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MOLECULAR DYNAMICS OF 1-METHYLPYRIDINIUM-4-ALDOXIME CHLORIDE

Pyridinium aldoximes are known as pharmacologically important nucleophilic agents that are effective antidotes against poisoning by organophosphorus compounds (pesticides, chemical warfare nerve agents, drugs used in treatment of cholinergic disorders) which cause long-term inactivation of acetylcholinesterase (AChE, E.C.3.1.1.7) via phosphorylation of its active site. The enzyme can be reactivated by site-directed nucleophiles that accept a serine-bound phosphate, such as cation of pyridinium aldoxime. The agents comprising quaternary nitrogen that promotes binding in the catalytic site were an early triumph of rational pharmacology based on deductions from classic structure-reactivity relations (1). We have performed a comparative experimental and theoretical FT-IR and FT-Raman spectroscopic study of the 1-methylpyridinium-4-aldoxime chloride. The aim of the study was an attempt to correlate the structural features of the title compound with its acido-basic properties, reactivity and coordination mode to the pentacyanoferrate(II) moiety which is used as model of a biologically important macromolecules. Theoretical calculations were performed using the Gaussian 03 suite of programs (2). The geometry of 1-methylpyridinium-4-aldoxime cation was optimized using B3LYP, 6-31++G(d, p) method. Bond distances and valence angles were in good agreement with characteristic values obtained from X-ray structure analysis of the closely related compounds (3). The theoretical vibrational spectra were interpreted by means of potential energy distributions. A complete vibrational assignments and analysis were preformed. The coordination mode of the title compound to the iron centre of isolated solid pentacyanoferrate(II) complex was deduced by comparing the positions of characteristic vibrational bands in FT-IR and FT-Raman spectra with the spectra of the free ligand. 1. Wilson, I. B. ; Ginsberg S., Biochim. Biophys. Acta 18 (1955), 168– 170. 2. Frisch, M. J ; Trucks, G. W. ; Schlegel, H. B. ; et. al., Gaussian 98 (Revision C.02), Gaussian, Inc., Pittsburg PA, (2004). 3. Van Havere, W. ; Lenstra, A. T. H. ; Geise Frisch H. J. ; et. al., Acta Cryst. B38 (1982), 1635-1637.

Pyridinium aldoxime; Molecular dynamics

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