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Abstract: The emergence of multidrug-resistant (MDR) bacterial pathogens is an alarming global health threat that demands new therapeutic strategies beyond conventional antibiotics. Here, we present a rationally designed antimicrobial peptide (AMP) derived from mammalian cathelicidins and defensins that selectively targets bacterial membranes with low cytotoxicity toward mammalian cells. Circular dichroism spectroscopy revealed that the peptide adopts an α-helical conformation upon membrane interaction, a key feature of its mechanism. Surface plasmon resonance and isothermal titration calorimetry demonstrated high-affinity and selective binding to bacterial lipid membranes. Functionally, the peptide was strongly bactericidal against clinical MDR Escherichia coli (E. coli) and clinically important ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.). Compared with the parent peptide LL-37, our AMP exhibited lower minimum inhibitory concentrations (MICs) and faster bactericidal kinetics across both Gram-negative and Gram-positive strains. Calcein leakage assays, showing effective membrane disruption. Importantly, cytotoxicity experiments with human epithelial (Caco-2) and immune (THP-1) cells indicated low cytotoxicity at concentrations exceeding bactericidal levels, supporting a favorable therapeutic window. ELISA quantifications of cytokines (IL-6, TNF-α) further suggested immunomodulatory effects at bactericidal concentrations. Transcriptomic profiling of E. coli treated with sub-lethal concentrations of the peptide exhibited upregulation of bacterial stress response pathways and downregulation of vital metabolic processes, reflecting the complex antimicrobial action of the peptide. Collectively, these findings highlight this LL-37-derived AMP as a promising candidate for treating MDR bacterial infections caused by E. coli and ESKAPE pathogens and for guiding the development of next-generation antimicrobial agents.

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Abstract: Conventional electronic circular dichroism (ECD) spectroscopy fails when it comes to distinguishing chiral compounds with identical or nearly similar spectra. But what if we could harness solid-state anisotropy to break this limitation? In this article, it is demonstrated how CD anisotropy (CDA) uncovers critical differences between two well-known packing polymorphs of finasteride despite their nearly similar pellet ECD spectra. Using ECD imaging (ECDi) and TDDFT-simulated spectra from X-ray structures, it is shown that the second polymorphic form exhibits a unique CDA signature, setting it apart from the first polymorphic form. This proof-of-concept study paves the way for a new strategy to differentiate chiral solid-state systems that conventional methods might struggle to resolve.

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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: We investigate two unusual phenomena in self-assembly of anisotropic molecules from isotropic (Iso) melt: a heat-capacity (Cp) maximum, and spontaneous formation of the recently discovered chiral liquid (Iso*). Based on experiments on new non-chiral monomers, dimers and polymers, we construct a statistical theory that shows why many complex mesostructures form in two stages: continuous equilibrium growth of nano-clusters in melt through strong interactions, causing the Cp-maximum, followed by establishment of positional long-range order (LRO) through a weak first-order transition. We also show why many achiral compounds additionally form an intermediate chiral Iso* liquid through what we find is a second-order transition. We propose that the first process is equivalent to “supramolecular polymerization” in solutions, where the lack of inter-cluster interaction rules out LRO. Furthermore, we argue that separation into a broad and a sharp transition is universal in condensed matter where strong interactions by themselves cannot lead to LRO, either because the clusters are 1D or due to strong frustration. Clusters must first grow to critical size when, at Tc, the combined weak interactions reach ~kBTc, prompting LRO formation. A situation similar to that in soft self-assembly is seen in spin ordering in magnetic crystals, but only near 0 K.

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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.