Melatonin Derivatives Water Solubility Brain Residence
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Melatonin's low water solubility limits its medicinal efficacy and requires the use of organic solvents, which increase toxicity and side effects, and its rapid penetration through the blood-brain barrier reduces its effectiveness.
Innovation Solution
Development of melatonin derivatives with enhanced water solubility through specific chemical modifications and reaction processes, including the use of solvents like tetrahydrofuran and catalysts like sodium hydride, resulting in a product with nearly 700 times higher water solubility than melatonin, reducing toxicity and prolonging brain residence time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If melatonin is dissolved in organic solvents to overcome low water solubility, then solubility is improved, but toxicity and side effects increase
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of melatonin through derivatization at the N1 position of the indole ring. By introducing different substituents (R1 and R2 groups with varying chain lengths and functional groups), the patent creates derivatives with altered solubility parameters while maintaining the core melatonin structure, thereby achieving water solubility improvement without relying on toxic organic solvents
Solution Approach 2:
The patent creates composite molecular structures by combining the melatonin core with additional functional groups and chains. The derivatives consist of the parent melatonin molecule复合ed with various substituents (such as carboxymethyl, hydroxymethyl, or longer alkyl chains), forming composite structures that simultaneously provide water solubility and retain biological activity while eliminating the need for organic solvents
2Duration of action of moving object
If melatonin is used in high doses to compensate for short brain residence time, then efficacy is improved, but toxicity increases
Solution Approach 1:
The patent modifies the physicochemical parameters of melatonin by changing its molecular structure through derivatization. The introduced substituents alter the molecule's polarity, molecular weight, and interaction properties with blood-brain barrier transporters, thereby extending brain residence time without requiring dose escalation that would lead to toxicity
Solution Approach 2:
The patent introduces intermediary functional groups and chains that act as mediators between the melatonin core and the biological environment. These intermediary structures (such as carboxymethyl or hydroxymethyl groups) facilitate longer retention in the brain by modifying transport and clearance mechanisms, allowing effective dosing without toxic side effects
3Quantity of substance
If chemical modifications are made to improve water solubility, then solubility is improved, but molecular structure complexity increases
Solution Approach 1:
The patent systematically varies specific parameters in the molecular structure (chain length n=1-4, types of substituents at R1 and R2 positions) while maintaining the core melatonin framework. This controlled parameter modification approach improves water solubility without introducing excessive structural complexity, as each derivative follows a consistent structural pattern based on N1-substitution
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 melatonin derivatives exhibit improved water solubility, reducing toxicity and side effects, prolonging brain residence time, and maintaining physiological functions similar to melatonin, facilitating research and applications in medicine, agriculture, and cosmetics.
Implementation Method 1
adding a catalyst while maintaining the solvent at 0° C. to obtain a first reaction solution
Implementation Method 2
concentrating the first reaction solution to obtain a residue of the first reaction solution
Implementation Method 3
purifying the residue of the first reaction solution by column chromatography to obtain the melatonin derivatives
Data Source
AI summary
The present disclosure discloses melatonin derivatives, a method thereof, and a use thereof. The method comprises: dissolving melatonin in a solvent, adding a catalyst while maintaining the solvent at 0° C. to obtain a first reaction solution, stirring the first reaction solution, adding reactants in the first reaction solution, continually stirring at room temperature or at refluxing reaction temperature until, when analyzing by thin layer chromatography, the first reaction solution is fully reacted, quenching the reaction with ice water, concentrating the first reaction solution to obtain a residue of the first reaction solution, and purifying the residue of the first reaction solution by column chromatography to obtain the melatonin derivatives.