I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[30280]
Open Access
Abstract: A new teaching resource comprised of raw X-ray diffraction data sets from crystallography experiments has been compiled. The aim of this resource is to provide a tool with which to plug the teaching gap between crystals and chemical structures present at various levels of education, as well as providing examples for early stage researchers and institutions without the requisite instrumentation to use for training. The data sets mirror the contents of the highly successful CSD Teaching Subset and include examples that demonstrate the effects of wavelength, crystal quality, and collection temperature. As crystallography underpins our understanding of chemical structure, exposure to the technique will be beneficial to students in terms of providing understanding of where the structures in the CSD Teaching Subset originate as well as insights into many overlapping fields such as scattering theory and symmetry. The resource will be available through the CCDC Web site and will provide links to the software required for data processing and documentation describing its use. It is hoped that this resource will expand with contributions from users in terms of both data and teaching exercises.
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Sep 2024
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[8682]
Open Access
Abstract: The benzyl-substituted phosphine–boranes PhCH2P(BH3)R2 [R = iPr (1H), Ph (2H), Cy (3H)] are accessible through either the reaction between R2PCl and PhCH2MgBr, followed by treatment with BH3·SMe2 or the reaction between R2P(BH)3Li and PhCH2Br. Treatment of 1H, 2H, or 3H with nBuLi, PhCH2Na, or PhCH2K gave the corresponding alkali metal complexes [{iPr2P(BH3)CHPh}Li(THF)]2 (1Li), [{Ph2P(BH3)CHPh}Li(OEt2)2] (2Li), [{Cy2P(BH3)CHPh}Li(TMEDA)] (3Li), [iPr2P(BH3)CHPh]Na (1Na), [{Ph2P(BH3)CHPh}Na(THF)2]2 (2Na), [Cy2P(BH3)CHPh]Na(THF)0.5 (3Na), [{iPr2P(BH3)CHPh}K]∞ (1K), [{Ph2P(BH3)CHPh}K(THF)]∞ (2K), and [{Cy2P(BH3)CHPh}K.0.5PhMe]∞ (3K). X-ray crystallography revealed that, while 2Li and 3Li crystallize as monomers, 1Li and 2Na crystallize as borane-bridged dimers. The potassium complexes 1K, 2K, and 3K all crystallize with polymeric structures, in which the monomer units are linked to each other through a range of both bridging BH3 groups and multihapto interactions between the potassium cations and the aromatic rings. The reactions between two equivalents of either 1Li or 3Li and Cp2Sn gave the corresponding dialkylstannylenes [{R2P(BH3)CHPh}2Sn] [R = iPr (1Sn), Cy (3Sn)]. These compounds were isolated as mixtures of the rac and meso diastereomers. X-ray crystallography reveals that rac-1Sn and rac-3Sn crystallize as discrete monomers each exhibiting two agostic-type B–H···Sn contacts.
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Jan 2024
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[16117]
Open Access
Abstract: Zˈ is a parameter used to denote the number of symmetry-independent molecules in the asymmetric unit of a crystal structure. High Zˈ (>1) crystal structures are relatively uncommon and are thought to arise through competition between intermolecular interactions of similar strength. As such high Zˈ crystal structures are challenging to predict and new examples are valuable in improving understanding in the field. Herein, we report the X-ray crystal structures of a series of shikimate esters, the asymmetric units of which exhibit high Zˈ values. Of special interest is the crystal structure of methyl shikimate, the asymmetric unit of which comprises 12 independent molecules; Zˈ = 12. This uncommonly large Zˈ value arises through a combination of factors, including the intrinsic homochirality of the molecule, the conformational inflexibility of the cyclohexene ring, the presence of multiple hydrogen bonding motifs, and both the cis- and trans-conformers of the ester moiety. Comparison of the X-ray crystal structures of shikimic acid, methyl shikimate, ethyl shikimate, and iso-propyl shikimate suggests that instances of high Zˈ in this series correlate with specific hydrogen bonding motifs influenced by the steric bulk of the ester. The results of this study provide important insights into factors that influence the formation of organic crystal structures where the value of Zˈ is greater than 1.
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Jan 2024
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[22240]
Open Access
Abstract: Single-crystal X-ray diffraction analysis of small molecule active pharmaceutical ingredients is a key technique in the confirmation of molecular connectivity, including absolute stereochemistry, as well as the solid-state form. However, accessing single crystals suitable for X-ray diffraction analysis of an active pharmaceutical ingredient can be experimentally laborious, especially considering the potential for multiple solid-state forms (solvates, hydrates and polymorphs). In recent years, methods for the exploration of experimental crystallization space of small molecules have undergone a `step-change', resulting in new high-throughput techniques becoming available. Here, the application of high-throughput encapsulated nanodroplet crystallization to a series of six dihydropyridines, calcium channel blockers used in the treatment of hypertension related diseases, is described. This approach allowed 288 individual crystallization experiments to be performed in parallel on each molecule, resulting in rapid access to crystals and subsequent crystal structures for all six dihydropyridines, as well as revealing a new solvate polymorph of nifedipine (1,4-dioxane solvate) and the first known solvate of nimodipine (DMSO solvate). This work further demonstrates the power of modern high-throughput crystallization methods in the exploration of the solid-state landscape of active pharmaceutical ingredients to facilitate crystal form discovery and structural analysis by single-crystal X-ray diffraction.
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Dec 2023
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I19-Small Molecule Single Crystal Diffraction
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Eman A. A.
Alkhudhayr
,
Dumitru
Sirbu
,
Miriam
Fsadni
,
Benjamin
Vella
,
Bening T.
Muhammad
,
Paul G.
Waddell
,
Michael R.
Probert
,
Thomas J.
Penfold
,
Toby
Hallam
,
Elizabeth
Gibson
,
Pablo
Docampo
Diamond Proposal Number(s):
[302080]
Open Access
Abstract: Organic–inorganic hybrid halide perovskite solar cells (PSCs) have attracted substantial attention from the photovoltaic research community, with the power conversion efficiency (PCE) already exceeding 26%. Current state-of-the-art devices rely on Spiro-OMeTAD as the hole-transporting material (HTM); however, Spiro-OMeTAD is costly due to its complicated synthesis and expensive product purification, while its low conductivity ultimately limits the achievable device efficiency. In this work, we build upon our recently introduced family of low-cost amide-based small molecules and introduce a molecule (termed TPABT) that results in high conductivity values (∼10–5 S cm–1 upon addition of standard ionic additives), outperforming our previous amide-based material (EDOT-Amide-TPA, ∼10–6 S cm–1) while only costing an estimated $5/g. We ascribe the increased optoelectronic properties to favorable molecular packing, as shown by single-crystal X-ray diffraction, which results in close spacing between the triphenylamine blocks. This, in turn, results in a short hole-hopping distance between molecules and therefore good mobility and conductivity. In addition, TPABT exhibits a higher bandgap and is as a result more transparent in the visible range of the solar spectrum, leading to lower parasitic absorption losses than Spiro-OMeTAD, and has increased moisture stability. We applied the molecule in perovskite solar cells and obtained good efficiency values in the ∼15% range. Our approach shows that engineering better molecular packing may be the key to developing high-efficiency, low-cost HTMs for perovskite solar cells.
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Nov 2023
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I19-Small Molecule Single Crystal Diffraction
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Bernhard
Kepplinger
,
Lina
Mardiana
,
Joseph
Cowell
,
Stephanie
Morton-Laing
,
Yousef
Dashti
,
Corinne
Wills
,
Emma C. L.
Marrs
,
John D.
Perry
,
Joe
Gray
,
Michael
Goodfellow
,
Jeff
Errington
,
Michael R.
Probert
,
William
Clegg
,
Jonathan
Bogaerts
,
Wouter
Herrebout
,
Nick E. E.
Allenby
,
Michael J.
Hall
Diamond Proposal Number(s):
[6749, 11145]
Open Access
Abstract: A genomic and bioactivity informed analysis of the metabolome of the extremophile Amycolatopsis sp. DEM30355 has allowed for the discovery and isolation of the polyketide antibiotic tatiomicin. Identification of the biosynthetic gene cluster was confirmed by heterologous expression in Streptomyces coelicolor M1152. Structural elucidation, including absolute stereochemical assignment, was performed using complementary crystallographic, spectroscopic and computational methods. Tatiomicin shows antibiotic activity against Gram‑positive bacteria, including methicillin‑resistant Staphylococcus aureus (MRSA). Cytological profiling experiments suggest a putative antibiotic mode‑of‑action, involving membrane depolarisation and chromosomal decondensation of the target bacteria.
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Sep 2022
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I19-Small Molecule Single Crystal Diffraction
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Hannes
Michaels
,
Matthias Johannes
Golomb
,
Byeong
Kim
,
Tomas
Edvinsson
,
Fabio
Cucinotta
,
Paul G.
Waddell
,
Michael R.
Probert
,
Steven J.
Konezny
,
Gerrit
Boschloo
,
Aron
Walsh
,
Marina
Freitag
Diamond Proposal Number(s):
[22240]
Open Access
Abstract: Emerging technologies in solar energy will be critical in enabling worldwide society in overcoming the present energy challenges and reaching carbon net zero. Inefficient and unstable charge transport materials limit current emerging energy conversion and storage technologies. Low-dimensional coordination polymers represent an alternative, unprecedented class of charge transport materials, comprised of molecular building blocks. Here, we provide a comprehensive study of mixed-valence coordination polymers from an analysis of the charge transport mechanism to their implementation as hole conducting layers. CuII dithiocarbamate complexes afford morphology control of 1D polymer chains linked by (CuI2X2) copper halide rhombi. Concerted theoretical and experimental efforts identified the charge transport mechanism at the transition to band-like transport with an modeled effective hole mass of 6 me. The iodide-bridged coordination polymer showed an excellent conductivity of 1 mS cm-1 and a hole mobility of 5.8 10-4 cm2(Vs)-1 at room temperature. Nanosecond selective hole injection into coordination polymer thin films was captured by nanosecond photoluminescenceof halide perovskite films. The coordination polymers constitute a sustainable, tunable alternative to the current standard of heavily doped organic hole conductors.
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Mar 2022
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[22240]
Abstract: Conventional redox mediators based on metal coordination complexes undergo electron transfer through the change in oxidation state of the metal center. However, electron transfer kinetics are offset toward preferred oxidation states when preorganized ligands constrain the reorganization of the coordination sphere. In contrast, we report here on dimeric copper(II/I) redox couples, wherein the extent of oxidation/reduction of two metal centers dictates the dynamic formation of dimer and monomer complexes: the dimeric (Cu(I))2 transitions to monomers of Cu(II). The bis(thiazole/pyrrole)-bipyridine tetradentate ligands stabilize both oxidation states of the unique redox systems. The dynamic dimer redox mediators offer a viable two-electron redox mechanism to develop efficient hybrid solar cells through inhibited recombination and rapid charge transport. Density functional theory calculations reveal inner reorganization energies for single-electron transfer as low as 0.27 eV, marking the dimeric complexes superior redox systems over single complexes as liquid and potentially solid-state electrolytes.
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Nov 2021
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I19-Small Molecule Single Crystal Diffraction
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Jessica L.
Andrews
,
Sten O.
Nilsson Lill
,
Stefanie
Freitag-Pohl
,
David C.
Apperley
,
Dmitry
Yufit
,
Andrei S.
Batsanov
,
Matthew T.
Mulvee
,
Katharina
Edkins
,
James F.
Mccabe
,
David J.
Berry
,
Michael R.
Probert
,
Jonathan W.
Steed
Diamond Proposal Number(s):
[11145]
Abstract: This work presents an updated solid-form discovery approach to the polymorphism of the antiarrhythmic drug mexiletine hydrochloride, in which experimental and computational techniques are combined to provide a rigorous characterization of the solid-form landscape of this compound. The resulting solid forms were characterized by powder and single-crystal X-ray diffraction, IR spectroscopy, differential scanning calorimetry, and 13C solid-state NMR. This approach reveals five solid-form types of mexiletine hydrochloride. Forms 1, 2, and 3 are mutually enantiotropically related anhydrous polymorphs, with Form 1 the room temperature stable form, Form 2 the high-temperature form, and Form 3 the thermodynamically stable polymorph between 148 and 167 °C. The final two forms termed Types A and B comprise two large families of isomorphous channel solvates, including a fourth nonsolvated form isostructural to the Type A solvates. We report 11 modifications of each solvate, in which a diverse range of solvents are included in the channels, without changing the fundamental structure of the drug framework. These experimental results go hand-in-hand with computational crystal structure prediction (using the AstraZeneca crystal structure prediction approach), which together suggest that it is unlikely further nonsolvated forms, at least with Z′ = 1, will be discovered under ambient conditions.
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Oct 2021
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[22240]
Open Access
Abstract: A new class of light-activated ruthenium(II) complex was designed as a potential blocker of biological functioning, especially for targeting redox reactions within mitochondria under light activation. Based on our concepts the complex [Ru(bipy)2(1-hydroxyanthra-9,10 quinone)]Cl (RU1) was prepared and studied to understand the preliminary reaction mechanisms and its excited state behaviour through a series of stability tests, electrochemistry, UV–Visible kinetics and femtosecond transient absorption spectroscopy experiments. Under white light in the presence of H2O2 two different reactions (fast and slow) appear to take place. The complex loses the quinone-based ligand and a resulting Ru(III) or Ru(V) species is produced. The complex RU1 shows potential to consume H2O2 from the one carbon metabolism in mitochondria, and hence may cut the energy cycle pathway of tumor cells.
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Aug 2020
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