Capsaicin, a Powerful •OH-Inactivating Ligand

Abstract

Oxidative conditions are frequently enhanced by the presence of redox metal ions. In this study, the role of capsaicin (8-methyl-N-vanillyl-6-nonenamide, CAP) in copper-induced oxidative stress was investigated using density functional theory simulations. It was found that CAP has the capability to chelate Cu(II), leading to complexes that are harder to reduce than free Cu(II). CAP fully turns off the Cu(II) reduction by Asc−, and slows down the reduction in this cation by O2•−. Therefore, CAP is proposed as an •OH-inactivating ligand by impeding the reduction in metal ions (OIL-1), hindering the production of •OH via Fenton-like reactions, at physiological pH. CAP is also predicted to be an excellent antioxidant as a scavenger of •OH, yielded through Fenton-like reactions (OIL-2). The reactions between CAP-Cu(II) chelates and •OH were estimated to be diffusion-limited. Thus, these chelates are capable of deactivating this dangerous radical immediately after being formed by Fenton-like reactions.

Theoretical insights into the antiradical activity and copper-catalysed oxidative damage of mexidol in the physiological environment

“…•− and AA − that have an order of magnitude higher rate constants (4.46 × 10 9 M −1 s −1 and 1.33 × 10 8 M −1 s −1 , respectively) [10]; hence MD does not contribute substantially to the reduction of free Cu(II).…”

“…) = 4.46 × 10 9 M −1 s −1 )[10]. However, complexation suppressed the rate constant of AA − -driven reduction of Cu(II) by about 10 8 times compared to free Cu(II).…”

“…However, Cu(I) is not the most stable or abundant form of copper in physiological environments. The concentration of Cu(I) is defined by the amount of Cu(II) ions undergoing reduction by hyperoxide radical (O ÁÀ 2 ) or deprotonated ascobic acid (AA − ) with the rate constants k = 4.46 × 10 9 M −1 s −1 and 1.33 × 10 8 M −1 s −1 , respectively [10]:…”

“…In evaluating the antioxidant activity of MD, one has to also consider that pyridines are very good coordinating ligands and therefore it is highly likely that MD forms chelates with trace metals [5,6]. Previous studies showed that the presence of transition metals such as Cu(I) can produce hydroxyl radicals via the Fenton-like reaction (1.1) [7][8][9][10][11]:…”

Current Trends in Computational Quantum Chemistry Studies on Antioxidant Radical Scavenging Activity

“…However, the fundamental disadvantage of implicit models is complete negation of intermolecular hydrogen bonds, which are often essential for proper simulation of antiradical activity 93 , 103 , 144 especially when abundant as in the case of capsaicin. 84 A mutual competition between intramolecular and intermolecular hydrogen bonds is also observed as a relevant factor modying hydrogen atom transfer proclivity. 47 The modeling of • OH and • OOH radicals, which are of primary interest in antioxidants research, is an excellent example of how the explicit water molecules can influence the results as well.…”