The Reduction Potential of the Couple O3 /O;

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provided by Elsevier - Publisher Connector Volume 140. number 2 FEBS LETTERS April 1982

THE REDUCTION POTENTIAL OF THE COUPLE O3 /O;-

Consequences for mechanisms of ozone toxicity

W. H. KOPPENOL Department of Chemistry, University of Maryland Baltimore County, Catonsville, MD 21228, USA

Received 12 January 1982

1. Introduction 0s+HzO+20;-+2H+ (1)

The toxicity of ozone, a major constituent of pho. At pH 7 Gibbs energies of formation (AGO;) for Oa, tochemical smog is well documented [ 11. According HZ0 and O;- are 39.1 [ 11, -37.6 and 7.6 kcal/mol*. to the Handbook of Chemistry and Physics [2], the The latter two values follow via AGO’ = -nFM”’ ozone molecule is a powerful two-electron oxidant from the reduction potential at pH 7 of the couples with a standard reduction potential of 2.07 V. The Oz/HzO, 0.82 V and 0,/O;-, -0.33 V [7]. From these products of this reaction are oxygen and water. Since data it is calculated that at this pH reaction (1) is two-electron reactions are normally slow, it might be most unlikely to occur, having a Gibbs energy change relevant to investigate the thermodynamics of two of 13.7 kcal. At alkaline pH, however, the reaction consecutive electron transfers, to determine whether becomes thermodynamically possible, because the other reactive oxygen species could be intermediates. Gibbs energy of formation for water is less negative. Secondary oxidizing agents might be formed [3] as To calculate the reduction potential of the couple suggested by the decrease of glutathione in red blood 0,/O;- one needs to know the Gibbs energy of for- cells upon exposure to ozone. One might suspect mation of the ozonide anion, O;-. This quantity can ‘OH radicals for this role since Oa in alkaline solution be estimated as follows. From radiation and flash were proposed to lead to the formation of the super- photolysis studies it is known that O’-, the anion of oxide anion [4], which upon reaction with a second the hydroxyl radical, reacts with oxygen to form O;- ozone molecule yields the ‘OH radical and oxygen. [g-lo]. The pK of equilibrium (2) is 11.9 [ll]: It is shown here that this reaction sequence is unlikely at pH 7. Instead, the ozone molecule is ‘OH 2 H’ •t O’- (2) thermodynamically a powerful one-electron oxidant by itself, and the ozonide anion, O;- can be a precursor At this pH, reaction (3) takes place: of the hydroxyl radical. These reactions might take place in addition to the well-characterized reactions 02 -I-o’- 2 o;- (3) of ozone with double bonds in unsaturated lipid molecules [.5,6]. The rate constants k3 and k_, are (3.0 f 0.5) X lo9 M-l. s-l and (5.0 + 0.5) X lo3 s-l, respectively [12], leading to a Gibbs energy of -7.8 * 0.1 kcal 2. Thermodynamics for this reaction in the forward direction via the rela- tion AGO’ = -RT In k3/k_, in which R is the gas con- The following reaction at alkaline pH [4]: stant and T the temperature in Kelvin. Based on a reduction potential of 1.4 f 0.1 V [13] at pH 14 for * Thermodynamic values for these and other oxygen radicals the couple ‘OH/OH- and a Eo’ of 0.82 V (pH 7) for are discussed elsewhere, together with various intercon- the couple Oz/HzO, one calculates a AGoi of4 f 2 kcal/ version reactions (W. H. K., A. Singh, in preparation) mol for the hydroxyl radical at pH 7. Thus, at pH 7:

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AGO;-(Oj-) = AGO; + 2.3 RT (11.9-7) + AGO’ (3) O;- reacts with another O;-: (reaction 3) 20;-+2H’+H,O,+20, AGO’=-24*4kcal = 3 t 2 kcal/mol (4) (9)

Combining the data for 0s and O;-, it follows that Pulse radiolysis studies in alkaline solutions indi- the standard reduction potential for the reaction: cate that the ozonide anion itself does not react, but first dissociates in Oa and O’- (see [ 121). If this also 03 (g) + e- h Oi- (as) (5) occurs at lower pH, reaction (7a) would be the pre- dominant way of decay of the ozonide radical. is 1.6 + 0.1 V. If at pH < 10.4 the ozonide radical is These thermodynamic data are plotted in an oxi- protonated ([ 141 (but see [ 121)) the standard potential dation state diagram of the system O?-HzOz (fig.1) at pH 7 for the reaction: [ 1.51. The slopes of the lines in fig.1 represent reduction potentials (legend). Ozone appears to be a very 0s (g) t e- t H’ --, HOj (aq) (6) strong one-electron oxidant as follows from the slope of the line joining 0s and O;-. would be higher, 1.8 f 0.1 V and the Gibbs energy of An attempt can now be made to calculate the formation of HO; is calculated to be -2 f 0.2 kcal. Gibbs energy of hydration for the ozonide radical. At this point there are thermodynamically 3 pos- sibilities:

1.0 - pti-7 (1) The ozonide radical (O;-) dissociates into the hydroxyl radical and oxygen: . ‘c,+

O;-+H++‘OH+02 (7a) a 0.5 Since the error in AGOk(Oj-) originates from that of w IZ the hydroxyl radical, it follows that this reaction has a standard (pH 7) Gibbs energy change of t 1 .l + 0.2 kcal. For reaction (7b): 0 HO; --, Oa + ‘OH (7b)

AGO’ is 5.7 kcal. Conversely, the reaction of oxygen with the hydroxyl radical should be favorable. Since J -I -0.5 0 no such reaction has been reported, it might be that it proceeds much slower than the reaction of ‘OH with n other solutes and/or itself, or that the ozonide anion Fig.1. Oxidation state diagram of the system 0, -H,O, is protonated at pH << 10.4. The oxygen formed in (Pgases = 1 atm, T = 25°C) at pH 7: abscissa, formal charge, reaction (7a) cannot be in an excited state, since the n, per oxygen atom; ordinate (left) n times reduction poten- production of ‘As O2 would require an additional tial, Eof, (right) Gibbs energy of formation per gramatom of 22.6 kcal/mol. oxygen.The numbers refer to the gradients. The two ordinates are related by AGo’ = -FA,!?‘, which represent reduction potentials, relative to the normal hydrogen electrode. This (2) O;- oxidizes another molecule: diagram was constructed as in [ 151. The Gibbs energy of formation of the ozonide radical (O;-) calculated here, enables 0~-+2H++e-~HzO+02 (8) one to calculate the reduction potentials of the couple 0,/O;-. O;- is located just below the dashed line which indi- cates that, at equilibrium, an appreciable part of the ozonide The standard reduction potential at pH 7 of this reac- anions will be converted to hydroxyl radicals. Since the latter tion is 1.8 + 0.1 V, as calculated from the Gibbs disappear rapidly due to its reactivity, O;- might function as energies of formation given above. a source of ‘OH radicals.

170 Volume 140. number 2 FEBS LETTERS April 1982

Table 1 N204/2 NO?- and the Gibbs dissociation energy of Gibbs energies of ozone and ozonide radicals N204 [21. It is concluded that the ozone molecule is a very Species AG”f AG’&pH 7) AGgydr. strong oxidizer by itself, and that the reaction product, (kcal/mol) (kcal/mol) (kcal/mol) the ozonide radical can thermodynamically yield the 0, 39.1 39.1 - hydroxyl radical, or be a strong oxidizer itself. The 0;- 3+2 322 -90 + 2 hydroxyl radical, and most likely the ozone molecule _ HOja -11 f 2 -2 f 2 itself [22] are capable of abstracting a hydrogen atom from biomolecules, which will lead to various chain a Values are based on pK = 10.4 [14] reactions in the presence of oxygen. These reactions amplify the damage, yielding other radicals such as Taking the electron affinity (EA) of ozone to be O;-, ROO’ and RO’ [23], and take presumably place 2.14 f 0.15 eV [16], and the Gibbs energy of forma- concomitant with the reaction of ozone with unsatu- tionofH’tobe 102.5kcal[17],avalueof-9052kcal rated lipid molecules, which might also produce vari- is calculated according to eq. (10): ous radicals [6].

AGo 103 (g) + l/2 H2 3 O;- (aq) + H’] = -EA + Acknowledgement

“Eydr. (O;-) + AGO, (H’) (10) I thank Dr J. Liebman for suggesting the analogy Gibbs energies of formation and hydration are col- between ozone and nitrogen dioxide. lected in table 1.

References 3. Discussion [II Mustafa, M. G. and Tierney, D. F. (1978) Am. Rev. Resp. Dis. 118, 1061-1090. The reduction potential of the couple 03/O;- PI Weast, R. C. ed (1970) Handbook of Chemistry and depends on the value for E”’ (‘OH/H,O). The theo- Physics, 5 1st edn, pp. D-67, -68 and -112, The Chemi- retical values for this couple derived from Born-Haber cal Rubber Co., Cleveland OH. type considerations [ 18 ,191 are typically 0.6 V higher [31 Freeman, B. A. and Mudd, J. B. (1981) Arch. Biochem. than the value derived from 3 independent expt [ 131. Biophys. 208, 212-220. Alder, M. G. and Hill, G. R. (1950) J. Am. Chem. Sot. Such a theoretical value would result in reduction [41 72,1884-1886. potentials for the couples 03/HOj and 03/O;- which 151 Menzel, D. B. (1976) in: Free Radicals in Biology would be correspondingly lower, 1.2 V and 1 .O V, (Pryor, W. A. ed) vol. 2, pp. 181-202, Academic Press, respectively, but still considerably higher than that New York. of the couple ‘Ag 02/O;-, 0.65 V [15]. Such values [61 Pryor, W. A. (1978) Photochem. Photobiol. 28, 787-801. are likely to have harmful implications, since singlet [71 Wood, P. M. (1974) FEBS Lett. 44,22-24. oxygen was already found to oxidize NADH, produc- 181 Heidt, L. J. and Landi, V. R. (1964) J. Chem. Phys. 41, ing 02- and NAD’ [20]. 176-178. The value of 1.6 V for the reduction potential of [91 Czapski, G. and Dorfman, L. M. (1964) J. Phys. Chem. the couple 0,/O;- is supported by the following con- 68,1169-1177. Adams, G. E., Boag, J. W. and Michael, B. D. (1966) siderations. Ozone and nitrogen dioxide are similar [lOI Proc. Roy. Sot. A 289,321-341. in shape and have electron affinities which are the 1111 Rabani, J. and Matheson, M. S. (1964) J. Am. Chem. same within the error, 2.14 _+0.15 and 2.3 f 0.2 eV, Sot. 86,3175-3176. respectively (see [20]). Assuming that the Gibbs 1121 Czapski, G. (1971) Annu. Rev. Phys. Chem. 22, hydration energies are also similar, one would expect 171-208. [I31 Heckner, K.-H. and Landsberg, R. (1965) Z. Phys. the couples N02/NOZ- and 0,/O;- to have reduction Chem. 230,63-72. potentials which are comparable. This is indeed the [I41 Buxton, G. V. (1969) Trans. Faraday Sot. 65, case, the value for the couple N02/N02- being smaller, 2150-2158. 0.9 1 V, as calculated from the value for the couple [ISI Koppenol, W. H. (1976) Nature 262,420-421.

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[16] Rothe, E. W., Tang, S. Y. and Reck, G. P. (1975) J. [20] Peters, G. and Rodgers, M. A. J. (1980) Biochem. Bio- Chem. Phys. 62,3829-3831. phys. Res. Commun. 96,770-776. [17] Rosseinsky, D. R. (1965) Chem. Rev. 65,467-490. [21] Lowe, J. P. (1977) J. Am.Chem. Sot. 99,5557-5570. [ 181 George, P. (1965) in: Oxidases and Related Redox Sys- [22] Kurz, M. E. and Pryor, W. A. (1978) J. Am. Chem. Sot. tems(King, T. E. et al. eds) pp. 3-36, Whey, New York. 100,7953-7959. [ 191 Berdnikov, V. M. and Bazhin (1970) Russ. J. Phys. [23] Koppenol, W. H. (1981) Clin. Resp. Physiol. 17 suppl., Chem. 44,395-398. 85-89.

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