Dipyrromethene NIR Dyes for Photostable Bioimaging
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Solution Overview
Problem
There is a scarcity of near-infrared (NIR) fluorescent dyes with desired absorption and emission properties, and existing cyanine dyes used for biological imaging suffer from poor photostability and complex synthetic routes, limiting their clinical application due to inability to bind effectively to molecules of interest for tracking or analysis.
Innovation Solution
Development of novel NIR fluorescent dyes with specific structural formulas that allow for covalent binding to molecules of interest, featuring fluoride, hydroxyl, and conjugation groups for enhanced stability and solubility, enabling pH-responsive fluorescence and improved imaging capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cyanine dyes are used for NIR fluorescent imaging, then absorption and emission properties are achieved, but photostability is poor and synthetic routes are complex
Solution Approach 1:
The patent changes the chemical structure parameters by replacing the cyanine dye framework with a novel dipyrromethene framework featuring specific substituents (R1-R8 groups including aryl, heteroaryl, and functional groups). This structural parameter change achieves both improved photostability and simplified synthesis by utilizing readily available starting materials and straightforward condensation reactions.
Solution Approach 2:
The patent creates composite molecular structures by combining the dipyrromethene core with various functional groups (carboxylic acids, amines, alcohols, ethers) and conjugation groups. These composite structures provide both the desired optical properties and enhanced photostability while maintaining ease of synthesis through modular assembly.
2Adaptability or versatility
If existing NIR dyes are used, then fluorescence imaging is possible, but ability to bind to molecules of interest is limited
Solution Approach 1:
The patent designs the dipyrromethene dye framework with multiple functional groups (carboxylic acids, amines, alcohols, ethers) that can serve different purposes: some groups enable covalent binding to biomolecules while others maintain water solubility and optical properties. This multi-functionality allows a single dye structure to achieve both binding capability and imaging sensitivity.
Solution Approach 2:
The patent applies different functional groups at specific positions (R1-R8) on the dipyrromethene framework. By placing conjugation groups at certain positions and water-solubilizing groups at others, the molecule achieves localized functionality: binding capability at one site and solubility/imaging properties at another, resolving the contradiction between adaptability and reliability.
3Ease of operation
If water solubility is enhanced, then biological imaging is improved, but fluorescence intensity may be reduced
Solution Approach 1:
The patent introduces water-solubilizing groups (hydroxyl, carboxylic acid, ether groups) at specific peripheral positions (R1-R8) of the dipyrromethene core, while keeping the central conjugated system intact. This localized modification enhances water solubility without significantly affecting the fluorescence intensity generated by the core structure.
Solution Approach 2:
The patent creates composite structures by combining the hydrophobic dipyrromethene core with hydrophilic functional groups. This composite approach allows the molecule to maintain both water solubility (from the polar groups) and high fluorescence intensity (from the conjugated core), resolving the contradiction between ease of operation and illumination intensity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The novel NIR fluorescent dyes exhibit strong absorption and emission in the NIR spectral region, high photostability, and the ability to form dye conjugates, leading to enhanced imaging sensitivity and specificity, with a significant increase in fluorescent intensity upon cellular uptake.
Implementation Method 1
Fluorescent near infra-red (NIR) dyes... strong absorption and emissions within the NIR spectral region... emission at 727 nm
Data Source
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AI summary
A compound of formula (I) is described in which each A, which may be the same or different, is a halide selected from fluoride, chloride, bromide and iodide, or is O-Y, wherein Y is a substituted or unsubstituted, saturated or unsaturated, straight or branched chain alkyl moiety. R1, R2, R3, R6, R7, and R8 are each independently H, OH, NO2 or O-L-X, wherein L is a spacer group, and X is a conjugation group or a water- solubilizing group. At least one of R1, R2, R3 is OH or O-L-X and at least one of R6, R7, and R8 is OH or O-L-X. R4 and R5, which may be the same or different, are each independently H; or are a substituted or unsubstituted, saturated or unsaturated, cyclic moiety; a substituted or unsubstituted, saturated or unsaturated heterocyclic moiety; or a substituted or unsubstituted, saturated or unsaturated, straight or branched chain alkyl moiety. Also described are dye conjugates comprising a compound of the invention.