The L-type calcium channel blockers, hantzsch 1,4-dihydropyridines, are not peroxyl radical-trapping, chain-breaking antioxidants

Chem Res Toxicol. 2006 Jan;19(1):79-85. doi: 10.1021/tx0502591.

Abstract

The antioxidant properties of Hantzsch 1,4-dihydropyridine esters and two dibenzo-1,4-dihydropyridines, 9,10-dihydroacridine (DHAC) and N-methyl-9,10-dihydroacridine (N-Me-DHAC), have been explored by determining whether they retard the autoxidation of styrene or cumene at 30 degrees C. Despite a claim to the contrary [(2003) Chem. Res. Toxicol. 16, 208-215], the Hantsch esters were found to be virtually inactive as chain-breaking antioxidants (CBAs), their reactivity toward peroxyl radicals being some 5 orders of magnitude lower than that of the excellent CBA, 2,2,5,7,8-pentamethyl-6-hydroxy-chroman (PMHC). DHAC was found to be about a factor of 10 less reactive than PMHC. From kinetic measurements using DHAC, N-deuterio-DHAC, and N-Me-DHAC, it is concluded that it is the N--H hydrogen in DHAC that is abstracted by peroxyl radicals, despite the fact that in DHAC the calculated C-H bond dissociation enthalpy (BDE) is about 11 kcal/mol lower than the N-H BDE. The rates of hydrogen atom abstraction by the 2,2-diphenyl-1-picrylhydrazyl radical (dpph*) have also been determined for the same series of compounds. The trends in the peroxyl and dpph* rate constants are similar.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemical synthesis
  • Antioxidants / chemistry
  • Benzene Derivatives / chemistry
  • Biphenyl Compounds / chemistry
  • Calcium Channel Blockers / chemistry*
  • Calcium Channels, L-Type / chemistry
  • Chromans / chemistry
  • Dihydropyridines / chemistry*
  • Free Radicals / chemistry
  • Hydrazines / chemistry
  • Kinetics
  • Nifedipine / chemistry
  • Nimodipine / chemistry
  • Oxidation-Reduction
  • Peroxides / chemistry*
  • Picrates
  • Styrene / chemistry

Substances

  • 10-methyl-9,10-dihydroacridine
  • Acridines
  • Antioxidants
  • Benzene Derivatives
  • Biphenyl Compounds
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Chromans
  • Dihydropyridines
  • Free Radicals
  • Hydrazines
  • Peroxides
  • Picrates
  • perhydroxyl radical
  • Styrene
  • Nimodipine
  • 2,2,5,7,8-pentamethyl-6-hydroxychroman
  • 1,4-dihydropyridine
  • cumene
  • 1,1-diphenyl-2-picrylhydrazyl
  • Nifedipine