Structure of 6,6,10,10-tetranitropentacyclo[5.3.0.02,5.03,9.04,8]decane, C10H8N4O8

Abstract

The pK a value for (E)-3-fluoro-4-PAM was found by potentiometric titration to be 8.2. Therefore, this compound meets the empirical pK a requirement for rapid reactivation of phosphonylated acetylcholinesterase. Since the corresponding pK a value of the nonfluorinated analog (4-PAM) is 8.6 (Ginsburg & Wilson, 1957; Poziomek, Kramer, Mosher & Michel, 1961), substitution of fluorine for hydrogen at the 3-position of the pyridine ring decreases the pK a by 0.4 pK a units, an effect expected from the electronwithdrawing properties of the fluorine atom. Preliminary studies indicate that the fluorine-substituted compound has an increased rate of dephosphonylation of enzyme relative to the unsubstituted parent compound, but less than that of 2-PAM (in spite of the similarities in pK a values). Thus, except for the fact that the fluorine substitution causes more stringent coplanarity between the oxime group and the pyridine ring, the effect of fluorine is confined to lowering the pK a value.