Bis-Cu(II)-Complex Probe for Selective Amino Acid Detection

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Solution Overview

Problem

Current methods for detecting cysteine and histidine in biological fluids are inefficient, often requiring long incubation times and are prone to interference from other amino acids like homocysteine and glutathione, with limited probes available for selective detection in aqueous environments and physiological conditions.

Innovation Solution

A novel bis-Cu(II)-complex of a bis-dipicolyl amine derivative is developed as a 'turn on' fluorescence probe for selective detection of cysteine and histidine, capable of imaging endogenous cysteine in live cells and detecting cyanide ions without interference from other amino acids, utilizing a synthesis process involving specific ligand coordination with metal ions and reaction in aq.-HEPES buffer medium.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If chemodosimetric reaction is used for detection of cysteine and histidine, then detection can be performed in physiological conditions, but incubation time is long (20 minutes to 1 hour or more)

Engineering Contradiction:
Improvedetection capability in physiological conditionsVSAvoidincubation time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent changes the chemical reaction mechanism from chemodosimetric reaction to Cu(II) complexation reaction. This parameter change in reaction type enables the detection to occur on millisecond time scale while maintaining compatibility with physiological conditions, thus resolving the contradiction between detection reliability and time consumption.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent substitutes the slow chemodosimetric reaction mechanism with a faster Cu(II) complexation mechanism. This substitution of chemical mechanism achieves rapid detection (millisecond scale) while preserving the ability to detect in physiological conditions, addressing both the time and reliability requirements.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Quantity of substance

If conventional molecular probes are used for detection, then detection of total thiol content can be achieved, but selectivity is poor due to interference from homocysteine and glutathione

Engineering Contradiction:
Improvedetection capabilityVSAvoidselectivity
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent introduces Cu(II) ions as an intermediary that mediates the detection process. The Cu(II) complex formed with the probe selectively binds to cysteine and histidine over homocysteine and glutathione, enabling selective detection while maintaining detection capability. This intermediary approach resolves the contradiction between quantity detection and measurement precision.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of manufacture

If organic solvents are used to solubilize the reagent, then reagent solubility is improved, but detection in pure aqueous environment is compromised

Engineering Contradiction:
Improvereagent solubilityVSAvoiddetection capability in aqueous environment
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent changes the solubility parameter of the reagent by designing a probe with appropriate hydrophilic-hydrophobic balance. This parameter change enables the reagent to be soluble in pure aqueous HEPES buffer (pH 7.4) without requiring organic solvents, thus maintaining both ease of manufacture and adaptability to physiological aqueous environments.

Inventive Principle:
Principle #35Parameter changes

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 probe enables rapid, selective, and quantitative estimation of cysteine and histidine in biological samples and live cells, with specific imaging capabilities and the ability to detect cyanide ions, overcoming previous limitations of interference and detection time.

Implementation Method 1

A novel bis-Cu(II)-complex of a bis-dipicolyl amine derivative is developed as a 'turn on' fluorescence probe for selective detection of cysteine and histidine

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

utilizing a synthesis process involving specific ligand coordination with metal ions

Methodology Applied
Scientific EffectComplexation: Chemical Bonding

Data Source

PatentUS10155776B2Method for selective detection and estimation of histidine and cystein
Publication Date: 2018.12.18 COUNCIL OF SCI & IND RES
  • US10155776B2 patent drawing
  • US10155776B2 patent drawing
  • US10155776B2 patent drawing

AI summary

The Invention relates to a novel receptor molecule for estimation of amino acids based on florescence enhancements. Particularly, the invention relates to a novel Cu (II)-complex as a turn-on luminescence probe for selective detection of cysteine and histidine in pure aqueous environment and in biological sample as well as for detection of cyanide ions among various anions under physiological conditions.