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 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.
Mulder
Peter
P
Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands, Department of Chemistry, Warsaw University, Pasteur 1, 02-093 Warsaw, Poland. peter.mulder@nrc.ca
Litwinienko
Grzegorz
G
Lin
Shuqiong
S
MacLean
Patricia D
PD
Barclay
L R C
LR
Ingold
K U
KU
D000166:Acridines / Q000138:chemical synthesis; D000975:Antioxidants / Q000737:chemistry; D001555:Benzene Derivatives / Q000737:chemistry; D001713:Biphenyl Compounds / Q000737:chemistry; D002121:Calcium Channel Blockers / Q000737:chemistry*; D020746:Calcium Channels, L-Type / Q000737:chemistry; D002839:Chromans / Q000737:chemistry; D004095:Dihydropyridines / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D006834:Hydrazines / Q000737:chemistry; D007700:Kinetics; D009543:Nifedipine / Q000737:chemistry; D009553:Nimodipine / Q000737:chemistry; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry*; D010851:Picrates; D020058:Styrene / Q000737:chemistry
C480178:10-methyl-9,10-dihydroacridine; D000166:Acridines; D000975:Antioxidants; D001555:Benzene Derivatives; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002839:Chromans; D004095:Dihydropyridines; D005609:Free Radicals; D006834:Hydrazines; D010545:Peroxides; D010851:Picrates; C049375:perhydroxyl radical; D020058:Styrene; D009553:Nimodipine; C120726:2,2,5,7,8-pentamethyl-6-hydroxychroman; C038806:1,4-dihydropyridine; C015763:cumene; C004931:1,1-diphenyl-2-picrylhydrazyl; D009543:Nifedipine