title: Chromatographic separation and NMR characterization of the isomers of MMB-4, a bis-(pyridiniumaldoxime).
abstract: 1,1'-Methylenebis{4-[(hydroxyimino)methyl]pyridinium) dichloride (MMB-4), a promising antidote for organophosphate poisoning, has been shown by chromatography and NMR to be a mixture of geometric isomers, predominantly the E/E form. The chromatographically separated isomers have been isolated, directly characterized by NMR to be E/E and E/Z isomers of high purity, and shown by HPLC and NMR to re-equilibrate in solution to the isomeric mixture found in bulk MMB-4. These findings clearly show that a minor component in MMB-4 is not an impurity, but a geometric isomer of the principal component and demonstrate the need to understand equilibrium processes for drug characterizations and isomer distributions of chemicals proposed for animal and human clinical trials. Evidence for the presence of the Z/Z isomer could not be found.
authors.affiliation: Physical Sciences Division, SRI International, Menlo Park, CA 94025, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Macauley
authors.forename: Ronald
authors.initials: R
authors.lastname: Spanggord
authors.forename: William
authors.initials: W
authors.lastname: Chrisman
authors.forename: Peter
authors.initials: P
authors.lastname: Lim
authors.forename: William
authors.initials: W
authors.lastname: Ellis
mesh_terms: D000931:Antidotes / Q000737:chemistry* / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010091:Oximes / Q000737:chemistry* / Q000302:isolation & purification; D013237:Stereoisomerism
chemical_list: D000931:Antidotes; D007202:Indicators and Reagents; D010091:Oximes; C005514:N,N'-monomethylenebis(pyridiniumaldoxime)