Catalytic strategies for the synthesis of environmentally-responsive poly(aminoesters) : applications for the delivery of messenger RNA
Abstract/Contents
- Abstract
- Polyesters are a remarkable class of polymeric materials that have been featured as biodegradable textiles, implantable biomedical devices, and drug delivery vehicles for therapeutic applications. However, the synthesis of polyesters with rich functional group diversity, narrow molecular weight distributions and targeted molecular weighs remains a significant challenge. The selective aerobic oxidation of 1,5-diols with [(neocuproine)Pd(OAc)]2(OTf)2 (neocuproine = 1,9-dimethylphenanthroline), A, yields cyclic lactones. A selection of functionalized 1,5-diols was investigated to explore the substrate scope and to determine compatible functional groups for the oxidative lactonization reaction using A. These studies led a general strategy for the synthesis of functionalized lactones, specifically N-substituted morpholin-2-ones. The organocatalytic ring-opening polymerization of N-acyl morpholin-2-ones occurs readily to generate functionalized poly(aminoesters) with N-acylated amines in the polyester backbone. The thermodynamics of the ring-opening polymerization depends sensitively on the hybridization of the nitrogen of the heterocyclic lactone. N-Acyl morpholin-2-ones polymerize readily to generate polymorpholinones, but the N-aryl or N-alkyl substituted morpholin-2-ones do not polymerize. Experimental and theoretical studies reveal that the thermodynamics of ring opening correlates to the degree of pyramidalization of the endocyclic N-atom. A wide range of novel polyesters was synthesized. Deprotection of the N-Boc protected polyaminoesters yields water-soluble, cationic materials. Three novel cationic water-soluble polyaminoesters (PAEs) were synthesized. These materials were shown to be stable in neutral D2O for over two days, however, upon exposure to alkaline or buffered conditions, two of the PAEs degraded rapidly and quantitatively to single small molecule products. An immolative mechanism is proposed to account for the exquisite selectivity of the observed in the controlled degradation. The rate of degradation is sensitive to pH, providing a new class of water-soluble materials which can be induced to degrade under specific environmental conditions.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Blake, Timothy R |
|---|---|
| Associated with | Stanford University, Department of Chemistry. |
| Primary advisor | Waymouth, Robert M |
| Thesis advisor | Waymouth, Robert M |
| Thesis advisor | Kool, Eric T |
| Thesis advisor | Xia, Yan |
| Advisor | Kool, Eric T |
| Advisor | Xia, Yan |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Timothy R. Blake. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Timothy Ray Blake
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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