Class of near infrared optical probes for biological applications

Patent metadata

Field	Value
Publication number	US-9845318-B2
Application number	US-201514612890-A
Country	US
Kind code	B2
Filing date	Feb 3, 2015
Priority date	Jun 6, 2011
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

Abstract

2,5-Bis(benzoxazol-2′-yl)benzene-1,4-diol derivatives (Zinhbo derivatives) are used to detect zinc ions and have particular application in vivo and in vitro. Zinhbo derivatives upon excitation give a florescence response emission that can be used to determine the presence of zinc cation in solution. Zinhbo derivatives complexed with zinc cations upon excitation can produce a florescence response emission in the visible and near infrared range. Zinhbo derivatives complexed with zinc cations exhibit a large stoke shift between the excitation and emission wavelengths.

First claim

The invention claimed is:

1. A method for detecting the presence of zinc ions in solution, the method comprising the steps of:
contacting a solution with a Zinhbo derivative defined by the formula:

where R 1 is an electron withdrawing group or a hydrogen atom; R 2 , R 3 , and R 4 are each individually selected from the group consisting of a hydrogen atom, an electron withdrawing group, and an electron donating group; and R 5 is a chelator group capable of forming a complex with a zinc cation;
exciting the solution with an excitation wavelength; and
measuring a fluorescence response emission in at least one of the visible or near infrared ranges;
wherein the fluorescence response emission of the Zinhbo derivative corresponds to a Zinhbo derivative complexed with a zinc ion indicating the presence of zinc ions in the solution.

2. The method of claim 1 , where the Zinhbo derivative includes an R 1 , R 3 , and R 4 that are hydrogen atoms and an R 2 that is an electron donating group.

3. The method of claim 1 , where R 5 is a linear polyamine chelator or a cyclic polyamine chelator.

4. The method of claim 1 , where the solution includes a solvent selected from the group consisting of aqueous solvents, protic solvents, and organic solvents.

5. A method for detecting the presence of zinc ions, the method comprising the steps of:
contacting living cells or a living organism with a Zinhbo derivative;
exciting the living cells or the living organism with an excitation wavelength; and
measuring a fluorescence response emission in at least one of the visible or near infrared range;
wherein the fluorescence response emission of the Zinhbo derivative corresponds to a Zinhbo derivative complexed with a zinc ion indicating the presence of zinc ions in the living cells or living organism;
where the Zinhbo derivative is defined by the formula:

where R 1 is an electron withdrawing group or a hydrogen atom: R 2 , R 3 , and R 4 are each individually selected from the group consisting of a hydrogen atom, an electron withdrawing group, and an electron donating group; and R 5 is a chelator group capable of forming a complex with a zinc cation.

6. The method of claim 5 , where the Zinhbo derivative includes an R 1 , R 3 , and R 4 that are hydrogen atoms and an R 2 that is an electron donating group.

7. The method of claim 6 , where the electron donating group is an alkyl group.

8. The method of claim 5 , where living cells are contacted with a Zinhbo derivative and the living cells are cancer cells.

9. The method of claim 5 , where a living organism is contacted with a Zinhbo derivative.

10. The method of claim 5 , wherein said step of contacting living cells or a living organism includes delivering the Zinhbo derivative internally to an organism.

11. The method of claim 5 , where R 5 is a linear polyamine chelator or a cyclic polyamine chelator.

12. The method of claim 1 , where the solution includes zinc ions and the fluorescence response emission corresponds to a complexed Zinhbo derivative.

13. The method of claim 5 , where the living cells or the living organism includes free zinc ions and the fluorescence response emission corresponds to a complexed Zinhbo derivative.

Assignees

• Univ Akron

Inventors

• Pang Yi
• Xu Yongqian

Classifications

• C07D413/10

  linked by a carbon chain containing aromatic rings · CPC title

• A61B5/14546

  for measuring analytes not otherwise provided for, e.g. ions, cytochromes · CPC title

• G01N33/52

  Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper {and including single- and multilayer analytical elements (immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72)} · CPC title

• C07D263/56

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2 · CPC title

• C07F3/06

  Zinc compounds · CPC title