Fluorescence Phenomena in Nerve-Labeling Styryl-Type Dyes

Several classes of diversely substituted styryl type dyes have been synthesized with the goal of extending their expected fluorescent properties as much towards red as possible given the constraint that they maintain drug-like properties and retain high affinity binding to their biological target. We report on the synthesis, optical properties of a series of styryl dyes ( ), and the anomalous photophysical behavior of several of these Donor-Acceptor pairs separated by long conjugated π-systems ( ). We further describe an unusual dual emission behavior with two distinct ground state conformers which could be individually excited to locally excited (LE) and twisted intramolecular charge transfer (TICT) excited state in push-pull dye systems ( , and ). Additionally, unexpected emission behavior in dye systems and wherein the amino- derivative displayed a dual emission in polar medium while the N,N-dimethyl derivative and other methylated derivatives showed only LE emission but did not show any TICT emission. Based on photophysical and nerve binding studies, we down selected compounds that exhibited the most robust fluorescent staining of nerve tissue sections. These dyes ( , , and ) were subsequently selected for in-vivo fluorescence imaging studies in rodents using the small animal multispectral imaging instrument and the dual-mode laparoscopic instrument developed in-house.