US 6,682,938 B1 · Glucose sensing molecules having selected fluorescent properties

Abstract

An analyte sensing fluorescent molecule that employs intramolecular electron transfer is designed to exhibit selected fluorescent properties in the presence of analytes such as saccharides. The selected fluorescent properties include excitation wavelength, emission wavelength, fluorescence lifetime, quantum yield, photostability, solubility, and temperature or pH sensitivity. The compound comprises an aryl or a substituted phenyl boronic acid that acts as a substrate recognition component, a fluorescence switch component, and a fluorophore. The fluorophore and switch component are selected such that the value of the free energy for electron transfer is less than about 3.0 kcal mol−1. Fluorescent compounds are described that are excited at wavelengths greater than 400 nm and emit at wavelengths greater than 450 nm, which is advantageous for optical transmission through skin. The fluorophore is typically selected from transition metal-ligand complexes and thiazine, oxazine, oxazone, or oxazine-one as well as anthracene compounds. The fluorescent compound can be immobilized in a glucose permeable biocompatible polymer matrix that is implantable below the skin.

Claims24

Dependent claims

A method of making a fluorescent compound that emits a signal that can be correlated to an analyte concentration, wherein the compound has the general formula:

wherein R1 is selected form the group consisting of hydrogen, lower aliphatic and aromatic functional groups;
wherein R2 and R4 are optional functional selected from the group consisting of hydrogen, lower aliphatic and aromatic functional groups and groups that form covalent bonds to a polymer matrix;
wherein L1 and L2 are optional linking groups having from zero to four atoms selected from the group consisting of nitrogen, carbon, oxygen, sulfur, and phosphorus;
wherein Z is a heteroatom selected from the group consisting of nitrogen, sulfur, oxygen and phosphorus;
wherein R3 is an optional group selected from the group consisting of hydrogen, lower aliphatic and aromatic functional groups and groups that form covalent bonds to a polymer matrix;
wherein F is a fluorophore with selected molecular properties;
the method comprising selecting F and Z to satisfy the following equation such that ΔG, the free energy for electron transfer, is less than about 3.0 kcal mol−1:
ΔG=23.06[E0(Zoxidation)−E0(Freduction)]−ΔE00],
wherein E0(Zoxidation) is the oxidation potential of Z, E0(Freduction) is the reduction potential of F, and ΔE00 is the energy of F in the excited state.

6 more elements

Dependencies are inferred from the claim text.

Glucose sensing molecules having selected fluorescent properties

Life of this patent

Glucose sensing molecules having selected fluorescent properties

Life of this patent

Abstract

Claims24