Cation-sensing composite structure and compounds for use therein

• US 5,958,782 A
• Filed: 02/27/1997
• Issued: 09/28/1999
• Est. Priority Date: 10/21/1993
• Status: Expired due to Term

• Current Assignee: Terumo Cardiovascular Systems Corporation (Terumo Corporation)
• Original Assignee: 3M Company
• Inventors: Trend, John E., Cross, Elisa M., Yafuso, Masao, Kipke, Cary A., Bentsen, James G., Halverson, Kurt J., Chou, Shih-Hung, Patil, Sanjay L.
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US08/810,969
• Time in Patent Office: 943 Days
• Field of Search: 422/58, 422/68.1, 422/82.05-82.07, 422/82.11, 436/73, 436/74, 436/79, 436/163, 436/164, 436/166, 436/172, 540/468-469, 558/44
• US Class Current: 436/79
• CPC Class Codes: C07D 498/18 Bridged systems
• CPC Class Codes: C09B 23/102 two heterocyclic rings linked carbon-to-carbon C09B7/00 takes precedence
• CPC Class Codes: G01N 31/22 using chemical indicators G01N31/02 takes precedence
• CPC Class Codes: G01N 31/221 for investigating pH value

Abstract

A fluorescent ionophoric compound is disclosed that includes a complexing moiety, such as a cryptand or crown-ether portion, and a fluorescing moiety such as a coumarin portion. The coumarin portion may be substituted at the 3-position with an electron withdrawing or polarizable group such as a substituted aromatic group or a substituted heterocyclic group having a heteroatom in at least one of its alpha positions. The compound, which exhibits good photostability, can be incorporated into cation-sensing composite structures by means of convenient points of covalent attachment.

Claims

1. A fluorescent ionophoric compound, comprising:

a complexing moiety for selective binding of an ion; and

a fluorescing moiety that contains close-lying nπ

* and π

π

* excited states, wherein the compound has a wavelength of maximum absorbance of at least about 350 nm;

wherein the ionophoric compound has the general formula;

##STR104## wherein;

T is O or N, with the proviso that when T is O, q is 0 and n is 0 to 2, and when

T is N, q is 1 and m and n are independently 0 or 1;

each R² independently is selected from the group consisting of;

hydrogen, halogen, a C₁ -C₁₀ alkyl, a C₁ -C₁₀ alkoxy, a C₂ -C₁₀ alkenyl, a C₁ -C₁₀ alkylamino, a C₁ -C₁₀ dialkylamino, and a group having the formula (CH₂ X)_a E in which X is O, NH, or a single bond, E is a tonal group that includes active hydrogen, and a is a whole number from 1 to 10;

R³ is selected from the group consisting of;

hydrogen, a C₁ -C₁₀ aryl, a C₅ -C₈ cycloalkyl, a C₆ -C₁₀ aryl, a heterocyclic group comprising at least one O, N, or S atom, a C₂ -C₁₀ alkenyl, and a group having the formula (CH₂ X)_b E in which X and E are defined above and b is a whole number from 0 to 10;

R¹ is a substituted heterocyclic or aromatic moiety and

Z is O or NR⁵, where R⁵ is hydrogen or a hydrocarbyl-containing group.

2. The compound of claim 1, wherein:

R¹ in a substituted heterocyclic moiety having the general formula;

##STR105## wherein Y and Y'"'"' independently are O, S, N_x, or CH_y where x is 0 or 1 and y is 1 or 2, with the proviso that at least one of Y and Y'"'"' must be O, S, or NH_x, and

each R⁴ group is independently selected from the group consisting of hydrogen, halogen, a hydrocarbyl-containing group, a hetero-acyclic group, a heterodic group, or a group having the formula (CH₂ X)_c E in which X is O, NH, or a single bond, E is a functional group that includes active hydrogen, and c is a whole number from 0 to 100, or both R⁴ groups together with the carbon atoms to which they are attached form a 5- or 6-membered ring which optionally can have one or more further R⁴ groups attached.

3. The compound of claim 1, wherein:

R¹ is a substituted heterocyclic moiety having the general formula;

##STR106## wherein Y and Y'"'"' independently are O, S, NH_x, or CH_y where x is 0 or 1 y is 1 or 2, with the proviso that at least one of Y and Y'"'"' must be O, S, or NH_x, and

each R⁴ group is independently selected from the group consisting of hydrogen, halogen, a C₁ -C₂₀ alkyl, a C₁ -C₂₀ alkoxy, a C₃ -C₁₈ cycloalkyl, a C₆ -C₁₈ aryl, a C₆ -C₁₈ aryloxy, a C₆ -C₁₈ hydroxyaryl, a C₆ -C₁₈ arylcarboxy, a C₆ -C₁₈ carboxyaryl, a C₂ -C₁₈ alkenyl, a C₁ -C₂₀ hydrocarbylamino, a C₆ -C₁₈ arylamino, a C₆ -C₁₈ aminoaryl, C₂ -C₂₀ di(hydrocarbyl)amino, a heterocyclic group having at least three ring atoms, carboxamide (--C(O)NR¹ R²), or a group having the formula (CH₂ X)_c E in which X is O, NH_x, or a single bond, E is a functional group that includes active hydrogen and c is a whole number from 0 to 25, or both R⁴ groups together with the carbon atoms to which they are attached form a 5- or 6-membered ring which optionally can have one or more further R⁴ groups attached.

4. The compound of claim 1, wherein the compound has a wavelength of maximum absorbance of at least about 390 nm and a wavelength of maximum emission of no more than about 480 nm.

5. The compound of claim 1, wherein the compound is selective for K⁺ and is attached to a substrate to form a cation-sensing structure, the structure being provided on a cassette having a fluid chamber and being in ion communication with K⁺ ions in fluids that are contained in the fluid chamber.

6. The compound of claim 1, wherein the compound is incorporated into an ion sensor attached to a cassette having a flow passage, wherein the ion sensor is capable of withstanding autoclave sterilization.

7. The compound of claim 1, wherein the compound is incorporated into an ion sensor attached to a cassette assembly comprising:

a first flow-through cassette casing having an inlet and an outlet and an opening covered with an ion-permeable membrane; and

a second ion sensing cassette body.

8. The compound of claim 1, wherein the compound is incorporated into an ion sensor attached to a cassette having a flow passage, wherein the sensor is disposed inside the flow passage of the cassette.

9. The compound of claim 1, wherein m and n are both 1, Z is 0, and T is N.

10. The compound of claim 1, wherein the wavelengths of maximum absorbance and emission are at least about 20 nm apart.

11. A cation-sensing composite structure, comprising:

a substrate; and

the fluorescent ionophoric compound of claim 1.

12. The sensing composite structure of claim 11, wherein the substrate comprises a polymer selected from the group consisting of polyvinylchloride, copolymers and terpolymers of vinylchloride, copolymers of styrene and at least one of maleic acid and maleic anhydride, copolymers of alkyl vinyl ether and at least one of maleic acid and maleic anhydride, polymers and copolymers of vinyldimethyl aziactone, and copolymers of one of acrylate esters, methacrylate esters, acrylamides, and methacrylamides with one of acrylic acid and methacrylic acid.

13. A method of detecting the presence of a cation, comprising the steps of:

a) contacting the sensing composite structure of claim 11 with a cation-containing medium and allowing or providing a means for the cations to diffuse to the sensing composite structure to form an equilibrium complex with the fluorescent ionophoric compound of the sensing composite, wherein the ionophoric compound complex, when exposed to light of a wavelength range centered around λ

₁, is capable of emitting light of a wavelength range centered around λ

₂, wherein λ

₂ is at least 10 nm greater than λ

₁, λ

₁ is at least about 380 nm, and λ

₂ is no more than about 500 nm; and

b) interrogating the complex with light of a wavelength range centered around λ

₁ for a time sufficient for the complex to emit visible light of wavelength λ

₂ which is collected and detected.

14. The method of claim 13, further comprising the step:

c) correlating the emitted light with the concentration of the cations to determine the cation concentration in the cation-containing medium.

15. The method of claim 14, wherein the cation is K⁺.

16. The method of claim 13, wherein the interrogating light of a wavelength range centered around λ

₁ is introduced by, and the emitted light of a wavelength range centered around λ

₂ is transported to the detector by, at least one optical fiber.

17. The method of claim 13, wherein the cation is a metal ion.

18. A cation sensing composite structure, comprising:

a substrate; and

the fluorescent ionophoric compound of claim 1, wherein the compound is covalently bound to the substrate through at least one R¹ or R² or R³ group by means of one of a bond and a multifunctional linking moiety, a first functionality of the linking moiety being complementary to a functionality of the R¹ or R² or R³ group and a second functionality of the linking moiety being complementary to a functional group on the substrate.

19. The sensing composite structure of claim 18, wherein the functionalities of the linking moiety independently are an amine, amide, ester, oxirane, olefin;

urea, silanol, carbamate, isocyanate, thioisocyanate, sulfonamide, sulfonyl chloride, sulfonic acid, carboxylic acid, carboxyl, chlorotriazine, hydrazine, hydrazide, or aldehyde.

20. The sensing composite structure of claim 18, wherein the linking moiety comprises a chain including 5 to 125 atoms selected from the group consisting of carbon, oxygen, nitrogen and sulfur.

21. The sensing composite structure of claim 18, wherein the substrate comprises a polymeric material.

22. The sensing composite structure of claim 21, wherein the polymeric material is coated on a membrane.

23. The sensing composite structure of claim 18, wherein the substrate is selected from the group consisting of hydrophilic porous polypropylene and hexanediamine functionalized cellulose.

24. The sensing composite structure of claim 23, wherein the substrate is substantially planar in shape.

25. The sensing composite structure of claim 18, wherein the substrate possesses a net negative charge.

26. The sensing composite structure of claim 18, wherein the composite structure comprises a powder that is adhered to a surface that is substantially planar.

27. A fluorescent ionophoric compound having the general formula:

##STR107## wherein m and n are independently 0 or 1;

Z is O or NH;

Y and Y'"'"' independently are O, S, NH_x, or CH_y where x is 0 or 1 and y is 1 or 2, with the proviso that at least one of Y and Y'"'"' must be O, S, or NH_x, each R² independently is a sterically non-interferring group;

R³ is a non-electron withdrawing group; and

each R⁴ group is independently hydrogen, halogen, a hydrocarbyl-containing group, a hetero-acyclic group, a heterocyclic group, or a group having the formula (CH₂ X)_c E in which X is O, NH, or a single bond, E is a functional group that includes active hydrogen, and c is a whole number from 0 to 100, or both R⁴ groups together with the carbon atoms to which they are attached form a 5- or 6-membered ring which optionally can have one or more further R⁴ groups attached,

wherein the compound has a wavelength of maximum absorbance of at least about 380 nm a wavelength of maximum emission of no more than about 500 nm.

28. The compound of claim 27, wherein m and n are both 1 and Z is 0.

29. A fluorescent ionophoric compound, comprising

a complexing moiety for selective binding of an ion;

and

a fluorescing moiety that contains close-lying nπ

* and π

π

* excited states,

wherein the compound has a wavelength of maximum absorbance of at lest about 350 nm,

the ionophoric compound having the formula;

##STR108## wherein Y is O, S, NH.