Is Caffeine a Good Scavenger of Oxygenated Free Radicals?

The reactions of caffeine (CAF) with different reactive oxygen species (ROS) have been studied using density functional theory. Five mechanisms of reaction have been considered, namely, radical adduct formation (RAF), hydrogen atom transfer (HAT), single electron transfer (SET), sequential electron proton transfer (SEPT), and proton coupled electron transfer (PCET). The SET, SEPT, and PCET mechanisms have been ruled out for the reactions of CAF with (OH)-O-center dot, O-2(center dot-), ROO center dot, and RO center dot radicals. It was found that caffeine is inefficient for directly scavenging O-2(center dot-) and (OOCH3)-O-center dot radicals and most likely other alkyl peroxyl radicals. The overall reactivity of CAF toward (OH)-O-center dot was found to be diffusion-controlled, regardless of the polarity of the environment, supporting the excellent (OH)-O-center dot scavenging activity of CAF. On the other hand, it is predicted to be a modest scavenger of (OCH3)-O-center dot, and probably of other alkoxyl radicals, and a poor scavenger of HOO center dot. RAF has been identified as the main mechanism involved in the direct ROS scavenging activity of CAF. The excellent agreement with the available experimental data supports the reliability of the present calculations.