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A Track-Based Molecular Synthesizer that Builds a Single-Sequence Oligomer through Iterative Carbon-Carbon Bond Formation

Research output: Contribution to journalArticlepeer-review

Charlie T. McTernan, Guillaume De Bo, David A. Leigh

Original languageEnglish
Pages (from-to)2964-2973
Number of pages10
JournalChem
Volume6
Issue number11
DOIs
Published5 Nov 2020

Bibliographical note

Funding Information: We thank the Engineering and Physical Sciences Research Council (EPSRC; EP/P027067/1), the European Research Council (ERC Advanced grant to D.A.L. 786630) and East China Normal University for funding, and the University of Manchester Mass Spectrometry Service Centre for high-resolution mass spectrometry. C.T.M. thanks the Leverhulme Trust and the Isaac Newton Trust, and Sidney Sussex College, Cambridge, for Fellowship support during the preparation of the manuscript. G.D.B. is a Royal Society University Research Fellow; D.A.L. is a Royal Society Research Professor. C.T.M. and G.D.B. planned the work. C.T.M. carried out the experiments and analyzed the data. D.A.L. directed the research. All authors contributed to the design of the project and the writing of the manuscript. The authors declare no competing interests. Funding Information: We thank the Engineering and Physical Sciences Research Council (EPSRC; EP/P027067/1 ), the European Research Council (ERC Advanced grant to D.A.L., 786630 ) and East China Normal University for funding, and the University of Manchester Mass Spectrometry Service Centre for high-resolution mass spectrometry. C.T.M. thanks the Leverhulme Trust and the Isaac Newton Trust, and Sidney Sussex College, Cambridge, for Fellowship support during the preparation of the manuscript. G.D.B. is a Royal Society University Research Fellow; D.A.L. is a Royal Society Research Professor. Publisher Copyright: © 2020 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

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Abstract

We report an artificial molecular machine that moves along a track, iteratively joining building blocks to form an oligomer of single sequence with a continuous backbone of carbon-carbon bonds. The rotaxane features a macrocycle bearing an aldehyde-terminated chain and an axle containing different phosphonium ylides separated by rigid spacers. Each ylide is large enough to block the passage of the macrocycle, trapping the ring between the stopper at the terminus of original threading and the next ylide along the track. Once a building block is reachable, it is removed from the track through a Wittig reaction that adds it to the terminus of the growing chain. Operation on a four-barrier tetra(phosphonium salt) track produces a tetra(diphenylpropane) of single sequence linked through alkene bonds. The prototype extends the principle for molecular machines that build polymers by moving along tracks to the synthesis of sequence-encoded chains with continuous carbon backbones. Sequence is crucial in the molecular world. Proteins are built from a common set of 20 amino acids, but different sequences afford materials as diverse as snake venom, muscle, and spider silk. However, the synthesis of artificial sequence polymers remains challenging. Biology uses molecular machines (e.g., ribosomes) for such tasks, inspiring the invention of artificial systems that move along tracks, picking off and joining building blocks in sequence. To date, such small-molecule machines have used amide formation to join building blocks, the same bonds the ribosome uses to make peptides. Here, we report on the design, synthesis, and operation of a track-based molecular machine that assembles a single-sequence oligomer with a continuous backbone of carbon-carbon bonds. This new class of de novo molecular synthesizer utilizes chemistry and reactivity patterns unavailable to biological machines. The long-term goal is for such molecular assemblers to ultimately be able to play significant roles in molecular construction. Molecular machines, such as ribosomes, are ubiquitous in biology. These natural systems are inspiring artificial systems that move along tracks, picking off and joining building blocks in sequence. To date, such small-molecule machines have used amide formation to connect building blocks, much like the ribosome. Here, the design, synthesis, and operation of a track-based molecular machine that iteratively forms a continuous backbone of carbon-carbon bonds is described. This new class of de novo molecular synthesizer utilizes chemistry and reactivity patterns unavailable to biological machines.

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