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4-(Chloroacetyl)pyridinium Salt:  A New Chromophoric and Solvatochromic Reagent of the Thiol Group

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journal contribution
posted on 06.03.1996, 00:00 authored by Michel Holler, Alain Burger, Jean-François Biellmann
N-(4‘-chlorobenzyl)-4-(chloroacetyl)pyridinium chloride was prepared from the N-(4‘-chlorobenzyl)-4-acetylpyridinium chloride by chlorination with sulfuryl chloride. This chloro ketone had a half life of 150 min at pH 7.3 and reacted specifically with thiols. The reaction product with pentanethiol crystallized as an enol whose structure was determined by X-ray diffraction. The structure indicated conjugation of the sulfur with the pyridinium ring. In solution this enol was in equilibrium with the corresponding ketone and with the hydrate or the hemiketal according to the solvent. The enol was the major species in DMSO while in water the ketone and the hydrate were major. This solvent dependent equilibrium was reflected in the variation of the absorption coefficient at the maximum wavelength at around 400 nm according to the solvent. The absorption maximum wavelength of the thioether, a negative solvatochrome, depended on the solvent and showed a close to linear relationship with the polarity index of Snyder. The enolic hydroxyl group has a pKa of 7.4 and the α thioether ketone a pKa of 7.9. The chloro ketone is a useful reagent to explore the environment of reactive cysteine residue in proteins, giving information on the polarity of the environment by the position of the absorption maximum wavelength and the pKa of the enolic hydroxyl group.