Application of NMR RDC’s, relaxation and self-diffusion for the study of dynamic processes of small molecules in solution

Spin-lattice Relaxation, self-Diffusion coefficients and Residual Dipolar Couplings (RDC’s) are the basis of well established Nuclear Magnetic Resonance techniques for the physicochemical study of small molecules (typically organic compounds and natural products with MW < 1000 Da), as they proved to be a powerful and complementary source of information about structural dynamic processes in solution. The work developed in this thesis consists in the application of the earlier-mentioned NMR techniques to explore, analyze and systematize patterns of the molecular dynamic behavior of selected small molecules in particular experimental conditions. Two systems were chosen to investigate molecular dynamic behavior by these techniques: the dynamics of ion-pair formation and ion interaction in ionic liquids (IL) and the dynamics of molecular reorientation when molecules are placed in oriented phases (alignment media). The application of NMR spin-lattice relaxation and self-diffusion measurements was applied to study the rotational and translational molecular dynamics of the IL: 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF4]. The study of the cation-anion dynamics in neat and IL-water mixtures was systematically investigated by a combination of multinuclear NMR relaxation techniques with diffusion data (using by H1, C13 and F19 NMR spectroscopy). Spin-lattice relaxation time (T1), self-diffusion coefficients and nuclear Overhauser effect experiments were combined to determine the conditions that favor the formation of long lived [BMIM][BF4] ion-pairs in water. For this purpose and using the self-diffusion coefficients of cation and anion as a probe, different IL-water compositions were screened (from neat IL to infinite dilution) to find the conditions where both cation and anion present equal diffusion coefficients (8% water fraction at 25 ºC). This condition as well as the neat IL and the infinite dilution were then further studied by 13C NMR relaxation in order to determine correlation times (c) for the molecular reorientational motion using a mathematical iterative procedure and experimental data obtained in a temperature range between 273 and 353 K. The behavior of self-diffusion and relaxation data obtained in our experiments point at the combining parameters of molar fraction 8 % and temperature 298 K as the most favorable condition for the formation of long lived ion-pairs. When molecules are subjected to soft anisotropic motion by being placed in some special media, Residual Dipolar Couplings (RDCs), can be measured, because of the partial alignment induced by this media. RDCs are emerging as a powerful routine tool employed in conformational analysis, as it complements and even outperforms the approaches based on the classical NMR NOE or J3 couplings. In this work, three different alignment media have been characterized and evaluated in terms of integrity using 2H and 1H 1D-NMR spectroscopy, namely the stretched and compressed gel PMMA, and the lyotropic liquid crystals CpCl/n-hexanol/brine and cromolyn/water. The influence that different media and degrees of alignment have on the dynamic properties of several molecules was explored. Different sized sugars were used and their self-diffusion was determined as well as conformation features using RDCs. The results obtained indicate that no influence is felt by the small molecules diffusion and conformational features studied within the alignment degree range studied, which was the 3, 5 and 6 % CpCl/n-hexanol/brine for diffusion, and 5 and 7.5 % CpCl/n-hexanol/brine for conformation. It was also possible to determine that the small molecules diffusion verified in the alignment media presented close values to the ones observed in water, reinforcing the idea of no conditioning of molecular properties in such media.Fundação para a Ciência e a Tecnologia - RECI/BBB-BQB/0230/201

Derivatization in Analytical Chemistry

Derivatization is one of the most widely used sample pretreatment techniques in Analytical Chemistry and Chemical Analysis. Reagent-based or reagent-less schemes offer improved detectability of target compounds, modification of the chromatographic properties and/or the stabilization of sensitive compounds until analysis. Either coupled with separation techniques or as a “stand alone” analytical procedure, derivatization offers endless possibilities in all aspects of analytical applications

The Origin and Early Evolution of Life

What is life? How, where, and when did life arise? These questions have remained most fascinating over the last hundred years. Systems chemistry is the way to go to better understand this problem and to try and answer the unsolved question regarding the origin of Life. Self-organization, thanks to the role of lipid boundaries, made possible the rise of protocells. The role of these boundaries is to separate and co-locate micro-environments, and make them spatially distinct; to protect and keep them at defined concentrations; and to enable a multitude of often competing and interfering biochemical reactions to occur simultaneously. The aim of this Special Issue is to summarize the latest discoveries in the field of the prebiotic chemistry of biomolecules, self-organization, protocells and the origin of life. In recent years, thousands of excellent reviews and articles have appeared in the literature and some breakthroughs have already been achieved. However, a great deal of work remains to be carried out. Beyond the borders of the traditional domains of scientific activity, the multidisciplinary character of the present Special Issue leaves space for anyone to creatively contribute to any aspect of these and related relevant topics. We hope that the presented works will be stimulating for a new generation of scientists that are taking their first steps in this fascinating field

Under the influence: Understanding the thermodynamic and optical properties of stimuli-responsive complex organic systems

A solid understanding of the optical and thermodynamic features of a chemical system is indispensable for the development and optimisation of new materials. Stimuli-responsive substances may be incorporated into optoelectronic devices, such as organic light-emitting diodes or sensory systems. Especially in recent years, photo-sensitive molecular aggregates and redox-switchable supramolecular architectures have proven their merit. Due to their flexible components, these noncovalently bound systems often exhibit perplexing behaviour when submitted to external stimuli, such as light or electric potential. Examples addressed in this thesis include substitution-pattern controlled fluorescence quantum yields and redox-induced switchable spectroscopic responses. While there are plenty of powerful experimental techniques around to examine the underlying mechanisms, high-level quantum-chemical approaches are often crucial for a final and conclusive interpretation of one’s experimental results. The aim of this thesis is to examine the broad scope of stimuli-responsive molecular aggregates and demonstrate the versatility of quantum-chemical methods to study their optical and thermodynamic properties. To this end, I will present six different publications separated into two parts, A and B, each contributing three papers. Due to the variety of the molecules studied in this work, computational protocols effectively tailored for each project had to be developed. The applied methods are used to study electronic as well as molecular structures and include solvent and finite-temperature effects for comparison to experiment. A major emphasis is put on the evaluation of excited states. In addition to the valuable knowledge we could gain about the underlying chemistry of the investigated systems, these protocols serve as a potent tool for the examination of similar problems. All papers include combined approaches of theory and experiment and, hence, showcase the efficient collaboration of experimental and theoretical groups. In part A, I will present a new class of fluorescent dyes: Diaminodicyanoquinones (DADQs). Owing to a large dipole moment, redox-activity, and tailorable fluorescence, DADQs are promising candidates for a variety of applications in the context of molecular electronics. Papers A1-A3 effectively follow a bottom-up approach examining monomers, aggregates in solution, and the solid state with a focus on their absorption and emission features. In all three publications, remarkable experimental observations are made including notably high quantum yields and counterintuitive concentration-dependent absorption peaks. In each case, a combination of multiple high-level state-of-the-art quantum-chemical approaches including DFT/MRCI (density functional theory/multi-reference configuration interaction) is utilised to thoroughly investigate the chemical systems and find explanations for the often unexpected experimental results. Part B presents three different redox-responsive supramolecular systems, each displaying intriguing thermodynamic or optical properties, which could only be fully unravelled by rigorous theoretical studies. Redox-responsiveness is induced either by incorporation of the organosulfur compound tetrathiafulvalene (TTF) or by complexation with a redox-active molecule such as cobaltocene. A variety of different quantum-chemical methods based on DFT and time-dependent DFT (TD-DFT) is employed in the course of part B to study switching mechanisms and rationalise thermodynamic features. In this way, the examined supramolecular structures are now equipped with an in-depth understanding of their often non-trivial chemical behaviour which paves the way towards applications in novel optoelectronic technologies.Ein klares Verständnis der optischen und thermodynamischen Eigenschaften chemischer Systeme ist unabdingbar für die Entwicklung und Optimierung neuer Materialien. Substanzen, die sich von äußeren Einflüssen steuern lassen, können in optoelektronische Geräte wie organische Leuchtdioden oder Sensorsysteme eingebaut werden. Besonders in den vergangenen Jahren haben photo-sensitive molekulare Aggregate und redox-schaltbare supramolekulare Architekturen ihren Wert unter Beweis gestellt. Aufgrund ihrer flexiblen Einzelkomponenten zeigen diese nichtkovalent gebundenen Systeme oftmals ein verblüffendes Verhalten, wenn sie durch äußere Reize wie Licht oder ein elektrisches Potenzial beeinflusst werden. Beispiele, die in dieser Dissertation adressiert werden, sind Substitutionsmuster-kontrollierte Fluoreszenzquantenausbeuten und redox-induzierte schaltbare spektroskopische Signale. Während es eine große Anzahl an vielseitigen experimentellen Methoden gibt, um die zugrundeliegenden Mechanismen zu studieren, ist oftmals die Verwendung anspruchsvoller quantenchemischer Ansätze vonnöten, um eine endgültige und schlüssige Interpretation der experimentellen Ergebnisse zu erhalten. Diese Arbeit ist darauf ausgerichtet, die Vielseitigkeit von durch äußere Reize steuerbare (eng. stimuli-responsive) molekulare Aggregate zu analysieren und die Flexibilität von quantenchemischen Methoden aufzuzeigen, die zur Untersuchung ihrer optischen und thermodynamischen Eigenschaften genutzt werden. Zu diesem Zweck werde ich sechs Publikationen vorstellen, aufgeteilt in zwei Teile, A und B, die jeweils drei Arbeiten beitragen. Aufgrund der Vielfältigkeit der untersuchten Moleküle wurden Berechnungsverfahren entwickelt, die im wesentlichen für jedes Projekt aufs Neue maßgeschneidert werden mussten. Die angewandten Methoden sind darauf ausgelegt, sowohl elektronische als auch molekulare Strukturen zu beschreiben und Solvatations- und Temperatureinflüsse für den Vergleich zu Experimenten mit einzubeziehen. Ein großes Augenmerk liegt auf der Analyse von angeregten Zuständen. Abgesehen von den wertvollen Erkenntnissen, die wir über die zugrundeliegende Chemie der untersuchten Systeme erhalten konnten, dienen die entwickelten Berechnungsansätze als leistungsfähiges Werkzeug für das Herangehen an ähnliche Probleme. Alle Publikationen beinhalten aus Theorie und Experiment kombinierte Ansätze und illustrieren damit die effiziente Zusammenarbeit von theoretisch und experimentell arbeitenden Forschungsgruppen. In Teil A werde ich eine neuartige Klasse von fluoreszierenden Farbstoffen vorstellen: Diaminodicyanochinone (DADQs). Aufgrund ihrer hohen Dipolmomente, Redoxaktivität und einstellbaren Fluoreszenz sind DADQs vielversprechende Kandidaten für eine Vielzahl von Anwendungen im Kontext der molekularen Elektronik. Publikationen A1-A3 folgen im wesentlichen einem Bottom-up-Ansatz, bei dem es um die Untersuchung von Monomeren, Aggregaten in Lösung und Festkörperstoffen geht, wobei ein Fokus auf deren Absorptions- und Emissionseigenschaften liegt. In allen drei Arbeiten sind erstaunliche experimentelle Beobachtungen gemacht worden wie beispielsweise extrem hohe Fluoreszenzquantenausbeuten oder kontraintuitive konzentrationsabhängige Absorptionsbanden. In jeder Untersuchung wurde eine Vielzahl an hochmodernen quantenchemischen Methoden inklusive des DFT/MRCI (Dichtefunktionaltheorie/Multireferenz-Konfigurationswechselwirkung) Ansatzes genutzt, um eine ausführliche Analyse der chemischen Systeme zu gewährleisten und Erklärungen für die unerwarteten experimentellen Beobachtungen zu finden. In Teil B werden drei verschiedene redox-stimulierbare supramolekulare Systeme präsentiert, die alle interessante thermodynamische und optische Eigenschaften aufzeigen, welche nur durch den sorgfältigen Einsatz von theoretischen Methoden vollkommen verstanden werden konnten. Redox-Stimulierbarkeit wurde entweder durch die Eingliederung der schwefelorganischen Verbindung Tetrathiafulvalen (TTF) oder durch Komplexierung mit einem redox-aktiven Molekül wie Cobaltocen induziert. Verschiedene quantenchemische auf DFT und zeitabhängiger DFT (TD-DFT) basierende Ansätze wurden in Teil B benutzt, um Schaltmechanismen zu untersuchen und thermodynamische Eigenschaften zu rationalisieren. Dadurch erhielten wir ein tiefes Verständnis der oftmals alles andere als trivialen chemischen Verhaltensweisen der supramolekularen Strukturen, was den Weg zur Anwendung in neuartigen, optoelektronischen Technologien ebnet

Formulation and evaluation of captopril loaded polymethacrylate and hydroxypropyl methycellulose microcapsules

Angiotensin-converting enzyme (ACE) inhibitors are some of the most commonly prescribed medications for hypertension. They are cited in many papers as the treatment most often recommended by guidelines and favoured over other antihypertensive drugs as first-line agents especially when other high-risk conditions are present, such as diabetic nephropathy. The development of captopril (CPT) was amongst the earliest successes of the revolutionary concept of structure-based drug design. Due to its relatively poor pharmacokinetic profile or short half-life of about 1 hour, the formulation of sustained-release microcapsule dosage form is useful to improve patient compliance and to achieve predictable and optimized therapeutic plasma concentrations. Currently, CPT is mainly administered in tablet form. One of the difficulties of CPT formulation has been reported to be its instability in aqueous solutions. CPT is characterized by a lack of a strong chromophore and, therefore, not able to absorb at the more useful UV–Vis region of the spectrum. For this reason, an accurate, simple, reproducible, and sensitive HPLC-ECD method was developed and validated for the determination of CPT in dosage forms. The method was successfully applied for the determination of CPT in commercial and developed formulations. Possible drug-excipient and excipient-excipient interactions were investigated prior to formulating CPT microcapsules because successful formulation of a stable and effective solid dosage form depends on careful selection of excipients. Nuclear magnetic resonance spectroscopy, Fourier transform infra-red spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used for the identification and purity testing of CPT and excipients. The studies revealed no thermal changes during stress testing of binary and whole mixtures which indicate absence of solid state interactions. There were no shifts, appearance and disappearance in the endothermic or exothermic peaks and on the change of other associated enthalpy values on thermal curves obtained with DSC method. Characteristic peaks for common functional groups in the FT-IR were present in all the mixtures indicating the absence of incompatibility. The techniques used in this study can be said to have been efficient in the characterization and evaluation of the drug and excipients. The technique of microencapsulation by oil-in-oil was used to prepare CPT microcapsules. The effects of polymer molecular weight, homogenizing speed on the particle size, flow properties, morphology, surface properties and release characteristics of the prepared CPT microcapsules were examined. In order to decrease the complexity of the analysis and reduce cost response surface methodology using best polynomial equations was successfully used to quantify the effect of the formulation variables and develop an optimized formulation thereby minimizing the number of experimental trials. There was a burst effect during the first stage of dissolution. Scanning electron microscopy (SEM) results indicated that the initial burst effect observed in drug release could be attributed to dissolution of CPT crystals present at the surface or embedded in the superficial layer of the matrix. During the preparation of microcapsules, the drug might have been trapped near the surface of the microcapsules and or might have diffused quickly through the porous surface. The release kinetics of CPT from most formulations followed Fickian diffusion mechanism. SEM photographs showed that diffusion took place through pores at the surface of the microcapsules. The Kopcha model diffusion and erosion terms showed predominance of diffusion relative to swelling or erosion throughout the entire test period. Drug release mechanism was also confirmed by Makoid-Banakar and Korsmeyer-Peppas models exponents which further support diffusion release mechanism in most formulations. The models postulate that the total of drug release is a summation of a couple of mechanisms; burst release, relaxation induced controlled-release and diffusional release. Inspection of the 2D contour and 3D response surfaces allowed the determination of the geometrical nature of the surfaces and further providing results about the interaction of the different variables used in central composite design (CCD). The wide variation indicated that the factor combinations resulted in different drug release rates. Lagrange, canonical and mathematical modelling were used to determine the nature of the stationery point of the models. This represented the optimal variables or stationery points where there is interaction in the experimental space. It is difficult to understand the shape of a fitted response by mere inspection of the algebraic polynomial when there are many independent variables in the model. Canonical and Lagrange analyses facilitated the interpretation of the surface plots after a mathematical transformation of the original variables into new variables. In conclusion, these results suggest the potential application of Eudragit® / Methocel® microcapsules as suitable sustained-release drug delivery system for CPT

Carbon Nanotubes for Electronics and Energy

Ever since their discovery, carbon nanotubes have been touted as a new material for the future and a correspondingly lengthy list of possible applications are often cited in the literature. This excitement for carbon nanotubes is a result of their richly varying physical, electronic and optical properties, where it is possible to have single, double and multiple carbon walls with each wall potentially being either semiconducting or metallic and possessing unique optical transitions covering the ultraviolet to infrared spectral range. However, to date the realization of many of the proposed applications has been hindered by exactly the characteristic that made carbon nanotubes so attractive in the first place, namely the inherent inhomogeneity and varying properties of as-prepared or grown material. In order to become a true advanced material of the future, methods to prepare carbon nanotubes with defined length, wall number, diameter, electronic and optical property are necessary. Additionally, such methods to sort carbon nanotubes must afford high purity levels, be amenable to large-scale preparation and be compatible with subsequent integration into device architectures. In this work these issues are addressed with the use of gel based sorting techniques, which with the use of an automated gel permeation system allows for the routine preparation of milligram quantities of metallic and semiconducting carbon nanotubes, chirality pure single walled carbon nanotubes and even double walled carbon nanotubes sorted by their outer-wall electronic type. Having developed techniques to prepare large quantities, methodologies to control the order and orientation of this 1 D nanomaterial on the macro scale are developed. Inks of carbon nanotubes with liquid crystal concentrations and aligned films thereof are developed and this newfound control over the electronic and structural property opened the door for energy related applications. For example the use of thin films as the transparent electrodes in silicon:carbon nanotube solar cells or as the light harvesting layer in combination with fullerenes with the goal of creating an all carbon solar cell. Likewise on the few nanotube level the unique optical transitions of different nanotube chiralities are used in the fabrication of nanoscale photosensitive elements

PhD students´day FMST 2023

The authors gave oral presentations of their work online as part of a Doctoral Students’ Day held on 15 June 2023, and they reflect the challenging work done by the students and their supervisors in the fields of metallurgy, materials engineering and management. There are 82 contributions in total, covering a range of areas – metallurgical technology, thermal engineering and fuels in industry, chemical metallurgy, nanotechnology, materials science and engineering, and industrial systems management. This represents a cross-section of the diverse topics investigated by doctoral students at the faculty, and it will provide a guide for Master’s graduates in these or similar disciplines who are interested in pursuing their scientific careers further, whether they are from the faculty here in Ostrava or engineering faculties elsewhere in the Czech Republic. The quality of the contributions varies: some are of average quality, but many reach a standard comparable with research articles published in established journals focusing on disciplines of materials technology. The diversity of topics, and in some cases the excellence of the contributions, with logical structure and clearly formulated conclusions, reflect the high standard of the doctoral programme at the faculty.Ostrav

Rapid Separation of Enantiomeric Impurities in Chiral Molecules by a Self-Referential Weak Measurement System

We propose a self-referential fast detection scheme for a frequency domain weak measurement system for the detection of enantiomeric impurities in chiral molecules. In a transmissive weak measurement system, the optical rotation (OR) is used to modify the pre-selected polarization state and the post-selection polarization state. We obtained the sum and difference of the optical rotations produced by the sample and the standard by rotating the quarter wave plate in the system. Then, we estimate the ratio of chiral molecules to enantiomeric impurities using the ratio of the central wavelength shifts caused by the addition and subtraction states described above. In this paper, our system has an optical resolution of 1.88 &#215; 10&#8722;5&#176;. At the same time, we completed the detection of the ratio of the two substances in the mixture of L-proline and D-proline in different proportions, which proved that our system can quickly detect the content of enantiomeric impurities in chiral molecules