Skip to main content
Journal cover image

A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity.

Publication ,  Journal Article
Rajic, Z; Tovmasyan, A; Spasojevic, I; Sheng, H; Lu, M; Li, AM; Gralla, EB; Warner, DS; Benov, L; Batinic-Haberle, I
Published in: Free Radic Biol Med
May 1, 2012

The Mn porphyrins of k(cat)(O(2)(.-)) as high as that of a superoxide dismutase enzyme and of optimized lipophilicity have already been synthesized. Their exceptional in vivo potency is at least in part due to their ability to mimic the site and location of mitochondrial superoxide dismutase, MnSOD. MnTnHex-2-PyP(5+) is the most studied among lipophilic Mn porphyrins. It is of remarkable efficacy in animal models of oxidative stress injuries and particularly in central nervous system diseases. However, when used at high single and multiple doses it becomes toxic. The toxicity of MnTnHex-2-PyP(5+) has been in part attributed to its micellar properties, i.e., the presence of polar cationic nitrogens and hydrophobic alkyl chains. The replacement of a CH(2) group by an oxygen atom in each of the four alkyl chains was meant to disrupt the porphyrin micellar character. When such modification occurs at the end of long alkyl chains, the oxygens become heavily solvated, which leads to a significant drop in the lipophilicity of porphyrin. However, when the oxygen atoms are buried deeper within the long heptyl chains, their excessive solvation is precluded and the lipophilicity preserved. The presence of oxygens and the high lipophilicity bestow the exceptional chemical and physical properties to Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin, MnTnBuOE-2-PyP(5+). The high SOD-like activity is preserved and even enhanced: log k(cat)(O(2)(.-))=7.83 vs 7.48 and 7.65 for MnTnHex-2-PyP(5+) and MnTnHep-2-PyP(5+), respectively. MnTnBuOE-2-PyP(5+) was tested in an O(2)(.-) -specific in vivo assay, aerobic growth of SOD-deficient yeast, Saccharomyces cerevisiae, where it was fully protective in the range of 5-30 μM. MnTnHep-2-PyP(5+) was already toxic at 5 μM, and MnTnHex-2-PyP(5+) became toxic at 30 μM. In a mouse toxicity study, MnTnBuOE-2-PyP(5+) was several-fold less toxic than either MnTnHex-2-PyP(5+) or MnTnHep-2-PyP(5+).

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Free Radic Biol Med

DOI

EISSN

1873-4596

Publication Date

May 1, 2012

Volume

52

Issue

9

Start / End Page

1828 / 1834

Location

United States

Related Subject Headings

  • Superoxide Dismutase
  • Spectrophotometry, Ultraviolet
  • Spectrometry, Mass, Electrospray Ionization
  • Saccharomyces cerevisiae
  • Oxidative Stress
  • Molecular Mimicry
  • Micelles
  • Mice, Inbred C57BL
  • Mice
  • Metalloporphyrins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rajic, Z., Tovmasyan, A., Spasojevic, I., Sheng, H., Lu, M., Li, A. M., … Batinic-Haberle, I. (2012). A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity. Free Radic Biol Med, 52(9), 1828–1834. https://doi.org/10.1016/j.freeradbiomed.2012.02.006
Rajic, Zrinka, Artak Tovmasyan, Ivan Spasojevic, Huaxin Sheng, Miaomiao Lu, Alice M. Li, Edith B. Gralla, David S. Warner, Ludmil Benov, and Ines Batinic-Haberle. “A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity.Free Radic Biol Med 52, no. 9 (May 1, 2012): 1828–34. https://doi.org/10.1016/j.freeradbiomed.2012.02.006.
Rajic Z, Tovmasyan A, Spasojevic I, Sheng H, Lu M, Li AM, et al. A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity. Free Radic Biol Med. 2012 May 1;52(9):1828–34.
Rajic, Zrinka, et al. “A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity.Free Radic Biol Med, vol. 52, no. 9, May 2012, pp. 1828–34. Pubmed, doi:10.1016/j.freeradbiomed.2012.02.006.
Rajic Z, Tovmasyan A, Spasojevic I, Sheng H, Lu M, Li AM, Gralla EB, Warner DS, Benov L, Batinic-Haberle I. A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity. Free Radic Biol Med. 2012 May 1;52(9):1828–1834.
Journal cover image

Published In

Free Radic Biol Med

DOI

EISSN

1873-4596

Publication Date

May 1, 2012

Volume

52

Issue

9

Start / End Page

1828 / 1834

Location

United States

Related Subject Headings

  • Superoxide Dismutase
  • Spectrophotometry, Ultraviolet
  • Spectrometry, Mass, Electrospray Ionization
  • Saccharomyces cerevisiae
  • Oxidative Stress
  • Molecular Mimicry
  • Micelles
  • Mice, Inbred C57BL
  • Mice
  • Metalloporphyrins