I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[35994]
Abstract: Gold catalysis provides access to a remarkable array of complex carbon scaffolds, but the use of silver salts to activate gold(I) chloride precatalysts can be problematic due to Ag(I) light sensitivity, hygroscopicity, redox activity, and interference with the desired catalysis. Although H-bond donors are a promising alternative to silver salts, they still suffer from much lower activity and narrower applicability, as Au–Cl cleavage remains rate limiting. To address these limitations, we have rationally designed a self-activating phosphine Au(I) chloride complex that incorporates a supramolecular chloride receptor in the form of an anthracene bisurea quintuple H-bond donor. In the absence of any additive, this complex promotes multiple intra- and intermolecular reactions, with a catalytic activity rivalling traditional inorganic chloride scavengers. Mechanistic studies for the model reaction show that the exceptional chloride binding ability of the anthracene bisurea unlocks access to a zwitterionic catalyst resting state where the Au─Cl bond has been cleaved, thus significantly reducing barriers for catalysis. The principles uncovered in this work show how supramolecular anion recognition moieties impact catalyst speciation and enhance performance, enabling for the first time H-bond donors to compete with inorganic chloride scavengers in terms of activity and generality.
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Jan 2026
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[30280]
Open Access
Abstract: Crystalline solvates, including hydrates, hold untapped potential in pharmaceutical development, yet their exploitation remains minimal due to the difficult and laborious task of unequivocally establishing their physical stabilities. We introduce Controlled Solvent-Activity Liquid-Assisted Grinding (CSA-LAG), a mechanochemical protocol that offers solvate phase boundary elucidation by varying the activity of a chosen solvent in defined binary/ternary mixtures and analysing the equilibrated resulting solid form. Using small API amounts, CSA-LAG reaches equilibrium within minutes and yields critical solvent activities that delimit neat, hydrated, solvated and competing-solvate domains. The method uses mixtures of known thermodynamic activities, requires far less material and time than traditional slurries and affords high reproducibility. Applied to four pharmaceutical compounds, CSA-LAG reproduces slurry boundaries and quantifies activity thresholds for single, stepwise and competitive solvations. Defining these boundaries enables rational form selection and process design either by avoiding or targeting solvates, whilst turning a month-scale empirical screening into a rapid, thermodynamically guided workflow.
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Jan 2026
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[35994]
Open Access
Abstract: A series of previously unknown bis(acylhydrazone)s with aliphatic (zero to four CH2 units) and aromatic (phenylene substituted) linkers was synthesized and structurally characterized. Aliphatic derivatives exhibited distinct conformational geometries and packing motifs, with linker length critically affecting hydrogen bond interactions and energies. Aromatic derivatives revealed three polymorphs of the meta-substituted structure with two of the forms related by temperature. Additionally, a bis(acylhydrazone) low-molecular-weight gelator was crystallized, revealing a unique and impressive hydrogen-bonded framework with large water channels (952 Å3) and strong aliphatic and aromatic stacking interactions. These findings highlight the potential of bis(acylhydrazone)s in crystal engineering and supramolecular chemistry, especially in coformer design and selection, and supramolecular gelator applications.
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Dec 2025
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I19-Small Molecule Single Crystal Diffraction
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Abstract: Proteolysis-targeting chimeras (PROTACs) represent a promising drug modality within the beyond Rule of Five (bRo5) chemical space but are hindered by extremely poor aqueous solubility and limited crystallisability, due to their flexible structures consisting of two ligand moieties joined chemically by a linker. While several X-ray structures have been reported of PROTACs in ternary complexes, to date no structures have been published of single-component densely packed PROTACs, from which an understanding of PROTACs’ intermolecular interactions, and therefore physical properties, can be developed. This thesis addresses these challenges through solid-state engineering approaches aimed at improving solubility and advancing pre-formulation strategies. The first single-component crystal structures of a cereblon-recruiting PROTAC ‘AZ1’ are reported, obtained via advanced crystallisation protocols combined with 3D electron diffraction and synchrotron X-ray diffraction. Despite their potential for hydrogen bonding, these structures are dominated by dispersive interactions, forming similar packing motifs across different crystalline forms. Generating amorphous phases of AZ1 by different methods can lead to distinct dissolution behaviours, suggesting that PROTACs can also exhibit pseudo-polyamorphism. Pre-formulation studies show that amorphous solid dispersions (ASDs) of PROTACs with HPMCAS polymer significantly enhance supersaturation upon dissolution compared to the pure amorphous drug, achievable at a relatively high weight-percentage of drug when synthesised via the slurry conversion method. In contrast, co-amorphous systems with small molecule co-formers failed to improve dissolution despite evidence of inter-component hydrogen bonding. Complementary crystallisation studies on lenalidomide, a molecular fragment of AZ1, explore low-solubility co-crystals for pulmonary drug delivery and gel-phase crystallisation to control polymorphism, highlighting novel avenues for managing solid state properties. Collectively, these findings contribute towards an understanding of how to overcome PROTACs’ poor pharmacokinetic properties through tailored solid-state strategies.
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Dec 2025
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[35882]
Open Access
Abstract: Here, we report a new tetrakis(formylpyridine) subcomponent that was designed to assemble with anilines and ZnII to afford a set of structurally distinct metal–organic cage structure types. By modulating the metal-to-ligand stoichiometry, we obtained a pseudo-cubic Zn8L6 cage and an open Zn6L3 trigonal prism, the former featuring a diastereomeric configuration of faces and vertices that had not been previously observed. Addition of a tritopic subcomponent yielded a Zn6L3L′2 heteroleptic capped trigonal prism, which could also be prepared via a combination of the homoleptic cages formed by the two individual ligands. The capped trigonal prism encapsulated the pollutant perfluorobutanesulfonate and the oxidant tetracyanoquinodimethane, both technologically relevant guests.
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Nov 2025
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[34390, 34452, 26668]
Open Access
Abstract: A series of new isostructural Ti-oxo clusters containing bridging bidentate 1,n-alkane diolate ligands with the formula [Ti4O4(O2PR2)4{O(CH2)nO}2] (R = Ph, n = 2–5; R = Cy, n = 2–4) were prepared by an alkoxide exchange strategy. The cluster with the 1,5-pentane diolate ligand undergoes productive photoredox chemistry in solution under UV light, resulting in the oxidation of one end of the alkane diolate, and subsequent cyclisation into the lactone tetrahydro-2H-pyran-2-ol, along with formation of a two-electron reduced Ti-oxo cluster stabilised by pyridine. Clusters with smaller bridging alkane diolates show no productive photoredox reactivity, except for R = Cy, n = 3, in which the photoredox products are unstable to further redox processes. Ultrafast electronic absorption spectroscopy studies reveal that all clusters undergo a similar initial photoexcitation step, therefore, productive redox pathways are controlled by the availability of a suitable transition state for rapid proton-coupled electron transfer from the initially generated pendant alkane diolate radicals {Ti–O(CH2)nO˙}. This is dependent on the flexibility (i.e. size) of the 1,n-alkane diolate ligand backbone. Interestingly, the productive photoredox pathway of the 1,5-pentane diolate cluster is turned off when the flexibility of the cluster is restricted in the single crystal phase.
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Nov 2025
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[35994]
Abstract: Porphyrin-containing Phthalocyanine Nanoporous Crystals (PNCs) have been prepared previously by the cocrystallisation of octa(2',6'-di-iso-propyphenoxy)phthalocyanine [(dipPhO)8Pc] and its metalated derivatives with metal-free tetraphenylporphyrin (TPP). Here we report the effect of the central cations (M = H2, Co, Cu, Zn) on heterodimer formation, both in solution and in cocrystallisations, for all sixteen possible combinations of (dipPhO)8PcM with TPPM. UV/visible spectroscopy shows a clear trend of Cu2+ > 2H+ > Co2+ > Zn2+ for encouraging or discouraging heterodimer formation, which can be rationalised by the propensity of the metal cation to bind to axial ligands when incorporated into porphyrin or phthalocyanine macrocycles. Attempted cocrystallisations of all 16 (dipPhO)8PcM/TPPM combinations yielded 13 heterodimer-based PNCs, with only (dipPhO)8PcZn failing to provide a cocrystal with TPPM (Co, Cu, Zn). This study further demonstrates the remarkable efficiency of (dipPhO)8PcM in directing the structure of PNC cocrystallisations. It suggests a simple method for placing two metal cations of choice within van der Waals distance of one another within a well-defined, predictable crystal structure.
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Nov 2025
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I19-Small Molecule Single Crystal Diffraction
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Esther Y. H.
Hung
,
Benjamin M.
Gallant
,
Robert
Harniman
,
Jakob
Moebs
,
Santanu
Saha
,
Khaled
Kaja
,
Charles
Godfrey
,
Shrestha
Banerjee
,
Nikolaos
Famakidis
,
Harish
Bhaskaran
,
Marina R.
Filip
,
Paolo
Radaelli
,
Nakita K.
Noel
,
Dominik J.
Kubicki
,
Harry C.
Sansom
,
Henry J.
Snaith
Diamond Proposal Number(s):
[36669]
Open Access
Abstract: Molecular piezoelectrics are a potentially disruptive technology, enabling a new generation of self-powered electronics that are flexible, high performing, and inherently low in toxicity. Although significant efforts have been made toward understanding their structural design by targeted manipulation of phase transition behavior, the resulting achievable piezoresponse has remained limited. In this work, we use a low-symmetry, zero-dimensional (0D) inorganic framework alongside a carefully selected ‘quasi-spherical’ organic cation to manipulate organic–inorganic interactions and thus form the hybrid, piezoelectric material [(CH3)3NCH2I]3Bi2I9. Using variable–temperature single crystal X-ray diffraction and solid-state nuclear magnetic resonance spectroscopy, we demonstrate that this material simultaneously exhibits an order–disorder and displacive symmetry-breaking phase transition. This phase transition is mediated by halogen bonding between the organic and inorganic frameworks and results in a large piezoelectric response, d33 = 161.5 pm/V. This value represents a 4-fold improvement on previously reported halobismuthate piezoelectrics and is comparable to those of commercial inorganic piezoelectrics, thus offering a new pathway toward low-cost, low-toxicity mechanical energy harvesting and actuating devices.
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Nov 2025
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I07-Surface & interface diffraction
I15-Extreme Conditions
I19-Small Molecule Single Crystal Diffraction
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Yang
Lu
,
Young-Kwang
Jung
,
Milos
Dubajic
,
Xinjuan
Li
,
Shabnum
Maqbool
,
Qichun
Gu
,
Xinyu
Bai
,
Yorrick
Boeije
,
Xian Wei
Chua
,
Alessandro J.
Mirabelli
,
Taeheon
Kang
,
Lars
Sonneveld
,
Youcheng
Zhang
,
Thomas A.
Selby
,
Capucine
Mamak
,
Kan
Tang
,
Zhongzheng
Yu
,
Tianjun
Liu
,
Miguel
Anaya
,
Stephen
Barlow
,
Seth R.
Marder
,
Bruno
Ehrler
,
Caterina
Ducati
,
Richard H.
Friend
,
Samuel D.
Stranks
Diamond Proposal Number(s):
[32266, 38601, 30043, 33123, 36628, 38508]
Abstract: Halide perovskites exhibit superior optoelectronic properties but lack precise thickness and band offset control in heterojunctions, which is critical for modular multilayer architectures such as multiple quantum wells. We demonstrate vapor-phase, layer-by-layer heteroepitaxial growth exemplified by CsPbBr3 deposition on single crystals of PEA2PbBr4 (PEA: 2-phenylethylammonium). Angstrom-level thickness control and subangstrom smooth layers enable quantum-confined photoluminescence of CsPbBr3 from monolayer, bilayer, and through to bulk. The interfacial structure controls the electronic structure from a Cs‒PEA-terminated interface (type II heterojunction) to a PEA‒PEA-terminated interface (type I heterojunction), with a layer-tunable band offset shift exceeding 0.5 electron volts. Electron transfer from CsPbBr3 to PEA2PbBr4 for a type II Cs‒PEA heterojunction results in delayed electron-hole recombination beyond 10 microseconds. Precise quantum confinement control and large band offset tunability unlock perovskite heterojunctions as platforms for scalable, superlattice-based optoelectronic applications.
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Nov 2025
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[30280]
Open Access
Abstract: A new metal–organic framework (MOF) comprising copper and 2,3-dihydroxyterephthalate (2,3-dhtp) has been prepared using solvothermal synthesis. The solid (chemical formula of the as-made material): Cu12(dhtp)4(H2dhtp)3(CH3CO2)2 2DMF·10H2O is flexible in that its pore size adapts to match the size of guest molecules that are adsorbed. Carboxylate-containing molecules of different sizes (acetate, benzoic acid and ibuprofen) can be accommodated within the pores of the material and are coordinated to a dimeric copper unit. The localisation of the adsorbate guest molecule, the mode of binding and relatively low symmetry of the MOF allows the system to be used as a crystalline sponge. The crystal structure determination of the as-synthesised acetate-bound MOF was accomplished using single-crystal X-ray diffraction using a synchrotron source, while the benzoate- and ibuprofen-bound structures were solved using electron diffraction. A more practical adsorbent can be formulated by growing the MOF on a cotton fabric substrate, and this is shown to adsorb ibuprofen in a similar manner to the powdered MOF.
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Nov 2025
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