Role of purines on the copper‐catalyzed oxidative damage in biological systems: Protection versus promotion

Abstract

AbstractOxidative damage to biomolecules is a serious health‐threatening issue, which leads to the development of several diseases. Oxidative conditions are frequently catalyzed by metal ions. In this study, the role of purines in the copper‐catalyzed oxidative stress was investigated using the density functional theory. The obtained results indicate that purines can have a dual behavior, acting as both protectors and promoters of oxidative stress. Their protection role arises from their known radical scavenging activity, as well as their ability to chelate Cu(II) leading to complexes that are—to some extent—harder to reduce than free Cu(II). Conversely, their pro‐oxidant role is a consequence of their reductant behavior, when deprotonated. Thus, the purines’ anions can reduce Cu(II) to Cu(I), making the latter available to be involved in Fenton‐like reactions. Consequently, mixtures of purines and Cu(II), at pHs where the fraction of deprotonated purines is rather significant, would yield •OH radicals. In turn, these very reactive radicals would damage biological targets such as lipids, proteins, and DNA.