Imperial College London

PROFESSOR NICHOLAS LONG

Faculty of Natural SciencesDepartment of Chemistry

Sir Edward Frankland BP Chair -Inorganic Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5781n.long Website CV

 
 
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Location

 

365ChemistrySouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

236 results found

Miller P, Apps S, Long N, Cobalt(-I) triphos dinitrogen complexes: activation and silyl-functionalisation of N2, Chemical Communications, ISSN: 1359-7345

JOURNAL ARTICLE

Zhang G, Lin S, Leow GH, Pang KT, Hernandez-Gil J, Long NJ, Eckersley R, Matsunaga T, Tang M-Xet al., 2019, QUANTIFICATION OF VAPORISED TARGETED NANODROPLETS USING HIGH-FRAME-RATE ULTRASOUND AND OPTICS, ULTRASOUND IN MEDICINE AND BIOLOGY, Vol: 45, Pages: 1131-1142, ISSN: 0301-5629

JOURNAL ARTICLE

Leow CH, Bush NL, Stanziola A, Braga M, Shah A, Hernandez-Gil J, Long NJ, Aboagye EO, Bamber JC, Tang M-Xet al., 2019, 3-D Microvascular Imaging Using High Frame Rate Ultrasound and ASAP Without Contrast Agents: Development and Initial In Vivo Evaluation on Nontumor and Tumor Models., IEEE Trans Ultrason Ferroelectr Freq Control, Vol: 66, Pages: 939-948

Three-dimensional imaging is valuable to noninvasively assess angiogenesis given the complex 3-D architecture of vascular networks. The emergence of high frame rate (HFR) ultrasound, which can produce thousands of images per second, has inspired novel signal processing techniques and their applications in structural and functional imaging of blood vessels. Although highly sensitive vascular mapping has been demonstrated using ultrafast Doppler, the detectability of microvasculature from the background noise may be hindered by the low signal-to-noise ratio (SNR) particularly in the deeper region and without the use of contrast agents. We have recently demonstrated a coherence-based technique, acoustic subaperture imaging (ASAP), for super-contrast vascular imaging and illustrated the contrast improvement using HFR contrast-enhanced ultrasound. In this work, we provide a feasibility study for microvascular imaging using ASAP without contrast agents, and extend its capability from 2-D to volumetric vascular mapping. Using an ultrasound research system and a preclinical probe, we demonstrated the improved visibility of microvascular mapping using ASAP in comparison to ultrafast power Doppler (PD) on a mouse kidney, liver, and tumor without contrast agent injection. The SNR of ASAP images improves in average by 10 dB when compared to PD. In addition, directional velocity mappings were also demonstrated by combining ASAP with the phase information extracted from lag-1 autocorrelation. The 3-D vascular and velocity mapping of the mouse kidney, liver, and tumor were demonstrated by stacking the ASAP images acquired using 2-D ultrasound imaging and a trigger-controlled linear translation stage. The 3-D results depicted clear microvasculature morphologies and functional information in terms of flow direction and velocity in two nontumor models and a tumor model. In conclusion, we have demonstrated a new 3-D in vivo ultrasound microvascular imaging technique with significantly

JOURNAL ARTICLE

Morse SV, Pouliopoulos AN, Chan TG, Copping MJ, Lin J, Long NJ, Choi JJet al., 2019, Rapid Short-pulse Ultrasound Delivers Drugs Uniformly across the Murine Blood-Brain Barrier with Negligible Disruption., Radiology, Vol: 291, Pages: 459-466

Background Previous work has demonstrated that drugs can be delivered across the blood-brain barrier by exposing circulating microbubbles to a sequence of long ultrasound pulses. Although this sequence has successfully delivered drugs to the brain, concerns remain regarding potentially harmful effects from disrupting the brain vasculature. Purpose To determine whether a low-energy, rapid, short-pulse ultrasound sequence can efficiently and safely deliver drugs to the murine brain. Materials and Methods Twenty-eight female wild-type mice underwent focused ultrasound treatment after injections of microbubbles and a labeled model drug, while three control mice were not treated (May-November 2017). The left hippocampus of 14 mice was exposed to low-energy short pulses (1 MHz; five cycles; peak negative pressure, 0.35 MPa) of ultrasound emitted at a rapid rate (1.25 kHz) in bursts (0.5 Hz), and another 14 mice were exposed to standard long pulses (10 msec, 0.5 Hz) containing 150 times more acoustic energy. Mice were humanely killed at 0 (n = 5), 10 (n = 3), or 20 minutes (n = 3) after ultrasound treatment. Hematoxylin-eosin (H-E) staining was performed on three mice. The delivered drug dose and distribution were quantified with the normalized optical density and coefficient of variation. Safety was assessed by H-E staining, the amount of albumin released, and the duration of permeability change in the blood-brain barrier. Statistical analysis was performed by using the Student t test. Results The rapid short-pulse sequence delivered drugs uniformly throughout the parenchyma. The acoustic energy emitted from the microbubbles also predicted the delivered dose (r = 0.97). Disruption in the blood-brain barrier lasted less than 10 minutes and 3.4-fold less albumin was released into the brain than with long pulses. No vascular or tissue damage from rapid short-pulse exposure was observable using H-E staining. Conclusion The rapid short-pulse ultrasound sequence is a minimally

JOURNAL ARTICLE

Clough TJ, Jiang L, Wong K-L, Long NJet al., 2019, Ligand design strategies to increase stability of gadolinium-based magnetic resonance imaging contrast agents, NATURE COMMUNICATIONS, Vol: 10, ISSN: 2041-1723

JOURNAL ARTICLE

Jantan KA, McArdle JM, Mognon L, Fiorini V, Wilkinson LA, White AJP, Stagni S, Long NJ, Wilton-Ely JDETet al., 2019, Heteromultimetallic compounds based on polyfunctional carboxylate linkers, NEW JOURNAL OF CHEMISTRY, Vol: 43, Pages: 3199-3207, ISSN: 1144-0546

JOURNAL ARTICLE

Rains JGD, ODonnelly K, Oliver T, Woscholski R, Long NJ, Barter LMCet al., 2019, Bicarbonate inhibition of carbonic anhydrase mimics hinders catalytic efficiency: Elucidating the mechanism and gaining insight toward improving speed and efficiency, ACS Catalysis, Vol: 9, Pages: 1353-1365, ISSN: 2155-5435

Carbonic anhydrase (CA) mimics are often studied with a focus on the hydration of CO2 for atmospheric carbon capture. Consequently, the reverse reaction (dehydration of HCO3–) has received minimal attention, so much so that the rate-limiting step of the dehydration reaction in CA mimics is currently unknown. The rate-limiting step of the hydration reaction is reported to be the bicarbonate-bound intermediate step, and thus is susceptible to product inhibition. It is not, however, clear if this inhibition is a consequence of an increase in the rate of the competing dehydration reaction or resulting from the strong affinity of bicarbonate to the mimic. To address this, insight into the dehydration reaction kinetics is needed. We therefore report the most comprehensive study of a CA mimic to date. The dehydration profile of the fastest small-molecule CA mimic, ZnL1S, was characterized, and consequently evidence for the rate-limiting step for the dehydration reaction was seen to be the bicarbonate-bound intermediate step, much like the hydration reaction. This experimental validation of the rate-limiting step was achieved through a variety of methods including NMR experiments and the effect of inhibitors, substrate concentration, and metal center on activity. With this understanding, an improvement in the favorability of the rate-limiting step was achieved, resulting in decreased bicarbonate inhibition. Thus, an increase in the mimic’s kcat for both reactions was observed, resulting in the largest rate constants of any small-molecule CA mimic reported to date (28 093 and 579 M–1 s–1 for hydration and dehydration, respectively). Enzyme-like kcat/km values were obtained for ZnL1S (5.9 × 105 M–1 s–1 for CO2 hydration), and notably there is only a difference of 2.5 orders of magnitude from the enzyme, the closest of any CA mimic reported in the literature. The results from this work can be applied to the development and improvement

JOURNAL ARTICLE

Wilkinson LA, Yue TTC, Massey E, White AJP, Long NJet al., 2019, Cyanoferrocenes as redox-active metalloligands for coordination-driven self-assembly, DALTON TRANSACTIONS, Vol: 48, Pages: 72-78, ISSN: 1477-9226

JOURNAL ARTICLE

Pensa E, Karpowicz R, Jabaoński A, Trzybiński D, Woźniak K, Šakić D, Vrček V, Long NJ, Albrecht T, Kowalski Ket al., 2019, Gold-Induced Desulfurization in a Bis(ferrocenyl) Alkane Dithiol, Organometallics, ISSN: 0276-7333

© 2019 American Chemical Society. Thiol-modified ferrocenes on gold have been archetypical model systems for many fundamental charge transfer and other studies, since both thiol-gold and ferrocene redox chemistry are considered to be well-understood. Thus unexpectedly, we found that for a representative of a new class of flexibly linked bis-ferrocenyl compounds, namely, 1-10-bis(1-ferrocenyl)decane dithiol, surface immobilization on gold failed. Instead, in the presence of gold, molecular decomposition took place, resulting in sulfur-based adlayers and well-defined molecular elimination products, for which we provide spectroscopic evidence. Careful control experiments and comparison with related ferrocene compounds provide insight into the mechanism of the observed elimination reactions, as a combined effect of the molecular structure and the nature of the gold/sulfur bond. These findings, thus, have a broader impact on the design of molecular adlayers, for example, in the context of surface functionalization in sensing or the synthesis of gold nanoparticles.

JOURNAL ARTICLE

Smith AJ, Gawne PJ, Ma MT, Blower PJ, Southworth R, Long NJet 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: 1477-9226

JOURNAL ARTICLE

Li B, Famili M, Pensa E, Grace I, Long NJ, Lambert C, Albrecht T, Cohen LFet al., 2018, Cross-plane conductance through a graphene/molecular monolayer/Au sandwich, NANOSCALE, Vol: 10, Pages: 19791-19798, ISSN: 2040-3364

JOURNAL ARTICLE

Apps SL, White AJP, Miller PW, Long NJet al., 2018, Synthesis and reactivity of an N-triphos Mo(0) dinitrogen complex, Dalton Transactions, Vol: 47, Pages: 11386-11396, ISSN: 1477-9234

The 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.

JOURNAL ARTICLE

Wilson LE, Jian X, White AJP, Long NJet al., 2018, Synthesis and Characterisation of Linear and Towards Cyclic Diferrocenes with Alkynyl Spacers, INORGANICS, Vol: 6, ISSN: 2304-6740

JOURNAL ARTICLE

Evans RJ, Hernandez-Gil J, Mohri Z, Chooi KY, Lavin-Plaza B, Phinikaridou A, Pease JE, Krams R, Botnar R, Long NJet 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

CONFERENCE PAPER

Gawne P, Man F, Fonslet J, Radia R, Bordoloi J, Cleveland M, Jimenez-Royo P, Gabizon A, Blower PJ, Long N, de Rosales RTMet 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 ARTICLE

Wang L, Long NJ, Li L, Lu Y, Li M, Cao J, Zhang Y, Zhang Q, Xu S, Yang Z, Mao C, Peng Met 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 ARTICLE

Zeng F, Wu Y, Li X, Ge X, Guo Q, Lou X, Cao Z, Hu B, Long NJ, Mao Y, Li Cet 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: 1433-7851

JOURNAL ARTICLE

Price TW, Firth G, Eling CJ, Kinnon M, Long NJ, Sturge J, Stasiuk GJet al., 2018, A F-18 radiolabelled Zn(II) sensing fluorescent probe, CHEMICAL COMMUNICATIONS, Vol: 54, Pages: 3227-3230, ISSN: 1359-7345

JOURNAL ARTICLE

Bamber J, Shah A, Bush N, Costa M, Harris-Birtill D, Lin S, Singh M, Scienti O, Darabara D, Elson D, ter Haar G, Rivens I, Long N, Tang Met al., Photoacoustic imaging and contrast agents in cancer research, Leeds Microbubble Symposium

CONFERENCE PAPER

Hau Leow C, Bush NL, Stanziola A, Braga M, Shah A, Hemández-Gil J, Long NJ, Aboagye EO, Bamber JC, Tang MXet al., 2018, High-Contrast 3D in Vivo Microvascular Imaging Using Scanning 2D Ultrasound and Acoutic Sub-Aperture Processing (ASAP), ISSN: 1948-5719

© 2018 IEEE. Non-invasive techniques for microvascular environment assessment are invaluable for clinical diagnosis and treatment monitoring. We recently developed a super contrast processing to suppress noise background in ultrafast Power Doppler, known an acoustic sub-aperture processing (ASAP), and demonstrate using 2D contrast enhance ultrasound. However, 2D imaging is insufficient to represent the 3D complex vascular environment. We therefore extend our study to demonstrate the feasibility of our technique for volumetric imaging. A pseudo-3D imaging technique was developed and demonstrated using a research system and preclinical transducer. A mouse liver was scanned using 2D ultrafast ultrasound and a mechanical translation stage. Initial results not only demonstrated a substantial noise reduction in 2D vascular images using ASAP, but also a high contrast volumetric rendering of a mouse liver. Our technique is ready for clinical use to provide better evaluation of angiogenesis.

CONFERENCE PAPER

Leow CH, Braga M, Bush NL, Stanziola A, Shah A, Hernández-Gil J, Long NJ, Aboagye EO, Bamber JC, Tang MXet al., 2018, Contrast vs Non-Contrast Enhanced Microvascular Imaging Using Acoustic Sub-Aperture Processing (ASAP): In Vivo Demonstration, ISSN: 1948-5719

© 2018 IEEE. Angiogenesis plays a vital role in the progression of cancer. Non-invasive imaging techniques capable of assessing the microenvironment are therefore of clinical interest. Although highly sensitive vascular mapping has been demonstrated using ultrafast Power Doppler (PD), the detectability of microvasculature from the background noise may be hindered by the low signal-to-noise ratio (SNR) in deeper region and without the use of contrast agents. We recently developed acoustic sub-aperture processing (ASAP) processing for super-contrast vasculature imaging. This technique relies on the spatial coherence of the backscattered echoes over different acquisitions to substantially reduce the noise floor compared to the power Doppler (PD) technique. In this study, we demonstrate the feasibility of applying ASAP processing for non-contrast enhanced microvascular imaging in preclinical condition, and compare it with contrast enhanced ASAP as well as ultrafast PD. Comparing to PD, ASAP exhibit SNR improvement up to 12 dB. Higher SNR and extra visibility of smaller vessel are also demonstrated in contrast enhanced images in comparison to the non-contrast images. In conclusion, we have demonstrated the feasibility of using ASAP in vivo for non-contrast microvascular imaging, and the added benefit of using contrast agents in microvascular imaging.

CONFERENCE PAPER

Parker D, Long NJ, Faulkner S, 2017, Challenges for chemistry in molecular imaging, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Vol: 375, ISSN: 1364-503X

JOURNAL ARTICLE

Leow CH, Braga M, Hernandez-Gil J, Long NJ, Aboagye EO, Tang MXet al., 2017, Multi-frame rate plane wave contrast-enhanced ultrasound imaging for tumour vascular imaging and perfusion quantification, ISSN: 1948-5719

© 2017 IEEE. Angiogenesis and blood flow dynamics play an important role in the development of malignant tumours and their response to treatment. While contrast enhanced ultrasound (CEUS) imaging with microbubble contrast agents as a tool for imaging angiogenesis and flow dynamics has shown great potential [1], recent development of plane wave high frame-rate (HFR) CEUS has offered new opportunities in such applications. In this study, we demonstrate an interleaved multi-frame rate plane wave CEUS imaging to quantify perfusion and to image vascular structure with improved resolution and contrast.

CONFERENCE PAPER

Lin S, Shah A, Hernandez-Gil J, Stanziola A, Harriss B, Matsunaga T, Long N, Bamber J, Tang MXet al., 2017, Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging, ISSN: 1948-5719

© 2017 IEEE. To explore the extravascular space, sub-micron phase-change droplets show widespread interest in medical imaging and therapy with various modalities, such as ultrasound and photoacoustic. Existing studies (Wilson 2012, Wei 2014) on such dual-modality contrast agents have demonstrated the generation of both optical and ultrasound contrast after optical activation. However these studies did not explore the option of acoustic activation. Furthermore, high boiling point perfluorocarbons were used in these studies. A low boiling point may be preferred, to minimise un-wanted bioeffects, especially when activating in deeper tissues. In this study, we demonstrate a versatile phase-change sub-micron contrast agent that can provide three modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound contrast with optical activation, and 3) ultrasound contrast with acoustic activation. This would add versatility of vaporisation triggering, offering new possibilities in dual mode imaging, molecular imaging and drug delivery.

CONFERENCE PAPER

Morse SV, Pouliopoulos AN, Chan T, Lin J, Copping M, Long NJ, Choi JJet al., 2017, Rapid short-pulse (RaSP) sequences improve the distribution of drug delivery to the brain in vivo, ISSN: 1948-5719

© 2017 IEEE. Focused 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.

CONFERENCE PAPER

Du S, Hernandez-Gil J, Dong H, Zheng X, Lyu G, Banobre-Lopez M, Gallo J, Sun L-D, Yan C-H, Long NJet al., 2017, Design and validation of a new ratiometric intracellular pH imaging probe using lanthanide-doped upconverting nanoparticles, DALTON TRANSACTIONS, Vol: 46, Pages: 13957-13965, ISSN: 1477-9226

JOURNAL ARTICLE

Leber R, Wilson LE, Robaschik P, Inkpen MS, Payne DJ, Long NJ, Albrecht T, Hirjibehedin CF, Heutz Set al., 2017, High-Vacuum Deposition of Biferrocene Thin Films on Room-Temperature Substrates, CHEMISTRY OF MATERIALS, Vol: 29, Pages: 8663-8669, ISSN: 0897-4756

JOURNAL ARTICLE

Gallo J, Harriss BI, Hernandez-Gil J, Banobre-Lopez M, Long NJet al., 2017, Probing T-1-T-2 interactions and their imaging implications through a thermally responsive nanoprobe, NANOSCALE, Vol: 9, Pages: 11318-11326, ISSN: 2040-3364

JOURNAL ARTICLE

Al-Owaedi OA, Bock S, Milan DC, Oerthel M-C, Inkpen MS, Yufit DS, Sobolev AN, Long NJ, Albrecht T, Higgins SJ, Bryce MR, Nichols RJ, Lambert CJ, Low PJet al., 2017, Insulated molecular wires: inhibiting orthogonal contacts in metal complex based molecular junctions, NANOSCALE, Vol: 9, Pages: 9902-9912, ISSN: 2040-3364

JOURNAL ARTICLE

Wilson LE, Hassenrueck C, Winter RF, White AJP, Albrecht T, Long NJet al., 2017, Ferrocene- and Biferrocene-Containing Macrocycles towards Single-Molecule Electronics, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 56, Pages: 6838-6842, ISSN: 1433-7851

JOURNAL ARTICLE

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