Fluorinated phosphorus compounds: Part 4. A lack of anticholinesterase activity for four tris(fluoroalkyl) phosphates

Whilst examining the chemistry of a series of tris(fluoroalkyl) phosphates as potential fire retardants, concern was raised over their possible anticholinesterase activity. Bimolecular rate constants (ki values) for the inhibition of bovine erythrocyte acetylcholinesterase (AChE) at 37°C and pH 7.4 were therefore sought for four fluoroalkyl phosphates: (CF3CH2O)3PO, (C2F5CH2O)3PO, (C3F7CH2O)3PO and (CF3CH2O)2P(O)OCH2C2F5. Under the experimental conditions used, none of them inhibited AChE; it was only possible to define their ki values as being less than 7–16 M−1 min−1. They are therefore at least a factor of 105 less potent inhibitors than the nerve agents sarin or soman, and should be non-toxic via the mechanism of direct inhibition of AChE.