Electrostatic Modification for Promotion of Flavin-Mediated Oxidation of a Probe for Flavin Detection

Electrostatic effects on the redox photochemistry of synthetic probes (1, 2, and 1-Zn) are examined by adjusting the thermodynamic driving force of their oxidation reactions. The redox photochemistry was simply controlled by introducing a zinc binding site (2,2'-dipicolylamine (DPA)) on the coumarin moiety of probe 2. Zinc complexation produced a positively charged environment on the coumarin (1-Zn), which lowered the electron density of a nearby 9 H-xanthene ring, attenuating the auto-oxidation of 1-Zn by 45 % compared with that of probe 1 at 298 K. The positive net charge of 1-Zn also provided an attractive Coulombic force toward the phosphate of flavin mononucleotide and flavin adenine dinucleotide, which lowered the reduction potential of the electron acceptor (isoalloxazine) and improved intermolecular electron transfer from the 9 H-xanthene ring to isoalloxazine. The flavin-mediated oxidation rate of 1-Zn was increased to 1.5 times that of probe 2. Probe 1-Zn showed highly selective sensing behaviour toward flavins, producing an intense brightness (ϵΦ_F =2.80×10³  m^-1  cm^-1 ) in the long-wavelength regions (λ_max =588 nm) upon flavin-mediated oxidation. Furthermore, probes 1-Zn and 2 were successfully applied to eosinophil imaging and the differential diagnosis of eosinophilia; this demonstrates their use as diagnostic tools.