Data-Driven Discovery of a New Fluorescent BASHY Dye for Bioimaging

Fluorescent molecules play a crucial role in biomedicine by facilitating the visualization and tracking of biological processes with sensitivity and specificity. However, tailoring their structure to meet the demands of live cell and in vivo imaging presents a significant challenge due to the intricate interplay of factors governing their structural and photophysical properties. In this study, we explored the potential of using multivariate linear free-energy relationships (mLFER) to optimize a multicomponent fluorescent platform. We prepared a small library of 20 fluorescent boronic-acid-derived salicylidenehydrazone (BASHY) complexes using a versatile reaction protocol and characterized their chemical stability in water-containing media. The obtained data served as input for the development of an mLFER model, enabling the prediction of a new BASHY dye and unraveling previously unknown mechanisms governing the stability of this unique platform of fluorescent dyes. The optimized dye was successfully employed in live cell experiments and in zebrafish larvae.