Phenyl di- n-pentylphosphinate: a convenient reactivatible inhibitor for studies on neuropathy target esterase (NTE) and protection against organophosphate-induced delayed polyneuropathy

Abstract

Phenyl di- n-pentylphosphinate was synthesised by interaction of phenyl phosphorodichloridate and n-pentyl magnesium bromide. The product was purified by silica chromatography (yield 25%). Although much more stable at physiological pH than its 4-nitrophenyl analogue, this ester is a good inhibitor of neuropathy target esterase (NTE): k a = 1.7 sX 10 5 M −1 min −1. It is a very weak anticholinesterase ( k a ∼- 10 M −1 min −1). In vivo only 5–10 mg kg is required to inhibit hen brain and spinal cord NTE. The inhibited NTE can be reactivated fully by incubation in vitro with iso-nitrosoacetophenone (1NAP) (19 mM at 37°C and pH 8.5 for 60 min): this property enables study to be made of the fate of inhibited NTE in vivo.