Estimation of in-situ fluid properties from the combined interpretation of nuclear, dielectric, optical, and magnetic resonance measurements

During the last few decades, the quantification of hydrocarbon pore volume from borehole measurements has been widely studied for reservoir descriptions. Relatively less effort has been devoted to estimating in-situ fluid properties because (1) acquiring fluid samples is expensive, (2) reservoir fluids are a complex mixture of various miscible and non-miscible phases, and (3) they depend on environmental factors such as temperature and pressure. This dissertation investigates the properties of fluid mixtures based on various manifestations of their electromagnetic properties from the MHz to the THz frequency ranges. A variety of fluids, including water, alcohol, alkane, aromatics, cyclics, ether, and their mixtures, are analyzed with both laboratory experiments and numerical simulations. A new method is introduced to quantify in-situ hydrocarbon properties from borehole nuclear measurements. The inversion-based estimation method allows depth-continuous assessment of compositional gradients at in-situ conditions and provides thermodynamically consistent interpretations of reservoir fluids that depend greatly on phase behavior. Applications of this interpretation method to measurements acquired in two field examples, including one in a gas-oil transition zone, yielded reliable and verifiable hydrocarbon compositions. Dielectric properties of polar liquid mixtures were analyzed in the frequency range from 20 MHz to 20 GHz at ambient conditions. The Havriliak-Negami (HN) model was adapted for the estimation of dielectric permittivity and relaxation time. These experimental dielectric properties were compared to Molecular Dynamics (MD) simulations. Additionally, thermodynamic properties, including excess enthalpy, density, number of hydrogen bonds, and effective self-diffusion coefficient, were computed to cross-validate experimental results. Properties predicted from MD simulations are in excellent agreement with experimental measurements. The three most common optical spectroscopy techniques, i.e. Near Infrared (NIR), Infrared, and Raman, were applied for the estimation of compositions and physical properties of liquid mixtures. Several analytical techniques, including Principal Component Analysis (PCA), Radial Basis Functions (RBF), Partial Least-Squares Regression (PLSR), and Artificial Neural Networks (ANN), were separately implemented for each spectrum to build correlations between spectral data and properties of liquid mixtures. Results show that the proposed methods yield prediction errors from 1.5% to 22.2% smaller than those obtained with standard multivariate methods. Furthermore, the errors can be decreased by combining NIR, Infrared, and Raman spectroscopy measurements. Lastly, the ¹H NMR longitudinal relaxation properties of various liquid mixtures were examined with the objective of detecting individual components. Relaxation times and diffusion coefficients obtained via MD simulations for these mixtures are in agreement with experimental data. Also, the ¹H-¹H dipole-dipole relaxations for fluid mixtures were decomposed into the relaxations emanate from the intramolecular and intermolecular interactions. The quantification of intermolecular interactions between the same molecules and different molecules reveals how much each component contributes to the total NMR longitudinal relaxation of the mixture as well as the level of interactions between different fluids. Both experimental and numerical simulation results documented in this dissertation indicate that selecting measurement techniques that can capture the physical property of interest and maximize the physical contrasts between different components is important for reliable and accurate in-situ fluid identificationPetroleum and Geosystems Engineerin

Hyaluronic Acid: Its Versatile Use in Ocular Drug Delivery with a Specific Focus on Hyaluronic Acid-Based Polyelectrolyte Complexes.

Extensive research is currently being conducted into novel ocular drug delivery systems (ODDS) that are capable of surpassing the limitations associated with conventional intraocular anterior and posterior segment treatments. Nanoformulations, including those synthesised from the natural, hydrophilic glycosaminoglycan, hyaluronic acid (HA), have gained significant traction due to their enhanced intraocular permeation, longer retention times, high physiological stability, inherent biocompatibility, and biodegradability. However, conventional nanoformulation preparation methods often require large volumes of organic solvent, chemical cross-linkers, and surfactants, which can pose significant toxicity risks. We present a comprehensive, critical review of the use of HA in the field of ophthalmology and ocular drug delivery, with a discussion of the physicochemical and biological properties of HA that render it a suitable excipient for drug delivery to both the anterior and posterior segments of the eye. The pivotal focus of this review is a discussion of the formation of HA-based nanoparticles via polyelectrolyte complexation, a mild method of preparation driven primarily by electrostatic interaction between opposing polyelectrolytes. To the best of our knowledge, despite the growing number of publications centred around the development of HA-based polyelectrolyte complexes (HA-PECs) for ocular drug delivery, no review articles have been published in this area. This review aims to bridge the identified gap in the literature by (1) reviewing recent advances in the area of HA-PECs for anterior and posterior ODD, (2) describing the mechanism and thermodynamics of polyelectrolyte complexation, and (3) critically evaluating the intrinsic and extrinsic formulation parameters that must be considered when designing HA-PECs for ocular application

Unconstrained Global Optimization of Molecules on Surfaces: From globally optimized structures to scanning-probe data

The adsorption of molecules on a surface plays a vital role in heterogeneous catalysis. For a proper unterstanding of the reaction mechanisms involved, the adsorption ge ometry of the molecules on the surface needs to be known. So far, experimental data from tunneling microscopes and spectroscopy, such as STM and IRAS are the main ways to obtain such knowledge. Due to the vast search space of adsorption geometries, especially for oligomers, optimizations using ab initio methods can be used to confirm the experimental data only if good initial guesses are available. Global optimization can serve two purposes in these situations. On the one hand it allows for a thorough investigation of the given search space, which can provide good initial guesses for subsequent high-level structural refinements. On the other hand, given a known reaction mechanism, it could also be used to find catalysts that influence e.g. the relevant bonds. With respect to this idea the topic of this thesis is to find a local optimization method cheap enough such that the total computational cost of global optimization does not exceed availability and yet good enough that the results are meaningful to the problem at hand. With this in mind multiple force field and semiempirical methods have been tested and evaluated mainly on benzene, acetophenone and ethyl pyruvate on Pt(111) surfaces. Some other adsorbates have also been tested shortly. In addition to these global optimization results, DFT geometry optimizations of ethyl pyruvate on Pt(111) have been performed and the structures of the best adsorption geometry from global optimization and from DFT are compared. Furthermore, from the DFT data STM images have been calculated that are compared to experimental results. The theoretical and experimental STM images agree well

Structural Studies of Superacidic Systems Using Neutron and High Energy X-ray Diffraction

The structure of two superacids in the liquid phase, hydrogen fluoride and fluorosulfuric acid, have been determined by neutron and high energy X-ray diffraction in this study. In addition the structure of a molecular Lewis acid, BF3, has been determined for the liquid state as well as the supercritical state. Experiments were also performed on solutions of the hydronium ion in fluorosulfuric acid by neutron and X-ray diffraction as well as by Raman spectroscopy. In addition this thesis presents the design and construction of sample cells for neutron and X-ray scattering experiments and the design and construction of a high vacuum/fluorine line capable of handling hydrogen fluoride as well as other fluorine containing species

Molecular aggregation of thiols and alcohols: study of non-covalent interactions by microwave spectroscopy

El estudio y comprensión de las interacciones no covalentes a nivel molecular es un campo que está en continuo desarrollo y cobra vital importancia para determinar el comportamiento estructural de muchas moléculas de interés químico, tecnológico o biológico. En esta tésis doctoral se han analizado las interacciones intermoleculares implicadas en la formación de agregados moleculares neutros, tanto dímeros como productos de microsolvatación, en fase gas. Los complejos intermoleculares se han generado mediante expansiones supersónicas pulsadas, caracterizándose posteriormente mediante espectroscopía de rotación. Este trabajo ha utilizado dos técnicas espectroscópicas, incluyendo un espectrómetro de microondas con transformada de Fourier (FTMW) de tipo Balle-Flygare en el rango de frecuencias 8-20 GHz, y un espectrómetro de transformada de Fourier de banda ancha con excitación multifrecuencia (CP-FTMW) cubriendo el rango espectral de 2-8 GHz. Los complejos intermoleculares estudiados han incluido moléculas con grupos alcohol y/o tiol, con objeto de analizar las diferencias entre las interacciones intermoleculares que implican átomos de oxígeno o azufre, en especial el enlace de hidrógeno. Se han estudiado moléculas incluyendo tanto sistemas cíclicos alifáticos (ciclohexanol, ciclohexanotiol) como aromáticos (furfuril alcohol, furfuril mercaptano, tienil alcohol, tienil mercaptano). Los enlaces de hidrógeno analizados han comprendido especialmente interacciones de tipo O-H···O, O-H···S y S-H···S. La formación de los complejos intermoleculares ha revelado en algunos de ellos una gran variedad conformacional, como la observación de seis isómeros del dímero de ciclohexanol. En el caso de los monohidratos se han observado en algunos casos desdoblamientos asociados a movimientos internos de gran amplitud, como la rotación de la molécula de agua en los monohidratos de ciclohexanol y tienil mercaptano. En los casos de moléculas quirales la dimerización ha permitido observar la estabilidad relativa de los diastereoisómeros homo o heteroquirales. El estudio experimental se ha completado con diferentes cálculos teóricos de orbitales moleculares, en especial teoría del funcional de la densidad, a fin de caracterizar las interacciones estructuralmente, energéticamente y mediante análisis topológico de la densidad electrónica. El conjunto de datos experimentales y teóricos permite aumentar la información existente sobre enlaces de hidrógeno con átomos de azufre, generalmente poco estudiados, y su comparación con los análogos oxigenados.The study and understanding of non-covalent interactions at molecular level is a field in continuous development and essential to determine the structural behavior of many molecules of chemical, technological or biological interest. In this PhD thesis, the intermolecular interactions involved in the formation of neutral molecular aggregates, both dimers and microsolvation products, have been analyzed in the gas phase. The intermolecular complexes were generated by pulsed supersonic expansions, and later characterized by rotational spectroscopy. This work has used two spectroscopic techniques, including a Balle-Flygare Fourier-Transform Microwave (FTMW) spectrometer in the 8-20 GHz frequency range, and a broadband Chirped-Pulse Fourier Transform Microwave (CP-FTMW) spectrometer covering the 2-8GHz spectral range. The intermolecular complexes studied have included molecules with alcohol and / or thiol groups, in order to analyze the differences between the intermolecular interactions involving oxygen or sulfur atoms, especially hydrogen bonds. Molecules that comprise both aliphatic (cyclohexanol) and aromatic (furfuryl alcohol, furfuryl mercaptan, thenyl alcohol, thenyl mercaptan) ring systems have been studied. The analyzed hydrogen bonds included especially O-H···O, O-H···S and S-H···S interactions. The formation of intermolecular complexes has revealed a great conformational diversity in some of them, such as the observation of six isomers of the cyclohexanol dimer. With regard to the monohydrates, tunnelling splittings associated with internal large amplitude motions have been observed in some cases, such as the rotation of the water molecule in the monohydrates of cyclohexanol, thenyl alcohol and thenyl mercaptan. In the case of chiral molecules, dimerization has made it possible to observe the relative stability of homo- or heterochiral diastereoisomers. The experimental study has been supported by different theoretical molecular orbital calculations, in particular Density Functional Theory (DFT) calculations, in order to characterize the interactions structurally, energetically and by a topological analysis of electron density. The set of experimental and theoretical data will advance the existing information on hydrogen bonds involving sulfur atoms, generally scarcely studied, and their comparison with the oxygenated analogues.Departamento de Química Física y Química InorgánicaDoctorado en Físic

An investigation of hydrogen bonded molecular systems using X-ray and neutron diffraction

The main focuses of this project have been investigations of a variety of hydrogen bonding systems for unusual behaviour such as disordered or migrating hydrogens/protons with both single crystal X-ray and neutron diffraction, crystallisation of a large number of molecular complexes of the chloranilic acid molecule, and examining the bifurcated hydrogen bond motif found in many of the chloranilic acid co-crystals discovered. The neutron single crystal diffraction instruments SXD and VIVALDI have been used to provide conclusive results in cases of suspected unusual hydrogen bond behaviour in molecular materials. 2,4-dihydroxybenzoic acid and its isomer 2,5-dihydroxybenzoic acid have been examined using X-ray and neutron diffraction to investigate possible disordered cooperative hydrogen bond systems. The energy difference of the three possible tautomers of 2,4-dihydroxybenzoic acid in different environments have been calculated in theoretical computations which concur with the neutron results. Single crystal neutron diffraction experiments were also carried out on isonicotinamidium formate, 2-iodoaniliium picrate, chloranilic acid 2,4-lutidine and malonic acid, where unusual behaviour in the hydrogen systems was also suspected. The molecular complexes of chloranilic acid with various pyridine-based molecules have been the main focus of the X-ray diffraction work of this thesis. Multiple crystallisations over a range of different conditions were set up for chloranilic acid with various series of molecules including lutidines (dimethylpyridines) and picolines (methylpyridines). This resulted in a large number of new crystal structures, determined by X-ray diffraction and all found to contain a bifurcated hydrogen bond motif producing two robust hydrogen-bonded supramolecular synthons. The investigation examines the bifurcated hydrogen bond interactions and the suitability of chloranilic acid complexes for crystal engineering. The two related supramolecular synthon units are discussed and difference Fourier maps and Hirshfeld surfaces used to examine the hydrogen bond architecture. Bromanilic acid co-crystals are also studied to examine the effect of the halogen in the crystal structures

Importance of Electrostatically Driven Non-Covalent Interactions in Asymmetric Catalysis

Computational chemistry has become a powerful tool for understanding the principles of physical organic chemistry and rationalizing and even predicting the outcome of catalytic and non-catalytic organic reactions. Non-covalent interactions are prevalent in organic systems and accurately capturing their impact is vital for the reliable description of myriad chemical phenomena. These interactions impact everything from molecular conformations and stability to the outcome of stereoselective organic reactions and the function of biological macromolecules. Driven by the emergence of density functional theory (DFT) methods that can account for dispersion-driven noncovalent interactions, there has been a renaissance in terms of computational chemistry shaping modern organic chemistry. DFT Studies of the origins of stereoselectivity in asymmetric organocatalytic reactions can not only provide key information on the mode of asymmetric induction, but can also guide future rational catalyst design. We start with an overview of weak intermolecular interactions and aromatic interactions. Special emphasis is given to the methods that one can use to study these ephemeral interactions. We next provide a brief account how computational chemistry has aided our understanding of chiral phosphoric acid (CPA) catalyzed reactions. Thereafter, three case studies showcasing the importance of non-covalent interactions in chiral NHC catalysis, CPA catalysis, and chiral nucleophilic catalysis has been elaborated. Each of these studies highlights the importance of electrostatically-driven non-covalent interactions in controlling reactivity and selectivity. Moreover, unprecedented activation modes are identified and new predictive selectivity models developed that can be used to rationalize the outcome of future reactions. Studying these reactions using state of art DFT methods, we aimed not only to contribute to the understanding of their selectivity and the importance of noncovalent interactions in catalysis, but also to bring a sound understanding that will enable the design of new reactions and better catalysts. Overall, this dissertation highlights the underappreciated role of electrostatic interactions in controlling reactivity and selectivity in asymmetric catalysis

STRUCTURE-PROPERTY RELATIONSHIPS IN TWO-COMPONENT LIQUIDS

This thesis tackles several two-component liquids where we currently have a poor understanding of their fundamental structures and influence on properties. A novel approach was taken to investigate hydrophobic interactions.1 Rather than studying the aqueous liquid, for which only very low hydrophobe concentrations are possible, the metastable glassy state formed by thermally annealing a H2O/C60 fullerene vapour deposit was examined. These ‘trapped solutions’ of fullerene in an amorphous solid water (ASW) matrix were prepared in newly built apparatus (Chapter 3) using deposition rates of about 5 H2O monolayers per second to give a total mass > 1 g without crystalline ice contamination. H2O desorption rate analysis indicated that the limits of ASW growth are associated with the influence of deposition rate on porosity and consequent decreases in deposit to cooling plate heat transfer with increasing deposit thickness. Characterisations by FT-IR, Raman, optical absorbance and photoluminescence spectroscopies, as well as by X-ray and neutron diffraction showed unexpected continual structural relaxation until their crystallisation to ice I at 150–160 K (Chapter 4).2 Contrary to Frank and Evans’s description of ‘iceberg’ hydration structures,3 for C60 in ASW there is a weakening of the average hydrogen bonding interaction and increases in dynamics of the first hydration layer. The present work tentatively supports theories of hydrophobic hydration forces involving a disconnection of water in the hydration shell from the extended hydrogen bonding network (Chapter 5).4-5 The intermolecular interactions in the chloroform–acetone (negative) and benzene–methanol (positive) azeotropes were investigated by Raman spectroscopy and neutron diffraction. Structural models of pure liquid chloroform and the chloroform-acetone azeotrope were prepared by Empirical Potential Structural Refinement6 of experimental data and described using radial distribution functions, spatial density functions, orientation correlation functions and Kirkwood correlation factors. These analyses revealed that ‘super dipole’ Cl3H - Cl3H - Cl3H self-associations in pure liquid chloroform (29 % molecules) may contribute to its good solvent quality and anaesthetic properties (Chapter 6),7 and that C2H6O - HCCl3 hydrogen bonding interactions are present in the chloroform-acetone azeotrope (Chapter 7). Through comparisons of radial distribution functions between ‘like’ and ‘unlike’ species in the azeotropes it is revealed that the azeotropic vapour pressure condition is not only characterised by the non-ideality of intermolecular interaction but also by significant deviations in mixing character from that of a regular mixture; the benzene-methanol azeotrope exhibit microscopic statistical demixing and the chloroform-acetone azeotrope exhibits transient complexation