Antimicrobial guanidinium and thiouronium functionalized polymers

Patent metadata

Field	Value
Publication number	US-2016338356-A1
Application number	US-201514715690-A
Country	US
Kind code	A1
Filing date	May 19, 2015
Priority date	May 19, 2015
Publication date	Nov 24, 2016
Grant date	—

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

1 . An antimicrobial cationic polymer, comprising a cationic subunit of formula (A-1):

wherein
atoms 1-6 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 and/or isothiouronium group.

2 . The cationic polymer of claim 1 , wherein the cationic polymer is selected from the group consisting of polycarbonates and polyurethanes.

3 . The cationic polymer of claim 1 , wherein the cationic polymer is capable of killing a Gram-positive bacterium, a Gram-negative bacterium, and/or a fungus.

4 . The cationic polymer of claim 1 , wherein m is 1 and n is 1.

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

wherein
atoms 1-6 are backbone atoms of the cationic polymer,
L′ is a divalent hydrocarbon radical comprising 2 to 30 carbons,
Q′ is *—N(H)—* or *—S—*,
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)—*.

6 . The cationic polymer of claim 5 , 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.

7 . The cationic polymer of claim 5 , wherein Q′ is *—N(H)—*.

8 . The cationic polymer of claim 5 , wherein Q′ is *—S—*.

9 . The cationic polymer of claim 5 , wherein Y′ is *—O—*.

10 . The cationic polymer of claim 5 , wherein R″ is methyl or ethyl.

11 . The cationic polymer of claim 5 , wherein X′ is a negative-charged counterion selected from the group consisting of chloride, bromide, iodide, acetate, benzoate, trifluoroacetate, hydrogen carbonate, methansulfonate, hydrogen sulfate, and dihydrogen phosphate.

12 . The cationic polymer of claim 1 , wherein the cationic polymer has a structure in accordance with formula (B-1):
Z′-P′-Z″  (B-1),

wherein
Z′ is a monovalent first end group comprising 1 to 40 carbons,
Z″ is a monovalent second end group selected from the group consisting of hydrogen and groups comprising 1 to 40 carbons, and
P′ is a polymer chain comprising the cationic subunit of formula (A-1).

13 . The cationic polymer of claim 12 , wherein P′ is a polycarbonate.

14 . The cationic polymer of claim 12 , wherein P′ is a polyurethane.

15 . The cationic polymer of claim 1 , wherein the cationic polymer has a structure in accordance with formula (B-2):
Z b -P b -C′-P b -Z b   (B-2),

wherein
each P b is an independent polymer chain comprising the cationic subunit,
C′ is a divalent linking group (core group) comprising 2 to 25 carbons, wherein C′ comprises two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, wherein the heteroatoms are covalently linked to respective polymer chains P b , and
each Z b is an independent monovalent end group selected from the group consisting of hydrogen and groups comprising 1 to 40 carbons.

16 . A method of killing a microbe, comprising contacting the microbe with the cationic polymer of claim 1 .

17 . A method of forming the cationic polymer of claim 1 , comprising:
forming an initial polymer by organocatalyzed ring opening polymerization of a cyclic carbonate monomer of formula (M-1):

wherein
ring atoms 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 with a protic acid, thereby forming the cationic polymer.

18 . The method of claim 17 , wherein each R′ is hydrogen and R″ is methyl or ethyl.

19 . A method of forming the cationic polymer of claim 1 , comprising:
forming an initial polymer by organocatalyzed ring opening polymerization of a cyclic carbonate monomer of formula (M-6):

wherein
the ring atoms are shown numbered 1 to 6,
L b is a divalent linking group comprising 1 or more carbons,
E′ is a substituent capable of undergoing a nucleophilic substitution reaction with thiourea to form an isothiouronium group,
each R′ is an independent monovalent radical selected from the group consisting of hydrogen and alkyl groups comprising 1 to 6 carbons, and
R″ is a monovalent radical selected from the group consisting of hydrogen and alkyl groups comprising 1 to 6 carbons; and
treating the initial polymer with thiourea, thereby forming the cationic polymer.

20 . An antimicrobial particle, comprising:
a core comprising silica; and a plurality of independent surface groups covalently linked to the core, wherein one or more of the surface groups comprises one or more cationic subunits of formula (A-2):

wherein
atoms 1-6 are backbone atoms of the surface groups,
L′ is a divalent hydrocarbon radical comprising 2 to 30 carbons,
Q′ is *—N(H)—* or *—S—*,
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)—*.

21 . A method of killing a microbe, comprising contacting the microbe with the particle of claim 20 .

22 . The method of claim 21 , where the microbe is a Gram-positive microbe, Gram-negative microbe, and/or a fungus.

23 . An antimicrobial composition comprising the cationic polymer of claim 1 and at least one other chemical component.

24 . The antimicrobial composition of claim 23 , wherein the antimicrobial composition is selected from the group consisting of soaps, shampoos, skin lotions, skin creams, cosmetics, mouthwashes, wound care agents, deodorants, surface cleaning agents, and laundry detergents.

25 . An antimicrobial cationic polycarbonate, comprising:
a cationic subunit of formula (A-4):

wherein
atoms 1-6 are backbone atoms of the cationic polycarbonate,
L′ is a divalent hydrocarbon radical comprising 2 to 30 carbons,

Assignees

• IBM
• Agency Science Tech & Res

Inventors

• Chin Willy
• Hedrick James L
• Ibrahim Nor Lizawati
• Lee Ashlynn L Z
• Ono Robert J
• Xu Qingxing
• Yang Yi Yan

Classifications

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C08G64/30

  using carbonates · CPC title

• C08G64/0241

  containing nitrogen · 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