Radical scavenging reactivity of catecholamine neurotransmitters and the inhibition effect for DNA cleavage

Abstract

Neurotransmitters such as catecholamines (dopamine, L-dopa, epinephrine, norepinephrine) have phenol structure and scavenge reactive oxygen species (ROS) by hydrogen atom transfer (HAT) to ROS. Radical scavenging reactivity of neurotransmitters with galvinoxyl radical (GȮ) and cumyloxyl radical (RȮ)in acetonitrile at 298 K was determined by the UV-vis spectral change. The UV-vis spectral change for HAT from catecholamine neurotransmitters to GȮ was measured by a photodiode array spectrophotometer, whereas HAT to much more reactive cumylperoxyl radical, which was produced by photoirradiation of dicumyl peroxide, was measured by laser flash photolysis. The second-order rate constants (kGO) were determined from the slopes of linear plots of the pseudo-first-order rate constants vs concentrations of neurotransmitters. The kGO value of hydrogen transfer from dopamine to GȮ was determined to be 23 M-1 s-1, which is the largest among examined catecholamine neurotransmitters. This value is comparable to the value of a well-known antioxidant: (+)-catechine (27 M-1 s-1). The kGO value of hydrogen transfer from dopamine to GO* increased in the presence of Mg2+ with increasing concentration of Mg2+. Such enhancement of the radical scavenging reactivity may result from the metal ion-promoted electron transfer from dopamine to the galvinoxyl radical. Inhibition of DNA cleavage with neurotransmitters was also examined using agarose gel electrophoresis of an aqueous solution containing pBR322 DNA, NADH, and catecholamine neurotransmitters under photoirradiation. DNA cleavage was significantly inhibited by the presence of catecholamine neurotransmitters that can scavenge hydroperoxyl radicals produced under photoirradiation of an aerated aqueous solution of NADH. The inhibition effect of dopamine on DNA cleavage was enhanced by the presence of Mg2+ because of the enhancement of the radical scavenging reactivity. © 2010 American Chemical Society.