochem. Z. 314, 118. 



Nakahara, a. &. Wang, J. H. (1958). /. Amer. chem. Sac. 80, 6526. 

 St. George, R. C. C. & Pauling, L. (1951). Science, 114, 629. 

 Stitt, F. & Coryell, C. D. (1939). J. Amer. chem. Soc. 61, 1263. 

 Wang, J. H., Nakahara, A. & Fleischer, E. B. (1958). /. Amer. chem. Soc. 80, 1109. 

 Wang, J. H. (1958). /. Amer. chem. Soc. 80, 3186. 



DISCUSSION 



Oxygenation of Haemoglobin 



Drabkin : I should like to ask Wang two questions : 



(1) Are your films 'dehydrated' ? Haurowitz (at the Barcroft Memorial Symposium) 

 postulated that a molecule of HjO had to be co-ordinated with the Fe before haemo- 

 globin could be oxygenated. Is his reported finding at all related to your spectroscopic 

 findings ? 



(2) Do your studies shed light on what happens to the protein (globin) when 

 haemoglobin is denatured ? 



Lemberg : My remarks are also directed to Wang. 



(1) The spectrum of your reduced film in nitrogen is rather a ferrohaemochrome 

 r spectrum than that of a ferrohaemoglobin. 



p (2) Would it not be advisable to use an imidazole not substituted on the nitrogen? 

 f A nitrogen-substituted imidazole appears to me a type of compound very different 

 from an imidazole compound Hke histidine in the peptide chain. 



