Polypyrroles as antioxidants: kinetic studies on reactions of bilirubin and biliverdin dimethyl esters and synthetic model compounds with peroxyl radicals in solution. Chemical calculations on selected typical structures.
[reaction: see text] Rate constants for hydrogen-atom transfer (HAT) from bilirubin dimethyl ester (BRDE) and biliverdin dimethyl ester (BVDE) to peroxyl radicals during inhibited autoxidation of styrene initiated by azo-bisisobutyronitrile (AIBN) were k(inh)(BRDE) = 22.5 x 10(4) and k(inh)(BVDE) = 10.2 x 10(4) M(-1) s(-1), and the stoichiometric factors (n) were 2.0 and 2.7, respectively. A synthetic tetrapyrrole (bis(dipyrromethene)) containing the alpha-central (2,2') CH2 linkage gave k(inh) = 39.9 x 10(4) M(-1) s(-1) and n = 2.3, whereas the beta-linked (3,3') isomer was not an active antioxidant. Several dipyrrinones were synthesized as mimics of the two outer heterocyclic rings of bilirubin and biliverdin. The dipyrrinones containing N-H groups in each ring were active antioxidants, whereas those lacking two such "free" N-H groups, such as N-CH3 dipyrrinones and dipyrromethenes, did not exhibit antioxidant activity. Overall, the relative k(inh) values compared to those of phenolic antioxidants, 2,6-di-tert-butyl-4-methoxyphenol (DBHA) and 2,6-di-tert-butyl-4-methylphenol (BHT), were 2,2'-bis(dipyrromethene) > BRDE > DBHA > dipyrrinones > BVDE > BHT. This general trend in antioxidant activities was also observed for the inhibited autoxidation of cumene initiated by AIBN. Chemical calculations of the N-H bond dissociation enthalpies (BDEs) of the typical structures support a HAT mechanism from N-H groups to trap peroxyl radicals. Intramolecular hydrogen bonding of intermediate nitrogen radicals has a major influence on the antioxidant activities of all compounds studied. Indeed, chemical calculations showed that the initial nitrogen radical from a dipyrrinone is stabilized by 9.0 kcal/mol because of H-bonding between the N-H remaining on one ring and the ground-state pyrrolyl radical of the adjacent ring in the natural zusammen structure. The calculated minimum structure of bilirubin shows strong intramolecular H-bonding of the N-H groups with carbonyl groups resulting in the known "ridge-tile" structure which is not an active HAT antioxidant. The calculated minimum structure of biliverdin is planar. BRDE is readily converted into BVDE by reaction with the electron-deficient DPPH* radical under argon in chlorobenzene. An electron-transfer mechanism is proposed for the initiating step in this reaction, and this is supported by the relatively low ionizing potential of a model dipyrrole representing the two central rings of bilirubin.
Chepelev
Leonid L
LL
Department of Chemistry, Carleton University, Ottawa, Ontario, Canada K1S 5B6.
Beshara
Cory S
CS
MacLean
Patricia D
PD
Hatfield
Gillian L
GL
Rand
Amy A
AA
Thompson
Alison
A
Wright
James S
JS
Barclay
L Ross C
LR
D000975:Antioxidants / Q000737:chemistry*; D001663:Bilirubin / Q000031:analogs & derivatives* / Q000737:chemistry; D001664:Biliverdine / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D012996:Solutions; D020058:Styrene / Q000737:chemistry
D000975:Antioxidants; D005609:Free Radicals; D011108:Polymers; D011758:Pyrroles; D012996:Solutions; C032217:bilirubin dimethyl ester; C067635:polypyrrole; D020058:Styrene; D006859:Hydrogen; D001664:Biliverdine; D001663:Bilirubin; D010100:Oxygen