Imperial College London

Professor Matthew J. Fuchter

Faculty of Natural SciencesDepartment of Chemistry

Professor of Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5815m.fuchter

 
 
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Location

 

110DMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Publication Type
Year
to

150 results found

Ward MD, Shi W, Gasparini N, Nelson J, Wade J, Fuchter MJet al., 2022, Best practices in the measurement of circularly polarised photodetectors, JOURNAL OF MATERIALS CHEMISTRY C, ISSN: 2050-7526

Journal article

Wan L, Wade J, Shi X, Xu S, Fuchter MJ, Campbell AJet al., 2022, Highly Efficient Inverted Circularly Polarized Organic Light Emitting Diodes (vol 12, pg 39471, 2020), ACS APPLIED MATERIALS & INTERFACES, Vol: 14, Pages: 27523-27523, ISSN: 1944-8244

Journal article

Wan L, Wade J, Salerno F, Arteaga O, Laidlaw B, Wang X, Penfold T, Fuchter MJ, Campbell AJet al., 2022, Inverting the Handedness of Circularly Polarized Luminescence from Light-Emitting Polymers Using Film Thickness (vol 13, pg 8099, 2019), ACS NANO, Vol: 16, Pages: 9962-9963, ISSN: 1936-0851

Journal article

Wan L, Liu Y, Fuchter M, Yan Bet al., 2022, Anomalous circularly polarized light emission caused by the chirality-driven topological electronic properties

<jats:title>Abstract</jats:title> <jats:p>Chirality of organic molecules is characterized by selective absorption and emission of circularly-polarized light (CPL). A consensus for chiral emission (absorption) is that molecular chirality determines the favored light handedness regardless of the light-emitting (incident) direction. Refreshing above textbook knowledge, we discover an unconventional CPL emission effect in organic light-emitting diodes (OLEDs), where counter-propagating CPLs exhibit opposite handedness. This direction-dependent CPL emission boosts the net polarization rate by orders of magnitude in OLED devices by resolving the long-lasting back-electrode reflection problem. The anomalous CPL emission originates in a ubiquitous topological electronic property in chiral materials, i.e., the orbital-momentum locking. Our work paves the way to design novel chiroptoelectronic devices and reveals that chiral materials, topological electrons, and CPL have intimate connections in the quantum regime.</jats:p>

Journal article

Yan H, Wade J, Wan L, Kwon S, Fuchter MJ, Campbell AJ, Kim J-Set al., 2022, Enhancing hole carrier injection via low electrochemical doping on circularly polarized polymer light-emitting diodes, JOURNAL OF MATERIALS CHEMISTRY C, Vol: 10, Pages: 9512-9520, ISSN: 2050-7526

Journal article

Wan L, Wade J, Wang X, Campbell A, Fuchter Met al., 2022, Engineering the sign of circularly polarized emission in achiral polymer – chiral small molecule blends as a function of blend ratio, Journal of Materials Chemistry C, Vol: 10, Pages: 5168-5172, ISSN: 2050-7526

Circularly polarized organic light-emitting diodes (CP-OLEDs) that demonstrate both state-of-the-art efficiency and strongly circularly polarized (CP) electroluminescence have proved a considerable technical challenge. Furthermore, multiple factors – from film thickness to device structure – have been shown to influence the sign of the emitted CP light, independent of the handedness (absolute stereochemistry) of the chiral emitter. Here we report CP-OLEDs using a blend of poly(9,9-dioctylfluorene-alt-bithiophene) (F8T2) and a chiral small molecule additive (1-aza[6]helicene, aza[6]H). We demonstrate CP-OLEDs with an impressive electroluminescence dissymmetry (gEL) > 0.3 and a current efficiency of 0.53 cd A−1 and brightness of 3023 cd m−2. While at low aza[6]H loadings, F8T2 blends are consistent with previous observations of CP dissymetric inversion as a function of film thickness/excitation mode, a higher loading of aza[6]H (∼40 wt%) removes such dependencies while retaining excellent g-factors. The materials disclosed will allow for further mechanistic studies of chiral polymeric materials and provide new opportunities for chiroptical optimisation in films and devices.

Journal article

Liu T, Shi W, Tang W, Liu Z, Schroeder BC, Fenwick O, Fuchter MJet al., 2022, High responsivity circular polarized light detectors based on quasi two-dimensional chiral perovskite films., ACS Nano, Vol: 16, Pages: 2682-2689, ISSN: 1936-0851

Circularly polarized light (CPL) has considerable technological potential, from quantum computing to bioimaging. To maximize the opportunity, high performance photodetectors that can directly distinguish left-handed and right-handed circularly polarized light are needed. Hybrid organic-inorganic perovskites containing chiral organic ligands are an emerging candidate for the active material in CPL photodetecting devices, but current studies suggest there to be a trade-off between the ability to differentially absorb CPL and photocurrent responsivity in chiral perovskites devices. Here, we report a CPL detector based on quasi two-dimensional (quasi-2D) chiral perovskite films. We find it is possible to generate materials where the circular dichroism (CD) is comparable in both 2D and quasi-2D films, while the responsivity of the photodetector improves for the latter. Given this, we are able to showcase a CPL photodetector that exhibits both a high dissymmetry factor of 0.15 and a high responsivity of 15.7 A W-1. We believe our data further advocates the potential of chiral perovskites in CPL-dependent photonic technologies.

Journal article

Howell SJ, Kenny LM, Lord S, Krebs MG, Arkenau T, Baird R, MacPherson IR, Bahl A, Clack G, Ainscow E, Barrett AGM, Dickinson PA, Fuchter MJ, Lehnert M, Ali S, McIntosh S, Coombes Cet al., 2022, A clinical study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in patients with advanced triple negative breast cancer (TNBC), San Antonio Breast Cancer Symposium, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

McNeish I, Spiliopoulou P, Spear S, Mirza H, Garner I, grundland-freile F, Cheng Z, Ennis D, Iyer N, McNamara S, Natoli M, Fuchter M, Brown Ret al., 2022, Dual G9A/EZH2 inhibition stimulates anti-tumour immune response in ovarian high-grade serous carcinoma, Molecular Cancer Therapeutics, Vol: 21, Pages: 522-534, ISSN: 1535-7163

Ovarian high-grade serous carcinoma (HGSC) prognosis correlates directly with presence of intratumoral lymphocytes. However, cancer immunotherapy has yet to achieve meaningful survival benefit in patients with HGSC. Epigenetic silencing of immunostimulatory genes is implicated in immune evasion in HGSC and re-expression of these genes could promote tumour immune clearance. We discovered that simultaneous inhibition of the histone methyltransferases G9A and EZH2 activates the CXCL10-CXCR3 axis and increases homing of intratumoral effector lymphocytes and natural killer cells whilst suppressing tumour-promoting FoxP3+ CD4 T cells. The dual G9A/EZH2 inhibitor HKMTI-1-005 induced chromatin changes that resulted in the transcriptional activation of immunostimulatory gene networks, including the re-expression of elements of the ERV-K endogenous retroviral family. Importantly, treatment with HKMTI-1-005 improved the survival of mice bearing Trp53-/- null ID8 ovarian tumours and resulted in tumour burden reduction. These results indicate that inhibiting G9A and EZH2 in ovarian cancer alters the immune microenvironment and reduces tumour growth and therefore positions dual inhibition of G9A/EZH2 as a strategy for clinical development.

Journal article

dos Santos JM, Sun D, Moreno-Naranjo JM, Hall D, Zinna F, Ryan STJ, Shi W, Matulaitis T, Cordes DB, Slawin AMZ, Beljonne D, Warriner SL, Olivier Y, Fuchter MJ, Zysman-Colman Eet al., 2022, An S-shaped double helicene showing both multi-resonance thermally activated delayed fluorescence and circularly polarized luminescence, JOURNAL OF MATERIALS CHEMISTRY C, Vol: 10, Pages: 4861-4870, ISSN: 2050-7526

Journal article

Ward MD, Wade J, Shi X, Nelson J, Campbell AJ, Fuchter MJet al., 2022, Highly selective high-speed circularly polarized photodiodes based on π-conjugated polymers, Advanced Optical Materials, Vol: 10, ISSN: 2195-1071

Chiral π-conjugated molecular systems that are intrinsically sensitive to the handedness of circularly polarized (CP) light potentially allow for miniaturized, low-cost CP detection devices. Such devices promise to transform several technologies, including biosensing, quantum optics, and communication of data encrypted by exploiting the spin angular momentum of light. Here a simple, bilayer organic photodiode (CP OPD) comprising an achiral π-conjugated polymer–chiral additive blend as the electron donor layer and an achiral C60 electron acceptor layer is realized. These devices exhibit considerable photocurrent dissymmetry gph, with absolute values as high as 0.85 and dark currents as low as 10 pA. Impressively, they showcase a linear dynamic range of 80 dB, and rise and fall times of ≈7 µs, which significantly outperforms all previously reported CP selective photodetectors. Mechanistically, it is shown that the gph is sensitive to the thickness of both the chiral donor and achiral acceptor layers and that a trade-off exists between the external quantum efficiency and gph. The fast-switching speeds of these devices, coupled with their large dynamic range and highly selective response to CP light, opens up the possibility of their direct application in CP sensing and optical communications.

Journal article

Greenfield J, Mihael G, Gibson R, Han G, Fuchter Met al., 2021, Efficient electrocatalytic switching of azoheteroarenes in the condensed phases, Journal of the American Chemical Society, Vol: 143, Pages: 15250-15257, ISSN: 0002-7863

Azo-based photoswitches have shown promise as molecular solar thermal (MOST) materials, due to their ability to storeenergy in their metastable Z isomeric form. The energy is then released, in the form of heat, upon photoisomerisation to thethermodynamically stable E form. However, obtaining a high energy density and recovering the stored energy with high efficiency requiresthe materials to be employed in the condensed phase and display a high degree of Z to E switching, respectively: both of which arechallenging to engineer. Here we show that arylazopyrazole motifs undergo efficient redox-induced Z to E switching in both the solutionand condensed phase, to a higher completeness of switching than achieved photochemically. This redox-initiated pathway lowers thebarrier to Z to E isomerization by 27 kJ/mol, whilst in the condensed phase, the efficiency of electrochemical switching is improved by overan order of magnitude relative to that in the solution state. The influence of the photoswitch’s phase, electrical conductivity, and viscosityon the electrochemical switching in the condensed phase is reported, culminating in a set of design rules to facilitate further investigations.We anticipate the use of an alternative stimulus to light will facilitate the application of MOST materials in situations where photo-triggeredheat release is unachievable or inefficient, e.g. indoor or at night. Furthermore, exploiting the electrocatalytic mechanism, whereby acatalytic amount of charge triggers Z to E switching via a redox process, bypasses the need for fine-tuning of the photoswitchingchromophore to achieve complete Z to E switching, thus providing an alternative approach to photoswitch molecular design.

Journal article

Krebs MG, Lord S, Kenny L, Baird RD, MacPherson I, Bahl A, Clack G, Ainscow E, Barrett AG, Dickinson P, Fuchter MJ, Lehnert M, Ali S, Mcintosh S, Coombes RCet al., 2021, First in human, modular study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in patients with advanced solid malignancies, Congress of the European-Society-for-Medical-Oncology (ESMO), Publisher: ELSEVIER, Pages: S458-S458, ISSN: 0923-7534

Conference paper

Laidlaw B, Eng J, Wade J, Shi X, Salerno F, Fuchter MJ, Penfold TJet al., 2021, On the factors influencing the chiroptical response of conjugated polymer thin films, Chemical Communications, Vol: 57, Pages: 9914-9917, ISSN: 1359-7345

We study the influence of the physical and chemical structure on the chiroptical response of fluorene-based polymeric systems, namely poly(9,9-dioctylfluorene) (PFO) and the donor–acceptor type copolymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT). We reveal the significance of electric-magnetic coupling, at both short (molecular-level) and intermediate (delocalised over multiple polymer chains) length scales, on the magnitude of the dissymmetry. These findings provide a framework for the design of new materials with enhanced chiroptical response.

Journal article

Schmidt J, Weatherby J, Sugden I, Santana-Bonilla A, Salerno F, Fuchter M, Johnson E, Nelson J, Jelfs Ket al., 2021, Computational screening of organic semiconductors: exploring side-group functionalisation and assembly to optimise charge transport in chiral molecules, Crystal Growth and Design, Vol: 21, Pages: 5036-5049, ISSN: 1528-7483

Molecular materials are challenging to design as their packing arrangement and hence properties are subject to subtle variations in the interplay of soft intermolecular interactions that are difficult to predict. The rational design of new molecular materials with tailored properties is currently hampered by the lack of knowledge of how a candidate molecule will pack in space and how we can control the polymorphs we can experimentally obtain. Here, we develop a simplified approach to aid the material design process, by the development of a screening process that is used to test 1344 helicene molecules that have potential as organic electronic materials. Our approach bridges the gap between single molecule design, molecular assembly, and the resulting charge-carrier mobilities. We find that fluorination significantly improves electron transport in the molecular material by up to 200%; the reference [6]helicene packing showed a mobility of 0.30 cm2 V-1 s-1, fluorination increased the mobility to up to 0.96 and 0.97 (13-fluoro[6]H and 4,13-difluoro[6]H), assuming an outer reorganisation energy of 0.30 eV. Side groups containing triple bonds largely lead to improved transfer integrals. We validate our screening approach through the use of crystal structure prediction to confirm the presence of favourable packing motifs to maximize charge mobility.

Journal article

Greenfield JL, Wade J, Brandt JR, Shi X, Penfold TJ, Fuchter MJet al., 2021, Pathways to increase the dissymmetry in the interaction of chiral light and chiral molecules, Chemical Science, Vol: 12, Pages: 8589-8602, ISSN: 2041-6520

The dissymmetric interaction between circularly polarised (CP) light and chiral molecules is central to a range of areas, from spectroscopy and imaging to next-generation photonic devices. However, the selectivity in absorption or emission of left-handed versus right-handed CP light is low for many molecular systems. In this perspective, we assess the magnitude of the measured chiroptical response for a variety of chiral systems, ranging from small molecules to large supramolecular assemblies, and highlight the challenges towards enhancing chiroptical activity. We explain the origins of low CP dissymmetry and showcase recent examples in which molecular design, and the modification of light itself, enable larger responses. Our discussion spans spatial extension of the chiral chromophore, manipulation of transition dipole moments, exploitation of forbidden transitions and creation of macroscopic chiral structures; all of which can increase the dissymmetry. Whilst the specific strategy taken to enhance the dissymmetric interaction will depend on the application of interest, these approaches offer hope for the development and advancement of all research fields that involve interactions of chiral molecules and light.

Journal article

Garner IM, Su Z, Hu S, Wu Y, McNeish IA, Fuchter MJ, Brown Ret al., 2021, Modulation of homologous recombination repair pathway gene expression by a dual EZH2 and EHMT2 histone methyltransferase inhibitor and synergy with PARP inhibitors in ovarian cancer., Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Wan L, Shi X, Wade J, Campbell AJ, Fuchter MJet al., 2021, Strongly Circularly Polarized Crystalline and β-Phase Emission from Poly(9,9-dioctylfluorene)-Based Deep-Blue Light-Emitting Diodes, Advanced Optical Materials, Vol: 9, ISSN: 2195-1071

A key challenge in the realization of circularly polarized polymer light-emitting diodes (CP-PLEDs) is the generation of highly circularly polarized deep-blue electroluminescence (EL). Here, by blending the achiral luminescent polymer poly(9,9-dioctylfluorene) (PFO) with a helically chiral molecule 1-aza[6]helicene the authors present CP-PLEDs with state-of-the-art device performance for deep-blue CP emission: for an inverted device with a semicrystalline microstructure a current efficiency (CE) of 1.13 cd A−1, a power efficiency (PE) of 0.81 lm W−1, and an EL dissymmetry (gEL) of −0.42 are achieved; for the planarized and extended “β-phase” chain conformation a CE of 1.23 cd A−1, a PE of 0.63 lm W−1, and a gEL of −0.44 are achieved. While these two phases achieve both high CE, as well as gEL, the latter affords the first demonstration of chiral β-phase emission from solid-state PFO devices. Such strongly circularly polarized light is generated from a supramolecular assembly of interacting planar polymer backbones. The authors rationalize that the strong chiroptical effects observed within such chiral β-phase PFO domains originate from coupled interchain aggregates. The findings not only demonstrate efficient deep-blue CP-PLEDs, but also provide insight into the mechanisms that underpin the strong CP emission from excitonically coupled polymer chains.

Journal article

LanyonHogg T, Ritzefeld M, Zhang L, Andrei SA, Pogranyi B, Mondal M, Sefer L, Johnston CD, Coupland CE, Greenfield JL, Newington J, Fuchter MJ, Magee AI, Siebold C, Tate EWet al., 2021, Photochemical Probe Identification of a Small‐Molecule Inhibitor Binding Site in Hedgehog Acyltransferase (HHAT)**, Angewandte Chemie, Vol: 133, Pages: 13654-13659, ISSN: 0044-8249

Journal article

Lanyon-Hogg T, Ritzefeld M, Zhang L, Pogranyi B, Mondal M, Sefer L, Johnston CD, Coupland CE, Andrei SA, Newington J, Magee AI, Siebold C, Tate EWet al., 2021, Photochemical probe identification of the small-molecule binding site in a mammalian membrane-bound O-acyltransferase, Angewandte Chemie International Edition, Vol: 60, Pages: 13542-13547, ISSN: 1433-7851

The mammalian membrane‐bound O ‐acyltransferase (MBOAT) superfamily is involved in biological processes including growth, development and appetite sensing. MBOATs are attractive drug targets in cancer and obesity; however, information on the binding site and molecular mechanisms underlying small‐molecule inhibition is elusive. This study reports rational development of a photochemical probe to interrogate a novel small‐molecule inhibitor binding site in the human MBOAT Hedgehog acyltransferase (HHAT). Structure‐activity relationship investigation identified single enantiomer IMP‐1575 , the most potent HHAT inhibitor reported to‐date, and guided design of photocrosslinking probes that maintained HHAT‐inhibitory potency. Photocrosslinking and proteomic sequencing of HHAT delivered identification of the first small‐molecule binding site in a mammalian MBOAT. Topology and homology data suggested a potential mechanism for HHAT inhibition which was confirmed via kinetic analysis. Our results provide an optimal HHAT tool inhibitor IMP‐1575 ( K i = 38 nM) and a strategy for mapping small molecule interaction sites in MBOATs.

Journal article

Wade J, Higgins SG, Heutz S, Lidzey DG, Fuchter MJ, Stingelin Net al., 2021, In memoriam Alasdair James Campbell (11 May 1961-27 February 2021), Journal of Materials Chemistry C, Vol: 9, Pages: 6100-6102, ISSN: 2050-7526

Journal article

Ward M, Wade J, Shi X, Nelson J, Campbell A, Fuchter Met al., 2021, Highly Selective Ultrafast Circularly Polarized Photodiodes Based on π-Conjugated Polymers

<jats:p>Chiral π-conjugated molecular systems that are intrinsically sensitive to the handedness of circularly polarized (CP) light potentially allow for miniaturized, low-cost CP detection devices. Such devices promise to transform several technologies, including biosensing, quantum optics and communication of data encrypted by exploiting the spin angular momentum of light. Here we realize a simple, bilayer organic photodiode (CP OPD) comprising an achiral π-conjugated polymer–chiral additive blend as the electron donor layer and an achiral C&lt;sub&gt;60&lt;/sub&gt; electron acceptor layer. These devices exhibit considerable photocurrent dissymmetry &lt;i&gt;g&lt;/i&gt;&lt;sub&gt;ph&lt;/sub&gt;, with absolute values as high as 0.85 and dark currents as low as 10 pA. Impressively, they showcase a linear dynamic range of 80 dB, and rise and fall times of 50 and 270 ns respectively, which significantly outperforms all previously reported CP selective photodetectors. Mechanistically, we show that the &lt;i&gt;g&lt;/i&gt;&lt;sub&gt;ph&lt;/sub&gt; is sensitive to the thickness of &lt;i&gt;both&lt;/i&gt; the chiral donor and achiral acceptor layers and that a trade-off exists between the external quantum efficiency (EQE) and &lt;i&gt;g&lt;/i&gt;&lt;sub&gt;ph&lt;/sub&gt;. The fast-switching speeds of these devices, coupled with their large dynamic range and highly selective response to CP light, opens up the possibility of their direct application in CP sensing and optical communication.</jats:p>

Journal article

Ward M, Wade J, Shi X, Nelson J, Campbell A, Fuchter Met al., 2021, Highly Selective Ultrafast Circularly Polarized Photodiodes Based on π-Conjugated Polymers

<jats:p>Chiral π-conjugated molecular systems that are intrinsically sensitive to the handedness of circularly polarized (CP) light potentially allow for miniaturized, low-cost CP detection devices. Such devices promise to transform several technologies, including biosensing, quantum optics and communication of data encrypted by exploiting the spin angular momentum of light. Here we realize a simple, bilayer organic photodiode (CP OPD) comprising an achiral π-conjugated polymer–chiral additive blend as the electron donor layer and an achiral C<jats:sub>60</jats:sub> electron acceptor layer. These devices exhibit considerable photocurrent dissymmetry <jats:italic>g</jats:italic><jats:sub>ph</jats:sub>, with absolute values as high as 0.85 and dark currents as low as 10 pA. Impressively, they showcase a linear dynamic range of 80 dB, and rise and fall times of 50 and 270 ns respectively, which significantly outperforms all previously reported CP selective photodetectors. Mechanistically, we show that the <jats:italic>g</jats:italic><jats:sub>ph</jats:sub> is sensitive to the thickness of <jats:italic>both</jats:italic> the chiral donor and achiral acceptor layers and that a trade-off exists between the external quantum efficiency (EQE) and <jats:italic>g</jats:italic><jats:sub>ph</jats:sub>. The fast-switching speeds of these devices, coupled with their large dynamic range and highly selective response to CP light, opens up the possibility of their direct application in CP sensing and optical communication.</jats:p>

Journal article

Schmidt JA, Weatherby JA, Sugden I, Santana-Bonilla A, Salerno F, Fuchter M, Johnson E, Nelson J, Jelfs Ket al., 2021, Computational Screening of Organic Semiconductors: Exploring Side-Group Functionalisation and Assembly to Optimise Charge Transport in Chiral Molecules

<jats:p>Molecular materials are challenging to design as their packing arrangement and hence properties are subject to subtle variations in the interplay of soft intermolecular interactions that are difficult to predict. The rational design of new molecular materials with tailored properties is currently hampered by the lack of knowledge of how a candidate molecule will pack in space and how we can control the polymorphs we can experimentally obtain. Here, we develop a simplified approach to aid the material design process, by the development of a screening process that is used to test 1344 helicene molecules that have potential as organic electronic materials. Our approach bridges the gap between single molecule design, molecular assembly, and the resulting charge-carrier mobilities. We find that fluorination significantly improves electron transport in the molecular material by up to 200%; the reference [6]helicene packing showed a mobility of 0.30 cm2 V-1 s-1, fluorination increased the mobility to up to 0.96 and 0.97 (13-fluoro[6]H and 4,13-difluoro[6]H), assuming an outer reorganisation energy of 0.30 eV. Side groups containing triple bonds largely lead to improved transfer integrals. We validate our screening approach through the use of crystal structure prediction to confirm the presence of favourable packing motifs to maximize charge mobility.</jats:p>

Journal article

Miguel-Blanco C, Murithi JM, Benavente ED, Angrisano F, Sala KA, van Schalkwyk DA, Vanaerschot M, Schwach F, Fuchter MJ, Billker O, Sutherland CJ, Campino SG, Clark TG, Blagborough AM, Fidock DA, Herreros E, Gamo FJ, Baum J, Delves MJet al., 2021, The antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957, Scientific Reports, Vol: 11, ISSN: 2045-2322

New antimalarial therapeutics are needed to ensure that malaria cases continue to be driven down, as both emerging parasite resistance to frontline chemotherapies and mosquito resistance to current insecticides threaten control programmes. Plasmodium, the apicomplexan parasite responsible for malaria, causes disease pathology through repeated cycles of invasion and replication within host erythrocytes (the asexual cycle). Antimalarial drugs primarily target this cycle, seeking to reduce parasite burden within the host as fast as possible and to supress recrudescence for as long as possible. Intense phenotypic drug screening efforts have identified a number of promising new antimalarial molecules. Particularly important is the identification of compounds with new modes of action within the parasite to combat existing drug resistance and suitable for formulation of efficacious combination therapies. Here we detail the antimalarial properties of DDD01034957-a novel antimalarial molecule which is fast-acting and potent against drug resistant strains in vitro, shows activity in vivo, and possesses a resistance mechanism linked to the membrane transporter PfABCI3. These data support further medicinal chemistry lead-optimization of DDD01034957 as a novel antimalarial chemical class and provide new insights to further reduce in vivo metabolic clearance.

Journal article

Shi W, Salerno F, Ward MD, Santana-Bonilla A, Wade J, Hou X, Liu T, Dennis TJS, Campbell AJ, Jelfs KE, Fuchter MJet al., 2021, Fullerene desymmetrization as a means to achieve single-enantiomer electron acceptors with maximized chiroptical responsiveness., Advanced Materials, Vol: 33, Pages: 1-7, ISSN: 0935-9648

Solubilized fullerene derivatives have revolutionized the development of organic photovoltaic devices, acting as excellent electron acceptors. The addition of solubilizing addends to the fullerene cage results in a large number of isomers, which are generally employed as isomeric mixtures. Moreover, a significant number of these isomers are chiral, which further adds to the isomeric complexity. The opportunities presented by single-isomer, and particularly single-enantiomer, fullerenes in organic electronic materials and devices are poorly understood however. Here, ten pairs of enantiomers are separated from the 19 structural isomers of bis[60]phenyl-C61-butyric acid methyl ester, using them to elucidate important chiroptical relationships and demonstrating their application to a circularly polarized light (CPL)-detecting device. Larger chiroptical responses are found, occurring through the inherent chirality of the fullerene. When used in a single-enantiomer organic field-effect transistor, the potential to discriminate CPL with a fast light response time and with a very high photocurrent dissymmetry factor (gph  = 1.27 ± 0.06) is demonstrated. This study thus provides key strategies to design fullerenes with large chiroptical responses for use as chiral components of organic electronic devices. It is anticipated that this data will position chiral fullerenes as an exciting material class for the growing field of chiral electronic technologies.

Journal article

Wade J, Brandt JR, Reger D, Zinna F, Amsharov KY, Jux N, Andrews DL, Fuchter MJet al., 2021, 500‐Fold Amplification of Small Molecule Circularly Polarised Luminescence through Circularly Polarised FRET, Angewandte Chemie, Vol: 133, Pages: 224-229, ISSN: 0044-8249

Journal article

Wade J, Hilfiker J, Brandt J, Liirò-Peluso L, Wan L, Shi X, Salerno F, Ryan S, Schöche S, Arteaga O, Jávorfi T, Siligardi G, Wang C, Amabilino D, Beton P, Campbell A, Fuchter Met al., 2020, Natural optical activity as the origin of the large chiroptical properties in π-conjugated polymer thin films, Nature Communications, Vol: 11, ISSN: 2041-1723

Polymer thin films that emit and absorb circularly polarised light have been demonstrated with the promise of achieving important technological advances; from efficient, high-performance displays, to 3D imaging and all-organic spintronic devices. However, the origin of the large chiroptical effects in such films has, until now, remained elusive. We investigate the emergence of such phenomena in achiral polymers blended with a chiral small-molecule additive (1-aza[6]helicene) and intrinsically chiral-sidechain polymers using a combination of spectroscopic methods and structural probes. We show that – under conditions relevant for device fabrication – the large chiroptical effects are caused by magneto-electric coupling (natural optical activity), not structural chirality as previously assumed, and may occur because of local order in a cylinder blue phase-type organisation. This disruptive mechanistic insight into chiral polymer thin films will offer new approaches towards chiroptical materials development after almost three decades of research in this area.

Journal article

Fuchter MJ, 2020, On the promise of photopharmacology using photoswitches: a medicinal chemist's perspective., Journal of Medicinal Chemistry, Vol: 63, Pages: 11436-11447, ISSN: 0022-2623

Photopharmacology is a growing area of endeavor that employs photoswitchable ligands to allow for light-dependent pharmacological activity. By coupling light to therapeutic action, improved spatial and temporal selectivity can be achieved and subsequently harnessed for new concepts in therapy. Tremendous progress has already been made, with photopharmacological agents now reported against a wide array of target classes, and light-dependent results demonstrated in a range of live cell and animal models. Several challenges remain however, especially in order for photopharmacology to truly impact the clinical management of disease. This perspective aims to summarize these challenges, particularly with attention to the medicinal chemistry that will be unavoidably required for the further translation of these agents/approaches. By clearly defining challenges for drug hunters, it is hoped that further research into the medicinal chemistry of photopharmacological agents will be stimulated; ultimately enabling full realization of the huge potential for this exciting field.

Journal article

Lam P-Y, Thawani AR, Balderas E, White AJP, Chaudhuri D, Fuchter MJ, Peterson Ret al., 2020, TRPswitch — a step function chemo-optogenetic ligand for the vertebrate TRPA1 channel, Journal of the American Chemical Society, Vol: 142, Pages: 17457-17468, ISSN: 0002-7863

Chemo-optogenetics has produced powerful tools for optical control of cell activity, but current tools suffer from a variety of limitations including low unitary conductance, the need to modify the target channel, or the inability to control both on and off switching. Using a zebrafish behavior-based screening strategy, we discovered “TRPswitch”, a photoswitchable non-electrophilic ligand scaffold for the transient receptor potential ankyrin 1 (TRPA1) channel. TRPA1 exhibits high unitary channel conductance, making it an ideal target for chemo-optogenetic tool development. Key molecular determinants for the activity of TRPswitch were elucidated and allowed for replacement of the TRPswitch azobenzene with a next-generation azoheteroarene. The TRPswitch compounds enable reversible, repeatable, and nearly quantitative light-induced activation and deactivation of the vertebrate TRPA1 channel with violet and green light, respectively. The utility of TRPswitch compounds was demonstrated in larval zebrafish hearts exogenously expressing zebrafish Trpa1b, where heartbeat could be controlled using TRPswitch and light. Therefore, TRPA1/TRPswitch represents a novel step-function chemo-optogenetic system with a unique combination of high conductance, high efficiency, activity against an unmodified vertebrate channel, and capacity for bidirectional optical switching. This chemo-optogenetic system will be particularly applicable in systems where a large depolarization current is needed or sustained channel activation is desirable.

Journal article

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