Cobalt oxine

What is the explanation of this protective action of cobalt At first it might seem that the cobalt combined with the oxine and thus denied it to the iron. But if this were so, nickel would be still more effective because the stability constant of nickel—oxine is much higher than that of cobalt—oxine (Table 11.2 also Albert, 1953). Yet nickel has no protective action at low concentrations. 

Discussion. Iron(III) (50-200 fig) can be extracted from aqueous solution with a 1 per cent solution of 8-hydroxyquinoline in chloroform by double extraction when the pH of the aqueous solution is between 2 and 10. At a pH of 2-2.5 nickel, cobalt, cerium(III), and aluminium do not interfere. Iron(III) oxinate is dark-coloured in chloroform and absorbs at 470 nm. 

Discussion. Various metals (e.g. aluminium, iron, copper, zinc, cadmium, nickel, cobalt, manganese, and magnesium) under specified conditions of pH yield well-defined crystalline precipitates with 8-hydroxyquinoline. These precipitates have the general formula M(C9H6ON) , where n is the charge on the metal M ion [see, however, Section 11.11(c)]. Upon treatment of the oxinates with dilute hydrochloric acid, the oxine is liberated. One molecule of oxine reacts with two molecules of bromine to give 5,7-dibromo-8-hydroxyquinoline ... 

In vitro plasmodiacidal activity has also been noted for 2-mercaptoquinoline-N-oxide and for 5-methyl oxine which has been used in humans to control cholera191,192). The antimalarial activity of the oxines is, unlike their antibacterial activity, insensitive to cobaltous antagonization195). This inability of cobalt to suppress antimalarial activity points to an inhibitory mechanism which does not depend upon peroxide formation. 

Extraction methods using 8-hydroxyqulnoline (oxine) have been applied to the separation of 10.5-minute Co 111 in the neutron activation analysis of cobalt in biological tissue samples (133), and for the separation of 24-minute U2 in neutron activation analysis (56). 

Since fef for complex formation is compounded of 2 and fe2 3, the net effect is not readily predictable. It should be noted that the observed value for fef has to be corrected for a reduction in the number of replaceable water molecules (by multiplying by a factor of 6/(6 — n) where n is the number of coordination positions occupied by the bound ligand). The net effect observed is a negative one, the reactivity order with NSA being Mg + > Mg(TP) > Mg(NTA) > Mg(ATP) whereas that for oxine [66] is more expectedly Mg > Mg(NTA) > Mg(ATP) > Mg(TP) ". Similar studies have been made with manganese(II), cobalt(II), zinc(II), and nickel(II) [70b]. 

Complexes of pyridine-2-carboxylic acid (picolinic add, picH) and its substituted derivatives commonly exhibit the N—O bidentate nature of this aromatic amino add. From aqueous solutions chelates are obtained with the coordinated carboxylic group deprotonated, or neutral ligand forms may be isolated from non-aqueous media. Bis chelates are common in either case with bivalent metal ions. The tris chelates of trivalent cobalt and manganese have been structurally characterized recently. The latter is tetragonally distorted in a structure similar to Mn (oxine)j. 

Cobalt is well known for its ability to break an oxidatively destructive chain reaction catalysed by another metal (cf. Baur and Preis, 1936). This suggested to the Dutch workers that the iron and copper complexes of oxine, pyrithione, and dimethyldithiocarbamic acid were oxidatively destroying thioctic acid (dihydrolipoic acid) (2.28) which is the essential coenzyme for the oxidative decarboxylation of pyruvic acid. This was confirmed when they found pyruvic acid accumulating in the medium (Sijpesteijn and Janssen, 1959 also personal communications from these authors). The receptor in all three examples is the small molecule (2.28) although, at the time, it caused surprise to find one of such low molecular weight. 

Cobalt, however, has a unique position. Not only is it protective in large amounts, but in traces also. As little as M/25000 cobaltous sulfate completely prevents the bacteriostatic effect of M/100000 oxine (Rubbo et aL, 1950) this antagonism is illustrated in Fig. 11.9. Table 11.7 shows how effective cobalt is in preventing the bactericidal action of oxine—iron. It is only a little less effective against oxine—copper. 

Cobalt also protects yeasts against oxine-copper (Nordbring-Hertz, 1955), but mycelial fungi are not protected, apparently because of their slow rate of growth (Anderson and Swaby, 1951). However, see the protective effects of cobalt on DMDC (dimethyldithiocarbamic acid) (p. 478). Cobalt uniquely protects trypanosomes against the lethal action of oxine, as shown in Table 11.8 (Williamson, 1959). 

Table 11.7 Protective action of cobalt against the bactericidal action of oxine-iron and oxine-copper. Staph, aureus in metal-depleted broth at pH 7.3 (20°C) m/25 000 oxine present in every tube...

Fig. 11.9 The antagonism between oxine and traces of cobalt. Staphylococcus aureus in nutrient broth at pH 7.2 (see p. 472)... 

Table 11.8 Protective effect of cobalt against the trypanocidal action of oxine. T. rhodesiense in horse-serum glucose saline at 37°C, incubated for 4 hours...

Cobalt antagonizes the action of sodium dimethyldithiocarbamate on Aspergillus niger ] xsi as it does that of oxine (copper-catalysed) on yeast (p. 472) (Dr A. Kaars Sijpesteijn, personal communication, 1969). [For the copper-activated bactericidal properties of DMDC, see Liebermeister (1950).]... 

Because parasites are dependent on the host cell for nutrients and essential components, the arguments mentioned previously for alteration of the optimal metal concentration and its application to antibacterial and antiviral therapy are equally valid in the case of parasites. The sequestration of zinc and subsequent biochemical effects may present an example of this and the behaviour is somewhat reminiscent of the early and classic demonstration of the mode of action of 8-hydroxyquinoline (oxine). This reagent is also trypanocidal and, as with bacterial systems, cobalt protects against the lethal action [88]. The mode of action of oxine is presumably the same as for bacteria (see Chapter 9). Other chelating agents studied in... 

Antagonism by cobalt of the toxic action of oxine-iron. It is evident that... 

PROTECTIVE ACTION OF COBALT AGAINST THE BACTERICIDAL ACTION OF OXINE-IRON AND OXINE-COPPER... 

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