Aryl Boronate Compounds for Selective ROS Sensing
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Solution Overview
Problem
Current methods for sensing hydrogen peroxide (H2O2) and other reactive oxygen species (ROS) often result in the formation of deleterious by-products, limiting their physiological application due to the electrophilic nature of the intermediates formed during sensing mechanisms.
Innovation Solution
Development of compounds, such as those represented by Formulas I and II, which undergo selective reactions with H2O2 or ROS to produce either a lactone or a fluorescent reporter moiety, allowing for the detection of these species without forming harmful intermediates, and can also produce persulfides in the presence of ROS.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional H2O2 sensing methods are used, then detection capability is achieved, but deleterious by-products are formed due to electrophilic intermediates
Solution Approach 1:
The patent converts the electrophilic nature of the sensing intermediate into a beneficial feature by designing the boronate ester to undergo selective 1,6-elimination that releases non-toxic payloads (fluorescent reporters or prodrugs) instead of forming harmful by-products. The electrophilic intermediate that would normally be harmful is instead harnessed to drive the elimination reaction that produces useful signaling molecules.
Solution Approach 2:
The boronate ester serves as an intermediary species that mediates between H2O2 detection and payload release. The electrophilic boronate intermediate formed upon H2O2 oxidation acts as a transient mediator that facilitates the 1,6-elimination reaction, enabling selective payload release without forming deleterious by-products from direct electrophilic attack on biological molecules.
2Ease of manufacture
If inorganic salts like Na2S or NaHS are used as H2S precursors, then convenient H2S production is achieved, but rapid concentration increase causes toxicity and fails to mimic natural enzymatic production
Solution Approach 1:
The patent employs small molecule donor compounds that are chemically engineered to release H2S or other reactive sulfur species through controlled hydrolysis or trigger-responsive mechanisms. These disposable-like molecules provide convenient H2S production while releasing it slowly and steadily, mimicking natural enzymatic production and avoiding the toxicity associated with rapid concentration increases from inorganic salts.
3Measurement precision
If aryl boronate esters undergo 1,6-elimination for H2O2 sensing, then selective payload release is achieved, but highly electrophilic 1,4-quinonemethide by-products are formed
Solution Approach 1:
The patent converts the potentially harmful electrophilic 1,4-quinonemethide by-product into a beneficial signaling payload. By carefully designing the boronate ester structure with appropriate substituents and leaving groups, the elimination reaction produces fluorescent reporters or bioactive prodrugs instead of harmful by-products, harnessing the electrophilic character for useful ends.
Solution Approach 2:
The patent modifies the chemical parameters of the boronate ester structure (substituents, leaving groups, aromatic ring composition) to change the nature of the elimination by-product from harmful electrophilic species to beneficial fluorescent reporters or prodrugs. This parameter optimization ensures selective H2O2 sensing without formation of deleterious by-products.
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
These compounds enable efficient and selective detection of H2O2 and ROS, producing either a detectable lactone or a fluorescent signal, and can generate persulfides, thereby providing a means to monitor oxidative stress and potential therapeutic applications without the drawbacks of existing methods.
Implementation Method 1
a lactone is produced upon oxidation of the boronate or diaminoboryl group of a compound of Formula I by the hydrogen peroxide (H2O2) and/or other reactive oxygen species (ROS)
Implementation Method 2
the reporter moiety produces a fluorescent compound upon reaction of the compound of Formula I with hydrogen peroxide (H2O2) and/or other reactive oxygen species (ROS)
Data Source
AI summary
Provided herein according to some embodiments of the invention are aryl boronate and/or aryl diaminoboryl compounds. Also provided are methods of detecting the presence of hydrogen peroxide (H2O2) and/or other reactive oxygen species (ROS) in a cell and/or tissue by contacting the cell and/or tissue with aryl boronate and/or aryl diaminoboryl compounds. Also provided according to embodiments of the invention are methods of producing persulfides in the presence of hydrogen peroxide (H2O2) and/or other reactive oxygen species (ROS) in a cell and/or tissue by contacting the cell and/or tissue with aryl boronate and/or aryl diaminoboryl compounds.