Functional derivatives of maleimide copolymers for nanodisc production

A disc-shaped nanoparticle comprising an amphiphilic copolymer and biological material;

• wherein one or more amphiphilic copolymers form a nanodisc having a hydrophilic outer surface, an annulus, and a hydrophobic inner core;
• the biological material is held in the annulus of the nanodisc;
• the biological material comprising complexes of hydrophobic molecules, lipids, proteins, or a combination thereof, derived from bacterial, mammalian, animal, fungal or plant cells or tissues;
• and
• the amphiphilic copolymer comprises Formula IA, Formula IB, or a combination thereof,
• wherein:
• i) Formula IA is represented as,
• wherein
• R1 is N;
• R2 is —(C1-C12)alkyl, alkanol, alkylamine, alkylamine oxide, or quaternary amine, wherein —(C1-C12)alkyl is substituted optionally with halo;
• or
• R1 and R2 taken together form a histamine, amino alkanediol, or alkyl ester of an amino acid residue;
• and
• R3 is a hydrogen, unsubstituted phenyl, or phenyl substituted by one or more non-polar substituents;
• provided that when R2 is alkanol or quaternary amine, R3 is unsubstituted phenyl, or phenyl substituted by one or more non-polar substituents;
• ii) Formula IB is represented as,
• wherein
• R1 is O or NH;
• when R1 is O, R2 is H;
• when R1 is NH:
• R2 is —(C1-C12)alkyl, alkanol, alkylamine, alkylamine oxide, quaternary amine, wherein —(C1-C12)alkyl is substituted optionally with halo;
• or
• R1 and R2 taken together form a histamine, amino alkanediol, or alkyl ester of an amino acid residue;
• and
• R3 is a hydrogen, unsubstituted phenyl, or phenyl substituted by one or more non-polar substituents;
• provided that when R1 is O and R2 is hydrogen, R3 is unsubstituted phenyl, or phenyl substituted by one or more non-polar substituents;
• wherein the oxygen anion of Formula IB has a positively charged monovalent counter ion;
• and
• iii) independently for Formula IA and IB, n is about 7 to about 200, and the monomer moieties labeled a and b are in an alternating, substantially alternating, largely alternating, or semialternating copolymer arrangement in the length of the copolymer backbone;
• wherein a=b=1 for the alternating copolymer arrangement;
• 1<a≤1.2 and b =1 for the substantially alternating copolymer arrangement;
• 1.2<a≤1.4 and b=1 for the largely alternating copolymer arrangement;
• or 1.7≤a≤2.3 and b=1 for the semialternating copolymer arrangement.

An amphiphilic copolymer comprising Formula IA, Formula IB, or a combination thereof, wherein:

• i) Formula IA is represented as,
• wherein
• R1 is N;
• R2 is ethyl-dimethylamine-oxide or propyl-dimethylamine-oxide;
• or
• R1 and R2 taken together form serinol, ethyl-glycine-methyl-ester or valine methyl ester;
• and
• R3 is a hydrogen, unsubstituted phenyl, or phenyl substituted by one or more non-polar substituents;
• ii) Formula IB is represented as,
• wherein
• R1 is NH;
• R2 is ethyl-dimethylamine-oxide or propyl-dimethylamine-oxide;
• or
• R1 and R2 taken together form serinol, ethyl-glycine-methyl-ester or valine methyl ester;
• and
• R3 is a hydrogen, unsubstituted phenyl, or phenyl substituted by one or more non-polar substituents;
• wherein the oxygen anion of Formula IB has a positively charged monovalent counter ion;
• and
• iii) independently for Formula IA and IB, n is about 7 to about 200, and the monomer moieties labeled a and b are in an alternating, substantially alternating, largely alternating, or semialternating copolymer arrangement in the length of the copolymer backbone;
• wherein a=b=1 for the alternating copolymer arrangement;
• 1<a≤1.2 and b =1 for the substantially alternating copolymer arrangement;
• 1.2<a≤1.4 and b=1 for the largely alternating copolymer arrangement;
• or 1.7≤a≤2.3 and b=1 for the semialternating copolymer arrangement.

An amphiphilic copolymer comprising Formula IA, Formula IB, or a combination thereof, wherein:

• i) Formula IA is represented as,
• wherein
• R1 is N;
• R2 is —(C1-C12)alkyl, alkanol, alkylamine, alkylamine oxide, or quaternary amine, wherein —(C1-C12)alkyl is substituted optionally with halo;
• or
• R1 and R2 taken together form a histamine, amino alkanediol, or alkyl ester of an amino acid residue;
• and
• R3 is a phenyl substituted by one or more methyl or —(C2-C12) alkyl groups;
• ii) Formula IB is represented as,
• wherein
• R1 is O or NH;
• when R1 is O, R2 is H;
• when R1 is NH:
• R2 is —(C1-C12)alkyl, alkanol, alkylamine, alkylamine oxide, quaternary amine, wherein —(C1-C12)alkyl is substituted optionally with halo;
• or
• R1 and R2 taken together form a histamine, amino alkanediol, or alkyl ester of an amino acid residue;
• and
• R3 is a phenyl substituted by one or more methyl or —(C2-C12)alkyl groups;
• wherein the oxygen anion of Formula IB has a positively charged monovalent counter ion;
• and
• iii) independently for Formula IA and IB, n is about 7 to about 200, and the monomer moieties labeled a and b are in an alternating, substantially alternating, largely alternating, or semialternating copolymer arrangement in the length of the copolymer backbone;
• wherein a=b=1 for the alternating copolymer arrangement;
• 1<a≤1.2 and b =1 for the substantially alternating copolymer arrangement;
• 1.2<a≤1.4 and b=1 for the largely alternating copolymer arrangement;
• or 1.7≤a≤2.3 and b=1 for the semialternating copolymer arrangement.

An amphiphilic copolymer comprising Formula IA, Formula IB, or a combination thereof, wherein:

• i) Formula IA is represented as,
• wherein
• R1 is N;
• R2 is —(C1-C12)alkyl, alkanol, alkylamine, alkylamine oxide, or quaternary amine, wherein —(C1-C12)alkyl is substituted optionally with halo;
• or
• R1 and R2 taken together form a histamine, amino alkanediol, or alkyl ester of an amino acid residue;
• and
• R3 is a hydrogen, unsubstituted phenyl, or phenyl substituted by one or more non-polar substituents;
• ii) Formula IB is represented as,
• wherein
• R1 is O or NH;
• when R1 is O, R2 is H;
• when R1 is NH:
• R2 is —(C1-C12)alkyl, alkanol, alkylamine, alkylamine oxide, quaternary amine, wherein —(C1-C12)alkyl is substituted optionally with halo;
• or
• R1 and R2 taken together form a histamine, amino alkanediol, or alkyl ester of an amino acid residue;
• and
• R3 is a hydrogen, unsubstituted phenyl, or phenyl substituted by one or more non-polar substituents;
• wherein the oxygen anion of Formula IB has a positively charged monovalent counter ion;
• and
• iii) independently for Formula IA and IB, n is about 7 to about 200, and the monomer moieties labeled a and b are in an alternating, substantially alternating, largely alternating, or semialternating copolymer arrangement in the length of the copolymer backbone;
• wherein a=b=1 for the alternating copolymer arrangement;
• 1<a≤1.2 and b =1 for the substantially alternating copolymer arrangement;
• 1.2<a≤1.4 and b=1 for the largely alternating copolymer arrangement;
• or 1.7≤a≤2.3 and b=1 for the semialternating copolymer arrangement;
• and
• provided that for Formula IA and IB, when R3 is a hydrogen, R1 is not O and R2 is not alkylamine oxide, (C1-C3) alkyl, quaternary amine, or alkanol;
• wherein the copolymer is cyclized by a crosslink between the two termini of the copolymer chain;
• or
• wherein the copolymer is:
• poly(styrene-alt-maleamic acid-1,3-propanediol) (7), poly(styrene-alt-maleimide-1,3-propanediol) (8), poly(styrene-alt-maleamic acid-methylamine) (9), poly (styrene-alt-maleamic acid-ethylamine) (10), poly(styrene-alt-maleamic acid-propylamine) (11), poly(styrene-alt-maleamic acid-glycine-methyl-ester) (12), poly(styrene-alt-maleamic acid-glycine-methyl-ester) (13), poly(styrene-alt-maleamic acid-glycine, valine-methyl-ester) (14), poly(ortho-methyl-stilbene-maleamic acid) (16), or poly(para-methyl-stilbene-maleamic acid) (18).