title: Reaction of tetracycline with biologically relevant chloramines.
abstract: Helicobacter pylori (H. pylori) infection triggers inflammatory processes with the consequent production of hypochlorous acid (HOCl), monochloramine (NH2Cl), and protein-derived chloramines. As the therapy for eradicating H. pylori is partially based on the use of tetracycline, we studied the kinetic of its consumption elicited by HOCl, NH2Cl, N-chloro-n-butylamine (NHCl-But, used as a lysine-derived chloramine model), and lysozyme-derived chloramines. In the micromolar concentration range, tetracycline reacted rapidly with HOCl, generating in the first few seconds intermediates of short half-life. In contrast, a slow tetracycline consumption was observed in the presence of high NH2Cl and NHCl-But concentrations (millimolar range). Similar chlorinated products of tetracycline were identified by mass spectrometry, in the presence of HOCl and NH2Cl. These results evidenced that tautomers of tetracycline are pivotal intermediates in all reactions. In spite of the low reactivity of chloramines towards tetracycline, it is evident that, in the concentration range where they are produced in a H. pylori infection (millimolar range), the reactions lead to oxidation and/or chlorination of tetracycline. This kind of reactions, which were also observed triggered by lysozyme-derived chloramines, could limit the efficiency of the tetracycline-based therapy.
authors.affiliation: Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile, C.P. 782 0436, Santiago, Chile.
authors.forename: J
authors.initials: J
authors.lastname: Benavides
authors.affiliation: Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Barrias
authors.affiliation: Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile, C.P. 782 0436, Santiago, Chile.
authors.forename: N
authors.initials: N
authors.lastname: Piro
authors.affiliation: Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile, C.P. 782 0436, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Arenas
authors.affiliation: Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Orrego
authors.affiliation: Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Santiago, Chile.
authors.forename: E
authors.initials: E
authors.lastname: Pino
authors.affiliation: Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Santiago, Chile.
authors.forename: L
authors.initials: L
authors.lastname: Villegas
authors.affiliation: Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile, C.P. 782 0436, Santiago, Chile.
authors.forename: E
authors.initials: E
authors.lastname: Dorta
authors.affiliation: Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Santiago, Chile. Electronic address: alexis.aspee@usach.cl.
authors.forename: A
authors.initials: A
authors.lastname: Aspée
authors.affiliation: Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile, C.P. 782 0436, Santiago, Chile. Electronic address: clopezr@uc.cl.
authors.forename: C
authors.initials: C
authors.lastname: López-Alarcón
mesh_terms: D000136:Acid-Base Equilibrium; D002700:Chloramines / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D006997:Hypochlorous Acid / Q000737:chemistry; D009113:Muramidase / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry; D013754:Tetracyclines / Q000737:chemistry*
chemical_list: D002700:Chloramines; D013754:Tetracyclines; D006997:Hypochlorous Acid; D009113:Muramidase
keywords: Chloramines; Hypochlorite; Hypochlorous acid; Lysozyme; Monochloramine; Tetracycline