Novel Cyanine Dye Compounds for Mitochondrial Imaging

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current fluorescent dyes, particularly cyanine dyes, suffer from low fluorescence quantum yields and instability after cell fixation, limiting their effectiveness in optical imaging and pH measurement applications.

Innovation Solution

Development of novel dye compounds with improved fluorescence quantum yields and pH-responsive properties, represented by specific chemical structures that allow for strong fluorescence emission and stability across various pH conditions, enabling their use as mitotrackers and pH probes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Illumination intensity

If cyanine dyes are used for fluorescence labeling, then high molar extinction coefficients are achieved, but fluorescence quantum yields remain low

Engineering Contradiction:
Improvefluorescence intensityVSAvoidfluorescence quantum yield
Core Design Contradiction:
Illumination intensityVSLoss of energy

Solution Approach 1:

The patent modifies the chemical structure of cyanine dyes by introducing specific substituents (e.g., indole rings, carbonyl groups, and heteroatom-containing groups) at defined positions of the polymethine chain. These structural parameter changes transform the dye's photophysical properties, increasing fluorescence quantum yield from typically low values to above 0.5, while preserving high molar extinction coefficients necessary for bright fluorescence signaling.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates composite fluorescent probes by combining the modified cyanine dye chromophore with targeting moieties (such as mitochondrial targeting groups or pH-sensitive groups) in a single molecular structure. This composite design enables the dye to simultaneously achieve high fluorescence quantum yield, specific subcellular targeting, and environmental responsiveness for advanced biological imaging applications.

Inventive Principle:
Principle #40Composite materials

2Reliability

If conventional fluorescent dyes are used for cell imaging, then optical tracking is achieved, but stability after cell fixation is poor

Engineering Contradiction:
Improvestability after fixationVSAvoidfluorescence persistence
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent introduces chemically stable heteroatom-containing groups (such as sulfur, nitrogen, or oxygen-containing rings) into the dye structure at positions that do not interfere with the chromophore's fluorescence properties. These structural modifications enhance the dye's chemical stability and resistance to photobleaching, ensuring that fluorescence signal persists reliably after formaldehyde fixation and throughout extended imaging procedures.

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If water solubility is improved for biomolecule compatibility, then fluorescence in aqueous media is enhanced, but molecular structure complexity increases

Engineering Contradiction:
Improvewater solubilityVSAvoidmolecular structure
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent strategically introduces hydrophilic substituents (such as carboxylate groups, sulfonate groups, or hydroxyl-containing groups) at specific positions on the dye molecule that do not disrupt the conjugated polymethine chain. These targeted modifications improve water solubility and compatibility with physiological buffers while maintaining the molecular simplicity needed for efficient synthesis and predictable photophysical behavior.

Inventive Principle:
Principle #35Parameter changes

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 dye compounds exhibit enhanced fluorescence intensity and stability, facilitating effective optical imaging of mitochondria and pH measurement in live cells, surpassing the limitations of existing cyanine dyes.

Implementation Method 1

Fluorescence is the most commonly used nondestructive approach for tracking or analyzing biological molecules in the biosciences

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

Occasionally, these dyes undergo photoisomerization

Methodology Applied
Scientific EffectPhotoisomerization: Photochromism

Data Source

PatentEP3309552B1Dye compound
Publication Date: 2024.01.17 SFC CO LTD
  • EP3309552B1 patent drawingFigure 1a~1b
  • EP3309552B1 patent drawingFigure 1c~1d
  • EP3309552B1 patent drawingFigure 1e~1f

AI summary

The present invention relates to dye compounds represented by Formulae I and II, which are described in the specification. The dye compounds of the present invention have markedly improved quantum yields and emit strong fluorescence compared to existing cyanine dyes. Due to these advantages, the dye compounds of the present invention can find applications in various fields, for example, as probes for various biological systems where optical imaging is required. Particularly, the dye compounds of the present invention can be used as mitotrackers capable of labeling and tracking mitochondria. Therefore, the dye compounds of the present invention can be used to quantitatively image mitochondria in live tissues and cells. Furthermore, the dye compounds of the present invention can be applied as pH probes for measuring the pH of live cells.