Dissertations / Theses on the topic 'Formation of supramolecules'

Supramolecular chemistry covers intermolecular interactions where non-covalent bonds are involved, and many of them are based on host-guest interactions. Cyclodextrins (CDs) are cyclic oligosaccharides consisting of 6-, 7- or 8-glucose units, which are called alpha-, beta- or gamma-CDs, respectively. They have hydrophobic interior and hydrophilic exterior, and are widely being used as hosts for various organic molecules. The formation of CD inclusion complexes with a variety of dyes has continuously drawn our interests, since CDs are readily available and have ability to include dye molecules altering their properties. The present thesis covers the study of inclusion complexes of CDs and chromophore dyes, largely in two ways; rotaxane and pseudorotaxane. The stable rotaxane structure is achieved with the synthesis of dye rotaxane. The introduction of CD ring around azo chromophore provides a simple way to improve the solubility and stability of azo dye. We have shown that by incorporating proper compounds as a coupler, azo dye rotaxanes can be used as pH indicators and metal ion sensors. We have described the synthesis of novel acetylene dye rotaxane using the Pd-catalyzed reaction of Heck-Cassar-Sonogashira-Hagihara type. Its fluorescence properties in the solid state as well as in solutions are examined and compared with those of free dye. Free dye, which has tetra-carboxylic groups, is found to be highly sensitive to various metal ions, exhibiting high Stern-Volmer constants, K(SV). On the contrary, acetylene dye rotaxane exhibits much less quenching against various quenchers. The appearance of fluorescent anisotropic structure has been observed by the formation of inclusion complex between acetylene dye and gamma-CD. Its structural nature is studied by various techniques, including fluorescence, fluorescence anisotropy, wide angle X-ray scattering (WAXD) and differential scanning calorimetry (DSC) measurements. Methyl orange, an acid azo dye, forms a dimeric inclusion complex with gamma-CD, resulting in the formation stable anisotropic aggregates. Several other azo dyes are found to form anisotropic supramolecule in the presence of gamma-CD, and their structural characteristic has been discussed in terms of the number and position of solubilizing groups.

The spontaneous formation of supramolecular assemblies has been viewed as a potential route to the creation of functional nano-scale architectures for a number applications in electronics. In this thesis a number of assemblies formed from molecular constituents deposited from the solution phase have been studied. The structures formed by two carboxylic acid derivatives on the highly oriented pyrolytic graphite (HOPG) surface from nonanoic acid solutions are presented. Quaterphenyl-tetracarboxylic acid (QPTC) molecules are observed to form a supramolecular network where all the constituents lay parallel to one another on the surface. The network is stabilised by four carboxylic acid dimer bonds per molecule in addition to admolecule-substrate interactions. Terphenyl-tetracarboxylic acid (TPTC) molecules form a much more complex structure with individuals orientating themselves in one of three directions to form a network with hexagonal symmetry but no translational order. To characterise such an unusual supramolecular morphology we introduce a rhombus tiling representation of the network where each molecule is schematically replaced with a lozenge rhombus producing a tiling. Such tilings have been studied previously in the literature and utilising this we are able to determine that the morphology is stabilised by entropic contributions to the free energy. In addition to this we present the tip-induced manipulation of the TPTC supramolecular network. The manipulation is performed by imaging the structure within a specific voltage bias range resulting the TPTC molecules reordering into a close packed structure. Returning the voltage to that conventional used for imaging causes the network to relax back into the open structure although with a different morphology. We then discuss the changes induced in these supramolecular networks when additional molecular species are introduced to the system. First, coronene and perylene are separately codeposited with QPTC resulting in the formation of a hexagonally ordered network with coronene or perylene located at the vertices of six QPTC molecules. This new structure is observed to form even when QPTC is deposited first. Second, the adsorption of coronene into the porous TPTC network is presented. When the TPTC network forms before the introduction of coronene we note little effect on the network morphology. However, when the molecules are mixed in the solution phase and deposited simultaneously we observe the non-uniform adsorption of coronene into the TPTC structure. At higher coronene concentrations we note the network forms with a different morphology shifted towards a more ordered state suggesting that when the molecules are deposited sequentially the system is kinetically trapped in the originally formed structure. We then present a series of studies of molecular adsorption on the Au (111) surface. First, hexaazatrinaphthylene (HATNA) molecules are observed to form stable supramolecular structures when deposited from ethanol solutions. A core hydrogen bonding junction is identified. The network switches between two domain orientations and we identify a linear defect where the two domains meet. Second, we report the adsorption of Tri( 4-bromophenyl) benzene (TBPB) on the Au (111) surface. TBPB forms three different structures at room temperature. When samples are heated during the deposition stage we observe the covalent coupling of pairs of molecules to form dimers. This reaction is confirmed by ToFSIMS experiments. The substrate is confirmed to play a significant role in the coupling process as subsequent experiments on HOPG failed to yield dimer formation. Finally we demonstrate the potential of a UHV-prepared sample by templating the adsorption of adamantanethiols. Finally, we demonstrate the adsorption of a solubilised derivative of perylene tetracarboxylic dianhydride (PTCDA). PTCDA molecules have poor solubility in most solvents commonly used for liquid deposition. The addition of alkane chains attached to the sides of the perylene core promotes the solubility of the molecule in these solvents whilst leaving the anhydride functionality intact. Deposition is performed from 1-phenyloctance solutions on HOPG. The molecules form an ordered structure characterised by a single molecule unit cell. The results presented in this thesis show that the understanding of supramolecular networks has progressed to the point where changes in the morphology can be induced via a variety of processes.

The chemical and physical properties of organic molecular crystals depend on both the molecular and crystal structure. The systematic approach to understanding and controlling crystal structure lies in the field of "crystal engineering". One strategy to emerge within crystal engineering has been the utilisation of specific interactions or couplings / synthons to predictably build supramolecular arrays such as tapes, ribbons or sheets. These arrays form a subset of the crystal structure. While many couplings take the form of cyclic motifs in which component interactions are of comparable strength, a cyclic coupling consisting of an O-- H^...N and a C-H^...O interaction was noted as having a potential use in designing supramolecular arrays. This type of strong / weak coupling is possible upon the interaction of an N-heterocycle with a carboxyl group. The following research describes the co-crystallisation of various N-heterocyclic bases with a number of olefinic and aliphatic dicarboxylic acids. The crystal structures of various complexes of phenazine, 1,10-phenanthroline and quinoxaline were solved from single-crystal X-ray diffraction data and are discussed. Two distinct strong / weak couplings were identified within the three sets of co-crystals. A comparison of the relative stabilities of the two couplings was made using the quinoxaline system. Supramolecular tapes were observed in all of the phenazine co-crystals and in three of the four quinoxaline co-crystals. (The stoichiometry of the phenazine co-crystals may be related to the position of the carboxyl groups on the participating acid.) The packing of the tapes is discussed with particular reference to tape topography and inter-tape C-H^...O interactions. Proton transfer occurred in four of the five co-crystals of 1,10-phenanthroline. Co-crystals were prepared via two methods: by growth from a solution and by grinding of a physical mixture of the starting components. Solid-state grinding was found to be a viable method for the preparation of co-crystals. Complexes of 1,10-phenanthroline prepared via the two routes were analysed using solid-state ¹³C MAS NMR and the effects of protonation on certain carbon resonances is discussed.

Thesis (MSc)--Stellenbosch University, 2014.
ENGLISH ABSTRACT: A theoretical and experimental study was performed in order to identify factors that influence the propensity of compounds containing anionic functional groups that are commonly found on pharmaceutical drug compounds to form hydrates. A Cambridge Structural Database (CSD) survey was initially undertaken to determine the propensity of different pharmaceutically acceptable anions to form hydrates. The results showed that hydrate formation will take place more regularly when the polarity of the functional group increases. Furthermore, if the charge distribution is very concentrated over the polar groups, hydrate formation will occur more readily. This observation was further investigated by performing a series of potential energy surface (PES) scans for the hydrogen bond (H-bond) in the structure of N-(aminoiminomethyl)-N-methylglycine monohydrate (creatine monohydrate) with various Density Functional Theory (DFT) and Wave Functional Theory (WFT) methods. WFT is often also referred to as ab initio, which refers to the construction of the wave function from first principles when this theory is applied. The scans revealed that several strong and directional H-bonds with different geometrical parameters between the carboxylate group and the water molecule are possible, which suggests that the H-bond plays an important role in driving the formation of pharmaceutical hydrates. A total of 44 hydrate structures were identified that have pharmaceutically acceptable functional groups. Optimisations in the gas phase and in an implicit solvent polarisable continuum solvent model with a variety of solvents showed that there is a significant dependence of the H-bond interaction energy on the anionic group as well as the steric density of surrounding substituents. It was found that the M06-2X method utilising the 6-311++G(d,p) basis set outperformed the other methods that were tested when compared to optimisations performed with the benchmark MP2/aug-cc-pVTZ level of theory. Furthermore, the strength of the H-bond was measured in the 44 experimentally determined structures by using a total of five generalized gradient approximation (GGA) methods, of which two methods contained the DFT-D3 correction. The results of these DFT methods were subsequently compared to results obtained at the benchmark MP2/aug-cc-pVTZ level of theory. The M06-2X method was identified as the most economical method to calculate H-bond energies. It was also found that the H-bond interaction energy shows a substantial dependence on the electrostatic environment. This was observed by a significant decrease in H-bond strength as the relative permittivity of the solvent increases. The effect of steric density on the H-bond interaction energy was investigated by performing hydrogen bond propensity calculations. These values were then compared to the interaction energies of each structure and the results showed that the presence of large bulky substituents can lead to an increase in bond energy by forcing the anionic functional group closer to the water molecule. Contrastingly, the bulky group can also push the anionic group away from the water molecule and result in a decrease in bond energy. Approximate values for the amount of stabilisation offered to the H-bonding system by the surrounding crystalline environment were calculated by optimising the H-bond geometrical parameters of selected compounds with a combination of the M06-2X and MP2 methods utilising the 6-311++G(d,p) basis set. The H-bond interaction energies were then calculated at the M06-2X/6-311++G(d,p) level of theory and compared to the H-bond interaction energies in geometries that have been fully optimised. After these energies were compared and the crystal packing of each structure was investigated, it was found that the packing of some structures within the crystalline environment limits the number of H-bonds that can be formed between the water and the compound of interest. Full optimisation calculations result in structures with cooperative stabilisation, such that more than one H-bond is found between the two fragments. The effect of substituents on H-bond interaction energy was investigated by the addition of six electron-donating and electron-withdrawing groups on four aromatic compounds with different anionic functional groups, namely carboxylate, nitrogen dioxide, sulfonate and phosphonate. It should also be mentioned that the nitrogen dioxide is not an anionic functional group, but it was included as it is a neutral radical that often forms hydrogen bonds. A total of 80 structures were optimised with a combination of the M06-2X and MP2 methods utilising the 6-311++G(d,p) basis set. This was followed by counterpoise corrected single point calculations at the M06-2X/6-311++G(d,p) level of theory. The results showed that the H-bond interaction energy bears no relationship to the inductive strength or the inductive ability of the substituents, but rather the ability of these substituents to rotate the anionic functional group and allow cooperative stabilisation of the H-bond. Furthermore, AIM analysis was performed for the substituted H-bonded aromatic structure. The results showed that electron-donating groups that are placed at the para position yield stronger H-bonds, which is once again accompanied by cooperative stabilisation. Electron-withdrawing groups with sufficient inductive effects can result in a weaker H-bond when placed at the meta position. The effect of water activity (aw) on the hydrate crystal formation was investigated experimentally by performing a series of crystallisations in various solvent mixtures. These mixtures consisted of water mixed with acetone, ethanol and ethyl acetate. A total of three organic acids were used in crystal formation, namely pyridine-4-carboxylic acid (isonicotinic acid), N-amino-iminomethyl-N-methylglycine (creatine) and benzene-1,3,5-tricarboxylic acid. It was found that water activity affects the formation of the hydrate as well as the anhydrous product. Additionally, nucleation and super saturation plays a large role in crystal formation and can serve as an effective technique when the formation of crystals of an appropriate shape and size is required for further analysis.
AFRIKAANSE OPSOMMING: 'n Teoretiese en eksperimentele studie was uitgevoer om faktore te identifiseer wat die geneigdheid van verbindings met anioniese funksionele groepe wat algemeen gevind word op farmaseutiese dwelm verbindings om die hidraat produk te vorm, affekteer. 'n Opname van strukture in die Cambridge Strukturele Databasis (CSD) is onderneem om die geneigdheid van verskillende farmaseutiese aanvaarbare anione om hidrate te vorm te bepaal. Die resultate het getoon dat hidraatvorming meer gereeld plaasvind indien die polariteit van die funksionele groepe toeneem. Verder is daar ook opgemerk dat 'n gekonsentreerde ladingsverspreiding op die polêre groepe ook tot 'n toename in hidraat vorming sal lei. Hierdie waarneming is verder ondersoek deur 'n reeks potensiële energie oppervlak (PES) skanderings van die waterstof binding (H-binding) vir die struktuur van N-amino-iminometiel-N-metielglisien monohidraat (kreatien monohidraat) met verskeie Digtheids-Funksionele Teorie (DFT) en Golffunksie Teorie (WFT) metodes uit te voer. Die skanderings het getoon dat verskeie sterk, gerigte H-bindings met verskillende geometriese parameters tussen die karboksilaatgroep en die watermolekule kan vorm. Hierdie bevindinge lê klem op die belangrike rol wat H-bindings in die vorming van farmaseutiese koolhidrate speel. 'n Totaal van 44 hidraat strukture met farmaseutiese aanvaarbare funksionele groepe was geïdentifiseer. Optimaliserings is in die gas fase asook in 'n implisiete kontinuum polariseerbare oplosmiddel model met 'n verskeidenheid oplosmiddels uitgevoer. Die resultate het 'n beduidende afhanklikheid van die H-binding interaksie-energie op die anioniese groep asook die steriese afkskerming van omringende groepe getoon. Daar is bepaal dat die M06-2X metode wat saam met die 6-311++G(d,p) basisstel die mees akkuraatste resultate gelewer het in vergelyking met die ander DFT metodes asook die MP2/aug-cc-pVTZ maatstaf. Die H-binding se sterkte is vir hierdie strukture bereken deur vyf GGA metodes te gebruik, waarvan twee metodes van die DFT-D3 korreksie gebruik maak. Die resultate van die berekeninge met hierdie DFT metodes is daarna vergelyk met resultate verkry met die MP2/aug-cc-pVTZ maatstaf. Daar is gevolglik bepaal dat die M06-2X metode die mees ekonomiese metode is om H-binding energië te bereken. Die H-binding interaksie energie toon 'n aansienlike afhanklikheid op die diëlektriese konstante van die oplosmiddel aan. Hierdie waarneming is op grond van 'n beduidende afname in die H-binding interaksie-energie indien die relatiewe permittiwiteit van die oplosmiddel verhoog word gemaak. Die effek van steriese digtheid is ondersoek deur waterstofbindinggeneigdheid waardes te bereken. Hierdie waardes is met die interaksie-energië van elke struktuur vergelyk. Die resultate dui daarop dat steries digte groepe tot 'n toename in interaksie energie kan lei wanneer die anioniese funksionele groep nader aan die water molekule gestoot word. Verder is dit ook moontlik vir hierdie steries digte groepe om die anioniese groep weg van die water molekule te stoot en gevolglik 'n afname in interaksie energie te veroorsaak. Benaderde waardes vir die hoeveelheid stabilisering wat die omringende kristallyne omgewing aan die H-binding bied is bereken deur die H-binding geometriese parameters van geselekteerde verbindings met die M06-2X en MP2 metodes en die 6-311++G (d,p) basisstel te optimaliseer. Die H-binding interaksie-energië is gevolglik by die M06-2X/6-311++G(d,p) vlak van teorie bereken en met die H-binding energië in strukture wat volledige optimaliseer is vergelyk. Nadat hierdie waardes vergelyk is, is daar gevind dat die pakking van strukture in the kristallyne omgewing verhoed dat sekere H-bindings tussen die water molekule en die verbinding van belang kan vorm. Strukture wat volledig optimaliseer is, lei tot strukture wat in staat is om koöperatiewe stabilisering te ondergaan. Koöperatiewe stabilisering word gekenmerk deur die vorming van meer as een H-binding tussen twee fragmente. Die effek van substituente op die H-binding interaksie energie is ondersoek deur die bevoeging van ses elektrondonor- en elektronontrekkendegroepe op vier aromatiese verbindings, naamlike die karboksilaatgroep , stikstofdioksied , sulfonaat en fosfonaat. Dit moet ook genoem word dat stikstofdioksied nie 'n anioniese funksionele groep is nie, maar dit was wel ingesluit omdat dit ‘n neutrale radikaal groep is wat dikwels waterstofbindings vorm. 'n Totaal van 80 strukture optimiserings was uitgevoer met 'n kombinasie van die M06-2X en MP2 metodes wat gebruik maak van die 6-311++G(d,p) basisstel. Dit is gevolg deur interaksie-energie berekeninge op die M06-2X/6-311++G(d,p) vlak van teorie. Die resultate het getoon dat daar geen verband tussen die induktiewe vermoë van die substituente en die sterkte van die H-binding is nie, dit is eerder die vermoë van hierdie substituente om die anioniese funksionele groep te laat roteer wat toelaat dat koöperatiewe stabilisering van die H-binding kan geskied. Die AIM analise is op 'n gesubstitueerde H-binding struktuur toegepas. Die resultate het getoon dat elektrondonorgroepe wat by die para posisie geplaas word tot sterker H-bindings sal lei, wat weereens met koöperatiewe stabilisering vergesel word. Elektrononttrekkendegroepe met sterk induktiewe effekte kan tot 'n swakker H-binding lei indien hulle by die meta posisie geplaas word. Die effek van water aktiwiteit (𝑎w) op hidraatkristalvorming is deur die uitvoering van 'n reeks kristallisasies in verskeie oplosmiddelmengsels ondersoek. Hierdie oplosmiddel mengsels bestaan uit water met asetoon, etanol of etielasetaat gemeng. Kristallisasies is vir drie organiese sure, naamlik piridien-4-karboksielsuur, N-amino-iminometiel-N-metielglisien monohidraat en 1,3,5-benseen tri-karboksielsuur uitgevoer. Daar is gevind dat water aktiwiteit 'n invloed op die vorming van die hidraat en watervrye produkte kan hê. Daarbenewens, speel water aktiwiteit 'n belangrike rol in die nukleasie fase van kristalvorming en kan as 'n effektiewe tegniek dien om kristalle van 'n toepaslike vorm en grootte vir verdere analise te verkry.

Thesis (MSc)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: This study aimed to combine the principles of crystal engineering with the properties of cyclotriphosphazene derivatives to construct supramolecular assemblies in the solid state. The ease with which the chloro substituents on cyclotriphosphazenes can be replaced makes them ideal candidates for this study. The substituents were chosen for their ability to form either hydrogen bonding interactions or halogen bonding interactions in the solid state. The cyclotriphosphazene derivatives were co-crystallised with various small organic molecules with complementary functional groups, as well as with other cyclophosphazene derivatives. The aim was to form co-crystals or solvates with these cyclophosphazene derivatives as co-crystals contain a wealth of information regarding the forces governing the aggregation of molecules in the solid state. Cyclotriphosphazenes, with their array of substituents, could broaden the range of potential interactions governing crystalline assembly. Fifteen cyclotriphosphazene derivatives were synthesised and characterised in this study. The novel crystal structures of two cyclotriphosphazene derivatives have been elucidated by single crystal X-ray diffraction. These are 2,2-bis(4-formylphenoxy)-4,4,6,6-bis[spiro(2',2"-dioxy-1',1"-biphenylyl)]cyclotriphosphazene and hexakis(4-cyano-phenoxy)cyclotriphosphazene. In the course of this study two novel polymorphs of hexakis(4-fluorophenoxy)cyclotri-phosphazene were identified and studied. The novel triclinic form undergoes an irreversible transformation to the previously reported monoclinic phase at high temperatures. The reported monoclinic phase, however, transforms to a monoclinic C phase in a single-crystal to single-crystal fashion. It is also suspected that this phase transformation is in fact reversible on cooling of the crystal to temperatures below -45 °C. One novel co-crystal structure of hexakis(4-pyridyloxy)cyclotriphosphazene with terephthalic acid was identified and characterised. However, analysis of the Cambridge Structural Database indicates that co-crystal formation with cyclophosphazenes is not a commonly occurring phenomenon. This leads to the conclusion that cyclotriphosphazenes can be used in crystal engineering as supramolecular building blocks, but their shape and size tend to inhibit the formation of co-crystals. Therefore co-crystal formers have to be chosen with great care.
AFRIKAANSE OPSOMMING: Die doel van hierdie studie was om die beginsels van kristalingenieurswese te kombineer met die eienskappe van siklotrifosfaseen afgeleides om sodoende supramolekulêre versamelings in die vastetoestand te bou. Die gemak waarmee die chloor substituente op die siklotrifosfaseenring vervang kan word, maak hierdie molekules ideaal vir hierdie studie. Die substituente is gekies op grond van hul potensiaal om waterstofbindings of intermolekulêre halogeenbindings in die vastetoestand te vorm. Ko-kristallisasie eksperimente is met die siklotrifosfaseen afgeleides en verskeie klein organiese molekules met komplementêre funksionele groepe uitgevoer, asook tussen die verskeie siklotrifosfaseen afgeleides met mekaar. Die doel was om mede-kristalle of solvate met hierdie siklotrifosfaseen afgeleides te vorm aangesien mede-kristalle ‘n magdom inligting bevat rakende die kragte wat die versameling van molekules in die vaste fase beheer. Die siklotrifosfaseen afgeleides wat ‘n wye verskeidenheid substituente kan dra, kan hierdeur die moontlike intermolekulêre interaksies wat die versameling in die kristallyne vaste fase beheer verbreed. In hierdie studie is vyftien siklotrifosfaseen afgeleides gesintetiseer en gekarakteriseer. Die voorheen onbekende kristalstrukture van twee siklotrifosfaseen afgeleides is in hierdie studie geïdentifiseer, naamlik 2,2-bis(4-formielfenoksie)-4,4,6,6-bis[spiro(2',2"-dioksie-1',1"-bifeniliel)]siklotrifosfaseen en heksa(4-sianofenoksie)siklotrifosfaseen. Die strukture is bepaal deur enkelkristal X-straaldiffraksie. In die loop van hierdie studie is twee voorheen onbekende polimorfs van heksa(4-fluorofenoksie)siklotrifosfaseen geïdentifiseer en bestudeer. Die nuwe trikliniese vorm ondergaan ‘n onomkeerbare faseverandering na die monokliniese vorm by hoë temperature. Die bekende monokliniese P fase ondergaan egter ‘n verdere faseverandering na ‘n monokliniese C fase. Hierdie geskied as ‘n enkel-kristal na ‘n enkel-kristal faseverandering. Daar word ook gespekuleer dat hierdie spesifieke faseverandering wel omkeerbaar is indien die kristal na -45 °C afgekoel word. Een nuwe mede-kristal tussen heksa(4-pyridieloksie)sikotrifosfaseen en 1,3-dibensoësuur is in hierdie studie geïdentifiseer en gekarakteriseer. ‘n Analise van die Cambridge Strukturele Databasis het egter aangedui dat die vorming van mede-kristalle nie ‘n alledaagse verskynsel is in sikotrifosfaseen afgeleides nie. Dit lei tot die gevolgtrekking dat sikotrifosfaseen molekules wel in kristalingenieurswese gebruik kan word as supramolekulêre boustene, maar dat die vorm en grootte van die molekules die kristallisering van mede-kristalle verhoed. Dus moet die molekules wat saam met die siklotrifosfaseen molekules gekristalliseer wil word, goed deurdink word.

Les origamis d’ADN et les Single Stranded Tiles (SST) semblent être deux des composants les plus prometteurs du domaine des nanotechnologies d’ADN en termes de conceptions et d'applications possibles. Dans cette thèse, nous avons exploré les aspects thermodynamiques et cinétiques sous-jacents à la formation de ces objets, ainsi que de nouvelles méthodes pour construire des nanoobjets programmables dynamiques. Notamment, l'étude du processus de formation a mis en évidence la présence inutile d'ions magnésium ou de molécules tampons dans le milieu, et de nouvelles conditions de formation ont été décrites. Le processus de fusion a été caractérisé à l'aide d'une nouvelle méthode d'électrophorèse sur gel quantifiée mettant en évidence un comportement non monotone et appelant une nouvelle définition de la température de fusion des origamis. De plus, nous avons démontré que la formation et la fusion pouvaient être contrôlées par la lumière en utilisant AzoDiGua, un intercalant d’ADN photosensible mis au point précédemment par notre groupe. Cela nous a permis d'observer pour la première fois un processus d'hybridation/déshybridation contrôlé par la lumière au sein d'origamis individuels à température constante et d'obtenir ainsi un mouvement contrôlé à l'échelle nanométrique. Nous avons également mis au point une méthode originale pour la formation isotherme d’ADN origamis et de SST à température ambiante constante et en l’absence de tout agent dénaturant. Cela nous a permis d'observer pour la première fois et in situ le pliage isotherme d'origamis individuels, démontrant ainsi que l'origami peut atteindre sa forme d'équilibre final en suivant une variété de voies de pliage
DNA origamis and Single Stranded Tiles (SST) appear to be two of the most promising components of the DNA nanotechnology field in terms of possible designs and applications. In this thesis, we explored the thermodynamic and kinetic aspects underlying DNA nanostructures formation as well as new practical ways to build dynamic programmable nano-objects. Notably, the study of the formation process evidenced the unnecessary presence of magnesium ions or buffering molecules in the medium, and new formation conditions have been described. The melting process triggered by temperature elevation was characterised using a new quantified gel electrophoresis method evidencing for the first time a non-monotonous behaviour and calling for a new definition of DNA origami melting temperature. Both formation and melting process were furthermore demonstrated to be controllable by light using AzoDiGua, a photosensitive DNA intercalator previously developed by our group. This allowed us to observe for the first time a light-controlled hybridisation / dehybridisation process within individual origamis at constant temperature and thus achieve a controlled motion at the nanoscale. We also established an original method for the isothermal formation of DNA origamis and SST at constant room temperature and without the presence of any denaturating agent. This allowed us to observe for the first time and in situ the isothermal folding of individual origamis, thus evidencing that origamis can reach their final equilibrium shape following a variety of folding pathways

Thesis (Ph. D.)--Textile and Fiber Engineering, Georgia Institute of Technology, 2006.
Srinivasarao, Mohan, Committee Chair ; Bunz, Uwe, Committee Co-Chair ; Griffin, Anselm, Committee Member ; Tolbert, Laren, Committee Member ; Park, Jung, Committee Member ; Beckham, Haskell, Committee Member. Includes bibliographical references.

On-surface supramolecular chemistry inspired the fabrication of a large variety of atomically controlled systems and on-surface synthesis allowed the production of low-dimensional materials with atomic precision. Since numerous surface-supported nanostructures are constantly developed, their possible applications stimulate diverse areas of research such as catalysis, organic electronics, surface sensing, surface functionalization and nanopatterning. Several protocols and interfacial approaches have been developed for the production of surface-supported supramolecular networks by self-assembly and by far, the increasing interest for nanomaterials with innovative functionalities has boosted the search in on-surface activation of chemical reaction for the covalent stabilization of more complex molecular architectures. Photochemistry was furthered as a promising approach for this purpose and pioneering examples allowed a deeper understanding of light-induced on-surface chemical reactions. However, the search in this field is still at its birth and further research is required. The Scanning Tunneling Microscope provides the necessary resolution for this studies in various conditions, including solid/liquid or solid/air interfaces or Ultra High Vacuum (UHV).
La chimica supra-molecolare di superficie ha permesso la produzione di numerose nanostrutture tramite l'utilizzo di protocolli di sintesi innovativi. In questo modo si sono ottenuti, tramite controllo strutturale a livello atomico e molecolare, numerosi materiali a ridotta dimensionalità. L'applicazione di tali scoperte si sviluppa nell'ambito della ricerca relativa alla catalisi, all'elettronica organica, alla funzionalizzazione e alla sensibilizzazione della superfici. Poiché esistono diversi approcci per per la produzione di tali strutture, la ricerca ha spinto i propri interessi verso la nano-fabbricazione di materiali per ottenerne, sfruttando varie tecniche, di innovativi, più stabili ed efficienti. La fotochimica di superficie in questo senso, permette di ottenere materiali molto complessi ed inoltre permette di capire i fenomeni alla base dei processi di sintesi indotta dalla luce, che ad oggi, non sono del tutto semplici da interpretare. La microscopia a scansione di tunneling (STM) fornisce l'opportuna risoluzione spaziale per questo tipo di studi, i cui principi sono ancora oggi oggetto di dibattito.

En termes de chimie supramoléculaire et de tectonique moléculaire, les métacyclophanes [1111] sont des composés attractifs pour la préparation et l’étude de réseaux moléculaires, car la particularité de ces composés est la stabilité exceptionnelle de la conformation l'encombrement stérique entre les groupes ortométhyliques des cycles aryles. Un tel type rigide d'échafaudage moléculaire aussi bien avec la présence de sites de liaison de terminaux est considéré comme un bloc de construction moléculaire très approprié pour la formation de différents types de réseaux moléculaires en utilisant principalement la coordination et la H-bonding. Dans le cadre de ce travail, nous avons étudié le rôle de la nature de la coordination des sites greffés sur le squelette métacyclophane macrocyclique afin d'améliorer leur capacité à former des réseaux de coordination dans la phase cristalline et les systèmes supramoléculaires en solution, une série de nouvelles [1111] métacyclophanes ont été synthétisés et caractérisés en solution et à l'état solide. Leur propension à lier différents cations métalliques dans la phase cristalline ainsi que des complexes en solution ont été étudiés
In terms of supramolecular chemistry and molecular tectonics,[1111]metacyclophanes are attractive compounds for the preparation and study of molecular networks since the particular feature of these compounds is determined by exceptional stability of the 1,3-Alternate conformation of their molecular platform due to the steric hindrance between the orto-methyl groups of aryl rings. Such rigid type of molecular scaffold both with presence of terminal binding sites is considered as a very suitable molecular building block for formation of different type molecular networks using primarily coordination and H-bonding. Through this work we investigated the role of the nature of the coordinating sites grafted on the metacyclophane macrocyclic backbone in order to enhance their ability to form coordination networks in the crystalline phase and the supramolecular systems in solution, a series of new [1111]metacyclophanes have been synthesized and characterized in solution and in the solid state. Their propensity to bind different metal cations in the crystalline phase as well as complexes in solution have been studied

La structure unique et les propriétés des fullerènes ont suscité l’intérêt des chercheurs, en particulier dans les domaines de l’électronique et de l’optoélectronique. Dans ce contexte, plusieurs mono- et de poly-adduits du fullerène ont été décrits pour leurs développements comme nouveaux matériaux originaux et comme polymères supramoléculaires. Nous présentons ici les synthèses et les études de nouveaux polymères supramoléculaires donneur-accepteur à base de penta(organo)[60]fullerènes. La parfaite régiosélectivité de la réaction de pentafonctionnalisation sur le [60]fullerène permet de former une cavité conique formée de cinq fragments éthynylaryles. A cette structure, différentes unités électro et/ou photoactives (tétrathiafulvalène et porphyrine de zinc) ont été liés par des liaisons covalentes via cinq réactions de cycloaddition 1,3- dipolaire. Le composé hôte-invité avec ses propriétés donneur-accepteur permet la formation d’assemblages par des interactions supramoléculaires. Nous avons réalisé les synthèses des penta(organo)[60]fullerènes comme nouveaux matériaux donneur-accepteur et nous avons étudié les propriétés des assemblages supramoléculaires en solution et à l’état solide
The unique structure and properties of fullerenes have attracted wide interest especially in electronic and optoelectronic fields. In this context, a variety of mono-and poly-fullerene adducts have been described for theirs interest in the development of new complex materials and supramolecular polymers. Here, we present the synthesis and studies of new donor-acceptor supramolecular polymers based on penta(organo)[60]fullerenes. The perfect regioselectivity of the [60]fullerene pentafunctionalization reaction has provided us a singular conical structure formed by five ethynylaryl fragments. To this structure different electro and/or photoactive fragments (tetrathiafulvalene or zinc-porphyrin) were covalently linked using five simultaneous 1,3-dipolar cycloaddition reactions. The formed host-cavity together with the donor-acceptor properties of these system allow their assembly by supramolecular interactions. We have realized the synthesis of these penta(organo)[60]fullerenes as new donor-acceptor materials and the studies of their remarkable supramolecular arrangement in solution and solid state

Cette these montre l'interet et l'importance de la spectrometrie de masse en mode d'ionisation electrospray (esms) pour la caracterisation et l'etude de la formation en solution d'edifices supramoleculaires complexes. Dans un premier temps, notre travail a consiste a etablir les conditions d'analyse par esms d'edifices supramoleculaires synthetiques particulierement gros et/ou labiles. Pour cela, nous avons ete tout d'abord amenes a proposer deux strategies nouvelles permettant d'etendre l'utilisation de l'esms a la caracterisation d'edifices fragiles ou difficiles a ioniser. Nous avons ainsi utilise l'electrochimie pour ioniser les especes neutres et nous avons montre que l'helium, utilise comme gaz dans le processus electrospray au lieu d'azote, permet de diminuer l'energie interne conferee aux ions lors de leur passage dans l'interface electrospray et par consequent de minimiser les fragmentations. Nous avons ainsi pu caracteriser plusieurs edifices synthetiques complexes, en particulier, des complexes de coordination possedant de tres nombreux centres metalliques. Dans un deuxieme temps, nous avons etabli les conditions experimentales permettant de suivre par esms, la formation, en solution, d'edifices supramoleculaires synthetiques complexes, afin d'acceder a leur mecanisme de formation. Apres avoir determine sur une serie de modeles simples, les conditions sous lesquelles l'image donnee par le spectre de masse es represente fidelement les especes presentes en equilibre, en solution, nous avons pu caracteriser les intermediaires thermodynamiques de formation de deux edifices pour lesquels les donnees de spectrophotometrie uv-visible etaient inexploitables. Nous avons egalement montre que l'esms permet de suivre la cinetique de formation de ces edifices supramoleculaires en determinant la nature des intermediaires cinetiques formes et leur evolution en solution en fonction du temps. Nous avons ainsi pu determiner un mecanisme de formation possible des helicates, mecanisme totalement insoupconne jusqu'alors. Nous proposons egalement un montage permettant le controle du temps de melange des especes afin d'atteindre des cinetiques rapides

Chemistry
Ph.D.
Understanding charge transport through molecular junctions and factors affecting the conductivity at the single molecule level is the first step in designing functional electronic devices using individual molecules. A variety of methods have been developed to fabricate metal-molecule-metal junctions in order to evaluate Single Molecule Conductance (SMC). Single molecule junctions usually are formed by wiring a molecule between two metal electrodes via anchoring groups that provide efficient electronic coupling and bind the organic molecular backbone to the metal electrodes. We demonstrated a novel strategy to fabricate single molecule junctions by employing the stabilization provided by the long range ordered structure of the molecules on the surface. The templates formed by the ordered molecular adlayer immobilize the molecule on the electrode surface and facilitate conductance measurements of single molecule junctions with controlled molecular orientation. This strategy enables the construction of orientation-controlled single molecule junctions, with molecules lacking proper anchoring groups that cannot be formed via conventional SMC methods. Utilizing Scanning Tunneling Microscopy (STM) imaging and STM break junction (STM-BJ) techniques combined, we employed the molecular assembly of mesitylene to create highly conductive molecular junctions with controlled orientation of benzene ring perpendicular to the STM tip as the electrode. The long range ordered structure of mesitylene molecules imaged using STM, supports the hypothesis that mesitylene is initially adsorbed on the Au(111) with the benzene ring lying flat on the surface and perpendicular to the Au tip. Thus, long range ordered structure of mesitylene facilitates formation of Au-π-Au junctions. Mesitylene molecules do not have standard anchoring groups providing enough contact to the gold electrode and the only assumable geometry for the molecules in the junction is via direct contact between Au and the π system of the benzene ring in mesitylene. SMC measurements for Au/mesitylene/Au junctions results in a molecular conductance value around 0.125Go, two orders of magnitude higher than the measured conductance of a benzene ring connected via anchoring groups. We attributed this conductance peak to charge transport perpendicular to the benzene ring due to direct coupling between the π system and the gold electrode that happens in planar orientation. The conductance we measured for planar orientation of benzene ring is two order of magnitude larger than conductance of junctions formed with benzene derivatives with conventional linkers. Thus, altering the orientation of a single benzene-containing molecule between the two electrodes from planar orientation to the upright attached via the linkers, results in altering the conductivity in a large order. Based on these findings, by utilizing STM imaging and STM-BJ in an electrochemical environment including potential induced self-assembly formation of terephthalic acid, we designed an electrochemical single molecule switch. Terephthalic acid forms large domains of ordered structure on negatively charged Au(111) surface under negative electrochemical surface potentials with the benzene ring lying flat on the surface due to hydrogen bonding between carboxylic acid groups of neighboring molecules. Formation of long range ordered structure facilitates direct contact between the π system of the benzene ring and the gold electrodes resulting in the conductance peak. On positively charged Au(111), deprotonation of carboxylic acid groups leads to absence of long range ordered structure of molecules with planar orientation and absence of the conductance peak. In this case alternating the surface (electrode) potential from negative to positive charge densities induces a transition in the adlayer structure on the surface and switches conductance value. Hence, electrochemical surface potential can, in principle, be employed as an external stimulus to switch single molecule arrangement on the surface and the conductance in the junction. The observation of conductance switching due to molecule’s arrangement in the junction lead to the hypothesis that for any benzene derivative, an orientation-dependent conductance in the junction due to the contact geometry (i.e. electrode-anchoring groups versus direct electrode-π contact) should be expected. Conventional techniques in fabricating single molecule junctions enable accessing charge transport along only one direction, i.e., between two anchoring groups. However, molecules such as benzene derivatives are anisotropic objects and we are able to measure an orientation-dependent conductance. In order to systematically study anisotropic conductivity at single molecule level, we need to measure the conductance in different and well-controlled orientations of single molecules in the junction. We employed the same EC-STM-BJ set up for SMC measurements and utilize electrochemical potential of the substrate (electrode) as the tuning source to variate the orientation of the single molecule in the junction. We investigated single molecule conductance of the benzene rings with carboxylic acid functional groups in two orientations: one with the benzene ring bridging between two electrodes using carboxylic acids as anchoring groups (upright); and one with the molecule lying flat on the substrate perpendicular to the STM tip (planar). Physisorption of these species on the Au (111) single crystal electrode surface at negative electrochemical potentials results in an ordered structure with the benzene ring in a planar orientation. Positive electrochemical potentials cause formation of the ordered structure with molecules standing upright due to coordination of a deprotonated carboxyl groups to the electrode surface. Thus, formation of the single molecule junction and consequently conductivity measurements is facilitated in two directions for the same molecule and anisotropic conductivity can be studied. In engineering well-ordered two-dimensional (2-D) molecular structures with controlled assembly of molecular species, pH can be employed as another tuning source for the molecular structures and adsorption in experiments conducted in aqueous solutions. Based on simple chemical principles, amine (NH2) groups are hydrogen bond acceptors and donors. Amines are soluble in water and protonation results in protonated (NH3+) and unprotonated (NH2) amine groups in acidic and moderately acidic/neutral solutions, respectively. Thus, amines are suitable molecular building blocks for fabricating 2-D supramolecular structures where pH is employed as a knob to manipulate intermolecular hydrogen bonding leading to phase transitions. We investigated pH induced structural changes in the 1,3,5–triaminobenzene (TAB) monolayer and the formation/disruption of hydrogen bonds between neighboring molecules. Our STM images indicate that in the concentrated acidic solution, the protonated amine groups of TAB are not able to form H-bonds and long range ordered structure of TAB does not form on the Au(111) surface. However, in moderately acidic solution (pH ~ 5.5) at room temperature, protonation on the ring carbon atom generates species capable of forming H-bonds leading to the formation of the long range ordered structures of TAB molecules. Utilizing EC-STM set up, we investigated the controllable fabrication of a TAB 2-D supramolecular structure based on amine-amine hydrogen bonding and effect of pH in formation of ordered/disordered TAB network.
Temple University--Theses

La formation contrôlée de nouveaux objets à l’échelle nanométrique représente un enjeu important pour le développement de nouveaux matériaux et de dispositifs électroniques. Dans ce contexte, l’objectif de cette thèse est de proposer de nouvelles stratégies pour contrôler la formation de nanostructures organiques sur des surfaces basées sur les concepts d’auto-assemblage supramoléculaire et de synthèse sur surface (on-surface synthesis) et d’étudier leurs propriétés. Tout d’abord, nous avons étudié par microscopie à effet tunnel (STM) en conditions ambiantes le contrôle de la taille des domaines formés à l’interface liquide-solide sur HOPG par une solution bimoléculaire d’acide trimésique (TMA) et d’acide benzoïque (BZA). Les résultats montrent que la formation des domaines est très sensible au rapport stœchiométrique entre les deux molécules et nécessite un réglage fin de ce dernier. Ensuite, nous avons étudié la polymérisation du 1,4-di(thiophen-2-yl)benzene (DTB) sur le Cu(111) sous ultra vide (UHV) par STM et par spectroscopie de photoélectrons (XPS), avec le soutien complémentaire de mesures de microscopie à force atomique non contact (nc-AFM) et d’une modélisation théorique basée sur la théorie de la fonctionnelle de la densité (DFT). Les résultats montrent la formation de chaînes hydrocarbonées non saturées interconnectées basée sur l’activation du C-S. Enfin, nous avons montré par STM et XPS sous UHV que l’utilisation du précurseur chiral bifonctionnel (R)-6-bromo-3-phenyl-2,3-dihydro-1H-inden-1-one (BrPhINDO) conduit à la formation de différentes structures liées de manière covalente sur le Cu(111) avec une inversion chirale induisant une racémisation partielle
The controlled formation of new objects at the nanoscale is an important challenge for the development of new materials and electronic devices. In this context, the objective of this thesis is to propose new strategies to control the formation of organic nanostructures on surfaces based on the concepts of supramolecular self-assembly and on-surface synthesis and investigate their properties. First, we studied by scanning tunneling microscopy (STM) at ambient conditions the control of the size of the domains formed at the liquid-solid interface on HOPG from a bimolecular solution of trimesic acid (TMA) and benzoic acid (BZA). The results show that the formation of the domains is very sensitive to the stoichiometry ratio between the two molecules and a fine-tuning of this latter is required. Then, we studied the polymerization of 1,4-di(thiophen-2-yl)benzene (DTB) on Cu(111) under ultra-high vacuum (UHV) by STM and photoelectron spectroscopy (XPS), supplemented by non-contact atomic force microscopy (nc-AFM) and theoretical modelling based on the density functional theory (DFT). The results show the formation of unsaturated hydrocarbon chains based on C-S activation. Finally, we demonstrated by STM and XPS under UHV that the use of the bifunctional chiral precursor (R)-6-bromo-3-phenyl-2,3-dihydro-1H-inden-1-one (BrPhINDO) leads to the formation of different covalently bonded structures on Cu(111) with chiral inversion inducing partial racemization

La formation de polymères de coordination poreux et chiraux ainsi que leur utilisation pour des processus énantiosélectifs est actuellement un des domaines de grand intérêt en chimie. La formation de ces matériaux est rendue possible par le biais des concepts développés dans le domaine de la tectonique moléculaire. Les travaux présentés dans cette thèse s’inscriventdirectement dans cette thématique. Les synthèses de tectons organiques chiraux sont présentées. Leur combinaison avec divers centres métalliques, via différentes méthodes de cristallisation, a permis l’obtention de monocristaux qui ont été étudiés par diffraction des rayons X sur monocristal. Dans un premier temps, des polymères de coordination homochiraux, obtenus par l’utilisation de tectons dotés de sites coordinants neutres sont présentés. Des réseaux de type cuboïde présentant des canaux monodimensionnels au sein de leur architecture sont notamment décrits. Par la suite, des édifices mono- et bi-dimensionnels de géométries diverses sont discutés. Pour certains de ces cristaux, des interactions de plus faible énergie que la liaison de coordination permettent la formation de réseaux moléculaires de plus haute dimensionnalité. Enfin, dans une dernière partie, l’utilisation de tectons dotés de sites coordinants chargés est discutée. Des réseaux tridimensionnels homochiraux poreux et robustes sont décrits. Ces derniers sont des candidats de choix pour des procédés énantiosélectifs de séparation. Leur propension à encapsuler des gaz (N2 et CO2) est présentée
The synthesis and the use of porous chiral coordination polymers for enantioselective processes are of current interest and prime importance in chemistry. These crystalline materials are mainly obtained by combinations of well-designed organic tectons and properly chosen metallic components. This thesis deals with the synthesis of organic chiral building blocks and their combinations with a variety of metallic salts leading to chiral coordination networks. In a first part, the use of tectons bearing neutral coordinating sites is described. Homochiral cuboid architectures displaying monodimensional channels are presented. In the second part, mono- and bi-dimensional networks of various geometries are described. In some cases, within crystals, interactions lower in energy than the coordination bond are observed and are responsible for the formation of molecular networks of higher dimensionality. Finally, the use of organic tectons displaying charged interaction sites is presented. Their combination with metallatectons under thermal treatments affords robust tridimensional homochiralarchitectures displaying cavities. These materials are interesting candidates for enantioselective recognition and separation. Their gas adsorption propensity (N2 and CO2) is briefly discussed

The pure silicate mesoporous material, MCM-41 having hexagonally packed cylindrical channels with a centre to centre distance of ca. 45 Å may be synthesised from a preparation containing only sodium silicate solution, a surfactant template molecule, water, and some acid. The preparation was optimised initially both for heated and unheated syntheses. The effects of aging in the gel, heating time and stirring were investigated. MCM-41 materials which were stable to calcination were prepared in an ambient temperature synthesis, with stability proportional to aging time in the gel. Heated preparations proved to have highest long range order after 3 days at 100°C in unstirred systems. The effect of pH during synthesis was then investigated. Preparations titrated against 1 M acid to maintain a constant pH during the whole of the synthesis developed much higher long-range order, as determined by the number and intensity of the observed X-ray diffraction peaks. A small counterion effect, dependant upon the type of acid used was noted. The most highly ordered materials were prepared from preparations titrated with sulphuric acid to maintain a pH of 10 during the synthesis. Heated preparations were more ordered than those carried out at ambient temperatures, although the addition of acid also promoted order in unheated syntheses. From these highly ordered materials X-ray diffraction patterns containing up to seven peaks were obtained using synchrotron radiation. These peaks could all be indexed to a hexagonal lattice. The intensity envelope for these peaks was modelled by the expected envelope for an array of cylinders. The data could not be fitted by a model containing only one cylinder, but required two concentric cylinders of different scattering length density. This indicates the presence of three regions in the MCM-41 framework. Firstly, a denser, continuous wall structure about 6 Å wide filling the regions between pores. Secondly, each pore is lined with a less dense silica region about 12 Å thick. The empty holes down the centre of each channel in this material have a radius of about 7 Å. The average bulk MCM-41 density calculated from the X-ray results and gas adsorption measurements was found to be low, around 0.83(5) g cm-3, with the denser part of the wall being 0.99 g cm-3 and the less dense lining of the pores 0.87 g cm-3. This low density model with porous walls is supported by results from neutron diffraction, inelastic and quasielastic neutron scattering measurements on hydrogen adsorbed in the pores of MCM-41, and by small angle neutron scattering using contrast variation on MCM-41 materials at all stages of preparation. Other possible interpretations of the data are presented and discussed. The behaviour of methane adsorbed in the channels of MCM-41 was also observed by quasielastic neutron scattering. Considerable alteration in the phase behaviour from that of bulk methane was observed. The melting point was depressed from 91 K in bulk methane to between 45 and 60 K for the confined methane in this system, and a liquid phase was still present in the pores at 180 K, around 70 K above the normal boiling point of the bulk material.

碩士
國立中央大學
化學學系
101
A series of supramolecular gelators, DN143, DX23, DX97,DX101 and DX47, based on anthracene or pyrene with perfluoroalkyl chain pyridine-2,6-dicarboxamides has been synthesized. All gelators show excellent gelation ability in many organic solvents. We have found that the presence of the perfluoroalkyl chains as well as the Pt(II) metal centers both contribute to the gel formation and have great effects on their resulting physical properties. A variety of spectroscopic methods have been applied to identify the intermolecular interactions upon gel formation and explore the photophysical properties. The primary driving forces for the gel formation are intermolecular hydrogen bonding, aromatic pi-pi, and C-H•••pi interactions. The supramolecular aggregates in these organogels are considered to be the J-type aggregation. SEM and TEM morphologies on the xerogels reveal that the gelators self-assembled into fibers or spheres. Interestingly, helical fiber and sphere-like morphologies were observed for DN143 and DX97. In addition, DX97 and DX101 containing Pt(II) metal centers and perfluoroalkyl chains exhibit unique properties. DX97 exhibit dual emission with both fluorescence at 406 nm and strong phosphorescence at 655 nm. In contrast, DX101 does not show any detectable phosphorescence but only fluorescence at 436 nm. Photocycloaddition product was identified for DX101 in chlorinated solvent under UV irradiation. The mechanism for the observed photochemistry likely involves singlet oxygen and proceeds with free-radical pathways.

The global pandemic of Human Immunodeficiency Virus (HIV) is responsible for the death of more than 39 million people. Currently, about 37 million people are infected with an estimated rate of 2.1 million new cases and 1.2 million HIV related deaths per annum. Over the past three decades, Antiretroviral Therapy (ART) has significantly improved HIV prognosis and health related quality of life. However, HIV still remains a significant public health and socio-economic concern due to the inability to cure or completely eradicate both long-lived latently infected cells and replication competent provirus from anatomical and lymphatic reservoirs. This has necessitated lifelong pharmacotherapy in order to keep the viral loads below detection and prevent progression of the infection to full blown Acquired Immune Deficiency Syndrome (AIDS). Presently, antiretroviral (ARVs) drugs used in the management of HIV are administered orally due to the volume and ambulatory nature of the lifelong therapeutic interventions. However, poor oral bioavailability, inadequate biodistribution and adverse side effects of many ARVs continue to preclude optimal therapeutic outcomes. In recent years, there has been an increased interest in the development of ARV delivery systems specifically tailored to improve HIV's therapeutic outcomes. Within this context, cyclodextrins (CyD) based drug delivery systems offer several possibilities for constructing an ARV drug delivery system with enhanced bioavailability, biodistribution and therapeutic performance. The traditional role of cyclodextrins (CyDs) in the pharmaceutical industry has been to enhance the aqueous solubility, physicochemical and physiological stability, the deliverability and therapeutic performance, and reduce the adverse side effects of several active pharmaceutical ingredients (APIs). Also, CyDs have been reported to modulate cytochrome P450 (CYP450) metabolism and p-glycoprotein (P-gp) efflux transport for enhanced drug pharmacokinetic profiles. Thus, this study was designed to explore the utility of CyD supramolecular systems in the development of an oral ARV delivery system with enhanced pharmacokinetic properties. Lopinavir (LPV), a potent inhibitor of HIV-1 protease and a Class 4 Biopharmaceutical Classification System (BSC) drug with poor oral bioavailability was chosen as our model drug. LPV's poor bioavailability is a combined effect of low aqueous solubility, P-gp efflux transport/low gastric permeability and CYP450 3A metabolism. Presently, LPV is clinically available as a co-formulation with suboptimal doses of ritonavir (RTV) which enhances oral bioavailability by inhibiting LPV's metabolism. The adverse side effects associated with RTV has made necessary the development of a RTV free LPV formulation. Also, paediatric formulations of LPV (even with RTV) is fraught with problems such as the presence of high quantities of ethanol and propylene glycol in the commercially available oral solution. Therefore, an in silico method was developed an validated experimentally (using ibuprofen as model drug) to study the host-guest molecular interaction between LPV and CyD, and to predict the best CyD molecule for developing a CyD based LPV delivery system. The predicted derivative of (2-hydroxyl)propyl-gamma-cyclodextrin (HP-γ-CyD) with a high degree of substitution (DS) that is, HP17-γ-CyD, was synthesized and evaluated comparatively with parent γ-CyD and commercially available HP-γ-CyD. The applicability of supercritical assisted spray drying (SASD), a non-toxic and cheap method for enhancing CyD complex formation was also evaluated. Then, polymer CyD (pCyD) sub-microcarriers were synthesized, loaded with LPV and evaluated for its ability to modulate drug release and enhance antiviral activity. The results suggests the application of in silico methodologies is a feasible approach for the rational and/or deductive development of CyD based drug delivery systems. The predicted HP17-γ-CyD facilitated a higher LPV amorphization and solubilization relative to the parent γ-CyD and commercially available HP-γ-CyD. Also, the application of SASD technique for preparing LPV-CyD complexes enhanced drug solubilization and complexation. With regards to the sub-microcarrier, results indicate the successful synthesis of a water soluble p(CyD) based on (2-hydroxyl)propyl-beta-cyclodextrin (HP-β-CyD) and methyl-beta-cyclodextrin (M-β-CyD) as monomers, and pyromellitic dianhydride as crosslinker. The physicochemical analysis of the LPV loaded pCyD revealed the successful preparation of sub-micron sized particles with good encapsulation efficiencies, a pCyD mediated amorphization of LPV and a significant increase in LPV solubilization and release. In vitro cytotoxicity of the pCyD and their LPV formulations revealed good safety profiles in Caco-2 and Sup-T1 cell lines. Results obtained from the in vitro antiviral assays revealed a dose independent HIV-1 inhibition by the synthesized pCyD and a CyD monomer dependent synergistic antiviral activity in their formulations. Overall, the study contributed to a better understanding of in silico methodologies as predictive tools for CyD selection in drug development. It was possible to completely avoid the tedious and time/resource consuming traditional approach of selecting CyD by calculating association constants from phase solubility studies or isothermal titration calorimetry. The application of SASD for drug-CyD complexation seems an interesting alternative to conventional spray drying and other methods of CyD solid complex formation. Also, considering the potential for drug dose reduction without a compromise on antiretroviral activity, the synthesized pCyDs represent a promising approach for formulating new alternatives to clinically available antiretroviral drugs. In conclusion, all the results obtained in this experimental work showed the interest of CyDs as promising vehicles for the development of ARV drug delivery systems with enhanced pharmacokinetic profiles.

Yes
We report on the use of non-equillibrium biocatalytic self-assembly and gelation to guide the reductive synthesis of gold nanoparticles. We show that biocatalytic rates simultaneously dictate supramolecular order and presentation of reductive phenols which in turn results in size control of nanoparticles that are formed.
BBSRC funding (BB/K007513/1); European Research Council under the European Union’s Seventh Framework Programme, ERC (Starting Grant EMERgE) grant agreement no. 258775.

碩士
高雄醫學大學
醫藥暨應用化學系碩士班
104
The metal-containing supramolecular complexes are often using pyridine derivatives as a coordinated bridging spacer ligand. It is rare to see isocyanides as coordinated bridging spacer ligands in supramolecular complexes. In order to expand the metal-driven isocyanide bridging spacer supramolecular chemistry, a series of iron-sulfur core complexes containing isocyanide ligands were synthesized by self-assembly reaction between [Cp2Fe2(µ-SEt)2(1,4-CNC6H5NC)2(BF4)2] (4(BF4)2) and transition metal complexes. Except the iron-sulfur core complexes, the ruthenium complex [(p-cymene)RuCl2]2 (5) and [(p-cymene)RuCl(CO2)]2 (6) also selected as the building unit to react with diisocyanide ligands to form the new type of metal-containing supramolecular complexes. The formulation of all iron-sulfur core and ruthenium complexes were confirmed by NMR and IR spectroscopy as well as the ESI-Mass spectrometry. The electrochemical behaviors study of these iron-sulfur core containing ruthenium complexes were examined to understand their electronic communication involving the bridging isocyanide spacer ligands.

Les réseaux organiques covalents (COFs) sont des réseaux bidimensionnels et tridimensionnels assemblés seulement par des atomes légers, c’est-à-dire de la première et deuxième rangée du tableau périodique. Ceux-ci ont montré des propriétés de porosité pouvant être exploitées dans le stockage, dans la catalyse et dans la séparation moléculaire. La plupart de ces matériaux ont été obtenus par une réaction finale de condensation, ce qui nuit à leurs cristallisations, donc à l’homogénéité et à la caractérisation détaillée de ces matériaux. Les p-xylylènes de Thiele et Tschitschibabin sont des molécules qui ont suscité l’intérêt pour leurs structures et leurs propriétés magnétiques. Subséquemment, Wittig a démontré que le remplacement des fragments diphénylméthylène par des fragments fluorénylidène sur le p-xylylène de Thiele donne des molécules pouvant s’oligomériser pour former un tétramère. Dans notre étude, nous avons examiné l’assemblage de dérivés fluorénylidène dans le but d’obtenir un COF. Tout d’abord, un dérivé linéaire similaire à ce que Wittig a obtenu a été synthétisé afin de vérifier l’assemblage à partir d’un cœur spirobifluorényle. Ces molécules se sont assemblées en tétramère, comme prévu, et en hexamère. Ces deux résultats ont pu être rationalisés par une étude à l’état solide par diffraction des rayons-X. L’empilement tridimensionnel a également été étudié pour ces deux molécules. Subséquemment, des dérivés tétraédriques ont été synthétisés afin d’étudier leurs assemblages. Un premier dérivé est resté sous sa forme quinoïdale et ne s’est pas assemblé, alors qu’un second dérivé a mené à un dimère partiellement assemblé. La structure de ce dernier suggère la formation d’un polymère linéaire pour ce composé dans le cas où il aurait été possible de l’assembler complètement.
Covalent organic frameworks (COFs) are ordered two-dimensional and three-dimensional frameworks assembled only from light atoms in the first and second rows of the periodic table. These frameworks have shown properties that make them potentially useful in the storage of molecular guests, in catalysis and in separation. COFs are typically obtained by a final condensation reaction, which makes their crystallization difficult and leads to materials that are inhomogeneous and impossible to characterize in detail. The p-xylylenes of Thiele and Tschitschibabin are molecules that have attracted interest because of their structures and magnetic properties. Subsequently, Wittig demonstrated that replacing diphenylmethylene fragments in these structures by fluorenylidene units allowed their oligomerisation to form tetrameric structures. In our study, we have investigated the assembly of fluorenylidene derivatives to obtain COFs. First, a linear derivative similar to that obtained by Wittig was prepared to verify the feasibility of assembly from a spirobifluorenyl core. These compounds were found to oligomerise to form a tetramer, as expected as well as a hexamer. Both results have been rationalized by a study of the crystal structures by X-ray diffraction. The three-dimensional packing has also been analyzed. Subsequently, tetrahedral derivatives were synthesized to study the possibility of analogous assembly leading to COFs. A first derivative was found to remain in its quinoidal form rather than oligomerise and a second derivative resulted in a partially assembled dimer. The structure of the latter suggests that a linear polymer could be formed by a further reaction.

Three distinct aspects, disorder, polymorphism and co-crystal formation have been addressed in molecular crystals in terms of intra- and intermolecular interactions involving halogens, weak hydrogen bonds and van der Waals interactions. A basic introductory chapter highlights the importance of these three aspects followed by a foreword to the contents. Chapter 1 employs in situ cryo-crystallization techniques to study the crystal and molecular structures of compounds which are liquids at room temperature. Section 1.1 deals with the crystal structure analyses of low melting chloro- and bromo-substituted anilines which reveal both the importance of hydrogen bonds and weak interactions involving different halogens. The halogen⋅⋅⋅halogen interactions are compared with fluorine and iodine substituted compounds to bring out the relevance of both size and polarizability characteristics. Section 1.2 describes the crystal structures of benzyl derivative compounds utilizing the concept of in situ cryo-crystallization. This analysis brings out the correlation between acidity of benzyl derivative compounds with its preference of either a (sp2)C-H⋅⋅⋅π or (sp3)C-H⋅⋅⋅π interactions in the crystal packing. Chapter 2 consists of two sections dealing with the preference of halogen⋅⋅⋅halogen interactions in supramolecular chemistry. Section 2.1 discusses a statistically large number of crystal structures in halogen substituted benzanilide compounds. It reveals the importance of hetero halogen F⋅⋅⋅X (Cl, Br), homo halogen X⋅⋅⋅X (F, Cl, Br, I), C-X⋅⋅⋅π and C-H⋅⋅⋅F interactions in terms of their directionality and preferences to complement a primary N-H⋅⋅⋅O hydrogen bond in directing the three-dimensional supramolecular assembly. Section 2.2 deals with solvent induced polymorphism which highlights the role of weak interactions in two case studies. The preference and directionality of C-H⋅⋅⋅F and Cl⋅⋅⋅Cl interactions lead to dimorphic modifications in case of 3-chloro-N-(2-fluorophenyl)benzamide whereas in case of 2-iodo-N-(4-bromophenyl)benzamide the interactions are through C-H⋅⋅⋅π and I⋅⋅⋅I contacts. Further, the analysis is supported using morphological evidence, DSC (Differential scanning calorimetry) and Powder X-ray diffraction data. Chapter 3 has three sections, concentrating on disorder and its consequence in crystal structures. Section 3.1 discusses the apparent shortening of the C(sp3)–C(sp3) bond analysed via a variable temperature X-ray diffraction study in racemic 1,1′-binaphthalene-2,2′-diyl diethyl bis(carbonate). Variable temperature single crystal X-ray diffraction studies show that the shortening is entirely due to positional disorder and not due to thermal effects. A supercell formation at T≤150 K depicts the formation of a Z'= 2 structure. Section 3.2 deals with crystal structure analysis of Ethyl-4-(2-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate which clarifies the discrepancy in the higher value of the residual electron density in the literature in terms of positional disorder of fluorine at ortho sites. The existence of fluorine atom at the para position on the phenyl ring of another isomeric molecule leads to disorder induced conformational polymorphism through the involvement of the ethyl group. The static disorder of ethyl group which is associated with only one molecule (Z′=2) could be resolved at 120 K. This supports the results of the previous section (3.1). Section 3.3 reports crystal structure analysis of disordered fluorine in benzanilide compounds. The preference of interactions involving fluorine in either ortho sites or meta sites could be one of the reasons for the positional disorder of both possible sites. With one of the structure showing high Z′ value due to differences in the occupancy of disordered fluorine atom. CSD (Cambridge Structural Database) analysis indicates that the percentage of disorder in halogenated crystal structures having halogen atom at either ortho site or meta site decreases from fluorine to iodine. Further, the analysis points out that the disorder in fluorine containing compounds is mostly localized at the fluorine position whereas for other halogenated disordered structures, the disorder appears at other parts of the molecule. Chapter 4 discusses co-crystal formation and analysis of intermolecular interactions. It consists of two sections. Section 4.1 discusses co-crystal formation of nicotinamide with benzoic acid and seven other derivatives by changing the functional group at different positions of benzoic acid. Hydroxyl (-OH) group at 4/3-postion of benzoic acid prefers phenol⋅⋅⋅pyridine synthon when at 2-position it prefers acid⋅⋅⋅pyridine synthon. The preference of amide anticatemer over dimer synthon is supported by additional C-H⋅⋅⋅O hydrogen bonds. In case of 3,5-dinitro-2-hydroxy benzoic acid, the disorder in hydroxyl (-OH) group at ortho site leads to salt formation. Section 4.2 describes co-crystal study of adenine and thymine (AT) as free nucleobases. This result reveals the formation of AT (2:1) complex with both Hoogsteen and “quasi-Watson-Crick” hydrogen bonds. The hydrogen bonded bases using the Hoogsteen and the “quasi-Watson-Crick” interactions generate a hexagonal supramolecular motif. Four water molecules are located inside the hexagonal void of this complex. A high temperature study on the same crystal shows that at 313K, one of the water molecules escapes from the lattice resulting in the small change in unit cell parameters. However, the space group remains the same and the hexagonal void remains unaltered. With further increase in temperature, the crystal deteriorates irreversibly which clearly brings out the importance of water molecule in the molecular recognition of adenine-thymine complex. Chapter 5 discusses crystal structure analysis of trans-atovaquone (antimalarial drug), its new polymorph form including one stereoisomer (cis) and five other derivatives with different functional groups. Based on the conformational features of these compounds and the characteristics of the nature of hydrogen bonding and other weak intra and intermolecular interactions, docking studies with cytochrome bc1 complex provide valuable insight into the atomistic details of protein-inhibitor interactions. The docking results reveal that atovaquone and its derivatives, owing to their nature of hydrogen bond and the propensity towards the formation of weaker hydrogen bonds involving the chlorine atom as well appear as good candidates for drug evaluation.

Three distinct aspects, disorder, polymorphism and co-crystal formation have been addressed in molecular crystals in terms of intra- and intermolecular interactions involving halogens, weak hydrogen bonds and van der Waals interactions. A basic introductory chapter highlights the importance of these three aspects followed by a foreword to the contents. Chapter 1 employs in situ cryo-crystallization techniques to study the crystal and molecular structures of compounds which are liquids at room temperature. Section 1.1 deals with the crystal structure analyses of low melting chloro- and bromo-substituted anilines which reveal both the importance of hydrogen bonds and weak interactions involving different halogens. The halogen⋅⋅⋅halogen interactions are compared with fluorine and iodine substituted compounds to bring out the relevance of both size and polarizability characteristics. Section 1.2 describes the crystal structures of benzyl derivative compounds utilizing the concept of in situ cryo-crystallization. This analysis brings out the correlation between acidity of benzyl derivative compounds with its preference of either a (sp2)C-H⋅⋅⋅π or (sp3)C-H⋅⋅⋅π interactions in the crystal packing. Chapter 2 consists of two sections dealing with the preference of halogen⋅⋅⋅halogen interactions in supramolecular chemistry. Section 2.1 discusses a statistically large number of crystal structures in halogen substituted benzanilide compounds. It reveals the importance of hetero halogen F⋅⋅⋅X (Cl, Br), homo halogen X⋅⋅⋅X (F, Cl, Br, I), C-X⋅⋅⋅π and C-H⋅⋅⋅F interactions in terms of their directionality and preferences to complement a primary N-H⋅⋅⋅O hydrogen bond in directing the three-dimensional supramolecular assembly. Section 2.2 deals with solvent induced polymorphism which highlights the role of weak interactions in two case studies. The preference and directionality of C-H⋅⋅⋅F and Cl⋅⋅⋅Cl interactions lead to dimorphic modifications in case of 3-chloro-N-(2-fluorophenyl)benzamide whereas in case of 2-iodo-N-(4-bromophenyl)benzamide the interactions are through C-H⋅⋅⋅π and I⋅⋅⋅I contacts. Further, the analysis is supported using morphological evidence, DSC (Differential scanning calorimetry) and Powder X-ray diffraction data. Chapter 3 has three sections, concentrating on disorder and its consequence in crystal structures. Section 3.1 discusses the apparent shortening of the C(sp3)–C(sp3) bond analysed via a variable temperature X-ray diffraction study in racemic 1,1′-binaphthalene-2,2′-diyl diethyl bis(carbonate). Variable temperature single crystal X-ray diffraction studies show that the shortening is entirely due to positional disorder and not due to thermal effects. A supercell formation at T≤150 K depicts the formation of a Z'= 2 structure. Section 3.2 deals with crystal structure analysis of Ethyl-4-(2-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate which clarifies the discrepancy in the higher value of the residual electron density in the literature in terms of positional disorder of fluorine at ortho sites. The existence of fluorine atom at the para position on the phenyl ring of another isomeric molecule leads to disorder induced conformational polymorphism through the involvement of the ethyl group. The static disorder of ethyl group which is associated with only one molecule (Z′=2) could be resolved at 120 K. This supports the results of the previous section (3.1). Section 3.3 reports crystal structure analysis of disordered fluorine in benzanilide compounds. The preference of interactions involving fluorine in either ortho sites or meta sites could be one of the reasons for the positional disorder of both possible sites. With one of the structure showing high Z′ value due to differences in the occupancy of disordered fluorine atom. CSD (Cambridge Structural Database) analysis indicates that the percentage of disorder in halogenated crystal structures having halogen atom at either ortho site or meta site decreases from fluorine to iodine. Further, the analysis points out that the disorder in fluorine containing compounds is mostly localized at the fluorine position whereas for other halogenated disordered structures, the disorder appears at other parts of the molecule. Chapter 4 discusses co-crystal formation and analysis of intermolecular interactions. It consists of two sections. Section 4.1 discusses co-crystal formation of nicotinamide with benzoic acid and seven other derivatives by changing the functional group at different positions of benzoic acid. Hydroxyl (-OH) group at 4/3-postion of benzoic acid prefers phenol⋅⋅⋅pyridine synthon when at 2-position it prefers acid⋅⋅⋅pyridine synthon. The preference of amide anticatemer over dimer synthon is supported by additional C-H⋅⋅⋅O hydrogen bonds. In case of 3,5-dinitro-2-hydroxy benzoic acid, the disorder in hydroxyl (-OH) group at ortho site leads to salt formation. Section 4.2 describes co-crystal study of adenine and thymine (AT) as free nucleobases. This result reveals the formation of AT (2:1) complex with both Hoogsteen and “quasi-Watson-Crick” hydrogen bonds. The hydrogen bonded bases using the Hoogsteen and the “quasi-Watson-Crick” interactions generate a hexagonal supramolecular motif. Four water molecules are located inside the hexagonal void of this complex. A high temperature study on the same crystal shows that at 313K, one of the water molecules escapes from the lattice resulting in the small change in unit cell parameters. However, the space group remains the same and the hexagonal void remains unaltered. With further increase in temperature, the crystal deteriorates irreversibly which clearly brings out the importance of water molecule in the molecular recognition of adenine-thymine complex. Chapter 5 discusses crystal structure analysis of trans-atovaquone (antimalarial drug), its new polymorph form including one stereoisomer (cis) and five other derivatives with different functional groups. Based on the conformational features of these compounds and the characteristics of the nature of hydrogen bonding and other weak intra and intermolecular interactions, docking studies with cytochrome bc1 complex provide valuable insight into the atomistic details of protein-inhibitor interactions. The docking results reveal that atovaquone and its derivatives, owing to their nature of hydrogen bond and the propensity towards the formation of weaker hydrogen bonds involving the chlorine atom as well appear as good candidates for drug evaluation.

碩士
國立臺灣大學
化學研究所
107
Forming supramolecular assemblies and controlling their behaviors via non-covalent interactions mimicking multi-functional materials have drawn much attention. Utilization of strong and directional interactions such as metal-ligand coordination can achieve spontaneous formation of selective, simple, and reversible supramolecular assemblies. However, it still remains a great challenge to monitor the underlying supramolecular assembly temporally. Herein, a new metal ion-responsive azacrown coumarin-conjugated photoluminescent polypeptide (ACCP) was designed and synthesized via in situ generated N-carboxyanhydride from the corresponding activated urethane monomer to exploit the metal ion-induced supramolecular assembly behaviors. After screening with various metal ions in either acetonitrile or chloroform, the results showed that ACCP˙Cu2+ exhibited blue emission in acetonitrile. However, ACCP dissolved in chloroform displayed strong fluorescence intensity enhancement only in the presence of either Hg2+ or Na+. In the combination of the absorption and the fluorescence profile, the morphologies of ACCP can be deduced. Notably, ACCP can also induce the formation of mercury nanoparticle. The morphologies of the mercury nanoparticle was 10 nm solid nanosphere stabilized by ACCP which was confirmed by transmission electron microscope. ACCP induced mercury nanoparticle was further used as the catalyst in Beckmann rearrangement. The preliminary results show that ACCP induced mercury nanoparticle was unable to catalyze the reaction due to the fact that the mercury nanoparticle was encapsulated compactly in the interior of the polymersome, rendering the mercury nanoparticles not accessible to the substrates. Further optimization of the reaction condition is required. Inspired by the ACCP induced mercury nanoparticle, polypeptide containing the pyridine ligands were designed and synthesized. Taking the advantage of the chirality in the polypeptide and the immobilization of the palladium via pyridine ligands, it is hoped to achieve good stereoselectivity in the synthesis of unnatural amino acid and the recover the palldium. A new synthetic strategy was developed to synthesize polymerizable monomer with the pyridine ligand to mitigate the contamination of the palladium needed to used in the original strategy. Based on this strategy, PPy-Lys, MPy-Lys, OPy-Lys, and Y-Lys were successfully synthesized, PPy-PLL and MPy-PLL were obtained in good yield with molecular weight around 8 kDa. PPy-PLL was further used as a ligand to C-H activation. The results revealed that PPy-PLL was unable to improve either yield or enantioselectivity. New ligands are required to achieve the C-H activation and high enantioselectivity.