INTERACTIONS OF AROMATIC COMPOUNDS 297 



SO that at pH 7.8 it should be in the ionized state. It is strange that the 

 replacement of the hydrogen atom of acetate by almost any group (except 

 in sarcosine and methoxyacetate) leads to poorer binding. Halogen atoms 

 decrease the binding in proportion to their size and this is not likely to be 

 due to decreased dispersion forces, but to steric factors or dipolar interac- 

 tions. It may well be that the acetate series fits onto the surface in a 

 different configuration than the sarcosine-methoxyacetate group, and cer- 

 tainly importance must be attached to the terminal methyl group in these 

 latter compounds, which could fit tightly into a cavity as suggested, con- 

 tributing 1-2 kcal/mole and serving to orient the entire molecule. Various 

 comparisons point to the following provisional assignments of binding 

 contributions for sarcosine; — C00~, 1.8 kcal/mole; — CHg— , 0.2 kcal/ 

 mole; — NH2+— . 1.1 kcal/mole, and — CH3, 1.0 kcal/mole. Further re- 

 lationships will be discussed in Volume II, Chapter 2, which will be con- 

 cerned with inhibition produced by analogs of substrates and coenzymes. 



Interaction of Substrate Analogs with Yeast Lactate Dehydrogenase 



All of the substrates or inhibitors for this enzyme have anionic carboxy- 

 late groups so it is likely that the active center contains a positively charged 

 cationic group. Dikstein (1959) determined the concentrations required 

 for 50% inhibition for a number of analogs and for the fatty acid series he 

 plotted plo.5 against the number of methylene groups. The slope of the 

 resulting straight line allowed the calculation of the free energy of transfer 

 of a methylene group from the solvent phase to the surface of the enzyme; 

 this was about 0.5 kcal/mole at 25° and represents the contribution to the 

 binding made by each methylene group. The intercept of the line with the 

 pip 5 axis allowed the calculation of the ion-ion interaction energy, from 

 which the equilibrium separation (assuming D = 30) was determined to 

 be about 11 A if a single cationic group is involved. The interaction of the 

 hydrocarbon chain with the enzyme surface in this series is thus of major 

 importance in determining the inhibitory potency. The enzyme cationic 

 group is most likely a 5-guanidino group of arginine. 



INTERACTIONS OF AROMATIC COMPOUNDS 



Due to the relatively high polarizability of aromatic ring systems, there 

 are often strong interactions with similar ring systems or polarizing groups, 

 particularly when the mutual orientation is such as to allow a close approach 

 over an appreciable surface of the molecules. Thus highly resonating mol- 

 ecules, composed of several aromatic rings with mobile electrons, tend 

 to form complexes in which the molecules lie in parallel planes, this being 

 the orientation consonant with the greatest dispersion interaction. It is 



