Triazine‐Based Sequence‐Defined Polymers with Side‐Chain Diversity and Backbone–Backbone Interaction Motifs

Abstract

Sequence control in polymers,well-known in nature, encodes structure and functionality.H ere we introduce an ew architecture,b ased on the nucleophilic aromatic substitution chemistry of cyanuric chloride,t hat creates an ew class of sequence-defined polymers dubbed TZPs.Proof of concept is demonstrated with two synthesized hexamers,h aving neutral and ionizable side chains.M olecular dynamics simulations show backbone-backbone interactions,i ncluding H-bonding motifs and pi-pi interactions.T his architecture is arguably biomimetic while differing from sequence-defined polymers having peptide bonds.The synthetic methodology supports the structural diversity of side chains knowninpeptides,aswell as backbone-backbone hydrogen-bonding motifs,a nd will thus enable new macromolecules and materials with useful functions.Sequence control in synthetic polymers has gained renewed interest, [1] because sequence leads to structure and function. Sequence-controlled polymers have repeated sequence motifs (e.g.,( ABC)n)w hereas sequence-defined polymers have monomers in any predetermined order (e.g.ABCADC). Thel atter polymers are epitomized by natural biopolymers such as polypeptides and poly(nucleic acids), where pendant side chains distinguish one monomer from another. In polypeptides,t he sequencing leads to diverse structures and functions that are vital to life,i ncluding material architectures,b iocatalysis,m olecular recognition, and transport across membranes.S equence in polymers was discussed in acritical review by Lutz et al. in 2013, including discussions of relevance to materials science.[1b] Some sequence-defined oligomers and polymers fold into conformational structures such as helices,and hence are called "foldamers", which have potential applications in materials science,c atalysis,a nd molecular recognition. [2] Construction of synthetic poly(peptides) using biomolecular machinery,solution synthesis,orsolid-phase synthesis,is well-established.[1b] Synthetic sequence-defined polymers typically have monomers selected from natural and unnatural alpha-amino acids,non-alpha-amino acids,and pseudo-amino acids.Peptoids have amide bonds in the backbone where the side chains are attached to an itrogen atom instead of ac arbon atom, prepared by the solid-phase submonomer synthesis approach without using amino acid monomers or protecting groups.[3] Until recently,m ost synthetic sequencedefined polymers have as imilarity to polypeptides by virtue of having amide bonds.With resurgent interest in sequence-controlled and sequence-defined polymers,a dditional bond-forming reactions are being implemented to create new polymer architectures [1g-r] Lutz et al. described alternating cycloaddition and amidation reactions in 2009 to create (AB) n sequencecontrolled polymer segments.[1h] This group employed the same or similar strategies 2014 and 2105 to design sequencedefined oligomers that encode digital information.[1i-l] The sequencing could be decoded with tandem mass spectrometry. [1k, l] In 2013, Madder et al. ...

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

“…Directly inspired by biologically accessible DNA systems—for example, nucleobase-coded chains—sequence-defined macromolecules have been synthesized employing template-based coding strategies26272829 or via the generation of regulated sequence alternating thymine hybrid polymers30, as well as the design of reactions with iterative protection/deprotection steps on supports3132. Further, bulk reactions have been conducted in flow systems based on iterative synthesis33.…”

Synthesis of New S-Triazine Bishydrazino and Bishydrazido-Based Polymers and Their Application in Flame-Retardant Polypropylene Composites

“…Materials having a heterocyclic moiety such as a s-triazine ring in their backbone chain have acquired special attention as a result of the significant influence on the end-product properties [12][13][14]. The sophisticated structure of the s-triazine ring as well as the exceptional reactivity of the starting material cyanuric chloride (TCT) has been employed as a basic core for preparation of an enormous number of derivatives, as a result of its commercial accessibility and the three chlorine atoms can be exchanged by distinct nucleophiles with the control of temperature that make it valuable in material [15][16][17][18][19][20][21] and industrial applications [22][23][24][25]. Recently, many scientists reported that polymer-based s-triazine has been used in the design and advancement of fire-retardant derivatives [26][27][28], metal adsorption [29], carbon dioxide capture [30][31][32] and covalent organic frameworks [24,25,28].…”

Multifunctional Homopolymers: Postpolymerization Modification via Sequential Nucleophilic Aromatic Substitution

“…In search of potential strategies to facilitate the synthesis of multifunctional homopolymers, we decided to explore the utility of 2,4,6-trichloro-1,3,5-triazine (TCT) for installing two reactive groups onto polymers for subsequent functionalization via straightforward nucleophilic aromatic substitution. Simanek and co-workers have extensively studied TCT for dendrimer synthesis, − and the compound has also been employed in a number of other ways, including as immobilized reagents, nucleophile scavengers, PET imaging probes, targeting conjugates, porous materials, and sequence-defined polymers . TCT undergoes sequential nucleophilic aromatic substitution reactions at increasing temperatures because each substitution step decreases the reactivity of the triazine ring through loss of σ-bond electron withdrawal of a chlorine atom and gain of π-orbital electronic donation of added nucleophiles .…”

“…Simanek and co-workers have extensively studied TCT for dendrimer synthesis, 41−48 and the compound has also been employed in a number of other ways, including as immobilized reagents, 49 nucleophile scavengers, 50 PET imaging probes, 51 targeting conjugates, 52 porous materials, 53 and sequence-defined polymers. 54 TCT undergoes sequential nucleophilic aromatic substitution reactions at increasing temperatures because each substitution step decreases the reactivity of the triazine ring through loss of σ-bond electron withdrawal of a chlorine atom and gain of π-orbital electronic donation of added nucleophiles. 55 TCT's controlled electrophilicity thus allows chemoselective and sequential functionalization that parallels previous multifunctional polymer synthesis techniques, yet can accommodate a broad scope of readily available nucleophiles.…”