Click-chemistry compounds with integrated copper-chelating ligands

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions require external Cu(I) chelators, which are toxic to cells and can have deleterious effects on biological samples.

Innovation Solution

The development of compounds that contain a copper-chelating ligand, which stabilizes the Cu(I) oxidation state and accelerates the CuAAC reaction without the need for external Cu(I) chelators.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If external Cu(I) chelators (such as THPTA or BTTAA) are used at high concentration to stabilize Cu(I) oxidation state, then the CuAAC reaction proceeds efficiently, but biocompatibility deteriorates due to cell toxicity and deleterious effects on biological samples

Engineering Contradiction:

Improvereaction efficiencyVSAvoidcell toxicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent combines the Cu(I) chelating ligand directly into the reporter molecule structure, merging two previously separate components (reporter molecule and chelator) into a single integrated compound. This eliminates the need for external chelators at high concentrations while maintaining Cu(I) stabilization and reaction efficiency.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The reporter molecule becomes self-sufficient by incorporating its own Cu(I) chelating capability. The integrated ligand stabilizes Cu(I) at the reaction site without requiring external chelating agents, enabling the system to serve itself and eliminate harmful external substances.

Inventive Principle:

Principle #25Self-service

2Temperature

If conventional CuAAC reactions are performed with external chelators, then the reaction can proceed under mild conditions, but the reaction speed is limited compared to reactions with integrated copper-chelating ligands

Engineering Contradiction:

Improvereaction conditions mildnessVSAvoidreaction speed

Core Design Contradiction:

TemperatureVSSpeed

Solution Approach 1:

The Cu(I) chelating ligand is positioned locally at the reaction site within the integrated reporter molecule structure. This local concentration of chelating capability at the precise location where Cu(I) is needed enhances reaction speed while maintaining mild overall reaction conditions.

Inventive Principle:

Principle #3Local quality

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 faster and higher-yield click reactions under mild conditions, improving biocompatibility and facilitating demanding applications such as detecting low abundance targets.

Implementation Method 1

The compounds of the disclosure contain a copper-chelating ligand that significantly stabilizes the Cu(I) oxidation state

Methodology Applied

Scientific EffectCoordination bonding: Chemical Bonding

Implementation Method 2

accelerates the copper-catalyzed azide-alkyne cycloaddition reaction

Methodology Applied

Scientific EffectCatalysis: Catalysis

Implementation Method 3

copper-catalyzed azide-alkyne [3+2] dipolar cycloaddition (CuAAC) to produce a triazole

Methodology Applied

Scientific EffectDipolar cycloaddition: Chemical Bonding

Data Source

PatentUS20250199009A1Click-chemistry functionalized compounds and methods of conjugation

Publication Date: 2025.06.19 AAT BIOQUEST

AI summary

The disclosure relates in general to click-chemistry functionalized compounds, biological conjugates and conjugation methods for use in biological assays.