Comparative study of the alkyl and peroxy radical-scavenging activity of 2-t-butyl-4-methoxyphenol (BHA) and its dimer, and their theoretical parameters.
BACKGROUND
2-t-Butyl-4-methoxyphenol (BHA) has considerable toxicity and undesirable potential tumor-promoting activities. To clarify the free radical mechanism of BHA-induced toxicity, the comparative radical-scavenging activity of BHA and its dimer (bis-BHA, 3,3'-ditert-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol) with or without 2-mercapto-1-methylimidazole (MMI) was studied using the induction period method.


METHODS
The induction period and propagation rate (Rp) were determined by differential scanning calorimetry (DSC) monitoring of polymerization of methyl methacrylate, initiated by the thermal decomposition of benzoyl peroxide (a source of the peroxy radical, PhCOO*) or 2,2'-azobisisobutyronitrile (a source of the alkyl radical, R*) under nearly anaerobic conditions. The anti-1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical- and O2(-)-scavenging activities were also investigated. Furthermore, theoretical parameters were calculated from the DEFT/B3LYP and HF/6-31G*//B3LYP levels.


RESULTS
For both PhCOO* and R* the inhibition rate constant (k(inh)) for BHA and bis-BHA was almost identical, but a marked decrease in the Rp(inh)/Rp(con) was found for the former. The BHA/MMI mixture (1:1 molar ratio) oxidized by R* reduced the total radical-scavenging activity by approximately 20% . BHA showed lower anti-DPPH radical- and higher O2(-)-scavenging activity.


CONCLUSIONS
Upon PhCOO* or R* scavenging, BHA with a lower BDE, IP(koopman's), electronegativity, and electrophilicity value, but not bis-BHA with higher corresponding values, highly suppressed propagation. This may be due to the formation of highly reactive free-radical intermediates, which are potentially toxic.
Kadoma
Yoshinori
Y
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Japan.
Ito
Shigeru
S
Yokoe
Ichiro
I
Fujisawa
Seiichiro
S
D000478:Alkylation; D001713:Biphenyl Compounds / Q000737:chemistry; D002083:Butylated Hydroxyanisole / Q000737:chemistry*; D019281:Dimerization; D016166:Free Radical Scavengers / Q000737:chemistry*; D006834:Hydrazines / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D010851:Picrates
C107674:2-mercapto-1-methylimidazole; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D006834:Hydrazines; D007093:Imidazoles; D010851:Picrates; D002083:Butylated Hydroxyanisole; C004931:1,1-diphenyl-2-picrylhydrazyl; D010100:Oxygen