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Abstract: Fluoroheterocyclic aldoximes were screened as therapeutic agents for the treatment of anticholinesterase poisoning. 2-Fluoropyridine-3- and -6-aldoxime, and 3-fluoropyridine-2- and -4-aldoxime, were synthesised. Attempts to obtain 3,5,6-trifluoropyridine-2,4-bis(aldoxime) and -2-aldoxime, however, proved unsuccessful. Pentafluorobenzaldoxime was prepared by oximation of pentafluorobenzaldehyde. Acid dissociation constants (pK a) and second-order rate constants (k ox−) of the fluorinated pyridinealdoximes towards sarin were measured. 2,3,5,6-Tetrafluoropyridine-4-aldoxime had the best profile: its k ox− approached that of the therapeutic oxime P2S (310 vs. 120lmol−1 min−1), but its higher pK a (9.1 vs. 7.8) fell short of the target figure of 8 required for reactivation of inhibited acetylcholinesterase in vivo. N-alkylation of the fluorinated pyridine-aldoximes may reduce their pK a nearer to 8 and enhance their therapeutic potential. [Copyright &y& Elsevier]

Anisotropic 14N couplings have been determined using electron paramagnetic resonance spectroscopy for the radicals, bis(trifluoromethyl)nitroxide and di-tert-butylnitroxide as isolated in a polycrystalline fluorotrichloromethane matrix at 77 K. The results show that the nitrogen 2pz orbital spin-population in bis(trifluoromethyl)nitroxide is 26%, as compared with 48% in di-tert-butylnitroxide, which is due mainly to the importance of the oxygen-localised canonical structure (CF3)2N–O&z.sbnd; and to spin-delocalisation onto the CF3 groups: it is the large oxygen atom spin density of 0.63 that determines the relatively high reactivity of bis(trifluoromethyl)nitroxide in hydrogen-atom transfer reactions. On the basis of their anisotropic and isotropic 14N couplings (measured in liquid fluorotrichloromethane), it is concluded that the configuration at the nitrogen centre is near-planar in both nitroxides. This result is supported by molecular orbital calculations made on these, and related molecules in order to evaluate some of the theoretical methods available to organic chemists. [Copyright &y& Elsevier]