Design, Synthesis, Physicochemical Properties, and Evaluation of Novel Iron Chelators with Fluorescent Sensors

Abstract

The synthesis of a range of novel 3-hydroxypyridin-4-ones and 3-hydroxypyran-4-ones linked with different coumarin substituents is described. These compounds have been developed in order to provide a series of molecular probes for the quantification of intracellular labile iron pools. An evaluation of the effect of iron(III) on fluorescence intensity was undertaken. Chelation of iron(III) causes quenching of fluorescence. The relationship between iron(III) concentration and the extent of fluorescence quenching indicates that the metal is chelated in a complex with a metal-to-ligand stoichiometry of 1:3. The fluorescence of hydroxypyridinone compounds was found to be more efficiently quenched by iron(III) than were the hydroxypyranones. The metal-to-ligand stoichiometry at which maximum quenching is observed was found to depend on the site at which coumarin is attached. The efficiency of fluorescence quenching by iron(III) is markedly influenced by solvent polarity and pH. The permeability of two representative fluorescent chelators across human erythrocyte ghost membranes was investigated. The rate of permeability for a series of probes was found to be related to the corresponding ClogP values.

Kojic Acid Derivatives as Histamine H3 Receptor Ligands

“…24) Kojic acid (P7) was functionalized to obtain a variety of gpyranone-containing precursors (Charts 2, 3). Benzyl kojic acid P8 was synthesized under basic conditions using highboiling solvents (cesium carbonate in anhydrous N,N-dimethylformamide (DMF) (a) 25) and soda lye in methanol (b), 26,27) respectively). Although side processes like ringopening of the vinylogous lactone caused by the attack of the aqueous alkali solution were expected, 28) yields ranged between 50% and 60% in both approaches.…”

“…(b) 26,27) Alternatively, a solution of P7 (5 g, 35.2 mmol) in methanol (40 ml) was added to a solution of sodium hydroxide (1.6 g, 38.7 mmol) in water (5 ml). This mixture was heated to reflux, benzyl bromide was added dropwise and reflux was continued for 12 h. The solution was allowed to cool to ambient temperature, the solvent removed by reduced pressure and the resulting brown solid was washed with water (15 ml) and methanol (10 ml).…”

Hydrogen-Bonded Supramolecular Array in the Crystal Structure of Ethyl 7-Hydroxy-2-Oxo-2h-Chromene-3-Carboxylate Monohydrate

“…First, resorcinol was formylated (Vilsmeier-Haack), 6 and subsequently condensed with ethyl malonate (Knoevenagel) and cyclized in a single step. 7 The solid was recrystallized in EtOH (5.6 g, 52%) to afford aggregates of yellow prisms (Scheme 1).…”

A New Ferric Ion-Selective Fluorescent Chemosensor with a Wide Dynamic Range

“…Since iron ion is paramagnetic, many iron sensors gave rise to the fluorescence-quenching process, 4,5 although the measurement of fluorescence enhancement upon binding with an analyte is more efficient.…”