Charged Linker Dyes Prevent Fluorescence Quenching

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Solution Overview

Problem

Existing dimeric and polymeric fluorescent or colored dyes do not achieve the desired increase in brightness due to intramolecular fluorescence quenching, limiting their effectiveness in analytical methods.

Innovation Solution

Development of water-soluble dyes with two or more fluorescent or colored moieties covalently linked by a charged linker, which reduces intramolecular fluorescence quenching through electrostatic repulsion, resulting in brighter and more intensely colored compounds.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Illumination intensity

If dimeric and polymeric compounds comprising two or more fluorescent and/or colored moieties are prepared to increase brightness, then the number of fluorescent moieties is increased, but intramolecular fluorescence quenching occurs and brightness is not achieved

Engineering Contradiction:
ImprovebrightnessVSAvoidintramolecular fluorescence quenching
Core Design Contradiction:
Illumination intensityVSObject-generated harmful factors

Solution Approach 1:

A charged linker molecule is introduced as an intermediary between fluorescent moieties to prevent direct harmful interactions. The linker's charge creates electrostatic repulsion that maintains spatial separation, preventing intramolecular quenching while still connecting the moieties into a dimeric or polymeric structure that increases overall brightness.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The physical and chemical parameters of the linker are specifically designed to control the spatial arrangement of fluorescent moieties. By adjusting the linker's charge, length, and flexibility, the distance and orientation between moieties are optimized to prevent quenching while maintaining structural integrity and water solubility.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If multiple fluorescent moieties are linked together to form dimeric and polymeric dyes, then the potential signal intensity is increased, but the dyes do not achieve the desired increase in brightness

Engineering Contradiction:
Improvenumber of fluorescent moietiesVSAvoidbrightness
Core Design Contradiction:
Quantity of substanceVSIllumination intensity

Solution Approach 1:

The charged linker serves as a mediator that enables the association of multiple fluorescent moieties while preventing the harmful effect of quenching. This allows the system to achieve the benefits of having multiple moieties (increased potential signal) without suffering from their negative interactions.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

Different parts of the dye molecule are given different functions: the fluorescent moieties provide light-emitting capability, while the charged linker provides spatial separation and electrostatic repulsion. This functional differentiation allows each component to optimize its role without interfering with others.

Inventive Principle:
Principle #3Local quality

3Measurement precision

If dimeric and polymeric dyes are developed to provide intense color and fluorescence, then the signal-to-noise ratio should improve, but intramolecular quenching reduces the signal

Engineering Contradiction:
Improvesignal-to-noise ratioVSAvoidintramolecular fluorescence quenching
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The charged linker acts as a protective intermediary that shields fluorescent moieties from each other, preventing energy transfer that would result in quenching. This maintains high signal intensity needed for improved signal-to-noise ratio in analytical measurements.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The electrostatic repulsion between charged linkers, which might seem to prevent close association of moieties, is actually converted into a beneficial effect by maintaining optimal separation distance that prevents quenching while still allowing the multiplicative brightness effect of multiple moieties.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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 dyes are significantly brighter than their monomeric counterparts, enabling intense color or fluorescence without prior illumination, and can be used for visual detection of analyte molecules in various analytical methods, including biomolecules, with improved signal-to-noise ratio.

Implementation Method 1

electrostatic repulsion of the charged linker acts to maintain the spatial distant between the fluorescent and/or colored moieties, and thus intramolecular fluorescence quenching is reduced and/or eliminated

Methodology Applied
Scientific EffectElectrostatic repulsion: Electrostatics

Implementation Method 2

Fluorescent and/or colored dyes are known to be particularly suitable for applications in which a highly sensitive detection reagent is desirable

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP3294811B1Ultra bright dimeric or polymeric dyes
Publication Date: 2024.02.28 SONY GROUP CORP
  • EP3294811B1 patent drawingFigure 1
  • EP3294811B1 patent drawingFigure 2
  • EP3294811B1 patent drawingFigure 3

AI summary

Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I): including stereoisomers, salts and tautomers thereof, wherein R1, R2, R3, R4, R5, L1, L2, L3, L4, M, m and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.