Hafnium(IV)-nitrilotriacetate and hafnium(IV)-fluoride complexes investigated using an ion-selective electrode

Po/yhe%on Vol. 4, No. II, pp. 1883-1886, 1985 Printed in Great Britain

0

0277-5x37/85 s3.00+ .oo 1985 Pergamon Prcs Ltd

HAFNIUM(JJ+NITRILOTRIACETATE AND HAFNIUM(IV)-FLUORIDE COMPLEXES INVESTIGATED USING AN ION-SELECTIVE ELECTRODE NICHOLAS E. IVORY and DAVID R. WILLIAMS* Department of Applied Chemistry, University of Wales Institute of Science and Technology, PO Box 13, Cardiff CFl 3XF, U.K. (Received 25 April 1985 ; accepted 10 May 1985) Abstract-Models of plutonium solution chemistry in vivo require formation constants which are difficult to obtain but hafnium(IV) is biochemically similar to plutonium(IV) in vivo. This paper reports the use of fluoride as a competing ligand to suppress metal ion hydrolysis and formation constants, determined using a fluoride ion-selective electrode, for the following systems-fluoride-H+, fluoride-hafnium(IV) and nitrilotriacetate-hafnium(IV) at 37”C, I = 150 mm01 dm- 3 sodium chloride.

Since the introduction of nuclear fission in the late 193Os, the element causing most public concern is undoubtedly plutonium, as it occurs in both weapons and energy production.‘*2 Many attempts have been made, and are still in progress, to determine the biochemistry of this man-made element.2s3 A deeper understanding of the mechanisms of transport, tissue deposition, toxicity and excretion of complexes of plutonium would greatly assist toxicologists and clinicians. Hopefully, such an approach might lead to a range of therapeuticals that could be used to treat plutonium-intoxicated patients.2 The chemistry of plutonium has been widely reviewed.3-7 The metal is unique in that it can exist simultaneously in all four of its oxidation states, (III), (IV), (V) and (VI). However, under physiological conditions it usually occurs as plutonium(IV). The human body is 70% water by weight and, when considering the biochemistry of plutonium, it is predominantly that of hydrolysis, polymerization and complex formation. The solubility product of plutonium(IV) hydroxide is of the order of 10m5’j mo15 dm-i5 and so investigations into the sites of physiological attack of plutonium(IV) in vivo must, of necessity, have the plutonium firmly complexed in order to maintain it in solution. The ligand of choice is usually a polycarboxylic acid, such as nitrilotriacetate(NTA). * Author to whom correspondence should be.addressed.

Various studiess*’ concerning the physiological distribution of plutonium(IV) species predominating in vivo agree with our previous broad classification of metal distribution” .into inert species, labile protein and low-molecular-weight complexes. The so-called inert plutonium species includes insoluble deposits of fluorides, hydroxides, oxides, and other polymeric aggregates in addition to protein complexes with ferritin and haemosiderin.‘0-‘2 The second fraction is transferrin-bound and this /?-globulin is responsible for transporting plutonium through the bloodstream.13*‘4 Finally, there is some evidence that the third fraction, the low-molecular-weight complexes, is mainly plutonium citrate.15 When soluble plutonium complexes are introduced into man, they initially complex with the iron transport protein transferrin and with citrate which carries the plutonium to the liver and bone marrow where it becomes associated with ferritin and haemosiderin. ’ 2 Clearly, any studies of this biochemistry and of competing complexes chosen to adapt such deposition mechanisms into excretion pathways, must be subject to the problems associated with the toxicity and radioactivity of the plutonium. Fortunately, Taylor et aZ.16have discovered that radiohafnium, when introduced into rats or hamsters, follows similar metabolic pathways to those for plutonium. In particular, it collects in the same target organs as plutonium(IV). Retention

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N. E. IVORY

and D. R. WILLIAMS

times of hafnium and plutonium in the plasma and in the liver are similar and the radiohafnium becomes bound to the iron transport protein transferrin in plasma and in liver cytosol in both the rat and the hamster. Indeed, these experiments using radiohafnium suggest that non-radioactive hafnium would be a good “surrogate” metal for studying the complexing of plutonium in uiuo. Chemically, plutonium and hafnium have many similarities which include relatively small sizes of the solvated ions, high charge densities, and a propensity towards hydrolysis and hydrolytic polymerization.r7a1* Even though hafnium does not display plutonium’s range of valency states, it does have the important valence of 4 which is the physiologicallyimportant state for plutonium in ho. Thus, we use hafnium(IV) solutions as models of plutonium complexing with ligands of biological interest. These solutions can be used in the open laboratory without the necessity for radiation protection. When plutonium model studies using hafnium are undertaken in animals, for example, the binding of hafnium to transferrin,lg it is necessary to use a powerful ligand such as the NTA anion in order to keep the hafnium in solution and to permit it to transfer to transferrin binding. Thus, the main aim of this research is to produce formation constants for hafnium-NTA complexing under physiological conditions of 37°C and 150 mmol dm-3 sodium chloride appropriate to blood plasma. EXPERIMENTAL Our standard glass electrodecalomel electrode potentiometric approach proved inapplicable to the hafnium-NTA-proton system because metalligand binding was too powerful.20 Rather, we found that it was necessary to introduce a competing ligand in order to moderate the hafnium ion’s avidity for NTA. We chose fluoride as a second ligand capable of competing with the hydroxide ion for hafnium on the basis of speciation plots generated using literature values for the hafnium hydroxy species’ ’ and hafnium fluoride species.22 In the absence of fluoride, hydroxy species are prevalent even at pH values below 1, whereas, in the presence of 30 mm01 dm- 3 fluoride, such hydrolysis can be suppressed right up to pH 6. As the fluoride ionselective electrode has been used for two decades,23 we decided to use this as an analytical tool rather than the glass electrode which is attacked by hydrofluoric acid, the silica in the glass being converted into fluorosilicic acid. This would have resulted in inaccurate readings from the glass electrode.24.25 The fluoride ion-selective electrode was supplied

by Orion Research Inc., and was of classical design employing a lanthanium fluoride membrane doped with 0.05 mol % europium fluoride and a filling solution of 1 mol dmm3 potassium fluoride solution saturated with potassium chloride and sodium chloride.26 This design of electrode is fairly free of interference effects other than those caused by the hydroxide, citrate and some other carboxylate ions. These were not found to be a problem in our studies as fairly low concentrations were used. The electrode was calibrated using a range of concentrations of standard fluoride solution with a constant ionic background strength of 150 mmol dm- 3 sodium chloride. Nernstian behaviour to within a O.l-mV drift over 1 h was found. Any variation from reproducibility with time arising because of pitting or coating of the membrane, was easily polished off using a fine polishing powder.27 The emf readings between this electrode and a calomel reference electrode was used as input for our standard potentiometric least-squares programmes. Protonation of fluoride was measured using the fluoride ion-selective electrode and a calomel reference electrode. The titration data produced was fed into a modified version of MINIQUAD,2892g which considered the fluoride ion as equivalent to the acid in conventional acid-based titrations. The value for monoprotonated fluoride, HF, is in good agreement with the results from other works,3&37 but the species HF; 38and H2F+ 3g*40in addition to H2F2,22 were not found in this study. Our values and the appropriate statistics are shown in Table 1. The hafnium fluoride interaction was quantified likewise and is reported in Table 1. Formation constants for the three higher complexes of 4 : 1,5 : 1 and 6: 1 fluoride: hafnium (the 410, 510 and 610 species, respectively) were apparently measurable but the 100,210 and 310 species were not detectable because this would have involved fluoride concentrations below the detection limit of the electrode. (approximately 10e6 mol dme3 F-). However, constants for the lower species were taken from the literatureZ2 and these have been determined by solvent extraction and by the iron redox electrode approach to potentiometry. We had some difficulty establishing the existence of the 510 species and the value reported is that obtained using the Bjerrum’s Zl,2 method. The speciation plot in Fig. 1 shows a preponderance of 410 and 610 species and very low levels of the 510 intermediate. The values obtained from the MINIQUAD assessment for the 410 and 610 species are in reasonable agreement with those reported by other workers.21,22*41,42 Bearing in mind that we used the fluoride electrode in preference to the glass electrode, it is interesting to

Hafniurn(IVjnitrilotriacetate

and hafnium(I~fluoride

complexes

1885

Table 1. Log formation constants at 37°C and Z = 150 mm01 dmm3 sodium chloride for the following systems : (a) fluoride (p)-proton (r), (b) hafnium (q)-fluoride (p) and (c) hafnium (qtnitrilotriacetate (p)

No.of

Species

(a) (b)

P

q

r

log Z&r

Standard deviation

1

0

1

3.003

0.0011

(MINIQUAD) 4 1 0 5 1 0 6 1 0

0.8009 0.3879

24.533 32.926

0.0246 0.0260

17.30

0.175

(ESTAZ) 1 0 1 0

(b) 4 6 (c)

30.158 Negative 40.481

1

1

0

note that the statistics found with the former method are not as good as those expected from the latter, the standard deviations being approximately an order of magnitude greater and the sum of the squares being two orders of magnitude larger than those for comparable glass electrode work. We must remember, however, that the glass electrode would not have worked in the presence of fluoride. The R factor obtained by both methods is of comparable magnitude and this value, along with the superimposability of the experimentally and theoretically produced formation curves, gives us confidence that these complexes are real and that the formation constant values are reliable. The data were also fed into the ESTAZ optimization program (see Table 1).43*44It is noteworthy that ESTA2 also failed to detect the existence of the 510 species. Hafnium-NTA

interaction

The literature values for this system suggest that the log fi is approximately 20,45*46 a magnitude

I 0

, 2

ML5

, 4

I 6

I 6

I

sum of squares

data

No. of

R factor

points

titrations

9.9 x 10-7

6.3 x lo-’

325

8

1.53 x 10-2

386

8

2.08 x lo-’

386

8

1.57 x 10-2

268

7

3.32 x lo-’

-

beyond simple potentiometric determination. However, by using fluoride as a competing ligand, we were able to quantify the system in terms of a constant. A good competing ligand ought not to form mixed-ligand complexes with the metal and ligand under study and fluoride fitted this description. Additionally, it suppressed the hydrolysis of hafnium during the titrations, as mentioned previously. Experimentally, we titrated an acid solution of hafnium into mixtures of solutions of the trisodium salt of NTA and sodium fluoride. The double-ligand system was analyzable by the ESTA2 program and the results are shown in Table 1, the species detected being the 110 species. The log formation constant agrees reasonably well with values suggested from ion exchange methods.47,48 Then et ak4’ have suggested that a second NTA ligand may be complexed as an eight-fold coordinated hafnium(IV) ion in a dodecahedral structure but this bis complex was not detected by our studies. Figure 2 shows the speciation for a

_1 9

lo

-1%~ [H+l

Fig. 1. Speciation plots of HfF,, HfF; and HfFiconcentrations, pH = O-10, calculated using the formation constants in Table 1. M = H@V).

Fig. 2. Speciation plots of HfF, HfFi- and HfNTA+ complexes, pH tX9, calculated using the formation constants in Table 1 for a typical fluoride and NTA competing-ligand titration. F- = L’ and NTA3- = L.

N. E. IVORY and D. R. WILLIAMS

1886

typical hafnium-NTA-fluoride pHs.

system at various

CONCLUSIONS It appears that fluoride ion-selective electrodes are a useful means of studying complexing between hafnium(IV) as a surrogate metal ion for plutonium(IV) in solution and they also permit computational studies to yield formation constants for hafnium with powerful ligands such as NTA. Furthermore, the presence of fluoride has successfully suppressed hydrolysis in this work. The fluoride electrode performed well at all times and the statistics produced for the formation constants are within an order of magnitude as good as those that could be expected from a non-glass-attacking ligand system studied using glass electrode potentiometry.

Acknowledgements-We acknowledge the assistanceof Dr John Duffield, Dr Kevin Murray, Dr Peter May, Dr Gillian Christie and Professor David Taylor in this study and UWIST for a maintenance grant for one of us (NEI).

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