Fluorogenic Probes for Selective ROS and RNS Detection
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Solution Overview
Problem
Current methods lack effective and selective detection and measurement techniques for reactive nitrogen species (RNS) and reactive oxygen species (ROS), particularly peroxynitrite and hypochlorite, which are crucial for understanding their roles in biological systems and diseases.
Innovation Solution
Development of aromatic amine compounds as fluorogenic probes that react specifically with RNS and ROS, such as peroxynitrite and hypochlorite, to form fluorescent compounds, enabling sensitive and selective detection and measurement through fluorescence properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional detection methods are used for ROS and RNS, then general detection capability is maintained, but sensitivity and selectivity for specific species like peroxynitrite and hypochlorite are insufficient
Solution Approach 1:
The patent divides the detection task into specialized segments by designing distinct fluorogenic probes for different reactive species. Each probe contains a specific luminophore-quencher arrangement optimized for detecting particular species (e.g., peroxynitrite, hypochlorite, superoxide), allowing high sensitivity and selectivity for each target while maintaining overall versatility through the family of related probes
Solution Approach 2:
The patent applies local quality by modifying specific regions of the probe molecules to enhance selectivity for particular ROS/RNS species. By adjusting the quencher group, linking moiety, or substituents on the aromatic ring, each probe achieves optimized local chemical properties that confer specificity for its target species while retaining the general fluorogenic detection mechanism
2Measurement precision
If fluorogenic probes with high selectivity for specific ROS/RNS are developed, then detection accuracy for those species improves, but the complexity of probe design and synthesis increases
Solution Approach 1:
The patent extracts the essential detection function into a modular fluorogenic probe structure consisting of a luminophore, quencher, and linking moiety. This extracted modular design allows high detection accuracy through optimized chemical interactions while simplifying synthesis by using standardized building blocks that can be combined through relatively simple coupling reactions
Solution Approach 2:
The patent achieves high detection accuracy by carefully adjusting chemical parameters such as the choice of luminophore, quencher group, and substituent patterns on the aromatic ring. These parameter changes are implemented through systematic variation of known chemical structures, allowing optimization of selectivity and sensitivity without requiring fundamentally complex or novel molecular architectures
3Measurement precision
If aromatic amine compounds are used as fluorogenic probes, then sensitivity and specificity for detecting peroxynitrite and hypochlorite are enhanced, but the ability to detect other ROS and RNS species may be reduced
Solution Approach 1:
The patent achieves universality by designing a family of aromatic amine-based fluorogenic probes where the core structure provides general reactivity toward electrophilic ROS/RNS species, while specific substituents and quencher groups confer selectivity for particular targets. This multi-functional design allows the same chemical framework to serve multiple detection purposes through systematic modification
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 aromatic amine compounds provide high sensitivity and specificity for detecting peroxynitrite and hypochlorite, allowing for accurate measurement and screening in various biological samples, facilitating the understanding of their physiological roles and pathological activities.
Implementation Method 1
When a first fluorophore is excited and transfers its absorbed energy to a second fluorophore, the energy transfer results in fluorescent signal at the emission wavelength of the second fluorophore
Implementation Method 2
The aromatic amine compounds provide high sensitivity and specificity for detecting peroxynitrite and hypochlorite, allowing for accurate measurement and screening in various biological samples
Data Source
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AI summary
Provided herein are compounds or fluorogenic probes which can be used as reagents for measuring, detecting and/or screening ROS or RNS such as peroxynitrite or hypochlorite. Provided also herein are methods that can be used to measure, directly or indirectly, the amount of peroxynitrite or hypochlorite in chemical samples and biological samples such as cells and tissues in living organisms. Specifically, the methods include the steps of contacting the fluorogenic probes disclosed herein with the samples to form one or more fluorescent compounds, and measuring fluorescence properties of the fluorescent compounds. Provided also herein are high-throughput screening fluorescent methods for detecting or screening peroxynitrite or compounds that can increase or decrease the level of peroxynitrite or hypochlorite in chemical and biological samples.