I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[20876]
Open Access
Abstract: Cyclic porphyrin oligomers have been studied as models for photosynthetic light-harvesting antenna complexes and as potential receptors for supramolecular chemistry. Here, we report the synthesis of unprecedented β,β-directly linked cyclic zinc porphyrin oligomers, the trimer (CP3) and tetramer (CP4), by Yamamoto coupling of a 2,3-dibromoporphyrin precursor. Their three-dimensional structures were confirmed by nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and single-crystal X-ray diffraction analyses. The minimum-energy geometries of CP3 and CP4 have propeller and saddle shapes, respectively, as calculated using density functional theory. Their different geometries result in distinct photophysical and electrochemical properties. The smaller dihedral angles between the porphyrin units in CP3, compared with CP4, result in stronger π-conjugation, splitting the ultraviolet–vis absorption bands and shifting them to longer wavelengths. Analysis of the crystallographic bond lengths indicates that the central benzene ring of the CP3 is partially aromatic [harmonic oscillator model of aromaticity (HOMA) 0.52], whereas the central cyclooctatetraene ring of the CP4 is non-aromatic (HOMA –0.02). The saddle-shaped structure of CP4 makes it a ditopic receptor for fullerenes, with affinity constants of (1.1 ± 0.4) × 105 M–1 for C70 and (2.2 ± 0.1) × 104 M–1 for C60, respectively, in toluene solution at 298 K. The formation of a 1:2 complex with C60 is confirmed by NMR titration and single-crystal X-ray diffraction.
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May 2023
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I03-Macromolecular Crystallography
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Arathy
Jose
,
Daniel
Guest
,
Remi
Legay
,
Graham J.
Tizzard
,
Simon
Coles
,
Mariliza
Derveni
,
Edward
Wright
,
Lester
Marrison
,
Alpha A.
Lee
,
Aaron
Morris
,
Matt
Robinson
,
Frank
Von Delft
,
Daren
Fearon
,
Lizbe
Koekemoer
,
Tetiana
Matviuk
,
Anthony
Aimon
,
Christopher J.
Schofield
,
Tika R.
Malla
,
Nir
London
,
Barnaby W.
Greenland
,
Mark C.
Bagley
,
John
Spencer
Diamond Proposal Number(s):
[19301]
Open Access
Abstract: The pentafluorosulfanyl (-SF5) functional group is of increasing interest as a bioisostere in medicinal chemistry. A library of SF5-containing compounds, including amide, isoxazole, and oxindole derivatives, was synthesised using a range of solution-based and solventless methods, including microwave and ball-mill techniques. The library was tested against targets including human dihydroorotate dehydrogenase (HDHODH). A subsequent focused approach led to synthesis of analogues of the clinically used disease modifying anti-rheumatic drugs (DMARDs), Teriflunomide and Leflunomide, considered for potential COVID-19 use, where SF5 bioisostere deployment led to improved inhibition of HDHODH compared with the parent drugs. The results demonstrate the utility of the SF5 group in medicinal chemistry.
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Feb 2022
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I19-Small Molecule Single Crystal Diffraction
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John D.
Wallis
,
Gregory J
Rees
,
Mateusz B.
Pitak
,
Alberth
Lari
,
Stephen P.
Day
,
Jonathan R.
Yates
,
Peter
Gierth
,
Kristian
Barnsley
,
Mark E.
Smith
,
Simon J.
Coles
,
John V.
Hanna
Diamond Proposal Number(s):
[8521]
Open Access
Abstract: A combination of charge density studies and solid state nuclear magnetic resonance (NMR) 1 J NC coupling measurements supported by periodic density functional theory (DFT) calculations is used to characterise the transition from an n - π * interaction to bond formation between a nucleophilic nitrogen atom and an electrophilic sp 2 carbon atom in a series of crystalline peri-substituted naphthalenes. As the N···C distance reduces there is a sharp decrease in the Laplacian derived from increasing charge density between the two groups at ca. N···C:1.8 Å, with the periodic DFT calculations predicting, and heteronuclear spin-echo NMR measurements confirming, the 1 J NC couplings of ~2-5 Hz for long C-N bonds (1.60-1.65 Å), and 1 J NC couplings of <1 Hz for N···C > 2.1 Å.
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Aug 2021
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Zahraa S.
Al-Taie
,
Joseph M.
Anderson
,
Laura
Bischoff
,
Jeppe
Christensen
,
Simon J.
Coles
,
Richard
Froom
,
Mari E.
Gibbard
,
Leigh F.
Jones
,
F. F. J.
De Kleijne
,
Patrick J.
Murphy
,
Emma C.
Thompson
Abstract: We report the preparation of a range of N-protected amino acid derived guanidine organocatalysts and their application to the Michael addition of 2-hydroxy-1,4-napthoquinone to β-nitrostyrene, achieving a maximum ee of 26%. Whilst these catalysts gave poor ees, the structural variation together with the X-ray crystallographic study of the intra- and intermolecular hydrogen bonding reported suggest that the C2-symmetric catalyst are lead compounds for the further development of this methodology.
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Apr 2021
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I19-Small Molecule Single Crystal Diffraction
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Alexander J.
Bukvic
,
Arron L.
Burnage
,
Graham J.
Tizzard
,
Antonio J.
Martinez-Martinez
,
Alasdair I.
Mckay
,
Nicholas H.
Rees
,
Bengt E.
Tegner
,
Tobias
Krämer
,
Heather
Fish
,
Mark R.
Warren
,
Simon J.
Coles
,
Stuart A.
Macgregor
,
Andrew S.
Weller
Diamond Proposal Number(s):
[20300, 17308]
Abstract: Using solid-state molecular organometallic (SMOM) techniques, in particular solid/gas single-crystal to single-crystal reactivity, a series of σ-alkane complexes of the general formula [Rh(Cy2PCH2CH2PCy2)(ηn:ηm-alkane)][BArF4] have been prepared (alkane = propane, 2-methylbutane, hexane, 3-methylpentane; ArF = 3,5-(CF3)2C6H3). These new complexes have been characterized using single crystal X-ray diffraction, solid-state NMR spectroscopy and DFT computational techniques and present a variety of Rh(I)···H–C binding motifs at the metal coordination site: 1,2-η2:η2 (2-methylbutane), 1,3-η2:η2 (propane), 2,4-η2:η2 (hexane), and 1,4-η1:η2 (3-methylpentane). For the linear alkanes propane and hexane, some additional Rh(I)···H–C interactions with the geminal C–H bonds are also evident. The stability of these complexes with respect to alkane loss in the solid state varies with the identity of the alkane: from propane that decomposes rapidly at 295 K to 2-methylbutane that is stable and instead undergoes an acceptorless dehydrogenation to form a bound alkene complex. In each case the alkane sits in a binding pocket defined by the {Rh(Cy2PCH2CH2PCy2)}+ fragment and the surrounding array of [BArF4]− anions. For the propane complex, a small alkane binding energy, driven in part by a lack of stabilizing short contacts with the surrounding anions, correlates with the fleeting stability of this species. 2-Methylbutane forms more short contacts within the binding pocket, and as a result the complex is considerably more stable. However, the complex of the larger 3-methylpentane ligand shows lower stability. Empirically, there therefore appears to be an optimal fit between the size and shape of the alkane and overall stability. Such observations are related to guest/host interactions in solution supramolecular chemistry and the holistic role of 1°, 2°, and 3° environments in metalloenzymes.
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Mar 2021
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I19-Small Molecule Single Crystal Diffraction
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Aaron J
Scott
,
Euan K.
Brechin
,
Stergios
Piligkos
,
Gopalan
Rajaraman
,
Mark
Murrie
,
Simon
Coles
,
Wim T.
Klooster
,
Gary S.
Nichol
,
Paul
Lusby
,
Lucy
Smythe
,
Arup
Sarkar
,
Julia
Vallejo
,
Emma
Regincos Marti
Diamond Proposal Number(s):
[22240]
Open Access
Abstract: Reaction of Ni(OTf)2 with the bisbidentate quaterpyridine ligand L results in the self-assembly of a tetrahedral, paramagnetic cage [NiII4L6]8+. By selectively exchanging the bound triflate from [OTf⊂NiII4L6](OTf)7 (1), we have been able to prepare a series of host-guest complexes that feauture an encapsulated paramagnetic tetrahalometallate ion inside this paramagnetic host giving [MIIX4⊂NiII4L6](OTf)6, where MIIX42− = MnCl42− (2), CoCl42− (5), CoBr42− (6), NiCl42− (7), CuBr42− (8) or [MIIIX4⊂NiII4L6](OTf)7, where MIIIX4− = FeCl4− (3), FeBr4− (4). Triflate-to-tetrahalometallate exchange occurs in solution and can also be accomplished through single-crystal-to-single-crystal transformations. Host-guest complexes 1-8 all crystallise as homochiral racemates in monoclinic space groups, wherein the four {NiN6} vertex within a single Ni4L6 unit possess the same Δ or Λ stereochemistry. Magnetic susceptibility and magnetisation data show that the magnetic exchange between metal ions in the host [NiII4] complex, and between the host and the MX4n- guest, are of comparable magnitude and antiferromagnetic in nature. Theoretically derived values for the magnetic exchange are in close agreement with experiment, revealing that large spin densities on the electronegative X-atoms of particular {MX4}n− guest molecules leads to stronger host-guest magnetic exchange interactions.
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Mar 2021
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I19-Small Molecule Single Crystal Diffraction
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Helen M.
O’connor
,
Sergio
Sanz
,
Aaron J.
Scott
,
Mateusz B.
Pitak
,
Wim T.
Klooster
,
Simon J.
Coles
,
Nicholas F.
Chilton
,
Eric J. L.
Mcinnes
,
Paul J.
Lusby
,
Høgni
Weihe
,
Stergios
Piligkos
,
Euan K.
Brechin
Diamond Proposal Number(s):
[11238]
Open Access
Abstract: Three new heterometallic [CrIII8NiII6] coordination cubes of formulae [CrIII8NiII6L24(H2O)12](NO3)12 (1), [CrIII8NiII6L24(MeCN)7(H2O)5](ClO4)12 (2), and [CrIII8NiII6L24Cl12] (3) (where HL = 1-(4-pyridyl)butane-1,3-dione), were synthesised using the paramagnetic metalloligand [CrIIIL3] and the corresponding NiII salt. The magnetic skeleton of each capsule describes a face-centred cube in which the eight CrIII and six NiII ions occupy the eight vertices and six faces of the structure, respectively. Direct current magnetic susceptibility measurements on (1) reveal weak ferromagnetic interactions between the CrIII and NiII ions, with JCr-Ni = + 0.045 cm−1. EPR spectra are consistent with weak exchange, being dominated by the zero-field splitting of the CrIII ions. Excluding wheel-like structures, examples of large heterometallic clusters containing both CrIII and NiII ions are rather rare, and we demonstrate that the use of metalloligands with predictable bonding modes allows for a modular approach to building families of related polymetallic complexes. Compounds (1)–(3) join the previously published, structurally related family of [MIII8MII6] cubes, where MIII = Cr, Fe and MII = Cu, Co, Mn, Pd.
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Feb 2021
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I19-Small Molecule Single Crystal Diffraction
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Abstract: National facilities provide state-of-the-art crystallographic instrumentation and processes and tend to act as an indicator for the direction of a community in the medium term. There has been a significant step up in terms of instrumentation and approach in the last 10 years which has driven data generation. This has had a significant impact on databases – in turn we observe a substantial change in the use of the Cambridge Structural Database (CSD) from relatively basic search/retrieve to gaining deep understanding about factors that govern the solid state. Databases are now able to drive new science in areas such as crystal engineering. Looking forward, we will see more automated pipelining of the data generation process, and this will require better integration with databases. Databases will provide more predictive power – and this will inform the science/crystallography that should be done.
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Oct 2020
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I19-Small Molecule Single Crystal Diffraction
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Zahraa S.
Al-Taie
,
Simon R.
Anetts
,
Jeppe
Christensen
,
Simon J.
Coles
,
Peter N.
Horton
,
Daniel M.
Evans
,
Leigh F.
Jones
,
Frank F. J.
De Kleijne
,
Shaun M.
Ledbetter
,
Yassin T. H.
Mehdar
,
Patrick J.
Murphy
,
Jack A.
Wilson
Diamond Proposal Number(s):
[15762]
Open Access
Abstract: The preparation of a range of amino acid derived guanidine organocatalysts is reported together with their application to the Michael addition of 2-hydroxy-1,4-napthoquinone to β-nitrostyrene, achieving a maximum ee of 56%. Some insight into the mechanism was sought by using X-ray crystallography and a detailed study of the intra- and intermolecular hydrogen bonding is reported.
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Jun 2020
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[15762]
Open Access
Abstract: Traditionally small-molecule crystallographers have not usually observed or recognized significant radiation damage to their samples during diffraction experiments. However, the increased flux densities provided by third-generation synchrotrons have resulted in increasing numbers of observations of this phenomenon. The diversity of types of small-molecule systems means it is not yet possible to propose a general mechanism for their radiation-induced sample decay, however characterization of the effects will permit attempts to understand and mitigate it. Here, systematic experiments are reported on the effects that sample temperature and beam attenuation have on radiation damage progression, allowing qualitative and quantitative assessment of their impact on crystals of a small-molecule test sample. To allow inter-comparison of different measurements, radiation-damage metrics (diffraction-intensity decline, resolution fall-off, scaling B-factor increase) are plotted against the absorbed dose. For ease-of-dose calculations, the software developed for protein crystallography, RADDOSE-3D, has been modified for use in small-molecule crystallography. It is intended that these initial experiments will assist in establishing protocols for small-molecule crystallographers to optimize the diffraction signal from their samples prior to the onset of the deleterious effects of radiation damage.
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Jul 2019
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