The coupling between electron and proton transfers has a long experimental and theoretical history in chemistry and biochemistry. To take just one example, the fact that acceptance of an electron triggers the addition of an acid or the removal of a base and vice versa for oxidations towers over all understanding of organic electrochemistry. Protoncoupled electron transfer (PCET) reactions also play a critical role in a wide range of biological processes, including enzyme reactions, photosynthesis, and respiration. A recent impressive review describes PCET reactions and phenomena. PCET is employed here as a general term for reactions in which both an electron and a proton are transferred, either in two separate steps or in a single step. Reactions in which the electron and proton transfer between the same donor and acceptor, that is, hydrogen atom transfer, are, of course, not considered here because we consider electrochemical PCET reactions in which electrons are flowing into or from an electrode while protons are transferred between acid and base. Molecular electrochemistry, through nondestructive techniques such as cyclic voltammetry, has proved to be very useful in characterizing electron transfers and deciphering mechanisms in which chemical reactions are associated with electron transfer. Therefore, it has been a convenient tool for the mechanistic study of reactions in which electron transfer is coupled to proton transfer, that is, in which an electron leaves or enters an electrode while a proton is transferred from or to the redox species. Until recently, PCET has been mostly thought of as stepwise electron and proton transfer (ET-PT or PT-ET). We thus review in an initial section (section 2) the analysis of such stepwise mechanisms both in aprotic media and in water. In aprotic media, * E-mail address: cyrille.costentin@univ-paris-diderot.fr. Cyrille Costentin was born in Normandy, France, in 1972. He received his undergraduate education at Ecole Normale Superieure (Cachan, France) and pursued his graduate studies under the guidance of Prof. Jean-Michel Saveant and Dr. Philippe Hapiot at the University of ParisDiderot (Paris 7), where he received his Ph.D. in 2000. After a year as a postdoctoral fellow at the University of Rochester, working with Prof. J. P. Dinnocenzo, he joined the faculty at the University of Paris-Diderot as an associate professor. He was promoted to professor in 2007. His interests include mechanisms and reactivity in electron transfer chemistry with particular recent emphasis on electrochemical and theoretical approaches to proton-coupled electron transfer processes. Chem. Rev. 2008, 108, 2145–2179 2145

Electrochemical Approach to the Mechanistic Study of Proton-Coupled Electron Transfer

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various Plasmodium species) can be considered a neglected disease in certain countries and with regard to availability and affordability of the antimalarials. Living organisms, especially plants, provide an innumerable number of molecules with potential for the treatment of many serious diseases. The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general description of the diseases, the current state of therapy and need for new therapeuticals, assay methods and strategies applied in the search for new plant derived natural products against these diseases and an overview on natural products of terpenoid origin with antiprotozoal potential were given. The present part II compiles the current knowledge on natural products with antiprotozoal activity that are derived from the shikimate pathway (lignans, coumarins, caffeic acid derivatives), quinones of various structural classes, compounds formed via the polyketide pathways (flavonoids and related compounds, chromenes and related benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts compile the literature on almost 900 different plant-derived natural products and their activity data, taken from over 800 references. These data, as the result of enormous efforts of numerous research groups world-wide, illustrate that plant secondary metabolites represent an immensely rich source of chemical diversity with an extremely high potential to yield a wealth of lead structures towards new therapies for NTDs. Only a small percentage, however, of the roughly 200,000 plant species on earth have been studied chemically and only a small percentage of these plants or their constituents has been investigated for antiprotozoal activity. The repository of plant-derived natural products hence deserves to be investigated even more intensely than it has been up to present.

The Potential of Secondary Metabolites from Plants as Drugs or Leads Against Protozoan Neglected Diseases – Part I

Potent antitumor activity of synthetic 1,2-Naphthoquinones and 1,4-Naphthoquinones.

Electrochemical parameters and techniques in drug development, with an emphasis on quinones and related compounds

Update 1 of: Electrochemical approach to the mechanistic study of proton-coupled electron transfer.

Trypanocidal activity and redox potential of heterocyclic- and 2-hydroxy-naphthoquinones

Synthesis of 2-Substituted Furanonaphthoquinones Using Directed Metalation and Cross Coupling Reactions

Synthesis of C-2 Unsubstituted Furanonaphthoquinones

A gentamicina e um antimicrobiano de baixo custo amplamente utilizado no tratamento da septicemia neonatal. Entretanto, existe um risco potencial de oto e nefrotoxicidade. Neste trabalho, buscou-se caracterizar o recem-nascido hospitalizado em uso de gentamicina e avaliar o cumprimento do protocolo de tratamento adotado em uma Instituicao publica de Belo Horizonte, Minas Gerais. Trata-se de um estudo transversal incluindo 63 recem-nascidos atendidos em uma maternidade publica no periodo de agosto, outubro e dezembro de 1999. Essa maternidade e referencia na assistencia a gestacao e ao parto de alto risco em Minais Gerais. A maioria dos recem-nascidos foi prematura (85,7%) e de baixo peso (90,5%). Apenas dois (3,2%) casos de septicemia foram confirmados por hemocultura. O protocolo adotado preconiza a administracao de doses de 2,5 mg/kg a intervalos de 24 horas para neonatos com peso inferior a 1200 g e 12 horas para aqueles com peso superior a esse. Observou-se que o esquema terapeutico foi adotado em 96,7% dos casos. Contudo, constatou-se uma utilizacao por tempo superior ao recomendado, frente a hemocultura negativa, em mais de 70,0% dos casos.

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Utilização de gentamicina no tratamento de neonatos atendidos em uma maternidade pública da região metropolitana de Belo Horizonte, Minas Gerais (1999)

Sérgia M. Starling

Papers

Trypanocidal activity and redox potential of heterocyclic- and 2-hydroxy-naphthoquinones

Synthesis of 2-Substituted Furanonaphthoquinones Using Directed Metalation and Cross Coupling Reactions

Synthesis of C-2 Unsubstituted Furanonaphthoquinones

Utilização de gentamicina no tratamento de neonatos atendidos em uma maternidade pública da região metropolitana de Belo Horizonte, Minas Gerais (1999)

Synthesis of 2-Substituted Furanonaphthoquinones Using Directed Metalation and Cross Coupling Reactions.