Use of nitrogen-containing heterocyclic radical substituted alkene compounds

Abstract

The invention relates to new use of a series of nitrogen-containing heterocyclic radical substituted alkene compounds, and more specifically relates to use of the compounds represented by general formula a or salts thereof in bioimaging, pH value detection, biomacromolecule detection or cell microenvironment detection, wherein Z, S1, S2 and R1 are defined as the specification. The compounds are utilized as the fluorescent dye for bioimaging, fluorescent pH probe for pH value detection and / or diagnostic agent for tumor cell detection. The compounds involved in the invention have excellent imaging effect, and shows the single component multicolor property, can be used for single component multicolor imaging or conventional imaging, etc., and haves enormous application prospect in bioimaging and tumor detection. (formula a).

Description

[0001] field of invention [0002] The invention relates to a series of new applications of alkene compounds substituted by nitrogen-containing heterocyclic groups. Background technique [0003] With the development of molecular biology, the study of organisms has entered the level of molecules or even single molecules, but the traditional immunohistochemistry and gene chip technology can only be limited to in vitro experiments, and cannot directly observe the researched objects, so it is urgent There is a need for an imaging method that can directly reveal molecular changes in tissues and cells at the molecular level. Fluorescent molecular imaging is sensitive to monitoring, rapid in imaging, free of radioactive hazards, and can observe multiple molecular events at the same time, so it is widely used in molecular biology research, especially in the research fields of brain nerve and tumor imaging. Fluorescence imaging technology has developed rapidly in the past two decades....

AI Technical Summary

Problems solved by technology

However, the luminescent properties of nitrogen-containing heterocyclyl-substituted alkene compounds have always remained at the theoretical stage (Dyes and pigments, 2007, 72 (3): 357-362., Chemical Physics Letters 268 (1997) 434-438, Chemical Physics Letters 444(2007) 71-75, Journal of Photochemistry and Photobiology A: Chemistry, 2011, 218(1): 76-86, ChemicalPhysics Letters 415(2005) 217-222,), rarely used in actual biological imaging or Its imaging properties were carefully studied (CA 2129933 describes aminostyrylpyridinium salts as fluorescent probes of viscosity)

The use of this class of compounds as fluorescent dyes for biological imaging has not been extensively covered, due to the traditional concept of fluorescent imaging requiring dyes that are preferably insensitive to pH and cellular environments in order to obtain narrow spectrum and multicolor imaging, but through our Studies have found that sensitive fluorescent dyes can reveal many new phenomena in biological imaging, especially in histological imaging, showing differences in the cellular microenvironment. This property can have important applications in many aspects, such as measuring the pH of the intracellular microenvironment , Differentiate between pathological tissues (such as tumors) and normal tissues, distinguish different organelles, etc.

[0007] Existing dyes for fluorescence imaging, such as commercial dyes based on the modification of dyes such as fluorescein, rhodamine, BODIPY and biscyanine, generally have some shortcomings in practical applications. First, the synthesis is complicated, the purification is difficult, and the yield obtained Low; and because the dye emits light in water, a strong fluorescent background is generated during imaging, and it is necessary to wash off the excess dye, which makes the imaging operation cumbersome and prolongs the imaging time, bringing new uncontrollable factors to the research

[0008] Most of the existing probes for pH detection are also modified based on dyes such as fluorescein, rhodamine, BODIPY and biscyanine, and there are deficiencies in these dyes. Literature (TrAC Trends in Analytical Chemistry 2010, 29 (9), pp 1004-1013 and Chem.Rev., 2010, 110 (5), pp 2709-2728) have well summarized the deficiencies of existing pH fluorescent probes and the demand for novel pH fluorescent probes, such as fluorescein-based probes Needle Stokes shift is small, 8-hydroxypyrene-1,3,6-trisulfonic acid dyes cannot enter cells, cyanine dyes are easy to photobleach, some dyes have poor photostability or low quantum yield

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