Publications
161 results found
Yahiya S, Saunders CN, Hassan S, et al., 2023, A novel class of sulphonamides potently block malaria transmission by targeting a Plasmodium vacuole membrane protein, Disease Models & Mechanisms, Vol: 16, Pages: 1-20, ISSN: 1754-8403
Phenotypic cell-based screens are critical tools for discovering candidate drugs for development, yet identification of the cellular target and mode of action of a candidate drug is often lacking. Using an imaging-based screen, we recently discovered an N-[(4-hydroxychroman-4-yl)methyl]-sulphonamide (N-4HCS) compound, DDD01035881, that blocks male gamete formation in the malaria parasite life cycle and subsequent transmission of the parasite to the mosquito with nanomolar activity. To identify the target(s) of DDD01035881, and of the N-4HCS class of compounds more broadly, we synthesised a photoactivatable derivative, probe 2. Photoaffinity labelling of probe 2 coupled with mass spectrometry identified the 16 kDa Plasmodium falciparum parasitophorous vacuole membrane protein Pfs16 as a potential parasite target. Complementary methods including cellular thermal shift assays confirmed that the parent molecule DDD01035881 stabilised Pfs16 in lysates from activated mature gametocytes. Combined with high-resolution, fluorescence and electron microscopy data, which demonstrated that parasites inhibited with N-4HCS compounds phenocopy the targeted deletion of Pfs16 in gametocytes, these data implicate Pfs16 as a likely target of DDD01035881. This finding establishes N-4HCS compounds as being flexible and effective starting candidates from which transmission-blocking antimalarials can be developed in the future.
Wan L, Yizhou L, Fuchter M, et al., 2023, Anomalous circularly polarized light emission in organic light-emitting diodes caused by orbital-momentum locking, Nature Photonics, Vol: 17, Pages: 193-199, ISSN: 1749-4885
Chiral circularly polarized (CP) light is central to many photonic technologies, from optical communication of spin information to novel display and imaging technologies. As such, there has been significant effort in the development of chiral emissive materials that allow for the emission of strongly dissymmetric CP light from organic light-emitting diodes (OLEDs). A consensus for chiral emission in such devices is that the molecular chirality of the active layer determines the favored light handedness of CP emission, regardless of the light-emitting direction. Here, we discover that, unconventionally, oppositely propagating CP light exhibits opposite handedness and reversing the current-flow in OLEDs also switches the handedness of the emitted CP light. This direction-dependent CP emission boosts the net polarization rate by orders of magnitude by resolving an established issue in CP-OLEDs, where the CP light reflected by the back electrode typically erodes the measured dissymmetry. Through detailed theoretical analysis, we assign this anomalous CP emission to a ubiquitous topological electronic property in chiral materials, namely the orbital-momentum locking. Our work paves the way to design new chiroptoelectronic devices and probes the close connections between chiral materials, topological electrons, and CP light in the quantum regime.
Griffiths R-R, Greenfield JL, Thawani AR, et al., 2022, Data-driven discovery of molecular photoswitches with multioutput Gaussian processes, CHEMICAL SCIENCE, Vol: 13, Pages: 13541-13551, ISSN: 2041-6520
Ward MD, Shi W, Gasparini N, et al., 2022, Best practices in the measurement of circularly polarised photodetectors (vol 10, pg 10452, 2022), JOURNAL OF MATERIALS CHEMISTRY C, ISSN: 2050-7526
Tyagi G, Greenfield JL, Jones BE, et al., 2022, Light Responsiveness and Assembly of Arylazopyrazole-Based Surfactants in Neat and Mixed CTAB Micelles, JACS AU, Vol: 2, Pages: 2670-2677
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- Citations: 1
Wade J, Salerno F, Kilbride R, et al., 2022, Controlling anisotropic properties by manipulating the orientation of chiral small molecules, Nature Chemistry, Vol: 14, Pages: 1383-1389, ISSN: 1755-4330
Chiral π-conjugated molecules bring new functionality to technological applications and represent an exciting, rapidly expanding area of research. Their functional properties, such as the absorption and emission of circularly polarised light or the transport of spin-polarised electrons, are highly anisotropic. As a result, the orientation of chiral molecules criticallydetermines the functionality and efficiency of chiral devices. Here we present a strategy to control the orientation of a small chiral molecule (2,2’-dicyano[6]helicene, CN6H): the use of organic and inorganic templating layers. Such templating layers can either force CN6H molecules to adopt a face-on orientation and self-assemble into upright supramolecular columns oriented with their helical axis perpendicular to the substrate, or an edge-onorientation with parallel-lying supramolecular columns. Through such control, we show that low- and high-energy chiroptical responses can be independently ‘turned on’ or ‘turned off’. The templating methodologies described here provide a simple way to engineer orientational control, and by association, anisotropic functional properties of chiral molecular systems for a range of emerging technologies.
Rushworth JL, Thawani AR, Fajardo-Ruiz E, et al., 2022, [5]-Helistatins: Tubulin-Binding Helicenes with Antimitotic Activity, JACS AU, Vol: 2, Pages: 2561-2570
Gonzalez A, Odaybat M, Le M, et al., 2022, Photocontrolled Energy Storage in Azobispyrazoles with Exceptionally Large Light Penetration Depths, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 144, Pages: 19430-19436, ISSN: 0002-7863
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- Citations: 1
Furlan F, Nodari D, Palladino E, et al., 2022, Tuning Halide Composition allows low dark current perovskite photodetectors with high specific detectivity, Advanced Optical Materials, Vol: 10, Pages: 1-8, ISSN: 2195-1071
Tuning halide composition in perovskites is a powerful approach demonstrated to enhance the performance of perovskite photovoltaic devices where such compositional modifications drive improvements in open-circuit voltage (Voc) and a reduction in nonradiative voltage losses. Similarly, photodetectors (PDs) operate as light to current conversion devices hence it is relevant to investigate whether performance enhancements can be achieved by similar strategies. Herein, perovskite PDs are fabricated with an inverted photodiode configuration based on a MAPb(I1-xBrx)3 perovskite (MA = methylammonium) active layer over the x = 0–0.25 composition range. Interestingly, it has been found that increasing the Br content up to 0.15 (15%) leads to a significant reduction in dark current (Jd), with values as low as 1.3 × 10−9 A cm−2 being achieved alongside a specific detectivity of 8.7 × 1012 Jones. Significantly, it has been observed an exponential relationship between the Jd of devices and their Voc over the 0–15% Br range. The superior performances of the 15% Br-containing devices are attributed to the reduction of trap states, a better charge extraction of photogenerated carriers, and an improvement in photoactive layer morphology and crystallinity.
Perez NH, Sherin PS, Posligua V, et al., 2022, Emerging properties from mechanical tethering within a post-synthetically functionalised catenane scaffold, Chemical Science, Vol: 13, Pages: 11368-11375, ISSN: 2041-6520
Maintaining close spatial proximity of functional moieties within molecular systems can result in fascinating emergent properties. Whilst much work has been done on covalent tethering of functional units for myriad applications, investigations into mechanically linked systems are relatively rare. Formation of the mechanical bond is usually the final step in the synthesis of interlocked molecules, placing limits on the throughput of functionalised architectures. Herein we present the synthesis of a bis-azide [2]catenane scaffold that can be post-synthetically modified using CuAAC ‘click’ chemistry. In this manner we have been able to access functionalised catenanes from a common precursor and study the properties of electrochemically active, emissive and photodimerisable units within the mechanically interlocked system in comparison to non-interlocked analogues. Our data demonstrates that the greater (co-)conformational flexibility that can be obtained with mechanically interlocked systems compared to traditional covalent tethers paves the way for developing new functional molecules with exciting properties.
Zhang Q, Kounde C, Mondal M, et al., 2022, Light-mediated multi-target protein degradation using arylazopyrazole photoswitchable PROTACs (AP-PROTACs), Chemical Communications, Vol: 58, Pages: 10933-10936, ISSN: 1359-7345
Light-activable spatiotemporal control of PROTAC-induced protein degradation was achieved with novel arylazopyrazole photoswitchable PROTACs (AP-PROTACs). The use of a promiscuous kinase inhibitor in the design enables this unique photoswitchable PROTAC to selectively degrade four protein kinases together with on/off optical control using different wavelengths of light.
Ward MD, Shi W, Gasparini N, et al., 2022, Best practices in the measurement of circularly polarised photodetectors, JOURNAL OF MATERIALS CHEMISTRY C, Vol: 10, Pages: 10452-10463, ISSN: 2050-7526
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- Citations: 4
Wan L, Wade J, Shi X, et 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
Wan L, Wade J, Salerno F, et 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
Wan L, Liu Y, Fuchter M, et 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>
Yan H, Wade J, Wan L, et 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
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- Citations: 5
Wan L, Wade J, Wang X, et 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.
Liu T, Shi W, Tang W, et 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.
Howell SJ, Kenny LM, Lord S, et 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
McNeish I, Spiliopoulou P, Spear S, et 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.
dos Santos JM, Sun D, Moreno-Naranjo JM, et 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
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- Citations: 8
Ward MD, Wade J, Shi X, et 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.
Greenfield J, Mihael G, Gibson R, et 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.
Krebs MG, Lord S, Kenny L, et 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
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- Citations: 1
Laidlaw B, Eng J, Wade J, et 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.
Schmidt J, Weatherby J, Sugden I, et 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.
Greenfield JL, Wade J, Brandt JR, et 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.
Garner IM, Su Z, Hu S, et 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
Wan L, Shi X, Wade J, et 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.
LanyonHogg T, Ritzefeld M, Zhang L, et 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
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