Quantification of foscarnet with chromogenic and fluorogenic chemosensors: indicator displacement assays based on metal ion coordination with a catechol ligand moietyElectronic supplementary information (ESI) available: Supplementary figures with pH-variable fluorescence, fluorescence spectra, and complex stability. See DOI: 10.1039/c1nj20460b

• Main Authors: Gaidamauskas, Ernestas, Crans, Debbie C, Parker, Helen, Saejueng, Kanokkarn, Kashemirov, Boris A, McKenna, Charles E
• Format: Article
• Language: English
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/c1nj20460b

The catechol moiety in a chromophore was used in an indicator displacement assay for the chemosensing of the antiviral drug foscarnet (trisodium phosphonoformate, abbreviated as PFA). Applications of two methods were investigated, namely UV-Vis absorption and fluorescence spectroscopy measuring coordination of a metal to a catechol-based indicator. Yb 3+ complexation with chromogenic pyrocatechol violet in 10 mM HEPES buffer at pH 7.0 yields a blue chemosensor that responds to the presence of PFA with the release of yellow pyrocatechol violet (PV). The YbPV coordination complex responds linearly to the PFA concentration with a 2 μM detection limit. Metal ion complexation of a range of metal ions (trivalent Al, Ga, In, Sc, La, Gd, Er, Yb, and Fe, and divalent Cu) to the fluorescent sensor 6,7-dihydroxy-4-methylcoumarin (also referred to as 4-methylesculetin and abbreviated ME) resulted in fluorescence quenching in 10 mM HEPES buffer at pH 7.0. Addition of foscarnet to the quenched coordination complex liberated the ligand fluorophore which could be observed by its fluorescence. The coordinating complex was optimized for determining foscarnet by varying the metal ion, resulting in increased sensitivity to the analyte and selectivity against phosphate. Cu 2+ was selected as the most effective ion and its performance in this assay was further investigated. The effect of the co-ligand in the ternary coordination complex, Cu 2+ -6,7-dihydroxy-4-methylcoumarin-co-ligand, was examined, and 2-picolylamine was found to be the optimal co-ligand. This ternary complex improves the detection limit of PFA to 0.5 μM and is stable for at least 72 hours, rendering it a potential sensor for PFA in chromatographic analysis. The coordination chemistry of ternary complexes of Cu, Yb, Al, Sc, Fe, In, Ga, Gd, Er, and La from catechol-containing chromophores and fluorophores for sensing of phosphonates such as Foscavir.