Multifunctionalized Sequence‐Defined Oligomers from a Single Building Block

Espeel, Pieter; Carrette, Lieselot L. G.; Bury, Katarzyna; Capenberghs, Sven; Martins, José; Prez, Filip Du; Madder, Annemieke

doi:10.1002/anie.201307439

Cited by 198 publications

(135 citation statements)

References 59 publications

(23 reference statements)

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“…In parallel, strategies involving the consecutive insertion of single monomer units (vinyl or acrylate) based on radical processes started to emerge for the synthesis of sequence-defined polymers3738. Further, notable synthetic strategies towards sequence-defined polymers conducted in bulk include the use of thiolactones394041 and multi-component reactions424344. Concomitant to the development of new synthetic approaches to sequence-defined polymers, selected applications of such molecules are emerging, for example, bio-inspired structures for which high sequence definition is essential4546.…”

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confidence: 99%

Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

et al. 2016

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Designing artificial macromolecules with absolute sequence order represents a considerable challenge. Here we report an advanced light-induced avenue to monodisperse sequence-defined functional linear macromolecules up to decamers via a unique photochemical approach. The versatility of the synthetic strategy—combining sequential and modular concepts—enables the synthesis of perfect macromolecules varying in chemical constitution and topology. Specific functions are placed at arbitrary positions along the chain via the successive addition of monomer units and blocks, leading to a library of functional homopolymers, alternating copolymers and block copolymers. The in-depth characterization of each sequence-defined chain confirms the precision nature of the macromolecules. Decoding of the functional information contained in the molecular structure is achieved via tandem mass spectrometry without recourse to their synthetic history, showing that the sequence information can be read. We submit that the presented photochemical strategy is a viable and advanced concept for coding individual monomer units along a macromolecular chain.

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Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

et al. 2016

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“…Thus, various approaches have been recently proposed to simplify multistep growth processes. [24][25][26][27][28][29][30] In addition, biochemical methodologies, which have been developed and optimized for bio-oligomer synthesis, can be adapted for the preparation of non-natural sequence-defined polymers. 1 For example, Fmoc-based protocols that were initially introduced for solid-phase peptide chemistry have been extensively studied for the preparation of synthetic oligomers.…”

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confidence: 99%

Synthesis of Non-Natural Sequence-Encoded Polymers Using Phosphoramidite Chemistry

2015

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Sequence-defined non-natural polyphosphates were prepared using iterative phosphoramidite protocols on a polystyrene solid support. Three monomers were used in this work: 2-cyanoethyl (3-dimethoxytrityloxy-propyl) diisopropylphosphoramidite (0), 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dimethyl-propyl) diisopropylphosphoramidite (1), and 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dipropargyl-propyl) diisopropylphosphoramidite (1'). Phosphoramidite coupling steps allowed rapid synthesis of homopolymers and copolymers. In particular, the comonomers (0, 1), (0, 1'), and (1, 1') were used to synthesize sequence-encoded copolymers. It was found that long encoded sequences could be easily built using phosphoramidite chemistry. ESI-HRMS, MALDI-HRMS, NMR, and size exclusion chromatography analyses indicated the formation of monodisperse polymers with controlled comonomer sequences. The polymers obtained with the comonomers (0, 1') and (1, 1') were also modified by copper-catalyzed azide-alkyne cycloaddition with a model azide compound, namely 11-azido-3,6,9-trioxaundecan-1-amine. (1)H and (13)C NMR analysis evidenced quantitative modification of the alkyne side-chains of the monodisperse copolymers. Thus, the molecular structure of the coding monomer units can be easily varied after polymerization. Altogether, the present results open up interesting avenues for the design of information-containing macromolecules.

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“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] The biomedical importance of thiolactones is predominantly due to the homocysteinilation of proteins, which is an important risk factor in the study of vascular diseases, such as atherosclerosis. 26 Homocysteinilation occurs when homocysteine thiolactone, a cyclic thioester of the non-protein α-amino acid homocysteine, reacts with the ε-amine group of lysine residues.…”

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confidence: 99%

Computational Study and Kinetic Analysis of the Aminolysis of Thiolactones

et al. 2015

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The aminolysis of three differently α-substituted γ-thiolactones (C4H5OSX, X = H, NH2, and NH(CO)CH3) is modeled based on CBS-QB3 calculated free energies corrected for solvation using COSMO-RS. For the first time, quantitative kinetic and thermodynamic data are provided for the concerted path and the stepwise path over a neutral tetrahedral intermediate. These paths can take place via an unassisted, an amine-assisted, or a thiol-assisted mechanism. Amine assistance lowers the free energy barriers along both paths, while thiol assistance only lowers the formation of the neutral tetrahedral intermediate. Based on the ab initio calculated rate coefficients, a kinetic model is constructed that is able to reliably describe experimental observations for the aminolysis of N-acetyl-dl-homocysteine thiolactone with n-butylamine in THF and CHCl3. Reaction path analysis shows that for all conditions relevant for applications in polymer synthesis and postpolymer modification, an assisted stepwise mechanism is operative in which the formation of the neutral tetrahedral intermediate is rate-determining and which is mainly amine-assisted at low conversions and thiol-assisted at high conversions.

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Multifunctionalized Sequence‐Defined Oligomers from a Single Building Block

Cited by 198 publications

References 59 publications

Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

Synthesis of Non-Natural Sequence-Encoded Polymers Using Phosphoramidite Chemistry

Computational Study and Kinetic Analysis of the Aminolysis of Thiolactones

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