Abstract
Catecholamines play a crucial role in signal transduction and are also expected to act as endogeneous antioxidants, but the mechanism of their antioxidant action is not fully understood. Here, we describe the impact of pH on the kinetics of reaction of four catecholamines (L-DOPA, dopamine, adrenaline, and noradrenaline) with model 2,2-diphenyl-1-picrylhydrazyl radical (dpph•) in methanol/water. The increase in pH from 5.5 to 7.4 is followed by a 2 order of magnitude increase in the rate constant, e.g., for dopamine (DA) kpH5.5 = 1,200 M–1 s–1 versus kpH7.4 = 170,000 M–1 s–1, and such rate acceleration is attributed to a fast electron transfer from the DA anion to dpph•. We also proved that at pH 7.0 DA breaks the peroxidation chain of methyl linoleate in liposomes assembled from neutral and negatively charged phospholipids. In contrast to no inhibitory effect during peroxidation in non-ionic emulsions, in bilayers one molecule of DA traps approximately four peroxyl radicals, with a rate constant kinh >103 M–1 s–1. Our results from a homogeneous system and bilayers prove that catecholamines act as effective, radical trapping antioxidants with activity depending on the ionization status of the catechol moiety, as well as microenvironment: organization of the lipid system (emulsions vs bilayers) and interactions of catecholamines with the biomembrane.
Highlights
The results of in vitro experiments on neuronal cell lines[5] and peripheral blood cells[6] suggest that catecholamines might act as endogenous antioxidants, because their protective effect against cell death[5] is associated with a decrease in the concentration of the intracellular reactive oxygen species (ROS)5a and can be mimicked by other antioxidants, e.g., analogues of α-tocopherol,5a,b catechol derivatives like 3,4-dihydroxymandelic acid, and catechol itself.5a In contrast, Ltyrosine and normetanephrine (Omethylated noradrenaline) do not protect neuronal lines against cell death,5a suggesting the crucial role of the catechol moiety in neuroprotective activity of catecholamines.5a This is not surprising because catechols are responsible for the excellent antioxidant activity of many natural compounds,[7] including flavonoids7f,g,8 and phenylpropanoids.[8]
We hoped that a brief survey of the accessible reports about the acidity of catecholamines would be helpful for a correct interpretation of this problem; we discovered that the discussion initiated 50 years ago is still vivid (!), with the hypothesis of a stronger acidity of phenolic hydroxyl supported by 1H NMR experiments[50] versus the arguments for superior deprotonation of the ammonium group at physiological pH, supported with 13C NMR and ab initio calculations.[51]
The large, 2 orders of magnitude, enhancement of their reactivity with an increase in pH from 5.5 to 7.4 provides the clear evidence that scavenging activity is correlated with deprotonation of hydroxyl groups, with participation of fast electron transfer from the phenolate anion to dpph in addition to much slower one-step hydrogen atom transfer (HAT)
Summary
In contrast to many papers describing the impact of catechols and catechol derivatives on the level of oxidative transmitters in the mammalian nervous system[1] and as hormones in blood circulation. They participate in a variety of motor and mental functions of the organism, and even a slight dysregulation of their activity may lead to pathological events;[1,2] for example, the motor symptoms in Parkinson’s disease (PD) are associated with severe depletion of dopamine.
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