Synthesis and High Antioxidant Activity of C-Alkyl Calix[4]resorcinarene and C-Alkyl Calix[4]pyrogallolarene Derivatives

Abstract

In the present work, we reported a successful synthesis and high antioxidant activity of C-alkylcalix[4]resorcinarene and C-alkylcalix[4]pyrogallolarene derivatives. The C-alkylcalix[4]resorcinarenes were prepared from a cyclization reaction of resorcinol and either pentanaldehyde or octanaldehyde in acidic condition. Meanwhile, the C-alkylcalix[4]pyrogallolarenes were prepared from a cyclization reaction of pyrogallol with pentanaldehyde or octanaldehyde. Four synthesized products, i.e. nBu-CR, nHep-CR, nBu-CP, and nHep-CP, were successfully prepared in 92.4-96.4% yield. The chemical structure of these products was elucidated by Fourier transform infrared (FTIR), liquid chromatography-mass spectrometry (LC-MS), and proton nuclear magnetic resonance (1H-NMR) analysis. The antioxidant activity assay of these compounds was evaluated through an in vitro assay employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. From the DPPH assay, it was found that the half-maximal inhibitory concentration (IC50) values of nBu-CR, nHep-CR, nBu-CP, and nHep-CP compounds were 25.1, 22.9, 11.5, and 21.9 µg mL-1, respectively. The IC50 value of the synthesized compounds was 2.0-4.3 times lower than the IC50 value of butylated hydroxytoluene (BHT) as the positive standard (49.9 µg mL-1), which is remarkable. This finding demonstrates that either C-alkylcalix[4]resorcinarenes or C-alkylcalix[4]pyrogallolarenes are better antioxidant agents than BHT. The nHep-CR compound was found as the best antioxidant agent from the other compounds due to weaker intramolecular and intermolecular hydrogen bonding as well as longer alkyl chain.