Electrochemistry of Quinones with Respect to their Role in Biomedical Chemistry

Abstract

Quinones are ubiquitous in nature and form one of the largest class of antitumor agents approved for clinical use. They are known to be efficient in inhibiting cancer cells growth. Under physiological conditions they can undergo non‐enzymatic one‐electron reduction to give the moderately toxic species of semiquinone radical‐anion. Thus, electrochemical study of quinones might provide a basic knowledge on semi‐quinone radicals formation in both in vivo and in vitro under different media. Several processes are outlined briefly and discussed in the present article. Previously we investigated the electrochemical and spectral properties of ω‐N‐quinonyl amino acids. Such quinone‐bearing peptides are known to be cytotoxic and of potential clinical significance. We were able to prove that the ω‐amino quinonyl compounds are very effective in producing stable semiquinone radicals. Moreover, a direct relation was found between the first reduction potentials of the quinonyl moiety and their reactivity towards the ω‐amino acids. In order to increase our knowledge of such amino quinonyl compounds and enlarge the arsenal of such cytotoxic compounds, a series of N,N‐diquinonyl amines (1–6) bearing an internal proton (stems from the NH moiety) were synthesized. Their electron‐transfer capabilities were probed by cyclic voltammetry measurements, in dichloromethane. It was found that the acidic NH group linking the two quinonyl moieties undergoes an initial electrochemical reduction step and generates a nitride anion. This step is followed by further reductions to yield quasi‐stable semiquinone radicals and polyanions, Since these acidic diquinones (1–6) serve also as a source of internal proton donors even in non‐polar medium, they might cause protonation of basic radical‐anions and polyanion intermediates during the various electrochemical stages. The processes are demonstrated and discussed by analyzing different mechanistic schemes. The successful generation of relatively stable semiquinone radicals is a prerequisite for the manifestation of site directed antitumor activity by these bis‐quinonyl amino derivatives. Based on the values of their redox potentials some of them could be promising candidates for clinical development.

New Nanosized Systems Doxorubicin—Amphiphilic Copolymers of N-Vinylpyrrolidone and (Di)methacrylates with Antitumor Activity

“…In general, the mechanism of DOX electrode reactions was analogous to classic quinone derivatives [83]. CVA curves were similar within the potential E range ca.…”

Electrochemical redox properties of bridged and non‐bridged annulenediones

“…Recently we published an article on the electrochemistry of quinones with respect to their role in biomedical chemistry. [ 9 ] The present work expands the scope of electrochemical redox properties to other types of quinones. They are shown in Scheme 1 and involve 14 derivatives of annulenediones (actual quinones of annulenes), of which four are non‐bridged annulenediones ( 1–4 ) and ten bridged annulenediones ( 5 – 14 ).…”

Substrate Specificity of the Flavoenzyme BhaC1 That Converts a C-Terminal Trp to a Hydroxyquinone

“…p -Quinones react via 1,4-reductive addition reactions, which generate the hydroquinone with covalent attachment. Reactions with nitrogen nucleophiles such as histidine, lysine, N-terminal amino acids, and purine and pyrimidine bases on DNA are slower than sulfur-based nucleophilic additions. − o- Hydroxy- p- quinones undergo substitution reactions by addition–elimination processes. Amino acid-derived quinones are used in Nature for covalent catalysis such as the quinone cofactors tryptophan tryptophylquinone (TTQ) − and topaquinone (TPQ) (Figure C).…”