Xanthene Dyes with Sulfonamide Groups for Reduced Aggregation
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Solution Overview
Problem
Conventional fluorescent dyes face issues such as inter-dye quenching, poor photostability, and sensitivity to pH changes, which limit their effectiveness in biological research and medical diagnostics, particularly due to their hydrophobic nature and tendency to form dimers, leading to reduced fluorescence intensity and background noise.
Innovation Solution
Development of fluorescent compounds with reactive sulfonamide groups that reduce dimer formation, enhance water solubility, and improve photostability, allowing for more efficient labeling of biomolecules with improved fluorescence quantum yield and specificity, while maintaining biological activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional fluorescent dyes are used, then fluorescence labeling is achieved, but inter-dye quenching and dimer formation occur leading to reduced fluorescence intensity
Solution Approach 1:
The patent modifies the chemical structure of fluorescent dyes by introducing sulfonamide groups instead of traditional sulfonate groups. This parameter change in the molecular structure alters the electrostatic properties and solubility characteristics of the dye, reducing hydrophobic interactions that lead to dimer formation and quenching, thereby maintaining high fluorescence intensity even at high labeling densities.
Solution Approach 2:
The invention creates a composite fluorescent dye structure combining the xanthene fluorophore core with sulfonamide functional groups. This composite structure integrates the fluorescent properties of the xanthene ring system with the solubility and anti-aggregation properties of the sulfonamide group, achieving both bright fluorescence and reduced dimer formation.
2Object-generated harmful factors
If sulfonate groups are added to reduce dimer formation, then dimer formation is reduced, but negative charges are introduced increasing risk of disrupting biological activity
Solution Approach 1:
The patent changes the functional group from sulfonate to sulfonamide, which has different electrostatic properties. The sulfonamide group is less ionized at physiological pH compared to sulfonate, reducing the negative charge density. This parameter change allows the dye to maintain solubility and prevent dimer formation while minimizing electrostatic interactions that could disrupt biomolecule structure and function.
3Illumination intensity
If conventional dyes are used with multiple dye molecules per target, then brightness is maximized, but quenching amongst multiple dyes reduces effective fluorescence intensity
Solution Approach 1:
By changing the functional group to sulfonamide, the patent alters the intermolecular interaction parameters of the dye. This reduces hydrophobic stacking and electrostatic attraction between adjacent dye molecules, allowing higher labeling densities without quenching. The modified parameter enables multiple dyes per target molecule to maintain additive or even super-additive fluorescence intensity.
4Reliability
If sulfonation is performed to improve photostability and water solubility, then photostability and solubility are improved, but solubility in nonpolar organic solvents decreases
Solution Approach 1:
The patent modifies the functional group from sulfonate to sulfonamide, which has different polarity and hydrogen bonding characteristics. The sulfonamide group maintains the water solubility improvement from sulfonation while having reduced polarity, thereby preserving some solubility in nonpolar organic solvents. This parameter change expands the solvent compatibility range for labeling reactions.
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 compounds exhibit reduced aggregation, increased solubility, and higher photostability, resulting in enhanced fluorescence signals and better signal-to-noise ratios, even at high degrees of labeling, making them suitable for various biomedical applications.
Implementation Method 1
Adding sulfonate groups to a dye has been shown to reduce dimer formation... the physical interaction amongst the attached dye molecules, which may lead to formation of nonfluorescent dye dimers
Implementation Method 2
Fluorescent dyes are widely used in biological research and medical diagnostics... the fluorescence intensity of the labeled target... fluorescence quantum yield
Data Source
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AI summary
The present invention relates to fluorescent dyes in general. The present invention provides a wide range of fluorescent dyes and kits containing the same, which are applicable for labeling a variety of biomolecules, cells and microorganisms. The present invention also provides various methods of using the fluorescent dyes for research and development, forensic identification, environmental studies, diagnosis, prognosis, and/or treatment of disease conditions.