Natural polyphenols are known to exhibit a lot of different biological properties, including antioxidant activity. For some polyphenols these activities ire attributed to the presence of a guaiacol moiety. In the present paper we focus oil the role of this moiety For this purpose nine different compounds were enzymatically synthesized from guaiacol To elucidate the structure-activity relationship of these polyphenols, DFT-(PCM)B3P86/6-311+G(2d,3pd)//(PCM)B3P86/6-31+G(d,p) Calculations Supported the experimental DPPH free radical scavenging activities. The antioxidant activities were correlated to (i) O-H BDEs (bond dissociation enthalpies), (ii) BDED (BDE of a second H atom abstraction from the phenoxyradicals), (iii) spin density, (iv) HOMO (highest Occupied molecular orbital) distribution, (v) IPs (Ionization potentials), (vi) Delta G and Delta G(#) free energies of HAT (H atom transfer), and (vii) HAT rate constants. BDED appeared to be the most important descriptor to understand file free radical scavenging ability of these compounds.