Pteridine-based fluorescent pH sensors designed for physiological applications

New derivatives of pteridine, namely 6,7-diphenyl-2-morpholinylpterin (DMPT) and 6-thienyllumazine (TLM) were designed and easily synthesized in a rational way for pH-fluorescence sensing near physiological pH. The dual-excitation ratiometric sensing was based on the distinct spectral properties of the fluorophore in its neutral and deprotonated states. Density Functional Theory (DFT) calculations were used to determine structures, gas phase acidities and pKa values for the new dyes. Substitutions on pterin (PT) and lumazine (LM) structures with phenyl, thienyl or morpholinyl groups enhanced the acidity of the new dyes. DMPT displays visible turn-on emission signals from blue to cyan (bluish-green) upon changing the pH from acidic to basic around pKa of 7.2. The advantages of the new pteridine dyes over those previously known pH sensors are discussed in details in terms of their facile preparation and functionalization, pKa tuning strategy, wide responsive and resolved signal around physiological pH, photostability, water solubility, and adequacy for intracellular pH measurements.

Visible fluorescence switching from blue to cyan under 350-nm UV lamp from the aqueous solution of a new pteridine-based pH indicator upon changing the pH around pKa of 7.2.Figure optionsDownload as PowerPoint slideHighlights
► We design fluorescent dyes based on pteridine for physiological applications.
► The new dyes are inherently more acidic than their parent compounds.
► The synthesis is simple and straightforward.
► The pH sensing is based on a dual-excitation ratiometric analysis.
► The new dyes exhibit visible emissions to naked human eyes.