title: Adding a Second Quinol to a Redox-Responsive MRI Contrast Agent Improves Its Relaxivity Response to H2O2.
abstract: The overproduction of reactive oxygen species has been linked to a wide array of health disorders. The ability to noninvasively monitor oxidative stress in vivo could provide substantial insight into the progression of these conditions and, in turn, could facilitate the development of better diagnosis and treatment options. A mononuclear Mn(II) complex with the redox-active ligand N,N'-bis(2,5-dihydroxybenzyl)-N,N'-bis(2-pyridinylmethyl)-1,2-ethanediamine (H4qtp2) was made and characterized. A previously prepared Mn(II) complex with a ligand containing a single quinol subunit was found to display a modest T1-derived relaxivity response to H2O2. The introduction of a second redox-active quinol both substantially improves the relaxivity response of the complex to H2O2and reduces the cytotoxicity of the sensor but renders the complex more susceptible to transmetalation. The addition of H2O2partially oxidizes the quinol subunits to para-quinones, concomitantly increasing the r1from 5.46 mM-1s-1to 7.17 mM-1s-1. The oxidation of the ligand enables more water molecules to coordinate to the metal ion, providing an explanation for the enhanced relaxivity. That the diquinol complex is only partially oxidized by H2O2is attributed to its activity as an antioxidant; the complex can both catalytically degrade superoxide and serve as a hydrogen atom donor.
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University , Auburn, Alabama 36849, United States.
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University , Auburn, Alabama 36849, United States.
authors.forename: Meghan B
authors.initials: MB
authors.lastname: Ward
authors.affiliation: Department of Chemistry and Pharmacy, University Erlangen-Nuremberg , 91058 Erlangen, Germany.
authors.forename: Alicja
authors.initials: A
authors.lastname: Franke
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University , Auburn, Alabama 36849, United States.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Ambrose
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University , Auburn, Alabama 36849, United States.
authors.forename: Zachary L
authors.initials: ZL
authors.lastname: Whaley
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University , Auburn, Alabama 36849, United States.
authors.forename: Thomas Miller
authors.initials: TM
authors.lastname: Bradford
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University , Auburn, Alabama 36849, United States.
authors.forename: John D
authors.initials: JD
authors.lastname: Gorden
authors.affiliation: Auburn University Magnetic Resonance Imaging Research Center , Auburn, Alabama 36849, United States.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Beyers
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University , Auburn, Alabama 36849, United States.
authors.forename: Russell C
authors.initials: RC
authors.lastname: Cattley
authors.affiliation: Department of Chemistry and Pharmacy, University Erlangen-Nuremberg , 91058 Erlangen, Germany.
authors.forename: Ivana
authors.identifier: http://orcid.org/0000-0002-1651-3359
authors.initials: I
authors.lastname: Ivanović-Burmazović
authors.affiliation: Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University , Auburn, Alabama 36849, United States.
authors.forename: Dean D
authors.initials: DD
authors.lastname: Schwartz
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University , Auburn, Alabama 36849, United States.
authors.forename: Christian R
authors.identifier: http://orcid.org/0000-0001-7293-1267
authors.initials: CR
authors.lastname: Goldsmith
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006873:Hydroquinones / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D008345:Manganese / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats
chemical_list: D000975:Antioxidants; D003287:Contrast Media; D006873:Hydroquinones; D009942:Organometallic Compounds; D008345:Manganese; D006861:Hydrogen Peroxide