Controlling the isomerization rate of Azo-BF2 switches using aggregation

Patent metadata

Field	Value
Publication number	US-10239893-B2
Application number	US-201615290881-A
Country	US
Kind code	B2
Filing date	Oct 11, 2016
Priority date	Aug 27, 2013
Publication date	Mar 26, 2019
Grant date	Mar 26, 2019

Abstract

Provided herein are photochromic organic compounds of Formula I or Formula II, which are useful as molecular switches capable of being triggered via a cis/trans isomerization process. Methods of using the molecular switch compounds to form photopharmaceutical compounds that may be used to provide selective spatiotemporal activation of pharmaceutical agents are also disclosed.

First claim

What is claimed is:

1. A method of controlling the isomerization rate of a compound, comprising:
(a) selecting a compound capable of isomerizing between a thermally stable isomer and a kinetic isomer, and wherein thermal relaxation is concentration-dependent;
(b) providing a solution of the compound having a preset concentration of the compound;
(c) exposing the solution to electromagnetic radiation having a wavelength effective to cause isomerization of the compound in the solution to the kinetic isomer; and
(d) shielding the solution from electromagnetic radiation to allow for thermal relaxation of the kinetic isomer, thereby controlling the isomerization rate of the compound, wherein the preset concentration is determined by:
(e) measuring the number of molecules of the compound per unit volume (concentration) that provides a desired half-life of the kinetic isomer, step (e) preceding step (b);
wherein the compound is of Formula II:

or a salt thereof, wherein
N═N—R 2 can be oriented cis or trans to the tricycle;
R 1 is H, CN, CO 2 H, CO 2 (C 1-6 -alkyl), C 1-6 -alkyl, C 6-19 -aryl, OH, O(C 1-6 -alkyl), OC(O)(C 1-6 -alkyl), NH 2 , NH(C 1-6 -alkyl), N(C 1-6 -alkyl) 2 , or NHC(O)(C 1-6 -alkyl);
R 2 is phenyl; and
R 3 , R 4 , R 5 , R 6 , Wand R 8 are each, independently, H, C 1-6 -alkyl, C 6-19 -aryl, OH, O(C 1-6 -alkyl), OC(O)(C 1-6 -alkyl), NH 2 , NH(C 1-6 -alkyl), N(C 1-6 -alkyl) 2 , NHC(O)(C 1-6 -alkyl) or a group corresponding to a small molecule pharmaceutical; or
R 3 and R 4 , R 4 and R 5 , R 5 and R 6 or R 7 and R 8 can, when taken together, form a fused aryl, fused heteroaryl, fused C 3-6 -cycloalkyl, or fused heterocycle, wherein the fused aryl, fused heteroaryl, fused cycloalkyl, or fused heterocycle can be optionally substituted one or more times with C 1-6 -alkyl, C 6-19 -aryl, OH, O(C 1-6 -alkyl), OC(O)(C 1-6 -alkyl), NH 2 , NH(C 1-6 -alkyl), N(C 1-6 -alkyl) 2 , or NHC(O)(C 1-6 -alkyl), wherein said step (c) takes place in a mammalian cell.

2. A method of controlling the isomerization rate of the compound:

comprising:
(a) providing a solution of the compound having a preset concentration of the compound;
(b) exposing the solution to electromagnetic radiation having a wavelength effective to cause isomerization of the compound in the solution to the kinetic isomer; and
(c) shielding the solution from electromagnetic radiation to allow for thermal relaxation of the kinetic isomer, thereby controlling the isomerization rate of the compound, wherein selecting the preset concentration of the compound comprises:
(i) extrapolating from a graph of concentration versus half-life or isomerization rate;
(ii) utilizing a look-up table of concentration versus half-life or isomerization rate for the compound; or
(iii) measuring the number of molecules of the compound per unit volume (concentration) that provides a desired half-life of the kinetic isomer.

3. The method of claim 2 , wherein the wavelength (λ) is between 400 nm and 1000 nm.

4. The method of claim 2 , wherein the preset concentration of the compound is between 1 mM and 5 M.

5. The method of claim 2 , wherein the solution is in a liquid or a solid state.

6. The method of claim 2 , wherein the solution comprises a solvent selected from the group consisting of a polar solvent, a non-polar solvent, a gel and a solid matrix.

Assignees

• Dartmouth College

Inventors

• Abrahamian Ivan
• Hughes Russell P
• Nelson Yin
• Qian Hai

Classifications

• A61N5/062 Primary

  Photodynamic therapy, i.e. excitation of an agent · CPC title

• A61N2005/0662

  Visible light · CPC title

• C07B2200/07

  Optical isomers · CPC title

• C07F5/022 Primary

  without C-boron linkages · CPC title

• C07F5/02

  Boron compounds · CPC title