Amine-Substituted Rhodamine Dyes That Resist Nonfluorescent Forms

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Solution Overview

Problem

Existing far-red and near-infrared rhodamine dyes suffer from poor performance due to their propensity to adopt a nonfluorescent form, limiting their use in biological imaging where autofluorescence and scattering are minimized.

Innovation Solution

A unique chemical modification strategy is applied to rhodamines, optimizing long-wavelength variants and enabling facile functionalization with different chemical groups, allowing for the synthesis of cell- and tissue-permeable labels for biological imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If far-red and near-infrared rhodamine dyes are used, then autofluorescence and scattering are minimized, but the dyes suffer from poor performance due to adopting a nonfluorescent form

Engineering Contradiction:

Improveautofluorescence and scatteringVSAvoidfluorescent performance

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent modifies the chemical structure of rhodamine dyes by changing parameters such as incorporating four-membered azetidine rings and adjusting substituent groups (e.g., at positions 3 and 6 of the xanthylium ring system). These structural parameter changes prevent the dyes from adopting nonfluorescent forms while maintaining their far-red/NIR excitation properties, thus resolving the contradiction between minimizing harmful factors and maintaining fluorescent performance.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates composite fluorescent compounds by combining rhodamine core structures with azetidine moieties and various functional groups. This composite approach allows the dye to simultaneously achieve far-red/NIR absorption, prevent nonfluorescent form adoption, and maintain brightness and photostability, thereby resolving the performance issue while preserving the advantage of reduced autofluorescence and scattering.

Inventive Principle:

Principle #40Composite materials

2Reliability

If rhodamine dyes are modified to improve brightness and photostability, then fluorescent performance is enhanced, but structural complexity increases

Engineering Contradiction:

Improvebrightness and photostabilityVSAvoidchemical structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the rhodamine structure by introducing separate four-membered azetidine rings at specific positions (3 and/or 6) of the xanthylium ring system. This segmentation allows independent optimization of fluorescent properties without requiring complete redesign of the entire molecular structure, thus enhancing brightness and photostability while controlling the increase in structural complexity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention applies local modifications to specific positions (3 and 6) of the rhodamine xanthylium ring system rather than uniformly modifying the entire structure. By placing azetidine groups and functional substituents at these specific locations, the patent locally enhances fluorescent performance (brightness and photostability) while minimizing the overall increase in molecular complexity.

Inventive Principle:

Principle #3Local quality

3Ease of manufacture

If existing rhodamine structures are used, then synthesis is simple, but long-wavelength variants suffer from poor fluorescent performance

Engineering Contradiction:

Improvesynthesis simplicityVSAvoidfluorescent performance at long wavelengths

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent incorporates four-membered azetidine rings and functional groups during the initial synthesis steps of the rhodamine dye, rather than adding them later. This preliminary action ensures that the fluorescent performance-enhancing structural features are built into the molecule from the start, allowing long-wavelength variants to achieve good fluorescent performance while maintaining relatively simple synthesis procedures.

Inventive Principle:

Principle #10Preliminary action

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 modified rhodamines exhibit improved brightness and photostability, facilitating advanced biological imaging in complex environments.

Implementation Method 1

Fluorescence imaging using far-red or near-infrared (NIR) light is desirable due to less scattering and lower autofluorescence

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS20260015335A1Amine-substituted fluorescent compounds

Publication Date: 2026.01.15 HOWARD HUGHES MEDICAL INST

AI summary

A compound of the following structure is provided: