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

174 results found

Constantin TA, Varela-Carver A, Greenland KK, de Almeida GS, Olden E, Penfold L, Ang S, Ormrod A, Leach DA, Lai C-F, Ainscow EK, Bahl AK, Carling D, Fuchter MJ, Ali S, Bevan CLet al., 2024, Correction: The CDK7 inhibitor CT7001 (Samuraciclib) targets proliferation pathways to inhibit advanced prostate cancer., Br J Cancer

Journal article

Shioukhi I, Batchu H, Schwartz G, Minion L, Deree Y, Bogoslavsky B, Shimon LJW, Wade J, Hoffman R, Fuchter MJ, Markovich G, Gidron Oet al., 2024, Helitwistacenes-combining lateral and longitudinal helicity results in solvent-induced inversion of circularly polarized light, Angewandte Chemie International Edition, ISSN: 1433-7851

Helicity is expressed differently in ortho- and para-fused acenes-helicenes and twistacenes, respectively. While the extent of helicity is constant in helicenes, it can be tuned in twistacenes, and the handedness of flexible twistacenes is often determined by more rigid helicenes. Here, we combine helicenes with rigid twistacenes consisting of a tunable degree of twisting, forming helitwistacenes. While the X-ray structures reveal that the connection does not affect the helicity of each moiety, their electronic circular dichroism (ECD) and circularly polarized luminescence (CPL) spectra are strongly affected by the helicity of the twistacene unit, resulting in solvent-induced sign inversion. ROESY NMR and TD-DFT calculations support this observation, which is explained by differences in the relative orientation of the helicene and twistacene moieties.

Journal article

Brand MC, Trowell HG, Fuchter MJ, Greenaway RLet al., 2024, Incorporating photoresponses into porous liquids, Chemistry: A European Journal, ISSN: 0947-6539

Porous liquids combine the properties of a porous solid with those of a liquid, creating a porous flowable media. Since their discovery, these materials have gathered widespread interest within the scientific community, with substantial numbers of new systems being discovered, often with a focus on increasing the pore volume and gas capacity. Which begs the question, what does the future hold for porous liquids? Recently, the first examples of photoresponsive porous liquids have emerged, allowing changes in porosity to be observed under UV irradiation. Here, we expand on our previous report of photoresponsive porous liquids and explore the conceptualisation of responsive porous liquids and how these materials could be developed with the ability to respond to light, thereby offering a potential mechanism of controllable uptake and release in these systems. This concept article summarises different approaches that could be used to incorporate a photoresponse in a porous liquid before discussing recently reported systems, alongside important factors to consider in their design. Finally, by taking inspiration from the methods used to translate porous solids into the liquid state, combined with the field of photoresponsive materials, we discuss potential strategies that could be employed to realise further examples of photoresponsive porous liquids.

Journal article

Sampieri A, Padilla-Flores T, Thawani AR, Lam P-Y, Fuchter MJ, Peterson R, Vaca Let al., 2023, The conducting state of TRPA1 modulates channel lateral mobility, Cell Calcium, Vol: 116, ISSN: 0143-4160

We have studied Danio rerio (Zebrafish) TRPA1 channel using a method that combines single channel electrophysiological and optical recordings to evaluate lateral mobility and channel gating simultaneously in single channels. TRPA1 channel activation by two distinct chemical ligands: allyl isothiocyanate (AITC) and TRPswitch B, results in substantial reduction of channel lateral mobility at the plasma membrane. Incubation with the cholesterol sequestering agent methyl-β-cyclodextrin (MβCD), prevents the reduction on lateral mobility induced by the two chemical agonists. This results strongly suggest that the open conformation of TRPA1 modulates channel lateral mobility probably by facilitating the insertion of the channel into cholesterol-enriched domains at the plasma membrane.

Journal article

Minion L, Wade J, Moreno-Naranjo JM, Ryan S, Siligardi G, Fuchter MJet al., 2023, Insights into the origins of inverted circular dichroism in thin films of a chiral side chain polyfluorene, CHIRALITY, Vol: 35, Pages: 817-825, ISSN: 0899-0042

Journal article

Reyser T, Paloque L, Nguyen M, Augereau J-M, Fuchter MJ, Lopez M, Arimondo PB, Hassell-Hart S, Spencer J, Di Stefano L, Benoit-Vical Fet al., 2023, Epidrugs as Promising Tools to Eliminate Plasmodium falciparum Artemisinin-Resistant and Quiescent Parasites., Pharmaceutics, Vol: 15, ISSN: 1999-4923

The use of artemisinin and its derivatives has helped reduce the burden of malaria caused by Plasmodium falciparum. However, artemisinin-resistant parasites are able, in the presence of artemisinins, to stop their cell cycles. This quiescent state can alter the activity of artemisinin partner drugs leading to a secondary drug resistance and thus threatens malaria eradication strategies. Drugs targeting epigenetic mechanisms (namely epidrugs) are emerging as potential antimalarial drugs. Here, we set out to evaluate a selection of various epidrugs for their activity against quiescent parasites, to explore the possibility of using these compounds to counter artemisinin resistance. The 32 chosen epidrugs were first screened for their antiplasmodial activity and selectivity. We then demonstrated, thanks to the specific Quiescent-stage Survival Assay, that four epidrugs targeting both histone methylation or deacetylation as well as DNA methylation decrease the ability of artemisinin-resistant parasites to recover after artemisinin exposure. In the quest for novel antiplasmodial drugs with new modes of action, these results reinforce the therapeutic potential of epidrugs as antiplasmodial drugs especially in the context of artemisinin resistance.

Journal article

Gemen J, Church J, Ruoko T-P, Durandin N, Białek M, Weißenfels M, Feller M, Kazes M, Odaybat M, Borin V, Kalepu R, Diskin-Posner Y, Oron D, Fuchter M, Priimagi A, Schapiro I, Klajn Ret al., 2023, Disequilibrating azobenzenes by visible-light sensitization under confinement, Science, Vol: 381, Pages: 1357-1363, ISSN: 0036-8075

Photoisomerization of azobenzenes from their stable E isomer to the metastable Z state is the basis of numerous applications of these molecules. However, this reaction typically requires ultraviolet light, which limits applicability. In this study, we introduce disequilibration by sensitization under confinement (DESC), a supramolecular approach to induce the E-to-Z isomerization by using light of a desired color, including red. DESC relies on a combination of a macrocyclic host and a photosensitizer, which act together to selectively bind and sensitize E-azobenzenes for isomerization. The Z isomer lacks strong affinity for and is expelled from the host, which can then convert additional E-azobenzenes to the Z state. In this way, the host–photosensitizer complex converts photon energy into chemical energy in the form of out-of-equilibrium photostationary states, including ones that cannot be accessed through direct photoexcitation.

Journal article

Griffiths K, Greenfield JL, Halcovitch NR, Fuchter MJ, Griffin JMet al., 2023, Systematic Investigation into the Photoswitching and Thermal Properties of Arylazopyrazole-based MOF Host-Guest Complexes, CRYSTAL GROWTH & DESIGN, Vol: 23, Pages: 7044-7052, ISSN: 1528-7483

Journal article

Constantin TA, Varela-Carver A, Greenland KK, de Almeida GS, Olden E, Penfold L, Ang S, Ormrod A, Leach DA, Lai C-F, Ainscow EK, Bahl AK, Carling D, Fuchter MJ, Ali S, Bevan CLet al., 2023, The CDK7 inhibitor CT7001 (Samuraciclib) targets proliferation pathways to inhibit advanced prostate cancer, British Journal of Cancer, Vol: 128, Pages: 2326-2337, ISSN: 0007-0920

BACKGROUND: Current strategies to inhibit androgen receptor (AR) are circumvented in castration-resistant prostate cancer (CRPC). Cyclin-dependent kinase 7 (CDK7) promotes AR signalling, in addition to established roles in cell cycle and global transcription, providing a rationale for its therapeutic targeting in CRPC. METHODS: The antitumour activity of CT7001, an orally bioavailable CDK7 inhibitor, was investigated across CRPC models in vitro and in xenograft models in vivo. Cell-based assays and transcriptomic analyses of treated xenografts were employed to investigate the mechanisms driving CT7001 activity, alone and in combination with the antiandrogen enzalutamide. RESULTS: CT7001 selectively engages with CDK7 in prostate cancer cells, causing inhibition of proliferation and cell cycle arrest. Activation of p53, induction of apoptosis, and suppression of transcription mediated by full-length and constitutively active AR splice variants contribute to antitumour efficacy in vitro. Oral administration of CT7001 represses growth of CRPC xenografts and significantly augments growth inhibition achieved by enzalutamide. Transcriptome analyses of treated xenografts indicate cell cycle and AR inhibition as the mode of action of CT7001 in vivo. CONCLUSIONS: This study supports CDK7 inhibition as a strategy to target deregulated cell proliferation and demonstrates CT7001 is a promising CRPC therapeutic, alone or in combination with AR-targeting compounds.

Journal article

Crassous J, Fuchter MJ, Freedman DE, Kotov NA, Moon J, Beard MC, Feldmann Set al., 2023, Materials for chiral light control, NATURE REVIEWS MATERIALS, Vol: 8, Pages: 365-371, ISSN: 2058-8437

Journal article

Shi W, Zhuang Q, Zhou R, Hou X, Zhao X, Kong J, Fuchter MJet al., 2023, Enantiomerically Pure Fullerenes as a Means to Enhance the Performance of Perovskite Solar Cells, ADVANCED ENERGY MATERIALS, Vol: 13, ISSN: 1614-6832

Journal article

Sbirkov Y, Schenk T, Kwok C, Stengel S, Brown R, Brown G, Chesler L, Zelent A, Fuchter MJ, Petrie Ket al., 2023, Dual inhibition of EZH2 and G9A/GLP histone methyltransferases by HKMTI-1-005 promotes differentiation of acute myeloid leukemia cells, FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, Vol: 11, ISSN: 2296-634X

Journal article

Yahiya S, Saunders CN, Hassan S, Straschil U, Fischer OJ, Rueda-Zubiaurre A, Haase S, Vizcay-Barrena G, Famodimu MT, Jordan S, Delves MJ, Tate EW, Barnard A, Fuchter MJ, Baum Jet 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.

Journal article

Wan L, Yizhou L, Fuchter M, Yan Bet 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.

Journal article

Pilgrim BS, Slater A, Collins B, Hiscock J, Leigh J, Sessler J, Peluso LL, Fuchter MJ, Friscic T, Ashbridge Zet al., 2022, MASC 2022: What challenges and opportunities do supramolecular chemists face in coming years?, CELL REPORTS PHYSICAL SCIENCE, Vol: 3

Journal article

Rushworth JL, Thawani AR, Fajardo-Ruiz E, Meiring JCM, Heise C, White AJP, Akhmanova A, Brandt JR, Thorn-Seshold O, Fuchter MJet al., 2022, [5]-Helistatins: Tubulin-Binding Helicenes with Antimitotic Activity, JACS AU, Vol: 2, Pages: 2561-2570

Journal article

Griffiths R-R, Greenfield JL, Thawani AR, Jamasb AR, Moss HB, Bourached A, Jones P, McCorkindale W, Aldrick AA, Fuchter MJ, Lee AAet al., 2022, Data-driven discovery of molecular photoswitches with multioutput Gaussian processes, CHEMICAL SCIENCE, Vol: 13, Pages: 13541-13551, ISSN: 2041-6520

Journal article

Ward MD, Shi W, Gasparini N, Nelson J, Wade J, Fuchter MJet al., 2022, Best practices in the measurement of circularly polarised photodetectors (vol 10, pg 10452, 2022), JOURNAL OF MATERIALS CHEMISTRY C, ISSN: 2050-7526

Journal article

Tyagi G, Greenfield JL, Jones BE, Sharratt WN, Khan K, Seddon D, Malone LA, Cowieson N, Evans RC, Fuchter MJ, Cabral JTet al., 2022, Light responsiveness and assembly of arylazopyrazole-based surfactants in neat and mixed CTAB micelles, JACS Au, Vol: 2, Pages: 2670-2677, ISSN: 2691-3704

The self-assembly of an arylazopyrazole-based photosurfactant (PS), based on cetyltrimethylammonium bromide (CTAB), and its mixed micelle formation with CTAB in aqueous solution was investigated by small angle neutron and X-ray scattering (SANS/SAXS) and UV–vis absorption spectroscopy. Upon UV light exposure, PS photoisomerizes from E-PS (trans) to Z-PS (cis), which transforms oblate ellipsoidal micelles into smaller, spherical micelles with larger shell thickness. Doping PS with CTAB resulted in mixed micelle formation at all stoichiometries and conditions investigated; employing selectively deuterated PS, a monotonic variation in scattering length density and dimensions of the micellar core and shell is observed for all contrasts. The concentration- and irradiance-dependence of the E to Z configurational transition was established in both neat and mixed micelles. A liposome dye release assay establishes the enhanced efficacy of photosurfactants at membrane disruption, with E-PS exhibiting a 4-fold and Z-PS a 10-fold increase in fluorescence signal with respect to pure CTAB. Our findings pave the way for external triggering and modulation of the wide range of CTAB-based biomedical and material applications.

Journal article

Wade J, Salerno F, Kilbride R, Kim DK, Schmidt J, Smith J, LeBlanc L, Wolpert E, Adeleke A, Johnson E, Nelson J, Mori T, Jelfs K, Heutz S, Fuchter Met 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.

Journal article

Gonzalez A, Odaybat M, Le M, Greenfield JL, White AJP, Li X, Fuchter MJ, Han GGDet 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

Journal article

Furlan F, Nodari D, Palladino E, Angela E, Mohan L, Briscoe J, Fuchter MJ, Macdonald TJ, Grancini G, McLachlan MA, Gasparini Net 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.

Journal article

Perez NH, Sherin PS, Posligua V, Greenfield JL, Fuchter MJ, Jelfs KE, Kuimova MK, Lewis JEMet 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.

Journal article

Zhang Q, Kounde C, Mondal M, Zhang L, Conole D, De Vita E, Fuchter M, Tate Eet 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.

Journal article

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, Vol: 10, Pages: 10452-10463, ISSN: 2050-7526

Journal article

Yan H, Wade J, Wan L, Kwon S, Fuchter MJ, Campbell AJ, Kim J-Set al., 2022, Enhancing hole carrier injection <i>via</i> 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, 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

Rushworth J, Thawani A, Fajardo-Ruiz E, Meiring J, Heise C, White A, Akhmanova A, Brandt J, Thorn-Seshold O, Fuchter Met al., 2022, [5]-Helistatins: Tubulin binding helicenes with antimitotic activity

<jats:p>Helicenes are high interest synthetic targets with unique conjugated helical structures that have found important technological applications. Despite this interest, helicenes have had limited impact in chemical biology. Herein, we disclose a first-in-class antimitotic helicene, helistatin 1 (HA-1), where the helicene scaffold acts as a structural mimic of colchicine, a known antimitotic drug. The synthesis proceeds via sequential Pd-catalyzed coupling reactions and a π-Lewis acid cycloisomerization mediated by PtCl2. HA-1 was found to block microtubule polymerisation in both cell-free and live cell assays. Not only does this demonstrate the feasibility of using helicenes as bioactive scaffolds against protein targets, but also suggests wider potential for the use of helicenes as isosteres of biaryls or cis-stilbenes - themselves common drug and natural product scaffolds. Overall, this study further supports future opportunities for helicenes for a range of chemical biological applications.</jats:p>

Journal article

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