96 results found
Montgomery KS, Davidson RWM, Cao B, et al., 2018, Effective macrophage delivery using RAFT copolymer derived nanoparticles, POLYMER CHEMISTRY, Vol: 9, Pages: 131-137, ISSN: 1759-9954
Rice B, LeBlanc LM, Otero-de-la-Roza A, et al., 2018, A computational exploration of the crystal energy and charge-carrier mobility landscapes of the chiral helicene molecule., Nanoscale
The potential of a given π-conjugated organic molecule in an organic semiconductor device is highly dependent on molecular packing, as it strongly influences the charge-carrier mobility of the material. Such solid-state packing is sensitive to subtle differences in their intermolecular interactions and is challenging to predict. Chirality of the organic molecule adds an additional element of complexity to intuitive packing prediction. Here we use crystal structure prediction to explore the lattice-energy landscape of a potential chiral organic semiconductor, helicene. We reproduce the experimentally observed enantiopure crystal structure and explain the absence of an experimentally observed racemate structure. By exploring how the hole and electron-mobility varies across the energy-structure-function landscape for helicene, we find that an energetically favourable and frequently occurring packing motif is particularly promising for electron-mobility, with a highest calculated mobility of 2.9 cm2 V-1 s-1 (assuming a reorganization energy of 0.46 eV). We also calculate relatively high hole-mobility in some structures, with a highest calculated mobility of 2.0 cm2 V-1 s-1 found for chains of helicenes packed in a herringbone fashion. Neither the energetically favourable nor high charge-carrier mobility packing motifs are intuitively obvious, and this demonstrates the utility of our approach to computationally explore the energy-structure-function landscape for organic semiconductors. Our work demonstrates a route for the use of computational simulations to aid in the design of new molecules for organic electronics, through the a priori prediction of their likely solid-state form and properties.
Brandt JR, Pospisil L, Bednarova L, et al., 2017, Intense redox-driven chiroptical switching with a 580 mV hysteresis actuated through reversible dimerization of an azoniahelicene, CHEMICAL COMMUNICATIONS, Vol: 53, Pages: 9059-9062, ISSN: 1359-7345
Brandt JR, Salerno F, Fuchter MJ, 2017, The added value of small-molecule chirality in technological applications, NATURE REVIEWS CHEMISTRY, Vol: 1, ISSN: 2397-3358
Calbo J, Weston CE, White AJP, et al., 2017, Tuning Azoheteroarene Photoswitch Performance through Heteroaryl Design, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 139, Pages: 1261-1274, ISSN: 0002-7863
Hazel P, Kroll SHB, Bondke A, et al., 2017, Inhibitor Selectivity for Cyclin-Dependent Kinase7: AStructural, Thermodynamic, and Modelling Study, CHEMMEDCHEM, Vol: 12, Pages: 372-380, ISSN: 1860-7179
Scott DJ, Fuchter MJ, Ashley AE, 2017, Designing effective 'frustrated Lewis pair' hydrogenation catalysts, CHEMICAL SOCIETY REVIEWS, Vol: 46, Pages: 5689-5700, ISSN: 0306-0012
Sundriyal S, Chen PB, Lubin AS, et al., 2017, Histone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti-Plasmodium activity, MEDCHEMCOMM, Vol: 8, Pages: 1069-1092, ISSN: 2040-2503
Sundriyal S, Moniot S, Mahmud Z, et al., 2017, Thienopyrimidinone based sirtuin-2 (SIRT2)-selective inhibitors bind in the ligand induced 'selectivity pocket'., Journal of Medicinal Chemistry, Vol: 60, Pages: 1928-1945, ISSN: 0022-2623
Sirtuins (SIRTs) are NAD-dependent deacylases, known to be involved in a variety of pathophysiological processes and thus remain promising therapeutic targets for further validation. Previously, we reported a novel thienopyrimidinone SIRT2 inhibitor with good potency and excellent selectivity for SIRT2. Herein, we report an extensive SAR study of this chemical series and identify the key pharmacophoric elements and physiochemical properties that underpin the excellent activity observed. New analogues have been identified with submicromolar SIRT2 inhibtory activity and good to excellent SIRT2 subtype-selectivity. Importantly, we report a co-crystal structure of one of our compounds (29c) bound to SIRT2. This reveals our series to induce the formation of a previously reported 'selectivity pocket', but to bind in an inverted fashion to what might be intuitively expected. We believe these findings will contribute significantly to understanding of the mechanism of action of SIRT2 inhibitors and to the identification of refined, second generation inhibitors.
Sundriyal S, Moniot S, Mahmud Z, et al., 2017, Thienopyrimidinone Based Sirtuin-2 (SIRT2)-Selective Inhibitors Bind in the Ligand Induced Selectivity Pocket, JOURNAL OF MEDICINAL CHEMISTRY, Vol: 60, Pages: 1928-1945, ISSN: 0022-2623
Weston CE, Kraemer A, Colin F, et al., 2017, Toward Photopharmacological Antimicrobial Chemotherapy Using Photoswitchable Amidohydrolase Inhibitors, ACS INFECTIOUS DISEASES, Vol: 3, Pages: 152-161, ISSN: 2373-8227
Weston CE, Krämer A, Colin F, et al., 2017, Toward Photopharmacological Antimicrobial Chemotherapy Using Photoswitchable Amidohydrolase Inhibitors., ACS Infect Dis, Vol: 3, Pages: 152-161
Photopharmacological agents exhibit light-dependent biological activity and may have potential in the development of new antimicrobial agents/modalities. Amidohydrolase enzymes homologous to the well-known human histone deacetylases (HDACs) are present in bacteria, including resistant organisms responsible for a significant number of hospital-acquired infections and deaths. We report photopharmacological inhibitors of these enzymes, using two classes of photoswitches embedded in the inhibitor pharmacophore: azobenzenes and arylazopyrazoles. Although both classes of inhibitor show excellent inhibitory activity (nM IC50 values) of the target enzymes and promising differential activity of the switchable E- and Z-isomeric forms, the arylazopyrazoles exhibit better intrinsic photoswitch performance (more complete switching, longer thermal lifetime of the Z-isomer). We also report protein-ligand crystal structures of the E-isomers of both an azobenzene and an arylazopyrazole inhibitor, bound to bacterial histone deacetylase-like amidohydrolases (HDAHs). These structures not only uncover interactions important for inhibitor binding but also reveal conformational differences between the two photoswitch inhibitor classes. As such, our data may pave the way for the design of improved photopharmacological agents targeting the HDAC superfamily.
Yang Y, Rice B, Shi X, et al., 2017, Emergent Properties of an Organic Semiconductor Driven by its Molecular Chirality, ACS Nano, Vol: 11, Pages: 8329-8338, ISSN: 1936-0851
Chiral molecules exist as pairs of nonsuperimposable mirror images; a fundamental symmetry property vastly underexplored in organic electronic devices. Here, we show that organic field-effect transistors (OFETs) made from the helically chiral molecule 1-azahelicene can display up to an 80-fold difference in hole mobility, together with differences in thin-film photophysics and morphology, solely depending on whether a single handedness or a 1:1 mixture of left- and right-handed molecules is employed under analogous fabrication conditions. As the molecular properties of either mirror image isomer are identical, these changes must be a result of the different bulk packing induced by chiral composition. Such underlying structures are investigated using crystal structure prediction, a computational methodology rarely applied to molecular materials, and linked to the difference in charge transport. These results illustrate that chirality may be used as a key tuning parameter in future device applications.
Ali S, Patel H, Periyasamy M, et al., 2016, ICEC0942, an orally bioavailable selective inhibitor of CDK7 for breast cancer, UK Breast Cancer Research Symposium, Publisher: SPRINGER, Pages: 195-195, ISSN: 0167-6806
Brandt JR, Wang X, Yang Y, et al., 2016, Circularly Polarized Phosphorescent Electroluminescence with a High Dissymmetry Factor from PHOLEDs Based on a Platinahelicene, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 138, Pages: 9743-9746, ISSN: 0002-7863
Chen PB, Ding S, Zanghi G, et al., 2016, Plasmodium falciparum PfSET7: enzymatic characterization and cellular localization of a novel protein methyltransferase in sporozoite, liver and erythrocytic stage parasites, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322
Davidson RWM, Fuchter MJ, 2016, Direct NHC-catalysed redox amidation using CO2 for traceless masking of amine nucleophiles, CHEMICAL COMMUNICATIONS, Vol: 52, Pages: 11638-11641, ISSN: 1359-7345
Scott DJ, Phillips NA, Sapsford JS, et al., 2016, Versatile Catalytic Hydrogenation Using A Simple Tin(IV) Lewis Acid, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 55, Pages: 14738-14742, ISSN: 1433-7851
Weston CE, Richardson RD, Fuchter MJ, 2016, Photoswitchable basicity through the use of azoheteroarenes, CHEMICAL COMMUNICATIONS, Vol: 52, Pages: 4521-4524, ISSN: 1359-7345
Weston CE, Richardson RD, Haycock PR, et al., 2016, "Arylazopyrazoles: Azoheteroarene Photoswitches Offering Quantitative Isomerization and Long Thermal Half-Lives (vol 136, pg 11878, 2014), JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 138, Pages: 10716-10716, ISSN: 0002-7863
Bultinck P, Cherblanc FL, Fuchter MJ, et al., 2015, Chiroptical Studies on Brevianamide B: Vibrational and Electronic Circular Dichroism Confronted, JOURNAL OF ORGANIC CHEMISTRY, Vol: 80, Pages: 3359-3367, ISSN: 0022-3263
Curry E, Green I, Chapman-Rothe N, et al., 2015, Dual EZH2 and EHMT2 histone methyltransferase inhibition increases biological efficacy in breast cancer cells, CLINICAL EPIGENETICS, Vol: 7, ISSN: 1868-7083
Di Fruscia P, Zacharioudakis E, Liu C, et al., 2015, The Discovery of a Highly Selective 5,6,7,8-Tetrahydrobenzo[4,5]thieno[ 2,3-d] pyrimidin-4(3H)-one SIRT2 Inhibitor that is Neuroprotective in an in vitro Parkinson's Disease Model, CHEMMEDCHEM, Vol: 10, Pages: 69-82, ISSN: 1860-7179
Fuchter MJ, 2015, Young Career Focus: Dr. Matthew J. Fuchter (Imperial College London, UK), SYNTHESIS-STUTTGART, Vol: 47, Pages: A152-A155, ISSN: 0039-7881
Fuchter MJ, 2015, Carbon-14 reprocessing at cardiff, Publisher: WILEY-BLACKWELL, Pages: 149-150, ISSN: 0362-4803
Malmquist NA, Sundriyal S, Caron J, et al., 2015, Histone Methyltransferase Inhibitors Are Orally Bioavailable, Fast-Acting Molecules with Activity against Different Species Causing Malaria in Humans, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 59, Pages: 950-959, ISSN: 0066-4804
Richardson RD, Baud MGJ, Weston CE, et al., 2015, Dual wavelength asymmetric photochemical synthesis with circularly polarized light, CHEMICAL SCIENCE, Vol: 6, Pages: 3853-3862, ISSN: 2041-6520
Scott DJ, Simmons TR, Lawrence EJ, et al., 2015, Facile Protocol for Water-Tolerant "Frustrated Lewis Pair"-Catalyzed Hydrogenation, ACS CATALYSIS, Vol: 5, Pages: 5540-5544, ISSN: 2155-5435
Udemba A, Smith G, Nguyen Q-D, et al., 2015, Design, synthesis and initial characterisation of a radiolabelled [F-18]pyrimidoindolone probe for detecting activated caspase-3/7, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 13, Pages: 5418-5423, ISSN: 1477-0520
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