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

J Org Chem. 2006 Jan 6;71(1):22-30. doi: 10.1021/jo051359e.


[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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemistry*
  • Bilirubin / analogs & derivatives*
  • Bilirubin / chemistry
  • Biliverdine / chemistry*
  • Free Radicals / chemistry
  • Hydrogen / chemistry
  • Kinetics
  • Models, Chemical*
  • Molecular Structure
  • Oxygen / chemistry
  • Polymers / chemistry*
  • Pyrroles / chemistry*
  • Solutions
  • Styrene / chemistry


  • Antioxidants
  • Free Radicals
  • Polymers
  • Pyrroles
  • Solutions
  • bilirubin dimethyl ester
  • polypyrrole
  • Styrene
  • Hydrogen
  • Biliverdine
  • Bilirubin
  • Oxygen