# US 10,501,581 B2 · Sequence-defined polymers and methods of making same and using same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,501,581 B2 - Document ID: US10501581B2 - Status: Granted - Kind: B2 - Application number: 14/830,374 - Filed: 2015-08-19 - Published: 2016-03-17 - Granted: 2019-12-10 - Earliest claimed: 2014-08-19 - Assignees: Cornell University - Applicants: Cornell University - Inventors: Christopher Akinleye Alabi; Mintu Porel - Web page: https://patentgrep.com/patent/US10501581B2 ## CPC - C08G 75/02: Polythioethers - C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS ## Abstract Methods of making sequence-defined polymers and sequence-defined polymers. The methods are based on the orthogonal reactivity of monomers having at least two different functional groups. The sequence-defined polymers can be used in various applications. For example, the SDPs (e.g., pH sensitive SDPs) are used in cell lysis methods or as molecular vehicles to transport drug cargo into cells. ## Claims ### Claim 1 A method of making a sequence-defined polymer (SDP) having 3 to 50 monomers comprising: a) contacting a first monomer having a free allyl group or a free acrylamide group and a first co-monomer having two thiol groups capable of reacting with the allyl group and the acrylamide group of the first monomer under conditions such that the allyl group or acrylamide group reacts with one of the thiol groups on the co-monomer to form a first SDP reaction product; b) contacting the first SDP reaction product with a second monomer having an allyl group and an acrylamide group such that i) the acrylamide group of the second monomer reacts with the unreacted thiol group of the first SDP reaction product without substantial reaction of the allyl group of the second monomer or ii) the allyl group of the second monomer reacts with the unreacted thiol group of the first SDP reaction product without substantial reaction of the acrylamide group of the second monomer to form a second SDP reaction product; c) optionally, contacting the second SDP reaction product with a second co-monomer having two thiol groups such that i) if the allyl group of the second monomer reacted in b), the acrylamide group of the second SDP product reacts with one of the thiol groups of the second co-monomer or ii) if the acrylamide group of the second monomer reacted in b), the allyl group of the second SDP product reacts with one of the thiol groups of the second co-monomer to form a third SDP reaction product; d) optionally, contacting the third SDP reaction product with a third monomer having an allyl group and an acrylamide group such that i) the acrylamide group of the third monomer reacts with the unreacted thiol group of the third SDP reaction product without substantial reaction of the allyl group of the third monomer or ii) the allyl group of the third monomer reacts with the unreacted thiol group of the third SDP reaction product without substantial reaction of the acrylamide group of the third monomer to form a fourth SDP reaction product; and e) optionally, repeating c) and d) from 1 to 47 times such that a sequence-defined polymer is formed. ### Claim 2 (depends on 1) The method of making a sequence-defined polymer of claim 1, wherein in a) a first monomer having a free allyl group is contacted with a first co-monomer having two thiol groups under conditions such that the allyl group reacts with one of the thiol groups on the co-monomer to form a first SDP reaction product; in b) the first SDP reaction product is contacted with a second monomer having an allyl group and an acrylamide group such that the acrylamide group of the second monomer reacts with the unreacted thiol group of the first SDP reaction product without substantial reaction of the allyl group of the second monomer to form a second SDP reaction product; in c) optionally, the second SDP reaction product is contacted with a second co-monomer having two thiol groups such that the allyl group of the second SDP product reacts with one of the thiol groups of the second co-monomer to form a third SDP reaction product; in d) optionally, the third SDP reaction product is contacted with a third monomer having an allyl group and an acrylamide group such that the acrylamide group of the third monomer reacts with the unreacted thiol group of the third SDP reaction product without substantial reaction of the allyl group of the third monomer to form a fourth SDP reaction product. ### Claim 3 (depends on 1) The method of making a sequence-defined polymer of claim 1, wherein the first monomer, the second monomer, the third monomer, or a combination thereof is an allyl acrylamide. ### Claim 4 (depends on 1) The method of making a sequence-defined polymer of claim 1, wherein the first co-monomer, the second co-monomer, or a combination thereof is an alkyl dithiol having 1 to 20 carbons. ### Claim 5 (depends on 1) The method of making a sequence-defined polymer of claim 1, wherein the first monomer has a fluorous tag and a sequence-defined polymer having a fluorous tag is formed. ### Claim 6 (depends on 5) The method of making a sequence-defined polymer of claim 5, wherein the sequence-defined polymer having a fluorous tag is contacted with a silica having fluorous moieties and the combination of the sequence-defined polymer having a fluorous tag and the silica having fluorous moieties is subsequently washed with a water:methanol mixture such that non-fluorous materials are removed from the silica and then washed with methanol to remove the sequence-defined polymer having a fluorous tag from the silica. ### Claim 7 (depends on 5) The method of making a sequence-defined polymer of claim 5, wherein the sequence-defined polymer having a fluorous tag is treated with an acid such that the fluorous tag is removed and the sequence-defined polymer is formed. ### Claim 8 (depends on 1) The method of making a sequence-defined polymer of claim 1, wherein the molar ratio of the first monomer to the first co-monomer is 1:0.5 to 1:10. ### Claim 9 (depends on 1) The method of making a sequence-defined polymer of claim 1, wherein at least one of the first monomer, second monomer, third monomer, or a combination thereof has the following structure: wherein R1 is selected from the group consisting of hydrogen, methyl, propyl, butyl, 2-methylpropyl, tridecyl, 2-(dimethylamino)ethyl, 2-hydroxyethyl, phenethyl, napthalen-2-ylmethyl, ### Claim 10 (depends on 1) The method of making a sequence-defined polymer of claim 1, wherein at least one of the first co-monomer, second co-monomer, or a combination thereof is ethane dithiol, 1,4-dithiothreitol, PEG dithiol, 1,3-propanedithiol, or 3-mercapto-2-(mercaptomethyl)propanoic acid. ### Claim 11 (depends on 1) The method of making a sequence-defined polymer of claim 1, wherein the molar ratio of the first monomer to the first co-monomer is 1:0.5 to 1:5.