730 7. MERCURIALS 



action of mercuria chloride by Koch in 1881, and the introduction of or- 

 ganic mercurials for diuresis, antisepsis, and other chemotherapeutic pur- 

 poses from 1900 to 1920. The marked toxicity of inorganic mercury was 

 recognized in antiquity and became a more critical problem over 400 years 

 ago, especially in processes such as fur felting for hats and more recently 

 in the widespread use of mercurials as plant fungicides for various rots and 

 rusts. There was a good deal of experimentation and speculation on the 

 nature of mercurial antisepsis between 1900 and 1940, but little of this is 

 pertinent to our present purposes. The early work was much concerned 

 with the examination of the validity of certain vague concepts, such as the 

 Arndt-Schulz law (which states that drugs stimulate in low concentration 

 and inhibit in high concentration), oligodynamic action, and the Ostwald 

 adsorption theory. Despite the fact that the combination of mercurials with 

 thiols, e.g. cysteine, has been known since 1875 at least, investigations on 

 the metabolic effects and enzyme inhibition are very sparse before 1930. 

 Actually the mercurials have been intensively used by biochemists for the 

 characterization of enzymes for only the past several years. Of the some 

 1350 publications on the effects of mercurials on isolated enzymes, only 4% 

 were issued prior to 1950, 16% from 1950 to 1956, and 80% from 1956 

 through 1964. By the time this volume goes to press, approximately half 

 of the publications on this aspect of the mercurials will have appeared after 

 1960. These figures indicate essentially that each newly isolated enzyme is 

 subjected to one or more mercurials for the purpose of detecting SH groups. 

 One of the major aims of this chapter is to attempt to determine the va- 

 lidity and usefulness of such determinations. 



CHEMICAL PROPERTIES 



The most commonly used inorganic mercury compound in inhibition work 

 is mercuric chloride (HgCla). Some fundamental properties of the Hg++ ion 

 and its halides are summarized in Table 7-1. It may be noted that although 

 the linearity of HgXg molecules is established and the configuration of 

 certain HgX4 complexes appears to be tetrahedral, the nature of the HgClg" 

 and HgCl4= ions is not clear and a planar arrangement is possible. The 

 aqueous solubility of HgClg increases with the concentration of NaCl, KCl, 

 or other halide present; thus the solubility of HgClg in Krebs-Ringer me- 

 dium is around 12.5 and in sea water around 27 g/100 ml (Barnes and 

 Stanbury, 1948). The deficiency in the ionic character of HgClg is indicated 

 by the high solubility in ethanol (26.3 g/100 ml) and even in ether (4.55 

 g/100 ml). Indeed, HgClg has been said to be reasonably lipid-soluble, a 

 fact of some importance in considering the distribution in the tissues. HgBrg 

 and Hglg are much less soluble than HgClg in water and seem to have no 

 advantages over HgClg in enzyme studies. 



