INTERACTION OF ORGANIC MOLECULES WITH PROTEINS 111 



you could have in a relatively close geometric position, because of the freedom 

 of motion of the ^NH+ side chain, a plus side group and an organic side chain 

 to supply the van der Waals forces, in order to complement the negative charge 

 on the anion and the organic part of the anion, respectively. 



However, if you go to serum globulin, which has a very large number of hy- 

 droxyl amino acids, there are enough of these side chains to rigidly hold in con- 

 figuration the carboxylic acid side chains and there are still plenty left over to 

 hold the ^NH+ rigidly. On that basis, then, we said the cationic side chain 

 was not free, so that it could not come into the neighborhood of a suitable leu- 

 cine or phenylalanine group and, consequently, you would not have a stable 

 complex with an organic anion. 



As I said, this was initially suggested in order to account for the differences 

 in proteins, but I think you can see that it also accounts for the differences in 

 the interaction of a given protein with the two types of ion, because, according 

 to this picture, if we now take a positively-charged small ion, it would have to 

 interact with the — C00~ group; but this group is blocked — or it is rigid — and 

 so you can not really get the necessary juxtaposition of the R and — C00~ side 

 chains so that you can obtain the additional van der Waals interaction to com- 

 plement this electrostatic interaction, to hold the plus-charged organic ion. 



Conseciuently, on this basis, you can see that we would have expected that a 

 cation, an organic cation of the same size as an anion which is bound strongly, 

 would not be bound strongly. Furthermore, if we go to gamma globulin, there 

 is no reason why it should behave any differently. It too has its carboxylic acid 

 groups strongly hindered, or rigidly held and, consequently, it too should not 

 bind organic cations. This, indeed, is the fact. 



These are some of the examples which I wanted to bring to your attention as 

 illustrations of specificities of various degrees and of the explanations which 

 we can give on a molecular basis. 



I hope that I have indicated that dyes are really only incidental to our work, 

 that they are just a convenience because it is easy to make these measurements 

 with dyes. I emphasize this particularly because Professor Hirschfelder brought 

 up the question as to whether the excited states might be involved. With dyes 

 you would immediately think how they absorb light, and consequently we have 

 special interactions here due to the existence of these excited states. In the few 

 cases where we have made similar measurements on the non-colored organic 

 ions, the results are substantially the same, so there is nothing special about the 

 dyes. The specialty arises in the nature of their molecular structure. 



These are some of the factors which can be involved. I think, while you can 

 not necessarily go from these systems to enzymatic and other biological sys- 

 tems, you, nevertheless, have certain features which are outlined here and which 

 act, you might say, as boundary conditions in order to give you some idea of 

 the limits within which the biological interactions must operate. 



