pH-Responsive Cy5 dyes having nucleophilic substituents for molecular imaging

Abstract pH-Responsive fluorescent pentamethine cyanine (Cy5) derivatives having nucleophilic substituents were synthesized. Cy5 derivatives 1-O having mercaptopropyl, hydroxypropyl, and aminopropyl groups on an indole nitrogen atom showed pH-dependent equilibria between a fluorescent open-ring structure ( 1-O ) and a non-fluorescent closed-ring structure ( 1-C ) in pH ranges 3–7, 6–7.5, and 8–9, respectively. pH-Responsive dyes 1a-C having a 1,3-thiazinane structure were easily internalized into A549 cells and converted to open-ring structure 1a-O in response to the relatively low pH of acidic compartments in the cells.