Inleriuolecular Forces 



Joseph O. Hirschfelder 



University of Wisconsin Naval Research Laboratory, Madison, Wis. 



MY KNOWLEDGE OF INTERMOLECULAR FORCES is limited to a Study of 

 the properties of small molecules. The problems of intermolecular 

 forces in biological systems are quite different. In this short talk I 

 would like to outline the similarities and the differences from a rather general 

 point of view. 



The geometrical structure of two biological molecules is the most important 

 factor in determining their intermolecular forces. It is very helpful to construct 

 molecular models of the sort that Linus Pauling and others have fabricated on 

 the basis of X-ray and electron diffraction studies. With these models one can 

 make preliminary estimates of the separations between each of the atoms in 

 molecule A and each of the atoms in molecule B when the two molecules are 

 held in a particular orientation. Knowing these separations we can turn the 

 theoretical cranks to determine the energy of interaction corresponding to this 

 orientation. Unfortunately the molecular models have one serious defect. Their 

 joints are rigid so that they do not become deformed in the same manner as the 

 real molecules when the attractive or the repulsive forces become large. I 

 understand that some biological molecules can completely change their shape 

 under the influence of even small stresses such as surface tension. This makes 

 the problem of determining intermolecular forces exceedingly difficult because 

 it means that we must take intra-molecular stresses and strains into considera- 

 tion at the same time that we are estimating the intermolecular interactions. 



Then, there is the problem of the additivity of intermolecular forces. In 

 most small molecule problems, it is a good approximation to assume that the 

 forces either between various groups on molecule A and other groups on mole- 

 cule B or else between various separate molecules are pairwise additive. In 

 calculating the interactions between biological molecules one might also be 

 tempted to assume this pairwise additivity. However, very frequently when 

 two biological molecules approach each other their charge distributions become 

 distorted so as to render such pairwise additivity inapplicable. 



Since biological molecules are swimming in a solvent possessing a large 

 dielectric constant, the energy of ionization is much smaller than in the gas 

 and the electrons are much less tightly bound within the molecules. Ions, 

 zwitterions, and structures possessing large dipole moments are common. Thus 



84 



