Oxetane-Substituted Compounds for Radiation Mitigation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current small molecule radiation mitigators face challenges in design and implementation of non-toxic and reliable delivery systems, particularly due to insolubility issues, which limit their administration to intravenous or systemic routes, and their storage in DMSO solutions often results in compound degradation and precipitation, affecting high-throughput screening assays.
Innovation Solution
Development of oxetane-substituted compounds that enhance aqueous solubility and stability, allowing for oral administration and effective radiation protection and mitigation by increasing the solubility of organic compounds in aqueous media, thereby overcoming solubility and storage issues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecule radiation mitigators are administered via intravenous or systemic delivery systems, then radiation protection efficacy is achieved, but delivery system complexity and toxicity increase
Solution Approach 1:
The patent modifies the chemical parameters of the small molecule radiation mitigators by introducing oxetane substituents, which fundamentally changes their solubility properties. This allows the compounds to be administered orally in aqueous solutions rather than requiring complex intravenous delivery systems, thereby reducing delivery system complexity while maintaining radiation protection efficacy
Solution Approach 2:
The oxetane-substituted compounds act as intermediaries that bridge the gap between lipophilic radiation-protective molecules and aqueous biological systems. The oxetane group serves as a solubility-enhancing mediator that allows oral administration without requiring liposomal or other complex solvent systems
2Stability of the object's composition
If lipophilic compounds are stored in DMSO solutions, then compound stability is maintained, but compound degradation and precipitation occur over time
Solution Approach 1:
The patent changes the solubility parameter of the compounds by introducing oxetane substituents, transforming them from DMSO-soluble to water-soluble compounds. This allows storage in aqueous solutions without the degradation and precipitation problems associated with DMSO storage, thereby improving both compound stability and assay reliability over extended periods
Solution Approach 2:
The patent replaces expensive and problematic DMSO storage solutions with simple, stable aqueous storage systems. The oxetane-substituted compounds can be stored in water-based solutions for extended periods without degradation, eliminating the need for costly specialized storage conditions
3Ease of operation
If compounds are designed for enhanced membrane permeability, then cellular uptake is improved, but aqueous solubility decreases
Solution Approach 1:
The patent applies local quality modification by introducing oxetane substituents at specific positions on the molecular structure. This localized modification enhances aqueous solubility without compromising the overall lipophilic character and membrane permeability properties of the core molecule, allowing both high solubility and high cellular uptake
Solution Approach 2:
The patent creates composite molecular structures that combine lipophilic core regions (for membrane permeability) with hydrophilic oxetane substituents (for aqueous solubility). This molecular composite approach allows the compound to exhibit both high membrane permeability and high aqueous solubility simultaneously
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 oxetane-substituted compounds demonstrate significant radiation protection and mitigation capabilities, both as radioprotectors and radiomitigators, improving survival rates and reducing radiation-induced damage in animal models, while also serving as effective solubilizers for compounds with poor aqueous solubility.
Implementation Method 1
oxetane-substituted compounds that enhance aqueous solubility and stability, allowing for oral administration and effective radiation protection and mitigation by increasing the solubility of organic compounds in aqueous media
Data Source
AI summary
A compound having the formula:wherein X is S, SO or SO2;one of R1, R2, and R3 is O and the others of R1, R2 and R3 are independently, the same or different, CH2, or CR13 wherein, R13 is an alkyl group, an alkenyl group, an alkynyl group, a trialkylsilyl group, or —(CH2)mOR15, wherein R15 is an alkyl group or an aryl group and m is an integer in the range of 1 to 10, and one of R5, R6, and R7 is O and the others of R5, R6 and R7 are independently, the same or different, CH2, or CR14 wherein, R14 is an alkyl group, an alkenyl group, an alkynyl group, a trialkylsilyl group, or —(CH2)nOR16, wherein R16 is an alkyl group or an aryl group and n is an integer in the range of 1 to 10;R4 and R8 are independently, the same or different, H, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a C1-C3 alkoxy group, an aryloxy group, or —(CH2)qOR17, wherein R17 is an alkyl group or an aryl group and q is an integer in the range of 1 to 10, provided that R4 is not a C1-C3 alkoxy group or an aryloxy group when R1 or R3 is O and R8 is not a C1-C3 alkoxy group or an aryloxy group when R5 or R7 is O;R9, R10, R11 and R12 are independently, the same or different, H, an alkyl group, an alkenyl group, an alkynyl group, or an aryl group.