Polymer-scaffolded dynamic combinatorial libraries

PhD ThesisThrough billions of years of evolution, nature has assembled a multitude of polymeric macromolecules capable of exquisite molecular recognition. This functionality is achieved by the precise control of amino acid sequence during the assembly of proteins, producing three-dimensional macromolecules with key residues anchored in the correct positions to interact with their targets. Developing ‘wholly-synthetic’ macromolecular analogues which mimic this function presents a considerable challenge to chemists, who lack the ‘biological machinery’ used by nature in the precision-assembly of polymers. In addressing this challenge, familiar chemical concepts, such as combinatorial methods and supramolecular interactions, have been adapted for application in the macromolecular arena. Working from a limited set of residues, synthetic macromolecules have been produced which display surprisingly high binding affinities towards target proteins, even possessing useful in vivo activities. These observations are all the more surprising when one considers the heterogeneity inherent within these synthetic macromolecular receptors, and provoke intriguing questions regarding our assumptions about the design of receptors

Glycomacromolecules: Addressing challenges in drug delivery and therapeutic development

Carbohydrate-based materials offer exciting opportunities for drug delivery. They present readily available, biocompatible components for the construction of macromolecular systems which can be loaded with cargo, and can enable targeting of a payload to particular cell types through carbohydrate recognition events established in biological systems. These systems can additionally be engineered to respond to environmental stimuli, enabling triggered release of payload, to encompass multiple modes of therapeutic action, or to simultaneously fulfil a secondary function such as enabling imaging of target tissue. Here, we will explore the use of glycomacromolecules to deliver therapeutic benefits to address key health challenges, and suggest future directions for development of next-generation systems

Cylindrical Zwitterionic Particles via Interpolyelectrolyte Complexation on Molecular Polymer Brushes

The fabrication of macromolecular architectures with high aspect ratio and well‐defined internal and external morphologies remains a challenge. The combination of template chemistry and self‐assembly concepts to construct peculiar polymer architectures via a bottom‐up approach is an emerging approach. In this study, a cylindrical template—namely a core–shell molecular polymer brush—and linear diblock copolymers (DBCP) associate to produce high aspect ratio polymer particles via interpolyelectrolyte complexation. Induced, morphological changes are studied using cryogenic transmission electron and atomic force microscopy, while the complexation is further followed by isothermal titration calorimetry and ξ‐potential measurements. Depending on the nature of the complexing DBCP, distinct morphological differences can be achieved. While polymers with a non‐ionic block lead to internal compartmentalization, polymers featuring zwitterionic domains lead to a wrapping of the brush template

Evidence of a common understanding of proximate and distal drivers of reef health

Marine management has typically prioritised natural science methodological traditions as an evidence base for decision-making; yet better integration of social science methods are increasingly shown to provide a more comprehensive picture to base management decisions. Specifically, perceptions-based assessments are gaining support, as they can provide efficient and holistic evaluation regarding management issues. This study focuses on coral reefs because they are particularly threatened ecosystems, due to their ecological complexity, socio-economic importance, and the range of environmental drivers that impact them. Research has largely concentrated on assessing proximate threats to coral reefs. Less attention has been given to distal drivers, such as socio-economic and governance factors. A common understanding of threats related to coral reef degradation is critical for integrated management that takes account of peoples’ concerns. This study compares perceptions of drivers of reef health among stakeholders (n = 110) across different sectors and governance levels, in four Caribbean countries. Interview data identified 37 proximate and 136 distal drivers, categorised into 27 themes. Five sub-groups of themes connecting proximate and distal drivers were identified. Perceptions of two of these narratives, relating to ‘fishing and socioeconomic issues’ and ‘reef management and coastal development’, differed among respondents from different countries and sectors respectively. However, the findings highlight a shared perception of many themes, with 18 of the 27 (67%) mentioned by > 25% of respondents. This paper highlights the application of perceptions data for marine management, demonstrating how knowledge of proximate and distal drivers can be applied to identify important issues at different context-specific scales

A Regenerable Biosensing Platform for Bacterial Toxins

Waterborne diarrheal diseases such as travelers’ diarrhea and cholera remain a threat to public health in many countries. Rapid diagnosis of an infectious disease is critical in preventing the escalation of a disease outbreak into an epidemic. Many of the diagnostic tools for infectious diseases employed today are time-consuming and require specialized laboratory settings and trained personnel. There is hence a pressing need for fit-for-purpose point-of-care diagnostic tools with emphasis in sensitivity, specificity, portability, and low cost. We report work toward thermally reversible biosensors for detection of the carbohydrate-binding domain of the Escherichia coli heat-labile enterotoxin (LTB), a toxin produced by enterotoxigenic E. coli strains, which causes travelers’ diarrhea. The biosensing platform is a hybrid of two materials, combining the optical properties of porous silicon (pSi) interferometric transducers and a thermoresponsive multivalent glycopolymer, to enable recognition of LTB. Analytical performance of our biosensors allows us to detect, using a label-free format, sub-micromolar concentrations of LTB in solution as low as 0.135 μM. Furthermore, our platform shows a temperature-mediated “catch-and-release” behavior, an exciting feature with potential for selective protein capture, multiple readouts, and regeneration of the sensor over consecutive cycles of use

Designing biodegradable alternatives to commodity polymers

The development and widespread adoption of commodity polymers changed societal landscapes on a global scale. Without the everyday materials used in packaging, textiles, construction and medicine, our lives would be unrecognisable. Through decades of use, however, the environmental impact of waste plastics has become grimly apparent, leading to sustained pressure from environmentalists, consumers and scientists to deliver replacement materials. The need to reduce the environmental impact of commodity polymers is beyond question, yet the reality of replacing these ubiquitous materials with sustainable alternatives is complex. In this tutorial review, we will explore the concepts of sustainable design and biodegradability, as applied to the design of synthetic polymers intended for use at scale. We will provide an overview of the potential biodegradation pathways available to polymers in different environments, and highlight the importance of considering these pathways when designing new materials. We will identify gaps in our collective understanding of the production, use and fate of biodegradable polymers: from identifying appropriate feedstock materials, to considering changes needed to production and recycling practices, and to improving our understanding of the environmental fate of the materials we produce. We will discuss the current standard methods for the determination of biodegradability, where lengthy experimental timescales often frustrate the development of new materials, and highlight the need to develop better tools and models to assess the degradation rate of polymers in different environments