Quantitative Structure-Activity Relationships for New Aerospace Fuels
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Quantitative Structure-Activity Relationships for New Aerospace Fuels Steven Trohalaki1 and Ruth Pachter Air Force Research Laboratory, Materials & Manufacturing Directorate Wright-Patterson Air Force Base, OH 45433-7702, U.S.A. ABSTRACT The design of new materials can be made more efficient if toxicity screening is performed in early rather than in late stages of development, especially for volatile materials such as lubricants, fire retardants, fuels, and fuel additives. In our continuing efforts to develop methods for the prediction of the toxicological response to materials of interest to the U.S. Air Force, we have constructed Quantitative Structure-Activity Relationships (QSARs) for thirteen newly proposed propellant compounds. We employed two previously published in vitro toxicity endpoints in primary cultures of isolated rat hepatocytes, which measured decrease in mitochondrial function and glutathione depletion [1]. Molecular descriptors were obtained using ab initio molecular orbital theory. QSAR models were then derived for each endpoint. Correlation coefficients for 2- and 3-parameter QSARs exceed 0.9, possibly enabling toxicity predictions for similar compounds. Insight into the biophysical mechanism of toxic response can be gained from interpretation of the descriptors comprising the QSARs. INTRODUCTION Hydrazine and its methylated derivatives are powerful reducing agents with a wide range of uses, including aerospace fuels. The introduction of hydrazine, monomethyl hydrazine, and 1,1dimethyl hydrazine as propellants grew out of a need for high-energy, noncryogenic, liquid fuels that can be used alone or mixed with other components. The toxicity of hydrazine propellants is a substantial operational concern to the U.S. Air Force as well as to the aerospace industry. The two most likely occupational exposure routes are inhalation and skin exposure [2]. Hydrazine and its derivatives enter the environment primarily from aerospace emissions and from manufacturing facilities. Toxic effects due to hydrazine exposure include liver damage, hypoglycemia, disorders of the central nervous system, interference with intermediary metabolism, induction of systemic lupus erythematosus, and carcinogenicity. Monoalkylated hydrazine derivatives are metabolically oxidized and form carbon-centered radicals [3]. Disubstituted derivatives, however, are oxidized to carbocations as well as to carbon-centered radicals [4]. Toxicity of hydrazine derivatives has been attributed to carbocations [5], carboncentered radicals [6], and to reactive oxygen species [7]. In view of the toxicity of hydrazines, alternative propellant compositions are currently under investigation. Several molecular components were synthesized and are currently being evaluated (by the Propulsion Directorate of the Air Force Research Laboratory, Edwards AFB, CA), including those listed in Table I. These high-energy chemicals (HECs) may be categorized as hydrazine-based, amine-based, triazole-based, and a quaternary ammonium salt. A preliminary report o
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