Pascal Bugnon

Bio: Pascal Bugnon is an academic researcher from University of Lausanne. The author has contributed to research in topics: Dissociation (chemistry) & Na+/K+-ATPase. The author has an hindex of 5, co-authored 10 publications receiving 792 citations. Previous affiliations of Pascal Bugnon include University of Adelaide.

Formation and properties of peroxynitrite as studied by laser flash photolysis, high-pressure stopped-flow technique, and pulse radiolysis.

Abstract: Flash photolysis of alkaline peroxynitrite solutions results in the formation of nitrogen monoxide and superoxide. From the rate of recombination it is concluded that the rate constant of the react...

High-Pressure Studies as a Novel Approach in Determining Inclusion Mechanisms: Thermodynamics and Kinetics of the Host-Guest Interactions for a-Cyclodextrin Complexes

Abstract: The first volume profiles for complex formation of α-cyclodextrins (α-CD) with diphenyl azo dyes (S) are presented as a new approach in understanding inclusion phenomena. The following dyes were selected: sodium 4-(4-diethylaminophenylazo)benzenesulfonate (1), sodium 4-(3-carboxy-4-hydroxy-5-methylphenylazo)benzenesulfonate (2), sodium 4-(4-hydroxy-3,5-dimethylphenylazo)benzenesulfonate (3), and sodium 2-hydroxy-3-methyl-5-(4-sulfamoylphenylazo)benzoate (4). The behavior of the dyes alone were first studied in aqueous solutions to rule out any competition reaction. Under the experimental conditions used for the stopped-flow kinetic studies, it has been proved that only monomeric species are present (no aggregation of the dye is formed by π−π stacking interactions). NMR experiments and kinetic evidences have shown that only directional binding of the dye via the sulfonate/sulfonamide group through the wide rim of the α-cyclodextrin was possible. The 1:1 complex was the only stoichiometric species formed. ...

High-pressure stopped-flow spectrometer for kinetic studies of fast reactions by absorbance and fluorescence detection

Abstract: The development of a stopped-flow instrument that operates over a temperature range of −40 to +100 °C and up to 200 MPa is described. The system has been designed so that measurements can be performed in absorbance and fluorescence modes simultaneously, without dismantling the unit. It can easily be combined with an optical system of a conventional ambient pressure setup by using light guides. Optimum optical performance and a wide operating wavelength range (220−850 nm) are achieved as the light is not passing through the pressurizing fluid. A special design for the pistons has been developed; thus, the apparatus has proven to be leak-free, even under extreme conditions (high pressure, low temperature, various solvents). The dead time of the system is found to be less than 2 ms at 298 K and is pressure independent up to 200 MPa. We examined the kinetics for the formation of the Mg2+−8-hydroxyquinoline chelate in aqueous solutions at pH 8.0 in order to develop a convenient alternative test method for high...

A Model for Sequential Threading of α-Cyclodextrin onto a Guest: A Complete Thermodynamic and Kinetic Study in Water

Abstract: The first variable-temperature and variable-pressure stopped-flow spectrophotometric study of the sequential threading of α-cyclodextrin (α-CD) onto the guest dye Mordant Orange 10, S, is reported. Complementary 1H one-dimensional (1D) variable-temperature kinetic studies and two-dimensional (2D) rotating-frame nuclear Overhauser effect spectroscopy (ROESY) and EXSY NMR studies are also reported. In aqueous solution at 298.2 K, the first α-CD threads onto S to form a 1:1 complex S·α-CD* with a forward rate constant k1,f = 15 200 ± 200 M-1 s-1 and dethreads with a reverse rate constant k1,r = 4.4 ± 0.3 s-1. Subsequently, S·α-CD* isomerizes to S·α-CD (k3,f = 0.158 ± 0.006 s-1, k3,f = 0.148 ± 0.006 s-1). This process can be viewed as a thermodynamically controlled molecular shuttle. A second α-CD threads onto S·α-CD* to form a 1:2 complex, S·(α-CD)2*, with k2,f = 98 ± 2 M-1 s-1 and k2,r = 0.032 ± 0.002 s-1. A second α-CD also threads onto S·α-CD to form another 1:2 complex, S·(α-CD)2, characterized by k4,f =...

Role of Oxidative Modifications in Atherosclerosis

Abstract: This review focuses on the role of oxidative processes in atherosclerosis and its resultant cardiovascular events. There is now a consensus that atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall. The oxidative modification hypothesis of atherosclerosis predicts that low-density lipoprotein (LDL) oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis. In support of this hypothesis, oxidized LDL can support foam cell formation in vitro, the lipid in human lesions is substantially oxidized, there is evidence for the presence of oxidized LDL in vivo, oxidized LDL has a number of potentially proatherogenic activities, and several structurally unrelated antioxidants inhibit atherosclerosis in animals. An emerging consensus also underscores the importance in vascular disease of oxidative events in addition to LDL oxidation. These include the production of reactive oxygen and nitrogen species by vascular cells, as well as oxidative modifications contributing to important clinical manifestations of coronary artery disease such as endothelial dysfunction and plaque disruption. Despite these abundant data however, fundamental problems remain with implicating oxidative modification as a (requisite) pathophysiologically important cause for atherosclerosis. These include the poor performance of antioxidant strategies in limiting either atherosclerosis or cardiovascular events from atherosclerosis, and observations in animals that suggest dissociation between atherosclerosis and lipoprotein oxidation. Indeed, it remains to be established that oxidative events are a cause rather than an injurious response to atherogenesis. In this context, inflammation needs to be considered as a primary process of atherosclerosis, and oxidative stress as a secondary event. To address this issue, we have proposed an "oxidative response to inflammation" model as a means of reconciling the response-to-injury and oxidative modification hypotheses of atherosclerosis.

Synthetic molecular motors and mechanical machines.

Abstract: The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Reconciling the chemistry and biology of reactive oxygen species

Abstract: There is a vast literature on the generation and effects of reactive oxygen species in biological systems, both in relation to damage they cause and their involvement in cell regulatory and signaling pathways. The biological chemistry of different oxidants is becoming well understood, but it is often unclear how this translates into cellular mechanisms where redox changes have been demonstrated. This review addresses this gap. It examines how target selectivity and antioxidant effectiveness vary for different oxidants. Kinetic considerations of reactivity are used to assess likely targets in cells and how reactions might be influenced by restricted diffusion and compartmentalization. It also highlights areas where greater understanding is required on the fate of oxidants generated by cellular NADPH oxidases and on the identification of oxidant sensors in cell signaling.

Oxyradicals and DNA damage

Abstract: A major development of carcinogenesis research in the past 20 years has been the discovery of significant levels of DNA damage arising from endogenous cellular sources. Dramatic improvements in analytical chemistry have provided sensitive and specific methodology for identification and quantitation of DNA adducts. Application of these techniques to the analysis of nuclear DNA from human tissues has debunked the notion that the human genome is pristine in the absence of exposure to environmental carcinogens. Much endogenous DNA damage arises from intermediates of oxygen reduction that either attack the bases or the deoxyribosyl backbone of DNA. Alternatively, oxygen radicals can attack other cellular components such as lipids to generate reactive intermediates that couple to DNA bases. Endogenous DNA lesions are genotoxic and induce mutations that are commonly observed in mutated oncogenes and tumor suppressor genes. Their mutagenicity is mitigated by repair via base excision and nucleotide excision pathways. The levels of oxidative DNA damage reported in many human tissues or in animal models of carcinogenesis exceed the levels of lesions induced by exposure to exogenous carcinogenic compounds. Thus, it seems likely that oxidative DNA damage is important in the etiology of many human cancers. This review highlights some of the major accomplishments in the study of oxidative DNA damage and its role in carcinogenesis. It also identifies controversies that need to be resolved. Unraveling the contributions to tumorigenesis of DNA damage from endogenous and exogenous sources represents a major challenge for the future.