CHEMICAL PROPERTIES 741 



be that the Hg++ concentration will be extremely low, the Hg being parti- 

 tioned between numerous complexes of different types, each one reducing 

 to some extent the reaction of Hg with enzymes. It must be clearly under- 

 stood that when inhibition is stated below to be by HgCla or Hg(N03)2 or 

 Hg acetate, it refers only to what was added and not to the dominant 

 form present or the active inhibitor. 



Complexes of Hg++ with Nucleotides and Nucleic Acids 



Complexes between Hg++ and certain purines and pyrimidines, especially 

 thymine, are quite stable (Table 7-4) (Katz, 1962), and complexes with 

 phosphates are probably formed readily; thus, one would expect nucleotides 

 and nucleic acids also to bind Hg++ rather well. Inagaki (1940) found var- 

 ious nucleotides, such as AMP, GMP, and IMP, to be precipitated by mer- 

 curic compounds, but unfortunately no further work has been done on these 

 complexes. One would like to know the nature and extent of the interactions 

 of mercurials with ATP, NAD, FAD, and related substances. However, 

 the studies of the reactions between Hg++ and nucleic acids have recently 

 been accelerated, and it is obvious that the results could be very important 

 in understanding the effects of mercurials on cellular growth and prolifera- 

 tion. Hg++ has been found to complex with nucleic acids from thymus 

 (Katz, 1952), plants (Trim, 1959), pneumococci (Dove and Yamane, 1960), 

 and tobacco mosaic virus (Katz and Santilli, 1962 b). The general effects 

 on the nucleic acids may be summarized briefly as follows: a decrease in 

 viscosity; an increase in turbidity, sedimentation constant, aggregation, 

 and the dimer : monomer ratio; an increase in the flexibility of the chains 

 with the assumption of a more compact configuration; and a change in the 

 ultraviolet absorption spectra (Katz, 1952; Thomas, 1954; Yamane and 

 Davidson, 1961). It was originally believed that the complexing is with the 

 phosphate groups, but the nature of the absorption spectrum changes, the 

 stoichiometry of the reactions, and the release of H+ indicate that the bases 

 are the sites of binding, the Hg:base combining ratio being 1 : 2 in most 

 cases, Hg apparently bridging the double strands of the DNA helix (Katz, 

 1962). The single-stranded tobacco mosaic virus RNA, however, gives a 

 combining ratio of 1 : 1, as expected (Katz and Santilli, 1962 a). It may be 

 noted that the combining ratio is 1 : 2 for guanine oligoribonucleotides, such 

 as GpCxpG (Lipsett, 1964). These complexes are usually completely reversi- 

 ble upon adding various Hg++ complexers (Cl~, cyanide, EDTA, or thiols), 

 and indeed the pneumococcal transforming DNA after demercuration retains 

 aU of its activity (Dove and Yamane, 1960), and the tobacco mosaic virus 

 after removal of the Hg++ regains its infectivity' (Singer and Fraenkel- 

 Conrat, 1962), these observations indicating that the original configurations 

 of the nucleic acids can be restored despite the apparently marked struc- 

 tural modifications occurring during reaction with Hg++. 



