Membrane-Organized Chemical Photoredox Systems

This project has three interrelated goals relevant to solar water photolysis, which are to develop: (1) vesicle-organized assemblies for H2 photoproduction that utilize pyrylium and structurally related compounds as combined photosensitizers and cyclic electroneutral transmembrane electron carriers; (2) transmembrane redox systems whose reaction rates can be modulated by light; and (3) homogeneous catalysts for water oxidation. In area (1), initial efforts to photogenerate H2 from vectorially-organized vesicles containing occluded colloidal Pt and commonly available pyrylium ions as transmembrane redox mediators were unsuccessful. New pyrylium compounds with significantly lower reduction potentials have been synthesized to address this problem and their apparent redox potentials in functioning systems have been now evaluated by using a series of occluded viologens. These studies provide an estimate of thermodynamic constraints imposed by these assemblies on hydrogen photoproduction. In area (2), spirooxazine-quinone dyads have been synthesized and their capacity to function as redox mediators across bilayer membranes has been evaluated through continuous photolysis and transient spectrophotometric measurements. These studies provide information on how quinone pools transfer charge in biomimetic systems designed to store solar energy as transmembrane electrochemical gradients. Photoisomerization of the spiro moiety to the ring-open mero form caused net quantum yields to decrease significantly, providing a basis for photoregulation of transmembrane redox; unexpectedly, both electrogenic and electroneutral pathways were observed, which were dependent upon the isomeric state of the chromophore (mero vs. spiro) and quinone substituent groups. Research on water oxidation (area 3) has been directed at understanding mechanisms of catalysis by cis,cis-[(bpy)2Ru(OH2)]2O4+ and related polyimine complexes. Using a variety of physical techniques, we have: (i) identified the redox state of the complex ion that is catalytically active; (ii) shown using 18O isotopic labeling that there are two reaction pathways, both of which involve participation of solvent H2 O; and (iii) detected by EPR and resonance Raman spectroscopies new species which may be key intermediates in the catalytic cycle. Analogs containing substituted bipyridine ligands have been synthesized to probe molecular details of these reactions whose understanding is necessary for rational design of superior catalysts

Reactivity of Peroxynitrite: Implications for Hanford Waste Management and Remediation

The purpose of this grant has been to provide basic chemical research in support of a major project undertaken at Brookhaven National Laboratory (BNL) whose purpose was to provide better understanding of the complex chemical processes occurring an nuclear storage tanks on the Hanford reservation. More specifically, the BNL grant was directed at evaluating the extend of radiation-induced formation of peroxynitrite anion (ONOO) in the tanks and its possible use in was incorporated as a subcontract EMSP 73824, but was later changed to an independent grant to avoid unnecessary duplication of administrative support at both WSU and BNL

Development of Sub-optimal Airway Protocols for the International Space Station (ISS) by the Medical Operation Support Team (MOST)

Airway management techniques are necessary to establish and maintain a patent airway while treating a patient undergoing respiratory distress. There are situations where such settings are suboptimal, thus causing the caregiver to adapt to these suboptimal conditions. Such occurrences are no exception aboard the International Space Station (ISS). As a result, the NASA flight surgeon (FS) and NASA astronaut cohorts must be ready to adapt their optimal airway management techniques for suboptimal situations. Based on previous work conducted by the Medical Operation Support Team (MOST) and other investigators, the MOST had members of both the FS and astronaut cohorts evaluate two oral airway insertion techniques for the Intubating Laryngeal Mask Airway (ILMA) to determine whether either technique is sufficient to perform in suboptimal conditions within a microgravity environment. Methods All experiments were conducted in a simulated microgravity environment provided by parabolic flight aboard DC-9 aircraft. Each participant acted as a caregiver and was directed to attempt both suboptimal ILMA insertion techniques following a preflight instruction session on the day of the flight and a demonstration of the technique by an anesthesiologist physician in the simulated microgravity environment aboard the aircraft. Results Fourteen participants conducted 46 trials of the suboptimal ILMA insertion techniques. Overall, 43 of 46 trials (94%) conducted were properly performed based on criteria developed by the MOST and other investigators. Discussion The study demonstrated the use of airway management techniques in suboptimal conditions relating to space flight. Use of these techniques will provide a crew with options for using the ILMA to manage airway issues aboard the ISS. Although it is understood that the optimal method for patient care during space flight is to have both patient and caregiver restrained, these techniques provide a needed backup should conditions not present themselves in an ideal manner

Dopamine D 4 Receptor-Deficient Mice Display Cortical Hyperexcitability

The dopamine D(4) receptor (D(4)R) is predominantly expressed in the frontal cortex (FC), a brain region that receives dense input from midbrain dopamine (DA) neurons and is associated with cognitive and emotional processes. However, the physiological significance of this dopamine receptor subtype has been difficult to explore because of the slow development of D(4)R agonists and antagonists the selectivity and efficacy of which have been rigorously demonstrated in vivo. We have attempted to overcome this limitation by taking a multidimensional approach to the characterization of mice completely deficient in this receptor subtype. Electrophysiological current and voltage-clamp recordings were performed in cortical pyramidal neurons from wild-type and D(4)R-deficient mice. The frequency of spontaneous synaptic activity and the frequency and duration of paroxysmal discharges induced by epileptogenic agents were increased in mutant mice. Enhanced synaptic activity was also observed in brain slices of wild-type mice incubated in the presence of the selective D(4)R antagonist PNU-101387G. Consistent with greater electrophysiological activity, nerve terminal glutamate density associated with asymmetrical synaptic contacts within layer VI of the motor cortex was reduced in mutant neurons. Taken together, these results suggest that the D(4)R can function as an inhibitory modulator of glutamate activity in the FC.Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Cepeda, Carlos. University of California at Los Angeles; Estados UnidosFil: Hurst, Raymond S.. University of California at Los Angeles; Estados UnidosFil: Flores Hernandez, Jorge. University of California at Los Angeles; Estados UnidosFil: Ariano, Marjorie A.. The Chicago Medical School; Estados UnidosFil: Falzone, Tomas Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Kozell, Laura B.. Oregon Health Sciences University; Estados UnidosFil: Meshul, Charles K.. Oregon Health Sciences University; Estados UnidosFil: Bunzow, James R.. Oregon Health Sciences University; Estados UnidosFil: Low, Malcolm J.. Oregon Health Sciences University; Estados UnidosFil: Levine, Michael S.. University of California at Los Angeles; Estados UnidosFil: Grandy, David K.. Oregon Health Sciences University; Estados Unido

Mechanistic Insight into Peroxydisulfate Reactivity: Oxidation of the cis,cis-[Ru(bpy)₂(OH₂)]₂O⁴⁺ "Blue Dimer"

One-electron oxidation of the μ-oxo dimer (cis,cis-[Ruᴵᴵᴵ(bpy)₂(OH₂)]₂O⁴⁺, {3,3}) to {3,4} by S₂O₈²⁻ can be described by three concurrent reaction pathways corresponding to the three protic forms of {3,3}. Free energy correlations of the rate constants, transient species dynamics determined by pulse radiolysis, and medium and temperature dependencies of the alkaline pathway all suggest that the ratedetermining step in these reactions is a strongly nonadiabatic dissociative electron transfer within a precursor ion pair leading to the {3,4}|SO₄²⁻|SO₄•− ion triple. As deduced from the SO₄•− scavenging experiments with 2-propanol, the SO₄•− radical then either oxidizes {3,4} to {4,4} within the ion triple, effecting a net two-electron oxidation of {3,3}, or escapes in solution with ∼25% probability to react with additional {3,3} and {3,4}, that is, effecting sequential one-electron oxidations. The reaction model presented also invokes rapid {3,3} + {4,4} → 2{3,4} comproportionation, for which kcₒₘ ∼5 × 10⁷ M⁻¹ s⁻¹ was independently measured. The model provides an explanation for the observation that, despite favorable energetics, no oxidation beyond the {3,4} state was detected. The indiscriminate nature of oxidation by SO₄•− indicates that its fate must be quantitatively determined when using S₂O₈²⁻ as an oxidant

Clinical Space Medicine Products as Developed by the Medical Operations Support Team (MOST)

Medical Operations Support Team (MOST) is introducing/integrating teaching practices associated with high fidelity human patient simulation into the NASA culture, in particular, into medical training sessions and medical procedure evaluations. Current/Future Products iclude: a) Development of Sub-optimal Airway Protocols for the International Space Station (ISS) using the ILMA; b) Clinical Core Competency Training for NASA Flight Surgeons (FS); c) Post-Soyuz Landing Clinical Training for NASA FS; d) Experimental Integrated Training for Astronaut Crew Medical Officers and NASA FS; and e) Private Clinical Refresher Training

Hurst's Rescaled Range Statistical Analysis for Pseudorandom Number Generators used in Physical Simulations

The rescaled range statistical analysis (R/S) is proposed as a new method to detect correlations in pseudorandom number generators used in Monte Carlo simulations. In an extensive test it is demonstrated that the RS analysis provides a very sensitive method to reveal hidden long run and short run correlations. Several widely used and also some recently proposed pseudorandom number generators are subjected to this test. In many generators correlations are detected and quantified.Comment: 12 pages, 12 figures, 6 tables. Replaces previous version to correct citation [19