Exactly controlled linear CO liberation: an A- and B-ring simultaneously extended flavonol-based red fluorescent photoCORM.

Abstract

The first visible/sun-light-triggered A/B-ring-naphthalene/biphenyl simultaneously extended flavonol based red fluorescent photoCORM, Nbp-flaH (2-([1,1'-biphenyl]-4-yl)-3-hydroxy-4H-benzo[g]chromen-4-one), was developed. By simultaneously extending π-conjugation on the A- and B-ring of 3-hydroxyflavone (FlaH), the absorption peak and emission peak of Nbp-flaH were largely red-shifted by 75 and 100 nm, respectively, relative to those of FlaH, thus emitting strong and bright red fluorescence (610 nm, near the phototherapeutic window), with a large Stokes shift of 190 nm. Therefore, Nbp-flaH can be triggered by visible/sun-light, and its location in living HeLa cells and the process of CO delivery can be real-time imaged and tracked in situ. By irradiation with visible light under O2, Nbp-flaH can release CO rapidly (t1/2 = 3.40 min) with a high yield (over 90%), and the dose of CO liberated can be quantitatively regulated within a safe and therapeutic dose range by changing the irradiation intensity or time or photoCORM dose. Nbp-flaH and its reaction products exhibit negligible toxicity (more than 85% cell viability, 24 h) and good permeability in live HeLa cells. This is the first A- and B-ring-simultaneously extended (to naphthalene and biphenyl, respectively) flavonol developed as a red fluorescent photoCORM, which can be triggered by visible/sun-light and deliver accurately and quantitatively controlled linear CO in live HeLa cells. Our work would provide not only a reliable method to precisely control the CO release dose for clinical CO therapy, but also a convenient tool for studying the biological role of CO.