Tomonori Kawashima

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

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 (GO*) and cumyloxyl radical (RO*) in acetonitrile at 298 K was determined by the UV-vis spectral change. The UV-vis spectral change for HAT from catecholamine neurotransmitters to GO* 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 (k(GO)) were determined from the slopes of linear plots of the pseudo-first-order rate constants vs concentrations of neurotransmitters. The k(GO) value of hydrogen transfer from dopamine to GO* 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 k(GO) value of hydrogen transfer from dopamine to GO* increased in the presence of Mg(2+) with increasing concentration of Mg(2+). 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 Mg(2+) because of the enhancement of the radical scavenging reactivity.

Stepwise vs. concerted pathways in scandium ion-coupled electron transfer from superoxide ion to p-benzoquinone derivatives

Superoxide ion (O2˙-) forms a stable 1 : 1 complex with scandium hexamethylphosphoric triamide complex [Sc(HMPA)(3)(3+)], which can be detected in solution by ESR spectroscopy. Electron transfer from O2˙- -Sc(HMPA)(3)(3+) complex to a series of p-benzoquinone derivatives occurs, accompanied by binding of Sc(HMPA)(3)(3+) to the corresponding semiquinone radical anion complex to produce the semiquinone radical anion-Sc(HMPA)(3)(3+) complexes. The 1 : 1 and 1 : 2 complexes between semiquinone radical anions and Sc(HMPA)(3)(3+) depending on the type of semiquinone radical anions were detected by ESR measurements. This is defined as Sc(HMPA)(3)(3+)-coupled electron transfer. There are two reaction pathways in the Sc(HMPA)(3)(3+)-coupled electron transfer. One is a stepwise pathway in which the binding of Sc(HMPA)(3)(3+) to semiquinone radical anions occurs after the electron transfer, when the rate of electron transfer remains constant with the change in concentration of Sc(HMPA)(3)(3+). The other is a concerted pathway in which electron transfer and the binding of Sc(HMPA)(3)(3+) occurs in a concerted manner, when the rates of electron transfer exhibit first-order and second-order dependence on the concentration of Sc(HMPA)(3)(3+) depending the number of Sc(HMPA)(3)(3+) (one and two) bound to semiquinone radical anions. The contribution of two pathways changes depending on the substituents on p-benzoquinone derivatives. The present study provides the first example to clarify the kinetics and mechanism of metal ion-coupled electron-transfer reactions of the superoxide ion.