The full spectrum tuning of fluorescent molecules via a one-pot multicomponent reaction

Abstract

Fluorogenic probes for imaging enable visualization and analysis of difficult-to-reach cells and organelles. However, there are limited efficient examples of tuning these fluorescent molecules to higher wavelengths. This is vital since different tissues are sensitive to varying wavelength emissions. To address this need, we report the discovery, tuning, structure-photophysical property relationships (SPPR), and time-dependent DFT (TD-DFT) computations of 400–700+ nm fluorescent pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolines and substituted imidazo[1,2-a]pyridin-3-amines. The syntheses involve the trimethylsilylcyanide (TMSCN) modified Groebke-Blackburn-Bienaymé (GBB) multicomponent reaction as well as the TMSCN modified GBB combined with subsequent condensation of an aldehyde, and Aza-Friedel-Crafts-Intramolecular Cyclization-Oxidation all in one pot. The SPPR reveals that electron-withdrawing strength in the para-position of the aminopyridine starting material has direct control over the absorption and fluorescence emission wavelengths of these molecules. The TD-DFT computations show the changes in the natural transition orbitals (NTOs) with differing substitutions to the parent molecule that dictate the observed excitations, emissions, and fluorescence intensities. These findings give insights and directions for tuning the fluorescent properties of these motifs for various uses as probes and imaging agents.