Mapping surface hydrophobic interactions in proteins is key to understanding molecular recognition, biological functions, and is central to many protein misfolding diseases. Herein, we report synthesis and application of new BODIPY-based hydrophobic sensors (HPsensors) that are stable and highly fluorescent for pH values ranging from 7.0 to 9.0. Surface hydrophobic measurements of proteins (BSA, apomyoglobin, and myoglobin) by these HPsensors display much stronger signal compared to 8-anilino-1-naphthalene sulfonic acid (ANS), a commonly used hydrophobic probe; HPsensors show a 10- to 60-fold increase in signal strength for the BSA protein with affinity in the nanomolar range. This suggests that these HPsensors can be used as a sensitive indicator of protein surface hydrophobicity. A first principle approach is used to identify the molecular level mechanism for the substantial increase in the fluorescence signal strength. Our results show that conformational change and increased molecular rigidity of the dye due to its hydrophobic interaction with protein lead to fluorescence enhancement.

Three BODIPY-based near-infrared fluorescent probes have been synthesized, characterized, and evaluated for the sensing and imaging of lysosomal pH inside living cells.

Three highly water-soluble near-infrared emissive polymeric BODIPY dyes (polymers A-C) were prepared by the palladium-catalyzed Suzuki polymerization of highly water-soluble 2,6-diiodo-3,5distyryl-BODIPY dyes with 1,4-phenyldiboronic acid and 2,7-bis(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-9,9-di[1-[2-(2-methoxyethoxy)ethoxy]ethyl]fluorene, respectively. Partial replacement of fluorine subunits of BODIPY cores at 4,4-positions of polymer C with ethynyl subunits resulted in a highly water-soluble BODIPY polymeric dye (polymer D). Polymers A-D show solubility of at least 20 mg mL À1 in aqueous solution. For comparison purposes, polymers E and F were prepared by palladium-catalyzed Sonogashira polymerization of highly water-soluble 2,6-diiodo-3,5-distyryl-BODIPY dye with highly water-soluble 1,4-diethynylbenzene and 2,6-diethynyl BODIPY dye bearing branched oligo(ethylene glycol)methyl ether residues, respectively. Upon comparison, polymer E shows low solubility in aqueous solution (0.1 mg mL À1 ), whereas polymer F is almost insoluble in aqueous solution (less than 0.05 mg mL À1 ), but both are soluble in organic solvents such as chloroform, DMSO and DMF (at least 10 mg mL À1 ).