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
journal contributionposted on 06.01.2006, 00:00 by Leonid L. Chepelev, Cory S. Beshara, Patricia D. MacLean, Gillian L. Hatfield, Amy A. Rand, Alison Thompson, James S. Wright, L. Ross C. Barclay
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 kinh(BRDE) = 22.5 × 104 and kinh(BVDE) = 10.2 × 104 M-1 s-1, and the stoichiometric factors (n) were 2.0 and 2.7, respectively. A synthetic tetrapyrrole (bis(dipyrromethene)) containing the α-central (2,2‘) CH2 linkage gave kinh = 39.9 × 104 M-1 s-1 and n = 2.3, whereas the β-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 kinh 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.