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Abstract: Deep eutectic solvents (DESs) have emerged as powerful environments to enhance enzymatic reactions, formulate therapeutic proteins, and develop protein-based biomaterials. Despite the wide range of properties that could be achievable through the compositional design of DESs, protein solubilization only happens in a relatively narrow range of hydrophilic DESs. Here, we use surface-modification for the generalized solubilization of proteins in both hydrophilic and hydrophobic DESs. Using surface-modified myoglobin as a model, we show that both DES polarity and hydrogen bond capacity play important roles in dictating the conformational state of the protein. In the hydrophilic DES the protein displays a near-native conformation with an improvement of the thermal stability of + 28 °C compared to aqueous solutions. In contrast, hydrophobic DESs stabilize partially folded intermediates which can refold from temperatures as high as 190 °C. As such, our approach provides a platform to generalize protein incorporation into anhydrous DESs that could be exploited in biocatalysis, biomolecule stabilization, and biomaterials.

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Abstract: Cellulose, a major structural component of plant cell walls, is a renewable biopolymer known for its mechanical strength and chemical versatility. Traditionally used in the paper and textile industries, it is now drawing increasing attention for applications in emerging fields such as bioplastics, pharmaceuticals, optics, and nanotechnology. This thesis aims to summarize research on the chemical modification of both cellulose fibers and cellulose nanocrystals (CNCs), highlighting how tailored modifications can produce materials with distinct properties and diverse applications. The modification of softwood based bleached kraft pulp (BKP) was made through the esterification of the hydroxyl groups found on the cellulose fibers using itaconic anhydride. Two methods were explored, mechanical kneading and gas-phase reactions, both gaining BKP-itaconate. The fibers were characterized by a variety of techniques, including Fourier transformed infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), titrations, powder X-ray diffraction (PXRD) and water absorption. Manuscript I explores fiber modification relative to chemical composition but also fiber confirmation and material properties. CNCs were studied in relation to the counterions and conjugation of azetidinium salts (Az-salts) to the sulfate groups. Paper II investigated the influence of different counter ions and sample preparation, i.e. sonication and drying temperature, on the CNCs alignment in films, visualizing their chiral nematic structures with polarized optical microscopy (POM) and UV-Vis. Paper III investigated the effects of Az-salts, the effective introduction of alkyl chains to the CNC surfaces, in relation to the rheological properties of the CNC suspensions. Additional work conducted at the B23-Beamline at Diamon Light source (UK) is presented, where Mueller Matrix Polarimetry (MMP) was used to understand the structuring and aggregation of CNCs in films depending on different additives.

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Abstract: A Capillary Zone Electrophoresis (CZE) fragment screening methodology was developed and applied to the human plasma protein Transthyretin (TTR), normally soluble, but could misfold and aggregate, causing amyloidosis. Termed Free Probe Peak Height Restoration (FPPHR), it monitors changes in the level of free ligand known to bind TTR (the Probe Ligand) in the presence of competing fragments. 129 fragments were screened, 12 of the 16 initial hits (12.4% hit rate) were co-crystallised with TTR, 11 were found at the binding site (92% confirmation rate). Subsequent analogue screens have identified a novel TTR-binding scaffold 4-(3H-pyrazol-4-yl)quinoline and its derived compounds were further studied by crystallography, circular dichroism (CD), isothermal titration calorimetry (ITC) and radiolabelled 125I-Thyroxine displacement assay in neat plasma. Two lead molecules had similar ITC Kd and 125I-Thyroxine displacement IC50 values to that of Tafamidis, adding another potential pipeline for transthyretin amyloidosis. The methodology is reproducible, procedurally simple, automatable, label-free without target immobilisation, non-fluorescence based and site-specific with low false positive rate, which could be applicable to fragment screening of many drug targets.

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Abstract: The ability to synthesise lemniscular molecules to allow for the study and application of their chiroptical properties is a notable technical challenge. Herein, we report the design and synthesis of enantiomers of a [5]helicenoid derived molecular lemniscate, in which two homochiral helicenes are linked via the formation of two azine motifs. We demonstrate that these molecules, and their helicenoid constituents, are also excellent chiral dopants that induce dissymmetry in the ground and excited states of the achiral emissive polymer F8BT, leading to high CPL activity. The ability to control the handedness of the helicenoid dopants via enantiopure synthesis affords control of the sign of CP emission. This manipulation of circularly polarised light is of great interest for optoelectronic technologies.

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Abstract: The development of chiral organic materials with strong non-reciprocal chiroptical features may have major implications for cutting-edge technological applications. In this work, a new ad hoc synthesized chiral 1,4-diketo-3,6-dithienylpyrrolo[3,4-c]pyrrole dye, bearing two (S)-3,7-dimethyl-1-octyl alkyl chains on the lactam moieties and functionalized with two lateral 9-anthracenyl π-conjugated units, exhibited strong non-reciprocal chiroptical properties in thin films, with some important differences between samples prepared by drop casting and spin coating. A detailed study was performed to unravel the intimate structure–property relationship, involving computational analysis, different microscopy techniques and synchrotron radiation Mueller matrix polarimetry imaging (SR-MMPi) investigation. Through SR-MMPi, exploiting the highly collimated synchrotron radiation (SR) light of Diamond Light Source B23 beamline, we determined the size of the linear contributions responsible for the strong non-reciprocal features, and how they manifest in the various 2D chiral meso-domains.