Receptor and method for citrate determination

• US 6,048,732 A
• Filed: 10/15/1997
• Issued: 04/11/2000
• Est. Priority Date: 10/16/1996
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Metzger, Axel, Anslyn, Eric V.
• Primary Examiner(s): WARDEN, JILL ALICE
• Application Number:
  US08/950,712
• Time in Patent Office: 909 Days
• Field of Search: 436/127, 436/128, 436/129, 436/166
• US Class Current: 436/129
• CPC Class Codes: G01N 31/22 using chemical indicators G01N31/02 takes precedence
• CPC Class Codes: G01N 33/52 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 Class Codes: Y10T 436/201666 Carboxylic acid

Abstract

A sensing composition for polycarboxylic acids which operates in competitive solvents. The composition includes a receptor and an indicator, both of which are mixed in a solvent. Addition of a polycarboxylic acid to the composition causes a change in the physical properties of the composition. Measurement of the amount of change in solution allows the concentration of polycarboxylic acid to be determined. The sensor is preferably selective for polycarboxylic acids, is sensitive, and may be used to analyze solutions of polycarboxylic acids.

Claims

1. A method for determining a concentration of a polycarboxylic acid in a solution, the method comprising:

adding the solution comprising the polycarboxylic acid to a composition, the composition comprising a receptor for the polycarboxylic acid, an indicator, and a solvent, the receptor being adapted to bind to the polycarboxylic acid during use, the indicator being adapted to bind to the receptor such that at least one physical property of the indicator are altered during use, wherein the receptor comprises a compound of the formula;

space="preserve" listing-type="equation">(R.sup.1).sub.n --X--(R.sup.2).sub.m

wherein X comprises carbocyclic systems or C1-C10 alkanes, n is an integer of at least 2, m is an integer of at least 1; and

wherein each of R¹ independently represents --(CH2)_y --NR³ --C(NR⁴)--NR⁵, or --(CH₂)_y --NR⁶ R⁷ ;

where y is an integer of at least 1;

where R³, R⁴, and R⁵ independently represent hydrogen, alkyl, aryl, alkyl carbonyl of 1 to 10 carbon atoms, or alkoxy carbonyl of 1 to 10 carbon atoms, or R⁴ and R⁵ together represent a cycloalkyl group,

where R⁶ represents hydrogen, alkyl, aryl, alkyl carbonyl of 1 to 10 carbon atoms, or alkoxy carbonyl of 1 to 10 carbon atoms;

where R⁷ represents hydrogen, alkyl, aryl, alkyl carbonyl of 1 o 10 carbon atoms, or alkoxy carbonyl of 1 to 10 carbon atoms;

or where R⁶ and R⁷ together represent a cycloalkyl group; and

wherein each of R² independently represents hydrogen, alkyl, alkenyl, alkynyl, phelnyl, phenylalkyl, arylalkyl aryl, or together with another group represent a carbocyclic ring; and

wherein n is at least equal to the number of carboxylic acid groups of the polycarboxylic acid;

allowing the polycarboxylic acid to interact with the receptor to substantially release the indicator from the receptors;

moitoring the change in the physical property of the indicator after the addition of the solution; and

calculating the concentration of the polycarboxylic acid in the solution based on the change in physical property of the indicator.

2. The method of claim 1, wherein monitoring the change in the physical property of the indicator comprises measuring, the change in absorption of the composition.

3. The method of claim 1, wherein monitoring the change in the physical property of the indicator comprises measuring the fluorescence of the composition.

4. The method of claim 1, wherein monitoring the change in the physical property of the indicator comprises measuring the absorption of the composition, and monitoring the change in the physical property of the indicator comprises measuring the fluorescence of the composition.

5. The method of claim 1, wherein the solution of the polycarboxylic acid is filtered prior to adding the solution to the composition.

6. The method of claim 1, further comprising adjusting the pH of the solution of the polycarboxylic acid to a value of at least 5.0 prior to adding the solution to the composition.

7. The method of claim 1, further comprising adjusting the pH of the solution of the polycarboxylic acid to a value of at least 5.0 prior to adding the solution to the composition, and wherein the solution of the polycarboxylic acid is filtered prior to adding the solution to the composition.

8. The method of claim 1, wherein a binding strength of the receptor to the indicator is less than a binding strength of the receptor to the polycarboxylic acid.

9. The method of claim 1 wherein the receptor comprises a compound of the general formula:

space="preserve" listing-type="equation">(R.sup.1).sub.n --X--(R.sup.2).sub.m

wherein X is a benzene ring, n is an integer of at least 3, m is an integer of 1 to 3;

wherein each of R¹ independently represents --(CH₂)_y --NR³ --C(NR⁴)--NR⁵ ;

where y is an integer of 1 to 10;

where R³, R⁴, and R⁵ independently represents hydrogen, alkyl, aryl, alkyl carbonyl of 1 to 10 carbon atoms, or alkoxy carbonyl of 1 to 10 carbon atoms, or R⁴ and R⁵ together represent a cycloalkyl group; and

wherein each of R² independently represents hydrogen, alkyl, alkenyl, or alkynyl.

10. The method of claim 1, wherein the receptor comprises a compound of the general formula:

space="preserve" listing-type="equation">(R.sup.1).sub.n --X--(R.sup.2).sub.m

wherein X is a benzene ring, n is 3, in is 3; and

wherein each of R¹ independently represents --CH₂ --NH₂ ; and

wherein each of R² independently represents hydrogen, alkyl, alkenyl, or alkynyl.

11. The method of claim 10 wherein the indicator comprises 5-carboxyfluoroscein.

12. A method for determining a concentration of citric acid in a solution, the method comprising:

adding the solution comprising the citric acid to a composition, the composition comprising a receptor for the citric acid, an indicator, and a solvent, the receptor being adapted to bind to the citric acid during use, the indicator beings adapted to bind to the receptor such that at least one physical property of the indicator are altered during use, wherein the receptor comprises a compound of the formula;

space="preserve" listing-type="equation">(R.sup.1).sub.n --X--(R.sup.2).sub.m

wherein X comprises carbocyclic systems or C₁ -C₁₀ alkanes, n is an integer of at least 3, m is an integer of at least 1; and

wherein each of R¹ independently represents --(CH2)_y --NR³ --C(NR⁴)--NR⁵, or --(CH₂)_y --NR⁶ R⁷ ;

where y is an integer of at least 1;

where R³, R⁴, and R⁵ independently represent hydrogen, alkyl, aryl, alkyl carbonyl of 1 to 10 carbon atoms, or alkoxy carbonyl of 1 to 10 carbon atoms, or R⁴ and R⁵ together represent a cycloalkyl group;

where R⁶ represents hydrogen, alkyl, aryl, alkyl carbonyl of 1 to 10 carbon atoms, or alkoxy carbonyl of 1 to 10 carbon atoms;

where R⁷ represents hydrogen, alkyl, aryl, alkyl carbonyl of 1 to 10 carbon atoms, or alkoxy carbonyl of 1 to 10 carbon atoms;

or where R⁶ and R⁷ together represent a cycloalkyl group; and

wherein each of R² independently represents hydrogen, alkyl, alkenyl, alkynyl, phenyl, phenylalkyl, arylalkyl aryl, or together with another group represent a carbocyclic ring;

allowing the polycarboxylic acid to interact with the receptor to substantially release the indicator from the receptor;

moitoring the change in the physical property of the indicator after the addition of the solution; and

calculating the concentration of the citric acid in the solution based on the change in physical property of the indicator.

13. The method of claim 12, wherein monitoring the chance in the physical property of the indicator comprises measuring the absorption of the composition, and wherein monitoring the change in the physical property of the indicator comprises measuring the fluorescence of the composition.

14. The method of claim 12, further comprising adjusting the pH of the solution of the citric acid to a value of at least 5.0 prior to adding the solution to the composition, and wherein the solution of the citric acid is filtered prior to adding the solution to the composition.

15. The method of claim 12, wherein monitoring the change in the physical property of the indicator comprises measuring the change in absorption of the composition.

16. The method of claim 12, wherein monitoring the change in the physical property of the indicator comprises measuring the fluorescence of the composition.

17. The method of claim 12, wherein the solution of the citric acid is filtered prior to adding the solution to the composition.

18. The method of claim 12, further comprising adjusting the pH of the solution of the polycarboxylic acid to a value of at least 5.0 prior to adding the solution to the composition.

19. The method of claim 12, wherein a binding strength of the receptor to the indicator is less than a binding strength of the receptor to the citric acid.

20. The method of claim 12 wherein the receptor comprises a compound of the general formula:

space="preserve" listing-type="equation">(R.sup.1).sub.n --X--(R.sup.2).sub.m

wherein X is a benzene ring, n is an integer of at least 3, m is an integer of 1 to 3;

wherein each of R¹ independently represents --(CH₂)_y --NR³ --C(NR⁴)--NR⁵ ;

where y is an integer of 1 to 10;

where R³, R⁴, and R⁵ independently represents hydrogen, alkyl, aryl, alkyl carbonyl of 1 to 10 carbon atoms, or alkoxy carbonyl of 1 to 10 carbon atoms, or R⁴ and R⁵ together represent a cycloalkyl group; and

wherein each of R² independently represents hydrogen, alkyl, alkenyl, or alkynyl.

21. The method of claim 12 wherein the receptor comprises a compound of the general formula:

space="preserve" listing-type="equation">(R.sup.1).sub.n --X--(R.sup.2).sub.m

wherein X is a benzene ring, n is 3, m is 3; and

wherein each of R¹ independently represents --CH₂ --NH₂ ; and

wherein each of R² independently represents hydrogen, alkyl, alkenyl, or alkynyl.

22. The method of claim 21 wherein the indicator comprises 5-carboxyfluoroscein.