Functionalized particles having modified phases

Patent metadata

Field	Value
Publication number	US-10618920-B2
Application number	US-201615173382-A
Country	US
Kind code	B2
Filing date	Jun 3, 2016
Priority date	Jun 3, 2016
Publication date	Apr 14, 2020
Grant date	Apr 14, 2020

Abstract

Modified silica particles are provided. Aspects of the particles include an outer layer that is composed of organically-modified silica comprising a siloxane-linked hydrophilic group, such as a charged functional group or a polar neutral functional group. The modified silica particles can form the basis of a variety of chromatography support materials. Also provided are methods of preparing the subject particles. Aspects of the methods include contacting silica particles with water, an ionic fluoride and an organosilane reagent comprising a hydrophilic moiety to produce modified silica particles wherein the hydrophilic moiety of the organosilane reagent is incorporated into an outer layer of the silica particles. Chromatography supports and kits including the subject particles and methods of using the same are also provided.

First claim

What is claimed is:

1. A modified silica particle, comprising an outer layer that is composed of organically-modified silica comprising a siloxane-linked hydrophilic group having one of formulae (Ib), (IIb) or (IIIb):

wherein:
Z is a hydrophilic moiety;
L 1 , L 2 and L 3 are each independently a covalent bond or a linker; and
T is a branching atom or branching group;

wherein the siloxane-linked hydrophilic group is in the outer layer below a particle surface.

2. The particle of claim 1 , wherein the hydrophilic moiety is selected from a nitrogen-containing heterocycle, amide, carbamate, carboxylic acid, carboxy ester, methyl ether, cyano, amine, ammonium, sulfonamide, sulfonate, urea, thiourea, hydroxyl, thiol, PEG, a zwitterionic group, and sulfonic acid.

3. The particle of claim 1 , wherein the hydrophilic moiety is a charged moiety.

4. The particle of claim 1 , wherein:
when the siloxane-linked hydrophilic group is of formula (Ib), L 1 is a C1-C6 alkyl and Z is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, —CONH 2 , —OCONHMe, —NHCOOMe, NHCONH 2 , —OMe, CN and SO 3 H;
when the siloxane-linked hydrophilic group is of formula (IIb), L 1 and L 2 are each independently a C1-C6 alkyl, wherein the combined length of L 1 and L 2 is 10 carbons or less, and Z is selected from —O— and —NR′—, wherein R′ is H, an alkyl or a substituted alkyl; and
when the siloxane-linked hydrophilic group is of formula (IIIb), L 1 , L 2 and L 3 are each independently a covalent bond or a C1-C6 alkyl, wherein the combined length of L 1 and L 2 is 10 carbons or less, and Z is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, —CONH 2 , —OCONHMe, —NHCOOMe, NHCONH 2 , —OMe, CN and SO 3 H.

5. The particle of claim 1 , wherein the organically-modified silica of the outer layer further comprises one or more additional distinct siloxane-linked organic group.

6. The particle of claim 1 , wherein the organically modified silica particle is surface modified with a chromatography stationary phase.

7. A method of preparing modified silica particles, the method comprising:
contacting silica particles with:
a. water;
b. an ionic fluoride; and
c. an organosilane reagent comprising a hydrophilic moiety;

to produce modified silica particles according to claim 1 wherein the hydrophilic moiety of the organosilane reagent is incorporated into an outer layer of the silica particles.

8. The method of claim 7 , wherein the hydrophilic moiety of the organosilane reagent is selected from a nitrogen-containing heterocycle, amide, carbamate, carboxylic acid, carboxy ester, methyl ether, cyano, amine, ammonium, sulfonamide, sulfonate, urea, thiourea, hydroxyl, thiol, PEG, a zwitterionic group and sulfonic acid.

9. The method of claim 7 , wherein the hydrophilic moiety is a charged moiety in an aqueous environment.

10. The method of claim 7 , wherein the organosilane reagent has one of formula (I), (II) and (III):

wherein:
Z is the hydrophilic moiety;
L, L 1 , L 2 and L 3 are each independently a covalent bond or a linker;
each R 1 is independently a lower alkyl;
T is a branching atom or branching group;
each X is independently a leaving group attached to the silicon atom; and
each a is independently 0, 1 or 2.

11. The method of claim 7 , further comprising, during the contacting step, heating the silica particles to improve particle stability.

12. The method of claim 7 , wherein the contacting step comprises contacting the particles with one or more additional organosilane reagent.

13. The method of claim 7 , wherein the contacting step comprises contacting the silica particles with the two or more distinct organosilane reagents each comprising a hydrophilic moiety.

14. The method of claim 12 , wherein the one or more additional organosilane reagent each independently have the formula R 1 a R 2 b SiX 4-a-b or R(R 1 a SiX 3-a ) n , wherein R 1 and R 2 are alkyl or substituted alkyl groups containing 1-4 carbon atoms, R is a substituted or unsubstituted aliphatic, cyclic, acrylic, or aromatic, X is a leaving group attached to the silicon atom, a and b are independently 0 or 1, wherein a plus b equals to 0, 1 or 2, and n is a positive integer of 2 to 8.

15. The method of claim 7 , wherein contacting occurs at a temperature and for a time sufficient to form a new surface on at least a portion of the plurality of silica particles.

16. The particle of claim 1 , wherein the particle comprises a solid core having a size ranging from about 50% to about 90% of the size of the entire particle.

17. The particle of claim 1 , wherein the particle has a diameter from about 0.5 μm to 50 μm.

18. The particle of claim 1 , wherein the organically-modified silica comprises a siloxane-linked hydrophilic group having formula (IIb).

19. The particle of claim 1 , wherein the organically-modified silica comprises a siloxane-linked hydrophilic group having formula (IIIb).

20. The particle of claim 1 , wherein the organically-modified silica also comprises the siloxane-linked hydrophilic group at the particle surface.

Assignees

• Agilent Technologies Inc

Inventors

• Chen Wu
• Li Yingyu
• Wei Ta-Chen
• Wang Xiaoli

Classifications

• C01B33/12

  Silica; Hydrates thereof, e.g. lepidoic silicic acid · CPC title

• B01J20/283

  based on silica · CPC title

• C07F7/1892

  by reactions not provided for in C07F7/1876 - C07F7/1888 · CPC title

• B01J20/22

  comprising organic material · CPC title

• C07F7/1804 Primary

  Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896) · CPC title