Non-Classical Reaction Behavior of Complex Molecular Systems Based on Coupled Assembly Processes
Complex molecular systems are key for device miniaturization, development of energy materials and efforts to mimic biological processes.1-3 Self-assembly, the power of molecules to autonomously form defined aggregates, is a key player in the emergence of complexity in molecular systems. Yet, the construction of such systems is not easy. Inspired by total synthesis in organic chemistry, a paradigm shift from one-step assembly to multi-step non-covalent synthesis was proposed: Complex molecular systems are not obtained in a single non-covalent assembly step, but rather in a combination of covalent and non-covalent reaction steps.4 This raises the question how to perform covalent organic reactions in combination with supramolecular structures. This is challenging because supramolecular structures are often assembled by weak forces, in continuous dynamic exchange and are highly sensitive to environmental changes.1-5 Thus, supramolecular substrates are difficult targets for common organic syntheses. Alike small details that drive the unrepeatable crystallization of a desired polymorph or a sudden drop in reactivity of a catalyst from a different source, recently also supramolecular chemistry reached a level of complexity in which underappreciated subtleties can have an unexpected major impact on a system.
Here, we study the reaction behavior of a system in which the in-situ formation of discotic 1,3,5-benzenetricarboxamide (BTA) monomers is linked to an intertwined non-covalent reaction network including self-assembly into helical BTA polymers. This system shows an unexpected phase-separation behavior in which a complex interplay of reactant/product concentrations, site-products and solvent purity determines the system composition. These insights allow us to offer a guide on how to design the synthesis of new materials in a covalent/non-covalent fashion. We suspect that the non-classical reaction behavior observed in our simple model system might also play a role in biological reaction networks, providing an additional – yet underappreciated – level of complexity in reaction networks of living systems.
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 T. Schnitzer, M. F. J. Mabesoone, S. A. H. Jansen, G. Vantomme, E. W. Meijer, manuscript submitted.