Photo-induced sequence defined macromolecules via hetero bifunctional synthons

Abstract

We report the first photochemical protocol for the generation of sequence defined macromolecules employing two hetero bifunctional photoreactive synthons, exploiting the orthogonal nature of photochemical - via the use of caged dienes - and thermally driven ligation protocols. We demonstrate that the iterative alternating synthon addition to an initial bifunctional core under irradiation at ambient temperature enables the generation of a macromolecule with up to 10 units (M = 3231.58 g mol(-1), Đ = 1.00). The resulting macromolecules are monodisperse and feature absolute chain end fidelity. The unit-by-unit construction of the macromolecule is evidenced by Nuclear Magnetic Resonance Spectroscopy, Electrospray Ionization Mass Spectrometry and Size Exclusion Chromatography. The fundamental principle demonstrated herein paves the way for employing photochemical strategies for the design of sequence defined polymers.

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

“…1a), in which each monomer carries a photoreactive benzaldehyde function as well as an ene functionality required for the photochemically induced Diels–Alder reaction. Contrary to our previous report—which employed two monomer types with separate diene and dienophile functions53—the herein presented monomers entail a dual diene/dienophile character. For example, monomer 1 (denoted M 1 ) includes on the one hand the benzaldehyde moiety reacting as diene under ultraviolet irradiation from its ortho -quinodimethane state and on the other hand a furan-protected maleimide.…”

“…Herein, we demonstrate how highly efficient photochemical reactions combined with a simple macromolecular design concept can lead to functional sequence-defined linear macromolecules. To achieve this diversity, we built on our initial approach for photochemical sequence control53, simplifying the concept while concomitantly showing its power to generate an entire sequence-defined polymer library. The simplicity and versatility of the photoreactions are such that the sequence order and functionality within the chains can be arbitrarily varied.…”

Dual side chain control in the synthesis of novel sequence-defined oligomers through the Ugi four-component reaction

“…Recently, other protocols for the stepwise synthesis of sequence-defined polymers were reported making use of orthogonal reactions providing sequence-defined macromolecules by the iterative application of Michael additions 40 and aminolysis reactions, 24 azide-alkyne cycloadditions and amidifications, 25 or photochemical couplings and retro Diels-Alder reactions. 26 Our group focusses on the use of multicomponent reactions to achieve sequence control. 27 The iterative application of the Passerini three-component reaction 45 (P-3CR) and the thiol-ene addition reaction enabled the introduction of different moieties at defined positions within the macromolecules without the need of protecting groups or activating agents.…”

Efficiency assessment of single unit monomer insertion reactions for monomer sequence control: kinetic simulations and experimental observations

“…1b). Note that the addition of the monomer to the radical fragment R-M • was considered to proceed with k p (2) k p (1) 770 000 L mol −1 s −1 k p (2) 420 000 L mol −1 s −1 k p (3) 245 000 L mol −1 s −1 k p (4) 157 500 L mol −1 s −1 k p (5) 113 750 L mol −1 s −1 k p (6) 91 875 L mol −1 s −1 k p (∞) 70 000 L mol −1 s −1 theoretical yield of 56% (at exactly x = 0.33, note that the absolute maximum is reached slightly above this monomer conversion) is obtained for the desired SUMI-2AB. 1b nicely demonstrate that chainlength effects must clearly play a role in the SUMI reactions when comparing these results with the experimentally derived theoretical yields (see below).…”