A Smart Photoswitchable Sensor for Differential Detection of Multiple Nucleotides In Two Photoswitchable States using Machine Learning Techniques

An azobenzene‐based tripodal sensor leverages the photoswitching property by undergoing reversible cis – trans photoisomerization where the two isomers of a sensor demonstrate differential binding affinities toward a series of biologically important nucleotides. This difference in binding behavior enables biologically important analytes, namely ATP, ADP, GTP, UMP, UTP, CTP, and inorganic phosphates to be detected and discriminated based on their interaction patterns with each isomeric form of the photoswitchable sensor, which can be reversibly tuned by light. The differential interactions of the two photoisomeric probes are clearly apparent based on their UV‐vis spectral responses, followed by the multivariate analysis of the spectral data in two and three dimensions. These results showcase the potential of the azobenzene‐based tripodal photoswitch that could double up as tunable molecular sensors upon photoisomerization, paving the way for their applications in biological sensing and analytical chemistry.