The novel catechol-BODIPY dyad, 8-(3,4-dihydroxyphenyl)-2,6-bis(ethoxycarbonyl)-1,3,5,7-tetramethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (FerriBRIGHT) was rationally designed with the aid of computational methods. FerriBRIGHT could be prepared by standard one-pot synthesis of BODIPY fluorophores from 3,4-bis(benzyloxy)benzaldehyde (1) and 3,5-dimethyl-4-(ethoxycarbonyl)pyrrole (3); however, isolating the dipyrrin intermediate 8-[3,4-bis(benzyloxy)phenyl]-2,6-bis(ethoxycarbonyl)-1,3,5,7-tetramethyl-4,4-diaza-s-indacene (7) prior to reaction with excess BF(3)center dot OEt(2) led to marked improvements in the isolated overall yield of the desired compound. In addition to these improvements in fluorophore synthesis, microwave-assisted palladium-catalyzed hydrogenolysis of benzyl ethers was used to reduce reaction times and catalyst loading in preparation of the desired compound. When FerriBRIGHT is exposed to excess FeCl(3), CuCl(2), [Co(NH(3))(5)Cl]Cl(2), 2,3-dichloro-5,6-dicyanobenzoqui none, or ceric ammonium nitrate in methanol, a significant enhancement of fluorescence is observed. FerriBRIGHT-Q, the product resulting from the oxidation of the pendant catechol to the corresponding quinone, was found to be the emissive species. FerriBRIGHT-Q was synthesized independently, isolated, and fully characterized to allow for direct comparison with the spectroscopic data acquired in solution. Biologically relevant reactive oxygen species, such as H(2)O(2), (center dot)OH, (1)O(2), O(2)(center dot-), and bleach (NaOCl), failed to cause any changes in the emission intensity of FerriBRIGHT. In accordance with the quantum mechanical calculations, the quantum yield of fluorescence for FerriBRIGHT (Phi(n) approximate to 0) and FerriBRIGHT-Q (Phi(n) = 0.026, lambda(ex)/lambda(em) = 490 nm/510 nm) suggests that photoinduced electron transfer between the catechol and the BODIPY dye is attenuated upon oxidation, which results in fluorescence enhancement. Binding studies of FerriBRIGHT with Ga(NO(3))(3), a redox-inactive analogue of Fe(III), provided conditional binding constant log beta(12)' = 13.3 +/- 0.2 for a [Ga(FerriBRIGHT)(2)](-) complex. A 2.8-fold enhancement of fluorescence intensity upon addition of Ga(III) to FerriBRIGHT suggests the possibility of metal ion sensing with this new class of compounds.
A Rationally Designed Fluorescent Probe for Redox Active Metals
Kennedy, D. P., Kormos, C. M., & Burdette, S. C. (2009). FerriBRIGHT: A Rationally Designed Fluorescent Probe for Redox Active Metals. Journal of the American Chemical Society, 131(24), 8578-8586. https://doi.org/10.1021/ja901653u