Macrocyclic Lanthanide Chelates with Phenylethynylpyridine Chromophores

Solution Overview

Problem

Existing luminescent lanthanide chelates have poor aqueous solubility and stability, limiting their effectiveness in bioaffinity assays, particularly in high-temperature conditions and presence of alternative metal ions.

Innovation Solution

Development of luminescent lanthanide chelates with substituted 4-(phenylethynyl)pyridine chromophores and triazamacrocyclic cores, incorporating reactive groups for biospecific binding and improved solubility, enabling high stability and sensitivity in bioassays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Illumination intensity

If conventional triazamacrocyclic ligands with 4-(phenylethynyl)pyridine chromophores are used, then luminescence properties are achieved, but aqueous solubility is poor

Engineering Contradiction:

Core Design Contradiction:

Illumination intensityVSQuantity of substance

Solution Approach 1:

The patent changes the chemical parameters of the ligand by introducing hydrophilic groups (carboxylates, phosphonates, sulfonates) at specific positions of the chromophore and macrocyclic core, transforming the hydrophobic conventional ligands into hydrophilic derivatives that maintain luminescence while achieving adequate aqueous solubility

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite molecular structures combining hydrophobic luminescent chromophores (4-(phenylethynyl)pyridine) with hydrophilic functional groups (carboxylate, phosphate, sulfonate moieties), forming amphiphilic ligands that exhibit both luminescence properties and improved aqueous solubility

Inventive Principle:

Principle #40Composite materials

2Illumination intensity

If conventional lanthanide chelates are used, then luminescence is achieved, but stability under high temperature and in presence of alternative metal ions is poor

Engineering Contradiction:

Core Design Contradiction:

Illumination intensityVSReliability

Solution Approach 1:

The patent inverts the conventional approach by making the chromophore part of the chelate complex rather than a separate appendage. The 4-(phenylethynyl)pyridine chromophore is integrated into the macrocyclic ligand structure itself, forming a rigidified chelate that prevents dissociation and improves thermal and chemical stability while maintaining luminescence

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent employs macrocyclic ring structures that wrap around the lanthanide ion in a curved, cage-like geometry, providing enhanced coordination stability and protecting the metal center from exchange with alternative metal ions and degradation at high temperatures

Inventive Principle:

Principle #14Spheroidality (Curvature)

3Adaptability or versatility

If reactive groups are added to enable biospecific binding, then conjugation capability is improved, but aqueous solubility and stability may deteriorate

Engineering Contradiction:

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent segments the ligand structure into distinct functional modules: a luminescent chromophore core, hydrophilic solubility-enhancing groups, and separate reactive conjugation groups ( NHS esters, maleimides, azides) positioned at strategic locations. This modular design allows the reactive groups to be added without compromising the stability of the core chelate structure

Inventive Principle:

Principle #1Segmentation

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 new lanthanide chelates exhibit enhanced aqueous solubility, stability, and luminescence, significantly improving assay sensitivity and tolerance to high temperatures and metal ions, allowing for more robust bioaffinity assays.

Implementation Method 1

luminescent lanthanide chelate design having substituted 4-(phenylethynyl)pyridine chromophores around an emitting lanthanide core. The chromophores have high molar absorptivity and luminescence with lanthanide ions.

Methodology Applied

Scientific EffectLuminescence: Luminescence

Implementation Method 2

The chromophores have high molar absorptivity

Methodology Applied

Scientific EffectAbsorption spectroscopy: Absorption Spectroscopy

Implementation Method 3

triazamacrocyclic ligands of the type disclosed in WO2013/011236

Methodology Applied

Scientific EffectChelation: Chemical Bonding

Data Source

PatentEP3212733B1New chromophoric structures for macrocyclic lanthanide chelates

Publication Date: 2019.08.28

AI summary

The present application discloses novel azamacrocyclic lanthanide chelate design (Formula (I)) having substituted 4-(phenylethynyl)pyridine chromophores around an emitting lanthanide core, e.g. an europium(III) ion. The chromophores exhibit high molar absorptivity and luminescence with lanthanide ions. The application also discloses a detectable molecule comprising a biospecific binding reagent conjugated to the luminescent chelate, luminescent lanthanide chelating ligand as well as a solid support conjugated with the chelates and their use in various assays.