Anwendung der in situ Pulverröntgendiffraktion zur Visualisierung von Festkörperprozessen

X-ray powder diffraction is as a powerful tool for structural analysis of crystalline compounds which do not grow as single crystals, but a polycrystalline bulk. When applied under non-ambient conditions, or when data are collected at consecutive time intervals, X-ray powder diffraction can be readily turned into a valuable method for in situ following, visualizing and ultimately explaining a number of solid state processes and chemical reaction. In the scope of my PhD work, an attempt to demonstrate the power and applicability of in situ X-ray powder diffraction in studying the reactivity of the solid state was made. In a period of almost 3 years, various systems were investigated when submitted under different external stimuli to initiate specific process and/or reaction in the solid state. The results described in this thesis were done working on six (independent) research projects, presented herein as separate case studies. (It should be noted that in parallel to the work performed on these six projects, research was done in several other topics, part of which is already published in scientific journals and the references are given in CV, attached at the end of the thesis).Die Röntgenpulverdiffraktion ist ein mächtiges Werkzeug zur strukturellen Analyse von kristallinen Verbindungen, welche nicht als Einkristalle, dafür aber als pulverförmiges Material vorliegen. Werden Pulverröntgendiffraktionsdaten unter Nicht-Umgebungsbedingungen oder in nacheinander folgenden Zeitintervallen aufgenommen, so zeigt sich die Bedeutsamkeit der Methode, um Festkörperprozesse und chemische Reaktionen in-situ zu verfolgen, sie zu visualisieren und eine wissenschaftliche Erklärung zu finden. Im Rahmen der vorliegenden Doktorthesis wurde ein Versuch unternommen, die Mächtigkeit und Anwendbarkeit der in-situ Pulverröntgendiffraktion anhand der Untersuchung der Reaktivität von Festkörpern zu demonstrieren. In einem Zeitraum von beinahe drei Jahren wurden verschiedene Systeme unterschiedlichst extern angeregt, um spezifische Prozesse und/oder Reaktionen in Festkörpern auszulösen. Die Ergebnisse, die in der vorliegenden Arbeit beschrieben werden, rühren von sechs (unabhängigen) Forschungsprojekten her, wobei diese hier in separaten Fallstudien beschrieben werden. (Nebenbei muss bemerkt werden, dass parallel zu den sechs beschriebenen Forschungsprojekten, Forschung auf verschiedenen anderen Themen durchgeführt wurde, welche teilweise bereits in wissenschaftlichen Zeitschriften publiziert wurden. Die Referenzen dazu sind im Lebenslauf am Ende der Arbeit gelistet.

Azo or Not: Crystallographic Insights into β-Naphthol Reds

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

The Crystal Structure of Zineb, 75 years later

Ethylene bis(dithiocarbamates) (EBDTCs) have been used as staple fungicides for over 75 years. The first industrially manufactured EBDTC was zineb, zinc ethylene bis(dithiocarbamate), marketed under the tradename Dithane. Even though zineb has been used as a fungicide since the 1940s, its crystal structure remained unknown. Herein, we describe the crystal structure of zineb (triclinic crystal system, space group P–1, a = 7.5094(9) Å, b = 9.4356(9) Å, c = 7.4120(7) Å, α = 107.945(8) °, β = 100.989(7) °, γ = 105.365(8) °, V = 460.07(10) Å3). The inorganic fragment of the structure consists of two Zn2+ cations, coordinated by the thiocarbamate group. There are four Zn–S bonds with lengths in the range of 2.325 – 2.426 Å, and one rather long Zn–S contact of 2.925(8) Å. Inorganic fragments are linked by organic EBDTC ligands to form extended, polymeric layers. The layers are packed in a ABAB manner, related by the inversion symmetry and held together by hydrogen bonding network. In this article, in addition to describing the crystal structure, we correlate the structural features with the vibrational spectroscopic and thermal characteristics of zineb, and we provide a short summary of the major developments of fungicides in the 20th century<br /

Soluble Thiabendazolium Salts with Anthelminthic Properties

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 syn-thesis 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. Fur-thermore, saccharin is a sweetener, while the acids taste sour. Therefore, the salts formed also result in an in-trinsic improvement of palatability. These results can inform new strategies for oral and chewable tablet for-mulations for treating helminthic infections

Neutron Vibrational Spectroscopic Study of the Acetonitrile:Acetylene (1:2) Cocrystal Relevant to Titan, Saturn’s Moon

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

Mechanosynthesis of a Coamorphous Formulation of Creatine with Citric Acid and Humidity–Mediated Transformation into a Cocrystal

We report a simple, efficient, and scalable mechanochemical method of preparation of new creatine fitness supplement with increased solubility (compared to the creatine monohydrate) and decreased acidity (compared to creatine hydrochloride)

Handling Fluorinated Gases as Solid Reagents Using Metal–Organic Frameworks

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

Transdermal hydrogen sulfide delivery enabled by open metal site metal-organic frameworks

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

Neutron Vibrational Spectroscopic Study of the Acetylene:Ammonia (1:1) Cocrystal Relevant to Titan, Saturn’s Moon

The surface of Titan, Saturn’s icy moon, is believed to be comprised 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 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 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

Defects Formation and Amorphization of Zn-MOF-74 Crystals by Post-Synthetic Interactions with Bidentate Adsorbates

The controlled introduction of defects into MOFs is a powerful strategy to induce new physiochemical properties and improve their performance for target applications. Herein, we present a new strategy for defect formation and amorphization.<br /