The medicinal use of mercurials can be traced back over 3000 years, although their modern therapeutic applications began with the discovery of the diuretic action of mercurous chloride in 1849. When Zeise discovered C2H5SH in 1834, he called it "mercaptan" (corpus mercurium captans) because the formation of mercury derivatives was a striking characteristic (1). The aryl mercurials, such as p-mercuribenzoate, were introduced as enzyme inhibitors in 1937, and the alkyl mercurials, such as methylmercuric chloride, in 1950. Organomercuric ions of the type R-Hg+ comprise a useful family of reagents that react specifically with thiol groups and can be used as titrants, reactivity probes, or reporter groups, depending upon the characteristics of group R. Such organomercuric ions are monovalent and react with a single thiol group:
In contrast, mercuric ion, Hg , tends to react with two thiol groups and to cross-link them. The reaction with either is reversible, but the binding is tight, so that the equilibrium generally lies far to the right, unless an excess of another thiol reagent or of cyanide is added, when the original thiol group can be regenerated. A slight complication is that mercuric ions exist in a variety of loose complexes with components of the aqueous solution, such as hydroxide and chloride ions (2).
The classical organomercurial reagent was p-mercuribenzoate (3):
which is often called p-chloromercuribenzoate, although the chloride component is simply a counterion, and it makes little difference what salt is used. It has useful spectroscopic properties, and its absorbance increases at 250 nm upon reaction with a thiol group. Many variants have been prepared and used subsequently. Nevertheless, such reagents are not widely used now, in part because the adduct is not irreversible, and the original reagents are always present in significant quantities, due to the reverse of Eq. (1). Such mercurial reagents can always react with any other constituents subsequently added. Ions such as hydroxyl and chloride, especially if present at high concentration, can also compete with thiol groups for the mercurial. Furthermore, the C—Hg bond is relatively weak, so Hg can exchange rapidly with the alkyl mercurial, and inorganic mercury can be split off rather readily.
Such reactions of cysteine thiol groups with mercurials are the most obvious, and one of the more useful, ways to make heavy-atom derivatives for X-ray crystallography determination of protein structure (see Isomorphous Replacement).
