Fluorescent Dyes with Phosphinic Acid Auxochromes for Large Stokes Shifts
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Solution Overview
Problem
Current fluorescent dyes face limitations in achieving compact structures with zero net charge, increased Stokes shifts, and efficient emission in aqueous media, which hinders their ability to penetrate live cells and provide effective labeling for biological imaging.
Innovation Solution
Development of novel fluorescent dyes with phosphine oxide, phosphinic acid, phosphinate, phosphonate, or phosphonamidate groups connected to a fluorophore, featuring a phosphorus atom directly linked to a fluorophore, allowing for increased Stokes shifts and efficient emission, and enabling cell permeation with neutral or zwitterionic properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Power
If traditional fluorescent dyes are used to achieve bright labeling, then emission efficiency is improved, but Stokes shift remains small (20-40 nm) limiting imaging flexibility
Solution Approach 1:
The patent changes the chemical structure parameters of fluorescent dyes by introducing phosphinic acid, phosphinate, phosphonate, and phosphonamidate groups as auxochromic substituents. This structural modification results in increased Stokes shifts (exceeding 100 nm) while maintaining bright fluorescence emission, enabling both high emission efficiency and imaging flexibility through multiple excitation/detection combinations
2Ease of operation
If dyes with compact structures and zero net charge are used to penetrate live cells, then cell permeation is improved, but Stokes shift remains small limiting imaging schemes
Solution Approach 1:
The patent modifies the charge and structural parameters of cell-permeant dyes by incorporating phosphorus-containing auxochromic groups. This results in zwitterionic or neutral molecules with compact structures that maintain cell permeation capability while achieving large Stokes shifts (>100 nm), thereby enabling both live cell penetration and flexible imaging schemes
3Adaptability or versatility
If dyes with increased Stokes shifts (>100 nm) are used to achieve imaging flexibility, then adaptability is improved, but emission efficiency decreases in aqueous media
Solution Approach 1:
The patent changes the chemical composition by introducing phosphorus-containing auxochromic groups (phosphinic acid, phosphinate, phosphonate, phosphonamidate) that simultaneously increase Stokes shift and maintain quantum yield in aqueous environments. This resolves the trade-off by achieving both large Stokes shifts (>100 nm) for imaging flexibility and sufficient emission efficiency for bright labeling
4Power
If cationic triarylmethane dyes are used to achieve bright fluorescence, then emission efficiency is improved, but non-specific binding and membrane staining occur
Solution Approach 1:
The patent changes the charge parameter of fluorescent dyes by introducing phosphorus-containing auxochromic groups that create zwitterionic or neutral species. This eliminates non-specific binding and membrane staining issues associated with cationic dyes while maintaining bright fluorescence emission, thereby improving both emission efficiency and specificity
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 dyes exhibit enhanced Stokes shifts, improved emission efficiency, and the ability to penetrate live cells, facilitating superior biological imaging with reduced phototoxicity and increased specificity, addressing the limitations of existing dyes.
Implementation Method 1
increased Stokes shifts (separation between the absorption and emission maxima)
Implementation Method 2
Fluorescent dyes are widely used as indispensable markers in biology, optical microscopy, and analytical chemistry
Data Source
Figure 1a~2a
AI summary
The novel compounds, in particular fluorescent dyes, of the invention have the general structural formula I below: wherein: each X1, X2, X3, X4 is independently selected from H, halogen (F, Cl, Br, I), CN, NO2, OR1, SR1, NR1R2, COR1, COOR1, CONR1R2, PO3R1R2, SO2R1, SO3R1 and R3, where: R1 and R2 may represent H, unsubstituted or substituted alkyl (including cycloalkyl), unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl, and wherein R1 and R2 can form together a substituted or unsubstituted 4-7 membered ring; R3 is alkyl, alkenyl, alkynyl, aryl or cycloalkyl, optionally substituted with one or more heteroatoms independently selected from N, O, S, halogen (F, Cl, Br, I), N3, amine, OH, OR1, OCOR1, aryl, COOR1, CONR1R2, PO3H2 and SO3H, where R1 and R2 are defined as above; Y is selected from OR1, NR1R2, or NR1R3, where R1, R2 and R3 are defined as above; Q is selected from O, S, SO2, NR, C(R3)2, Si(R3)2, Ge(R3)2, P(=O)R3, P(=O)OR3,where R3 is defined as above, and wherein Q and X1, taken together with the atoms to which they are bonded, can form a substituted or unsubstituted 5-7 membered ring; L and M are independently selected from OR1, SR1, NR1R2 and R3, where R1, R2 and R3 are defined as above, and wherein L and M, taken together with the atoms to which they are bonded, can form a substituted or unsubstituted 5-7 membered ring; Z is selected from O, S, NR1, CR1R3 or aryl, where R1 and R3 are defined as above, and wherein Z and X4, taken with the atoms to which they are bonded, can form a substituted or unsubstituted 5-7 membered ring.