Tuning the antioxidant property of potential calixdrug calix[4]tyrosol: role of aza and thia linkages

Calix[4]arenes are the most renowned and widely studied calix[n]arenes, which are established to have quite a few biological (e.g., antibacterial, antifungal, antioxidant, etc.) activities. Among these, calix[4]tyrosol is experimentally recognized to be a potential antioxidant molecule, though its quantum chemical explanation is hitherto unknown. A molecular-level understanding of these molecules, with potential to act as drug as well as radical scavengers, would define strategies to tune and improve their efficacy. This work explores the conformational favorites of calix[4]tyrosol, its radical scavenging ability toward nine prototype oxyradicals, its metal chelation ability toward Cu(I/II) ions, and its photophysical properties. More importantly, some novel antioxidant systems are designed through inclusion of aza- and thia- linkages in calix[4]tyrosol. Our results support the experimental findings suggesting the cone conformer of calix[4]tyrosol to be the most stable one due to the presence of strong intramolecular hydrogen bonding. On top of this, our findings signify calix[4]tyrosol as a potential prooxidant. Among all the calix[4]aromatics, the newly designed aza-calix[4]tyrosol is found to have the finest antioxidant property.