Polyamine and Zwitterionic Buffer Design for Wide pH Range

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Solution Overview

Problem

Current amines used as buffers in biological systems have limitations such as narrow pH buffering range, stability issues, and solubility problems, leading to suboptimal yields in fermentation and protein purification processes.

Innovation Solution

Development of polyamines and zwitterionic buffers derived from reactions between amines, alcohols, and acrylonitrile, followed by derivatization with monochloroacetic acid or sodium vinyl sulfonate, which extend the buffering range and improve stability, resulting in enhanced buffering capacity and reduced chelation interactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If traditional amines are used as buffers, then buffering capacity is provided, but pH buffering range is narrow

Engineering Contradiction:
ImprovepH buffering rangeVSAvoidbuffering capacity
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent combines multiple amine groups with different pKa values into polyamine structures, creating buffers that can operate across multiple pH ranges simultaneously. This merging of buffering functions extends the overall pH buffering range while maintaining adequate buffering capacity through the cooperative action of multiple amine groups.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention creates composite buffer systems by synthesizing polyamines with multiple different amine groups (primary, secondary, tertiary) that have distinct pKa values. This composite structure allows the buffer to provide coverage across a broader pH range while maintaining reliability through the distributed buffering capacity of its constituent groups.

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If amines are used as buffers, then pH control is achieved, but chelation and negative interactions occur

Engineering Contradiction:
ImprovepH controlVSAvoidchelation and negative interactions
Core Design Contradiction:
Ease of operationVSObject-generated harmful factors

Solution Approach 1:

The patent introduces zwitterionic groups with opposite charges to local regions of the buffer molecule, creating internal charge balance. This local quality modification reduces the buffer's tendency to engage in harmful chelation interactions with metal ions and other system components, while preserving the essential pH control capability of the amine groups.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention converts the potentially harmful chelating ability of amines into a beneficial feature by introducing zwitterionic groups that create internal charge compensation. The same molecular structure that could cause harmful interactions now provides internal stability and reduced external reactivity, improving compatibility with biological systems.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Reliability

If conventional buffers are used, then basic buffering function is provided, but stability and solubility issues arise

Engineering Contradiction:
Improvebuffer stabilityVSAvoidsolubility
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent creates composite molecular structures combining hydrophobic amine groups with hydrophilic zwitterionic moieties. This composite architecture provides both enhanced stability through internal charge balance and improved solubility through the polar zwitterionic groups' interaction with water, resolving the trade-off between stability and solubility.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The invention modifies the chemical parameters of buffer molecules by introducing zwitterionic groups, which change the overall charge distribution and polarity of the molecule. This parameter change simultaneously improves stability through internal charge compensation and enhances solubility through increased hydrophilicity.

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 new buffers provide a broader pH buffering range and increased stability, improving yields and shelf life of proteins and amino acids, while minimizing negative interactions, thus optimizing fermentation and purification processes.

Implementation Method 1

Amines are very useful compounds in the buffering of biological systems. Each class of amine has various limitations which require choosing an amine based on multiple factors to select the best amine.

Methodology Applied
Scientific EffectBuffering:

Implementation Method 2

The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range

Methodology Applied
Scientific EffectpKa:

Implementation Method 3

Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability

Methodology Applied
Scientific EffectZwitterionic buffering:

Implementation Method 4

The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range

Methodology Applied
Scientific EffectChemical reaction: Chemical Bonding

Data Source

PatentUS7939659B2Biological buffers with wide buffering ranges
Publication Date: 2011.05.10 TPAT IP
  • US7939659B2 patent drawing
  • US7939659B2 patent drawing
  • US7939659B2 patent drawing

AI summary

Amines and amine derivatives that improve the buffering range, and/or reduce the chelation and other negative interactions of the buffer and the system to be buffered. The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range, derivatives that result in polyamines that have the same pKa yields a greater buffering capacity. Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability.