The Synthesis And Application Of Novel Mitochondria-targeting NIR Emitting Fluorescent Dye

Mitochondria are organelles with double membranes, which provide energy for vitalmovement, and play an important role in many cellular processes. Meanwhile, mitochondria arethe main sites that many bioactive small molecules， such as reactive oxygen species (ROS) andreactive nitrogen species (RNS) produce. These small molecules are tightly related to majordiseases like Alzheimer’s disease, Parkinson’s disease, neuronal cell death and cancer.It is well known that fluorescence analysis is widely used to biological analysis chemistry andbiomedicine, owning to its high sensitivity, selectivity, low biological cytotoxicity as well aseasy operation. Thus, it is necessary to develop fluorescent dyes accumulating in mitochondria,which can promote advances in monitoring mitochondrial molecular events by furtherconstructing fluorescent probes. However, the existing fluorescent dyes that are used tomitochondria imaging still have some shortages, such as excitation and emission wavelengthsbeing in visible region, small Stokes shift, large toxicity and long incubation time. In order torealize the rapid detection and dynamic imaging for molecular events, a novel dye with highsensitive under the complex mitochondria biology background are highly desired. Meanwhile,this new mitochondria targeted dye also has longer emission wavelength, large Stokes shift andlow toxicity.To meet these requirements, we designed and synthetized a series of Near-infraredmitochondria targeted fluorescent dyes, and then applied to biological systems fluorescenceimaging. These studies are as follows:(1). A long chain conjugated system was fabricated as a long wavelength fluorescence dye(Spring Red) framework, and pH-responsive dimethyl amino was used to regulate itsfluorescence, which strongly fluoresce under basic environment of mitochondria. Additionally,we used-H,-CH3,-OCH to substitute dimethyl amine group to compare mitochondria targetedcapability of four dyes.We synthesized four dyes, and characterized their structures and fluorescence properties. Theresults showed that maximum emission wavelengths are all in Near-infrared region, and Stokesshift is quite large. Fluorescence images in lives and in vivo demonstrated, Sping Red preferablylocates to mitochondria without obvious cytotoxicity.(2). We designed a new Near-infrared BODIPY dye, aza-BODIPY-Cy7. This dye is synthesized using the material of Dye-H as the starting material. As the introduction ofboron-fluoride bonds, a rigid conjugate planar structure is formed. Emission wavelength of thedye should be in Near-infrared region, and fluorescence quantum yield is highly improved.