Redox reactions are integral parts of many cellular processes. Thus, they are extensively studied in vitro and in vivo. Electrochemistry
(EC) represents a pure instrumental approach to characterize direct and indirect effects of redox reactions on bioorganic
molecules. EC may give rise to the formation of complex mixtures of intermediates, products, and by-products. Accordingly,
efficient analytical techniques such as liquid chromatography–mass spectrometry (LC–MS) need to be applied for comprehensive
characterization of the reaction mixtures obtained. Small molecules, peptides, proteins, and nucleic acids are common targets
of EC–LC–MS studies, and this review is intended to give an overview on these important life science applications.
Redox reactions are essential for life. There are two important groups of biologically important redox reactions: enzymatic
and nonenzymatic reactions. Enzymatic redox reactions often involve complex mechanisms of several enzymes. The electrons are
transported by flavin- or heme-containing coenzymes from one reaction to another. These reactions represent an integral part
of many metabolic pathways. Biological energy, for instance, is stored and released by means of redox reactions. Cellular
respiration is the oxidation of glucose to carbon dioxide and the reduction of oxygen to water; photosynthesis involves the
reduction of carbon dioxide into sugars and the oxidation of water into molecular oxygen. Furthermore, oxidoreductases such
as the members of the cytochrome P450 superfamily generate structural complexity during natural product biosynthesis, and
they play a central role in the biotransformation of drugs and toxins ("phase I metabolisms"). Biotransformation reactions
involving xenobiotics are usually indented to make them more polar and, thus, enable a more rapid excretion. Biotranformation
can lead to a loss or gain of activity. Furthermore, in some cases reactive intermediates are produced that can bind to proteins,
lipids, and nucleic acids giving rise to cellular damage.
Biologically important redox reactions can also involve nonenzymatic processes. Reactive oxygen species (ROS) are natural
by-products of the normal metabolism of oxygen. However, during times of environmental stress (for example, UV or heat exposure)
ROS levels can increase dramatically. The availability of ROS can be important for an organism, as they are used by the immune
system as a way to attack and kill pathogens. Furthermore, some ROS function as physiological regulators of intracellular
signalling pathways. In the majority of cases, however, ROS production is considered harmful. ROS can react with proteins,
lipids, and nucleic acids, which usually gives rise to cell damage called oxidative stress. In humans oxidative stress is thought to be involved in the pathogenesis of different kinds of disease, including neurodegenerative
disease, cardiovascular disease, and cancer.
Because of their importance, biological redox reactions are extensively studied in in vitro and in vivo models. Electrochemistry
(EC) was found to be a competent approach to complement existing assays in characterizing direct and indirect effects of redox
reactions on bioorganic molecules. Electrochemistry was particularly useful in synthesizing oxidation products as well as
reactive intermediates, which can be trapped by different kinds of electrophiles and nucleophiles. Moreover, electrochemistry
is a purely instrumental approach. Thus, experimental conditions including the electrochemical potential, the electrode material,
pH, as well as the kind and concentration of reactants, can precisely be controlled. Furthermore, electrochemistry is considered
to be fast and automatable, which provides cost-savings.
Redox reactions may give rise to the formation of complex mixtures of intermediates, products, and by-products. Different
kinds of analytical techniques can be used for comprehensive analysis. Particularly, mass spectrometry (MS) has found widespread
application for that purpose. Mass spectrometric techniques enable qualitative (that is, identification and structure elucidation)
and quantitative analysis. Among the different ionization techniques available, electrospray ionization (ESI) is the most
commonly applied technique. ESI allows the MS characterization of a large variety of compounds ranging from small molecules
to large biopolymers. The importance of EC–ESI-MS techniques is emphasized by the large number of reviews that have been published
in recent years (1–13). Particularly in life sciences, EC–ESI-MS has found widespread application. The present review is intended
to give a short overview on recent advances in that important field of research (Figure 1).
Figure 1: Summarizing sketch of the different kinds of applications that are realizable with EC–(LC)ESI-MS in metabolomics,
proteomics, and nucleic acids research.