744 7. MERCURIALS 



if maximal penetration is desired, it is probably best to use the alkyl or 

 the unsubstituted-phenylmercurials, since the C00~ and SO3" groups will 

 reduce the permeability. 



(d) Configuration. Although HgClg is linear, as shown by Raman spectra 

 and electron diffraction, the organic mercurials for some reason are ap- 

 parently not. Dipole moment studies (e.g., for phenylmercuric chloride, 

 ju = 2.99) suggest that the angle of the C — Hg — X bonds is around 130° 

 or higher (Sipos et al., 1955). The moment is directed as foUows: 



+ - 

 R - Hg - X 



(e) Molecular size. The organic mercurials are, of course, larger than the 

 simple complexes of Hg++. This may be of importance in the reaction with 

 the SH groups of proteins and enzymes, since steric factors may impede the 

 approach of the mercurial to SH groups not exposed on the surface. A re- 

 duction in volume was one of the reasons for the introduction of the alkyl 

 mercurials by W. L. Hughes (1950). In addition, penetration into cells will 

 depend to some extent on the molecular size. Other factors will be discussed 

 relative to enzyme inhibition. 



(f ) Affinities for ligands. The organic mercurial ions in solution tend to 

 complex with various ligands in the same way as the Hg++ ion, forming 

 complexes of the type R-Hg-L. The affinities seem to be somewhat less 

 for the organic mercurial ions than for Hg++, although very few have been 

 studied. Simpson (1961) gave the dissociation constants for MM complexes 

 (Table 7-5), and generally the pii's are around 1.3 units less than for the 

 Hg++ complexes. Nevertheless, the affinities are of sufficient magnitude so 

 that at pH 7 there is perhaps 500 times as much MM-OH as MM+, and if 

 much Cl~ is present there may be 100 times as much MM-Cl as MM-OH 

 (Hughes, 1957). Rowland (1952) determined the equilibrium constant, 

 ii:=(RHg-OH) (H+) (Cl-)/(RHg-Cl), for a variety of diuretic mercurials, 

 and found a mean value for ])K of 9.9, so that at pH 7 and (Ch) = 100 mM 

 the ratio (RHg-Cl)/(RHg-OH) is around 100 as for MM. Ledoux (1953) 

 reported the interaction of p-MB with nucleic acid and from the spectral 

 changes assumed a complex to be formed with the carbonyl group of pyri- 

 midines. Various complexes of PM and amino acids were obtained by Smalt 

 et al. (1957) but were claimed to dissociate rather readily. The remarkably 

 tight complex of PM and thyroxine has been investigated by Frieden and 

 Naile (1954). One must thus assume that in solution in most physiological 

 media the organic mercurials will exist in a variety of complexes, and that 

 this will be an important factor in determining the degree of reaction with 

 proteins and enzyme SH groups. 



One characteristic of the organic mercurials is the weakness of the C — Hg 

 bond, the energy of which is only 15-19 kcal/mole (CottreU, 1954), so that 



