title: Hypobromous acid, a powerful endogenous electrophile: Experimental and theoretical studies.
abstract: Hypobromous acid (HOBr) is an inorganic acid produced by the oxidation of the bromide anion (Br(-)). The blood plasma level of Br(-) is more than 1,000-fold lower than that of chloride anion (Cl(-)). Consequently, the endogenous production of HOBr is also lower compared to hypochlorous acid (HOCl). Nevertheless, there is much evidence of the deleterious effects of HOBr. From these data, we hypothesized that the reactivity of HOBr could be better associated with its electrophilic strength. Our hypothesis was confirmed, since HOBr was significantly more reactive than HOCl when the oxidability of the studied compounds was not relevant. For instance: anisole (HOBr, k2=2.3×10(2)M(-1)s(-1), HOCl non-reactive); dansylglycine (HOBr, k2=7.3×10(6)M(-1)s(-1), HOCl, 5.2×10(2)M(-1)s(-1)); salicylic acid (HOBr, k2=4.0×10(4)M(-1)s(-1), non-reactive); 3-hydroxybenzoic acid (HOBr, k2=5.9×10(4)M(-1)s(-1), HOCl, k2=1.1×10(1)M(-1)s(-1)); uridine (HOBr, k2=1.3×10(3)M(-1)s(-1), HOCl non-reactive). The compounds 4-bromoanisole and 5-bromouridine were identified as the products of the reactions between HOBr and anisole or uridine, respectively, i.e. typical products of electrophilic substitutions. Together, these results show that, rather than an oxidant, HOBr is a powerful electrophilic reactant. This chemical property was theoretically confirmed by measuring the positive Mulliken and ChelpG charges upon bromine and chlorine. In conclusion, the high electrophilicity of HOBr could be behind its well-established deleterious effects. We propose that HOBr is the most powerful endogenous electrophile.
authors.affiliation: Department of Chemistry, Faculty of Sciences, São Paulo State University (UNESP), 17033-360, Bauru, São Paulo, Brazil. Electronic address: vfximenes@fc.unesp.br.
authors.forename: Valdecir Farias
authors.initials: VF
authors.lastname: Ximenes
authors.affiliation: Department of Chemistry, Institute of Chemistry, Campinas State University (UNICAMP), 13083-861, Campinas, São Paulo, Brazil.
authors.forename: Nelson Henrique
authors.initials: NH
authors.lastname: Morgon
authors.affiliation: Department of Chemistry, Faculty of Sciences, São Paulo State University (UNESP), 17033-360, Bauru, São Paulo, Brazil.
authors.forename: Aguinaldo Robinson
authors.initials: AR
authors.lastname: de Souza
mesh_terms: D001959:Bromates / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D001959:Bromates; C027664:hypobromous acid
keywords: Hypobromous acid; Hypochlorous acid; Myeloperoxidase; Reactive electrophilic species; Reactive oxygen species