Mitochondria-targeted spin traps

Synthesis, superoxide spin trapping, and mitochondrial uptake

Micael Hardy, Florent Poulhés, Egon Rizzato, A. Rockenbauer, Karol Banaszak, Hakim Karoui, Marcos Lopez, Jacek Zielonka, Jeannette Vasquez-Vivar, Savitha Sethumadhavan, Balaraman Kalyanaraman, Paul Tordo, Olivier Ouari

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 Mito 10-DEPMPO are the best candidates for potential mitochondria-specific spin traps for use in biologically relevant systems.

Original languageEnglish
Pages (from-to)1155-1165
Number of pages11
JournalChemical Research in Toxicology
Volume27
Issue number7
DOIs
Publication statusPublished - Jul 21 2014

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Spin Trapping
Mitochondria
Superoxides
Bearings (structural)
Carbon
Guanidine
Discrete Fourier transforms
Cell-Free System
Free Radicals
Anions
Derivatives
Geometry
Research
Mito-DIPPMPO
nitrones

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

Cite this

Mitochondria-targeted spin traps : Synthesis, superoxide spin trapping, and mitochondrial uptake. / Hardy, Micael; Poulhés, Florent; Rizzato, Egon; Rockenbauer, A.; Banaszak, Karol; Karoui, Hakim; Lopez, Marcos; Zielonka, Jacek; Vasquez-Vivar, Jeannette; Sethumadhavan, Savitha; Kalyanaraman, Balaraman; Tordo, Paul; Ouari, Olivier.

In: Chemical Research in Toxicology, Vol. 27, No. 7, 21.07.2014, p. 1155-1165.

Research output: Contribution to journalArticle

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, O 2014, 'Mitochondria-targeted spin traps: Synthesis, superoxide spin trapping, and mitochondrial uptake', Chemical Research in Toxicology, vol. 27, no. 7, pp. 1155-1165. https://doi.org/10.1021/tx500032e
Hardy, Micael ; Poulhés, Florent ; Rizzato, Egon ; Rockenbauer, A. ; Banaszak, Karol ; Karoui, Hakim ; Lopez, Marcos ; Zielonka, Jacek ; Vasquez-Vivar, Jeannette ; Sethumadhavan, Savitha ; Kalyanaraman, Balaraman ; Tordo, Paul ; Ouari, Olivier. / Mitochondria-targeted spin traps : Synthesis, superoxide spin trapping, and mitochondrial uptake. In: Chemical Research in Toxicology. 2014 ; Vol. 27, No. 7. pp. 1155-1165.
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AU - Banaszak, Karol

AU - Karoui, Hakim

AU - Lopez, Marcos

AU - Zielonka, Jacek

AU - Vasquez-Vivar, Jeannette

AU - Sethumadhavan, Savitha

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