Volume 26 Issue 7 - May 23, 2014 PDF
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Reduction of Carbadox Mediated by Reaction of Mn(III) with Oxalic Acid
Wan-Ru Chen1,2,*, Cun Liu 1, Stephen A. Boyd1, Brian J. Teppen1, Hui Li1
1 Department of Plant, Soil and Microbial Sciences, Michigan State University, USA
2 Department of Environmental Engineering, National Cheng Kung University, Tainan, Taiwan
 
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The quinoxaline 1,4-di-N-oxide derivatives with antimicrobial activity (carbadox and olaquindox in this study) are food additives for animal feeds to prevent epidemics and increase the growth rate and weight gain. [1] Owing to their quindoxin moiety, they are suspected of inducing strand scission in DNA and have long been recognized as genotoxic. [2-3] As carbadox enters the environment, a significant fraction is sorbed by soils, and both soil organic matter and clay minerals plausibly contribute to sorption. [4] Manganese oxides/hydroxides are common soil minerals that exist as colloidal particles and/or coatings on soil components. Under anoxic condition the reductive dissolution of manganese oxides by organic acids produces soluble MnIII species, which is capable of oxidizing a variety of organic compounds including organic pollutants and humic substances.[5]

In this study, the capability of an abiotic system consisting of MnO2 in oxalic acid that generates Mn intermediate was revealed to extensively reduce two quinoxaline-di-N-oxides, carbadox and oalquindox – compounds previously recognized to be reduced under biotic conditions. The importance of Mn was demonstrated by correlating Mn concentration and the reaction rate. Mn, functioning as a catalyst in the reaction, was stabilized by oxalate to yield MnC2O4+ complex which couples with carbadox or oalquindox forming a three-membered complex (Figure 1). Besides manonic acid, no other organics tested in this study behave the same as oxalic acid to induce the transformation. The formation of C2O4-2 and CO2-• radical within the complex was proposed mainly responsible for carbadox and oalquindox reduction. The partially reduced products were identified as their N4-oxide monodesoxy derivatives. Formation of N4-oxide monodesoxy derivatives is of special concern because they exhibit mutagenic activity and adsorb stronger to soil than their parent compounds. These results suggest that the co-existence of MnO2 and oxalic acid will likely affect the fate of quinoxaline-di-N-oxides and make them more persistent in the aquatic environment via reduction transformation.

Figure1. Proposed reaction pathway for carbadox reduction, intermediate product uinoxaline-di-N-oxide/Mn/oxalate is ternary complex formation, and associated free energy profile (left-bottom inset) calculated by DFT/PCM methods.


References:

  1. WHO. Toxicological Evaluation of Certain Veterinary Drug Residues in Food; World Health Organization: Geneva, 1991.
  2. Azqueta, A.; Arbillaga, L.; Pachon, G.; Cascante, M.; Creppy, E. E.; Lopez de Cerain, A. A quinoxaline 1,4-di-N-oxide derivative induces DNA oxidative damage not attenuated by vitamin C and E treatment. Chem. Biol. Interact. 2007, 168, 95−105.
  3. Ganley, B.; Chowdhury, G.; Bhansali, J.; Daniels, J. S.; Gates, K. S. Redox-activated, hypoxia-selective DNA cleavage by quinoxaline 1,4-di-N-oxide. Bioorg. Med. Chem. 2001, 9, 2395−2401.WHO. Toxicological Evaluation of Certain Veterinary Drug Residues in Food; World Health Organization: Geneva, 1991.
  4. Strock, T. J.; Sassman, S. A.; Lee, L. S. Sorption and related properties of the swine antibiotic carbadox and associated N-oxide reduced metabolites. Environ. Sci. Technol. 2005, 39, 3134−42.
  5. Taube, H. Catalysis of the reaction of chlorine and oxalic acid. Complexes of trivalent manganese in solutions containing oxalic acid. J. Am. Chem. Soc. 1947, 69, 1418−28.
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