Screening of Ruthenium Complexes as the Protein Light Switches for Protein Detection

Ruthenium(II)-dipyrido3,2-a:2',3'-c phenazine (dppz) complexes (Ru-dppz complexes) can function as the molecular light switches for DNA assay, but their applications to protein detection remain a challenge because proteins possess more structural complexity than nucleic acids. Herein, we develop for the first time a computational virtual screening strategy to screen light switches for protein detection. We find that the binding affinity between Ru-dppz complexes and proteins relies on the structure and ratio of auxiliary and dppz ligands, and it plays a key role in light-switching performance. We discover that Ru(dppz)2dip2+ (dip = 4,7-diphenyl-1,10-phenanthroline) can function as the human serum albumin (HSA) light switch, and it exhibits strong hydrophobic and π-cation interactions with HSA to achieve a 280.0-fold luminescence enhancement, which is 2 orders of magnitude higher than the parent complex Ru(dip)32+. Moreover, Ru(dppz)2dip2+ displays a rapid response time (2dip]2+ for rapid detection of HSA. Notably, this strategy can be extended to screen the β-lactoglobulin light switch that exhibits a 346.1-fold luminescence enhancement. This research provides a universal approach for the discovery of high-performance protein light switches with promising applications in biomedical research and clinical diagnostics.