308 



6. INTEEACTIONS OF INHIBITORS WITH ENZYMES 



Examples of Group Changes and Inhibitions by Related Compounds 



In order to demonstrate some of the inherent difficulties in interpreting 

 the effects of group modification, the following examples are presented as 

 typical of situations often found in inhibition studies. 



(a) Molecular polarizations by groups and the resulting clipole moments. 

 The total dipole moment of a molecule cannot be accurately estimated 

 from the moments of the groups present because inductive or resonance 

 effects alter electronic distributions over considerable distances. Many inhi- 

 bition studies involve the addition or elimination of simple groups on an 

 aliphatic chain or aromatic nucleus. The dipole moments of some alkyl 

 and phenyl halogens are given in Table 6-28. In CH3CI the moment is less 



Table 6-28 

 Dipole Moments of Halogen Derivative " 



" From Wheland (1955, p. 213). 



that the C-Cl moment (2.3) because of the oppositely directed three C— H 

 moments (0.4), but is greater than would be expected due to the polar- 

 ization of the methyl group by the C— CI bond. In CH3CH2CI the moment 

 is higher because the ethyl group has a greater polarizability than the 

 methyl group, and the propyl compound has a still higher moment. How- 

 ever, beyond this there is essentially no change. This indicates that 

 such inductive effects can extend along an aliphatic chain about three 

 carbon atoms with decrement. One might expect phenyl-Cl to have a mo- 

 ment even higher than the C-Cl bond because the benzene ring is quite 

 polarizable, but actually the moments are lower than the alkyl compounds. 

 The explanation is that resonance occurs between the following structures: 



CI 



\/ 



CI 



A 



C1+ 



%/ 



C1+ 



C1+ 



./ 



