Boryl Ether Oxidative Fragmentation for Toxic By-Product Elimination
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Solution Overview
Problem
Current peroxide-mediated drug release systems face challenges due to the toxicity of quinone methide or acrolein by-products, necessitating the development of alternative structural motifs that can release compounds in the presence of hydrogen peroxide without generating toxic by-products.
Innovation Solution
The use of compounds with a specific structure, including a cleavable linker group and a cargo moiety, that undergo oxidative fragmentation to release active moieties upon reaction with hydrogen peroxide, avoiding the formation of toxic by-products and allowing for controlled release rates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If aryl or vinyl boronates are used as oxidative triggers to promote drug release from the benzylic or allylic position, then drug release is achieved, but toxic quinone methide or acrolein by-products are generated
Solution Approach 1:
The patent extracts and removes the harmful quinone methide or acrolein by-products from the reaction system by replacing the traditional aryl or vinyl boronate triggers with alternative structural motifs that do not generate these toxic compounds upon oxidative cleavage
Solution Approach 2:
The patent converts the harmful oxidative cleavage reaction that previously produced toxic by-products into a beneficial process that generates non-toxic by-products, while maintaining the desired drug release function through alternative boronate structural designs
2Reliability
If enzymes are used to initiate prodrug unraveling, then selective drug release is achieved, but enzymes cannot access sterically hindered sites
Solution Approach 1:
The patent introduces hydrogen peroxide as an intermediary agent that can penetrate sterically hindered sites where enzymes cannot access, while still enabling selective prodrug unraveling through the designed boronate trigger structures that respond to peroxide-mediated oxidation
Solution Approach 2:
The patent replaces the enzyme-catalyzed mechanism with a peroxide-mediated oxidation mechanism, substituting a biological catalytic system with a chemical oxidation system that has superior accessibility to sterically hindered sites while maintaining selectivity through molecular design
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 effectively release therapeutic agents in oxidatively stressed environments, such as cancer and neurodegenerative conditions, while minimizing toxicity and achieving targeted delivery, as demonstrated by the release of fluorophores in cellular models.
Implementation Method 1
H2O2 is an attractive agent for initiating prodrug unraveling
Implementation Method 2
compounds that undergo oxidative fragmentation to release active moieties upon reaction with hydrogen peroxide
Data Source
AI summary
A compound, or a pharmaceutically acceptable salt thereof, having a structure of:wherein L is a cleavable linker group;X is a cargo moiety-containing group; andR1 and R2 are each independently hydrogen, alkyl, or substituted alkyl; or R1 and R2 together form a boronic ester ring or a substituted boronic ester group.