Publications
306 results found
Walter ERH, Lee LC-C, Leung PK-K, et al., 2024, Mitochondria-targeting biocompatible fluorescent BODIPY probes., Chem Sci, Vol: 15, Pages: 4846-4852, ISSN: 2041-6520
An increase in the mitochondrial membrane potential (MMP) is a characteristic feature of cancer and cardiovascular disease. Therefore, it remains of crucial importance to develop new and improved fluorescent probes that are sensitive to the MMP, to report on mitochondrial health and function. Reported here are the design, synthesis, photophysical properties and biological characterisation of a series of BODIPY dyes, BODIPY-Mito-n, for mitochondria-targeted fluorescence imaging applications. Six BODIPY-Mito-n analogues were synthesised under mild conditions, and displayed excellent fluorescence quantum yields of between 0.59 and 0.72 in aqueous environments at physiological pH (pH = 7.4). The incorporation of poly(ethylene glycol) (PEG) chains to the triarylphosphonium cation moiety significantly improved the biocompatibility of the probes (BODIPY-Mito-6, IC50 > 50 μM). All BODIPY-Mito-n compounds demonstrated a high MMP-sensitive localisation in the mitochondria, with Pearson's correlation coefficients (PCC) of between 0.76 and 0.96. Compounds BODIPY-Mito-2 and BODIPY-Mito-6 revealed the highest sensitivity to the MMP, with a decrease in the emission intensity of 62% and 75%, respectively following MMP depolarisation. It is anticipated that the highest MMP sensitivity and enhanced biocompatibility of BODIPY-Mito-6 could lead to the development of new probes for mitochondrial imaging in the future.
Bennett TLR, Long NJ, 2023, A convenient synthesis of ferrocene-(ethynylphenyl)thioacetates., Dalton Trans, Vol: 52, Pages: 16465-16471
Ferrocene is popular within the field of molecular electronics due to its well-defined electronic properties. However, where the conductance of highly-conjugated oligophenylethylenes has been widely studied, work on analogous ferrocenyl systems has been relatively rare, possibly due to difficulties associated with the synthesis of molecules containing terminal thioacetates, which are often used to bind molecules to metallic electrodes. Herein, a widely applicable synthetic methodology is demonstrated which can be used to synthesize a variety of conjugated ferrocene-alkyne systems terminated with thioacetates, including symmetric, asymmetric and multi-ferrocene systems. Conjugation of the ferrocene units to their terminal atoms is then shown through the use of both UV/Vis spectroscopy and cyclic voltammetry. This work paves the way for future studies and applications of conjugated ferrocene systems in the field of nanoelectronics.
Yue TTC, Ge Y, Aprile FA, et al., 2023, Site-Specific <SUP>68</SUP>Ga Radiolabeling of Trastuzumab Fab via Methionine for ImmunoPET Imaging, BIOCONJUGATE CHEMISTRY, ISSN: 1043-1802
Aboagye E, Teh JH, Amgheib A, et al., 2023, Evaluation of [18F]AlF-EMP-105 for molecular imaging of 2 C-Met, Pharmaceutics, Vol: 15, Pages: 1-13, ISSN: 1999-4923
C-Met is a receptor tyrosine kinase that is overexpressed in a range of different cancer types, and has been identified as a potential biomarker for cancer imaging and therapy. Previously, a 68Ga-labelled peptide, [68Ga]Ga-EMP-100, has shown promise for imaging c-Met in renal cell carcinoma in humans. Herein, we report the synthesis and preliminary biological evaluation of an [18F]AlF-labelled analogue, [18F]AlF-EMP-105, for c-Met imaging by positron emission tomography. EMP-105 was radiolabelled using the aluminium-[18F]fluoride method with 46 ± 2% RCY and >95% RCP in 35–40 min. In vitro evaluation showed that [18F]AlF-EMP-105 has a high specificity for c-Met-expressing cells. Radioactive metabolite analysis at 5 and 30 min post-injection revealed that [18F]AlF-EMP-105 has good blood stability, but undergoes transformation—transchelation, defluorination or demetallation—in the liver and kidneys. PET imaging in non-tumour-bearing mice showed high radioactive accumulation in the kidneys, bladder and urine, demonstrating that the tracer is cleared predominantly as [18F]fluoride by the renal system. With its high specificity for c-Met expressing cells, [18F]AlF-EMP-105 shows promise as a potential diagnostic tool for imaging cancer.
Lim Kee Chang W, Chan T, Raguseo F, et al., 2023, Rapid short-pulses of focused ultrasound and microbubbles deliver a range of agent sizes to the brain, Scientific Reports, Vol: 13, ISSN: 2045-2322
Focused ultrasound and microbubbles can non-invasively and locally deliver therapeutics and imaging agents across the blood–brain barrier. Uniform treatment and minimal adverse bioeffects are critical to achieve reliable doses and enable safe routine use of this technique. Towards these aims, we have previously designed a rapid short-pulse ultrasound sequence and used it to deliver a 3 kDa model agent to mouse brains. We observed a homogeneous distribution in delivery and blood–brain barrier closing within 10 min. However, many therapeutics and imaging agents are larger than 3 kDa, such as antibody fragments and antisense oligonucleotides. Here, we evaluate the feasibility of using rapid short-pulses to deliver higher-molecular-weight model agents. 3, 10 and 70 kDa dextrans were successfully delivered to mouse brains, with decreasing doses and more heterogeneous distributions with increasing agent size. Minimal extravasation of endogenous albumin (66.5 kDa) was observed, while immunoglobulin (~ 150 kDa) and PEGylated liposomes (97.9 nm) were not detected. This study indicates that rapid short-pulses are versatile and, at an acoustic pressure of 0.35 MPa, can deliver therapeutics and imaging agents of sizes up to a hydrodynamic diameter between 8 nm (70 kDa dextran) and 11 nm (immunoglobulin). Increasing the acoustic pressure can extend the use of rapid short-pulses to deliver agents beyond this threshold, with little compromise on safety. This study demonstrates the potential for deliveries of higher-molecular-weight therapeutics and imaging agents using rapid short-pulses.
Hamill JM, Ismael A, Al-Jobory A, et al., 2023, Quantum Interference and Contact Effects in the Thermoelectric Performance of Anthracene-Based Molecules, JOURNAL OF PHYSICAL CHEMISTRY C, Vol: 127, Pages: 7484-7491, ISSN: 1932-7447
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- Citations: 2
Long NJ, Bhargava S, 2022, Professor Edward Abel, FRSC, CBE (1931-2021), DALTON TRANSACTIONS, Vol: 51, Pages: 16781-16783, ISSN: 1477-9226
Cooper SM, Siakalli C, White AJP, et al., 2022, Synthesis and anti-microbial activity of a new series of bis(diphosphine) rhenium(v) dioxo complexes, DALTON TRANSACTIONS, Vol: 51, Pages: 12791-12795, ISSN: 1477-9226
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- Citations: 7
Wilkinson LA, Bennett TLR, Grace IM, et al., 2022, Assembly, structure and thermoelectric properties of 1,1 '-dialkynylferrocene 'hinges', CHEMICAL SCIENCE, ISSN: 2041-6520
Frei A, Rigby A, Yue TTC, et al., 2022, To chelate thallium(i) - synthesis and evaluation of Kryptofix-based chelators for Tl-201, DALTON TRANSACTIONS, Vol: 51, Pages: 9039-9048, ISSN: 1477-9226
Cooper SM, White AJP, Eykyn TR, et al., 2022, N-Centered Tripodal Phosphine Re(V) and Tc(V) Oxo Complexes: Revisiting a [3+2] Mixed-Ligand Approach, INORGANIC CHEMISTRY, Vol: 61, Pages: 8000-8014, ISSN: 0020-1669
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- Citations: 2
Bennett TLR, Alshammari M, Au-Yong S, et al., 2022, Multi-component self-assembled molecular-electronic films: towards new high-performance thermoelectric systems, CHEMICAL SCIENCE, Vol: 13, Pages: 5176-5185, ISSN: 2041-6520
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- Citations: 9
Sheppard SA, Bennett TLR, Long NJ, 2022, Development and Characterisation of Highly Conjugated Functionalised Ferrocenylene Macrocycles, EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Vol: 2022, ISSN: 1434-1948
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- Citations: 3
Li Z, Li B, Wu X, et al., 2022, Organometallic-functionalized interfaces for highly efficient inverted perovskite solar cells, SCIENCE, Vol: 376, Pages: 416-+, ISSN: 0036-8075
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- Citations: 380
Bourke S, Urbano L, Midson MM, et al., 2022, Nearly monodispersed, emission-tuneable conjugated polymer nanoparticles, Sensors & Diagnostics, Vol: 1, Pages: 1185-1188
<jats:p>We describe the synthesis of monodispersed, silica encapsulated conjugated polymer nanoparticles, their colour tunability and use in imaging HeLa cells.</jats:p>
Baker CA, Romain C, Long NJ, 2021, Cation-π interactions enabling hard/soft Ti/Ag heterobimetallic cooperativity in lactide ring-opening polymerisation, CHEMICAL COMMUNICATIONS, Vol: 57, Pages: 12524-12527, ISSN: 1359-7345
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- Citations: 4
Braga M, Leow CH, Gil JH, et al., 2021, Investigating CXCR4 expression of tumor cells and the vascular compartment: A multimodal approach, PLoS One, Vol: 16, Pages: 1-21, ISSN: 1932-6203
The C-X-C chemokine receptor 4 (CXCR4) is G protein-coupled receptor that upon binding to its cognate ligand, can lead to tumor progression. Several CXCR4-targeted therapies are currently under investigation, and with it comes the need for imaging agents capable of accurate depiction of CXCR4 for therapeutic stratification and monitoring. PET agents enjoy the most success, but more cost-effective and radiation-free approaches such as ultrasound (US) imaging could represent an attractive alternative. In this work, we developed a targeted microbubble (MB) for imaging of vascular CXCR4 expression in cancer. A CXCR4-targeted MB was developed through incorporation of the T140 peptide into the MB shell. Binding properties of the T140-MB and control, non-targeted MB (NT-MB) were evaluated in MDA-MB-231 cells where CXCR4 expression was knocked-down (via shRNA) through optical imaging, and in the lymphoma tumor models U2932 and SuDHL8 (high and low CXCR4 expression, respectively) by US imaging. PET imaging of [18F]MCFB, a tumor-penetrating CXCR4-targeted small molecule, was used to provide whole-tumor CXCR4 readouts. CXCR4 expression and microvessel density were performed by immunohistochemistry analysis and western blot. T140-MB were formed with similar properties to NT-MB and accumulated sensitively and specifically in cells according to their CXCR4 expression. In NOD SCID mice, T140-MB persisted longer in tumors than NT-MB, indicative of target interaction, but showed no difference between U2932 and SuDHL8. In contrast, PET imaging with [18F]MCFB showed a marked difference in tumor uptake at 40–60 min post-injection between the two tumor models (p<0.05). Ex vivo analysis revealed that the large differences in CXCR4 expression between the two models are not reflected in the vascular compartment, where the MB are restricted; in fact, microvessel density and CXCR4 expression in the vasculature was comparable between U2932 and SuDHL8 tumors. In conclusion, we success
Osborne BE, Yue TTC, Waters ECT, et al., 2021, Synthesis and <i>ex vivo</i> biological evaluation of gallium-68 labelled NODAGA chelates assessing cardiac uptake and retention, DALTON TRANSACTIONS, Vol: 50, Pages: 14695-14705, ISSN: 1477-9226
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- Citations: 1
Teh JH, Braga M, Allott L, et al., 2021, A kit-based aluminium-[F-18]fluoride approach to radiolabelled microbubbles, Chemical Communications, Vol: 57, Pages: 11677-11680, ISSN: 1359-7345
The production of 18F-labelled microbubbles (MBs) via the aluminium-[18F]fluoride ([18F]AlF) radiolabelling method and facile inverse-electron-demand Diels–Alder (IEDDA) ‘click’ chemistry is reported. An [18F]AlF-NODA-labelled tetrazine was synthesised in excellent radiochemical yield (>95% RCY) and efficiently conjugated to a trans-cyclooctene (TCO) functionalised phospholipid (40–50% RCY), which was incorporated into MBs (40–50% RCY). To demonstrate the potential of producing 18F-labelled MBs for clinical studies, we also describe a kit-based approach which is amenable for use in a hospital radiopharmacy setting.
Walter ERH, Cooper SM, Boyle JJ, et al., 2021, Enzyme-activated probes in optical imaging: a focus on atherosclerosis, DALTON TRANSACTIONS, Vol: 50, Pages: 14486-14497, ISSN: 1477-9226
Wu Y, Chau H, Thor W, et al., 2021, Solid‐Phase Peptide Macrocyclization and Multifunctionalization via Dipyrrin Construction, Angewandte Chemie, Vol: 133, Pages: 20463-20469, ISSN: 0044-8249
<jats:title>Abstract</jats:title><jats:p>We introduce a new and highly efficient synthetic protocol towards multifunctional fluorescent cyclopeptides by solid‐phase peptide macrocyclization via dipyrrin construction, with full scope of proteinogenic amino acids and different ring sizes. Various bicyclic peptides can be created by dipyrrin‐based crosslinking and double dipyrrin‐ring formation. The embedded dipyrrin can be either transformed to fluorescent BODIPY and then utilized as cancer‐selective targeted protein imaging probe in vitro, or directly employed as a selective metal sensor in aqueous media. This work provides a valuable addition to the peptide macrocyclization toolbox, and a blueprint for the development of multifunctional dipyrrin linkers in cyclopeptides for a wide range of potential bioapplications.</jats:p>
Wu Y, Chau H-F, Thor W, et al., 2021, Solid-Phase Peptide Macrocyclization and Multifunctionalization via Dipyrrin Construction, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 60, Pages: 20301-20307, ISSN: 1433-7851
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- Citations: 8
Jiang L, Mak H-N, Walter ERH, et al., 2021, A fluorescent probe for the discrimination of oxidation states of palladium, CHEMICAL SCIENCE, Vol: 12, Pages: 9977-9982, ISSN: 2041-6520
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- Citations: 8
Chau H-F, Wu Y, Fok W-Y, et al., 2021, Lanthanide-Based Peptide-Directed Visible/Near-Infrared Imaging and Inhibition of LMP1, JACS AU, Vol: 1, Pages: 1034-1043
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- Citations: 12
Farleigh M, Pham TT, Yu Z, et al., 2021, New Bifunctional Chelators Incorporating Dibromomaleimide Groups for Radiolabeling of Antibodies with Positron Emission Tomography Imaging Radioisotopes, BIOCONJUGATE CHEMISTRY, Vol: 32, Pages: 1214-1222, ISSN: 1043-1802
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- Citations: 6
Boltersdorf T, Gavins FNE, Long NJ, 2021, Long-lived lanthanide emission <i>via</i> a pH-sensitive and switchable LRET complex, CHEMICAL SCIENCE, ISSN: 2041-6520
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- Citations: 2
Walter E, Ge Y, Mason J, et al., 2021, A coumarin-porphyrin FRET break-apart probe for heme oxygenase-1, Journal of the American Chemical Society, Vol: 143, Pages: 6460-6469, ISSN: 0002-7863
Heme oxygenase-1 (HO-1) is a vital enzyme in humans that primarily regulates free heme concentrations. The overexpression of HO-1 is commonly associated with cardiovascular and neurodegenerative diseases including atherosclerosis and ischemic stroke. Currently, there are no known chemical probes to detect HO-1 activity, limiting its potential as an early diagnostic/prognostic marker in these serious diseases. Reported here are the design, synthesis, and photophysical and biological characterization of a coumarin–porphyrin FRET break-apart probe to detect HO-1 activity, Fe–L1. We designed Fe–L1 to “break-apart” upon HO-1-catalyzed porphyrin degradation, perturbing the efficient FRET mechanism from a coumarin donor to a porphyrin acceptor fluorophore. Analysis of HO-1 activity using Escherichia coli lysates overexpressing hHO-1 found that a 6-fold increase in emission intensity at 383 nm was observed following incubation with NADPH. The identities of the degradation products following catabolism were confirmed by MALDI-MS and LC–MS, showing that porphyrin catabolism was regioselective at the α-position. Finally, through the analysis of Fe–L2, we have shown that close structural analogues of heme are required to maintain HO-1 activity. It is anticipated that this work will act as a foundation to design and develop new probes for HO-1 activity in the future, moving toward applications of live fluorescent imaging.
Bennett TLR, Wilkinson L, Lok JMA, et al., 2021, Synthesis, electrochemistry and optical properties of highly conjugated alkynyl-ferrocenes and -biferrocenes, Organometallics, Vol: 40, Pages: 1156-1162, ISSN: 0276-7333
Sonogashira reactions are utilized herein to react iodo-ferrocenes and -biferrocenes with terminal alkyne ligands, functionalized with both pyridine and thioanisole groups. High-yielding reactions generate both monoalkynyl and dialkynyl derivatives, the ratio of which can be altered through changes in the reaction stoichiometry. This methodology allowed us to synthesize a large family of derivatives, comprising four symmetrical derivatives (3xx, where x represents a phenyl-substituted terminal alkyne) and six less-studied asymmetrical derivatives (3xy, where x and y represent two different phenyl-substituted terminal alkynes), as well as a number of their biferrocenyl analogues (6x, 7xx, and 7xy), including the first known examples of asymmetrically disubstituted biferrocenes. We examined the electrochemical behavior of all the systems in solution through the use of cyclic voltammetry and demonstrate that these highly conjugated alkynyl ligands exert delicate redox control over the central ferrocene motif. We also note that these substituents display some control over the mixed-valence character present in biferrocene monocations, with thioanisole substituents imparting almost an order of magnitude higher Kc than their pyridyl analogues, and asymmetric systems displaying rare characteristic properties of mixed-valence isomers. The electronic structure of these systems was further elucidated through a combination of UV/vis spectroscopy and density functional theory calculations. Our methodology provides a facile and adaptable route toward the isolation of a number of novel ferrocene and biferrocene derivatives. From our perspective, the asymmetric nature of these systems, along with the delicate and predictable redox control that these ligands exert on the central ferrocene unit(s), could lead to applications in molecular electronics, where these properties have previously shown promise in the fabrication of diodes and rectifiers, as well as in the synthesis of donor
Wang X, Ismael A, Almutlg A, et al., 2021, Optimised power harvesting by controlling the pressure applied to molecular junctions, Chemical Science, Vol: 12, Pages: 5230-5235, ISSN: 2041-6520
A major potential advantage of creating thermoelectric devices using self-assembled molecular layers is their mechanical flexibility. Previous reports have discussed the advantage of this flexibility from the perspective of facile skin attachment and the ability to avoid mechanical deformation. In this work, we demonstrate that the thermoelectric properties of such molecular devices can be controlled by taking advantage of their mechanical flexibility. The thermoelectric properties of self-assembled monolayers (SAMs) fabricated from thiol terminated molecules were measured with a modified AFM system, and the conformation of the SAMs was controlled by regulating the loading force between the organic thin film and the probe, which changes the tilt angle at the metal-molecule interface. We tracked the thermopower shift vs. the tilt angle of the SAM and showed that changes in both the electrical conductivity and Seebeck coefficient combine to optimize the power factor at a specific angle. This optimization of thermoelectric performance via applied pressure is confirmed through the use of theoretical calculations and is expected to be a general method for optimising the power factor of SAMs.
Omoruyi U, Page SJ, Apps S, et al., 2021, Synthesis and characterisation of a range of Fe, Co, Ru and Rh triphos complexes and investigations into the catalytic hydrogenation of levulinic acid, Journal of Organometallic Chemistry, Vol: 935, Pages: 1-12, ISSN: 0022-328X
The coordination chemistry of the N-triphos ligand (NP3Ph, 1b) has been investigated with range of Fe, Co and Rh precursors and found to form either tridentate or bidentate complexes. Reaction of NP3Ph with [Rh(COD)(CH3CN)2]BF4 resulted in the formation of the tridentate complex [Rh(COD)(κ3 NP3Ph)]BF4 (3) in the solid state, however, in solution a bidentate complex predominates in more polar solvents. Reaction of NP3Ph with Fe carbonyl precursors revealed the formation of the bidentate complexes [Fe(CO)3(κ2-NP3Ph)Fe(CO)4] (4) and [Fe(CO)3(κ2-NP3Ph)] (5), while reaction with FeBr2 resulted in the paramagnetic bidentate complex [Fe(Br)2(κ2-NP3Ph)] (6). Reaction of NP3Ph with CoCl2 gave a dimeric Co species [(κ2-NP3Ph)CoCl(κ1,κ2-NP3Ph)CoCl3] (7), while Zn powder reduction of NP3Ph Co halides resulted in the formation of the tridentate complexes of the type: [Co(X)(k3-NP3Ph)]. The related triphos Ru complex, [Ru(CO3)(CO)(κ3-CP3Ph)] (2), has also been isolated and characterised. Preliminary catalytic hydrogenation of levulinic acid (LA) was conducted with 2 and 3. The Ru complex was found to be catalytically active, giving high conversions of LA to form gamma valerolactone (GVL) and 1,4-pentandiol (1,4-PDO), while 3 was found to be catalytically inactive. In situ catalytic testing with 1b and Fe(BF4)2.6H2O resulted in low conversions of LA while a combination of 1b and Co(BF4)2.6H2O gave higher conversions 75% yields of GVL.
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