206 6. INTERACTIONS OF INHIBITORS WITH ENZYMES 



actions, lead to the shortest distances between atoms, usually 1-2 A, and 

 (c) they involve high binding energies of the order of 50-100 kcal/mole. 

 Covalent bonds are, however, not necessarily electrically symmetrical and 

 when they join two unlike atoms it is probable that the bond will possess 

 some ionic character, i.e., the electrons will be attracted more to one of 

 the atoms (the relative ability of atoms to attract electrons is termed their 

 electronegativity), resulting in a fractional negative charge on the more 

 electronegative atom and an equal positive charge on the other atom. 

 This gives such a bond a dipolar character which is of great importance in 

 intermolecular interactions. Although in many instances covalent bonds 

 are formed between enzymes and inhibitors (generally called a chemical 

 reaction of the inhibitor with the enzyme), these situations present no spe- 

 cial problems here and will be discussed in connection with the inhibitors 

 reacting in this manner. The following examples may be mentioned: the 

 formation of mercaptide bonds between mercurials or arsenicals and the 

 sulfhydryl groups of the enzyme, the alkylation of sulfhydryl groups by 

 iodoacetate, the acetylation of amino or hydroxyl groups on the enzyme, 

 the reaction of amino groups with fluorodinitrobenzene, and the phosphor- 

 ylation of serine by the organophosphorus compounds. 



lon-lon-lnteractions 



A point charge in a homogeneous medium possesses an electrical field of 

 radial symmetry, the intensity of which decreases with distance from the 

 charge according to the expression: 



a ze 



Electrical field strength = F = -^ = — - (6-1) 



where q is the magnitude of the charge, d is the distance from the charge to 

 the point in question, z is the valence of the ion, and e is the electronic 

 charge. The dielectric constant D depends on the medium in which the charge 

 is immersed and particularly on the polar nature of the molecules making 

 up this medium: for a vacuum D = \ and for water at 37.5° Z) = 74.1. 

 The important question of the dielectric constant will be discussed in some 

 detail following the presentation of the interaction types and for the pres- 

 ent the interactions are assumed to take place in a vacuum. Ions of finite 

 dimensions are considered here to have their total charge concentrated at 

 a central point. When the charge is in electrostatic units (esu) and the dis- 

 tance in centimeters, the field strength is given in dynes/esu. At a distance 

 of 5 A from an electron in a vacuum the field strength would be — 4.8 X 10"^" 

 esu/(5xl0-^ cm)2 = — 1.92x10^ dynes/esu, the field strength being of 

 the same sign as the charge from which it originates. Since 1 dyne/esu — 

 300 volts/cm, the field strength can also be written as — 1.92 X 10^x300= 



