Dinuclear Metal Complexes for Phosphate Ester Detection

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Solution Overview

Problem

Existing methods for studying phosphorylation and dephosphorylation reactions, particularly in the context of protein function and disease, are limited by the low water solubility of synthetic ligands used in laboratory studies, which hinders their utility in understanding biological processes and detecting phosphate esters.

Innovation Solution

Development of water-soluble ligands like 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane and its conjugates that form dinuclear metal complexes, enabling the detection of phosphate esters through MALDI-TOF mass spectrometry and dye displacement methods, and their use in forming functionalized polyacrylamide gels for electrophoretic separations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If synthetic ligands are used to form dinuclear metal complexes for studying phosphorylation reactions, then the catalytic function is achieved, but the water solubility is low which limits their utility in biological studies

Engineering Contradiction:
Improvecatalytic functionVSAvoidwater solubility
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent modifies the ligand structure by introducing hydrophilic groups (such as carboxylate, phosphate, or hydroxyl groups) to change the solubility parameters of the ligand. This allows the ligand to maintain its catalytic function while becoming water-soluble, thus resolving the contradiction between catalytic reliability and ease of operation in aqueous biological systems

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite ligand structures that combine hydrophobic regions (for maintaining catalytic activity and metal binding) with hydrophilic regions (for water solubility). This composite approach allows the ligand to function effectively in aqueous environments while preserving its catalytic capabilities

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If conventional detection methods are used for phosphate esters, then the process is simple, but the detection precision and differentiation capability are insufficient

Engineering Contradiction:
Improvedetection processVSAvoidphosphate ester detection
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent employs dye displacement methods where the dinuclear metal complex-dye assembly changes color or fluorescence properties upon binding phosphate esters. This provides a visually detectable signal that maintains operational simplicity while dramatically improving detection precision and differentiation capability

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The patent uses the dinuclear metal complex as an intermediary that enhances the detection of phosphate esters. The complex acts as a mediator between the phosphate ester and the detection system (mass spectrometry or dye), amplifying the signal and improving measurement precision while keeping the overall process relatively simple

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of manufacture

If non-conjugated ligands are used, then the synthesis is simpler, but the additional functionality for detection and separation is limited

Engineering Contradiction:
Improveligand synthesisVSAvoiddetection and separation functionality
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent designs ligands with multiple functional groups that provide both the core catalytic function and additional detection/separation capabilities. For example, ligands are equipped with both metal-binding sites and dye-binding sites or mass-tag groups, allowing a single ligand structure to serve multiple functions including catalysis, detection, and separation

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 use of these dinuclear metal complexes allows for effective detection and differentiation of phosphate esters, enhancing the understanding of biological processes and aiding in the identification and quantification of phosphoproteins, thereby facilitating the exploration of molecular origins of diseases.

Implementation Method 1

methods for detecting phosphate esters in a sample by MALDI-TOF (Matrix-Assisted Laser Desorption/Ionization Time-of-Flight) mass spectrometry

Methodology Applied
Scientific EffectMALDI-TOF mass spectrometry: Time of Flight

Implementation Method 2

their use in forming functionalized polyacrylamide gels for electrophoretic separations

Methodology Applied
Scientific EffectElectrophoresis: Electrophoresis

Data Source

PatentUS9689840B2Conjugates of 1,4,7-triazacyclononanes, dinuclear metal complexes of such conjugates, and methods of use for both 1,4,7-triazacyclononanes and conjugate
Publication Date: 2017.06.27 BIO RAD LABORATORIES INC
  • US9689840B2 patent drawing
  • US9689840B2 patent drawing
  • US9689840B2 patent drawing

AI summary

Conjugates of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropanes with a variety of conjugating members are used in the formation of dinuclear metal complexes which bind to phosphate esters. By virtue of their conjugated forms, the complexes are incorporated into chromatographic media, affinity binding reagents, and dyes, which make the complexes useful in a wide range of assays, separations, and purifications. In addition, dinuclear metal complexes of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropanes that are not so conjugated are used in the detection of phosphate esters of biological species by either MALDI-TOF mass spectrometry or by dye displacement.