142 INTRODUCTION TO IMMUNOCHEMICAL SPECIFICITY 



are due to the fact that in most cases there is mutual neutralization 

 of positive and negative charges (see p. 120), with resulting loss 

 of attraction for water molecules. Restoring freedom of motion to 

 water molecules previously bound to the antigen or antibody surface 

 causes an increase in entropy, and this might be more than enough 

 to compensate for the loss of entropy due to the decreased mobility 

 of the antibody molecules. For instance, Epstein, Doty, and Boyd 

 (1956) calculated that in the reaction studied by them the release 

 of about twenty-four water molecules accounted for the observed 

 A6"°. In line with this argument, Karush (1958) found a negative 

 entropy change of about nine units for the reaction of antibody with 

 his lactose-hapten "lac," where there is no charge to be neutralized. 



The one large negative entropy change in study 1 of Table 10-1 is 

 harder to explain. However, it should be remembered that, in the 

 first place, it is based on a value of AF° which was merely assumed 

 and, in the second place, hemocyanin is a rather special antigen in a 

 number of ways, being much larger and more multivalent than most 

 antigens and constituting an associating and dissociating system. 

 Steiner and Kitzinger (1956) suggested that a change in the state of 

 association of the hemocyanin might account for the large enthalpy 

 change observed and for the large negative entropy change calculated 

 from this value. 



A third feature of the results of Table 10-1 is that the enthalpy 

 (heat content) changes are small, with the exception, again, of that 

 found in study 1. Aside from this perhaps atypical value, the largest 

 enthalpy change in the table is the — 9.7 kcal. per mole calculated by 

 Karush (1958) for the reaction of antibody with the "lac" hapten. 

 This is definitely on the small side when compared with the AH° 

 of —94.03 kcal. per mole for the reaction of hydrogen and oxygen to 

 form water, or the — 26.4 kcal. per mole for the reaction of carbon 

 and oxygen to form carbon monoxide. It is also of interest that, in 

 all cases where AH° is not zero, or so close to zero that its exact 

 magnitude is not known, it is negative, i.e., the reaction is exothermic. 



The enthalpy changes of all the antibody-antigen or antibody-hapten 

 reactions studied, with the exception of that in study 1, are too small 

 to account for the firmness of the bond and the fact that the reaction 

 goes to substantial completion. Obviously, in many, perhaps most, 

 cases the major portion of the driving force of the reaction AF° is 



