285
Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_20,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 20
Electrochemistry Investigation of Drugs Encapsulated
in Cyclodextrins
Romana Sokolová and Ilaria Degano
Abstract
The biological electron transfer reactions play an important role in the bioactivity of drugs; thus, the
knowledge of their electrochemical behavior is crucial. The formation of radicals during oxidation or
reduction, the presence of short-living intermediates, the determination of reaction mechanisms involving
electron and proton transfers, all contribute to the comprehension of drug activities and the determination
of their mode of action and their metabolites. In addition, if a drug is encapsulated in the cyclodextrin
cavity, its electrochemical properties can change compared to a free drug molecule. Here we describe the
combination of cyclic voltammetry, UV–Vis spectroelectrochemistry, GC-MS, HPLC-DAD, and
HPLC-MS/MS as techniques for evaluating the oxidation mechanism of a drug encapsulated in the cavity
of a cyclodextrin. The cavity of cyclodextrin plays a significant role in increasing the stability of the encapsulated products; therefore the identification of oxidation intermediates as semiquinone and benzofuranone derivatives of quercetin is possible in these conditions. The differences in oxidation potentials of the
bioactive flavonol quercetin and its cyclodextrin complex relating to its antioxidant activity and the oxidation mechanism are herein discussed.
Key words Drug oxidation, Drug–cyclodextrin complex, Electron transfer, Stability of intermediates,
Oxidation
mechanism,
Chromatography,
Mass
spectrometry,
Cyclic
voltammetry,
Spectroelectrochemistry
1 Introduction
Electrochemical methodologies have been successfully used to
explain correlations between chemical structure, oxidation potential, and biological activity of electroactive species [1]. For instance,
the antioxidant properties of bioactive compounds, allowing them
to prevent the formation of reactive oxygen species (ROS) often
generated at sites of inflammation and injury, or to neutralize free
radicals and minimize the oxidative stress resulting from a variety
of insults [2, 3], are closely related to their redox properties and in
particular to their ability to act as electron donors, i.e., to act as
reducing agents. Such properties can be deduced from the oxida-
Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_20,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 20
Electrochemistry Investigation of Drugs Encapsulated
in Cyclodextrins
Romana Sokolová and Ilaria Degano
Abstract
The biological electron transfer reactions play an important role in the bioactivity of drugs; thus, the
knowledge of their electrochemical behavior is crucial. The formation of radicals during oxidation or
reduction, the presence of short-living intermediates, the determination of reaction mechanisms involving
electron and proton transfers, all contribute to the comprehension of drug activities and the determination
of their mode of action and their metabolites. In addition, if a drug is encapsulated in the cyclodextrin
cavity, its electrochemical properties can change compared to a free drug molecule. Here we describe the
combination of cyclic voltammetry, UV–Vis spectroelectrochemistry, GC-MS, HPLC-DAD, and
HPLC-MS/MS as techniques for evaluating the oxidation mechanism of a drug encapsulated in the cavity
of a cyclodextrin. The cavity of cyclodextrin plays a significant role in increasing the stability of the encapsulated products; therefore the identification of oxidation intermediates as semiquinone and benzofuranone derivatives of quercetin is possible in these conditions. The differences in oxidation potentials of the
bioactive flavonol quercetin and its cyclodextrin complex relating to its antioxidant activity and the oxidation mechanism are herein discussed.
Key words Drug oxidation, Drug–cyclodextrin complex, Electron transfer, Stability of intermediates,
Oxidation
mechanism,
Chromatography,
Mass
spectrometry,
Cyclic
voltammetry,
Spectroelectrochemistry
1 Introduction
Electrochemical methodologies have been successfully used to
explain correlations between chemical structure, oxidation potential, and biological activity of electroactive species [1]. For instance,
the antioxidant properties of bioactive compounds, allowing them
to prevent the formation of reactive oxygen species (ROS) often
generated at sites of inflammation and injury, or to neutralize free
radicals and minimize the oxidative stress resulting from a variety
of insults [2, 3], are closely related to their redox properties and in
particular to their ability to act as electron donors, i.e., to act as
reducing agents. Such properties can be deduced from the oxida-