{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/132721"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/132721","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Modular synthesis for cooperative small molecule ligands and chemical education","abstract":"Modular synthesis can be leveraged as both a synthetic strategy for accessing cooperatively binding small molecule ligands as well as a pedagogic framework for chemical education. Mimicking hemoglobin’s cooperative binding to oxygen stands as an unclimbed mountain in the field of protein mimicry despite countless efforts in developing cooperatively binding ligands and the reference to hemoglobin in those reports. 9,9’-bianthracene was determined to have the potential to serve as a cooperative scaffold given its rigidity and pseudosymmetry which allows the adoption of a global conformation to a higher energy state that prepays the enthalpic cost upon binding of a first equivalent of a guest. The coupling of function-infused building blocks enables the synthesis of a collection of model tetra-pyridyl bianthracene systems that do exhibit positive cooperativity. This result supports the notion that the 9,9’-bianthracene could serve as a scaffold for positive cooperativity if the pyridine rings are to be exchanged with metal-schiff bases complexes that are capable of reversibly forming µ-oxo bridges with molecular oxygen. As a framework for chemical education, modular synthesis serves the role of reducing the barrier to entry in organic chemistry and enabling students to discover structure-function relationships with the assistance of data science tools. Across four courses, we’ve developed a sequence of activities that introduce students to fundamental techniques such as K-nearest neighbors, K-medoids clustering, modularization of target molecules to identify repeating bond-types, and optimization of molecular function by identifying high-performing building blocks. Students also get hands-on experience in the power of modular synthesis to perform a classic diazo synthesis, a modern Suzuki-Miyaura cross-coupling that leverages a general purification procedure that enabled the development of an automated small molecule synthesis platform, an aerobic Suzuki-Miyaura coupling that generates an organic photovoltaic candidate for them to characterize and compare to a ML model. At the end of the sequence as well as the end of this dissertation, Organic Chemistry II students were challenged to shatter the traditional research-education barrier by synthesizing a collection of kinase inhibitor candidates. One student was able to successfully synthesize a molecule that is not reported in the literature and that molecule is currently undergoing screening against over 80 cell lines in collaboration with the CELLerator platform at UIUC.","abstract_html":"Modular synthesis can be leveraged as both a synthetic strategy for accessing cooperatively binding small molecule ligands as well as a pedagogic framework for chemical education. Mimicking hemoglobin’s cooperative binding to oxygen stands as an unclimbed mountain in the field of protein mimicry despite countless efforts in developing cooperatively binding ligands and the reference to hemoglobin in those reports. 9,9’-bianthracene was determined to have the potential to serve as a cooperative scaffold given its rigidity and pseudosymmetry which allows the adoption of a global conformation to a higher energy state that prepays the enthalpic cost upon binding of a first equivalent of a guest. The coupling of function-infused building blocks enables the synthesis of a collection of model tetra-pyridyl bianthracene systems that do exhibit positive cooperativity. This result supports the notion that the 9,9’-bianthracene could serve as a scaffold for positive cooperativity if the pyridine rings are to be exchanged with metal-schiff bases complexes that are capable of reversibly forming µ-oxo bridges with molecular oxygen. As a framework for chemical education, modular synthesis serves the role of reducing the barrier to entry in organic chemistry and enabling students to discover structure-function relationships with the assistance of data science tools. Across four courses, we’ve developed a sequence of activities that introduce students to fundamental techniques such as K-nearest neighbors, K-medoids clustering, modularization of target molecules to identify repeating bond-types, and optimization of molecular function by identifying high-performing building blocks. Students also get hands-on experience in the power of modular synthesis to perform a classic diazo synthesis, a modern Suzuki-Miyaura cross-coupling that leverages a general purification procedure that enabled the development of an automated small molecule synthesis platform, an aerobic Suzuki-Miyaura coupling that generates an organic photovoltaic candidate for them to characterize and compare to a ML model. At the end of the sequence as well as the end of this dissertation, Organic Chemistry II students were challenged to shatter the traditional research-education barrier by synthesizing a collection of kinase inhibitor candidates. One student was able to successfully synthesize a molecule that is not reported in the literature and that molecule is currently undergoing screening against over 80 cell lines in collaboration with the CELLerator platform at UIUC.","abstract_has_math":false,"creators":["Green, Nolan Michael"],"institution":"University of Illinois Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Burke, Martin D","Moore, Jeffrey S","van der Donk, Wilfred A","Hergenrother, Paul J"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-12","date_published":"2025-12","updated_at":"2026-07-22T22:25:07Z","subjects":["Modular synthesis, cooperative binding, chemical education"],"languages":["en"],"rights":["Copyright 2025 Nolan Green"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/132721","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Burke, Martin D","Moore, Jeffrey S","van der Donk, Wilfred A","Hergenrother, Paul J"]},{"key":"dc:creator","label":"Author","values":["Green, Nolan Michael"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-12","2025-07-28"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Modular synthesis, cooperative binding, chemical education"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2025 Nolan Green"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/132721"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Modular synthesis can be leveraged as both a synthetic strategy for accessing cooperatively binding small molecule ligands as well as a pedagogic framework for chemical education. Mimicking hemoglobin’s cooperative binding to oxygen stands as an unclimbed mountain in the field of protein mimicry despite countless efforts in developing cooperatively binding ligands and the reference to hemoglobin in those reports. 9,9’-bianthracene was determined to have the potential to serve as a cooperative scaffold given its rigidity and pseudosymmetry which allows the adoption of a global conformation to a higher energy state that prepays the enthalpic cost upon binding of a first equivalent of a guest. The coupling of function-infused building blocks enables the synthesis of a collection of model tetra-pyridyl bianthracene systems that do exhibit positive cooperativity. This result supports the notion that the 9,9’-bianthracene could serve as a scaffold for positive cooperativity if the pyridine rings are to be exchanged with metal-schiff bases complexes that are capable of reversibly forming µ-oxo bridges with molecular oxygen. As a framework for chemical education, modular synthesis serves the role of reducing the barrier to entry in organic chemistry and enabling students to discover structure-function relationships with the assistance of data science tools. Across four courses, we’ve developed a sequence of activities that introduce students to fundamental techniques such as K-nearest neighbors, K-medoids clustering, modularization of target molecules to identify repeating bond-types, and optimization of molecular function by identifying high-performing building blocks. Students also get hands-on experience in the power of modular synthesis to perform a classic diazo synthesis, a modern Suzuki-Miyaura cross-coupling that leverages a general purification procedure that enabled the development of an automated small molecule synthesis platform, an aerobic Suzuki-Miyaura coupling that generates an organic photovoltaic candidate for them to characterize and compare to a ML model. At the end of the sequence as well as the end of this dissertation, Organic Chemistry II students were challenged to shatter the traditional research-education barrier by synthesizing a collection of kinase inhibitor candidates. One student was able to successfully synthesize a molecule that is not reported in the literature and that molecule is currently undergoing screening against over 80 cell lines in collaboration with the CELLerator platform at UIUC.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-12-01","The student, Nolan Green, accepted the attached license on 2025-07-18 at 09:30.","The student, Nolan Green, submitted this Dissertation for approval on 2025-07-18 at 09:33.","This Dissertation was approved for publication on 2025-07-28 at 09:27.","DSpace SAF Submission Ingestion Package generated from Vireo submission #22653 on 2026-02-19 at 20:07:49"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Modular synthesis for cooperative small molecule ligands and chemical education"]}]}],"canonical_facts":{"dc:contributor":["Burke, Martin D","Moore, Jeffrey S","van der Donk, Wilfred A","Hergenrother, Paul J"],"dc:creator":["Green, Nolan Michael"],"dc:date":["2025-12","2025-07-28"],"dc:description":["Modular synthesis can be leveraged as both a synthetic strategy for accessing cooperatively binding small molecule ligands as well as a pedagogic framework for chemical education. Mimicking hemoglobin’s cooperative binding to oxygen stands as an unclimbed mountain in the field of protein mimicry despite countless efforts in developing cooperatively binding ligands and the reference to hemoglobin in those reports. 9,9’-bianthracene was determined to have the potential to serve as a cooperative scaffold given its rigidity and pseudosymmetry which allows the adoption of a global conformation to a higher energy state that prepays the enthalpic cost upon binding of a first equivalent of a guest. The coupling of function-infused building blocks enables the synthesis of a collection of model tetra-pyridyl bianthracene systems that do exhibit positive cooperativity. This result supports the notion that the 9,9’-bianthracene could serve as a scaffold for positive cooperativity if the pyridine rings are to be exchanged with metal-schiff bases complexes that are capable of reversibly forming µ-oxo bridges with molecular oxygen. As a framework for chemical education, modular synthesis serves the role of reducing the barrier to entry in organic chemistry and enabling students to discover structure-function relationships with the assistance of data science tools. Across four courses, we’ve developed a sequence of activities that introduce students to fundamental techniques such as K-nearest neighbors, K-medoids clustering, modularization of target molecules to identify repeating bond-types, and optimization of molecular function by identifying high-performing building blocks. Students also get hands-on experience in the power of modular synthesis to perform a classic diazo synthesis, a modern Suzuki-Miyaura cross-coupling that leverages a general purification procedure that enabled the development of an automated small molecule synthesis platform, an aerobic Suzuki-Miyaura coupling that generates an organic photovoltaic candidate for them to characterize and compare to a ML model. At the end of the sequence as well as the end of this dissertation, Organic Chemistry II students were challenged to shatter the traditional research-education barrier by synthesizing a collection of kinase inhibitor candidates. One student was able to successfully synthesize a molecule that is not reported in the literature and that molecule is currently undergoing screening against over 80 cell lines in collaboration with the CELLerator platform at UIUC.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-12-01","The student, Nolan Green, accepted the attached license on 2025-07-18 at 09:30.","The student, Nolan Green, submitted this Dissertation for approval on 2025-07-18 at 09:33.","This Dissertation was approved for publication on 2025-07-28 at 09:27.","DSpace SAF Submission Ingestion Package generated from Vireo submission #22653 on 2026-02-19 at 20:07:49"],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/132721"],"dc:language":["en"],"dc:rights":["Copyright 2025 Nolan Green"],"dc:subject":["Modular synthesis, cooperative binding, chemical education"],"dc:title":["Modular synthesis for cooperative small molecule ligands and chemical education"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:07Z"}