Strongly fluorescent indolizine-based coumarin analogs†

Abstract

It is now possible to prepare 2-oxo-2H-pyrano[2,3-b]indolizine-3-carboxylates with an ordered arrangement of various substituents directly from pyridinium salts and diethyl 2-(ethoxymethylene)malonate, allowing for refined control of their photophysical properties. Facile entry into some previously unknown derivatives is disclosed to demonstrate the potential of this method. The use of substituted picolinium salts, as well as further functionalization of the pyrrole ring, permitted easy introduction of new moieties upon the dye, which enabled fine-tuning of the photophysical properties. The obtained dyes possess absorption and emission spectrum in the blue–green region and fluorescence quantum yields reaching 92%. The parent 2-oxo-pyrano[2,3-b]indolizine-3-carboxylate turned out to be an electron-deficient system with a low-lying LUMO, an electronic transition energy of 2.7 eV and possessing a large oscillator strength. Almost complete overlap of the HOMO and LUMO in the 2-oxo-pyrano[2,3-b]indolizine core is responsible for the large fluorescence quantum yields for almost all prepared derivatives. The reason for maintaining the large emission intensity in polar solvents is that the increase in the dipole moment is accompanied with a significant change in its orientation in space. Fluorescence imaging studies have proven that 2-oxo-pyrano[2,3-b]indolizines penetrate the membrane of living cells. A positively charged analog was synthesized and used to stain intracellular organelles in the H9c2 cell line. This compound did not penetrate the cell membrane, however after permeabilization, it specifically stained the nucleus.