Modular synthesis for cooperative small molecule ligands and chemical education
type: CreativeWork
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 coupli…
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 coupli…
author: Green, Nolan Michael
language: en
keywords: Modular synthesis, cooperative binding, chemical education
date published: 2025-12
date modified: 2026-07-22T22:25:07Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois Urbana-Champaign

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2142/132721