The `photometric selection' approach as a high throughput, sample tolerant, low cost and highly automatable method of carrying out serial crystallography is presented. Crystalline samples are loaded and distributed onto a simple transparent substrate and an in-line camera identifies crystals using image recognition algorithms from the computer vision project OpenCV. In contrast to established serial techniques, which generally require that crystal samples be refined with narrow size distributions and defined habits, the sample requirements when using photometric selection are shown to be minimal. We demonstrate how broadly effective photometric selection can be by collecting high-quality datasets from three exemplar systems: a small-molecule organometallic, a small-molecule organic and a metal-organic framework system. In contrast to previously established grid-scanning techniques, data collection using photometric selection can be up to six times faster.

Small molecule synchrotron serial crystallography (smSSX) is used to monitor irreversible photodimerization in α- trans -cinnamic acid, enabling structure determination of intermediate states and quantification of batch-level reaction heterogeneity.

While advanced crystallization methods controlling microcrystal size and shape are common for pharmaceutical targets, there are few examples where such methods are applied to inorganic functional materials. This is surprising, considering the impact of particle size on numerous useful properties. As an archetypal photoswitch exhibiting photoinduced linkage isomerism (PLI), sodium nitroprusside dihydrate (SNP2H2O) is an ideal prototype for the design of advanced inorganic microcrystallization approaches. Slow evaporation in water characteristically gives long (>1 mm) lath-like crystals with a broad size distribution. These samples are undesirable for in situ photocrystallography, where small crystals of ideally plate habit are preferred to maximize light penetration. This article explores the influence of solvent, temperature and crystallization method on the formation of homogeneous microcrystal batches of SNP2H2O at small (ca. 5 mL) scale, targeting a plate-like habit and an average size of (50 +/- 10) mu m in the two dimensions parallel to the plate. Successful experiments utilize an acetonitrile antisolvent methodology, delivering a narrow crystal size distribution in the correct range. Steady-state photocrystallography measurements on crystals grown by controlled vs. uncontrolled methodologies showcase how regulating crystal particle attributes can minimise variability in the excited state population, reinforcing the importance of these parameters for real photoswitching applications where achieving a reproducible response is often key. A previously unknown mixed methanol : water solvate of SNP is also reported that is metastable in air.

We present the first known example of single crystal X-ray diffraction of small molecule crystals in a flow crystallisation environment via serial crystallography. Towards radiation damage mitigation, high-throughput screening and kinetic studies.

The ability to synthesise lemniscular molecules to allow for the study and application of their chiroptical properties is a notable technical challenge. Herein, we report the design and synthesis of enantiomers of a [5]helicenoid derived molecular lemniscate, in which two homochiral helicenes are linked via the formation of two azine motifs. We demonstrate that these molecules, and their helicenoid constituents, are also excellent chiral dopants that induce dissymmetry in the ground and excited states of the achiral emissive polymer F8BT, leading to high CPL activity. The ability to control the handedness of the helicenoid dopants via enantiopure synthesis affords control of the sign of CP emission. This manipulation of circularly polarised light is of great interest for optoelectronic technologies.

In line with the dramatic and continuing improvements in X-ray generation technologies for laboratory and accelerator sources around the world, reports of X-ray-induced processes in chemical crystalline materials are on the rise. These observations are challenging the traditional viewpoint that radiation damage is only of significant concern for protein structure determinations, encouraging small molecule crystallographers to identify and address X-ray-induced effects in a broadening range of susceptible materials. This review explores the recent investigations into X-ray damage and X-ray-induced transformations in chemical crystalline materials and discusses state-of-the-art methodologies to quantify and mitigate the effects of the X-ray probe on single-crystal and microcrystalline powder samples.

Colour-changing chemical sensors have found important applications in the detection of low concentrations of volatile organic compounds (VOCs). Among the most promising molecular materials are platinum pincer complexes that display rapid colour changes when exposed to a variety of VOCs. In the solid state, these rapid responses have been linked to changes in non-covalent interactions between the platinum pincer molecules and the guest VOCs. To gain a better understanding of the interactions involved, we have studied the manipulation of vapochromic or solvatochromic properties in a series of square planar platinum(ii) pincer complexes through structural modification of the monodentate ligand occupying the fourth coordination site. The platinum(ii) complexes are based on the 1,3-di(pyridine)benzene tridentate linker (N<^>C<^>N) skeleton with the fourth site occupied by a monodentate, anionic ligand L. The formulae of the complexes synthesised are [Pt(N<^>C(C(O)OMe)<^>N)(L)] (L = (NCO) (6), (NCS) (7), (OC(O)Me) (8), (OC(O)CF3) (9), (OS(O)2CF3) (10), and (OS(O)2(C6H4Me)) (11)), and the crystalline solids and solutions of these materials have been tested for solvatochromic or vapochromic changes with VOCs including dichloromethane, acetonitrile, diethyl ether, methanol and water. The complexes 6 and 7 crystallised as yellow solids, with no solvent voids in the crystal lattice. Single-crystal X-ray analyses showed that the intermolecular Pt & ctdot;Pt separations were too long for direct Pt & ctdot;Pt interactions. Neither material displayed solvatochromic or vapochromic properties. However, when the fourth ligand was an acetate group, complex 8, the solid displayed vapochromism, changing colour from an orange water-containing crystalline form to an anhydrous yellow form, and a blue form when treated with methanol vapour. A crystal structure analysis showed that in the orange form adjacent pincer molecules were linked together through a hydrogen bonding network involving lattice water molecules, supported by pi & ctdot;pi stacking interactions. Complexes 9 and 10 both showed solvatochromism, forming a bright yellow solid when crystallised from dichloromethane but forming an orange solid when recrystallised from acetonitrile. Complex 11 displayed both vapochromic and solvatochromic properties. This complex was isolated as a purple solid, turning yellow upon treatment with methanol droplets or vapour, but this colour change could be reversed upon addition of acetonitrile.

When Olga Kennard founded the Cambridge Crystallographic Data Centre in 1965, the Cambridge Structural Database was a pioneering attempt to collect scientific data in a standard format. Since then, it has evolved into an indispensable resource in contemporary molecular materials science, with over 1.25 million structures and comprehensive software tools for searching, visualizing and analyzing the data. In this perspective, we discuss the use of the CSD and CCDC tools to address the multiscale challenge of predictive materials design. We provide an overview of the core capabilities of the CSD and CCDC software and demonstrate their application to a range of materials design problems with recent case studies drawn from topical research areas, focusing in particular on the use of data mining and machine learning techniques. We also identify several challenges that can be addressed with existing capabilities or through new capabilities with varying levels of development effort.

One of the most important challenges in the pharmaceutical industry is to produce crystals with desired size and shape distributions, to enhance the critical quality attributes of the drug product, such as efficacy, and to improve manufacturability during downstream processing, such as filtration, drying and granulation. The paper provides a framework for effective crystal shape and size tuning, based on a systematic exploration of standard techniques, such as the linear cooling and supersaturation control (SSC), and novel methods based on the systematic combination of several techniques, namely direct nucleation control (DNC), wet milling, SSC and shape modification additives. The crystallization of lovastatin, which is notorious for its challenging needle-shaped crystals, with an extremely high aspect ratio, was used as a case study, and polypropylene glycol (PPG-4000), at different concentrations, was used as an effective shape modifier from small-scale tests studied previously. The proposed techniques were implemented in the case of seeded and unseeded systems. It was demonstrated that the combination of temperature cycling and polymer additive enhances greatly the control over the aspect ratio and crystal size distribution, compared to conventional linear cooling and SSC strategies. The implementation of wet milling at the beginning of the process, or the introduction of seeds, enhances even further the control of the critical quality attributes of the crystalline product.

The switching behavior of the novel hybrid material (FA)Na[Fe(CN) 5 (NO)].H 2 O ( 1 ) in response to temperature ( T ), light irradiation and electric field ( E ) is studied using in situ X-ray diffraction (XRD). Crystals of 1 display piezoelectricity, pyroelectricity, second and third harmonic generation. XRD shows that the FA + are disordered at room-temperature, but stepwise cooling from 273–100 K induces gradual ordering, while cooling under an applied field ( E =+40 kVcm −1 ) induces a sudden phase change at 140 K. Structural-dynamics calculations suggest the field pushes the system into a region of the structural potential-energy surface that is otherwise inaccessible, demonstrating that application of T and E offers an effective route to manipulating the crystal chemistry of these materials. Photocrystallography also reveals photoinduced linkage isomerism, which coexists with but is not correlated to other switching behaviors. These experiments highlight a new approach to in situ studies of hybrid materials, providing insight into the structure–property relationships that underpin their functionality.

X-ray diffraction analysis typically affords the static 3D structures of given compounds or materials, but to understand chemical processes, the visualization of fast structural changes is desirable. Time-resolved femtosecond crystallography has now been used to monitor the structural dynamics of a photoactive metal-organic framework.

Over the last three decades, the technology that makes it possible to follow chemical processes in the solid state in real time has grown enormously. These studies have important implications for the design of new functional materials for applications in optoelectronics and sensors. Light-matter interactions are of particular importance, and photocrystallography has proved to be an important tool for studying these interactions. In this technique, the three-dimensional structures of light-activated molecules, in their excited states, are determined using single-crystal X-ray crystallography. With advances in the design of high-power lasers, pulsed LEDs and time-gated X-ray detectors, the increased availability of synchrotron facilities, and most recently, the development of XFELs, it is now possible to determine the structures of molecules with lifetimes ranging from minutes down to picoseconds, within a single crystal, using the photocrystallographic technique. This review discusses the procedures for conducting successful photocrystallographic studies and outlines the different methodologies that have been developed to study structures with specific lifetime ranges. The complexity of the methods required increases considerably as the lifetime of the excited state shortens. The discussion is supported by examples of successful photocrystallographic studies across a range of timescales and emphasises the importance of the use of complementary analytical techniques in order to understand the solid-state processes fully.

AbstractThe increasing availability of ultrabright Light Sources is facilitating the study of smaller crystals at faster timescales but with an increased risk of severe X-ray damage, leading to developments in multi-crystal methods such as serial crystallography (SX). SX studies on crystals with small unit cells are challenging as very few reflections are recorded in a single data image, making it difficult to determine the orientation matrix for each crystal and thus preventing the combination of the data from all crystals for structure solution. We herein present a Small-Rotative Fixed-Target Serial Synchrotron Crystallography (SR-FT-SSX) methodology, in which rotation of the serial target through a small diffraction angle $$(\varphi )$$ ( φ ) at each crystal delivers high-quality data, facilitating ab initio unit cell determination and atomic-scale structure solution. The method is benchmarked using microcrystals of the small-molecule photoswitch sodium nitroprusside dihydrate, obtaining complete data to dmin = 0.6 Å by combining just 66 partial datasets selected against rigorous quality criteria.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Paul R. Raithby opened discussion of the paper by Maria Diaz Lopez: In the pair distribution function (PDF) analysis of intermolecular hydrogen bonds, what error bars would normally be acceptable for a good quality analysis? Maria Diaz Lopez answered: In the paper the uncertainties in the atomic positions were ca

There is a need to develop rapidly responsive chemical sensors for the detection of low concentrations of volatile organic solvents (VOCs). Platinum pincer complexes have shown promise as sensors because of their colours and vapochromic and solvatochromic properties, that may be related to the non-covalent interactions between the pincer complexes and the guest VOCs. Here we report an investigation into a series of Pt(II) complexes based on the 1,3-di(pyridine)benzene tridentate (N⁁C⁁N) skeleton with the formula [Pt(N⁁C(R)⁁N)(CN)] (R = C(O)Me 2, C(O)OEt 3, C(O)OPh 4) with the fourth coordination site occupied by a cyanide ligand. Solid-state samples of the complexes have been tested with a range of volatiles including methanol, ethanol, acetone, dichloromethane and water, and while 2 displays thermochromism, 3 and 4 display rapidly reversible vapochromism and solvatochromism. These results are correlated with X-ray powder and single crystal X-ray structural data including an assessment of the crystal packing and the void space in the crystalline space. The cyanide ligand and the R substituents are involved in hydrogen bonding that creates the voids within the structures and interact with the solvent molecules that influence the Pt⋯Pt separation in the crystalline state.

We present a charge density study of two linkage isomer photoswitches, [Pd(Bu4dien)(NO2)]BPh4·THF (1) and [Ni(Et4dien)(NO2)2] (2) using Hirshfeld Atom Refinement (HAR) methods implemented via the NoSpherA2 interface in Olex2. HAR is used to explore the electron density distribution in the photoswitchable molecules of 1 and 2, to gain an in-depth understanding of key bonding features and their influence on the single-crystal-to-single-crystal reaction. HAR analysis is also combined with ab initio calculations to explore the non-covalent interactions that influence physical properties of the photoswitches, such as the stability of the excited state nitrito-(η1-ONO) isomer. This insight can be fed back into the crystal engineering process to develop new and improved photoswitches that can be optimised towards specific applications.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.