Magnesium ion selective membranes

Patent metadata

Field	Value
Publication number	US-12050193-B2
Application number	US-201917256282-A
Country	US
Kind code	B2
Filing date	Jun 21, 2019
Priority date	Jul 4, 2018
Publication date	Jul 30, 2024
Grant date	Jul 30, 2024

Abstract

Magnesium ion selective electrode membranes and the preparation thereof. The membranes are rendered highly selective for magnesium ions by the addition of acidic groups to the preferably PVC membrane, either by introducing a lipophilic compound comprising an acidic group covalently linked to a C4-C18 alkyl-substituted phenyl group (e.g. bis-4-octylphenyl phosphoric acid) into the membrane comprising the magnesium selective ionophore (e.g. a neutral ionophore 1,10-phenanthroline derivative) or by covalently linking an acidic (e.g. a carboxylic) group to the ionophore (e.g. a 1,10-phenanthroline derivative).

First claim

The invention claimed is:

1. A magnesium ion selective membrane comprising:
a. an ionophore that is not charged; and
b. a lipophilic compound comprising an acidic group, wherein the lipophilic compound is a compound of the formula I:

wherein A comprises an acidic group,
wherein one, two or all three of R 18 , R 19 and R 20 is a C 4-18 group, which is a C 4-18 alkyl group, a C 4-18 alkenyl group, a C 4-18 alkynyl group, or an amide-containing C 4-18 group, wherein said C 4-18 group is linear at positions 1, 2 and 3, counting from the phenyl group, or in total only has one side chain at said positions 1, 2 and 3,
and wherein any remaining of R 18 , R 19 and R 20 independently are hydrogen, or a linear C 1-18 alkyl,
or a salt of said lipophilic compound.

2. The membrane according to claim 1 , wherein the ionophore is a phenanthroline compound which is 1,10-phenanthroline or a substituted form thereof.

3. The membrane according to claim 2 , wherein the phenanthroline compound is a compound of the formula II:

wherein each of R 1 -R 6 is any of:
H;
any of F, Cl, Br, I, NO 2 , CN, or CF 3 ;
C 1-18 alkyl;
C 1-18 aryl;
C 1-18 alkenyl;
(CH 2 ) m Y, wherein m is 0 or an integer from 1 to 4, Y is any of —OR 7 , —NR 7 R 8 , —OCOR 7 , —NR 7 COR 8 , —COR 7 , —COOR 7 , SO 3 R 7 , —OSiR 7 R 8 R 9 , —PO 4 R 7 R 8 , —PO 3 R 7 R 8 , wherein each of R 7 , R 8 , and R 9 are any of H, alkyl, branched alkyl, aryl, or substituted aryl; or
C n —R 10 R 11 , wherein n is 0 or an integer between 1 and 17 inclusive, R 10 is C, N, NCO, or CH 2 —Z—CH 2 wherein Z is any of O, NH, S, OCO, or CO, R 11 is

and R 11 is linked to R 10 at any of positions 3, 4, 5, 6, 7, or 8 of R 11 , R 12 -R 17 are any of H, C 1-18 alkyl, C 1-18 aryl, or deleted, provided that if R 11 is linked to R 10 at position 3 of R 18 then R 12 is deleted, if R 18 is linked to R 10 at position 4 of R 11 then R 13 is deleted, if R 18 is linked to R 10 at position 5 of R 18 then R 14 is deleted, if R 18 is linked to R 10 at position 6 of R 18 then R 15 is deleted, if R 11 is linked to R 10 at position 7 of R 18 then R 16 is deleted, if R 18 is linked to R 10 at position 8 of R 11 then R 17 is deleted,
provided that one of R 1 -R 6 is other than H and that each of the C atoms at positions 2 and 9 of the 1,10-phenanthroline is bonded, by the bond which does not participate in the fused ring structure, to an H.

4. The membrane according to claim 3 , wherein R 1 to R 6 include a total of at least 6 carbon atoms.

5. The membrane according to claim 3 , wherein one or more of R 1 , R 2 , R 3 , R 4 , R 5 and R 6 is an alkyl group having between 1 and 18 carbon atoms.

6. The membrane according to claim 3 , wherein the phenanthroline compound is 4-undecyl-1,10-phenanthroline or 4,7-diundecyl-1,10-phenanthroline.

7. The membrane according to claim 1 , wherein the acidic group comprised within group A of formula I is selected from the group consisting of: a carboxylic acid, a sulfonic acid, a sulfuric acid monoester, a sulfonamide, a phosphonic acid, a phosphoric acid, an arsenic acid, a sulfinic acid, and a thiocarboxylic acid.

8. The membrane according to claim 7 , wherein the lipophilic compound is a compound of the formula:

9. The membrane according to claim 1 , wherein only one of R 18 , R 19 or R 20 is a C 4-18 alkyl group and the others are hydrogen.

10. The membrane according to claim 1 , wherein R 19 is a C 4-18 alkyl group as defined in claim 1 and R 18 and R 20 are hydrogen.

11. The membrane according to claim 1 , wherein said C 4-18 alkyl group(s) comprise(s) at least 6 carbon atoms.

12. The membrane according to claim 1 , wherein the lipophilic compound is a lipophilic salt and said lipophilic salt is hemi-calcium bis[4-octylphenyl]phosphate, hemi-magnesium bis[4-octylphenyl]phosphate or a mixture thereof.

13. The membrane according to claim 12 , wherein the lipophilic salt is a mixture containing at least 50% hemi-magnesium bis[4-octylphenyl]phosphate.

14. The membrane according to claim 1 , wherein the molar ratio between the ionophore and the lipophilic compound or the anion of the lipophilic salt is between 2:1 and 1:1.

15. A process for preparing a magnesium ion selective membrane comprising mixing the components specified in claim 1 in a solvent, dispensing the resulting solution on a desired support and allowing the solvent to evaporate.

16. An electrode for determining the magnesium ion concentration of a liquid sample comprising the membrane of claim 1 .

17. A potentiometric sensor for determining the magnesium ion concentration of a liquid sample comprising the electrode of claim 16 and a reference electrode.

18. A method for determining the magnesium ion concentration of a liquid sample comprising contacting said sample with a potentiometric senor according to claim 17 and determining the magnesium ion concentration based on signal provided by said potentiometric sensor.

19. A method for diagnosing a disease or disorder, said method comprising performing the method according to claim 18 on a sample of a subject, said method further comprising comparing the magnesium ion concentration in said sample with a reference magnesium ion concentration, to diagnose hypomagnesemia or hypermagnesemia in said subject.

20. A method for determining the magnesium ion concentration of a liquid sample comprising contacting said sample with an electrode according to claim 16 and determining the magnesium ion concentration based on signal provided by said electrode.

21. A method for diagnosing a disease or disorder, said method comprising performing the method according to claim 20 on a sample of a subject, said method further comprising comparing the magnesium ion concentration in said sample with a reference magnesium ion concentration to diagnose hypomagnesemia or hypermagnesemia in said subject.

22. A magnesium ion selective membrane comprising:
i) an ionophore covalently linked to an acidic group via a spacer wherein said spacer comprises at least one carbon atom; or
ii) a salt of said ionophore covalently linked to an acidic group,
wherein the ionophore is not charged.

Assignees

• Radiometer Medical Aps

Inventors

• Nygaard Thomas Pedersen
• Schneider Palle
• Neilson Peter Jakobsen
• Hansen Thomas Steen
• Laursen Thomas

Classifications

• B01D71/301

  Polyvinylchloride · CPC title

• G01N33/50

  Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q) · CPC title

• B01D67/0002

  Organic membrane manufacture · CPC title

• G01N27/3335 Primary

  the membrane containing at least one organic component (G01N27/3271 takes precedence; aspects concerning the enzyme reagent in enzyme electrodes C12Q1/001) · CPC title