Single-crystal-to-single-crystal translation of a helical supramolecular polymer to a helical covalent polymer.

Polymers possessing helical conformation in the solid state are in high demand. We report a helical peptide-polymer via the topochemical ene-azide cycloaddition (TEAC) polymerization. The molecules of the designed Gly-Phe-based dipeptide, decorated with ene and azide, assemble in its crystals as ß-sheets and as supramolecular helices in two mutually perpendicular directions. While the NH…O H-bonding facilitates ß-sheet-like stacking along one direction, weak CH…N H-bonding between the azide-nitrogen and vinylic-hydrogen of molecules belonging to the adjacent stacks arranges them in a head-to-tail manner as supramolecular helices. In the crystal lattice, the azide and alkene of adjacent molecules in the supramolecular helix are suitably preorganized for their TEAC reaction. The dipeptide underwent regio- and stereospecific polymerization upon mild heating in a single-crystal-to-single-crystal fashion, yielding a triazoline-linked helical covalent polymer that could be characterized by single-crystal X-ray diffraction studies. Upon heating, the triazoline-linked polymer undergoes denitrogenation to aziridine-linked polymer, as evidenced by differential scanning calorimetry, thermogravimetric analysis, and solid-state NMR analyses.

Ultrahigh Degree of Cationic Disorder, Configurational Entropy in New Type of High-Entropy Pseudobrookite Phase.

High-entropy ceramics exhibit various excellent properties owing to their high configurational entropy, which is caused by multi-principal elements sharing one lattice site. The configurational entropy will further increase significantly if multi-principal elements randomly share two different lattice sites. For this purpose, pseudobrookite phase containing two cationic lattice sites (A and B sites) is selected, and corresponding high-entropy pseudobrookite (M2+ 0.4M3+ 1.2)Ti1.4O5 is synthesized. Herein, the distribution of the 2-valent and 3-valent cations in the A and B sites are analysed in depth. The distance between the A and B sites in the crystal structure models which are constructed by the Rietveld analysis is calculated and defined as distance d. Meanwhile, the atomic column positions in the STEM images are quantified by a model-based mathematical algorithm, and the corresponding distance d are calculated. By comparing the distance d, it is determine that the 2-valent and 3-valent cations are jointly and disorderly distributed in the A and B sites in high-entropy (M2+ 0.4M3+ 1.2)Ti1.4O5. The density functional theory (DFT) simulations also demonstrate that this type of crystal structure is more thermodynamically stable. The higher degree of cationic disorder leads to a higher configurational entropy in high-entropy (M2+ 0.4M3+ 1.2)Ti1.4O5, and endows high-entropy (M2+ 0.4M3+ 1.2)Ti1.4O5 with very low thermal conductivity (1.187-1.249 W m-1 K-1).

Gas Release as an Efficient Strategy to Tune Mechanical Properties and Thermoresponsiveness of Dynamic Molecular Crystals.

Dynamic molecular crystals combining multiple and finely tunable functionalities are attracting and an increasing attention due to their potential applications in a broad range of fields as efficient energy transducers and stimuli-responsive materials. In this context, a multicomponent organic salt, piperazinium trifluoroacetate (PZTFA), endowed with an unusual multidimensional responsive landscape is reported. Crystals of the salt undergo smooth plastic deformation under mechanical stress and thermo-induced jumping. Furthermore, via controlled crystal bending and release of trifluoroacetic acid from the lattice, which is anticipated from the design of the material, both the mechanical response and the thermoresponsive behavior are efficiently tuned while partially preserving the crystallinity of the system. In particular, mechanical deformation hampers guest release and hence the macroscopic jumping effect, while trifluoroacetic acid release stiffens the crystals. These complex adaptive responses establish a new crystal engineering strategy to gain further control over dynamic organic crystals.

Cross-Linking CdSO4-Type Nets with Hexafluorosilicate Anions to Form an Ultramicroporous Material for Efficient C2H2/CO2 and C2H2/C2H4 Separation.

A 44.610.8 topology hybrid ultramicroporous material (HUM), {[Cu1.5F(SiF6)(L)2.5]·G}n, (L = 4,4'-bisimidazolylbiphenyl, G = guest molecules), 1, formed by cross-linking interpenetrated 3D four-connected CdSO4-type nets with hexafluorosilicate anions is synthesized and evaluated in the context of gas sorption and separation herein. 1 is the first HUM functionalized with two different types of fluorinated sites (SiF6 2- and F- anions) lining along the pore surface. The optimal pore size (≈5 Å) combining mixed and high-density electronegative fluorinated sites enable 1 to preferentially adsorb C2H2 over CO2 and C2H4 by hydrogen bonding interactions with a high C2H2 isosteric heat of adsorption (Qst) of ≈42.3 kJ mol-1 at zero loading. The pronounced discriminatory sorption behaviors lead to excellent separation performance for C2H2/CO2 and C2H2/C2H4 that surpasses many well-known sorbents. Dynamic breakthrough experiments are conducted to confirm the practical separation capability of 1, which reveal an impressive separation factor of 6.1 for equimolar C2H2/CO2 mixture. Furthermore, molecular simulation and density functional theory (DFT) calculations validate the strong binding of C2H2 stems from the chelating fix of C2H2 between SiF6 2- anion and coordinated F- anion.

Polymorphism-driven Distinct Nanomechanical, Optical, Photophysical, and Conducting Properties in a Benzothiophene-quinoline.

Polymorphic forms of organic conjugated small molecules, with their unique molecular shapes, packing arrangements, and interaction patterns, provide an excellent opportunity to uncover how their microstructures influence their observable properties. Ethyl-2-(1-benzothiophene-2-yl)quinoline-4-carboxylate (BZQ) exists as dimorphs with distinct crystal habits - blocks (BZB) and needles (BZN). The crystal forms differ in their molecular arrangements - BZB has a slip-stacked column-like structure in contrast to a zig-zag crystal packing with limited π-overlap in BZN. The BZB crystals characterized by extended π-stacking along [100] demonstrated semiconductor behavior, whereas the BZN, with its zig-zag crystal packing and limited stacking characteristics, was reckoned as an insulator. Monotropically related crystal forms also differ in their nanomechanical properties, with BZB crystals being considerably softer than BZN crystals. This discrepancy in mechanical behavior can be attributed to the distinct molecular arrangements adopted by each crystal form, resulting in unique mechanisms to relieve the strain generated during nanoindentation experiments. Waveguiding experiments on the acicular crystals of BZN revealed the passive waveguiding properties. Excitation of these crystals using a 532 nm laser confirmed the propagation of elastically scattered photons (green) and the subsequent generation of inelastically scattered (orange) photons by the crystals. Further, the dimorphs display dissimilar photoluminescence properties; they are both blue-emissive, but BZN displays twice the quantum yield of BZB. The study underscores the integral role of polymorphism in modulating the mechanical, photophysical, and conducting properties of functional molecular materials. Importantly, our findings reveal the existence of light-emitting crystal polymorphs with varying electric conductivity, a relatively scarce phenomenon in the literature.

Leveraging Halogen Interactions for a Supramolecular Nanotube.

We demonstrate the formation of supramolecular nanotubes from molecular triangles in a single crystal by balancing the hydrogen bonds and halogen interactions between individual macrocycles. Thereby, we template the supramolecular nanotube growth by intermolecular interactions encoded directly in the macrocycles instead of those provided by the crystallization solvent. Ultimately, we show that replacing bromines for iodines in the macrocycle is necessary to achieve this supramolecular organization by enhancing the strength of the halogen interactions and concomitant reduction of the detrimental hydrogen bonds. We investigated the nature and the interplay of the individual intermolecular interactions by analysis of the experimental single crystal data and quantum chemical calculations. This work enriches the available toolbox of supramolecular interactions and will aid and abet the development of rationally-designed materials with a long-range 1D tubular organization.

Electrostatic Surface Potentials and Chalcogen-Bonding Motifs of Substituted 2,1,3-Benzoselenadiazoles Probed via 77Se Solid-State NMR Spectroscopy.

Chalcogen bonds (ChB) are moderately strong, directional, and specific non-covalent interactions that have garnered substantial interest over the last decades. However, ChB applications are currently hampered by a lack of methods to characterize and control chalcogen bonds. We report on the influence of various substituents (halogens, cyano, and methyl groups) on the observed self-complementary ChB networks of 2,1,3-benzoselenadiazoles. From molecular electrostatic potential calculations, we show that the electrostatic surface potentials (ESP) of the σ-holes on selenium are largely influenced by the electron-withdrawing character of these substituents. Structural analyses via X-ray diffraction reveal a variety of ChB geometries and binding modes that are rationalized via the computed ESP maps, although the structure of 5,6-dimethyl-2,1,3-benzoselenadiazole also demonstrates the influence of steric interactions. 77Se solid-state magic-angle spinning NMR spectroscopy, in particular the analysis of the selenium chemical shift tensors, is found to be an effective probe able to characterize both structural and electrostatic features of these self-complementary ChB systems. We find a positive correlation between the value of the ESP maxima at the σ-holes and the experimentally measured 77Se isotropic chemical shift, while the skew of the chemical shift tensor is established as a metric which is reflective of the ChB binding motif.

Investigating the Mechanism of Triboluminescence: Insights from Structural and Electrostatic Characterization of Copper Thiocyanate Complexes.

Triboluminescence is a phenomenon in which light is generated through mechanical stress; it has emerging applications in stress-sensing devices. Although the prevailing mechanistic model indicates that light emits from charge separation and recombination in fracture planes arising from polar structures, its application in designing triboluminescent materials remains limited owing to numerous exceptions. This study provides insights into the essential requirements for triboluminescence by investigating the structural and electrostatic properties of fractured crystals of copper thiocyanate complexes. The examined fracture plane indicated that charge pairs (which are essential for light emission) form when intermolecular interactions are disrupted during fracturing. On the basis of the nature of these charges, we successfully suppressed triboluminescence by inhibiting the formation of intermolecular interactions disrupted in the examined complexes. Furthermore, we induced its re-emergence by creating an alternative fracture plane through controlled manipulation of the molecular network. This demonstrative deactivation and reactivation of triboluminescence underscores the critical role of intermolecular disruption in generating charge pairs, a prerequisite for triboluminescence.

Transition Behaviors of Isostructural Hydrogen-Bonded Frameworks Composed of Naphthalene, Quinoxaline, and Pyrazinopyrazine Derivatives.

A series of isostructural reticular frameworks with systematic differences on chemical structures allows us to disclose correlations between specific structural factors and properties, providing insights for designing novel porous materials. However, even slight differences in the molecular structure often lead to non-isostructural polymorphic frameworks particularly in the case of hydrogen-bonded organic frameworks (HOFs) because the structures of HOFs are based on a subtle balance of reversible interactions. In this study, we found that three simple analogues of tetracarboxylic acids with naphthalene, quinoxaline, and pyrazinopyrazine cores (NT, QX, and PP, respectively) yielded isostructural solvated HOFs (NT-1, QX-1, and PP-1, respectively), where hydrogen-bonded sql-networked sheets were slip-stacked with closely similar manners. More importantly, these isostructural HOFs underwent structural transformations in different manners upon removal of the guest solvents. Comparison of the crystal structures of the HOFs before and after the transformation revealed that intermolecular interactions of the core significantly affected on rearrangements of hydrogen bonds in the transformation. The results suggest the potential to control the properties and functions of isostructural HOFs by elements in the core.

Perfect Polar Alignment of Parallel Beloamphiphile Layers: Improved Structural Design Bias Realized in Ferroelectric Crystals of the Novel "Methoxyphenyl Series of Acetophenone Azines".

An improved design is described for ferroelectric crystals and implemented with the "methoxyphenyl series" of acetophenone azines, (MeO-Ph, Y)-azines with Y=F (1), Cl (2), Br (3), or I (4). The crystal structures of these azines exhibit polar stacking of parallel beloamphiphile monolayers (PBAMs). Azines 1, 3, and 4 form true racemates whereas chloroazine 2 crystallizes as a kryptoracemate. Azines 1-4 are helical because of the N-N bond conformation. In true racemates the molecules of opposite helicity (M and P) are enantiomers A(M) and A*(P) while in kryptoracemates they are diastereomers A(M) and B*(P). The stacking mode of PBAMs is influenced by halogen bonding, with 2-4 showcasing a kink due to directional interlayer halogen bonding, whereas fluoroazine 1 demonstrates ideal polar stacking by avoiding it. Notably, (MeO-Ph, Y)-azines display a stronger bias for dipole parallel alignment, attributed to the linearity of the biphenyl moiety as compared to the phenoxy series of (PhO, Y)-azines with their non-linear Ph-O-Ph moiety. The crystals of 1-4 all feature planar biphenyls and this synthon facilitates their crystallization through potent triple T-contacts and enhances their nonlinear optical (NLO) performance by increasing conjugation length and affecting favorable chromophore conformations in the solids.

Controllable Structural Transformation of Non-Porous Propyl-Malonate Hexakis[60]fullerene by Chloroform Uptake/Release.

The design of dynamic structures with high recognition host-guest materials capable to host selectively small volatile molecules is an emergent field of research with both fundamental and applied implications. The challenge of exploring novel materials with advanced functionalities has led to the development of dynamic crystalline structures promoted by soft interactions. Here, a new pure organic dynamic framework based on hexakis[60]fullerene that are held together by weak van der Waals interactions is described. This crystalline structure is capable of absorbing and releasing chloroform, through internal structural reorganization. This research provides new insight into the design of organic molecular crystals for selective adsorption applications.

Optimizing Drug Development: Harnessing the Sustainability of Pharmaceutical Cocrystals.

Environmental impacts of the industrial revolution necessitate adoption of sustainable practices in all areas of development. The pharmaceutical industry faces increasing pressure to minimize its ecological footprint due to its significant contribution to environmental pollution. Over the past two decades, pharmaceutical cocrystals have received immense popularity due to their ability to optimize the critical attributes of active pharmaceutical ingredients and presented an avenue to bring improved drug products to the market. This review explores the potential of pharmaceutical cocrystals as an ecofriendly alternative to traditional solid forms, offering a sustainable approach to drug development. From reducing the number of required doses to improving the stability of actives, from eliminating synthetic operations to using pharmaceutically approved chemicals, from the use of continuous and solvent-free manufacturing methods to leveraging published data on the safety and toxicology, the cocrystallization approach contributes to sustainability of drug development. The latest trends suggest a promising role of pharmaceutical cocrystals in bringing novel and improved medicines to the market, which has been further fuelled by the recent guidance from the major regulatory agencies.

Analysis of the Dissolution Behavior of Theophylline and Its Cocrystal Using ATR-FTIR Spectroscopic Imaging.

Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging is a powerful tool to visualize the distribution of components, and it has been used to analyze drug release from tablets. In this work, ATR-FTIR spectroscopic imaging was applied for observing the dissolution of molecular crystals from tablet compacts. The IR spectra provided chemically specific information about the transformation of crystal structures during the dissolution experiments. Theophylline (TPL) anhydrate and its cocrystals were used as model systems of molecular crystals. The IR spectra during the dissolution of TPL revealed information about the crystal structure of TPL, which transformed from anhydrate to monohydrate in water. During a dissolution test of a model cocrystal system, it was suggested that an active pharmaceutical ingredient (API) and a coformer were dissolved in water simultaneously. The IR spectra that were acquired during the dissolution of a cocrystal tablet showed new spectral bands attributed to the API after 5 min. This suggested that the precipitation of API was observed during the dissolution experiment. Measurements from ATR-FTIR spectroscopic imaging can visualize the drug release from the tablet and determine the transformation of molecular crystals during their dissolution. These results will have an impact on clarifying the dissolution mechanism of molecular crystals.

Repurposing of Antifungal Drug Flucytosine/Flucytosine Cocrystals for Anticancer Activity against Prostate Cancer Targeting Apoptosis and Inflammatory Signaling Pathways.

This study aimed to repurpose the antifungal drug flucytosine (FCN) for anticancer activity together with cocrystals of nutraceutical coformers sinapic acid (SNP) and syringic acid (SYA). The cocrystal screening experiments with SNP resulted in three cocrystal hydrate forms in which two are polymorphs, namely, FCN-SNP F-I and FCN-SNP F-II, and the third one with different stoichiometry in the asymmetric unit (1:2:1 ratio of FCN:SNP:H2O, FCN-SNP F-III). Cocrystallization with SYA resulted in two hydrated cocrystal polymorphs, namely, FCN-SYA F-I and FCN-SYA F-II. All the cocrystal polymorphs were obtained concomitantly during the slow evaporation method, and one of the polymorphs of each system was produced in bulk by the slurry method. The interaction energy and lattice energies of all cocrystal polymorphs were established using solid-state DFT calculations, and the outcomes correlated with the experimental results. Further, the in vitro cytotoxic activity of the cocrystals was determined against DU145 prostate cancer and the results showed that the FCN-based cocrystals (FCN-SNP F-III and FCN-SYA F-I) have excellent growth inhibitory activity at lower concentrations compared with parent FCN molecules. The prepared cocrystals induce apoptosis by generating oxidative stress and causing nuclear damage in prostate cancer cells. The Western blot analysis also depicted that the cocrystals downregulate the inflammatory markers such as NLRP3 and caspase-1 and upregulate the intrinsic apoptosis signaling pathway marker proteins, such as Bax, p53, and caspase-3. These findings suggest that the antifungal drug FCN can be repurposed for anticancer activity.

Multicomponent Amorphous Solid Forms of Telmisartan: Insights into Mechanochemical Activation and Physicochemical Attributes.

The present work aims to explore the new solid forms of telmisartan (TEL) with alpha-ketoglutaric acid (KGA) and glutamic acid (GA) as potential coformers using mechanochemical approach and their role in augmentation in physicochemical parameters over pure crystalline TEL. Mechanochemical synthesis was performed using 1:1 stoichiometric ratio of TEL and the selected coformers in the presence of catalytic amount of ethanol for 1 h. The ground product was characterized by PXRD, DSC, and FTIR. The new solid forms were evaluated for apparent solubility, intrinsic dissolution, and physical stability. Preliminary characterization revealed the amorphization of the mechanochemical product as an alternate outcome of cocrystallization screening. Mechanistic understanding of the amorphous phase highlights the formation of amorphous-mediated cocrystallization that involves three steps, viz., molecular recognition, intermediate amorphous phase, and product nucleation. The solubility curves of both multicomponent amorphous solid forms (TEL-KGA and TEL-GA) showed the spring-parachute effect and revealed significant augmentation in apparent solubility (8-10-folds), and intrinsic dissolution release (6-9-folds) as compared to the pure drug. Besides, surface anisotropy and differential elemental distributions in intrinsic dissolution compacts of both solid forms were confirmed by FESEM and EDX mapping. Therefore, amorphous phases prepared from mechanochemical synthesis can serve as a potential solid form for the investigation of a cocrystal through amorphous-mediated cocrystallization. This has greater implications in solubility kinetics wherein the rapid precipitation of the amorphous phase can be prevented by the metastable cocrystal phase and contribute to the significant augmentation in the physicochemical parameters.

π-Diamond: A Diamondoid Superstructure Driven by π-Interactions.

Modulating the arrangement of superstructures through noncovalent interactions has a significant impact on macroscopic shape and the expression of unique properties. Constructing π-interaction-driven hierarchical three-dimensional (3D) superstructures poses challenges on account of limited directional control and weak intermolecular interactions. Here we report the construction of a 3D diamondoid superstructure, named π-Diamond, employing a ditopic strained Z-shaped building block comprising a porphyrin unit as bow-limb double-strapped with two m-xylylene units as bowstring. This superstructure, reminiscent of diamond's tetrahedral carbon composition, is composed of double-walled tetrahedron (DWT) driven solely by π-interactions. Hetero-π-stacking between porphyrin and m-xylylene panels drive the assembly of four building blocks predominantly into a DWT, which undergoes extension to create an adamantane unit and eventually a diamondoid superstructure wherein each porphyrin panel is shared by two neighboring tetrahedra through hetero-π-stacking. π-Diamond exhibits a solid-state fluorescent quantum yield 44 times higher than that of tetraphenylporphyrin along with excellent photocatalytic performance. The precise 3D directionality of π-interactions, achieved through strained multipanel building blocks, revolutionizes the assembly of hierarchical 3D superstructures driven by π-interactions.

Utilizing "Latent" Carbon: Repositioning Hydrogen-Bonded Synthons and Assemblies via Halogen Bonding to π-Systems.

Molecules bearing carboxylic acid, amide, and hydroxyl groups are ubiquitous in crystal engineering, where robust hydrogen-bonded synthons centred on these functionalities enable reliable crystal structure design. We now show that halogen bonding to the carbon π-system of such molecules, traditionally ignored in crystal engineering, permits the recognition and directional assembly of the resulting hydrogen-bonded structural subunits, leaving the archetypal hydrogen-bonded ring, ladder, and chain homosynthons intact, but repositioned in space. When applied to heteromolecular synthons, this enables rearranging more complex hydrogen-bonded motifs and the evolution of binary cocrystals into ternary ones through "latent" carbon-based recognition sites, demonstrating a rational approach to build higher-order solid-state supramolecular assemblies.

Perovskite-like Liquid-Crystalline Materials Based on Polyfluorinated Imidazolium Cations.

Hybrid Organic-Inorganic Halide Perovskites (HOIHPs) represent an emerging class of semiconducting materials, widely employed in a variety of optoelectronic applications. Despite their skyrocket growth in the last decade, a detailed understanding on their structure-property relationships is still missing. In this communication, we report two unprecedented perovskite-like materials based on polyfluorinated imidazolium cations. The two materials show thermotropic liquid crystalline behavior resulting in the emergence of stable mesophases. The manifold intermolecular F⋅⋅⋅F interactions are shown to be meaningful for the stabilization of both the solid- and liquid-crystalline orders of these perovskite-like materials. Moreover, the structure of the incorporated imidazolium cation was found to tune the properties of the liquid crystalline phase. Collectively, these results may pave the way for the design of a new class of halide perovskite-based soft materials.

Hierarchical Self-Assembly of Curved Aromatics: From Donor-Acceptor Porphyrins to Triply Periodic Minimal Surfaces.

A saddle-shaped π-extended zinc porphyrin containing a peripheral pyridyl ligand undergoes quantitative self-assembly into a cyclic trimer. The trimer has a prismatic structure with negatively curved side walls, which promote the formation of supramolecular organic frameworks stabilized by dispersion interactions. The first framework type, UWr-1, has the npo topology, with a hexagonal structure analogous to the Schwartz H triply periodic minimal surface. Co-crystallization of the trimer with either C60 and C70 produces the isomorphous cubic UWr-2 and UWr-3 phases, characterized by the ctn network topology and a structural relationship to the Fischer-Koch minimal surface S. All three phases contain complex labyrinths of solvent-filled channels, corresponding to very large probe-accessible volumes (68 % to 76 %). The UWr-2 network could be partly desolvated while retaining its long range dimensional order, indicating remarkable strength of the dispersion interactions in the crystal. A theoretical analysis of noncovalent interactions shows the role of geometrical matching between the negatively curved porphyrin units and positively curved fullerenes.

Crystal Engineering of MOF-Derived Bimetallic Oxide Solid Solution Anchored with Au Nanoparticles for Photocatalytic CO2 Reduction to Syngas and C2 Hydrocarbons.

Considering that CO2 reduction is mostly a multielectron reaction, it is necessary for the photocatalysts to integrate multiple catalytic sites and cooperate synergistically to achieve efficient photocatalytic CO2 reduction to various products, such as C2 hydrocarbons. Herein, through crystal engineering, we designed and constructed a metal-organic framework-derived Zr/Ti bimetallic oxide solid solution support, which was confirmed by X-ray diffraction, electron microscopy and X-ray absorption spectroscopy. After anchoring Au nanoparticles, the composite photocatalyst exhibited excellent performances toward photocatalytic CO2 reduction to syngas (H2 and CO production rates of 271.6 and 260.6 µmol g-1 h-1) and even C2 hydrocarbons (C2H4 and C2H6 production rates of 6.80 and 4.05 µmol g-1 h-1). According to the control experiments and theoretical calculations, the strong interaction between bimetallic oxide solid solution support and Au nanoparticles was found to be beneficial for binding intermediates and reducing CO2 reduction, highlighting the synergy effect of the catalytic system with multiple active sites.