Design, Synthesis and Evaluation of Near Infrared Fluorescent pH Indicators at Physiological Range

摘要

Biochemical processes frequently involve protonation and deprotonation, resulting in pH changes that can be monitored with pH indicators. In heterogenous media such as tissue where indicator concentration or visual observation is limited, highly sensitive pH indicators with reduced tissue autofluorescence are needed. Because of the reduced tissue autofluorescence in the near infrared (NIR) region, NIR fluorescence dyes such as indocyanine green (ICG) and its derivatives have been used to image molecular processes. Removing one of the N-subsitituent of ICG led to pH-sensitive dyes operating in the NIR region and at physiologically relevant range. Further modification of the compound and synthetic procedure allowed their conjugation to peptides for specific delivery to target cells and tissues. Synthetic strategy and preliminary results on the spectral and biological properties of such dyes and their bioconjugates are described.