Special Issue "Quinones and Hydroxyquinones. Target Molecules and Building Blocks in Organic Synthesis"

Guest Editor
Prof. Dr. Spyros Spyroudis
Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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Chemistry of hypervalent iodonium organic compounds and applications in synthesis; Transition metals in organic synthesis; Chemistry of hydroxyquinones

Manuscript ID: molecules-quinones-20081028-il-Bittner
Type of Paper: Review
Title: Pyrroloquinoline Quinone (PQQ) and Amino Acids
Authors: Shmuel Bittner and Yana Sutovsky
Affiliation: Department of Chemistry, Ben Gurion University of the Negev, Beer Sheva, Israel
E-mail: bittner@bgu.ac.il
Abstract: PQQ, the cofactor for glucose dehydrogenase is a primaryfocus of this review. It has provoked considerable interest due to its presence in foods, its use as growth promoter in culture of animal, plant, or microbial cells and its antioxidant properties. PQQ is the non-covalently bound prosthetic group of many quinoproteins catalyzing reactions in the periplasm of Gram-negative bacteria. There are close contacts between PQQ and amino acids. PQQ is biosynthesized via annulation of peptidyl glutamicacid and tyrosine residues stemming from their modificationas components of a precursor peptide substrate. The exact pathwayfor PQQ biogenesis is still not fully understood. Labeling studies showed that all carbon and nitrogen atoms of PQQ are derived from the amino acids glutamate (Glu) and tyrosine (Tyr). Genetic studies have identified all the genes required for the assembly of the coenzyme. PQQ is very reactive towards various nucleophilic reagents including amino acids. PQQ reacts readily with some amino acids to yield oxazole derivatives or imidazole derivatives. The oxazole derivatives are formed via Schiff bases that can undergo either oxidative decarboxylation or oxidative dealdolation leading to variety in the structure of the R group which is either an hydrogen or the side chain of amino acid. These oxazole and imidazole derivatives have no redox-catalytic activity and they might be the major products from PQQ in biological fluids. The analytical determination of PQQ is via derivatives with amino acids using UV-Vis spectroscopy, fluorescence spectroscopy, isotachophoresis and HPLC methods. PQQ is important for human health, and its role as a vitamin in mammals has recently been suggested. PQQ-amino acid adducts show potent growth-stimulating effect for microorganisms, protect against CCl₄-induced liver injury, inhibits hydrocortisone-induced cataract formation, and display strong radical scavenging activities. These PQQ-amino acids adducts also enhance DNA synthesis activity in human fibroblasts and display nerve growth factor-inducing activity. In this review we will discuss the most important aspects of the above mentioned PQQ-amino acids interaction, which has attracted much recent attention.
Keywords: pyrroloquinoline quinone; PQQ; amino acids; quinoenzymes; biosynthesis

Manuscript ID: molecules-quinones-20081104-gr-Valavanidis
Type of Paper: Article
Title: Quinone Derivatives: Synthesis, Mechanisms of Cytotoxic Action and Evaluation of Antitumour Activities
Author: Athanasios Valavanidis
Affiliation: Department of Chemistry, Laboratory of Organic Chemistry, University of Athens, University Campus Zografou, 15784, Athens, Greece
E-mail: valavanidis@chem.uoa.gr
Abstract: Quinones are widely distributed chemical compounds in nature but also are found in humans as endogenous compounds of biological importance. Quinone moieties are present in many drugs, such as anthracyclines. Which are used clinically in the treatment of solid cancers. In this respect, antitumour quinones are currently the focus of intensive research with numerous synthetic preparations of quinone derivatives and the evaluation of their cytotoxic activity. The present review presents a series of the most important synthetic research programmes on the preparation of biologically active quinones. Especially 1,4-naphthoquinones, indole-based quinones, azanaphthoquinones, anthraquinones, anthracene-diones, and their derivatives. These studies use many types of reagents (such as activated arenes) and synthetic mechanisms and then studied the structure-activity relationships of their cytotoxicity.
The mechanisms by which quinones are cytotoxic has been attributed to two chemical properties: firstly, redox cycling , wherein the sequential reduction and re-oxidation of the quinone results in the generation of reactive oxygen species (ROS) and free radicals, and secondly, electrophilic arylation of critical cellular nucleophiles. This review presents a series of important studies differentiating among those mechanisms and determine chemical reactivity of individual quinones and their derivatives.
Finally, we present the results of evaluation of antitumour reactivities of some substituted quinones and their therapeutic index as antitumour drugs.

Manuscript ID: molecules-quinones-20081125-uk-Tyman
Type of Paper: Review
Title: Synthesis of Natural Products from 1,4-benzo and 2-halogenonaphtho-1,4-quinones
Author: J H P Tyman
Affiliation: Department of Chemistry, Brunel University, Uxbridge, Middlesex, UB8 3PH, UK
Abstract: Quinones are widely distributed natural products, predominantly as antibiotics but in numerous other categories [1,2]. We have used benzoquinones for obtaining hydroquinones and 2-halogeno-1,4-naphthoquinones for complex anthraquinones. The hydroquinone miconidin, 2-n-butyl-5-methoxy-1,4-dihydroxybenzene has been synthesised from o-vanillin. Reaction with n-butyl lithium, reduction and Teuber oxidatiion afforded primin, 2-n-butyl-5-methoxybenzo-1,4-quinone and miconidin by reduction. In rhe anthraquinones, we have synthesised kermesic acid, 1-methyl-2-carboxy-3,5,6,8-tetrahydroxy-9,10-anthraquinone from methyl 6-chlotro-2,5,8-trihydroxynaphtho-1,4-quinone-3-carboxylat [3]. Our study of carminic acid, 1-methyl-2-carboxy-3,4.5.8-tetrahydroxy-7-glucosyl-9,10-anthraquinone gave its synthesis from the Diels-Alder addition reactions of 2-chloronaphthazarin [4].
References: 1. Thomson, R.H. Naturally Occurring Quinones, Academic Press, London, 1971.
2. Tyman, J.H.P. Synthetic and Natural Phenols, Ch. 14, 1996, Elsevier; E books 2008.
3. Bingham, S.J. and Tyman, J.H.P. The synthesis of kermesic acid by acetylation-aided tautomerism of 6-chloro-2,5,8-trihydroxynaphtho-1,4-quinone Tetrahedron, 2008, 64, 3471-347.
4. Allevi, P.; Anastasia, M.; Bingham, S.; Ciuffreda, P.; Fiecchi, A.; Cighetti, C.; Muir, M.; Scala, A. and Tyman, J.H.P. Synthesis of Carminic Acid, the Colourant Principle of Cochineal J. Chem. Soc. Perkin Trans. 1, 1998, 575-582.

Type of Paper: Article
Title: Langmuir Monolayer of Ubiquinol at the Air-water Interface
Authors: Yann Roche†, Pierre Peretti and Sophie Bernard*
Affiliation: University Paris Descartes, CNRS UPR 2228, Biomedical Research Center, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France. * Corresponding author. Tel.: +33-1-42862046, Fax: +33-1-42862085. E-mail: sophie.bernard@parisdescartes.fr, † Present address: UMR Plante-Microbes-Environnement, INRA, 17 rue Sully, 21065 Dijon, France.
Abstract: Ubiquinol-10 (UQ10H2) and ubiquinol-4 (UQ4H2) were obtained by chemical reduction and spread pure or mixed with dipalmitoyl-phosphatidylcholine (DPPC) at the airwater interface of a through confined in an oxygen-free chamber to form Langmuir monolayers. The surface pressure-area isotherms of pure UQH24 and UQH210 monolayers show higher collapse surface pressure and molecular area values than their respective oxidized forms ubiquinone-4 (UQ4) and ubiquinone-10 (UQ10). Analysis of constituents miscibility, excess area (Aex) and free energy of mixing (ΔGm), calculated from compression isotherms of mixed films, shows that the hydroquinone ring of ubiquinol allows to minimize the interaction with DPPC in the case of DPPC-UQ(H2)4 films, possibly through intermolecular hydrogen bonding, but not significantly for DPPC-UQ(H2)10 mixtures. The hydroxyquinone ring is thus proposed to counteract the hydrophobic/steric effects of isoprenoid chain for pure UQ4H2 and UQ10H2 monolayers and for DPPC-UQH24 mixed films. This redox-dependant organization of UQ4 when mixed with phospholipids could be of great significance regarding the biological activity of short-chain ubiquinone analogs.
Keywords: Ubiquinone; Ubiquinol; Antioxydant Activity; Phospholipid; Langmuir Monolayer; Redox state; Chemical Reduction.