Poly-β-peptides from functionalized β-lactam monomers and antibacterial compositions containing same
Disclosed is a method of making β-polypeptides. The method includes polymerizing β-lactam-containing monomers in the presence of a base initiator and a co-initiator which is not a metal-containing molecule to yield the product β-polypeptides. Specifically disclosed are methods wherein the base initiator is potassium t-butoxide, lithium bis(trimethylsilyl)amide (LiN(TMS) 2 ), potassium bis(trimethyl-silyl)amide, and sodium ethoxide, and the reaction is carried out in a solvent such as chloroform, dichloromethane, dimethylsulfoxide, or tetrahydrofuran.
1. A method of making β-polypeptides comprising polymerizing β-lactam-containing monomers in an organic solvent in the presence of a base initiator and a co-initiator which is not a metal-containing molecule, wherein the co-initiator is a compound of formula
wherein X is independently a leaving group and R is independently a base-stable moiety selected from the group consisting of linear, branched, or cyclic alkyl, alkenyl, alkynyl, substituted or unsubstituted aryl, and substituted or unsubstituted arylalkyl, or R and X, together with the carbon atom to which they are attached, define a substituted or unsubstituted, five- to twelve-membered ring having an intramolecular leaving group; and
wherein the co-initiator is a cyclic anhydride;
to yield a β-polypeptide.
2. The method of claim 1 , wherein at least one of the β-lactam-containing monomers is selected from the group consisting of:
wherein
R 3 , R 4 , R 5 , and R 6 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1 -C 6 -alkyl, aryl, C 1 -C 6 -alklyaryl, amino, protected-amino, amino-C 1 -C 6 -alkyl, and protected-amino-C 1 -C 6 -alkyl.
3. The method of claim 2 , wherein at least one of the β-lactam-containing monomer is selected from the group consisting of:
wherein at least one of R 3 , R 4 , R 5 , or R 6 is selected from the group consisting of amino, protected amino, amino-C 1 -C 6 -alkyl and protected amino-C 1 -C 6 -alkyl.
4. The method of claim 1 , wherein the base initiator is selected from the group consisting of KOtBu, LiN(TMS) 2 , KN(TMS) 2 , NaOEt, Sc(N(TMS) 2 ) 3 , Al 2 (N(Me) 2 ) 6 , Al(N(TMS) 2 ) 3 , Zn(N(TMS) 2 ) 2 , Sn(N(TMS) 2 ) 2 , and CpTi(N(Me) 2 ) 2 Cl.
5. The method of claim 2 , comprising polymerizing the β-lactam-containing monomers in a solvent selected from the group consisting of chloroform, dichloromethane, dimethylsulfoxide, and tetrahydrofuran.
6. The method of claim 1 , comprising polymerizing at least two different β-lactam-containing monomers to yield a co-polymer.
7. The method of claim 1 , comprising polymerizing the β-lactam-containing monomers at a temperature ≦about 50° C.
8. The method of claim 1 , comprising polymerizing the β-lactam-containing monomers at a temperature ≦about 30° C.
9. A method of making β-polypeptides comprising:
polymerizing β-lactam-containing monomers in the presence of a base initiator and a co-initiator which is not a metal-containing molecule, wherein the β-lactam-containing monomers include a monomer selected from the group consisting of:
wherein R 3 , R 4 , R 5 , and R 6 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1 -C 6 -alkyl, aryl, C 1 -C 6 -alklyaryl, amino, protected-amino, amino-C 1 -C 6 -alkyl, and protected-amino-C 1 -C 6 -alkyl;
wherein at least one of R 3 , R 4 , R 5 , or R 6 is selected from the group consisting of amino, protected amino, amino-C 1 -C 6 -alkyl, and protected amino-C 1 -C 6 -alkyl;
wherein the co-initiator is a compound of formula
wherein X is independently a leaving group and R is independently a base-stable moiety selected from the group consisting of linear, branched, or cyclic alkyl, alkenyl, alkynyl, substituted or unsubstituted aryl, and substituted or unsubstituted arylalkyl, or R and X, together with the carbon atom to which they are attached, define a substituted or unsubstituted, five- to twelve-membered ring having an intramolecular leaving group;
wherein the co-initiator is a cyclic anhydride; and
wherein the base initiator is selected from the group consisting of KOtBu, LiN(TMS) 2 , KN(TMS) 2 , NaOEt, Sc(N(TMS) 2 ) 3 , Al 2 (N(Me) 2 ) 6 , Al(N(TMS) 2 ) 3 , Zn(N(TMS) 2 ) 2 , Sn(N(TMS) 2 ) 2 , and CpTi(N(Me) 2 ) 2 Cl.
10. The method of claim 9 , comprising polymerizing the β-lactam-containing monomers in a solvent selected from the group consisting of chloroform, dichloromethane, dimethylsulfoxide, and tetrahydrofuran.
11. The method of claim 9 , comprising polymerizing at least two different β-lactam-containing monomers to yield a co-polymer.
12. The method of claim 9 , comprising polymerizing the β-lactam-containing monomers at a temperature ≦about 50° C.
13. The method of claim 9 , comprising polymerizing the β-lactam-containing monomers at a temperature ≦about 30° C.