602 6. ARSENICALS 



Arsenious Acid and the Arsenites 



Arsenious acid exists only in solution and is formed when arsenic tri- 

 oxide is dissolved in water: 



AS2O3 + H2O ±? 2 AsO(OH) 



In much of the early metabolic work, arsenic trioxide was dissolved in acid 

 solution and then neutralized with NaOH; this gives the same result as 

 dissolving sodium metaarsenite (NaAsOg), which is now generally used. 

 Arsenic trioxide exists in at least three different forms and the aqueous 

 solubilities differ: the vitreous form is the most soluble (3.7% at 37°), 

 the octahedral form is less soluble (2.8%), and the monoclinic form is the 

 least soluble (1.8%); saturated solutions are thus around 100 raM. The 

 solubility varies with the pH but appreciable changes occur only far outside 

 the biological pH range (Garrett et al., 1940). Arsenic trioxide dissolves 

 very slowly in water; after 4 months of agitation in water, equilibrium is 

 still not completely reached (Schnellbach and Rosin, 1929). The rate of 

 solution is accelerated by alkalinization and increased temperature. 



Since arsenite is commonly used in metabolic studies, it is important to 

 inquire into the state of the substance in solution near neutrality. Inasmuch 

 as the piiT^ is generally given as 9.22 (Sellers et al, 1964) [there is disagree- 

 ment as to the exact value and a p^fiC^ of 9.62 was obtained by Garrett et 

 al. (1940)], there would be relatively little of the anionic arsenite (AsOg") 

 at physiological pH's. There is thus some question as to whether the term 

 "arsenite" is strictly correct for designating the substance, but since it 

 has been so commonly used it will be retained here. The conductance of 

 solutions of arsenious acid is low, indicating the weak ionization. The 

 monomeric form has been assigned different structures in solution, including 

 metaarsenious acid (HAsOg) and orthoarsenious acid (H3ASO3), which 

 correspond exactly to metaphosphorous acid (HPO2) and orthophospho- 

 rous acid (H3PO3); solid salts are either meta- or orthoarsenites (generally 

 the former), but these give no information on the state in solution. We 

 shall write arsenious acid as HAsOg or AsO(OH) for simplicity, but more 

 highly hydrated forms must be considered as included. Solutions of arsenic 

 trioxide are acid (around pH 5) and of arsenite salts are alkaline, and both 

 must be adjusted to the correct pH before use. There is a second -pK^ near 

 13.5, probably corresponding to the formation of HAsOg^, but this is not 

 biologically important. The protonation of arsenious acid to form As(0H)2+ 

 (or AsO+ or As+++) occurs, but the ])K^ is around 1 so, that it also need 

 not be taken into account. The importance of polymerization has been 

 debated for many years. In strongly alkaline solutions (> pH 12), poly- 

 mers exist in appreciable amounts: in 0.1 M NaOH solution there may be 

 about 25% as the dimer, HAsaO^", and 10% of the trimer, HAs306= (Gar- 



