Molekulárne systémy predstavujú jeden zo smerov súčasného výskumu nových nanoelektronických zariadení. Organické molekuly nachádzajú uplatnenie v rôznych aplikáciách, ako sú napríklad solárne články, displeje alebo kvantové počítače. Rast vysokokvalitných molekulárnych vrstiev s požadovanými vlastnosťami často vyžaduje využitie samousporiadavaných štruktúr, hlboké pochopenie rozhrania kovu a organických molekúl a tiež dynamiky rastu molekulárnych vrstiev. Predkladaná práca sa zaoberá predovšetkým samousporadanými štruktúrami bifenyl-dikarboxylovej kyseliny (BDA) na Cu (1 0 0) a Ag (1 0 0), ktoré boli skúmané v UHV s využitím STM, XPS a LEEM. V prípade BDA-Ag je podrobne opísaných niekoľko chemicky a štrukturálne odlišných molekulárnych fáz. Ďalej boli BDA a TCNQ molekuly skúmané na grafene pripravenom na Ir (1 1 1). Okrem toho sa organo-kovové systémy syntetizovali depozíciou atómov Ni a Fe s molekulami TCNQ a BDA. Záverečná časť tejto práce popisuje povrchovú syntézu grafénových nanoribonov (7-AGNR) na špecicky štrukturovanom substráte Au (16 14 15) z prekurzorových molekúl DBBA. Rekonštrukcia povrchu po raste bola analyzovaná pomocou STM a elektronické vlastnosti 7-AGNRs pomocou ARPES.

One of the main subjects of this thesis is to design a novel synthetic route to covalently functionalize carbon nanotubes with various molecules in a non-toxic way on both surface and suspension. Functionalized carbon nanotubes are of great interest in the field of molecular electronics, materials science and nano-bio applications because of their remarkable structural, chemical and physical properties. First, the single-walled carbon nanotubes are functionalized with gold nanoparticles by the route, which involves silanization and copper-free click chemistry (SPAAC). We characterize the functionalized nanotubes through XPS, IR and Raman spectroscopic techniques to identify the surface attachment of molecules after each step. We observe a drastic change in homogeneity and functionalization density of single-walled carbon nanotubes with gold nanoparticles concerning solvent through TEM. Employing the same route, biomolecules such as fluorescent dyes and single-stranded DNA molecules are integrated with SWNTs. Fluorescence lifetime analysis of AF647 functionalized SWNTs is reduced compared to free dye due to the fluorescence quenching phenomenon of carbon nanotubes. Functionalized SWNTs are characterized with FLIM, SEM, and Raman for better correlation at the same area of interest. Furthermore, the nanotubes are resolved at the nanoscale level through STORM imaging technique with a limited photon budget. Single-stranded DNA molecules of different lengths are used to investigate the fluorescence quenching as they are distance-dependent. DNA-PAINT is engaged in imaging the functionalized SWNTs with an unlimited photon budget, overcoming STORM's challenge. Lastly, the route is transferred to surface-grown CNTs through the CVD technique, in which both the gold nanoparticles and fluorescent dyes are grafted with nanotubes selectively. CVD is carried out on different substrates Si/SiO2, quartz substrate and quartz coverslip for substrate functionalization. Catalyst deposition plays a significant role in not only the CVD growth but also in the lifetime analysis of the substrate functionalized nanotubes. We observe similar fluorescence quenching of nanotubes in the substrate compared with nanotubes functionalized in suspension. Surface-grown nanotubes in the optically transparent substrate can be resolved through STORM at the nanoscale level. In conclusion, we demonstrate a synthetic design to functionalize SWNTs which provides the possibility to be versatile and non-toxic. Moreover, we show that the nanotubes can be functionalized through this route homogeneously and selectively on both surface and suspension. This work lays the foundation for tailoring SWNTs with not only a wide range of molecules and to study their functional characteristics but also to carry out functionalization on different substrates for various applications.

Thesis (M.Sc.(Chemistry)) -- University of Limpopo, 2020 / Breast cancer is a malignant tumour that starts in the cells of the breast. Many studies revealed aromatase (CYP19A1) and cyclin-dependent kinase 2 (CDK2) as possible therapeutic targets regarding breast cancer treatment, because they play crucial roles in anti-apoptotic processes during cell proliferation. Quinoxaline derivatives have attracted a great deal of attention due to their biological activities against fungi, virus, bacteria and cancer. Computer modelling was employed in order to reduce time and cost by searching the library of molecules and identifying those which are likely to bind to the drug target. A library of new one hundred (100) nitro and amino quinoxaline alkyne derivatives were successfully designed and screened against target proteins (CYP19A1 and CDK2) using virtual screening technique and thirteen (13) molecules were identified to be hit compounds against both targets with the docking score ranging from -6.143 to -8.372 kcal/mol as a measure of binding affinity. The hit compounds were subjected to IFD in order to identify tight binding through intermolecular interactions with active site residues of the binding pocket of the target proteins. All identified nitro and amino quinoxaline alkyne derivatives were successfully synthesised in a multi-step reaction sequence and their spectroscopic analysis (NMR, FTIR and MS) were in good agreement with the proposed structures in a good to moderate yield. The newly synthesised novel amino and nitro-quinoxaline derivatives were evaluated for anti-proliferative activity against breast cancer (MCF-7). Compound 59 showed to possess good inhibition against MCF-7 with an IC50 of 9.102 μM, whereas compounds 34, 54, 56 and 61 showed promising activity against MCF-7 with an IC50 value of < 50 μM. However, the MTT assay results showed that 59 was found to be toxic with an IC50 value of 0.205 μM against Raw 264.7 cell line. The dose response investigations showed that 31 and 34 have the promising anti-cancer activity against CYP19A and the correlation between molecular modelling (in-silico) and CYP19A inhibition activities (in- vitro), was established as compounds 31 and 34 were identified to bind to the drug target (CYP19A) with the docking score of -8.372 and 7.630 kcal/mol respectively. All the synthesized compounds were evaluated for the antitubercular activity against Mtb H37Rv strain as a secondary study. Compounds 57-62 with nitro-quinoxaline derivatives exhibited stronger inhibitory effects on Mtb H37Rv strain. In addition, compounds 60 and 62 were found to be most active against Mtb H37Rv with the high activity at MIC90 of <0.65 and <0.64 μM respectively. All active compounds are currently investigated for their cytotoxicity which have not been investigated before / National Research Foundation (NRF) and SASOL Inzalo Foundation

Dans cette thèse, la formation de monocouches auto-assemblées de différentes molécules de chalcogénure et de molécules p-conjuguées planaire et leurs caractéristiques structurelles et électroniques ont été systématiquement étudiées principalement par spectroscopie photoélectronique à rayons X effectuée utilisant la lumière synchrotron, microscopie à effet tunnel à balayage et diffraction d'électrons à faible énergie. Une étude de la formation de structures hybrides organiques-inorganiques auto-assemblées a été réalisée par assemblage couche par couche d'un dithiol sur ZnO (0001) avec dépôt de métal intermédiaire. De plus en complément de l'étude des molécules comportant un atome de chalcogènure, les caractéristiques d'adsorption du sélénium et du soufre ont été étudiées. La spectroscopie XPS à haute résolution et la spectroscopie de structure fine d’absorption au seuil d’excitation (NEXAFS) ont permis d'étudier les caractéristiques des monocouches auto-assemblées du sélénure de benzène et du sélénophène sur Cu (100) et dihexyldiselénure sur Ni (111) et Pd (111) et ont montré en particulier l’existence de processus de rupture de liaison Se-C ainsi que l’existence de différents sites d'adsorption de molécules. Ces conclusions ont été soutenues par l'étude de l'adsorption atomique du sélénium, qui montre également l'existence de différents sites d'adsorption pour le Se atomique avec différents environnements chimiques. Ces conclusions sont principalement basées sur une étude XPS haute résolution des spectres caractéristiques Se3d, Se3p, du spectre de bande de valence et de l'imagerie LEED. La formation de monocouche de 5,5-bis (mercaptéthyl) -2,20-bipyridine (BPD) avec terminaison SH libre sur ZnO(0001) a été démontrée, permettant le greffage ultérieur d'Ag et Ni et de l’ assemblage d’une autre couche de BPD sur cette couche de métal-dithiol. Les changements dans les propriétés électroniques ont été déterminés à partir des spectres de la bande de valence. La molécule π-conjuguée, NTCDA, a été déposée sur différentes surfaces métalliques et sa morphologie structurelle et ses propriétés chimiques par rapport à la surface métallique ont été étudiées. Les molécules NTCDA affichent une structure « couchée » avec deux domaines différents sur Ag (110) et Cu (100) mais trois domaines sur la surface de Cu (111). Par rapport à celui sur la surface inerte de Au, une forte interaction entre les molécules et les substrats de Cu, Ag existe et joue un rôle important dans la détermination de l'orientation et de l'état de liaison des films organiques. / In this thesis, the formation of self-assembled monolayers of different chalcogenide molecules and planer π-conjugated molecules and their electronic and structural characteristics were systematically studied mainly by synchrotron based X-ray photoelectron spectroscopy, scanning tunneling microscopy and low energy electron diffraction. A study of formation of hybrid organic-inorganic self assembled structure was performed by layer by layer assembly of a dithiol on ZnO(0001) with intermediate metal deposition. Additionally as a complement to the study of chalcogen head group molecules the adsorption characteristics of selenium and sulfur were investigated. The high resolution XPS and near edge absorption fine structure spectroscopy allowed to investigate the characteristics of self-assembled monolayers of benzene selenide and selenophene on Cu (100), and dihexyldiselenide on Ni(111) and Pd(111) and showed in particular the existence of Se-C bond breaking processes and existence of different adsorption sites of molecules. These conclusions were supported by the study of atomic selenium adsorption, which also shows existence different adsorption sites for the atomic Se with different chemical environments. These conclusions are mainly based on high resolution XPS study of characteristic Se3d, Se3p spectra, valance band spectrum and LEED imaging. The formation of a 5,5- bis (mercaptomethyl)-2,20- bipyridine (BPD) with SH termination on ZnO(0001) was demonstrated allowing subsequent grafting of Ag and Ni and further assembly of BPD on this metal-dithiol layer. The changes in electronic properties were determined from valence band spectra. The large π-conjugated molecule, NTCDA, was deposited on different metal surfaces and its structure morphology and chemical properties with respect to the metal surface was investigated. The NTCDA molecules displays a lying down structure with two different domains on Ag (110) and Cu(100) but three domain on Cu(111) surface. Compared with the one on the inert Au surface, a strong interface interaction between the molecules and Cu, Ag substrates plays an important role in determining the orientation and bonding state of the organic films.

PhD (Chemistry) / Department of Chemistry

MSc (Chemistry) / Department of Chemistry

MSc (Chemistry) / Department of Chemistry / The computational study of biologically active molecules is particularly important for drug development because it provides crucial information about the properties of a molecule, which determine its biological activities. The current work considers the results of a computational study of myristinin A and a structurally-related molecule (2-(4-hydroxyphenyl)-4-[2,4,6-trihydroxy-3-(9tetradecenoyl)phenyl]-3,4-dihydro-2H-benzopyran-7-ol, here denoted as DBPO). The two compounds pertain to the class of acylphloroglucinols. They were firstly isolated from Horsfieldia amygdaline, and they exhibit a variety of biological activities, including potent anti-inflammatory activity, potent DNA-damaging activity and DNA-polymerase ß inhibition. Their molecular structures differ only by the acyl chain. Both molecules have a bulky substituent meta to the acyl group consisting of a ring system (2-(4-hydroxyphenyl)-3,4-dihydro-2H-chromen-7-ol). The DBPO molecule can exist as cis and trans isomers in relation to the double bond present in the R chain, and both isomers are here investigated individually. The OHs ortho to the acyl group can form an intramolecular hydrogen bond (referred to as the first IHB) with the sp2 O atom of the acyl group. The phenol OHs neighbouring the substituent ring system can form O–Hπ interaction with the aromatic rings of the substituent, if suitable oriented. This study focuses on the identification of the stable conformers of these molecules (considering all the possible geometries obtainable by rotations about relevant single bonds), and of the factors stabilising the conformers. Full-optimisation calculations were performed in vacuo and also in three conveniently selected solvents. The results show that the dominant stabilising factors are the first IHB and the O–Hπ interactions. Other factors which have significant influence on conformational preferences are the orientation of the ring systems of the substituent, the orientation of the OHs on substituent, the mutual orientation of the OHs of the phloroglucinol moiety and also the orientation of the acyl chain. The results in solution are consistent with the findings of other acylphloroglucinols, for instance, the narrowing of the energy gaps and the increase of the dipole moment with the increase of solvent polarity. / NRF

Les microARN (miARN) constituent une classe de petits ARN non-codants qui jouent un rôle clé dans la régulation de l’expression des gènes au niveau post-transcriptionnel. De nombreuses études ont démontré que la surexpression de certains miARN est liée au développement de plusieurs types de cancer. C’est pour cette raison les miARN représentent une nouvelle classe de cibles thérapeutiques à haute potentielle. Dans ce contexte, l’objectif de mon travail de thèse était la découverte de nouveaux inhibiteurs de la production de miARN oncogène. Dans ce but, j’ai suivi deux approches, différentes mais complémentaires : (i) le criblage d’une petite librairie de composés et (ii) la conception et la synthèse de nouveaux conjugués en tant que ligands de précurseurs de miARN (pré-miARN). En particulier, nous avons ciblé les miARN-372 et -373 qui sont oncogènes dans plusieurs cancers, tels que le cancer gastrique. Nous avons ainsi démontré que certains des composés criblés ou synthétisés sont capables de se lier efficacement à la structure secondaire en tige-boucle de pré-miARN avec une haute affinité, conduisant à l’inhibition de la production des miARNs correspondants. Par ailleurs, nous avons montré que certains composés possèdent une activité anti-proliférative spécifique pour les cellules de cancer gastrique et que cette activité est directement liée à une diminution de la production de miARN ciblés et au rétablissement de la traduction de ARN messenger / MicroRNAs (miRs) are a class of small non-coding RNAs that act as regulators of gene expression at the post-transcriptional level. Increasing evidence has indicated that the deregulation of miR expression is linked to various human cancers and therefore, miRs represent a new class of potential drug targets. In this context, my PhD project focused on the discovery of new inhibitors of oncogenic miRs production. Toward this aim, two different but complementary approaches were followed: (i) the screening of small libraries of compounds and (ii) the design and synthesis of new classes of conjugates as binders of miRNA precursors (pre-miRs). In particular, we focused our attention on miR-372 and miR-373, two oncogenic miRs overexpressed in various cancers, such as gastric cancer. We showed that some of the screened or of the newly synthesized compounds are able to efficiently bind to stem-loop structured precursors of the targeted miRs with high affinity, thus inhibiting the production of their corresponding mature miRs at the level of Dicer cleavage. Moreover, we found compounds bearing a specific anti-proliferative activity in gastric cancer cells overexpressing targeted miRs and this activity is directly linked to a decrease in the production of oncogenic miR-372 and -373 and to the restoration of normal mRNA translation.

Title: Theory of aggregates of photosynthetic molecules: spectroscopy, structure, transport phenomena Author: Ján Lalinský Institute: Institute of Physics of Charles University Supervisor of the master thesis: RNDr. Tomáš Mančal, PhD., Institute of Physics of Charles University Abstract. A theory of absorption of light in an isotropic solution of molecules was formulated on the basis of electromagnetic theory of par- ticles with attention to relativistic nature of their interaction and its im- pact on the spectrum of circular dichroism. Calculations of the absorption spectra of simple systems were performed to demonstrate the properties of the mathematical model. Also calculations of the absorption spectra of the models of the bacteriochlorophyll dimer which were proposed as possible basic unit in the lamellar model of the interior of a chlorosome were performed. The experimental spectra of solution of non-aggregated bacteriochlorophyll were used to fit the parameters of the mathematical model of the molecule and for these parameters the spectra of the pro- posed models of a dimer were calculated. It has been found that the new non-electrostatic terms in the description of the mutual interaction of the parts of the molecule are negligible for calculations of ordinary absorption spectrum, but they have...

In forensic anthropology, laboratory-based (LBM) and field-based (FM) models can be used to develop new methods and to research the stability and rate at which bio-molecules degrade. In this study, both these methods were used to investigate the effects that temperature, time after death (TAD) and other environmental factors had on the concentration of and change in molecular structure (increase in free pyrrole content, ninhydrin reactive nitrogen (NRN) and iron). of collagen, haemoglobin (Hb) and DNA in porcine teeth For the LBM, porcine teeth were heated at 900C for 0-4 hours, 1 hour intervals, (total number of teeth n=35). A porcine FM was established at the Miertjie Le Roux Experimental Farm of the University of Pretoria. From the decomposing pigs, teeth were collected at TAD intervals of 20 days (n=35). The morphology of the teeth were evaluated and recorded. Methods for collagen and DNA isolation, quantification of protein, collagen, haemoglobin (Hb), free pyrrole content (FPC), ninhydrin reactive nitrogen (NRN), total iron, Fe2+ and Fe3+ as well as a real-time PCR method for the detection of mitochondrial cytb gene in porcine teeth were established. These methods were used to determine the concentration and structural integrity of these molecules in the LBM and FM teeth. The morphology of the LBM teeth was regular with only minor changes in colour with time heated. The collagen and Hb concentration did not change with time. A decrease in total iron (not statistically significant) and Fe3+ (p=0.014; R2=0.74) was found and was associated with an increase in Fe2+ (p=0.014; R2=0.965). No change in free pyrolle content was found. The total protein concentration determined using the Biuret method showed a decrease with time (p=0.009; R2=0.99). For DNA, a linear decrease in concentration (p=0.00; R2=0.93) was found. This DNA could still be used for the successful amplification of the cytb gene. As for DNA a similar decrease in NRN (p=0.00; R2=0.99) was also found whether this is related to protein or DNA degradation is unknown. From this data the total protein, DNA and NRN showed a definite time related change in concentration. For the field model the teeth were brown, cracked, weathered and corroded. As for LBM, there were no time related changes in mass and collagen content. A significant decrease in total protein concentration (p=0.00; R2=0.52) and FPC (p=0.01; R2=0.98) was observed. Hb, FPC and iron levels (total iron, Fe3+ and Fe 2) did not change with time but concentrations FPC and iron were higher than those found in the LBM. Also total protein concentration although it decreases with time was also increased when compared to the LBM (sentence is awkward, re-word). This could be due to increase bacteria activity that results in an increase in protein biomass, iron accumulation and pyrolle synthesis. In contrast Hb levels were the same as LBM and are species specific and not related to increased bacterial activity. NRN showed a time related decrease in concentration (p=0.09; R2=0.99) and was also twice that found in the LBM. This is related to decomposition of porcine protein and DNA as well as that derived from bacteria. A decrease in DNA concentration with time was found (p=0.00; R2=0.88). DNA from all samples and could be used for the amplification of cytb. In conclusion the LBM allows for rapid method development and the investigation of the effect of single factors on the integrity of bio-molecules such as protein and DNA. The FM can then be used to further investigate the effect of many additional environmental factors on the concentration and structure of the same bio-molecules. Using both models, it was found that total protein, DNA and NRN showed a time related change in concentration while the concentration of collagen and Hb remained constant. Copyright / Dissertation (MSc)--University of Pretoria, 2011. / Anatomy / unrestricted