The title compound, [Ag2(C19H20N2)4]Cl·0.5C2H4Cl2, can be readily generated by treatment of (1-benzyl-3-(2,4,6-tri­methyl­phen­yl)imidazolium chloride with sodium bis­(tri­methyl­sil­yl)amide followed by silver chloride. The mol­ecular structure of the compound was confirmed using NMR spectroscopy and single-crystal X-ray diffraction analysis. The crystal structure of the title compound at 110 K has monoclinic (P21/c) symmetry. The represented silver compound is of inter­est with respect to anti­bacterial properties and the structure displays a series of weak inter­molecular hydrogen-bonding inter­actions with the chloride counter-anion.

The title compound, [Ir(C15H10N)2(C19H12N4)]PF6·CH3OH, crystallizes in the C2/c space group with one monocationic iridium complex, one hexa­fluorido­phosphate anion, and one methanol solvent mol­ecule of crystallization in the asymmetric unit, all in general positions. The anion and solvent are linked to the iridium complex cation via hydrogen bonding. All bond lengths and angles fall into expected ranges compared to similar compounds.

In the title compound, C21H27BF2N2O4, a highly fluorescent boron–dipyrromethene dye, the methyl­propionate moieties have different conformations. In the crystal, weak C—H⋯F and C—H⋯O inter­actions link the mol­ecules. Some optical properties are presented.

The title compound, [Ru(C12H14NO2)2(C12H8N2)]PF6 crystallizes in the tetra­gonal Sohnke space group P41212. The two bidentate chiral salicyloxazoline ligands and the phenanthroline co-ligand coordinate to the central RuIII atom through N,O and N,N atom pairs to form bite angles of 89.76 (15) and 79.0 (2)°, respectively. The octa­hedral coordination of the bidentate ligands leads to a propeller-like shape, which induces metal-centered chirality onto the complex, with a right-handed (Δ) absolute configuration [the Flack parameter value is −0.003 (14)]. Both the complex cation and the disordered PF6− counter-anion are located on twofold rotation axes. Apart from Coulombic forces, the crystal cohesion is ensured by non-classical C—H⋯O and C—H⋯F inter­actions.

A new triazole-based N-heterocyclic carbene IrI cationic complex with a tetra­fluorido­borate counter-anion and hemi-solvating di­chloro­methane, [Ir(C8H12)(C8H15N3)(C18H15P)]BF4·0.5CH2Cl2, has been synthesized and structurally characterized. There are two independent ion pairs in the asymmetric unit and one di­chloro­methane solvent mol­ecule per two ion pairs. The cationic complex exhibits a distorted square-planar conformation around the IrI atom, formed by a bidentate cyclo­octa-1,5,diene (COD) ligand, a tri­phenyl­phosphane ligand, and an N-heterocyclic carbene (NHC). There are several close non-standard H⋯F hydrogen-bonding inter­actions that orient the tetra­fluorido­borate anions with respect to the IrI complex mol­ecules. The complex shows promising catalytic activity in transfer hydrogenation reactions. The structure was refined as a non-merohedral twin, and one of the COD mol­ecules is statistically disordered.

The title compound, C8H8ClNO2, is significantly distorted from planarity, with a twist angle between the planes through the hy­droxy­benzene and acetamide groups being 23.5 (2)°. This conformation is supported by intra­molecular C—H⋯O and N—H⋯Cl contacts. In the crystal, N—H⋯O hydrogen-bonding contacts between acetamide groups and O—H⋯O contacts between hydroxyl groups form tapes propagating parallel to [103].

The crystal structure of a glycosyl­ated porphyrin (P_Gal2) system, C70H70N4O12, where two iso­propyl­idene protected galactose moieties are attached to the meso position of a substituted tetra­aryl porphyrin is reported. This structure reveals that the parent porphyrin is planar, with the galactose moieties positioned above and below the porphyrin macrocycle. This orientation likely prevents porphyrin–porphyrin H-type aggregation, potentially enhancing its efficiency as a photosensitizer in photodynamic therapy. Notable non-bonding C—H⋯O and C—H⋯π inter­actions among adjacent P_Gal2 systems are observed in this crystal network. Additionally, the tolyl groups of each porphyrin can engage in π–π inter­actions with the delocalized π-systems of neighboring porphyrins.

The title compound, C14H20NO5+·Cl−, was prepared as a racemate of R,R- and S,S-enanti­omers by reduction of the corresponding hy­droxy­imino­ketone. In the crystal, layers are formed via hydrogen bridges of four ammonium groups to chloride ions; these lamellae are connected via inter­digitated benzoic ester groups.

The title compound, C14H12O3, is an α-hy­droxy­carb­oxy­lic acid whose ortho­rhom­bic polymorph has been reported earlier [Qiu et al. (2007). Inorg. Chim. Acta, 360, 1819–1824]. The asymmetric unit contains two complete mol­ecules. Classical hydrogen bonds, as well as C—H⋯O contacts, connect the mol­ecules to infinite chains along the crystallographic c-axis direction.

The title compound, C18H12Cl3O4P, is the symmetric phosphate derived from para-chloro­phenol and phospho­ric acid. Two of the three aromatic moieties adopt syn-orientation towards the P=O bond while the last chloro­phenol ring is pointing away from this bond. In the extended structure, C—H⋯O bonds connect the individual mol­ecules into sheets lying perpendicular to the crystallographic b axis.

A confiscated package of street drugs was characterized by the usual mass spectral (MS) and FT–IR analyses. The confiscated powder material was highly crystalline and was found to consist of two very different species, accidentally of sizes convenient for X-ray diffraction. Thus, one each was selected and redundant com­plete sets of data were collected at 100 K using Cu Kα radiation. The selected crystals contained: (a) 1,2-diphenyl-2-(pyrrolidin-1-yl)ethanone hy­dro­chloride hemihydrate or 1-(2-oxo-1,2-di­phenyl­eth­yl)pyrrolidin-1-ium chloride hemihydrate, C18H20NO+·Cl−·0.5H2O, (I), a synthetic cathinone called `α-D2PV', and (b) the sugar myo-inositol, C6H12O6, (II), probably the only instance in which the drug and its diluent have been fully characterized from a single confiscated sample. Moreover, the structural details of both are rather attractive showing: (i) inter­esting hydrogen bonding observed in pairwise inter­actions by the drug mol­ecules, mediated by the chloride counter-anions and the waters of crystallization, and (ii) π–π inter­actions in the case of the phenyl rings of the drug which are of two different types, namely, π–π stacking and edge-to-π. Finally, the inositol crystallizes with Z' = 2 and the resulting diastereoisomers were examined by overlay techniques.

The crystal structure of a new 1:1 cocrystal of carbamazepine and S-naproxen (C15H12N2O·C14H14O3) was solved from powder X-ray diffraction (PXRD). The PXRD pattern was measured at the high-resolution beamline CRISTAL at synchrotron SOLEIL (France). The structure was solved using Monte Carlo simulated annealing, then refined with Rietveld refinement. The positions of the H atoms were obtained from density functional theory (DFT) ground-state calculations. The symmetry is ortho­rhom­bic with the space group P212121 (No. 19) and the following lattice parameters: a = 33.5486 (9), b = 26.4223 (6), c = 5.3651 (10) Å and V = 4755.83 (19) Å3.

The structures of five ammonium salt forms of mono­sulfonated azo dyes, derivatives of 4-(2-phenyldiazen-1-yl)benzenesulfonate, with the general formula [NH4][O3S(C6H4)NN(C6H3)RR']·XH2O [R = OH, NH2 or N(C2H4OH)2; R' = H or OH] are presented. All form simple layered structures with alternating hydro­phobic (organic) and hydro­philic (cation, solvent and polar groups) layers. To assess for isostructural behaviour of the ammonium cation with M+ ions, the packing of these structures is compared with literature examples. To aid this comparison, the corresponding structures of four potassium salt forms of the mono­sulfonated azo dyes are also presented herein. Of the five ammonium salts it is found that three have isostructural equivalents. In two cases this equivalent is a potassium salt form and in one case it is a rubidium salt form. The isostructurality of ion packing and of unit-cell symmetry and dimensions tolerates cases where the ammonium ions form somewhat different inter­action types with coformer species than do the potassium or rubidium ions. No sodium salt forms are found to be isostructural with any ammonium equivalent. However, similarities in the anion packing within a single hydro­phobic layer are found for a group that consists of the ammonium and rubidium salt forms of one azo anion species and the sodium and silver salt forms of a different azo species.

Beauveriolides, including the main beauveriolide I {systematic name: (3R,6S,9S,13S)-9-benzyl-13-[(2S)-hexan-2-yl]-6-methyl-3-(2-methyl­prop­yl)-1-oxa-4,7,10-tri­aza­cyclo­tridecane-2,5,8,11-tetrone, C27H41N3O5}, are a series of cyclo­depsipeptides that have shown promising results in the treatment of Alzheimer's disease and in the prevention of foam cell formation in atherosclerosis. Their crystal structure studies have been difficult due to their tiny crystal size and fibre-like morphology, until now. Recent developments in 3D electron diffraction methodology have made it possible to accurately study the crystal structures of submicron crystals by overcoming the problems of beam sensitivity and dynamical scattering. In this study, the absolute structure of beauveriolide I was determined by 3D electron diffraction. The cyclo­dep­si­peptide crystallizes in the space group I2 with lattice parameters a = 40.2744 (4), b = 5.0976 (5), c = 27.698 (4) Å and β = 105.729 (6)°. After dynamical refinement, its absolute structure was determined by comparing the R factors and calculating the z-scores of the two possible enanti­omorphs of beauveriolide I.

This report presents a comprehensive investigation into the synthesis and characterization of Schiff base com­pounds derived from benzene­sul­fon­amide. The synthesis process, involved the reaction between N-cyclo­amino-2-sulf­anil­amide and various substituted o-salicyl­aldehydes, resulted in a set of com­pounds that were subjected to rigorous characterization using advanced spectral techniques, including 1H NMR, 13C NMR and FT–IR spectroscopy, and single-crystal X-ray diffraction. Furthermore, an in-depth assessment of the synthesized com­pounds was conducted through Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis, in conjunction with docking studies, to elucidate their pharmacokinetic profiles and potential. Impressively, the ADMET analysis showcased encouraging drug-likeness properties of the newly synthesized Schiff bases. These computational findings were substanti­ated by mol­ecular properties derived from density functional theory (DFT) calculations using the B3LYP/6-31G* method within the Jaguar Module of Schrödinger 2023-2 from Maestro (Schrodinger LLC, New York, USA). The ex­plor­ation of frontier mol­ecular orbitals (HOMO and LUMO) enabled the computation of global reactivity descriptors (GRDs), encompassing charge separation (Egap) and global softness (S). Notably, within this analysis, one Schiff base, namely, 4-bromo-2-{N-[2-(pyr­rol­idine-1-sul­fonyl)phenyl]car­box­imid­oyl}phenol, 20, em­erged with the smallest charge separation (ΔEgap = 3.5780 eV), signifying heightened potential for biological properties. Conversely, 4-bromo-2-{N-[2-(piper­idine-1-sul­fonyl)phenyl]car­box­imid­oyl}phenol, 17, exhibited the largest charge separation (ΔEgap = 4.9242 eV), implying a relatively lower propensity for biological activity. Moreover, the synthesized Schiff bases displayed re­marke­able inhibition of tankyrase poly(ADP-ribose) polymerase enzymes, integral in colon cancer, surpassing the efficacy of a standard drug used for the same purpose. Additionally, their bioavailability scores aligned closely with established medications such as trifluridine and 5-fluoro­uracil. The ex­plor­ation of mol­ecular electrostatic potential through colour mapping delved into the electronic behaviour and reactivity tendencies intrinsic to this diverse range of mol­ecules.

The coordination of hydro­tris­[3-(2-furyl)pyrazol-1-yl]borate (Tp2-Fu, C21H16BN6O3) to lan­tha­nide(III) ions is achieved for the first time with the com­plex [Ln(Tp2-Fu)2](BPh4)·xCH2Cl2 (1-Ln has Ln = Ce and x = 2; 1-Dy has Ln = Dy and x = 1). This was accom­plished via both hydrous (Ln = Ce) and anhydrous methods (Ln = Dy). When isolating the dysprosium analogue, the filtrate produced a second crop of crystals which were revealed to be the 1,2-borotropic-shifted product [Dy(κ4-Tp2-Fu)(κ5-Tp2-Fu*)](BPh4) (2) {Tp2-Fu* = hydro­bis­[3-(2-furyl)pyrazol-1-yl][5-(2-furyl)pyrazol-1-yl]borate}. We con­clude that the pres­ence of a strong Lewis acid and a sterically crowded coordination environment are contributing factors for the 1,2-borotropic shifting of scorpionate ligands in conjunction with the size of the conical angle with the scorpionate ligand.

The receptor ability of diethyl N,N'-(1,3-phenyl­ene)dicarbamate (1) to form host–guest com­plexes with theophylline (TEO) and caffeine (CAF) by mechanochemistry was evaluated. The formation of the 1–TEO com­plex (C12H16N2O4·C7H8N4O2) was preferred and involves the conformational change of one of the ethyl carbamate groups of 1 from the endo conformation to the exo conformation to allow the formation of inter­molecular inter­actions. The formation of an N—H⋯O=C hydrogen bond between 1 and TEO triggers the conformational change of 1. CAF mol­ecules are unable to form an N—H⋯O=C hydrogen bond with 1, making the conformational change and, therefore, the formation of the com­plex impossible. Conformational change and selective binding were monitored by IR spectroscopy, solid-state 13C nuclear magnetic resonance and single-crystal X-ray diffraction. The 1–TEO com­plex was characterized by IR spectroscopy, solid-state 13C nuclear magnetic resonance, powder X-ray diffraction and single-crystal X-ray diffraction.

We report on the latest advancements in Microcrystal Electron Diffraction (3D ED/MicroED), as discussed during a symposium at the National Center for CryoEM Access and Training housed at the New York Structural Biology Center. This snapshot describes cutting-edge developments in various facets of the field and identifies potential avenues for continued progress. Key sections discuss instrumentation access, research applications for small mol­ecules and biomacromolecules, data collection hardware and software, data reduction software, and finally reporting and validation. 3D ED/MicroED is still early in its wide adoption by the structural science community with ample opportunities for expansion, growth, and innovation.

By studying the structures of (μ-1,4,10,13-tetra­thia-7,16-di­aza­cyclo­octa­deca­ne)bis[iodidopalladium(II)] diiodide penta­(diiodine), [Pd2I2(C12H26N2S4)](I)2·5I2 or [Pd2I2([18]aneN2S4)](I)2·(I2)5, and 4,7,13,16,21,24-hexa­oxa-1,10-diazo­niabi­cyclo­[8.8.8]hexa­cosane triiodide iodide hemi­penta­(diiodine) di­chloro­methane mono­solvate, C18H38N2O62+·I3−·I−·2.5I2·CH2Cl2 or [H2([2.2.2]cryptand)](I3)(I)(I2)2.5·CH2Cl2, we confirm the structural variety of extended polyiodides achievable upon changing the shape, charge and dimensions of the cation template, by altering the synthetic strategy adopted and/or the experimental conditions. Although it is still often difficult to characterize discrete [I2m+n]n− polyiodides higher than I3− on the basis of structural parameters, such as I—I bond distances, FT–Raman spectroscopy appears to identify them as aggregates of I2, I− and (symmetric or slightly asymmetric) I3− building blocks linked by I⋯I inter­actions of varying strengths. However, because FT–Raman spectroscopy carries no information about the topological features of extended polyiodides, the two techniques should therefore be applied in combination to enhance the analysis of this kind of compounds.

The well-known copper car­box­yl­ate dimer, with four car­box­yl­ate ligands ex­ten­ding outwards towards the corners of a square, has been employed to generate a series of crystalline com­pounds. In particular, this work centres on the use of the 4-hy­droxy­benzoate anion (Hhba−) and its deprotonated phe­nol­ate form 4-oxidobenzoate (hba2−) to obtain complexes with the general formula [Cu2(Hhba)4–x(hba)xL2–y]x−, where L is an axial coligand (including solvent mol­ecules), x = 0, 1 or 2, and y = 0 or 1. In some cases, short hy­dro­gen bonds result in complexes which may be represented as [Cu2(Hhba)2(H0.5hba)2L2]−. The main focus of the investigation is on the formation of a variety of extended networks through hy­dro­gen bonding and, in some crystals, coordinate bonds when bridging coligands (L) are employed. Crystals of [Cu2(Hhba)4(di­ox­ane)2]·4(di­ox­ane) consist of the expected Cu dimer with the Hhba− anions forming hy­dro­gen bonds to 1,4-di­ox­ane mol­ecules which block network formation. In the case of crystals of com­position [Et4N][Cu2(Hhba)2(H0.5hba)2(CH3OH)(H2O)]·2(di­ox­ane), Li[Cu2(Hhba)2(H0.5hba)2(H2O)2]·3(di­ox­ane)·4H2O and [Cu2(Hhba)2(H0.5hba)2(H0.5DABCO)2]·3CH3OH (DABCO is 1,4-di­aza­bicyclo­[2.2.2]octa­ne), square-grid hy­dro­gen-bonded networks are generated in which the complex serves as one type of 4-con­necting node, whilst a second 4-con­necting node is a hy­dro­gen-bonding motif assembled from four phenol/phenolate groups. Another two-dimensional (2D) network based upon a related square-grid structure is formed in the case of [Et4N]2[Cu2(Hhba)2(hba)2(di­ox­ane)2][Cu2(Hhba)4(di­ox­ane)(H2O)]·CH3OH. In [Cu2(Hhba)4(H2O)2]·2(Et4NNO3), a square-grid structure is again apparent, but, in this case, a pair of nitrate anions, along with four phenolic groups and a pair of water mol­ecules, combine to form a second type of 4-con­necting node. When 1,8-bis­(di­methyl­amino)­naphthalene (bdn, `proton sponge') is used as a base, another square-grid network is generated, i.e. [Hbdn]2[Cu2(Hhba)2(hba)2(H2O)2]·3(di­ox­ane)·H2O, but with only the copper dimer complex serving as a 4-con­necting node. Complex three-dimensional networks are formed in [Cu2(Hhba)4(O-bipy)]·H2O and [Cu2(Hhba)4(O-bipy)2]·2(di­ox­ane), where the potentially bridging 4,4'-bi­pyridine N,N'-dioxide (O-bipy) ligand is employed. Rare cases of mixed car­box­yl­ate copper dimer complexes were obtained in the cases of [Cu2(Hhba)3(OAc)(di­ox­ane)]·3.5(di­ox­ane) and [Cu2(Hhba)2(OAc)2(DABCO)2]·10(di­ox­ane), with each structure possessing a 2D network structure. The final com­pound re­por­ted is a simple hy­dro­gen-bonded chain of com­position (H0.5DABCO)(H1.5hba), formed from the reaction of H2hba and DABCO.

Using a 1:1 cocrystal of (E)-N-(3,4-di­fluoro­phen­yl)-1-(pyridin-4-yl)methanimine with acetic acid, C12H8F2N2·C2H4O2, we investigate the influence of F atoms introduced to the aromatic ring on promoting π–π inter­actions. The cocrystal crystallizes in the triclinic space group P1. Through crystallographic analysis and com­putational studies, we reveal the mol­ecular arrangement within this co­crystal, demonstrating the presence of hydrogen bonding between the acetic acid mol­ecule and the pyridyl group, along with π–π inter­actions between the aromatic rings. Our findings highlight the importance of F atoms in promoting π–π inter­actions without necessitating full halogenation of the aromatic ring.

Geminal and vicinal bis­(tri­fluoro­methane­sulfonate) esters are highly reactive alkyl­ene synthons used as potent electrophiles in the macrocyclization of imid­azoles and the transformation of bypyridines to diquat derivatives via nucleophilic substitution reactions. Herein we report the crystal structures of methyl­ene (C3H2F6O6S2) and ethyl­ene bis­(tri­fluoro­methane­sulfonate) (C4H4F6O6S2), the first examples of a geminal and vicinal bis­(tri­fluoro­methane­sulfonate) ester characterized by single-crystal X-ray diffraction (SC-XRD). With melting points slightly below ambient temperature, both reported bis­(tri­fluoro­methane­sulfonate)s are air- and moisture-sensitive oils and were crys­tallized at 277 K to afford two-com­ponent non-merohedrally twinned crystals. The dominant inter­actions present in both com­pounds are non-classical C—H⋯O hydrogen bonds and inter­molecular C—F⋯F—C inter­actions between tri­fluoro­methyl groups. Mol­ecular electrostatic potential (MEP) cal­culations by DFT-D3 helped to qu­antify the polarity between O⋯H and F⋯F contacts to rationalize the self-sorting of both bis­(tri­fluoro­methane­sulfonate) esters in polar (non-fluorous) and non-polar (fluorous) domains within the crystal structure.

3D electron diffraction (3D ED), or microcrystal electron diffraction (MicroED), has become an alternative technique for determining the high-resolution crystal structures of compounds from sub-micron-sized crystals. Here, we considered l-alanine, α-glycine and urea, which are known to form good-quality crystals, and collected high-resolution 3D ED data on our in-house TEM instrument. In this study, we present a comparison of independent atom model (IAM) and transferable aspherical atom model (TAAM) kinematical refinement against experimental and simulated data. TAAM refinement on both experimental and simulated data clearly improves the model fitting statistics (R factors and residual electrostatic potential) compared to IAM refinement. This shows that TAAM better represents the experimental electrostatic potential of organic crystals than IAM. Furthermore, we compared the geometrical parameters and atomic displacement parameters (ADPs) resulting from the experimental refinements with the simulated refinements, with the periodic density functional theory (DFT) calculations and with published X-ray and neutron crystal structures. The TAAM refinements on the 3D ED data did not improve the accuracy of the bond lengths between the non-H atoms. The experimental 3D ED data provided more accurate H-atom positions than the IAM refinements on the X-ray diffraction data. The IAM refinements against 3D ED data had a tendency to lead to slightly longer X—H bond lengths than TAAM, but the difference was statistically insignificant. Atomic displacement parameters were too large by tens of percent for l-alanine and α-glycine. Most probably, other unmodelled effects were causing this behaviour, such as radiation damage or dynamical scattering.

The highly cytotoxic macrocyclic trichothecene Isororidin A (C29H40O9) was isolated from the fungus Myrothesium verrucaria endophytic on the wild medicinal plant `Datura' (Datura stramonium L.) and was characterized by one- (1D) and two-dimensional (2D) NMR spectroscopy. The three-dimensional structure of Isororidin A has been confirmed by X-ray crystallography at 0.81 Å resolution from crystals grown in the ortho­rhom­bic space group P212121, with one mol­ecule per asymmetric unit. Isororidin A is the epimer of previously described (by X-ray crystallography) Roridin A at position C-13' of the macrocyclic ring.

The title compound, 3-[(benzo-1,3-dioxol-5-yl)amino]-4-meth­oxy­cyclo­but-3-ene-1,2-dione, C12H9NO5 (3), is a precursor to an anti­mycobacterial squaramide. Block-shaped crystals of a monoclinic form (3-I, space group P21/c, Z = 8, Z' = 2) and needle-shaped crystals of a triclinic form (3-II, space group P-1, Z = 4, Z' = 2) were found to crystallize concomitantly. In both crystal forms, R22(10) dimers assemble through N—H⋯O=C hydrogen bonds. These dimers are formed from crystallographically unique mol­ecules in 3-I, but exhibit crystallographic Ci symmetry in 3-II. Twinning by pseudomerohedry was encountered in the crystals of 3-II. The conformations of 3 in the solid forms 3-I and 3-II are different from one another but are similar for the unique mol­ecules in each polymorph. Density functional theory (DFT) calculations on the free mol­ecule of 3 indicate that a nearly planar conformation is preferred.

Growing high-quality crystals remains a necessary part of crystallography and many other techniques. This article tabulates and describes several techniques and variations that will help individuals grow high-quality crystals in preparation for crystallographic techniques and other endeavors, such as form screening. The discussion is organized to focus on low-tech approaches available in any laboratory.

The reaction of titanium(IV) chloride with sodium hexa­fluoro­iso­pro­pox­ide, carried out in hexa­fluoro­iso­propanol, produces titanium(IV) hexa­fluoro­iso­pro­pox­ide, which is a liquid at room temperature. Recrystallization from coordinating solvents, such as aceto­nitrile or tetra­hydro­furan, results in the formation of bis-solvate com­plexes. These com­pounds are of inter­est as possible Ziegler–Natta polymerization catalysts. The aceto­nitrile com­plex had been structurally characterized previously and adopts a distorted octahedral structure in which the nitrile ligands adopt a cis configuration, with nitro­gen lone pairs coordinated to the metal. The low-melting tetra­hydro­furan com­plex has not provided crystals suitable for single-crystal X-ray analysis. However, the structure of chlorido­tris­(hexa­fluoro­isopropoxido-κO)bis­(tetra­hydro­furan-κO)titanium(IV), [Ti(C3HF6O)3Cl(C4H8O)2], has been obtained and adopts a distorted octa­hedral coordination geometry, with a facial arrangement of the alkoxide ligands and adjacent tetra­hydro­furan ligands, coordinated by way of metal–oxygen polar coordinate inter­actions.

A series of organotin heterocycles of general formula [{Me2C(C6H3CH2)2O}SnR2] [R = methyl (Me, 4), n-butyl (n-Bu, 5), benzyl (Bn, 6) and phenyl (Ph, 7)] was easily synthesized by a Barbier-type reaction assisted by the sonochemical activation of metallic magnesium. The 119Sn{1H} NMR data for all four com­pounds confirm the presence of a central Sn atom in a four-coordinated environment in solution. Single-crystal X-ray diffraction studies for 17,17-dimethyl-7,7-di­phenyl-15-oxa-7-stanna­tetra­cyclo­[11.3.1.05,16.09,14]hepta­deca-1,3,5(16),9(14),10,12-hexa­­ene, [Sn(C6H5)2(C17H16O)], 7, at 100 and 295 K con­firmed the formation of a mono­nuclear eight-membered heterocycle, with a conformation depicted as boat–chair, resulting in a weak Sn⋯O inter­action. The Sn and O atoms are surrounded by hydro­phobic C—H bonds. A Hirshfeld surface analysis of 7 showed that the eight-membered heterocycles are linked by weak C—H⋯π, π–π and H⋯H noncovalent inter­actions. The pairwise inter­action energies showed that the cohesion between the heterocycles are mainly due to dispersion forces.

The crystal structures of 16 boron sub­phthalo­cy­an­ines (BsubPcs) with structurally diverse axial groups were analyzed and com­pared to elucidate the impact of the axial group on the inter­molecular π–π inter­actions, axial-group inter­actions, axial bond length and BsubPc bowl depth. π–π inter­actions between the iso­indole units of adjacent BsubPc mol­ecules most often involve concave–concave packing, whereas axial-group inter­actions with adjacent BsubPc mol­ecules tend to favour the convex side of the BsubPc bowl. Furthermore, axial groups that contain O and/or F atoms tend to have significant hy­dro­gen-bonding inter­actions, while axial groups containing arene site(s) can participate in π–π inter­actions with the BsubPc bowl, both of which can strongly influence the crystal packing. Bulky axial groups did tend to disrupt the π–π inter­actions and/or axial-group inter­actions, preventing some of the close packing that is seen in BsubPcs with less bulky axial groups. The atomic radius of the heteroatom bonded to boron directly influences the axial bond length, whereas the axial group has minimal impact on the BsubPc bowl depth. Finally, the crystal growth method did not generally appear to have a significant impact on the solid-state arrangement, with the exception of water occasionally being incorporated into crystal structures when hygroscopic solvents were used. These insights can help with the design and fine-tuning of the solid-state structures of BsubPcs as they continue to be developed as functional materials in organic electronics.

The activation of C—C bonds by transition-metal com­plexes is of continuing inter­est and aceto­nitrile (MeCN) has attracted attention as a cyanide source with com­paratively low toxicity for organic cyanation reactions. A di­iron end-on μ-η1:η1-CN-bridged com­plex was obtained from a crystallization experiment of an open-chain iron–NHC com­plex, namely, μ-cyanido-κ2C:N-bis­{[(aceto­nitrile-κN)[3,3'-bis­(pyridin-2-yl)-1,1'-(methyl­idene)bis­(benzimidazol-2-yl­idene)]iron(II)} tris­(hexa­fluoro­phos­phate), [Fe2(CN)(C2H3N)2(C25H18N6)2](PF6)3. The cyanide appears to originate from the MeCN solvent by C—C bond cleavage or through carbon–hy­dro­gen oxidation.

Treating the amide acetanilide (N-phenyl­acetamide, C8H9NO) with aqueous strong acids allowed the structures of five hemi-protonated salt forms of acetanilide to be elucidated. N-(1-Hy­droxy­ethyl­idene)anilinium chloride–N-phenyl­acetamide (1/1), [(C8H9NO)2H][Cl], and the bromide, [(C8H9NO)2H][Br], triiodide, [(C8H9NO)2H][I3], tetra­fluoro­borate, [(C8H9NO)2H][BF4], and di­iodo­bromide hemi(diiodine), [(C8H9NO)2H][I2Br]·0.5I2, analogues all feature centrosymmetric dimeric units linked by O—H⋯O hy­dro­gen bonds that extend into one-dimensional hy­dro­gen-bonded chains through N—H⋯X inter­actions, where X is the halide atom of the anion. Protonation occurs at the amide O atom and results in systematic lengthening of the C=O bond and a corresponding shortening of the C—N bond. The size of these geometric changes is similar to those found for hemi-protonated paracetamol structures, but less than those in fully protonated paracetamol structures. The bond angles of the amide fragments are also found to change on protonation, but these angular changes are also influenced by conformation, namely, whether the amide group is coplanar with the phenyl ring or twisted out of plane.

Three structurally diverse 5-phenyl­tetra­zolato (Tz) Ti, Zr, and Ta com­plexes, namely, (C2H8N)[Ti2(C7H5N4)5(C2H6N)4]·1.45C6H6 or (Me2NH2)[Ti2(NMe2)4(2,3-μ-Tz)3(2-η1-Tz)2]·1.45C6H6, (1·1.45C6H6), [Zr2(C7H5N4)6(C2H6N)2(C2H7N)2]·1.12C6H6·0.382CH2Cl2 or [Zr2(Me2NH)2(NMe2)2(2,3-μ-Tz)3(2-η1-Tz)2(1,2-η2-Tz)]·1.12C6H6·0.38CH2Cl2 (2·1.12C6H6·0.38CH2Cl2), and (C2H8N)2[Ta2(C7H5N4)8(C2H6N)2O]·0.25C7H8 or (Me2NH2)2[Ta2(NMe2)2(2,3-μ-Tz)2(2-η1-Tz)6O]·0.25C7H8 (3·0.25C7H8), where TzH is 5-phenyl-1H-tetra­zole, have been synthesized and structurally characterized. All three com­plexes are dinuclear; the Ti center in 1 is six-coordinate, whereas the Zr and Ta atoms in 2 and 3 are seven-coordinate. The coordination environments of the Ti centers in 1 are similar, and so are the ligations of the Ta centers in 3. In contrast, the two Zr centers in 2 bear a different number of ligands, one of which is a bidentate η2-5-phenyl­tetra­zolato ligand that has not been observed previously for d-block elements. The di­methyl­amido ligand, present in the starting materials, remained un­changed, or was converted to di­methyl­amine and di­methyl­ammonium during the synthesis. Di­methyl­amine coordinates as a neutral ligand, whereas di­methyl­ammonium is retained as a hy­dro­gen-bonded entity bridging Tz ligands.

The crystal structures of two coordination com­pounds, (acetato-κO)(2,2'-bi­py­ri­dine-κ2N,N')(1,10-phenanthroline-κ2N,N')copper(II) acetate hexa­hydrate, [Cu(C2H3O2)(C10H8N2)(C12H8N2)](C2H3O2)·6H2O or [Cu(bipy)(phen)Ac]Ac·6H2O, and (acetato-κO)bis­(2,2'-bi­py­ri­dine-κ2N,N')copper(II) acetate–acetic acid–water (1/1/3), [Cu(C2H3O2)(C10H8N2)2](C2H3O2)·C2H4O2·3H2O or [Cu(bipy)2Ac]Ac·HAc·3H2O, are reported and com­pared with the previously published structure of [Cu(phen)2Ac]Ac·7H2O (phen is 1,10-phenanthroline, bipy for 2,2'-bi­py­ri­dine, ac is acetate and Hac is acetic acid). The geometry around the metal centre is penta­coordinated, but highly distorted in all three cases. The coordination number and the geometric distortion are both discussed in detail, and all com­plexes belong to the space group Poverline{1}. The analysis of the geometric parameters and the Hirshfeld surface properties dnorm and curvedness provide information about the metal–ligand inter­actions in these com­plexes and allow com­parison with similar systems.

Historically, knowledge of the mol­ecular packing within the crystal structures of organic semi­con­duc­tors has been instrumental in understanding their solid-state electronic properties. Nowadays, crystal structures are thus becoming increasingly important for enabling engineering properties, understanding poly­mor­phism in bulk and in thin films, exploring dynamics and elucidating phase-transition mech­a­nisms. This review article introduces the most salient and recent results of the field.

The technique of time-resolved macromolecular crystallography (TR-MX) has recently been rejuvenated at synchrotrons, resulting in the design of dedicated beamlines. Using pump–probe schemes, this should make the mechanistic study of photoactive proteins and other suitable systems possible with time resolutions down to microseconds. In order to identify relevant time delays, time-resolved spectroscopic experiments directly performed on protein crystals are often desirable. To this end, an instrument has been built at the icOS Lab (in crystallo Optical Spectroscopy Laboratory) at the European Synchrotron Radiation Facility using reflective focusing objectives with a tuneable nanosecond laser as a pump and a microsecond xenon flash lamp as a probe, called the TR-icOS (time-resolved icOS) setup. Using this instrument, pump–probe spectra can rapidly be recorded from single crystals with time delays ranging from a few microseconds to seconds and beyond. This can be repeated at various laser pulse energies to track the potential presence of artefacts arising from two-photon absorption, which amounts to a power titration of a photoreaction. This approach has been applied to monitor the rise and decay of the M state in the photocycle of crystallized bacteriorhodopsin and showed that the photocycle is increasingly altered with laser pulses of peak fluence greater than 100 mJ cm−2, providing experimental laser and delay parameters for a successful TR-MX experiment.

The use of artificial intelligence to process diffraction images is challenged by the need to assemble large and precisely designed training data sets. To address this, a codebase called Resonet was developed for synthesizing diffraction data and training residual neural networks on these data. Here, two per-pattern capabilities of Resonet are demonstrated: (i) interpretation of crystal resolution and (ii) identification of overlapping lattices. Resonet was tested across a compilation of diffraction images from synchrotron experiments and X-ray free-electron laser experiments. Crucially, these models readily execute on graphics processing units and can thus significantly outperform conventional algorithms. While Resonet is currently utilized to provide real-time feedback for macromolecular crystallography users at the Stanford Synchrotron Radiation Lightsource, its simple Python-based interface makes it easy to embed in other processing frameworks. This work highlights the utility of physics-based simulation for training deep neural networks and lays the groundwork for the development of additional models to enhance diffraction collection and analysis.

This article describes the High-Pressure Freezing Laboratory for Macromolecular Crystallography (HPMX) at the ESRF, and highlights new and complementary research opportunities that can be explored using this facility. The laboratory is dedicated to investigating interactions between macromolecules and gases in crystallo, and finds applications in many fields of research, including fundamental biology, biochemistry, and environmental and medical science. At present, the HPMX laboratory offers the use of different high-pressure cells adapted for helium, argon, krypton, xenon, nitrogen, oxygen, carbon dioxide and methane. Important scientific applications of high pressure to macromolecules at the HPMX include noble-gas derivatization of crystals to detect and map the internal architecture of proteins (pockets, tunnels and channels) that allows the storage and diffusion of ligands or substrates/products, the investigation of the catalytic mechanisms of gas-employing enzymes (using oxygen, carbon dioxide or methane as substrates) to possibly decipher intermediates, and studies of the conformational fluctuations or structure modifications that are necessary for proteins to function. Additionally, cryo-cooling protein crystals under high pressure (helium or argon at 2000 bar) enables the addition of cryo-protectant to be avoided and noble gases can be employed to produce derivatives for structure resolution. The high-pressure systems are designed to process crystals along a well defined pathway in the phase diagram (pressure–temperature) of the gas to cryo-cool the samples according to the three-step `soak-and-freeze method'. Firstly, crystals are soaked in a pressurized pure gas atmosphere (at 294 K) to introduce the gas and facilitate its inter­actions within the macromolecules. Samples are then flash-cooled (at 100 K) while still under pressure to cryo-trap macromolecule–gas complexation states or pressure-induced protein modifications. Finally, the samples are recovered after depressurization at cryo-temperatures. The final section of this publication presents a selection of different typical high-pressure experiments carried out at the HPMX, showing that this technique has already answered a wide range of scientific questions. It is shown that the use of different gases and pressure conditions can be used to probe various effects, such as mapping the functional internal architectures of enzymes (tunnels in the haloalkane dehalogenase DhaA) and allosteric sites on membrane-protein surfaces, the interaction of non-inert gases with proteins (oxygen in the hydrogenase ReMBH) and pressure-induced structural changes of proteins (tetramer dissociation in urate oxidase). The technique is versatile and the provision of pressure cells and their application at the HPMX is gradually being extended to address new scientific questions.

Cryo-electron microscopy (cryo-EM) has witnessed radical progress in the past decade, driven by developments in hardware and software. While current software packages include processing pipelines that simplify the image-processing workflow, they do not prioritize the in-depth analysis of crucial metadata, limiting troubleshooting for challenging data sets. The widely used RELION software package lacks a graphical native representation of the underlying metadata. Here, two web-based tools are introduced: relion_live.py, which offers real-time feedback on data collection, aiding swift decision-making during data acquisition, and relion_analyse.py, a graphical interface to represent RELION projects by plotting essential metadata including interactive data filtration and analysis. A useful script for estimating ice thickness and data quality during movie pre-processing is also presented. These tools empower researchers to analyse data efficiently and allow informed decisions during data collection and processing.

To identify starting points for therapeutics targeting SARS-CoV-2, the Paul Scherrer Institute and Idorsia decided to collaboratively perform an X-ray crystallographic fragment screen against its main protease. Fragment-based screening was carried out using crystals with a pronounced open conformation of the substrate-binding pocket. Of 631 soaked fragments, a total of 29 hits bound either in the active site (24 hits), a remote binding pocket (three hits) or at crystal-packing interfaces (two hits). Notably, two fragments with a pose that was sterically incompatible with a more occluded crystal form were identified. Two isatin-based electrophilic fragments bound covalently to the catalytic cysteine residue. The structures also revealed a surprisingly strong influence of the crystal form on the binding pose of three published fragments used as positive controls, with implications for fragment screening by crystallography.

Complex I (proton-pumping NADH:ubiquinone oxidoreductase) is the first component of the mitochondrial respiratory chain. In recent years, high-resolution cryo-EM studies of complex I from various species have greatly enhanced the understanding of the structure and function of this important membrane-protein complex. Less well studied is the structural basis of complex I biogenesis. The assembly of this complex of more than 40 subunits, encoded by nuclear or mitochondrial DNA, is an intricate process that requires at least 20 different assembly factors in humans. These are proteins that are transiently associated with building blocks of the complex and are involved in the assembly process, but are not part of mature complex I. Although the assembly pathways have been studied extensively, there is limited information on the structure and molecular function of the assembly factors. Here, the insights that have been gained into the assembly process using cryo-EM are reviewed.

Mevalonate kinase is central to the isoprenoid biosynthesis pathway. Here, high-resolution X-ray crystal structures of two mevalonate kinases are presented: a eukaryotic protein from Ramazzottius varieornatus and an archaeal protein from Methanococcoides burtonii. Both enzymes possess the highly conserved motifs of the GHMP enzyme superfamily, with notable differences between the two enzymes in the N-terminal part of the structures. Biochemical characterization of the two enzymes revealed major differences in their sensitivity to geranyl pyrophosphate and farnesyl pyrophosphate, and in their thermal stabilities. This work adds to the understanding of the structural basis of enzyme inhibition and thermostability in mevalonate kinases.

The widespread adoption of cryoEM technologies for structural biology has pushed the discipline to new frontiers. A significant worldwide effort has refined the single-particle analysis (SPA) workflow into a reasonably standardized procedure. Significant investments of development time have been made, particularly in sample preparation, microscope data-collection efficiency, pipeline analyses and data archiving. The widespread adoption of specific commercial microscopes, software for controlling them and best practices developed at facilities worldwide has also begun to establish a degree of standardization to data structures coming from the SPA workflow. There is opportunity to capitalize on this moment in the maturation of the field, to capture metadata from SPA experiments and correlate the metadata with experimental outcomes, which is presented here in a set of programs called EMinsight. This tool aims to prototype the framework and types of analyses that could lead to new insights into optimal microscope configurations as well as to define methods for metadata capture to assist with the archiving of cryoEM SPA data. It is also envisaged that this tool will be useful to microscope operators and facilities looking to rapidly generate reports on SPA data-collection and screening sessions.

Data acquisition and processing for cryo-electron tomography can be a significant bottleneck for users. To simplify and streamline the cryo-ET workflow, Tomo Live, an on-the-fly solution that automates the alignment and reconstruction of tilt-series data, enabling real-time data-quality assessment, has been developed. Through the integration of Tomo Live into the data-acquisition workflow for cryo-ET, motion correction is performed directly after each of the acquired tilt angles. Immediately after the tilt-series acquisition has completed, an unattended tilt-series alignment and reconstruction into a 3D volume is performed. The results are displayed in real time in a dedicated remote web platform that runs on the microscope hardware. Through this web platform, users can review the acquired data (aligned stack and 3D volume) and several quality metrics that are obtained during the alignment and reconstruction process. These quality metrics can be used for fast feedback for subsequent acquisitions to save time. Parameters such as Alignment Accuracy, Deleted Tilts and Tilt Axis Correction Angle are visualized as graphs and can be used as filters to export only the best tomograms (raw data, reconstruction and intermediate data) for further processing. Here, the Tomo Live algorithms and workflow are described and representative results on several biological samples are presented. The Tomo Live workflow is accessible to both expert and non-expert users, making it a valuable tool for the continued advancement of structural biology, cell biology and histology.

The Swiss Light Source facilitates fragment-based drug-discovery campaigns for academic and industrial users through the Fast Fragment and Compound Screening (FFCS) software suite. This framework is further enriched by the option to utilize the Smart Digital User (SDU) software for automated data collection across the PXI, PXII and PXIII beamlines. In this work, the newly developed HEIDI webpage (https://heidi.psi.ch) is introduced: a platform crafted using state-of-the-art software architecture and web technologies for sample management of rotational data experiments. The HEIDI webpage features a data-review tab for enhanced result visualization and provides programmatic access through a representational state transfer application programming interface (REST API). The migration of the local FFCS MongoDB instance to the cloud is highlighted and detailed. This transition ensures secure, encrypted and consistently accessible data through a robust and reliable REST API tailored for the FFCS software suite. Collectively, these advancements not only significantly elevate the user experience, but also pave the way for future expansions and improvements in the capabilities of the system.

Cryo-electron tomography (cryo-ET) enables molecular-resolution 3D imaging of complex biological specimens such as viral particles, cellular sections and, in some cases, whole cells. This enables the structural characterization of molecules in their near-native environments, without the need for purification or separation, thereby preserving biological information such as conformational states and spatial relationships between different molecular species. Subtomogram averaging is an image-processing workflow that allows users to leverage cryo-ET data to identify and localize target molecules, determine high-resolution structures of repeating molecular species and classify different conformational states. Here, STOPGAP, an open-source package for subtomogram averaging that is designed to provide users with fine control over each of these steps, is described. In providing detailed descriptions of the image-processing algorithms that STOPGAP uses, this manuscript is also intended to serve as a technical resource to users as well as for further community-driven software development.

Metalloproteins are ubiquitous in all living organisms and take part in a very wide range of biological processes. For this reason, their experimental characterization is crucial to obtain improved knowledge of their structure and biological functions. The three-dimensional structure represents highly relevant information since it provides insight into the interaction between the metal ion(s) and the protein fold. Such interactions determine the chemical reactivity of the bound metal. The available PDB structures can contain errors due to experimental factors such as poor resolution and radiation damage. A lack of use of distance restraints during the refinement and validation process also impacts the structure quality. Here, the aim was to obtain a thorough overview of the distribution of the distances between metal ions and their donor atoms through the statistical analysis of a data set based on more than 115 000 metal-binding sites in proteins. This analysis not only produced reference data that can be used by experimentalists to support the structure-determination process, for example as refinement restraints, but also resulted in an improved insight into how protein coordination occurs for different metals and the nature of their binding interactions. In particular, the features of carboxylate coordination were inspected, which is the only type of interaction that is commonly present for nearly all metals.

CdaA is the most widespread diadenylate cyclase in many bacterial species, including several multidrug-resistant human pathogens. The enzymatic product of CdaA, cyclic di-AMP, is a secondary messenger that is essential for the viability of many bacteria. Its absence in humans makes CdaA a very promising and attractive target for the development of new antibiotics. Here, the structural results are presented of a crystallographic fragment screen against CdaA from Listeria monocytogenes, a saprophytic Gram-positive bacterium and an opportunistic food-borne pathogen that can cause listeriosis in humans and animals. Two of the eight fragment molecules reported here were localized in the highly conserved ATP-binding site. These fragments could serve as potential starting points for the development of antibiotics against several CdaA-dependent bacterial species.