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Conference paperZhang G, Harput S, Shah A, et al., 2019,
Photoacoustic Super-Resolution Imaging using Laser Activation of Low-Boiling-Point Dye-Coated Nanodroplets in vitro and in vivo
, IEEE International Ultrasonics Symposium (IUS), Publisher: IEEE, Pages: 944-947, ISSN: 1948-5719- Cite
- Citations: 2
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Conference paperLahri R, Rahman M, Hernandez-Gil J, et al., 2019,
Examination of zinc ferrites vs. iron oxides as contrast agents for microwave systems
, 13th European Conference on Antennas and Propagation (EuCAP), Publisher: IEEE, ISSN: 2164-3342- Author Web Link
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- Citations: 3
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Journal articleSmith A, Blower P, Southworth R, et al., 2018,
Synthesis, gallium-68 radiolabelling and biological evaluation of a series of triarylphosphonium-functionalized DO3A chelators
, Dalton Transactions, Vol: 47, Pages: 15448-15457, ISSN: 1477-9234Radiolabelled lipophilic cations that accumulate in mitochondria according to the magnitude of the mitochondrial membrane potential can be used to report non-invasively on mitochondrial dysfunction in cardiovascular disease, cardiotoxicity, and cancer. While several such cations are already commercially available for SPECT imaging, PET offers greater promise in terms of sensitivity, resolution, and capacity for dynamic imaging and pharmacokinetic modelling. We have therefore synthesised a series of three triarylphosphonium-functionalised DO3A chelators for positron emitter gallium-68, with differing alkyl-functionalisation motifs to provide opportunities for tunable lipophilicity as a means of optimising their pharmacokinetics. To assess their capacity to report on mitochondrial membrane potential, we assessed their pharmacokinetic profiles in isolated tumour cells and isolated perfused rat hearts before and after mitochondrial depolarisation with the ionophore CCCP. All three compounds radiolabelled with over 97% RCY and exhibited log D values of between −3.12 and −1.81. In vitro assessment of the uptake of the radiotracers in cultured tumour cells showed a three-fold increase in uptake compared to unchelated [68Ga]Ga(III). However, each complex exhibited less than 1% retention in healthy hearts, which was not significantly diminished by mitochondrial depolarisation with CCCP. This preliminary work suggests that while this approach is promising, the lipophilicity of this class of tracers must be increased in order for them to be useful as cardiac or cancer imaging agents.
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Journal articleLi B, Famili M, Pensa E, et al., 2018,
Cross-plane conductance through a graphene/molecular monolayer/Au sandwich
, Nanoscale, Vol: 10, Pages: 19791-19798, ISSN: 2040-3364The functionalities offered by single-molecule electrical junctions are yet to be translated into monolayer or few-layer molecular films, where making effective and reproducible electrical contact is one of the challenging bottlenecks. Here we take a significant step in this direction by demonstrating that excellent electrical contact can be made with a monolayer biphenyl-4,4′-dithiol (BPDT) molecular film, sandwiched between gold and graphene electrodes. This sandwich device structure is advantageous, because the current flows through the molecules to the gold substrate in a ‘cross-plane’ manner, perpendicular to the plane of graphene, yielding high-conductance devices. We elucidate the nature of the cross-plane graphene/molecule/Au transport using quantum transport calculations and introduce a simple analytical model, which captures generic features of the current–voltage characteristic. Asymmetry in junction properties results from the disparity in electrode electrical properties, the alignment of the BPDT HOMO–LUMO energy levels and the specific characteristics of the graphene electrode. The experimental observation of scalability of junction properties within the junction area, in combination with a theoretical description of the transmission probability of the thiol–graphene contact, demonstrates that between 10% and 100% of the molecules make contact with the electrodes, which is several orders of magnitude greater than that achieved to date in the literature.
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Journal articleWilson LE, Jian X, White AJP, et al., 2018,
Synthesis and characterisation of linear and towards cyclic diferrocenes with alkynyl spacers
, Inorganics, Vol: 6, ISSN: 2304-6740Ferrocenediyl systems offer a motif that incorporates multiple functionality and redox-active centers, enabling these units to be used as molecular scaffolds in linear and cyclic compounds. Herein, we discuss a new modular methodology for the synthesis and incorporation of ferrocenediyl motifs within extended conjugated systems. We have synthesized a family of compounds featuring ferrocenediyl-ethynyl units with various para-substituted aromatic linkages. Extended linear, open-chain species have been isolated and understanding towards the analogous cyclic compounds gained. The new compounds have been probed using NMR, mass spectrometry, cyclic voltammetry and X-ray crystallography to gain further understanding of their structural and electronic properties.
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Journal articleApps SL, White AJP, Miller PW, et al., 2018,
Synthesis and reactivity of an N-triphos Mo(0) dinitrogen complex
, Dalton Transactions, Vol: 47, Pages: 11386-11396, ISSN: 1477-9234The preparation and reactivity of a novel molybdenum dinitrogen complex supported by a nitrogen-centred tripodal phosphine ligand (N-triphos, N(CH2PPh2)3, NP3Ph) are reported. Reaction of N-triphos with [MoX3(THF)3] (X = Cl, Br, I) gave the Mo(III) complex [MoX3(κ2-NP3Ph)(THF)] (1), where bidentate N-triphos coordination was observed. Reduction of this complex in the presence of dppm (bis(diphenylphosphino)methane) gave the dinitrogen complex [Mo(N2)(dppm)(κ3-NP3Ph)] (2), which exhibits moderate dinitrogen activation. An additional hydride complex, [Mo(H)2(dppm)(κ3-NP3Ph)] (4), was produced either as a minor side product during the reduction step, or as a major product by direct hydrogenation of the dinitrogen complex 2. The reactivity of the dinitrogen complex 2 with a range of Lewis acids was also investigated. At low temperatures, protic or borane Lewis acids (H+, BBr3 and tris(pentafluorophenyl)borane (BCF)) were found to coordinate to the apical nitrogen atom of the N-triphos ligand, with no conclusive evidence of any functionalisation of the dinitrogen ligand. Alkali metal Lewis acid addition to 2 resulted in the unexpected rearrangement of the N-triphos ligand to form [Mo(dppm)(PMePh2)(PCP)][B(C6F5)4] (7), where PCP, [Ph2PCNHCH2PPh2] is the carbenic ligand formed upon rearrangement from the reaction of 2 with M[B(C6F5)4] (M = Li, Na or K). Single crystal X-ray diffraction of complexes 1, 2, 4 and 7 provided structural confirmation of the N-triphos molybdenum complexes described.
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Conference paperEvans RJ, Hernandez-Gil J, Mohri Z, et al., 2018,
DEVELOPING NEW TARGETED MOLECULAR CONTRAST AGENTS FOR IMAGING INFLAMMATION OF VULNERABLE PLAQUES
, Annual Meeting of the British-Atherosclerosis-Society (BAS), Publisher: OXFORD UNIV PRESS, Pages: S3-S4, ISSN: 0008-6363 -
Journal articleGawne P, Man F, Fonslet J, et al., 2018,
Manganese-52: applications in cell radiolabelling and liposomal nanomedicine PET imaging using oxine (8-hydroxyquinoline) as an ionophore
, DALTON TRANSACTIONS, Vol: 47, Pages: 9283-9293, ISSN: 1477-9226 -
Journal articleWang L, Long NJ, Li L, et al., 2018,
Multi-functional bismuth-doped bioglasses: combining bioactivity and photothermal response for bone tumor treatment and tissue repair
, LIGHT-SCIENCE & APPLICATIONS, Vol: 7, ISSN: 2047-7538 -
Journal articleZeng F, Wu Y, Li X, et al., 2018,
Custom-made ceria nanoparticles show a neuroprotective effect by modulating phenotypic polarization of the microglia
, Angewandte Chemie International Edition, Vol: 57, Pages: 5808-5812, ISSN: 1521-3757The neuroprotective effect of ceria nanoparticles in the context of brain disorders has been explained by their antioxidant effect. However, the in-depth mechanism remains unknown. As resident immune cells in the brain, microglia exert a variety of functional reprogramming termed as polarization in response to stress stimuli. Herein, custom-made ceria nanoparticles were developed and found to scavenge multiple reactive oxygen species with extremely high efficiency. These nanoparticles drove microglial polarization from a pro-inflammatory phenotype to an anti-inflammatory phenotype under pathological conditions. Pretreatment of these nanoparticles changed the microglial function from detrimental to protective for the neuronal cells by blocking the pro-inflammatory signaling. This work not only helps to elucidate the mechanism of ceria-nanoparticle-mediated neuroprotection but also provides a new strategy to rebalance the immuno-environment by switching the equilibrium of the phenotypic activation of microglia.
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Journal articlePrice TW, Firth G, Eling CJ, et al., 2018,
A F-18 radiolabelled Zn(II) sensing fluorescent probe
, CHEMICAL COMMUNICATIONS, Vol: 54, Pages: 3227-3230, ISSN: 1359-7345 -
Conference paperMilan DC, Al-owaedi O, Bock S, et al., 2018,
Insulated molecular wires: Inhibiting orthogonal contacts in metal complex
, 255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727 -
Conference paperBamber J, Shah A, Bush N, et al., 2018,
Photoacoustic imaging and contrast agents in cancer research
, Leeds Microbubble Symposium -
Conference paperLeow CH, Marta B, Stanziola A, et al., 2017,
Multi-Frame Rate Plane Wave Contrast-Enhance Ultrasound Imaging for Tumour Vasculature Imaging and Perfusion Quantification
, IEEE International Ultrasonics Symposium (IUS), Publisher: IEEE, ISSN: 1948-5719A multi-frame rate plane wave imaging strategy is developed to simultaneously image tumor vasculature and quantify tumor perfusion. Customised imaging sequences interleaving a short but high frame rate (HFR) plane wave imaging sequence with a long but low frame rate imaging (LFR) sequence were implemented using a programmable ultrasound research platform. The results from a spatio-temporal coherence processing technique of ours demonstrated a significant improvement in the SNR and vasculature contrast when compared with the existing ultrafast Power Doppler (PD) using the same data. Initial perfusion quantification using LFR imaging was also demonstrated. Mean time intensity curve and some parametric measures were generated. Combining both structural and functional perfusion imaging using the multiframe rate sequences, a better evaluation of the tumour angiogenesis can be assessed.
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Conference paperMorse SV, Pouliopoulos AN, Chan T, et al., 2017,
Rapid short-pulse (RaSP) sequences improve the distribution of drug delivery to the brain in vivo
, IEEE UFFC, Publisher: IEEE, ISSN: 1948-5719Focused ultrasound and microbubbles have been shown to locally and noninvasively open the blood-brain barrier. Despite encouraging results in human patients, several performance and safety features, such as poor drug distribution, high drug accumulation along vessels and small sites of red blood cell extravasation, have been unavoidable. We have recently developed a new ultrasound sequence - rapid short-pulse (RaSP) sequence - designed to suppress these adverse features by promoting safer modes of cavitation activity throughout capillaries. In our RaSP sequences, low-pressure short ultrasonic pulses are emitted at kHz pulse repetition frequencies (PRF) and grouped into bursts. We have shown in vitro that RaSP sequences prolong microbubble lifetime and increase their mobility, enhancing the distribution of acoustic cavitation activity. Here we evaluate the ability of RaSP sequences to improve the in vivo performance and safety of ultrasound-mediated drug delivery to the brain.
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Contact
Professor Nick Long
Email: n.long@imperial.ac.uk
Telephone: +44 (0)20 7594 5781
Location
501J
Molecular Sciences Research Hub
White City Campus
