287
chemical studies as biological metabolites transported by rat
cardiomyocytes [2]. Moreover, studies concerning the metabolic
products of flavonoid quercetin processed by rat colonic flora fit
the decomposition pathways found in the recent studies of flavonol
quercetin oxidation mechanism [17].
The complete elucidation of the oxidation or reduction mechanism requires the use of analytical separation techniques and
online spectroelectrochemical methods [18, 19]. In situ UV–Vis
spectroelectrochemistry is an efficient technique giving information about the changes in absorption spectra during electrolysis at
controlled potential. Spectroelectrochemical measurements are
performed in optically transparent thin-layer electrochemical cells
[20, 21]. Additionally, in situ FTIR spectroelectrochemistry can
characterize reactions occurring at the electrode surfaces by monitoring the change in absorbance of vibrations belonging directly to
the functional groups participating in the redox process. The conversion of compounds to reduced or oxidized molecules shows a
clear isosbestic point in absorption spectra and thus this technique
successfully points out the presence of short-lived intermediates
and occurring subsequent reactions. Based on the principles mentioned above, we recently disclosed the difference in the oxidation
mechanisms of flavonols (as quercetin, fisetin, rhamnazin, and
rhamnetin) and flavanones (taxifolin) or flavones (luteolin) [13,
21–24]. The oxidation of flavonols (containing in their chemical
structure one hydroxyl group at C3 position and a double bond
between C2 and C3 atoms) leads to the formation of a benzofuranone derivative, through the 2e
−
/2H
+
oxidation of catechol group
at ring B and subsequent nucleophilic addition of water. The
absorption spectrum of the benzofuranone derivative was detected
by UV–Vis spectroelectrochemical oxidation and also by chemical
homogeneous oxidation by atmospheric oxygen. GC-MS and
HPLC-MS/MS analyses and data interpretation confirmed its formation. Neither taxifolin (lacking the double bond between C2
and C3 atoms) nor luteolin (lacking the hydroxyl group at position
C3) did not follow this oxidation pathway, and hydroxylated molecules were found as their oxidation products.
Significantly, the principles and analytical strategies mentioned
above are valid also for the study of electroactive drugs encapsulated in the cavity of a cyclodextrin molecule. Cyclodextrins (CDs)
are supramolecules, which form truncated cones and can form
complexes with a variety of guest molecules, depending on the size
of their hydrophobic cavity and possible chemical modification of
their rims. The external of the cyclodextrin is hydrophilic; thus
encapsulation may enhance the solubility in water and thus the
bioavailability of the drug [25]. These supramolecular complexes
are also widely studied by electrochemistry [26].
Several possible behaviors can be observed when performing
electroanalytical experiments on CD complexes. The CD-drug
Electrochemistry Investigation of Drugs Encapsulated in Cyclodextrins
chemical studies as biological metabolites transported by rat
cardiomyocytes [2]. Moreover, studies concerning the metabolic
products of flavonoid quercetin processed by rat colonic flora fit
the decomposition pathways found in the recent studies of flavonol
quercetin oxidation mechanism [17].
The complete elucidation of the oxidation or reduction mechanism requires the use of analytical separation techniques and
online spectroelectrochemical methods [18, 19]. In situ UV–Vis
spectroelectrochemistry is an efficient technique giving information about the changes in absorption spectra during electrolysis at
controlled potential. Spectroelectrochemical measurements are
performed in optically transparent thin-layer electrochemical cells
[20, 21]. Additionally, in situ FTIR spectroelectrochemistry can
characterize reactions occurring at the electrode surfaces by monitoring the change in absorbance of vibrations belonging directly to
the functional groups participating in the redox process. The conversion of compounds to reduced or oxidized molecules shows a
clear isosbestic point in absorption spectra and thus this technique
successfully points out the presence of short-lived intermediates
and occurring subsequent reactions. Based on the principles mentioned above, we recently disclosed the difference in the oxidation
mechanisms of flavonols (as quercetin, fisetin, rhamnazin, and
rhamnetin) and flavanones (taxifolin) or flavones (luteolin) [13,
21–24]. The oxidation of flavonols (containing in their chemical
structure one hydroxyl group at C3 position and a double bond
between C2 and C3 atoms) leads to the formation of a benzofuranone derivative, through the 2e
−
/2H
+
oxidation of catechol group
at ring B and subsequent nucleophilic addition of water. The
absorption spectrum of the benzofuranone derivative was detected
by UV–Vis spectroelectrochemical oxidation and also by chemical
homogeneous oxidation by atmospheric oxygen. GC-MS and
HPLC-MS/MS analyses and data interpretation confirmed its formation. Neither taxifolin (lacking the double bond between C2
and C3 atoms) nor luteolin (lacking the hydroxyl group at position
C3) did not follow this oxidation pathway, and hydroxylated molecules were found as their oxidation products.
Significantly, the principles and analytical strategies mentioned
above are valid also for the study of electroactive drugs encapsulated in the cavity of a cyclodextrin molecule. Cyclodextrins (CDs)
are supramolecules, which form truncated cones and can form
complexes with a variety of guest molecules, depending on the size
of their hydrophobic cavity and possible chemical modification of
their rims. The external of the cyclodextrin is hydrophilic; thus
encapsulation may enhance the solubility in water and thus the
bioavailability of the drug [25]. These supramolecular complexes
are also widely studied by electrochemistry [26].
Several possible behaviors can be observed when performing
electroanalytical experiments on CD complexes. The CD-drug
Electrochemistry Investigation of Drugs Encapsulated in Cyclodextrins