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Mimicking nature's precision polymers and oligomers with aromatic amides

English title Mimicking nature's precision polymers and oligomers with aromatic amides
Applicant Kilbinger Andreas F. M.
Number 153037
Funding scheme Project funding (Div. I-III)
Research institution Département de Chimie Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Organic Chemistry
Start/End 01.10.2014 - 31.12.2017
Approved amount 420'000.00
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All Disciplines (2)

Discipline
Organic Chemistry
Material Sciences

Keywords (6)

solid supported synthesis; aramides; supramolecular chemistry; helices; polymers; template polymerization

Lay Summary (German)

Lead
Die Polymerchemie hat in den letzten 50 Jahren erhebliche Fortschritte gemacht. Für viele Polymerisationsmethoden kann man heute das Molekulargewicht der Polymere gut kontrollieren und auch die Abfolge der einzelnen Bausteine (Monomere) innerhalb der Polymerkette festlegen.Trotzdem ist es noch ein langer Weg von den heutigen Polymerisationsfähigkeiten der Synthesechemiker bis zur vollständigen Sequenzkontrolle, die uns die Natur vormacht. So kann der Synthesechemiker beispielsweise nur die Abfolge von ganzen Monomerblöcken festlegen (wobei die genaue Anzahl der Monomereinheiten innerhalb der Blöcke von Kette zu Kette noch stark variiert), die Natur hat es aber geschafft, die Abfolge jedes einzelnen Monomerbausteins ganz präzise zu kontrollieren. Dieses Projekt versucht neue synthetische Methoden der Sequenzkontrolle zu finden und für die Polymerchemie auszunutzen.
Lay summary

Die Natur als Vorbild für Präzisions-Oligomere und Polymere

Die Natur schafft es, Monomerbausteine in genau definierter Abfolge aneinander zu binden. Aus dieser hohen Präzision ergibt sich direkt eine grosse Vielfalt an Funktionalität. So kann die Natur z.B. mit nur wenigen Bausteinen (Aminosäuren) durch Variation der Sequenz eine sehr grosse Vielfalt von Materialien (Proteinen) herstellen, die so vielfältig sein können wie Spinnenfäden, Muskelgewebe oder ein Skorpiongift. 

In diesem Forschungsvorhaben versuchen wir einige Aspekte der von der Natur vorgemachten Kontrolle synthetisch zu übernehmen. In einem der beiden Teilprojekte  wollen wir kurze kettensteife Moleküle herstellen, die Nucleobasen in der Seitenkette tragen. Diese Verbindungen sollen es ermöglichen, durch Basenpaarung (ähnlich wie man es in der natürlichen DNA findet) als Template für entsprechende Monomerbausteine zu dienen und so eine sequenzkontrollierte Oligomerisierung zu ermöglichen. 

Im anderen Teilprojekt werden aus verschiedenen Monomerbausteinen (aromatische Aminosäuren) kurze Oligomere sequenzkontrolliert hergestellt und diese dann anschliessend mit etwas weniger Kontrolle polymerisiert. Dadurch, dass die im Polymer aufeinanderfolgenden Segmente selbst eine definierte Sequenz aufweisen, entstehen so lange Polymerketten, die sich in Lösung zu grossen Helices anordnen sollen. 

In beiden Teilprojekten steht daher die Monomer-Sequenzkontrolle im Mittelpunkt der Forschung. Die Realisierung dieser Sequenzkontrolle versuchen wir in Anlehnung an die von der Natur genutzten Methoden zu erreichen.

 

Direct link to Lay Summary Last update: 08.10.2014

Responsible applicant and co-applicants

Employees

Collaboration

Group / person Country
Types of collaboration
Prof. Dr. A. Fink / University of Fribourg, Switzerland Switzerland (Europe)
- Research Infrastructure
Dr. Tommaso Casalini Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
FriMat (Fribourg Center of Nanomaterials) Switzerland (Europe)
- Research Infrastructure

Associated projects

Number Title Start Funding scheme
182059 Synthesis of precision polymers 01.10.2019 Project funding (Div. I-III)
137774 Functional nanoscopic objects via polymerisation of sequence-controlled oligoaramides 01.10.2011 Project funding (Div. I-III)

Abstract

The aim of this research proposal is twofold: the first sub-project deals with new ways of synthesising well-defined sequence controlled oligomers. Here, the focus of the work is the development of a new synthetic strategy rather than exploiting an existing method to generate new materials. The second sub-project is a continuation of an ongoing SNSF funded research project and focuses on the synthesis of giant helices with tuneable inner diameter. Here, the focus lies on the preparation of large and potentially functional helices and existing techniques such as the Merrifield solid supported synthesis will be used to achieve partial sequence control within these polymers.Sub-project A: Solid supported non-covalent templation of oligomers - mimicking transcription and translationThis first sub-project aims at the important challenge of developing novel innovative synthetic pathways to precision macromolecules by the mimicry of vital aspects of natural protein synthesis. With a combination of classical solid supported synthesis and templated synthesis, we aim to prepare rigid rod-like molecules. These rod-like oligomers will carry natural nucleobases in their side chains, allowing the templated synthesis of their oligomeric complements. Taking our cue from nature, a fundamental advantage of this templation approach is that once the sequence information has been encoded, many copies can be prepared in a straightforward manner. This simplification in synthesis will be evaluated towards its molecular weight limits. This self-replication of the template simplifies the preparation of rigid rod-like molecules and allows the synthesis of monomer sequence and molecular weight controlled materials. Such shape persistent oligomers and polymers are believed to be important scaffold-like building blocks for the bottom-up construction of functional 2D and 3D structures on the nanoscopic scale. In addition, these rigid rod templates can be used to translate the encoded length and/or sequence control into other polymeric structures. For this purpose, structurally different monomers will be attached to the template via the complementary nucleobases. Under condensation/polymerisation conditions, these pre-aligned monomers will be linked to form an oligomer/polymer that follows the contour of the rigid rod-like template. The templated material which is attached to the template via hydrogen bonds can be cleaved from the template and the solid supported template reused for the next synthesis cycle. In this approach, it is important that the material used as the template can template the synthesis of itself. This allows the synthesis of larger amounts of sequence-controlled oligomers which in turn allows the construction of even longer and more complex templates. Finally, the supported templates can serve as the blueprint for the synthesis of other polymeric materials, mimicking the natural translation process. This sub-project aims at new macromolecular design strategies rather than the development of a particular application. However, once the fundamental synthetic procedures have been developed, a broad spectrum of applications will be accessible.Sub-project B: Synthesis of giant hollow helices - mimicking secondary structure formationThe second sub-project aims at preparing linear polymers that will fold into a helix exhibiting an inner void with a diameter determined by the primary structure, i.e. the sequence of monomers used. This sub-project is a continuation of a previous SNSF project (details see below). The proposed trigger to fold the linear pre-polymer into a helix has so far been the cleavage of an amide N-protecting group. This has been shown to lead to a conformational change from a cis to a trans amide bond and is expected to result in the transformation from a random linear coil to a defined helix. In order to achieve the helical shape, three-centre hydrogen bonds are exploited as additional non-covalent links between neighbouring monomer units. Significant progress has been made in the first funding period of this project and many synthetic challenges have been solved. Nonetheless, the helical polymeric material still remains elusive. This proposal therefore aims at a two-fold synthetic strategy to achieve this worthwhile goal: a continuation of the existing synthetic strategy is proposed that builds on the progress and the achievements obtained to date. The main limiting factors of this synthetic approach are the overall yields of the multi-step macromonomer syntheses. We believe that these can finally be significantly improved if the oligomers are prepared on solid support with an automated modified peptide synthesiser. This will give access to larger amounts of material and simplify purification. More time and effort can thus be spent on optimising the polymerization of the macromonomers to form helices.The second and new approach to large helices relies on an entirely different trigger. While the above helices form due to formation of stabilised three-centre hydrogen bonds regardless of the solvent polarity, the new strategy uses side chain amphiphilicity to direct the folding and the shape of the final structure. A synthetically less demanding monomer carrying either a hydrophobic or a hydrophilic side chain will be prepared. These will be condensed in a sequence controlled manner giving a linear (para-linked) oligomer with one defined angle or kink due to a meta-linked monomer unit. The polycondensation of these macromonomers will lead to an amphiphilic polymer which should fold into a helical shape if exposed to a hydrophilic or hydrophobic side chain selective solvent. This strategy approach is synthetically much less challenging but could also lead to the same class of helically shaped polymers with tuneable inner diameters. As larger amounts of macromonomers can be accessible more readily this approach can also be used to optimise the automated solid supported synthesis.
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