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Functional Cyclic Carbonate Monomers and Polycarbonates: Synthesis and Biomaterials Applications
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The present work describes a selection of strategies for the synthesis of functional aliphatic polycarbonates. Using an end-group functionalization strategy, a series of DNA-binding cationic poly(trimethylene carbonate)s was synthesized for application as vectors for non-viral gene delivery. As the end-group functionality was identical in all polymers, the differences observed in DNA binding and in vitro transfection studies were directly related to the length of the hydrophobic poly(trimethylene carbonate) backbone and the number of functional end-groups. This enabled the use of this polymer system to explore the effects of structural elements on the gene delivery ability of cationic polymers, revealing striking differences between different materials, related to functionality and cationic charge density.

In an effort to achieve more flexibility in the synthesis of functional polymers, polycarbonates were synthesized in which the functionalities were distributed along the polymer backbone. Through polymerization of a series of alkyl halide-functional six-membered cyclic carbonates, semicrystalline chloro- and bromo-functional homopolycarbonates were obtained. The tendency of the materials to form crystallites was related to the presence of alkyl as well as halide functionalities and ranged from polymers that crystallized from the melt to materials that only crystallized on precipitation from a solution. Semicrystallinity was also observed for random 1:1 copolymers of some of the monomers with trimethylene carbonate, suggesting a remarkable ability of repeating units originating from these monomers to form crystallites.

For the further synthesis of functional monomers and polymers, azide-functional cyclic carbonates were synthesized from the bromo-functional monomers. These were used as starting materials for the click synthesis of triazole-functional cyclic carbonate monomers through Cu(I)-catalyzed azide–alkyne cycloaddition. The click chemistry strategy proved to be a viable route to obtain structurally diverse monomers starting from a few azide-functional precursors. This paves the way for facile synthesis of a wide range of novel functional cyclic carbonate monomers and polycarbonates, limited only by the availability of suitable functional alkynes.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. , 73 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 911
Keyword [en]
DNA condensation, gene delivery, ionomers, polyplexes, self-assembly, amphiphiles, biodegradable, biological applications of polymers, transfection, cyclic carbonate monomers, polycarbonates, semicrystalline polymers, click chemistry, triazoles, cycloaddition
National Category
Organic Chemistry Polymer Chemistry Biochemistry and Molecular Biology
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-169677ISBN: 978-91-554-8310-4 (print)OAI: oai:DiVA.org:uu-169677DiVA: diva2:510531
Public defence
2012-05-04, Häggsalen, Ångströmlaboratoriet, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2012-04-13 Created: 2012-03-05 Last updated: 2012-04-19Bibliographically approved
List of papers
1. Efficient DNA Binding and Condensation Using Low Molecular Weight, Low Charge Density Cationic Polymer Amphiphiles
Open this publication in new window or tab >>Efficient DNA Binding and Condensation Using Low Molecular Weight, Low Charge Density Cationic Polymer Amphiphiles
2010 (English)In: Macromolecular rapid communications, ISSN 1022-1336, E-ISSN 1521-3927, Vol. 31, no 15, 1378-1382 p.Article in journal (Refereed) Published
Abstract [en]

A new class of biodegradable cationic macromolecules for DNA binding and condensation was developed by end-group-functionalization of poly(trimethylene carbonate). A series of one- and two-armed structures was synthesized and their interaction with DNA was evaluated. To aid data interpretation, a non-linear modeling method was applied to show efficient DNA binding that was intimately related to cationic charge density and macromolecular architecture. One-armed, low charge density structures were consistently found to bind to DNA at lower charge ratios than their two-armed, high charge density counterparts. This suggests that polymer backbone structure and characteristics are important considerations in the development of efficient cationic polymer systems for DNA condensation and delivery.

Keyword
DNA condensation, gene delivery, ionomers, polyplexes, self-assembly
National Category
Polymer Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-135391 (URN)10.1002/marc.201000141 (DOI)000280944700011 ()
Available from: 2010-12-07 Created: 2010-12-06 Last updated: 2017-12-11Bibliographically approved
2. Low Charge Density Cationic Polymers for Gene Delivery: Exploring the Influence of Structural Elements on In Vitro Transfection
Open this publication in new window or tab >>Low Charge Density Cationic Polymers for Gene Delivery: Exploring the Influence of Structural Elements on In Vitro Transfection
2012 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 12, no 6, 840-848 p.Article in journal (Refereed) Published
Abstract [en]

A series of end-functionalized poly(trimethylene carbonate) DNA carriers, characterized by low cationic charge density and pronounced hydrophobicity, was used to study structural effects on in vitro gene delivery. As the DNA-binding moieties were identical in all polymer structures, the differences observed between the different polymers were directly related to the functionality and length of the polymer backbone. The transfection efficiency and cytotoxicity of the polymer/DNA complexes were thus found to be dependent on a combination of polymer charge density and functionality, highlighting the importance of such structural considerations in the development of materials for efficient gene delivery.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2012
Keyword
amphiphiles, biodegradable, biological applications of polymers, gene delivery, transfection
National Category
Polymer Chemistry Biochemistry and Molecular Biology
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-169673 (URN)10.1002/mabi.201100480 (DOI)000304711200014 ()
Available from: 2012-03-05 Created: 2012-03-05 Last updated: 2017-12-07Bibliographically approved
3. Synthesis and polymerization of alkyl halide-functional cyclic carbonates
Open this publication in new window or tab >>Synthesis and polymerization of alkyl halide-functional cyclic carbonates
2011 (English)In: Polymer, ISSN 0032-3861, E-ISSN 1873-2291, Vol. 52, no 25, 5716-5722 p.Article in journal (Refereed) Published
Abstract [en]

To increase the diversity in functional aliphatic polycarbonates, a series of novel chloro- and bromo-functional six-membered cyclic carbonate monomers were synthesized. Despite asymmetry in the monomer functionalities, homopolymerization of the monomers afforded semicrystalline polycarbonates with a high tendency to crystallize from the melt and/or on precipitation from a THF solution. Melting points were found in the 90-105 degrees C or 120-155 degrees C range for polymers comprising methyl or ethyl moieties, respectively, in the backbone. The monomers were further copolymerized with trimethylene carbonate to form random copolymers. Even among some of these random copolymers elements of semicrystallinity were found as confirmed by melting endotherms in DSC. The results clearly show that the incorporation of alkyl halide functionalities in aliphatic polycarbonates may lead to materials with a high ability to form crystallites, even in random copolymers, likely driven by polar interactions due to the presence of the halide functionalities.

Keyword
Cyclic carbonate monomers, Polycarbonates, Semicrystalline polymers
National Category
Chemical Sciences Polymer Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-165694 (URN)10.1016/j.polymer.2011.10.027 (DOI)000297539000004 ()
Available from: 2012-01-10 Created: 2012-01-09 Last updated: 2017-12-08Bibliographically approved
4. Diversity in cyclic carbonates: Synthesis of triazole-functional monomers using click chemistry
Open this publication in new window or tab >>Diversity in cyclic carbonates: Synthesis of triazole-functional monomers using click chemistry
2012 (English)In: Polymer Chemistry, ISSN 1759-9962, Vol. 3, no 6, 1399-1401 p.Article in journal (Refereed) Published
Abstract [en]

Triazole-functional cyclic carbonates are presented as a new class of functional monomers for ring-opening polymerisation. Starting from bromo-functional six-membered cyclic carbonates, a series of triazole-functional monomers was synthesised using click chemistry. This synthetic strategy allows for facile synthesis of a great number of structurally diverse monomers from just a few azide-functional precursors.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2012
National Category
Polymer Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-169676 (URN)10.1039/C2PY20152F (DOI)000303773600005 ()
Available from: 2012-03-13 Created: 2012-03-05 Last updated: 2013-01-08Bibliographically approved

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