CHELATION 479 



groups and hence extracts easily into a non-polar solvent. The 1:1 

 chelate is polar. A polar group not involved in the union with the 

 metal would, of course, remain unchanged and reduce lipid solubility. 

 The number of different complexes formed by a given metal with a 

 ligand is a function of its coordination number. 



Biological systems necessarily contain many different ions able to 

 participate in chelate complexes, and the nature of competition must 

 be considered. In general, most chelating agents form complexes of 

 varying stability with metal ions in the order (from most to least sta- 

 ble): Cu++, Ni++, Co++, Zn++, Cd++, Fe+ + , Mn++, Mg++ (276). 

 Thus copper will displace any of the other listed ions, magnesium none. 

 However, some biologically important chelating substances do not fol- 

 low this rough rule; a ,a'-dipyridyl and o-phenanthroline, for example, 

 have a specific affinity for iron. 



Stability of metal chelates is usually expressed by the constant K, the 

 formation (or dissociation) constant, a measure of the equilibrium: 



M + xA ±=; MA, (6) 



in which M = metal, A = ligand, and x = the number of ligand mole- 

 cules per metal atom in the complex. Ideally, K is expressed by: 



(MA,) m 



K ~ (mxaT* (7) 



in which brackets indicate activities (276). Values of log K may be 

 very high, e.g., 23 for the copper-oxine complex; it is obvious that negli- 

 gible amounts of free copper can exist in the presence of excess oxine. 



Factors which fundamentally determine K are discussed by Calvin 

 (59); Chabarek et al. (63) decribe the use, under biological conditions, 

 of a plot of the negative logarithm of metal concentration against pH 

 for prediction of the behavior of chelate systems. The ligand may be 

 considered as a Lewis base; at low pH more of it is bound by protons 

 and, consequently, the metal chelates are less stable under acid condi- 

 tions. 



Many normal cell metabolites are chelating agents; examples of such 

 metabolites include amino and hydroxy acids, porphyrins, peptides, 

 and polyphosphates. Some of these may owe their biological function 

 to their chelating properties. Chelation is almost certainly necessary to 

 the function of the manganese-requiring peptidases (289), and quite 

 likely it is essential to the action of other metalloenzymes and electron 

 or oxygen transport systems (59, 97). 



We may approach the question of fungistatic action by first noting 

 that chelating agents are often powerful inhibitors of metalloenzymes 



