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CN-121986142-A - Fluorescent dye for detecting presence of analyte in sample and composition containing dendritic polymer

CN121986142ACN 121986142 ACN121986142 ACN 121986142ACN-121986142-A

Abstract

The present disclosure relates to compounds comprising a and B, wherein one or more a groups are linked to one or more B groups by an electron-conducting conjugate bond configured to delocalize one or more electrons between a and B, a method of detecting the presence or absence of an analyte in a sample or organism comprising contacting the sample with a composition comprising a dendrimer structure and a compound, exposing the sample to light of a wavelength capable of exciting the compound in the composition, and detecting the presence or absence of light emitted by the composition, and a method of forming a dendrimer composition comprising contacting the dendrimer with a compound comprising a compound as provided herein, thereby forming a dendrimer composition, and contacting the dendrimer composition with a probe under conditions in which the dendrimer composition binds to the probe.

Inventors

  • WAN SHULIN
  • M. Yale University
  • Chi Teng
  • HOU WENJUAN
  • JIANG NAN
  • WANG JING

Assignees

  • 百进生物科技公司

Dates

Publication Date
20260505
Application Date
20241009
Priority Date
20231009

Claims (20)

  1. 1. A compound comprising; One or more a groups are connected to one or more B groups by an electron-conducting conjugate bond configured to delocalize one or more electrons between a and B; wherein a is an electron-receiving group, an electron-donating group, or a fluorophore; Wherein B is an electron-receiving group, an electron-donating group, or a fluorophore, and Wherein the compound is free of A, B or a combination thereof repeating units.
  2. 2. The compound according to claim 1, wherein each conjugated bond is independently N bond units selected from the group consisting of single bonds, triple bonds, C=N groups, amide bonds, click reaction bonds, benzene ring bonds, heterocyclic bonds, and combinations thereof, and Wherein n is greater than or equal to 1.
  3. 3. The compound of claim 1, further comprising one or more water-soluble groups attached to A, B or both.
  4. 4. A compound according to any one of claims 1-3, wherein the compound has a maximum absorption in the wavelength range 300 nm to 450 nm, optionally 365 nm to 830 nm.
  5. 5. A compound according to any one of claims 1-3, wherein the compound has a maximum emission in the wavelength range of 365 nm and 830 nm.
  6. 6. A compound according to any one of claims 1-3, wherein a has a maximum absorption of the wavelength ranges 300 nm and 450 nm, optionally 300 nm and 600 nm, when not conjugated to B.
  7. 7. A compound according to any one of claims 1-3, wherein the compound is of a structure comprising or consisting of a linked to 1 to 10B groups, optionally having the formula: 。
  8. 8. a compound according to any one of claims 1-3, wherein the compound comprises or consists of B linked to 1 to 10 a groups, optionally having the structure: 。
  9. 9. a compound according to any one of claims 1-3, wherein B has a maximum absorption in the wavelength range of 150 nm and 450 nm when not conjugated to a.
  10. 10. A compound according to any one of claims 1-3, wherein B has a maximum emission in the wavelength range of 150 nm and 830 nm when not conjugated with a.
  11. 11. A compound according to any one of claims 1-3, wherein one or more water-soluble groups are attached to a and one or more water-soluble groups are attached to B.
  12. 12. The compound of claim 11, wherein the one or more water-soluble groups comprise one or more ethylene units linked by oxygen.
  13. 13. A compound according to any one of claims 1-3, wherein the compound can have a molar extinction coefficient greater than 5000 cm -1 M -1 as measured at maximum emission of the compound.
  14. 14. A compound according to any one of claims 1-3, wherein a is a structure selected from: Wherein: R1, R2, R7, R8, R9, R13, R14, R15, R19, R20, R23, R24, R29, R30, R52, and R53 are independently selected from the group consisting of a bond to B, a (C 1 -C 20 ) -alkyl, (C 1 -C 20 ) -heteroalkyl, and combinations thereof that form a ring structure; at least one of R1 and R2 is a bond to B; at least one of R7, R8 and R9 is a bond to B; At least one of R13, R14 and R15 is a bond to B; At least one of R19 and R20 is a bond to B; at least one of R23 and R24 is a bond to B; at least one of R29 and R30 is a bond to B; at least one of R52 and R53 is a bond to B; R3、R4、R5、R6 R10、R11、R12、R16、R17、R18、R21、R22、R25、R26、R27、R28、R31、R33、R35、R37、R39、R40、R42、R44、R46、R47、R48、R50、R51、R54 And one or more of R55 is optionally independently H, (C 1 -C 50 ) -heterocarbyl or fused to form a ring optionally further comprising R54, R55, or both, or R32, R34, R36, R38, R41, R43, R45 and R49 are a bond to B, and Wherein X is C, si, O, S, P, N, se or Te.
  15. 15. The compound of claim 14, wherein R3、R4、R5、R6、R10、R11、R12、R16、R17、R18、R21、R22、R25、R26、R27、R28、R31、R33、R35、R37、R39、R40、R42、R44、R46、R47、R48、R50、R51、R54 and R55 are independently a water-soluble linker, optionally Wherein n is an integer from 5 to 15, m is an integer from 1 to 5, and R71 is independently selected from H and a bond to a second structure, optionally a dendrimer or probe.
  16. 16. A compound according to any one of claims 1-3, wherein B is a structure selected from: Wherein: R56, R58 and R60 are a bond to A, and R57, R59, R61 and R62 are independently a water-soluble group, optionally a (C 1 -C 50 ) heterocarbyl group.
  17. 17. The compound of claim 1, wherein the compound comprises: wherein each n is independently selected from integers from 5 to 15, optionally 10 to 11.
  18. 18. A compound according to any one of claims 1-3, further comprising a probe.
  19. 19. The compound of claim 18, wherein the probe molecule is a protein or fragment thereof, including but not limited to an antibody or fragment thereof, a nucleic acid, a phospholipid, a polysaccharide, a triglyceride, an aptamer, avidin, streptavidin, neutravidin, avidin DN, avidin D, or a cell.
  20. 20. The compound of claim 18, wherein the F/P ratio of the composition is from 5 to 100, optionally from 10 to 30, wherein the F/P ratio is defined as the total number of molecules of the compound present in the composition divided by the total number of molecules of the probe present in the composition.

Description

Fluorescent dye for detecting presence of analyte in sample and composition containing dendritic polymer Cross Reference to Related Applications The present application is based on and claims priority from U.S. provisional application No. 63/543,191 filed on 10/2023, the contents of which are incorporated herein by reference in their entirety. Technical Field The present specification relates to compounds having desirable fluorescent properties, methods of making and methods of use. Background Imaging techniques for detecting, tracking and identifying biological materials are of increasing importance in medical diagnostics, therapeutics and research. Among the mechanisms of specifically detecting targets, fluorescence techniques show a powerful capability in terms of detection capability and are safer than other prior art. Many probe molecules, including antibodies, peptides and nucleic acids, can be readily labeled to specifically bind a target, thereby identifying the presence, location and amount of that particular target in a cell, tissue or subject. Labeling these probe molecules requires robust (robust) fluorophores that not only have excellent specificity, but also have the ability to be easily detected in complex settings. Conventional uv dyes may have a lower extinction coefficient and lower quantum yield, which may lead to a reduction in brightness, thereby limiting their use as functional dyes in certain applications. The effective fluorescence/photon ratio of such conventional dyes may also be low, in part because the dye may quench upon close contact. Traditional compositions comprising such dye molecules conjugated directly to probes may have a low brightness, thereby limiting their use in detection methods. Accordingly, there remains a continuing need to develop improved compositions with tunable excitation and emission spectra (profiles) and/or increased brightness, and methods of using such compositions. Disclosure of Invention The following summary of the disclosure is provided to facilitate an understanding of some of the innovative features unique to the present disclosure and is not intended to be a full description. A full appreciation of the various aspects of the disclosure can be gained by taking the entire specification, claims, drawings, and abstract as a whole. Improved compositions and methods of using the compositions to detect the presence or absence of an analyte are disclosed. These compositions may provide improved solubility in aqueous solvent systems, reduced quenching, increased extinction coefficient, and/or tunable excitation and emission spectra (profiles), thereby improving methods of using these compositions. Provided herein are compounds comprising a and B, wherein one or more a groups are connected to one or more B groups by an electron-conducting conjugated bond (electron conducting conjugated bond) configured to delocalize one or more electrons between a and B, wherein a is an electron-receiving group, an electron-donating group, or a fluorophore, wherein B is an electron-receiving group, an electron-donating group, or a fluorophore, and wherein the compound is free of repeat units of A, B or a combination thereof, and optionally wherein a and B are structurally different. Optionally, each conjugated bond is independently N conjugated bond units selected from the group consisting of a single bond, a triple bond, a c=n group, an amide bond, a click reaction bond, a benzene ring bond, a heterocyclic bond, and combinations thereof, and wherein N is greater than or equal to 1. Optionally or additionally, the compound further comprises one or more water-soluble groups attached to A, B or both. Alternatively or additionally, each conjugated bond is independently N conjugated bond units selected from the group consisting of a single bond, a triple bond, a c=n group, an amide bond, a click reaction bond, a benzene ring bond, a heterocyclic bond, and combinations thereof, and wherein N is ≡1, optionally N is ≡2. Alternatively or additionally, the electron-conducting conjugated bond is a conjugated single bond. Alternatively or additionally, a is a conjugated ring structure dye. Optionally or additionally, B is a conjugated ring structure dye. In any of the foregoing aspects, the compound optionally has a maximum absorption in the wavelength ranges of 300 nm and 450nm, optionally 365 nm and 830 nm. In any of the foregoing aspects, the compound optionally has a maximum emission in the wavelength range of 365 nm and 830 nm. Optionally, a has a maximum absorption in the wavelength range of 300 nm and 450nm, optionally 300 nm and 600 nm, when not conjugated to B. Optionally, B has a maximum absorption in the wavelength ranges of 150 nm and 450nm when not conjugated to a, and optionally B has a maximum emission in the wavelength ranges of 150 nm and 830 nm when not conjugated to a. In any of the foregoing aspects, the compound is optionally of a structure comprising or consist