Therapeutic azulenyl nitrone antioxidants

The reactions of nitrones with free radicals have been widely studied both in vitro and in vivo. In comparison to classical chain-breaking phenolic antioxidants (such as Vitamin E and butylated hydroxytoluene [BHT]), conventional phenyl-substituted nitrones have much higher oxidation potentials. Azulenyl-substituted nitrones have lower oxidation potentials than conventional nitrones and react efficiently with free radicals in vitro and in vivo. The design and synthesis of novel azulenyl nitrones with yet lower oxidation potentials, prepared from commercially available guaiazulene, has produced several 1,2-trans -bis-azulenyl ethene compounds with enhanced antioxidant activity. A convenient 1H NMR-based assay for assessing the potency of chain-breaking antioxidants has shown these novel nitrones to be more than 300 times more potent in inhibiting the free radical-mediated aerobic peroxidation of cumene than α-phenyl-N-tert-butyl nitrone (PBN) and the experimental stroke drug NXY-059. The low oxidation potential of these novel nitrones and the stability of the corresponding radical cation have been implicated in the explanation of the increased antioxidant potency of these second generation azulenyl nitrones. Based on the results of these in vitro studies, the first of these novel compounds, stilbazulenyl nitrone (STAZN), was investigated in animal models of disease known to involve free radical-mediated pathology. In view of STAZN's marked lipophilicity and anticipated blood brain barrier permeability, neurodegenerative conditions were investigated. All animal experiments were performed at the University of Miami by members of the Ginsberg research group. STAZN was neuroprotective in traumatic brain injury in rats. It also provided exceptional neuroprotection in an animal model of stroke. The concentration of STAZN required for neuroprotection was 300–600 times less than doses of PBN or NXY-059 required for similar effect. Thus, the benefits of greater antioxidant potency sought by lowering the oxidation potential of nitrones appear to have been reaped both in vitro and in vivo. In spite of the challenges and difficulties in understanding free radical-mediated pathology, this work establishes that considerations such as redox potential and lipophilicity can provide a very fruitful rationale for the design of therapeutic azulenyl nitrone antioxidants. ^

Soil Carbon Dioxide and Methane Efflux From an Everglades Tree Island and Ridge Landscape

The influence water levels have on CO2 and CH4 efflux were investigated at the Loxahatchee Impoundment Landscape Assessment (LILA) research facility, located in Boynton Beach, FL, USA. Measurements of CO2 efflux were taken for 24 h periods four times for one year from study plots. Laboratory incubations of intact soil cores were sampled for CO2, CH4, and redox potential. Additionally, soil cores from wet and dry condition were incubated for determination of enzyme activity and macronutrient limitation on decomposition of organic matter from study soils. Water levels had a significant negative influence on CO2 efflux and redox, but did not significantly influence CH4 efflux. Study plots were significantly different in CH4 efflux and redox potential. Labile carbon was more limiting to potential CO2 and CH4 production than phosphorus, with the effect significantly greater from dry conditions soils. Enzyme activity results were variable with greater macronutrient responses from dry condition soils.