The Use and Abuse of the dppho Radical

The (2,2-diphenyl-1-picrylhydrazyl)dpphop-radical is approaching one hundred years of age. It was discovered by Goldschmidt and Renn in 1922 in a more general work on hydrazyl radicals (R2NNRo),1 radicalsthat generally are persistent but not stable. The dppho radical is intensely colored in purple and is also stable essentially because of the steric hindrance of the NO2 groups around the divalent N.2These two qualities have paved the way to an extensive use of this radical in procedures that are scientifically sound and others that are not.The interest in the chemistry of this radical is witnessed by the numbers. Scopus lists 15,488 papers with the 'word' dpphlimiting the search to the decade 2004 - 2014. Most of these works include outcomes from the so-called "dpph test" which consists in the addition of a certain amount of a potentialantioxidantto a dpphosolution and in theevaluation (via UV-vis spectroscopy) of the % of dppho decayed after anarbitrary and often variable time (minutes to hours).3This test is based on the ability that dppho has to abstract H-atoms from weak H-X bonds (X = O, N, S), reaction 1. Common H-atom donors are phenols, non-tertiary aromatic amines andthiols, compounds thatgenerally have marked antioxidant abilities. ndppho+ X-H dpph-H + products (1) The concentration of antioxidant required to reduce by 50% theinitial quantityof dppho is erroneously taken as a measure of the effectiveness of the antioxidant. With a symbolism borrowed from toxicology circles, this quantity is called IC50(a lower value indicates a better antioxidant).However, the values of IC50reported in the literature for the same compound very often vary dramatically (e.g., ascorbic acid IC50 from 1.35 to 629 mM).3 In fact, the IC50is merelyrelated to the stoichiometry, n, of reaction 1 and thus is a stationaryparameter.The antioxidant abilitymust instead be relatedto a kinetic parameter because the antioxidant must be a swiftH-atom donor in order to slow down the rate of oxidation.4It is therefore more appropriate to assess the antioxidant ability of a compound through the rate of reaction 1 rather than the stoichiometry. Another inexhaustible source of mistake is the scarce attention,which is noticeable in many papers,to solvent effects.Solvents do influence the antiradical and antioxidant properties of H-atom donors. The mechanism by which dppho abstracts H-atoms from phenols is, for instance, largely dependent on the nature of the solvent. In apolar solvents, the transition state structures for reaction 1 show that it cannot be described as occurring exclusively by eithera H-atom transfer (HAT) or a protoncoupledelectron- transfer (PCET)mechanism.5On the other hand, in ionizing solvents reaction 1 occurs for phenols via a sequential proton-loss electrontransfer(SPLET) mechanism.6 (1) Goldschmidt, S.; Renn, K. Ber. Deutsch. Chem. Gesel. 1922, B55, 628. (2) Williams, D. E. J. Am. Chem. Soc. 1966, 88, 5665. Williams,D. E. J. Am. Chem. Soc. 1967, 89, 4280. (3) Pyrzynska, K.;P?kal, A. Anal. Methods2013, 5, 4288. (4) Foti, M. C. J.Pharm. Pharmacol. 2007, 59, 1673. (5) Foti, M. C.; Daquino, C.; Mackie, I. D.; DiLabio, G. A.; Ingold, K. U. J. Org. Chem. 2008, 73, 9270. (6) Foti, M. C.; Daquino, C.; Geraci, C. J.Org. Chem. 2004, 69, 2309. Litwinienko, G.; Ingold, K. U. J. Org. Chem. 2004, 69, 5888.