Functionalized particles having modified phases

Patent metadata

Field	Value
Publication number	US-2017349612-A1
Application number	US-201615173382-A
Country	US
Kind code	A1
Filing date	Jun 3, 2016
Priority date	Jun 3, 2016
Publication date	Dec 7, 2017
Grant date	—

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.

2 . The particle of claim 1 , wherein the hydrophilic moiety is selected from a nitrogen-containing hetereocycle, 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 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 10 , wherein the organosilane reagent has one of the following structures:

wherein:
each n is independently an integer from 1 to 18;
each X is independently a leaving group attached to the silicon atom; and
R 2 -R 7 and R′ are each independently H, an alkyl or a substituted alkyl.

12 . The method of claim 10 , wherein the organosilane reagent has one of the following structures:

wherein:
n and m are independently an integer from 1 to 18;
each X is independently a leaving group attached to the silicon atom;
Z 1 is selected from —O—, —NR′— and —N + (R′) 2 —, wherein each R′ is independently H, an alkyl or a substituted alkyl;

T 2 is selected from a trisubstituted carbon or nitrogen atom; and
R 2 -R 7 and R′ are each independently H, an alkyl or a substituted alkyl.

13 . The method of claim 11 , wherein X is selected from Cl, OCH 3 , OC 2 H 5 , (CH 3 ) 2 N, (CH 3 CH 2 ) 2 N, I, Br, CN, OOCH 3 , O(CO)CH 3 and O 3 SCF 3 .

14 . The method of claim 7 , further comprising, after the contacting step, modifying the surface of the modified silica particles with a chromatography stationary phase.

15 . The method of claim 14 , comprising modifying the surface of the modified silica particles with a long chain organosilane reagent to produce the chromatography stationary phase.

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

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

18 . 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.

19 . The method of claim 17 , 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, arylic, 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.

20 . 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.

Assignees

• Agilent Technologies Inc

Inventors

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

Classifications

• C07F7/1892

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

• B01J20/22

  comprising organic material · CPC title

• C07F7/0838

  Compounds with one or more Si-O-Si sequences (compounds with a ring containing only alternating Si and O atoms, i.e. cyclosilanes C07F7/21) · CPC title

• B01J20/283

  based on silica · CPC title

• B01J20/28016

  Particle form · CPC title