Electronic and Steric Tuning of Excited State Proton Transfer in Water

The photoinduced proton transfer powers a myriad of chemical and biological processes. Rational design for such functionality requires the fundamental understanding of structure-photoacidity and thermodynamics-kinetics relationships. Herein, we systematically tune chemical structure at electron donor and acceptor moieties of an archetypal photoacid, the green fluorescent protein (GFP) chromophore. We quantitatively demonstrate that thermodynamic driving force of excited-state proton transfer (ESPT) in water is governed by intramolecular (electronic, steric) and intermolecular (electronic) effects exerted by the substituent. To rationalize the observed kinetics, we propose different treatments for fluorescent and nonfluorescent photoacids with driving force dependent on relative rates of ESPT and Franck-Condon relaxation. In particular, the addition of Franck-Condon excess energy to free energy difference better predicts ESPT rate/occurrence in a revised Förster equation for nonfluorescent photoacids. Furthermore, the thermodynamics-kinetics relationship for ESPT in these GFP-chromophore derivatives follows Bell-Evans-Polanyi principle, offering the desirable predictive power for engineerable photoacids with targeted properties.