Ligand functionalized polymers
Ligand functionalized substrates, methods of making ligand functionalized substrates, and methods of using functionalized substrates are disclosed.
1. A method of separating a biological species from a fluid comprising: contacting the fluid with a ligand-functionalized polymer comprising a carbonyl-functional (co)polymer functionalized with pendent guanidinyl groups, whereby a precipitate or complex comprising the polymer and the biological species is formed, and separating the precipitate or complex from the fluid.
2. The method of claim 1 wherein the pendent guanidinyl groups are of the formula:
wherein
R 1 is H, C 1 -C 12 alkyl, or C 5 -C 12 (hetero)aryl,
R 2 is a covalent bond, a C 2 to C 12 alkylene, or a C 5 -C 12 (hetero)arylene,
a
or a
R 9 is C 2 to C 12 alkylene or C 5 -C 12 (hetero)arylene,
each R 3 is independently H, —OH, C 1 -C 12 alkyl, or C 5 -C 12 (hetero)aryl,
each R 4 is H, C 1 -C 12 alkyl, C 5 -C 12 (hetero)aryl, or —N(R 3 ) 2 .
3. The method of claim 1 wherein the pendent guanidinyl groups are of the formula:
wherein
R 1 is H, C 1 -C 12 alkyl, or C 5 -C 12 (hetero)aryl,
R 9 is C 2 to C 12 alkylene or C 5 -C 12 (hetero)arylene,
each R 3 is independently H, —OH, C 1 -C 12 alkyl, or C 5 -C 12 (hetero)aryl,
each R 4 is H, C 1 -C 12 alkyl, C 5 -C 12 (hetero)aryl, or —N(R 3 ) 2 , preferably H, or
C 1 -C 4 alkyl,
R 5 is a divalent alkylene.
4. The method of claim 1 wherein the carbonyl-functional (co)polymer is selected from the group consisting of (co)polymers of: acrolein, vinyl methyl ketone, vinyl ethyl ketone, vinyl isobutyl ketone, diacetone (meth)acrylamide, acetonyl acrylate, carbon monoxide copolymer, and diacetone (meth)acrylate (co)polymers.
5. The method of claim 2 where the (co)polymer comprises polymerized monomer units of the formula:
wherein
R 1 is H, C 1 -C 12 alkyl, or C 5 -C 12 (hetero)aryl,
R 2 is a covalent bond, a C 2 to C 12 alkylene, or a C 5 -C 12 (hetero)arylene,
a
or a
R 9 is C 2 to C 12 alkylene or C 5 -C 12 (hetero)arylene,
each R 3 is independently H, —OH, C 1 -C 12 alkyl, or C 5 -C 12 (hetero)aryl,
R 4 is H, C 1 -C 12 alkyl, C 5 -C 12 (hetero)aryl, or —N(R 3 ) 2 ,
X is —O— or —NR 3 —
R 6 is a C 2 to C 12 alkylene, and
R 7 is H or CH 3 .
6. The method of claim 2 where the (co)polymer comprises polymerized monomer units of the formula:
wherein
R 1 is H, C 1 -C 12 alkyl, or C 5 -C 12 (hetero)aryl,
R 2 is a covalent bond, a C 2 to C 12 alkylene, or a C 5 -C 12 (hetero)arylene,
a
or a
R 9 is C 2 to C 12 alkylene or C 5 -C 12 (hetero)arylene,
each R 3 is independently H, C 1 -C 12 alkyl, or C 5 -C 12 (hetero)aryl, preferably H or C 1 -C 4 alkyl,
R 4 is H, C 1 -C 12 alkyl, C 5 -C 12 (hetero)aryl, or —N(R 3 ) 2 , preferably H, or C 1 -C 4 alkyl,
and
R 7 is H or CH 3 .
7. The method of claim 1 wherein the ligand-functionalized polymer further comprises hydrophilic monomer units.
8. The method of claim 2 wherein the ligand-functionalized polymer has the formula:
-(M Lig ) y -(M Hydrophil ) x -(M hydrophob ) z -(M CO ) w* -,
where
-(M CO ) w are carbonyl functional monomer units having “w” polymerized monomer units,
-(M Hydrophil ) x - are hydrophilic monomer units having “x” polymerized monomer units,
-(M hydrophob ) z - are hydrophobic monomer units having “z” polymerized monomer units
(M Lig ) y are ligand functional monomer units having “y” polymerized monomer units,
y is 10 to 100 wt. % of the monomer units;
x is 0 to 90 wt. % of the monomer units; and
w* may be comprise 0 to 90 wt. % of the monomer units, and
z is 0 to 20 wt. %, based on 100 wt. % total monomers.
9. The method of claim 1 wherein the biological species is selected from cells, cell debris, viruses, proteins, nucleic acids, and endotoxins.
10. The method of claim 9 wherein the cells are selected from archaea, bacteria, and eucaryota.
11. The method of claim 1 wherein the biological fluid is derived from a cell culture or fermentation process.
12. The method of claim 1 wherein the fluid comprises a solution of a purified protein or enzyme after separating the precipitate.
13. The method of claim 1 wherein the separated precipitate comprises a purified protein or enzyme.
14. The method of claim 1 wherein the fluid has a salt content of at least 50 millimolar.
15. The method of claim 1 wherein the fluid has a salt content of at least 100 millimolar.
16. The method of claim 1 wherein the ligand-functionalized polymer is used in amount of 0.01 micrograms/mL to about 5000 micrograms/mL of fluid.
17. The method of claim 1 wherein the amount of ligand-functionalized polymer relative to the amount of biological species is from of 0.01% to 100% by weight.
18. The method of claim 1 wherein the ligand-functional polymer is coated on a substrate.
19. The method of claim 1 comprising contacting a substrate with the fluid, the substrate having an ungrafted coating of the ligand-functionalized polymer.
20. The method of claim 18 , wherein the coated substrate has a crosslinked coating of the ligand-functional (co)polymer.
21. The method of claim 18 wherein the coated substrate has an ungrafted, uncrosslinked coating on the substrate.