B23-Circular Dichroism
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Diamond Proposal Number(s):
[33225]
Open Access
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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Jun 2025
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B23-Circular Dichroism
I22-Small angle scattering & Diffraction
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Diamond Proposal Number(s):
[29045]
Open Access
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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May 2025
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B23-Circular Dichroism
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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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May 2025
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B23-Circular Dichroism
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Abstract: The interaction between lipids and proteins impacts on a multitude of cellular processes and may contribute to the onset of several pathologies and ageing. Such processes are frequently linked to oxidative stress, whereby polyunsaturated fatty acids act as substrates for in vivo lipoxidation. The subsequent lipid peroxidation and/or isomerisation is known to affect membrane organization, as well as to modify proteins and DNA, leading to functional alterations. Aim of this study was to evaluate the capacity of UV denaturation experiments to induce lipid modification and to investigate the influence of lipid presence on the conformational stability of selected soluble model proteins. To this end, the UV-denaturation experiment developed at the B23 beamline of the Diamond Light Source (UK) is employed, which high photon flux and brilliance of the incident beamlight induce protein denaturation when repeated consecutive synchrotron radiation circular dichroism spectra are acquired in the far-UV region, diagnostic of protein folding. This allows the estimation of protein photostability. Our findings show that the presence of lipid vesicles (SUVs) significantly impacts the UV-denaturation of proteins, preserving the native structure in proteins with a high helical content. This suggests that lipids may play a protective role against light-induced damage to proteins.
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May 2025
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B23-Circular Dichroism
I04-1-Macromolecular Crystallography (fixed wavelength)
I04-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
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Open Access
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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May 2025
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B23-Circular Dichroism
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Rituparno
Chowdhury
,
Marco D.
Preuss
,
Hwan-Hee
Cho
,
Joshua J. P.
Thompson
,
Samarpita
Sen
,
Thomi K.
Baikie
,
Pratyush
Ghosh
,
Yorrick
Boeije
,
Xian Wei
Chua
,
Kai-Wei
Chang
,
Erjuan
Guo
,
Joost
Van Der Tol
,
Bart W. L.
Van Den Bersselaar
,
Andrea
Taddeucci
,
Nicolas
Daub
,
Daphne M.
Dekker
,
Scott T.
Keene
,
Ghislaine
Vantomme
,
Bruno
Ehrler
,
Stefan C. J.
Meskers
,
Akshay
Rao
,
Bartomeu
Monserrat
,
E. W.
Meijer
,
Richard H.
Friend
Diamond Proposal Number(s):
[32194]
Abstract: Current organic light-emitting diode (OLED) technology uses light-emitting molecules in a molecular host. We report green circularly polarized luminescence (CPL) in a chirally ordered supramolecular assembly, with 24% dissymmetry in a triazatruxene (TAT) system. We found that TAT assembled into helices with a pitch of six molecules, associating angular momentum to the valence and conduction bands and obtaining the observed CPL. Cosublimation of TAT as the “guest” in a structurally mismatched “host” enabled fabrication of thin films in which chiral crystallization was achieved in situ by thermally triggered nanophase segregation of dopant and host while preserving film integrity. The OLEDs showed external quantum efficiencies of up to 16% and electroluminescence dissymmetries ≥10%. Vacuum deposition of chiral superstructures opens new opportunities to explore chiral-driven optical and transport phenomena.
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Mar 2025
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B23-Circular Dichroism
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Leah E. M.
White
,
Tiberiu-M.
Gianga
,
F.
Pradaux-Caggiano
,
Chiara
Faverio
,
Andrea
Taddeucci
,
Henry S.
Rzepa
,
Christian
Jonhannesen
,
Lauren E.
Hatcher
,
Giuliano
Siligardi
,
David R.
Carbery
,
G. Dan
Pantos
Diamond Proposal Number(s):
[33876]
Open Access
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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Mar 2025
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B23-Circular Dichroism
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Maryam
Abooali
,
Stephanie
Schlichtner
,
Xi
Lei
,
Nijas
Aliu
,
Sabrina
Ruggiero
,
Sonia
Loges
,
Martin
Ziegler
,
Franziska
Hertel
,
Anna-Lena
Volckmar
,
Albrecht
Stenzinger
,
Petros
Christopoulos
,
Michael
Thomas
,
Elena
Klenova
,
N. Helge
Meyer
,
Stergios
Boussios
,
Nigel
Heaton
,
Yoh
Zen
,
Ane
Zamalloa
,
Shilpa
Chokshi
,
Luca
Urbani
,
Sophie
Richard
,
Kavitha
Kirubendran
,
Rohanah
Hussain
,
Giuliano
Siligardi
,
Dietmar
Cholewa
,
Steffen M.
Berger
,
Inna M.
Yasinska
,
Elizaveta
Fasler-Kan
,
Vadim V.
Sumbayev
Diamond Proposal Number(s):
[24509, 20755, 21202]
Open Access
Abstract: V-domain Ig-containing suppressor of T cell activation (VISTA) is a unique immune checkpoint protein, which was reported to display both receptor and ligand activities. However, the mechanisms of regulation of VISTA activity and functions by factors of tumour microenvironment (TME) remain unclear and understanding these processes is required in order to develop successful personalised cancer immunotherapeutic strategies and approaches. Here we report for the very first time that VISTA interacts with another immune checkpoint protein galectin-9 inside the cell most likely facilitating its interaction with TGF-β-activated kinase 1 (TAK1). This process is required for protection of lysosomes, which is crucial for many cell types and tissues. We found that VISTA expression can be differentially controlled by crucial factors present in TME, such as transforming growth factor beta type 1 (TGF-β) and hypoxia as well as other factors activating hypoxic signalling. We confirmed that involvement of these important pathways modulated by TME differentially influences VISTA expression in different cell types. These networks include: TGF-β-Smad3 pathway, TAK1 (TGF-β-activated kinase 1) or apoptosis signal-regulating kinase 1 (ASK1)-induced activation of activating transcription factor 2 (ATF-2) and hypoxic signalling pathway. Based on this work we determined the five critical functions of VISTA and the role of TME factors in controlling (modulating or downregulating) VISTA expression.
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Feb 2025
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B23-Circular Dichroism
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Gianluigi
Albano
,
Marco
Bertuolo
,
Francesco
Zinna
,
Andrea
Taddeucci
,
Tamas
Javorfi
,
Rohanah
Hussain
,
Gianluca M.
Farinola
,
Gennaro
Pescitelli
,
Angela
Punzi
,
Giuliano
Siligardi
,
Lorenzo
Di Bari
Diamond Proposal Number(s):
[36727]
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.
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Jan 2025
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B23-Circular Dichroism
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Abstract: The accumulation of plastic waste in the environment is an ecological disaster and will require multiple solutions to tackle the problem. Despite recent initiatives to close the plastics loop, only 9% of plastic was recycled in 2019, with the remaining waste either incinerated or accumulating in landfills or natural environments, posing hazards to both living and non-living systems. Bioplastics, derived from renewable sources, have been investigated as green alternatives to conventional fossil-based plastics. However, costly synthetic routes and low recyclability continue to challenge the growth of bioplastics. Poly(lactic acid) (PLA) is the most popular polymer for commercial bioplastics, but its recycling is limited by challenging mechanical recycling and slow biodegradation. A team of researchers from King’s College London has developed a generalisable biocatalysis engineering strategy to enhance the use of enzymes to depolymerise a broad class of plastics, in a publication recently published in Cell Reports Physical Science. This novel approach is 84 times faster than the 12-week-long industrial composting process currently used for recycling bioplastic materials.
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Jan 2025
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