Voltage sensitive dyes

Abstract

Voltage sensitive dyes comprising boron and related compositions and methods are provided. In some embodiments, a voltage sensitive dye comprises an electron acceptor comprising boron. The electron acceptor may be attached (e.g., covalently) to at least one electron donating group and at least one polar group. For instance, the electron acceptor may comprise optionally substituted boron dipyrromethene (e.g., optionally substituted 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene). The point of attachment and chemical nature of the electron donating group(s) and polar group(s) may be selected to impart beneficial properties to the voltage sensitive dye. For instance, the voltage sensitive dye may have an extended difference in the dipole moment between the ground and electronic states due at least in part to the position of the electron donating group(s). The voltage sensitive dyes, described herein, may have high specificity, high signal to noise ratio, fast responsivity, high voltage sensitivity, high photostability, and/or high brightness.

What is claimed is: 
     
         1 . A composition of matter, comprising a compound of Formula I: 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein:
 R 1  and R 2  are independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, or an electron donating group, provided that at least one of R 1  and R 2  is an electron donating group; 
 each R 3  is independently hydrogen, optionally substituted alkyl, halo, or a linking group; 
 each R 4  is hydrogen or optionally substituted alkyl; 
 Ring A is optionally substituted arylene or optionally substituted heteroarylene; 
 R 5  is optionally substituted acylene, optionally substituted alkenylene, optionally substituted alkylene, optionally substituted alkynylene, substituted amino, optionally substituted arylene, optionally substituted heteroalkenylene, optionally substituted heteroalkylene, optionally substituted heteroalkynylene, optionally substituted heteroarylene, —O—, or optionally substituted thiolene; and 
 X is a polar group, wherein X comprises a positively charged moiety, provided that the positively charged moiety is not a metal. 
 
     
     
         2 . (canceled) 
     
     
         3 . A voltage-sensitive dye, comprising:
 an electron acceptor comprising boron;   an electron donating group attached to the electron acceptor; and   a polar group attached to the electron acceptor, wherein a maximum absorbance wavelength in methanol of the voltage-sensitive dye is greater than or equal to about 600 nm.   
     
     
         4 . The voltage-sensitive dye of  claim 3 , wherein the polar group is charged. 
     
     
         5 . The voltage-sensitive dye of  claim 3 , wherein the polar group is positively charged. 
     
     
         6 . The voltage-sensitive dye of  claim 3 , wherein the polar group is zwitterionic. 
     
     
         7 . The voltage-sensitive dye of  claim 3 , wherein the polar group has a log(P) of less than or equal to about 0. 
     
     
         8 . The voltage-sensitive dye of  claim 3 , wherein a peak absorbance wavelength in methanol of the voltage-sensitive dye is greater than or equal to about 600 nm and less than or equal to about 900 nm. 
     
     
         9 . The voltage-sensitive dye of any preceding  claim 3 , further comprising a biological molecule. 
     
     
         10 . The voltage-sensitive dye of  claim 3 , wherein the biological molecule is a cell-surface targeting group. 
     
     
         11 . The voltage-sensitive dye of  claim 3 , wherein the biological molecule is attached to the electron acceptor. 
     
     
         12 . The voltage-sensitive dye of  claim 3 , wherein the biological molecule is attached to the polar group. 
     
     
         13 . The composition of  claim 1 , wherein R 1  and R 2  are independently hydrogen, optionally substituted alkyl, or an electron donating group. 
     
     
         14 . The composition of  claim 1 , wherein R 1  and R 2  are independently optionally substituted alkyl or an electron donating group. 
     
     
         15 . The composition of  claim 1 , wherein R 1  is an electron donating group. 
     
     
         16 . The composition of  claim 1 , wherein R 1  is not an electron donating group. 
     
     
         17 . The composition of  claim 1 , wherein R 1  and R 2  are independently an electron donating group. 
     
     
         18 - 58 . (canceled) 
     
     
         59 . The composition of  claim 1 , wherein Formula I has the structure: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         60 . The composition of  claim 1 , wherein Formula I has the structure: 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein q is 1 to 20. 
     
     
         61 . (canceled) 
     
     
         62 . A method, comprising:
 exposing a cell membrane to a voltage sensitive dye comprising an electron acceptor comprising boron, an electron donor, and a polar group, wherein a maximum absorbance wavelength in methanol of the voltage-sensitive dye is greater than or equal to about 600 nm.   
     
     
         63 . The method of  claim 62 , further comprising allowing the voltage sensitive dye to orient in the cell membrane such that at least a portion of the electron acceptor is positioned within the cell membrane and at least a portion of the polar group is positioned outside the surface of the cell membrane. 
     
     
         64 . The method of  claim 62 , further comprising determining a change in a potential across the cell membrane using the voltage-sensitive dye.