CHEMICAL PROPERTIES 743 



It will be useful to summarize briefly some of the important differences 

 between the organic mercurials and HgClg. 



(a) Functionality. HgClg is bifunctional in the sense that it can react 

 with two ligands to form L-Hg-L complexes, whereas the organic mercu- 

 rials are monofunctional in that they can react with only one ligand to 

 give R-Hg-L. Hg++ can also form cyclic mercaptides with two adjacent 

 SH groups but the organic mercurials cannot. These differences are often 

 very important in the reactions with thiols and enzymes, and in fact one 

 of the major reasons for the preference of many investigators for the or- 

 ganic mercurials, especially in the quantitative titration of SH groups, is 

 their monofunctional nature. 



(b) Aqueous solubility. The organic mercurials are less soluble than HgClg 

 and occasionally this has created a problem if higher concentrations are 

 required. However, in most titration or inhibition studies, the concentra- 

 tion required is seldom over 1 mM, and this can be easily attained in most 

 cases. Phenylmercuric chloride is soluble to the extent of only 0.16 toM in 

 distiUed water, but a good deal more soluble in salt solutions, and the in- 

 troduction of anionic groups increases the solubility. It is well known that 

 23-chloromercuribenzoic acid, which for many years was the only commonly 

 used mercurial, does not readily go into solution at neutral pH. It is there- 

 fore usual, to dissolve it in dilute KOH or NaOH solutions (0.01-0.05 M) 

 and adjust to the desired pH with HCL* However, the sodium salt is now 

 commercially available and dissolves readily. The phenylsulfonic acid is 

 also more soluble than the benzoic acid derivative. The solubility will be 

 determined, as with HgClj, by the concentrations of various complexing 

 substances in the medium; thus the solubility is reasonably high in most 

 physiological media containing over 100 mM Cl~, or various other ions 

 such as pyrophosphate or sulfate, concentrations around 10 mM of mer- 

 curial being readily obtained. 



(c) Lipid solubility. The unsubstituted alkyl and aryl mercurials are more 

 soluble than the Hg++ ion and its complexes in lipids. Hughes (1957) has 

 estimated that the simple alkyl mercurials are around 100 times more sol- 

 uble in lipids than in water. This property wiU presumably allow the organ- 

 ic mercurials to penetrate more readily than inorganic mercury into cells 

 and tissues, and evidence for this is provided by the greater central nervous 

 system toxicity of the organic mercurials (page 951). In this connection, 



* Although I have no definite evidence that strongly alkaline media are detrimental 

 to p-MB, I would prefer not to use 1 M NaOH solution to dissolve the material, as 

 has been done by some (e.g., Snodgrass et al., 1960), since, as we shall see, the C — Hg 

 bond is weak and dissociation is a possibiltiy, and, furthermore, such strongly alkaline 

 solutions are not necessary. For most work it is satisfactory to dissolve p-chloromer- 

 curibenzoic acid in 0.02 M KOH or NaOH at approximately 2 mg/ml or 7.4 mM. 



