Synthesis of a novel series of bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase

Figures & data

Scheme 1 Symmetrical bisquaternary xylene-linked compounds.

Scheme 2 AChE inhibited by chlorpyrifos.

Scheme 3 Synthesis of symmetric bisquaternary compounds.

Scheme 4 Synthesis of 2,2′-bis(hydroxyiminomethyl)-1,1′-(1,3-phenylenedimethyl)-bispyridinium dibromide.

Table I.  Reactivation potencies (%)^a of tested oximes. Time of inhibition by chlorpyrifos –30 min; time of reactivation by AChE reactivators –10 min; pH 8; temperature 25°C.

	Compound	% (10^− 3 M)	% (10^− 5 M)
Synthesized oximes	6a	19	3
	6b	26	39
	6c	41	68
	7a	0	0
	7b	5	0
	7c	8	0
	8a	20	0
	8b	37	25
	8c	34	8
Reference Compounds	2-PAM (1)	38	4
	TMB-4 (2)	66	38
	obidoxime (3)	63	35
	HI-6 (4)	20	11
	MMC (5)	45	10

^a Mean value of three independent determinations.

Figure 1 Efficacy of tested oximes in reactivation of chlorpyrifos-inhibited AChE.

Scheme 5 Lengths and angles of linking chains in 6, 7 and 8.

Scheme 6 Bell-shaped curve of reactivation process.