216 



6. INTERACTIONS OF INHIBITORS WITH ENZYMES 



Table 6-1 

 Bond Moments and Electronegativity Differences " 



° The dipole moments were taken from Smyth (1955, p. 244) with the positive pole 

 being the hydrogen atom in each case. Exact correlation with the electronegativity 

 difference is not to be expected because of size differences between the atoms and 

 the occurrence of orbital hybridization. 



groups attached to the atoms. The important C— H bond may be cited as 

 an example: although its moment is generally given as 0.4 with the direction 

 C — H"^, there is good evidence that, at least in some cases, the dipole 

 is reversed as C+-H~ (Wheland, 1955, p. 207; Smyth, 1955, p. 240). The 

 reason for this direction, unexpected from the relative electronegativities, 

 is probably the s;9-hybridization in the bond and the unequal distribution 

 of electrons around the carbon atom; the resultant moment will depend on 

 the groups attached to the carbon atom. This situation is mentioned because 

 it is wished to emphasize the variability in bond moments. Carbon can par- 

 ticipate in hydrogen bonding (hydrogen cyanide and acetaldehyde) so in 

 these cases the hydrogen atom must be positive. 



The energy of the — H •••• bond probably ranges from 4-6 kcal/mole 

 and other biologically common hydrogen bonds are weaker: for example, the 

 N— H ••• bond may be in the range 2-3 kcal/mole and the N— H ••• N 

 bond between 1-2 kcal/mole. Nitrogen is less electronegative than oxygen 

 and has a greater covalent radius; thus the moments are smaller and the 

 distance between the dipoles somewhat larger when nitrogen forms a hy- 

 drogen bond, both of which would decrease the bond energy. It is evident 

 from the electrostatic nature of the hydrogen bond that it will vary in 

 stability with changes in pH or ionic strength; stability is generally reduced 

 by decrease in pH or increase in ionic strength. The energy of activation 

 for the formation or rupture of hydrogen bonds is quite low and thus they 

 show high mobility. Since the formation of hydrogen bonds between a 



