140 research outputs found

    H2S-based fluorescent imaging for pathophysiological processes

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    Hydrogen sulfide (H2S), as an important endogenous signaling molecule, plays a vital role in many physiological processes. The abnormal behaviors of hydrogen sulfide in organisms may lead to various pathophysiological processes. Monitoring the changes in hydrogen sulfide is helpful for pre-warning and treating these pathophysiological processes. Fluorescence imaging techniques can be used to observe changes in the concentration of analytes in organisms in real-time. Therefore, employing fluorescent probes imaging to investigate the behaviors of hydrogen sulfide in pathophysiological processes is vital. This paper reviews the design strategy and sensing mechanisms of hydrogen sulfide-based fluorescent probes, focusing on imaging applications in various pathophysiological processes, including neurodegenerative diseases, inflammation, apoptosis, oxidative stress, organ injury, and diabetes. This review not only demonstrates the specific value of hydrogen sulfide fluorescent probes in preclinical studies but also illuminates the potential application in clinical diagnostics

    The design and synthesis of novel fluorescent coumarin-based derivatives as chemosensory for the application of toxic metal ion detection

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    The rise of humankind has caused pollution, increasing damage to the environment. The actions of humans over hundreds of years have led to an increase in the release of heavy metal cations in concentrations that are toxic to plants, animals and humans. These toxic metals can find their way into humans’ diets through water sources or bioaccumulation in plants and animals such as fish. Heavy metals such as lead and mercury are known to cause serious health issues when consumed, affecting the functioning of the circulatory and nervous systems and causing developmental disorders. Other metal cations, such as iron and copper, can be found in the human body. However, detrimental health issues can occur when normal concentrations are disturbed (either too high or too low). Iron, for example, can be toxic if in excess in the human body, causing damage to the liver and heart and can cause neuroinflammation and Alzheimer’s disease. Many methods have been employed to detect and measure the concentrations of toxic metal cations. However, these methods are performed in a laboratory and need skilled operators using expensive equipment. This results in long and tedious sample collection, long feedback time and costly analysis. Chemosensors have been researched and proposed as a cost-effective, on-site, real-time alternative for use as metal detectors. Chemosensory can selectively detect specific metal cations and can be sensitive up to the nanomolar range. Various chemosensors have been synthesised and screened for their colourimetric and fluorometric abilities. Colourimetric chemosensors can be used to visually detect cationic and anionic analytes, whereas fluorometric chemosensors are used to detect anions using their emission properties which handheld devices can measure.Thesis (PhD) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 202

    The design and synthesis of novel fluorescent coumarin-based derivatives as chemosensory for the application of toxic metal ion detection

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    vital:69851The rise of humankind has caused pollution, increasing damage to the environment. The actions of humans over hundreds of years have led to an increase in the release of heavy metal cations in concentrations that are toxic to plants, animals and humans. These toxic metals can find their way into humans’ diets through water sources or bioaccumulation in plants and animals such as fish. Heavy metals such as lead and mercury are known to cause serious health issues when consumed, affecting the functioning of the circulatory and nervous systems and causing developmental disorders. Other metal cations, such as iron and copper, can be found in the human body. However, detrimental health issues can occur when normal concentrations are disturbed (either too high or too low). Iron, for example, can be toxic if in excess in the human body, causing damage to the liver and heart and can cause neuroinflammation and Alzheimer’s disease. Many methods have been employed to detect and measure the concentrations of toxic metal cations. However, these methods are performed in a laboratory and need skilled operators using expensive equipment. This results in long and tedious sample collection, long feedback time and costly analysis. Chemosensors have been researched and proposed as a cost-effective, on-site, real-time alternative for use as metal detectors. Chemosensory can selectively detect specific metal cations and can be sensitive up to the nanomolar range. Various chemosensors have been synthesised and screened for their colourimetric and fluorometric abilities. Colourimetric chemosensors can be used to visually detect cationic and anionic analytes, whereas fluorometric chemosensors are used to detect anions using their emission properties which handheld devices can measure.Thesis (PhD) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 202

    Pristine iota-Carrageenan and Chemically Functionalized Guar gum Polysaccharides for Metal-ion Complexation and CuS-based Nanocomposite Preparation

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    Natural polysaccharides are ubiquitous in nature and have been widely used in human history as food, materials, fuels, and medicine. To cope with climate crisis and develop a more sustainable economy, promoting the use of natural polysaccharides and other products from oxygenic photosynthesis is of great interest. In this work, anionic iota-carrageenan (CG) polysaccharide was employed to prepare an iota-carrageenan/CuS covellite (CG/CuS) nanocomposite using a gel/liquid interface precipitation process similarly to chemobrionics. This approach showed how pristine natural polysaccharides such as CG could be effortlessly utilized to develop high-end products for humidity and temperature sensing. Despite great potential of pristine natural polysaccharides in fabricating novel materials, chemical modifications of natural polysaccharides still play a crucial role in altering and enriching physical, chemical and biological properties, as well as applications of natural polysaccharides. Due to fascinating physicochemical properties, biodegradability, biocompatibility, natural abundancy and low cost, non-ionic guar gum (GG) polysaccharide was chosen as a model material to study how chemical modifications can substantially change properties of GG and extend its applications. An extensive analysis on reported chemical modification approaches of GG was conducted to examine recent advances in this field, as well as structure-property relationships and applications of GG-based materials. Among the four commonly used chemical reactions on GG, namely, nucleophilic reactions, graft polymerization, partial oxidation and cross-linking, nucleophilic reactions were adopted in this study due to the simplicity, accessibility and diversity of chemical reaction conditions and reagents. Different nucleophilic reactions were successfully carried out in aqueous medium at room temperature without using toxic organic solvents, allowing the introduction of different organic functional groups and moieties such as amine, thiol, xanthate, benzoic acid, catechol and tosylate to GG. The chemical modification of GG by xanthate and benzoic acid groups was chosen for further study due to their great potential applications. Being a soft base according to the hard and soft acid and base (HSAB) theory, xanthate functional groups on guar gum-xanthate (GG-X) allowed GG-X to coordinate more strongly to a wide range of soft metal ions, which have great potential in heavy metal removal, wastewater treatment, cross-linked hydrogel preparation, etc. In addition, GG-X offered dual functionalities as a surfactant and an organic matrix in the formation of GG-X/CuS nanocomposite colloidal dispersions, which showed printability and electrical responsiveness in humidity sensing. Benzoic acid moieties contain aromatic benzene rings and carboxylic acid groups, which offer interesting intermolecular interactions, coordination chemistry and swelling properties at mildly acidic environments to GG. Guar gum-benzoic acid (GG-BA) was found biocompatible to living cells (mouse embryonic fibroblasts and human mammary epithelial cells). Therefore, GG-BA could be explored further as coacervates and cross-linked hydrogels for biomedical applications, e.g. wound dressing, bioadhesives and drug delivery.Naturliga polysackarider är allmänt förekommande i naturen och har använts i stor utsträckning i människohistoria som mat, material, bränsle och medicin. För att klara av klimatkrisen och utveckla en mer hållbar ekonomi är det av stort intresse att främja användningen av naturliga polysackarider och andra produkter från syreproducerande fotosyntes. I detta arbete användes anjonisk jota-karragenan (CG) polysackarid för att framställa en jota-karragenan/CuS covellit (CG/CuS) nanokomposit med användning av en gel/vätskegränssnittsutfällningsprocess som liknar kemobrionik. Detta tillvägagångssätt visade hur orörda naturliga polysackarider utan ansträngning kunde användas för att utveckla avancerade produkter för fukt- och temperaturavkänning. Trots den stora potentialen hos orörda naturliga polysackarider vid tillverkning av nya material, spelar kemiska modifieringar av naturliga polysackarider fortfarande en avgörande roll för att förändra och berika fysiska, kemiska och biologiska egenskaper samt tillämpningar av naturliga polysackarider. På grund av fascinerande fysikalisk-kemiska egenskaper, biologisk nedbrytbarhet, biokompatibilitet, naturlig överflöd och låg kostnad, valdes nonjonisk guargummi (GG) polysackarid som modellmaterial för att studera hur kemiska modifieringar kan väsentligt förändra egenskaperna hos GG och utöka dess tillämpningar. En omfattande analys av rapporterade metoder för kemisk modifiering av GG genomfördes för att undersöka de senaste framstegen inom detta område, såväl som struktur-egenskapsförhållanden och potentiella tillämpningar av GG-baserade material. Bland de fyra vanligaste kemiska reaktionerna på GG, nämligen nukleofila reaktioner, ymppolymerisation, partiell oxidation och tvärbindning, antogs nukleofila reaktioner i denna studie på grund av enkelheten, tillgängligheten och mångfalden av kemiska reaktionsförhållanden och reagens. Olika nukleofila reaktioner genomfördes framgångsrikt i vattenhaltigt medium vid rumstemperatur utan att använda giftiga organiska lösningsmedel, vilket möjliggjorde införandet av olika organiska funktionella grupper och delar såsom amin, tiol, xantat, bensoesyra, katekol och tosylat till GG. Den kemiska modifieringen av GG av xantat- och bensoesyragrupper valdes för vidare studier på grund av deras stora potentiella tillämpningar. Som en mjuk bas från teorin om hård och mjuk syra och bas (HSAB) tillät xantatgrupper på guargummi-xantat (GG-X) GG-X att koordinera starkare till ett brett spektrum av mjuka metalljoner, som har stor potential vid borttagning av tungmetaller, avloppsvattenbehandling, tvärbunden hydrogelberedning etc. Dessutom erbjöd GG-X dubbla funktioner som ett ytaktivt ämne och en organisk matris vid bildning av GG-X/CuS nanokomposit kolloidal dispersion, som visade tryckbarhet och elektrisk känslighet vid fuktavkänning. Bensoesyradelar innehåller aromatiska bensenringar och karboxylsyragrupper, vilket erbjuder intressanta intermolekylära interaktioner, koordinationskemi och svällningsegenskaper i milt sura miljöer till GG. Guargummi-bensoesyra (GG-BA) visade sig vara biokompatibel med levande celler (embryonala musfibroblaster och humana bröstepitelceller). Därför skulle GG-BA kunna utforskas vidare som koacervat och tvärbundna hydrogeler för biomedicinska tillämpningar, t.ex. sårförband, bioadhesiver och läkemedelstillförsel

    Functional Nanomaterials in Biomedicine

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    The great success of nanotechnology promotes a tremendous revolution in the biomedical field. Functional nanomaterials have been widely applied for the treatment of various diseases, such as cancer, bacterial infection, diabetes, inflammation, and neurodegenerative disorders. Various therapeutic nanoplatforms have been developed with therapeutic functions and intelligent properties. However, the development of nanomedicine suffers from several challenges prior to their clinical applications. For instance, disease detection in an early stage is a critical challenge for nanomedicine. It is difficult to detect disease markers (e.g., proteins, genes, or cancer circulating cells), so nanoprobes with high sensitivity and selectivity are required. Moreover, to overcome drug resistance, it is highly desirable to develop functional nanomedicines with the combination of multiple therapeutic modalities, such as chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, radiotherapy, starving therapy, and immunotherapy. Additionally, the stability and degradability of most nanomedicines in biofluids should be carefully evaluated before their administration to humans. This book provides researchers with the latest investigations and findings in this field

    Fluorescent methods to detect and discover peptide and protein interactions in vitro

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    The unique properties of peptide and protein interactions have been exploited in the field of medicine for uses like protein-targeted therapeutic, and diagnostic agents. However, such developments would not be possible without an understanding of these biomolecules. As such, it essential to develop methods that allow the study of these unique interactions. In this work, small fluorescent molecules were utilised for the development of such techniques. A novel probe, CyMT was developed for multimodal mass spectrometry and fluorescence imaging within a single sample. The probe proved to be successful in the imaging of isolated insulin protein samples, first with fluorescence microscopy, followed immediately with mass spectrometry imaging. A second probe, NpMT was also designed and synthesised for future testing. Following from previous work on the development of a novel fluorescent redox sensor for protein tagging, the assessment of novel fluorescent scaffolds was performed. The fluorescent properties of FCR1 and NpFR1 were assessed computationally for compatibility with the HaloTag protein tagging system. This work revealed the suitability of FCR1 for future incorporation into the HaloTag. Further computational studies on NpFR1 helped to uncover the most suitable computation methods that would allow for further assessment and future developments of this sensor. Finally, efforts were directed towards developing a novel peptide-receptor binding assay. The fluorescence probe, BNp-COOH, was designed with two functional moieties - one for solid-phase peptide synthesis attachment, and another as a pull-down partner. The fluorescence allows identification of receptor binding events, while the pull-down partner enables subsequent isolation and characterisation of the interaction. The work outlined here, describes a novel set of tools for the study of peptide and protein interactions. These tools have the potential to enhance our understanding of these interactions

    Shifting Gears Towards the Red: Novel Boron-Based Fluorophores for Bioimaging Applications

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    Advancements in near-infrared (NIR) fluorescence imaging have enabled greater tissue penetration depths, high spatial resolution, reduced photon scattering, and minimal interference from tissue autofluorescence. Hence, NIR fluorophores exist as viable candidates for biological imaging applications, as well as providing unique insights into complex biological processes to better understand disease etiology. In this work, a series of novel boron-based coumarin and rhodamine-like fluorophores were developed and tested. Initially, modifications to the coumarin scaffold were investigated to develop more red-shifted dyes, whereby incorporation of a p-conjugated bridge was determined to be a critical component. Confocal microscopy studies with A549 lung cancer cells showed clear differences in the intra-cellular distributions of the fluorophores. The lipophilic carborane coumarin derivatives exhibited superior selectively within lipid droplets. In contrast, the polar boronic acid hydrazone-coumarins displayed intracellular localisation within the endoplasmic reticulum. A library of boron-containing rhodamine-like probes were also synthesised. All compounds exhibited near-infrared emission wavelengths with large Stokes shifts. Furthermore, modifications to the terminal boron moiety were not found to impact the overall red-shift of the molecules, although increasing the donor group strength favourably enhanced this shift. The low brightness of some of the probes, related to rhodamine spirocyclisation, meant that conclusive intracellular localisations could not be confirmed. The near-IR emitting nature of the rhodamine-like probes was recognised as a highly advantageous tool for bioimaging applications. Two fluorescent-labelled ligands with varying linker lengths, of the allosteric adamantyl benzamide P2X7R antagonist were prepared, based on the para-MIDA ester rhodamine-like fluorophore. Both probes were utilised in preliminary fluorescence studies, whereby the near-IR emitting nature of the fluorophore was retained despite conjugation to biomolecules. As well, a longer emission wavelength was observed with a shorter linker length. This research ultimately highlights the versatility of boron as a unique element in fluorescence and biological imaging applications

    Sequential recognition capability of a novel flavin-dipicolyl analogue toward zinc and phosphate ion: A model capable of selective recognition of AMP over ADP/ATP

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    A novel flavin-dipicolylamine conjugate was designed for highly selective and sequential recognition of zinc and phosphate ions based on OFF-ON-OFF mode of detection. While lower detection limits were obtained toward zinc ion recognition in the two solvents studied here, different stoichiometric requirement and hence different mode of coordination was also observed and evaluated. Furthermore, the DPF-zinc complex was found to be highly selective for phosphate anion over other anions studied. Variation in the detection limit for phosphate over pyrophosphate was observed making it a model capable of differentiating between AMP from ADP or ATP
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