Scalable anion capture macrocycles
View Patent ↗The present disclosure concerns scalable single-pot synthesis, anion binding features, liquid-liquid extraction of salts of the triazolophane macrocycle of Formula (I): wherein the substituents R are independently selected from the group consisting of a linear and branched alkyl, a linear and branched alkyl substituted with an ionizable functional group such as an amine or carboxylic acid, a linear and branched alkoxy (R=—OR), an alkyl comprising —O(CH 2 CH 2 O) n CH 3 , where n is 1-20, an amide —CO—NR 1 R 2 , where R 1 is any alkyl, organic substituent, R 2 is any alkyl, organic substituent, wherein R 1 and R 2 may be identical or different, —OCO—R, wherein R is any alkyl, organic substituent, an aromatic ring and their substituted analogues, any length and sequence of natural and unnatural amino acids that make up a peptide chain, and —C≡C—R where R is any alkyl, organic substituent.
1 . A triazolophane macrocycle of Formula (I) comprising:
wherein the substituents R are independently selected from the group consisting of a linear and branched alkyl, a linear and branched alkyl substituted with an ionizable functional group such as an amine or carboxylic acid, a linear and branched alkoxy —OR 3 , where R 3 is any alkyl, an alkyl comprising —O(CH 2 CH 2 O) n CH 3 , where n is 1-20, an amide —CO—NR 1 R 2 , where R 1 is any alkyl, R 2 is any alkyl, wherein R 1 and R 2 may be identical or different, —OCO—R 4 , wherein R 4 is any alkyl, an aromatic ring or their substituted analogues, any length and sequence of natural and unnatural amino acids that make up a peptide chain, and —C≡C—R 5 where R 5 is any alkyl.
2 . The triazolophane macrocycle of Formula (I) according to claim 1 , wherein the substituents R are identical.
3 . The triazolophane macrocycle of Formula (I) according to claim 1 , wherein the triazolophane macrocycle of Formula (I) consists of Formula (IA):
4 . A method of synthesizing a triazolophane macrocycle of Formula (I) according to claim 1 , the method comprising:
converting
in a single-pot synthesis according to Scheme (I):
5 . The method of synthesizing the triazolophane macrocycle of Formula (I) according to claim 4 , wherein the substituents R are identical.
6 . The method of synthesizing the triazolophane macrocycle of Formula (I) according to claim 4 , wherein the triazolophane macrocycle of Formula (I) consists of Formula (IA):
wherein the method comprises converting
in a single-pot synthesis according to Scheme (IA):
7 . A method of increasing the yield and scale of the single-pot synthesis of triazolophane macrocycle of Formula (I) according to claim 1 , the method comprising reacting
in the presence of a halide salt as a template according to Scheme (X):
8 . The method of increasing the yield and scale of the single-pot synthesis of the triazolophane macrocycle of Formula (I) according to claim 7 , wherein the substituents R are identical.
9 . The method of increasing the yield and scale of the single-pot synthesis of the triazolophane macrocycle of Formula (I) according to claim 7 , the method comprising reacting
in the presence of the halide salt as a template according to Scheme (Y):
10 . The method of claim 7 , wherein the halide salt comprises an anion selected from the group consisting of chloride, fluoride and iodide.
11 . The method of claim 7 , wherein the halide salt is a chloride salt.
12 . The method of claim 11 , wherein the chloride salt is tetrabutylammonium chloride.
13 . A complex comprising:
(a) an anion; and
(b) a triazolophane macrocycle of Formula (I) according to claim 1 .
14 . The complex according to claim 13 , wherein the triazolophane macrocycle of Formula (I) has identical substituents R.
15 . The complex according to claim 13 , wherein the triazolophane macrocycle of Formula (I) consists of Formula (IA):
16 . The complex of claim 13 , wherein the anion is selected from the group consisting of chloride, fluoride, iodide, bromide, hydroxide, sulfide, hydrogen sulfide, cyanide, azide, organosulfides, alkoxides, bifluoride, borohydride, tetrafluoroborate, hydride, bisulfide, selenide, hydrogen selenide, superoxide, peroxide, and hypochlorite.
17 . The complex of claim 13 , wherein a ratio of the complex comprising the triazolophane macrocycle of Formula (I):anion is selected from the group consisting of 1:1 (macrocycle:anion), 2:1 (macrocycle:anion), and 3:2 (macrocycle:anion).
18 . A method of removing an anion from a solution containing the anion, wherein the method comprises:
(a) contacting the solution with a triazolophane macrocycle of Formula (I) according to claim 1 ;
(b) forming a complex, said complex comprising the anion and the triazolophane macrocycle of Formula (I); and
(c) removing the complex from the solution.
19 . The method of removing an anion from a solution containing the anion according to claim 18 , wherein the triazolophane macrocycle of Formula (I) has identical substituents R.
20 . The method of removing an anion from a solution containing the anion according to claim 18 , wherein the triazolophane macrocycle of Formula (I) consists of Formula (IA):