An Fe(II) complex of pyridine-2,6-di-(monothiocarboxylic acid) - a novel bacterial metabolic product

Tetrahedron Letters
1978.0

Abstract

The culture medium of an as-yet unidentified Pseudomonas strain turns dark blue upon addition of ferric citrate and changes to reddish brown when shaken with air. An amorphous powder was extracted with isopropanol, and its main component was isolated via chromatography (silica gel 60, ethyl acetate/methanol 4:1) and ion exchange resin (Lewatit S 100) purification. The pigment contains a redox system: its brown form can be reduced by Na₂S₂O₄ to a blue product (stable only in the presence of excess reducing agent and easily reoxidized by air to the starting material). Electron, IR (strong structured band with a maximum at 1580 cm⁻¹), NMR (presence of Fe) and electron impact mass spectra did not provide structural information; field desorption (FD) mass spectra measured after admixture of Na₂CO₃ or K₂CO₃ yielded ions of mass 450 plus one, two or three alkali metal atoms, consistent with an osmometric molecular weight determination (~350). Electrophoresis at pH 6.9 (phosphate buffer) and 8.0 (triethyl ammonium bicarbonate buffer) showed migration to the anode. A methanolic solution of the brown pigment reacted slowly with diazomethane; gas chromatography analysis of the reaction product identified pyridine-2,6-di-(monothiocarboxylic acid) di-S-methyl ester (structure confirmed by synthesis). Treatment of the free acid (A) with Fe salts resulted in blue or brown complexes, and the brown complex obtained was identical to the natural product (by IR, ESCA, FD spectra and chromatographic behavior). The Mossbauer spectrum of the brown complex (chemical shift +0.244 mm/s relative to Fe metal, quadrupole splitting 2.36 mm/s) indicated the presence of Fe(II); the ESCA spectrum showed no metals other than Fe. All evidence points towards the formulation of the brown complex (free acid) with a 1:2 Fe/ligand ratio (though higher aggregates with the same ratio cannot be rigorously excluded). Complexes 1 and 2 exhibit antibiotic activity, which may result from interference with the active sites of iron sulfur proteins involved in biological redox systems.

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