Organic S(VI) fluorides have garnered substantial interest for covalent drug discovery and chemoproteomics due to their ambient stability and unique electrophilic reactivity. Sulfuryl fluoride (SO 2 F 2 ) is the ideal reagent for the synthesis of various S(VI)–F moieties, yet it is a toxic greenhouse gas, often making it incompatible with laboratory settings. Developing a strategy for handling SO 2 F 2 that is amenable to high-throughput reaction discovery would enhance its utility in the laboratory without necessitating specialized equipment or extensive safety measures. Herein, we report a strategy to safely store reactive SO 2 F 2 within a metal–organic framework (MOF) for its facile application to the synthesis of electrophilic, bioactive molecules. The solid SO 2 F 2 –Mg 2 (dobdc) reagent can be stored for at least five months with minimal gas loss due to the strong yet reversible interaction between SO 2 F 2 and Mg 2+ centers in the MOF, as confirmed by single-crystal X-ray diffraction. Using this reagent, we prepare a range of drug-like arylfluorosulfates, saturated N -heterocyclic sulfamoyl fluorides, and N -heteroarene sulfamoyl fluorides. These findings represent the first experimental study of SO 2 F 2 adsorption within a MOF and the first use of MOFs for late-stage fluorosulfurylation, paving the way towards a general approach to carefully handle dangerous, reactive gases as solid reagents.

The orderly arrangement of molecules in crystals provides a unique platform for the control of reactivity, where spatial vicinity and orientation of the molecules determine the course of the reaction. Common wisdom assumes that the densest crystal packings of the reactant molecules are most favorable for pressure-induced topochemical reactions. Based on thermodynamic and spatial arguments, here we show that the densest crystal packing may not be the most optimal platform for chemical synthesis. Instead, introducing void space within the crystal lattice significantly improves and even enables chemical reactions. In the case of sorbic acid confined between brucite-type layers, this reactivity is used to modify the optical, spectroscopic and magnetic properties of 2D layers and to synthesize a retrievable polymeric product.

A common strategy for developing emissive covalent organic frameworks (COFs) with varied properties is incorporating diverse chromophoric monomers. Herein, an alternative approach is adopted to demonstrate that a simple alteration in just one atom (oxygen vs. sulfur) in monomer design can result in significant differences in the physical, chemical, and photophysical properties of the resulting COFs. Specifically, monomers with the same symmetry but containing either urea or thiourea functionalities are used to synthesize two crystalline, fully conjugated emissive COFs, COF-SMU-2 (urea-based), and COF-SMU-3 (thiourea-based), with sql type topology. Steady-state (both in solid state and solution), time-resolved, and broadband femtosecond transient absorption spectroscopies reveal the excited-state exciton dynamics of the two COFs, explaining the dramatic differences in their photoluminescence behaviors. Further, density functional theory (DFT) studies are performed, which confirm the occurrence of charge transfer in these systems. A direct impact of the single atom variation is also observed during I2 adsorption studies. Taken together, this study presents new routes to fabricate COFs with distinct properties by making single-atom modulations, and widens the scope of developing emissive COFs capable of demonstrating excited-state charge transfer, with potential applications in optoelectronics and environmental remediation.

Cocrystals are of tremendous significance for the pharmaceutical industry, due to their favorable properties when compared to their salt analogs. The dpKa rule, commonly used in the identification of a cocrystal, meets shortcomings in the 0 <= dpKa <= 3 range, where salts and cocrystals ought to emerge. In this project, we probed the salt vs. cocrystal nature, using the strength of hydrogen bondings through the local mode analysis, in the case example of the product formed between thiobendazole and fumaric acid. Moreover, we employed a topological analysis of the electronic density to quantify the covalency of such interactions.

Fluorine is an increasingly common substituent in pharmaceuticals and agrochemicals because it improves the bioavailability and metabolic stability of organic molecules. Fluorinated gases represent intuitive building blocks for the late-stage installation of fluorinated groups, but they are generally overlooked because they require the use of specialized equipment. We report a general strategy for handling fluorinated gases as benchtop-stable solid reagents using metal-organic frameworks (MOFs). Gas-MOF reagents are prepared on gram-scale and used to facilitate fluorovinylation and fluoroalkylation reactions. Encapsulation of gas-MOF reagents within wax enables stable storage on the benchtop and controlled release into solution upon sonication, which represents a safer alternative to handling the gas directly. Furthermore, our approach enables high-throughput reaction development with these gases.

Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter involved in many physiological processes that are integral to proper cellular functioning, including chemical signaling, redox balancing, and modification of vital proteins. Due to its profound anti-inflammatory and antioxidant properties, H2S plays important roles in preventing inflammatory skin disorders and improving wound healing. Transdermal H2S delivery is a therapeutically viable option for the man-agement of such disorders. However, current small-molecule H2S donors are not optimally suited for transdermal deliv-ery and typically generate electrophilic byproducts that may lead to undesired toxicity. Here, we demonstrate that H2S release from metal-organic frameworks (MOFs) bearing coordinatively unsaturated metal centers is a promising alterna-tive for controlled transdermal delivery of gaseous H2S without the release of unwanted byproducts. In particular, exten-sive gas sorption measurements and powder X-ray diffraction (PXRD) studies of eleven MOFs support that the Mg-based framework Mg2(dobdc) (dobdc4− = 2,5-dioxidobenzene-1,4-dicarboxylate) is uniquely well-suited for transdermal H2S delivery due to its strong yet completely reversible binding of H2S, high capacity (14.7 mmol/g or 33.3 wt% at 1 bar and 25 °C), and lack of toxicity. In addition, Rietveld refinement of high-quality synchrotron PXRD data from a H2S-dosed mi-crocrystalline sample of Mg2(dobdc) supports that the high H2S capacity of this framework arises due to the presence of three distinct binding sites: at the Mg centers through a Mg⋅⋅⋅S interaction (primary site), through a short S⋅⋅⋅S interaction to the polarized H2S molecules at the primary sites (secondary site), and in the center of the pores (tertiary site). Last, we demonstrate that transdermal delivery of H2S from this framework is sustained over a 24 h period through porcine skin. Not only is this significantly longer than sodium sulfide (Na2S), but this represents the first example of controlled trans-dermal delivery of pure H2S gas. Overall, H2S-loaded Mg2(dobdc) is an easily accessible, solid-state source of H2S, ena-bling safe storage and transdermal delivery of this therapeutically relevant gas.

The surface of Titan, Saturn's icy moon, is believed to be composed of various molecular minerals with a great diversity in structure and composition. Under the surface conditions, 93 K and 1.45 atm, most small molecules solidify and form minerals, including acetylene and ammonia. These two compounds can not only form single-component solids but also a 1:1 binary cocrystal that exhibits intriguing rotor phase behavior. This cocrystal is a putative mineral on Titan and other planetary bodies such as comets. In addition, the structure of the cocrystal is relevant to fundamental science as it can help better understand the emergence of rotor phases. Here, we present a detailed vibrational neutron spectroscopic study supported by a neutron powder diffraction study on the cocrystal and the single-phase solids. The experimentally observed spectral bands were assigned based on theoretical calculations. The established spectra-properties correlations for the cocrystal corroborate the observed properties. To the best of our knowledge, this study presents the first example of the application of neutron vibrational spectroscopy in studying Titan-relevant organic minerals.

Saturn’s moon Titan features a surface composed of various organic solids with pronounced compositional and structural diversity. On top of the icy core, the surface experiences temperature of ~93 K and pressure of ~1.45 atm. Under these conditions, most small organic molecules exist as solids and form Titanean minerals. Acetonitrile and acetylene are two of these molecules, which can form single-component molecular solids, but also a 1:2 binary cocrystal. Here we present a combined neutron vibrational spectroscopic study, neutron powder diffraction study, and theoretical modeling of the cocrystal and the corresponding single-phase solids. This combined study resulted in insightful spectra–structure–properties correlations for the cocrystal and the molecular solids. Furthermore, we observed quenching of the high-temperature form of acetonitrile in the presence of the cocrystal, which supports the possibility of the existence of metastable solids as minerals on Titan. The results presented in this study further the knowledge of the putative structure and composition of the surface of Titan, and, at the same time, contributes to better understanding of the fundamental thermodynamic properties of two of the smallest organic molecules in the Universe.

In {\delta}-Ag2/3V2O5 with charge degrees of freedom in V, it is known that the charge ordering state and physical properties of V that appear at low temperatures depend strongly on the ordering state of Ag. In this study, we focused on the Ag ions in the interlayer and studied the structure using synchrotron radiation powder diffraction in dependence on temperature. We found that when the sample is slowly cooled from room temperature and ordering occurs at the Ag sites, V4+/V5+ charge ordering of V and subsequent V4+-V4+ structural dimers are produced. Although quenching the sample from room temperature suppresses the ordering of Ag, annealing at around 160 K promotes partial ordering of Ag and allows a metastable phase to be realized. This metastable phase is maintained even when the temperature is lowered again, producing a remarkable change in low-temperature properties. These results indicate that the ordered state of Ag, which is the key to control the charge-ordered state and physical properties, can be controlled by low-temperature annealing. The results of this study may provide a methodology for the realization of metastable states in a wide range of material groups of vanadium compounds, where competition among various charge ordered states underlies the physical properties.

This article presents a perspective on the state of the art in the structure determination of microporous carbon-capture materials and paths toward future progress in this field, as discussed the NIST workshop of the same title.

The NIST Workshop: Integrating Crystallographic and Computational Approaches to Carbon-Capture Materials for the Mitigation of Climate Change took place from October 31–November 1, 2023 at the National Cybersecurity Center of Excellence (NCCoE) Compound in Rockville, MD, which is an off-campus NIST facility. This workshop provided a forum for experimentalists and theorists working on the structural aspects of CO 2 capture and sequestration materials to review the current state of the art in this field and discuss opportunities for collaborative research required to develop tools for rapid determination of the structure and its effect on the direct air capture performance in porous solid sorbents. We had a total of 33 international participants (18 invited speakers) from 17 institutions who were experimentalists and theorists from academia, government, and industry. The workshop was a great success.

Layered hybrid organic-inorganic compounds of the transition metal hydroxides, in which part of the hydroxide ions are exchanged for organic ligands that act as spacers of the 2-dimensional inorganic layers, elicit new or enhanced properties. The interlayer ligands enable fine-tuning of the physicochemical properties of the metal hydroxide layers, including their magnetism. Specifically, within the Co(OH)(2) family of transition ion hydroxides, this approach has been leveraged to stabilize antiferromagnetic and ferrimagnetic ground states for pillared and layered complexes, respectively. Here, we further investigate the effects of changing dimensionality, local Co coordination, and interlayer spacing on the magnetic ground state of brucite-like beta-Co(OH) layered complexes. We report the hydrothermal synthesis of a new crystalline material, Co(OH)(sorb), where the inorganic layers are spaced by monotopic, doubly unsaturated sorbate ligands (sorb = [C6H7O2](-)). The material was structurally characterized using powder X-ray and neutron diffraction measurements and the crystal structure was solved ab initio from powder diffraction data and refined using the Rietveld method. The magnetic susceptibility and magnetization measurements reveal canted antiferromagnetic ordering with T-N = 41.7 K. This report augments our understanding of tuning magnetism through dimensionality in layered complexes and represents a step forward in the design of new 2D layered hybrid compounds.

Emissive covalent organic frameworks (COFs) have recently emerged as next-generation porous materials with attractive properties such as tunable topology, porosity, and inherent photoluminescence. Among the different types of COFs, substoichiometric frameworks (so-called Type III COFs) are especially attractive due to the possibility of not only generating unusual topology and complex pore architectures but also facilitating the introduction of well-defined functional groups at precise locations for desired functions. Herein, the first example of a highly emissive (PLQY 6.8%) substoichiometric 2D-COF (COF-SMU-1) featuring free uncondensed aldehyde groups is reported. In particular, COF-SMU-1 features a dual-pore architecture with an overall bex net topology, tunable emission in various organic solvents, and distinct colorimetric changes in the presence of water. To gain further insights into its photoluminescence properties, the charge transfer, excimer emission, and excited state exciton dynamics of COF-SMU-1 are investigated using femtosecond transient absorption spectroscopy in different organic solvents. Additionally, highly enhanced atmospheric water-harvesting properties of COF-SMU-1 are revealed using FT-IR and water sorption studies.The findings will not only lead to in-depth understanding of structure-property relationships in emissive COFs but also open new opportunities for designing COFs for potential applications in solid-state lighting and water harvesting.

Metal-organic frameworks (MOFs) are porous, crystalline materials constructed from organic linkers and inorganic nodes with potential utility in gas separations, drug delivery, sensing, and catalysis. Small variations in MOF synthesis conditions can lead to a range of accessible frameworks with divergent chemical or photophysical properties. New meth-ods to controllably access phases with tailored properties would broaden the scope of MOFs that can be reliably prepared for specific applications. Herein, we demonstrate that simply increasing the reaction concentration during the solvother-mal synthesis of M2(dobdc) (M = Mg, Mn, Ni; dobdc4− = 2,5-dioxido-1,4-benzenedicarboxylate), also known as MOF-74, unexpectedly leads to trapping of a kinetic intermediate termed CORN-MOF-1 (CORN = Cornell University). In-depth spec-troscopic, crystallographic, and computational studies support that CORN-MOF-1 has a similar structure to M2(dobdc) but with partially protonated linkers and charge-balancing or coordinated formate groups in the pores. The resultant vari-ation in linker spacings causes CORN-MOF-1 (Mg) to be strongly photoluminescent in the solid state, whereas H4dobdc and Mg2(dobdc) are weakly emissive due to excimer formation. In addition, CORN-MOF-1 variants can be converted into high-quality samples of the thermodynamic M2(dobdc) phases by heating in N,N-dimethylformamide (DMF). Overall, our findings support that high-concentration synthesis provides a straightforward method to identify new kinetic MOF phas-es with different properties from known materials and to produce highly porous samples of MOFs, paving the way for the discovery and gram-scale synthesis of framework materials.

Thiabendazole is an anthelmintic drug used to treat strongyloidiasis (threadworm), cutaneous and visceral larva migrans, trichinosis, and other parasites. The active pharmaceutical ingredient is typically administered orally as tablets that should be chewed before swallowing. Current formulations combine the active ingredient with excipients, including sodium saccharinate as a sweetener. Thiabendazole's low aqueous solubility hinders fast dissolution and absorption through the mucous membranes. We sought to reformulate this medicine to improve both solubility and palatability. We utilized the possibility of protonation of the azole nitrogen atom and selected four different hydrogen donors: saccharin, fumaric, maleic, and oxalic acids. Solvothermal synthesis resulted in salts with each co-former, whereas neat and liquid-assisted grinding enabled the synthesis of additional formulations. Product formation was observed by powder X-ray diffraction. To better understand the structural basis of the proton transfer, we solved the crystal structures of the salts with saccharin, maleic acid, and oxalic acid using single-crystal X-ray diffraction. The structure of the salt with fumaric acid was solved by powder X-ray diffraction. We further characterized the salts with vibrational spectroscopic and thermoanalytical methods. We report a broad tunability of the aqueous solubility of thiabendazole by salt formation. Reformulation with maleic acid provided a 60-fold increase in solubility, while saccharin and oxalic acid gave a modest improvement. Fumaric acid resulted in a solid with only slightly higher solubility. Furthermore, saccharin is a sweetener, while the acids taste sour. Therefore, the salts formed also result in an intrinsic improvement of palatability. These results can inform new strategies for oral and chewable tablet formulations for treating helminthic infections.

Fluorine is ubiquitous in the pharmaceutical and agrochemical industries because it improves the bioavailability and metabolic stability of molecules. However, most modern fluoroalkylation and fluorovinylation protocols rely on reagents that are expensive, explosive, or otherwise challenging to use. Fluorinated gaseous reagents are promising alternatives that are overlooked for late-stage functionalization because they require specialized equipment. Herein, we report a general strategy for safely handling inexpensive fluorinated gaseous building blocks as benchtop-stable solid reagents using porous metal–organic frameworks (MOFs). Gas–MOF reagents are employed to facilitate novel fluorovinylation and fluoroalkylation reactions, which represent safe, efficient, and atom-economical alternatives to current methods. Our approach enables high-throughput reaction development with any gaseous reagent, opening the door for the development of myriad new synthetic transformations.

We report the phase diagram for the binary creatine-citric acid mixture which features a stable and broad eutectic region. Combinations containing 10-60 mol% creatine yield a deep eutectic solvent with a glass transition temperature at 270 K. Addition of up to 70 mol% water to the binary mixture affords retention of the eutectic nature and a handle to vary solvent viscosity and polarity.

β-Naphthol reds are a group of widely used pigments with prominent historical, commercial, and cultural significance. In in-dustry, and especially within the art and heritage community, they are known as azo pigments. However, β-naphthols, very often, are not azo pigments. Due to enol/keto tautomerization of the 1-arylhydrazone-2-naphthol skeleton, these pigments oftentimes crystallize as hydrazones (keto). Therefore, proper characterization is necessary for understanding their intrinsic physicochemical properties and chemical reactivity in the solid state, as well as stability and lightfastness. Here, we focused on two representative β-naphthol reds, pigment red 40 (PR40) and pigment red 4 (PR4). Using single-crystal X-ray diffraction, we provide decisive proof that both of these pigments are keto/hydrazones in the solid state. Therefore, the frequent yet erroneous designation as azo pigments should be avoided. To confirm the bulk structure, we performed powder diffraction experiments, followed by Rietveld refinement. We complemented the diffraction experiments with spectroscopic (IR, Raman, UV-vis) and thermal (TGA, DSC) analyses. Furthermore, we studied the lightfastness of both chromophores in solution and solid state. While the solid state pigments were stable over the course of the experiment, UV irradiation of solutions resulted in degradation, which was studied by chromatographic and mass-spec techniques. We hope that this research will bring to light the necessity of proper solid-state characterization of β-naphthol reds, as well as pigments as a whole.

beta-Naphthol reds are a group of widely used pigments with prominent historical, commercial, and cultural significance. In industry, and especially within the art and heritage community, they are known as azo pigments. However, beta-naphthols, very often, are not azo pigments. Because of enol/keto tautomerization of the 1-arylhydrazone-2-naphthol skeleton, these pigments oftentimes crystallize as hydrazones (keto). Therefore, proper characterization is necessary for understanding their intrinsic physicochemical properties and chemical reactivity in the solid state, as well as their stability and lightfastness. Crystallographic studies have indicated that beta-naphthol reds tend to adopt the hydrazone form in the solid state. Here, we continue these structural investigations, and we focused on two prominent beta-naphthol reds, pigment red 40 (PR40) and pigment red 4 (PR4). Using single-crystal X-ray diffraction, we provide decisive proof that both of these pigments are keto/hydrazones in the solid state. Therefore, the frequent yet erroneous designation as azo pigments should be avoided. To confirm the bulk structure, we performed powder diffraction experiments, followed by Rietveld refinement. We complemented the diffraction experiments with spectroscopic (IR, Raman, UV-vis) and thermal (TGA, DSC) analyses. Furthermore, we studied the lightfastness of both chromophores in solution and the solid state. While the solid-state pigments were stable over the course of the experiment, UV irradiation of solutions resulted in degradation, which was studied by chromatographic and mass-spectrometry techniques. We hope that this research will bring to light the necessity of proper solid-state characterization of beta-naphthol reds, as well as pigments as a whole.