Antimicrobial guanidinium and thiouronium functionalized polymers

Patent metadata

Field	Value
Publication number	US-10779539-B2
Application number	US-201715645838-A
Country	US
Kind code	B2
Filing date	Jul 10, 2017
Priority date	May 19, 2015
Publication date	Sep 22, 2020
Grant date	Sep 22, 2020

Abstract

Antimicrobial cationic polycarbonates and polyurethanes have been prepared comprising one or more pendent guanidinium and/or isothiouronium groups. Additionally, antimicrobial particles were prepared having a silica core linked to surface groups comprising a guanidinium and/or isothiouronium group. The cationic polymers and cationic particles can be potent antimicrobial agents against Gram-negative microbes, Gram-positive microbes, and/or fungi.

First claim

What is claimed is:

1. A method, comprising:
conducting an organocatalyzed ring opening polymerization of a cyclic carbonate monomer using a particle comprising i) a core and ii) alcohol and/or amine surface groups covalently linked to the core, the surface groups capable of initiating the ring opening polymerization, thereby forming an initial polymer-modified particle, the cyclic carbonate monomer having a structure according to formula (M-1):

wherein
ring atoms of (M-1) are numbered 1 to 6,
each B′ is an independent acid-labile protecting group,
L′ is a divalent hydrocarbon radical comprising 2 to 30 carbons,
each R′ is an independent monovalent radical selected from the group consisting of hydrogen and alkyl groups comprising 1 to 6 carbons,
R″ is a monovalent radical selected from the group consisting of hydrogen and alkyl groups comprising 1 to 6 carbons, and
Y′ is *—O—* or *—N(H)—*; and
treating the initial polymer-modified particle with a protic acid, thereby forming a second polymer-modified particle comprising a cationic polymer chain covalently linked to one of the surface groups, the cationic polymer chain comprising a cationic subunit of formula (A-1):

wherein
atoms numbered 1, 2, 3, 4, 5, and 6 of (A-1) are backbone atoms of the cationic polymer,
m is 1 or 2,
n is 0 or 1, wherein when m is 2, n is 0,
each R′ is an independent monovalent radical selected from the group consisting of hydrogen and alkyl groups comprising 1 to 6 carbons,
R″ is a monovalent radical selected from the group consisting of hydrogen and alkyl groups comprising 1 to 6 carbons, and
each Q″ is an independent group comprising a guanidinium group.

2. The method of claim 1 , wherein each R′ is hydrogen.

3. The method of claim 1 , wherein R″ is methyl or ethyl.

4. The method of claim 1 , wherein Y′ is *—O—*.

5. The method of claim 1 , wherein Y′ is *—N(H)—*.

6. The method of claim 1 , wherein the cationic polymer chain is a polycarbonate.

7. The method of claim 1 , wherein the second polymer-modified particle is capable of killing a Gram-positive bacterium, a Gram-negative bacterium, and/or a fungus.

8. The method of claim 1 , wherein m is 1 and n is 1.

9. The method of claim 1 , wherein (M-1) is

wherein n is a positive integer having a value of 1 to 6.

10. The method of claim 1 , wherein (M-1) is

wherein n is a positive integer having a value of 1 to 6.

11. The method of claim 1 , wherein (M-1) is

12. The method of claim 1 , wherein the cationic subunit has a structure according to formula (A-2):

wherein
atoms numbered 1, 2, 3, 4, 5, and 6 of (A-2) are backbone atoms of the cationic polymer,
L′ is a divalent hydrocarbon radical comprising 2 to 30 carbons,
Q′ is *—N(H)—*,
each R′ is an independent monovalent radical selected from the group consisting of hydrogen and alkyl groups comprising 1 to 6 carbons,
R″ is a monovalent radical selected from the group consisting of hydrogen and alkyl groups comprising 1 to 6 carbons,
X′ is a negative-charged counterion, and
Y′ is *—O—* or *—N(H)—*.

13. The method of claim 1 , wherein L′ is selected from the group consisting of 1,2-ethylene, 1,3-propylene, 1,4-butylene, 1,5-pentylene, 1,4-cyclohexylene, and 1,4-phenylene.

14. The method of claim 1 , wherein the core of the particle is silica.

15. The method of claim 1 , wherein the core of the particle is a silica gel.

16. The method of claim 1 , wherein the surface groups comprise amine groups.

17. The method of claim 1 , wherein the particle has a median size between 5 nm and 200 micrometers.

18. The method of claim 1 , wherein the cationic polymer chain is capable of forming a complex by non-covalent interactions with a biologically active material selected from the group consisting of drugs and genes.

Assignees

• IBM
• Agency Science Tech & Res
• Coral Bay Ii Llc

Inventors

• Chin Willy
• Hedrick James L
• Lee Ashlynn L Z
• Ono Robert J
• Yang Yi Yan
• Xu Qingxing

Classifications

• C08G18/755

  and at least one isocyanate or isothiocyanate group linked to a secondary carbon atom of the cycloaliphatic ring, e.g. isophorone diisocyanate · CPC title

• A01N47/44 Primary

  Guanidine; Derivatives thereof · CPC title

• C08G18/6681

  with compounds of group C08G18/32 or C08G18/3271 and/or polyamines of C08G18/38 · CPC title

• C08G18/3831

  containing urethane groups · CPC title

• C08G64/0241

  containing nitrogen · CPC title