Mitochondria-targeted spin traps: synthesis, superoxide spin trapping, and mitochondrial uptake. Chem Res Toxicol 2014 Jul 21;27(7):1155-65
Date
06/04/2014Pubmed ID
24890552Pubmed Central ID
PMC5452977DOI
10.1021/tx500032eScopus ID
2-s2.0-84904659978 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
Development of reliable methods and site-specific detection of free radicals is an active area of research. Here, we describe the synthesis and radical-trapping properties of new derivatives of DEPMPO and DIPPMPO, bearing a mitochondria-targeting triphenylphosphonium cationic moiety or guanidinium cationic group. All of the spin traps prepared have been observed to efficiently trap superoxide radical anions in a cell-free system. The superoxide spin adducts exhibited similar spectral properties, indicating no significant differences in the geometry of the cyclic nitroxide moieties of the spin adducts. The superoxide adduct stability was measured and observed to be highest (t1/2 = 73 min) for DIPPMPO nitrone linked to triphenylphosphonium moiety via a short carbon chain (Mito-DIPPMPO). The experimental results and DFT quantum chemical calculations indicate that the cationic property of the triphenylphosphonium group may be responsible for increased superoxide trapping efficiency and adduct stability of Mito-DIPPMPO, as compared to the DIPPMPO spin trap. The studies of uptake of the synthesized traps into isolated mitochondria indicated the importance of both cationic and lipophilic properties, with the DEPMPO nitrone linked to the triphenylphosphonium moiety via a long carbon chain (Mito10-DEPMPO) exhibiting the highest mitochondrial uptake. We conclude that, of the synthesized traps, Mito-DIPPMPO and Mito10-DEPMPO are the best candidates for potential mitochondria-specific spin traps for use in biologically relevant systems.
Author List
Hardy M, Poulhés F, Rizzato E, Rockenbauer A, Banaszak K, Karoui H, Lopez M, Zielonka J, Vasquez-Vivar J, Sethumadhavan S, Kalyanaraman B, Tordo P, Ouari OAuthors
Micael Joel Hardy PhD Visiting Assistant Professor in the Biophysics department at Medical College of WisconsinBalaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin
Jeannette M. Vasquez-Vivar PhD Professor in the Biophysics department at Medical College of Wisconsin
Jacek M. Zielonka PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCyclic N-Oxides
Mitochondria, Heart
Organophosphonates
Pyrroles
Rats
Spin Trapping
Superoxides
