Abstract

In the understanding of hemoglobin function, physical chemistry played a crucial role in the interval between purely physiological and purely structural methods. The indirect but rigorous methods of physical chemistry led to important results, and to the interpretation of the phenomenology of hemoglobin behaviour in terms of structure and mechanism. The first important result was the establishment of the true molecular weight of the hemoglobin molecule, which osmometry and ultracentrifuge independently reached at about the same time (1925). However, several difficulties arose in the attempt to interpret the saturation curve of hemoglobin in terms of these new structural conceptions. The so-called intermediate-compound hypothesis never allowed a real understanding of hemoglobin behaviour. But the hypotheses which the models required to meet the experimental data were the starting point of fruitful conclusions. From Adair's differential stability to Pauling's interaction energy between the hemes and to Wyman's conformational change of the whole molecule, one can follow a rational path and study the origins of modern allosteric conceptions. Wyman's use of thermochemistry (1951) presumably represents the turning point at which maturation of ideas turns into a real change