COMPOSITIONS AND METHODS RELATING TO MOLECULAR CERIUM-OXIDE NANOCLUSTERS

• US 20190308884A1
• Filed: 12/06/2017
• Published: 10/10/2019
• Est. Priority Date: 12/06/2016
• Status: Active Grant

• Current Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Original Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Inventors: CHRISTOU, George, MITCHELL, Kylie J.
• Granted Patent: US 11,207,663 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 33/244 Lanthanides; Compounds thereof medicinal preparations containing radioactive lanthanides for use in therapy or testing in vivo A61K51/00
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: B01J 23/10 of rare earths
• CPC Class Codes: C01F 17/235 Cerium oxides or hydroxides
• CPC Class Codes: C01F 17/30 Compounds containing rare earth metals and at least one element other than a rare earth metal, oxygen or hydrogen, e.g. La4S3Br6 C01F17/247 - C01F17/294 take precedence
• CPC Class Codes: C01P 2002/77 by unit-cell parameters, atom positions or structure diagrams
• CPC Class Codes: C01P 2004/64 Nanometer sized, i.e. from 1-100 nanometer

Abstract

Described herein are compositions and methods relating to molecular cerium-oxide nanoclusters. In an aspect, described herein are methods of synthesizing molecular cerium-oxide nanocluster compositions and compositions thereof. In an aspect, described herein are methods of scavenging reactive oxygen species utilizing molecular cerium-oxide nanoclusters as described herein. Also described herein are pharmaceutical compositions and methods of use. Pharmaceutical compositions as described herein can comprise a therapeutically effective amount of a compound (such as a composition comprising one or more molecular cerium-oxide nanoclusters), or a pharmaceutically acceptable salt of the compound, and a pharmaceutically acceptable carrier. Methods of treating oxidative stress are also described herein, comprising administering pharmaceutical compositions as described herein to a subject in need thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

Claims

1. ) A method of synthesizing a molecular cerium-oxide nanocluster composition, comprising:

providing a cerium source, an organic acid, and a solvent; and

mixing the cerium source and the organic acid in a ratio of about 1;

2 to about 1;

4 in the presence of a solvent to create a reaction mixture at a temperature and a pressure for a period of time to create a composition of molecular cerium-oxide nanoclusters containing a plurality of molecular cerium-oxide nanoclusters.

6. ) The method of claim 1, wherein the cerium source is (NH₄)₂[Ce(NO₃)₆ or Ce(NO₃)₃.

7. ) The method of claim 1, wherein the organic acid is of the formula X₁CO₂H, X₁Y₁PO₂H, or X₁ PO₃H.

8. ) The method of claim 7, wherein X₁ and Y₁ are selected from the group consisting of:

an alkyl group, an aromatic group, substituted phenyls, a plurality of connected phenyls, linear or branched aliphatic, alicyclic groups, and a combination thereof.

9. ) The method of claim 1, further comprising adding a reducing agent to the reaction mixture comprising the cerium source and the organic acid, wherein the reaction mixture has a ratio about 1:

2;

1 to about 1;

4;

1 of cerium source;

organic acid;

reducing agent.

10. ) The method of claim 9, wherein the reducing agent is of the formula X₂I or a sulfate-based agent.

11. ) The method of claim 10, wherein X₂ is selected from the group consisting of K and NH₄.

12. ) The method of claim 1, wherein the solvent is a mixture of pyridine (py) and H₂O in a ratio of py:

H₂O of about 1;

2 to about 1;

10.

16. ) The method of claim 1, further comprising adding a crystallization agent to the reaction mixture to create a crystalline molecular cerium-oxide nanocluster composition containing crystalline molecular cerium-oxide nanoclusters.

17. ) The method of claim 16, wherein the crystallization agent is MeNO₂ or MeCN.

25. ) The method of claim 9, wherein the reducing agent is NH₄I or KI.

26. ) A composition, comprising the products of claim 1.

2-5. -5) (canceled)

13-15. -15) (canceled)

18-24. -24) (canceled)

27. ) A composition, comprising a molecular cerium-oxide nanocluster of the formula [Ce_xO_y(OH)_w(H₂O)_l(RCO₂)_z(L)_m]ⁿ, [Ce_xO_y(OH)_w(H₂O)_l(RPO₂)_z(L)_m]ⁿ or [Ce_xO_y(OH)_w(H₂O)_l(RPO₃)_z(L)_m]ⁿ of cerium nuclearity of 19 to 100, wherein l, m, n, w, x, y, z are integers of 0 or greater.

28. ) The composition of claim 27, wherein R is selected from the group consisting of:

Ph, CH₃, CH₃CH₂, an aromatic group, a polyaromatic group, a substituted phenyl, a polyphenyl group, a linear or branched aliphatic groups, a substituted linear or branched aliphatic group, a linear or branched alicyclic group, and combinations thereof.

29. ) The composition of claim 27, wherein L is one or more neutral organic molecules.

30. ) The composition of claim 27, wherein L is MeCN or pyridine.

31. ) The composition of claim 27, wherein the molecular cerium-oxide nanocluster has a formula of Ce₁₉O₁₈(OH)₉(PhCO₂)₂₇(py)₃(H₂O), Ce₂₄O_36-x-y(OH)_x(H₂O)_y(PhCO₂)₃₀(py)₄, Ce₃₈O_62-x-y(OH)_x(H₂O)_y(CH₃CH₂CO₂)₃₆(py)₈, or Ce₄₀O₅₆(OH)_x(H₂O)_2-x(CH₃CO₂)_46-y(py)₄(MeCN)_y.

32. ) The composition of claim 27, wherein the molecular cerium-oxide nanocluster composition has a ratio of Ce³⁺/Ce⁴⁺ of about 0 to 0.5.

33. ) The composition of claim 27, wherein the composition comprises one or more of Ce₆O₄(OH)₄(H₂O)₄(dmb)₁₂, Ce₁₆O₁₇(OH)₆(O₂CPh)₂₄(HO₂CPh)₃(H₂O), Ce₁₉O₁₈(OH)₁₀(O₂CPh)₂₆(H₂O)(py)₃, Ce₂₄O₂₇(OH)₉(O₂CPh)₃₀(py)₄, Ce₂₄O₂₈(OH)₈(PhCO₂)₃₀(py)₄], Ce₃₈O54(OH)₈(EtCO₂)₃₆(py)₈, Ce₄₀O₅₆(OH)₂(MeCO₂)₄₄(MeCO₂H)_2/0(MeCN)_0/2(py)₄, individually or in combination.

34-50. -50) (canceled)

51. ) A method of scavenging free radicals, comprising:

delivering a composition to an environment containing free radicals, wherein the composition comprises one or more molecular cerium-oxide nanoclusters with the following formula;

[Ce_xO_y(OH)_w(H₂O)_l(RCO₂)_z(L)_m]ⁿ, [Ce_xO_y(OH)_w(H₂O)_l(RPO₂)_z(L)_m]ⁿ or [Ce_xO_y(OH)_w(H₂O)_l(RPO₃)_z(L)_m]ⁿ of cerium nuclearity of 19 to 100, wherein l, m, n, w, x, y, z are integers of 0 or greater.

52-57. -57) (canceled)