A major challenge affecting the likelihood of a new drug reaching the market is poor oral bioavailability derived from low aqueous solubility. Nanocrystals are rapidly becoming a platform technology to address poor solubility issues, although several challenges including stabilisation and control of particle size distribution for nanosuspensions still need to be addressed. The aim of this study was to revisit the simplest approach of re-precipitation and to identify the critical parameters, including the effect of different stabilisers as well as process conditions. We utilised a combined approach of both experiments and molecular modelling and simulation, not only to determine the optimum parameters but also to gain mechanistic insight. The experimental studies utilised three rather distinct, relatively insoluble drugs, the hypoglycaemic glibenclamide, the anti-inflammatory ibuprofen, and the anti-malarial artemisinin. The choice of crystal growth inhibitors/stabilizers was found to be critical and specific for each drug. The effect of the process variables, temperature, stirring rate, and the solute solution infusion rate into the anti-solvent, was rationalized in terms of how these factors influence the local supersaturation attained at the earliest stages of precipitation. Coarse grained simulation of antisolvent crystallisation confirmed the accepted two step mechanism of nucleation at high supersaturation which involves aggregation of solute particles followed by nucleation. Recovery of nanocrystals from nanosuspensions is also a technical challenge. A novel approach involving the use of carrier particles to recovery the nanocrystals was developed and shown to be able to recover more than 90% of the drug nanocrystals. The phase stability of nanocrystals along with bulk crystals for the model compound glycine was explored using molecular dynamics simulation. The simulations were consistent with experimental data, a highlight being the ¿ phase transforming to the ¿ phase at temperature >400K and 20kbar respectively, as expected. Nanocrystals of ¿, ¿ and ¿ glycine, however did not show any phase transformation at high temperature. In summary the study demonstrates that standard crystallization technology is effective in producing nanocrystals with the primary challenge being physico-chemical (rather than mechanical), involving the identification of molecule-specific crystal growth inhibitors and/or stabilizers. The developed nanocrystal recovery method should enable the production of nanocrystals-based solid dosage forms. The molecular simulation studies reveal that crystal-crystal phase transformations can be predicted for hydrogen-bonded systems. / HEC Pakistan and University of Malakand KP (Khyber Pakhtunkhwa)

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No description available.

Plasticizers are a commonly used additive used in the polymer industry to make the plastic more pliable by reducing the glass transition temperature, Tg and Young's modulus, Y. As the plasticizer aids in polymer process-ability and making it suitable for applications from industrial cables to sensitive medical equipment, the mechanism of plasticization is not fully understood. There are three theories used to explain plasticization: lubricity theory, gel theory, and free volume theory. The latter is a fundamental concept of polymer science that is used to calculate many polymer properties, but they all do not give a clear picture on plasticization. With molecular dynamics (MD) simulation, a coarse-grained (CG) model - which consist of a simple bead-spring model that generalizes particles as a bead and connects them via a finite spring – is used to explore the impact of plasticizer size throughout the polymer system. The interaction characteristics of the plasticizer is explored by representing the plasticizer molecules as a single bead of varying size. This gives better control on the variability of the mixture and pinpoint the significant contributions to plasticization. A path to understanding the the mechanism of plasticization will give insight in glass formation, and can later be used to find an optimal plasticizer architecture to minimize the migration of the additive by tuning the compatibility. Current results show a decoupling between the Tg and Y of the polymer-additive system. The overall understanding of finite-size effects shows: as additive of increasing size is added, the polymer free volume increases which in-turn would decrease the Y, but Tg is shown to increase because the polymer and additive are not as mobile to reduce caging effect of monomeric units. / Thesis / Master of Applied Science (MASc)

No description available.

Yes / The use of peptides to nucleate, grow, and stabilize nanoparticles in aqueous media via non-covalent interactions offers new possibilities for creating functional, water-dispersed inorganic/organic hybrid materials, particularly for Au nanoparticles. Numerous previous studies have identified peptide sequences that both possess a strong binding affinity for Au surfaces and are capable of supporting nanoparticle growth in water. However, recent studies have shown that not all such peptide sequences can produce stable dispersions of these nanoparticles. Here, via integrated experiments and molecular modeling, we provide new insights into the many factors that influence Au nanoparticle growth and stabilization in aqueous media. We define colloidal stability by the absence of visible precipitation after at least 24 hours post-synthesis. We use binding affinity measurements, nanoparticle synthesis, characterization and stabilization assays, and molecular modeling, to investigate a set of sequences based on two known peptides with strong affinity for Au. This set of biomolecules is designed to probe specific sequence and context effects using both point mutations and global reorganization of the peptides. Our data confirm, for a broader range of sequences, that Au nanoparticle/peptide binding affinity alone is not predictive of peptide-mediated colloidal stability. By comparing nanoparticle stabilization assay outcomes with molecular simulations, we establish a correlation between the colloidal stability of the Au nanoparticles and the degree of conformational diversity in the surface-adsorbed peptides. Our findings suggest future routes to engineer peptide sequences for bio-based growth and dispersion of functional nanoparticles in aqueous media. / Air Office of Scientific Research, grant number FA9550-12-1-0226.

Organic conjugated polymers (CPs) are emerging materials for advanced electronic applications such as organic photovoltaics (OPVs), field-effect transistors (OFETs), light-emitting diodes (OLEDs), flexible and wearable electronics, and biomedicals. High-spin donor-acceptor CPs have been investigated for their potential applications in magnetic and spintronic devices. Inter-chain charge transfer among these high-spin polymers mainly depends on the nature of the local structure of the thin film and pi-stacking between the polymer chains. However, the microscopic structural details of high-spin polymeric materials are rarely studied, especially in the liquid phase, and remain largely unexplored. This study examined the effects of oligomer chain length, side chain, and processing temperature on the organization of the high-spin cyclopentadithiophene-benzobisthiadiazole donor-acceptor conjugated polymer in chloroform solvent. We have found that the oligomers exhibit ordered aggregation based on chain length, with an average pi-stacking distance of 3.38±0.03 (angstrom), aligning well with the experiment. During the solution processing of CPs, smart polymers are widely used for controlling the device performance. Polymethyl-methacrylate (PMMA) is a smart polymer exhibiting solvation behavior in aqueous alcohol mixtures that is different from individual solvents. However, a thorough understanding of the microscopic details underlying PMMA cosolvency remains elusive, which is essential for tailoring smart polymers for advanced applications. Using molecular dynamics simulation, this study elucidates the PMMA's cosolvency behavior in a binary mixture of aqueous tert-butanol and successfully captures the re-collapsing behavior observed experimentally. We have observed that the excess hydrogen bonding between PMMA and water mimics the re-collapsing pattern, suggesting a key role in PMMA's cosolvency. Efforts to discover new organic molecules are hindered by the vast chemical space. Machine learning (ML) approaches offer a promising solution to accelerate the development of new materials. However, predicting properties accurately with ML models typically involves high computational costs and complexity. This study employs a first-generation ML model, ridge regression, to predict the electronic properties — electronic gap, HOMO, LUMO, and singlet-triplet gap of pi-conjugated organic molecules. This research provides molecular-level insights to control device performance by managing aggregation in thin films and reduces the effort required to screen for desirable organic CPs. These findings will facilitate the development of new organic molecules tailored for advanced electronic devices.

Le stockage géologique du carbone dans les veines de charbon est une solution transitoire pour lutter contre le réchauffement climatique. La faisabilité de ce stockage à un coût abordable reste incertaine, en particulier parce que l'injection de dioxide de carbone dans les veines de charbon est lente. Les projets pilotes ont montré que la perméabilité du réservoir diminue lors de l'injection, suite au gonflement du charbon induit par l'adsorption préférentielle du dioxyde de carbone par rapport au méthane présent naturellement. Ce mémoire de thèse est consacré à l'étude de ce gonflement. Un premier travail théorique a consisté à étendre les équations constitutives de poromécanique classique dans les cas où l'adsorption sur des surfaces ou dans des micropores devient significative. Nous avons montré que le comportement poromécanique du solide ne peut être compris que si la dépendance de l'adsorption en fonction de la déformation du milieu poreux est connue. Le couplage entre adsorption et déformation est peu étudié dans la littérature et difficile à mesurer expérimentalement. Dans ce travail, nous avons utilisé la simulation moléculaire qui permet facilement de contrôler indépendamment la pression du fluide adsorbé et la déformation du milieu poreux. A l'aide de simulations moléculaires d'adsorption dans des systèmes modèles unidimensionnels, nous avons validé les nouvelles équations consitutives. Nous avons montré également que l'adsorption peut dépendre de la déformation de façon complexe et qu'elle est très sensible à la structure des micropores. Les résultats de simulations moléculaires d'adsorption dans un modèle moléculaire réaliste de la matrice organique du charbon nous ont permis de montrer que le gonflement du charbon en présence de fluide peut être expliqué par l'adsorption dans les micropores, mais pas dans les mésopores. Nous avons étudié numériquement le couplage entre adsorption et déformation dans le charbon. Le gonflement estimé en associant les simulations moléculaires d'adsorption aux nouvelles équations constitutives de poromécaniques est en bon accord avec les mesures expérimentales. De même, nous avons simulé l'adsorption de mélanges de dioxide de carbone et de méthane dans le charbon à des températures et pressions représentatives des conditions souterraines. Le résultat de ces simulations a permis d'estimer le gonflement différentiel durant l'injection de carbone pour des veines de charbon à différentes profondeurs. / Pas de résumé en anglais

Mass transfer intervening during the process of immersion influences the final composition of the product. These transfers primarily depend on the size of the immersed products, as well as temperature, the concentration and the nature of the solution of immersion. The main objective of this work is to study the mass transfer phenomena (water loss and solid gain) in solid/liquid system constituted of vegetable product (eggplant) immerged in salt solution. We determined the kinetic studies of eggplant in different salts solutions with two concentrations (saturation and 20%) at 3°C. The physicochemical properties of solution and salt such as molar concentration, molecular weight and ionic type affected the mechanism of water loss and solid gain. Knowledge about interaction ions/vegetable pectin is important for new product formulation. Determination of partition coefficient of ion in equilibrium system showed that the main physicochemical properties of ions and solution are ionic radius, electronegativity, ionic force and molar concentration. Mathematical predictive model was developed to predict the partition coefficient of ions in food/ solution system. Molecular dynamics simulations using a dynamic force field have been carried out to investigate the absorption of ions (K+, Na+, Ca2+, Mg2+, Cl-) in pectin/water/ion/aqueous solution system. Four systems were used. The results showed that the ionic type (cation and anion) influence the type and number of interactions between pectin-ion and water-ion and then offered an explicit description transfer phenomena and distribution of ions in the system solid/liquid / Les transferts de matière intervenant au cours du procédé d’immersion dépendent essentiellement de la taille des produits immergés, la température, la concentration et la nature de la solution d'immersion. L’objectif principal de ce travail porte sur l’étude des transferts dans un système solide/liquide constitué d’un produit végétal (aubergine) et d’une solution saline. Afin de parvenir à une bonne maîtrise de ces paramètres, les études cinétiques ont été conduites à 3°C sur des aubergines immergées dans des solutions salines avec deux concentrations. Les propriétés des solutions et des sels telles que la concentration molaire, la masse molaire et surtout la nature ionique influencent le mécanisme de perte et de gain. Les connaissances sur les interactions ions/pectines végétaux sont importants pour la formulation de nouveaux produits La détermination du coefficient de partage des ions à l’équilibre dans le système aubergine/solution ont montré que les principales propriétés des ions et des solutions influençant le coefficient de partage sont le rayon ionique, l’électronégativité, la force ionique et la concentration molaire. Un modèle mathématique a permis de prédire le coefficient de partage des ions dans ce système. Dans le but d’expliquer l’absorption des ions par la phase solide, une simulation par dynamique moléculaire a été menée sur un système pectine-eau-sels. Quatre systèmes ont été utilisés. Les résultats obtenus ont montré que la nature ionique influencent la nature et le nombre d’interaction entre pectine-ion et eau-ion et donc offrent une description explicite des phénomènes de transferts et distribution des ions dans le système solide/liquide

The outstanding properties of carbon nanotubes (CNTs) have stimulated a large number of researches to explore the potential of using them as reinforcement in polymer composites. Although many studies have reported the enlighten improvement of the materials properties by using CNTs as reinforcement, there are no promising and optimal results have been concluded to date. This thesis aims at studying the mechanical properties on thermoset polymer, Epoxy, by employing a small amount of carbon nanotubes as reinforcement. Two different types of nanotube-based composites are prepared i.e. a raw single-walled carbon nanotube (SWNT) composites and a functionalized single-walled carbon nanotube (FSWNT) composite. Chemical functionalization on SWNTs with carboxyl functional group (COOH) aims at modifying the end caps of nanotubes, so to provide covalent bonding of SWNTs to the polymer matrix during manufacturing of composite systems. Different weight percentages (wt %) of each type of SWNTs are added into the composite system. Standard test methods are performed on these nanotube composite systems and satisfactory results were achieved when the weight percentages of both types of SWNTs increased. Through the comparison between two systems (raw SWNTs and FSWNTs), the FSWNT reinforced composite is found to provide a better improvement on the mechanical properties as compared with the SWNT reinforced system. The integrity of both composite systems is examined by using Scanning Electronic Microscopy (SEM). The SEM images of the composites indicated the derivation in wetting and bonding between the nanotubes (both SWNTs and FSWNTs) and epoxy resin, and the FSWNTs provide an eminent dispersion when compared with the SWNTs in the composite system. Moreover, thermal testings are employed to further investigate the interfacial interaction between the nanotubes and the polymer matrix. xiv Molecular Dynamics (MD) simulations are also carried out to investigate the structural change of a SWNT under different temperature-controlled manufacturing environments. Swivel of the SWNT was noticed as the temperature increased. Such alteration in structure form can provide physical interlocking between SWNT and its surrounding polymer system. Thus, its overall mechanical and thermal properties can be enhanced.