The L-Type Calcium Channel Blockers, Hantzsch 1,4-Dihydropyridines, Are Not Peroxyl Radical-Trapping, Chain-Breaking Antioxidants

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 °C. Despite a claim to...

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Published in:Chemical research in toxicology 2006-01, Vol.19 (1), p.79-85
Main Authors: Mulder, Peter, Litwinienko, Grzegorz, Lin, Shuqiong, MacLean, Patricia D, Barclay, L. R. C, Ingold, K. U
Format: Article
Language:English
Subjects:
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
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Summary: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 °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.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx0502591