Fluorescence phenomena in nerve-labeling styryl-type dyes

Abstract

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 (d1-d14), and the anomalous photophysical behavior of several of these Donor-Acceptor pairs separated by long conjugated π-systems (d7-d10). 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 (d7, d9 and d10). Additionally, unexpected emission behavior in dye systems d7 and d8 wherein the amino- derivative d7 displayed a dual emission in polar medium while the N,N-dimethyl derivative d8 and other methylated derivatives d12-d14 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 (d7, d9, and d10) 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.

Rapid fluorescence imaging of spinal cord following epidural administration of a nerve-highlighting fluorophore

“…A potential shortage of this imaging technology may be that the BMB is not a near-infrared probe. The development of this technology by using a newly designed fluorescent probe with long-wavelength emission 61 , 62 should be one of the future directions.…”