Doctor of Philosophy / Chemistry / Christer B. Aakeroy / A series of co-crystallizations between four biimidazole based compounds with nine symmetric aliphatic di-acids and fifteen perfluorinated halogen-bond donors were carried out to determine if a MEPS based ranking can be used to effectively assign selectivity in hydrogen- and halogen-bond interactions. The results suggested that a simple electrostatic view provides a reliable tool for successfully implementing the practical co-crystal synthesis with desired connectivity. MEPS based selectivity guidelines for halogen-bond interactions were explored in co-crystallizations between twelve asymmetric ditopic acceptors and nine halogen-bond donors. If the difference between the two acceptor sites is below 35 kJ/mol, no selectivity was observed; above 65 kJ/mol halogen bond selectivity dominates and mid ΔE range was recognized as the grey area where predictions cannot be made. To examine competition between hydrogen and halogen bonds, five heteroaryl-2-imidazoles were co-crystallized with fifteen halogen-bond donors. It was found that halogen bonds prefer best the acceptor site, demonstrating that a suitably activated halogen-bond donor can compete with a strong hydrogen-bond donor. The benefits of ‘double activation’ for promoting halogen bond effectiveness was explored with nine haloethynylnitrobenzenes. The positive potential on halogen atoms was enhanced through a combination of an sp-hybridized carbon and electron-withdrawing nitro group(s). Iodoethynylnitrobenzenes were identified as the most effective halogen-bond donors reported to date and the compounds were exploited for the interaction preferences of nitro group and nitro⋯X-Csp interactions were identified as synthetic tools for energetic co-crystal assembly. A synthetic strategy for the deliberate assembly of molecular polygons was developed utilizing bifurcated halogen bonds constructed from N-oxides and complementary halogen-bond donors via co-crystallization. A convenient, effective, and scalable protocol for stabilizing volatile liquid chemicals with co-crystallization was achieved. Through the use of halogen-bonding, liquid iodoperfluoroalkanes were transformed into crystalline materials with low-vapor pressure, considerable thermal stability and moisture resistance. To stabilize the energetic compound ethylenedinitramine, a co-crystallization approach targeting the acidic protons was employed. Eight co-crystals were obtained and the acceptors were identified as supramolecular protecting groups leading to diminished reactivity and enhanced stability while retaining the desirable energetic properties.

Synthèse et utilisation de mimes de quadruplexes contraints pour l'évaluation de ligands II est maintenant bien connu que l'ADN simple brin peut s'associer sous différentes conformations telles que la double hélice, les triplexes, les i-motifs ou bien encore les G-quadruplexes. Ces dernières années les structures de type quadruplexes (G-quadruplexes et i-motif) ont suscité un certain intérêt notamment pour leur implications au niveau cellulaire (maintenance des télomères, activation de gènes…). C'est pourquoi de nombreuses équipes travaillent sur le développement de ligands affins pour ces structures qui pourraient agir en tant qu'anticancéreux. Cependant, le fait que les quadruplexes présentent un polymorphisme important(variabilité du nombre de brins dans la structure, des différents types de boucles et de l'orientation des brins) rend la compréhension des interactions entre un ligand et le quadruplexe plus difficile. Dans ce contexte, l'équipe développe un nouveau concept, « Template Assisted Synthesis of Quadruplexes » (TASQ) dont le but est d'obtenir un quadruplexe ne présentant qu'une topologie de façon contrôlée afin de permettre des études plus précises sur la façon dont un ligand pourrait interagir avec les quadruplexes. La première partie de ce manuscrit reporte l'évaluation par résonnance plasmonique de surface de complexes métalliques en tant que ligands de G-quadruplexe. Ces études reposent sur l'utilisation d'un premier mime de G-quadruplexe parallèle sur lequel deux séries de complexes sont testées : des métalloporphyrines et des ligands de type salphen. La seconde partie du manuscrit décrit la synthèse de mimes de G-quadruplexes antiparallèle. Elle repose sur l'utilisation du gabarit peptidique qui relié aux séquences spécifiques d'oligonucléotides de façon adéquat contraint la structure. Pour se faire, deux réactions chimiosélectives ont été utilisées : la cycloaddition 1,3 dipolaire de Huisgen et la ligation oxime. Les travaux reportés concernent trois types de structure mimant un i-motifs, des G-quadruplexes tétramoléculaires ou bimoléculaires. / Synthesis and use of constrained quadruplexe mimic for the ligand evaluation It has now been shown that single stranded DNA can fold into hairpin, triplex, i-motif and G-quadruplexe structures containing non canonical base pairing. In particular quadruplex structures (G-quadruplexes and i-motif) have generated interest because the formation is considered to have important consequences at the cellular level (telomere maintenance, oncogene activation…). Therefore, the design of small molecules (ligands) targeting quadruplexes is under development, in particular to obtain anticancerous molecules. Nevertheless G-quadruplexes exhibit a wide structural polymorphism (different kind of loop, strand orientation, number of strands) making investigation of ligand tricky. In this context, we have developed a new concept called 'Template Assisted Synthesis of Quadruplex' (TASQ) with aim to constrain the G-quadruplex in a single conformation which enables the study of the interactions of ligand more specifically for a single topology. In the first part of this manuscript, we describe studies by using surface plasmon resonance (SPR) of metal complexes as G-quadruplex ligands. The investigation was performed using a first parallel G-quadruplex as model to interact with two kinds of metal complexes: metalloporphyrins and salphen. The second part of the manuscript reports the work concerning the synthesis of antiparallel quadruplexes. The strategy is based on the use of a peptide scaffold in which the suitable oligonucleotide sequences are anchored with specific orientation. For this purpose two compatible chemistries are used (1,3 dipolar Huisgen cycloaddition and oxime ligation). Three kinds of antiparallel quadruplexe mimics have been investigated: i-motif, tetramolecular G-quadruplexes and loop-constrained G-quadruplexes.

Le concept central de cette thèse est de mettre en avant trois grandes propriétés du liquide ionique, c'est à dire ses propriétés structurées et structurantes qui sont complémentaires à leurs propriétés usuelles (conductivité ionique, stabilité thermique, stabilité électrochimique), mais il ne s’agit là que d’une facette du travail. En effet, la synthèse des liquides ioniques rédox est l’un des ancrages fort de ce travail : ainsi des liquides ioniques biredox (porteur de groupements redox à la fois sur l’anion et le cation) ont pu être synthétisés pour la première fois. Cette électro-activité apporte un éclairage nouveau dans le développement d'électrolytes pour les supercondensateurs dont nos capacités spécifiques sont deux à cinq fois plus grandes que les valeurs de la littérature dans le domaine. Parallèlement, des liquides ioniques redox ont été associés à des nanotubes de carbone; les composites obtenus (nommé bucky Gel redox) ont été mis en œuvre avec succès comme matériaux d’électrode pour l’étude des dynamiques des cascades de transferts électroniques et ioniques. Outre l’obtention de ces résultats électrochimiques, les liquides ioniques ont été structurés par synthèse supramoléculaire. Ainsi des liquides ioniques polymérisés ont été obtenus et mis en forme par électrofilage puis testés en tant qu’électrolyte solide dans un dispositif supercondensateur. Les propriétés électrochimiques de l’ensemble de ces objets liquides ioniques ont fait l’objet d’études approfondies par voltammétrie cyclique, spectroscopie d’impédance électrochimique, cyclages galvanostatiques et microscopie électrochimique à balayage. Les résultats obtenus valident totalement le concept de départ dans le fait jouer sur les chimies moléculaire, supramoléculaire et macromoléculaire des liquides ioniques pour améliorer les dispositifs de stockage électrochimique de l’énergie. / The central concept of this project is to highlight three major ionic liquid properties. It lies on the control of the structured and structuring properties that are considered as complementary to the usual ionic liquids properties (ionic conductivity, thermal stability, electrochemical stability). However, this is a relatively small part of this work. The strong key point is the synthesis of redox ionic liquids. In this work a new biredox ionic liquids (contaning redox moieties both on the anion and the cation constituting the ionic liquid) have been successfully synthesized for the first time. This electro-activity opens the development of electrolytes for supercapacitors whose the specitific capacity is between two and five times larger than the values found in the literature. Meanwhile, redox ionic liquids have been associated with carbon nanotubes; the obtained composites were implemented as electrode materials for the study of dynamic electron transfer and ionic transfer. Besides these results, ionic liquids have been structured by supramolecular chemistry. Polymerized ionic liquids were obtained, shaped by electrospinning and tested as a solid electrolyte in a supercapacitor system. The electrochemical properties of these components (electrolyte materials or electrode materials) have been extensively studied by cyclic voltammetry, electrochemical impedance spectroscopy, galvanostatic cycling and scanning electrochemical microscopy. The results completely validate the original concept to take advantage of molecular, supramolecular and macromolecular chemistries of ionic liquids to improve electrochemical energy storage devices.

Contrôler les forces supramoléculaires et chirales a toujours été un défi pour la communauté scientifique. Dynablocks sont amphiphile basés sur des liaisons covalentes réversibles (imine) qui, dans l’eau, s’auto–assemblent en mésophases. Avec un nouveaux aldéhydes chargés et avec divers types d'amines (pKa et chaînes de PEG variables) dynablocks chargées ont été utilisés pour ajuster les surfaces micellaires (inversion noyau/coquille). Nous avons également étudié les propriétésd'auto-réplication (autopoiesis) et leur intérêt pour les premiers réplicateurs de la Terre prébiotique. Dynablocks non chargés ont plutôt été utilisés pour l'étude des structures à haute concentration et pour l’amplification chirale. Dans ce dernier,peptides amphiphiles dynablocks agissaient comme gelators avec une matrice formée d’un réseau 3D entrelacé. Une torsion supramoléculaire a été observée et une amplification chirale au niveau de la morphologie des structures a pu être détectée par AFM et TEM. / Taking the control over supramolecular and chiral forces has always been a challenge for the scientific community. Dynablocks are amphiphiles based on reversible imine covalent bond that, in water, self-assemble in mesophases. With a new charged aldehyde, charged dynablocks were used to tune the surface of the assemblies directing the charged heads inward or outward, changing the PEG units and the pKa of the amines. Moreover, we continued the study on focusing the interest on self-replicating properties (autopoiesis), topic that provides insights for the first replicators that could have appeared in the prebiotic Earth. Non-charged dynablocks were instead employed for the study of structures in high concentration and for chiral amplification. In this latter, peptide amphiphilic dynablocks acted as gelators with a typical 3D intertwined network matrix. A supramolecular twist was observed and a chiral amplification in the structures morphologies was detected in AFM and TEM pictures.

As propriedades no estado sólido de um insumo farmacêutico ativo (IFA) estão diretamente relacionadas com a eficácia terapêutica de um medicamento. Entre todas as propriedades físicas e químicas, que são dependentes doarranjo cristalinodo IFA, destaca-se a solubilidade e a estabilidade, que são as características mais importantes de um fármaco, na medida em que podem alterar a biodisponibilidade. Dentro dessa perspectiva, a engenharia de cristaistem cada vez mais se consolidado como uma estratégia para aperfeiçoar as propriedades no estado sólido de um IFA. Neste trabalho, oito novas formas sólidas cristalinas, entre sais e cocristais, dos fármacos com ação anti-tuberculose etionamida (ETH), etambutol (ETB) e isoniazida (INH), foram preparadas e tiveram suas estruturas cristalinas determinadas por difração de raios X por monocristal. Além disso, todas as modificações cristalinas obtidas foram caracterizadas por difração de raios X por policristais, espectroscopia vibracional no infravermelho e Raman, calorimetria exploratória diferencial, termogravimetria e microscopia ótica térmica. Por fim, estudos de solubilidade em equilíbrio e de estabilidade em atmosfera úmida também foram realizados. A nova modificação cristalina da ETH, o sal nitrato de ETH, foi planejada visando melhorar a solubilidade aquosa deste IFA (∼0,4 mg mL-1). Este é o primeiro relato de uma estrutura de ETH que cristalizou com quatro independentes pares iônicos (ETH+/NO3-) na unidade assimétrica. A análise do empacotamento cristalino e das interações intermoleculares permitiu estabelecer os atributos estruturais que explicam a menor estabilidade térmica e a elevada solubilidade (cerca de 300 vezes maior) deste sal, em comparação com a forma neutra da ETH. A preparação dos novos sais de ETB foi feito considerando o cárater básico da molécula, o que permitiu a obtenção de três novos sais a partir da reação do ETB com os ácidos oxalico, maleico e tereftálico. O desenho dessas formas sólidas teve como principal objetivo minimizar os efeitos da elevada higroscopicidade do ETB, que é tão prejudicial para formulações farmacêuticas. Este objetivo foi alcançado, uma vez que o sal oxalato de ETB, reportado neste trabalho, mostrou ser não-higroscópico. Por fim, quatro novos cocristais da INH, sendo dois cocristais polimórficos, foram preparados por meio de reações estequiométricas deste IFA com ácidos carboxílicos aromáticos derivados do ácido benzóico. O desenho dessas novas modificações cristalinas teve como intuito principal explorar a diversidade de síntons supramoleculares formados entre a INH e moléculas contendo o grupo COOH. A análise dos empacotamentos cristalinos das formas I e II do cocristal INH-PABA, mostrou que este é um típico caso de polimorfismo orientacional. Portanto, os resultados desta dissertação trazem importantes contribuições científicas para a diversidade de formas sólidas, apresentando revelância para o setor farmacêutico no que se refere ao desenvolvimento de novas formulações contendo fármacos anti-tuberculose. / Solid state properties of an active pharmaceutical ingredients (API) are directly related to drug performance. Among all physical and chemical properties dependent on the crystal arrangement of a drug, stability and solubility are the main ones that alter its bioavailability. In this sense, crystal engineering is a strategy to improve solid state properties of drugs. In this work, eigth new multicomponent solid forms (salts and cocrystals) of the tuberculostatic drugs ethionamide (ETH), ethambutol (ETB) and isoniazid (INH) were prepared and their crystal structures were elucidated by single crystal X-ray diffraction. In addition, the crystal modifications were also characterized by powder X-ray diffraction, infrared and Raman vibrational spectroscopy, differential scanning calorimetry, thermogravimetry and Hot-stage microscopy. Finally, equilibrium solubility studies and stability experiments in humid atmosphere were also performed. The new supramolecular modification of ETH, ethionamide nitrate salt, was designed in order to improve the aqueous solubility of the API (∼0.4 mg ml-1). This salt is the first ETH structure that has been crystallized with four independent ionic pairs (ETH+/NO3-) in the asymmetric unit. The analysis of crystal packing and intermolecular interactions allowed to establish the structural attributes that explain the lower thermal stability and high solubility (about 300 times higher) of this salt compared to the neutral ETH form. Due its high hygroscopicity, ETB is known for catalyzing the degradation of isoniazid and rifampicinin pharmaceutical formulations. In order to avoid or even minimize these mutual drug-drug interactions, in this work we have focused on the development of less hygroscopic multicomponent solid forms of ETB. The preparation of the new ETB crystal modifications was carried out considering the pKa values of the molecule, which allowed the design of three new salts (namely oxalate, maleate and terephthalate). These salts were obtained from the reaction of ETB with the carboxylic acids: oxalic, maleic and terephthalic. The hygroscopic nature of these salts was evaluated and all of them were found to be hygroscopic, with exception of ETB oxalate. Finally, four novel INH cocrystals, being two polymorphic forms, with aromatic carboxylic acids derivatives were rationally prepared. The design of these crystal forms aimed to explore the diversity of supramolecular synthons formed between INH and molecules containing COOH. The crystal packing analysis of the INH-PABA cocrystals (polymorphs I and II), showed that this is a typical case of orientational polymorphism. Therefore, the scientific contributions of this work show the diversity of the solid forms and define candidates to new anti-tuberculosis API\'s solid formulations.

O estudo das reações de agregação em sistemas automontados é de grande interesse científico pela grande variedade de aplicações que tais colunas podem desempenhar. O presente trabalho teve como objetivo investigar as propriedades gerais de colunas supramoleculares formadas por complexos de coordenação que contêm platina, paládio e zinco. Esta investigação foi feita através do método semiempírico PM7. Os agregados supramoleculares investigados tiveram suas geometrias otimizadas e foram submetidos a cálculos termoquímicos. Pôde-se investigar as influências do metal e dos ligantes nos mecanismos gerais e propriedades das colunas, uma vez que utilizaram-se dois ligantes distintos. Estudou-se compostos de coordenação cujos ligantes foram o 2,6-bis(1H-1,2,4-triazol-5-il)piridina e oligofenilenoetinilenos (OPE) piridínicos. Realizou-se cálculos utilizando o modelo de solvatação contínua COSMO com água e metilciclohexano (MCH), o que permitiu avaliar os efeitos dos solventes nas energias de dimerização dos sistemas estudados. Os resultados obtidos para os derivados de OPE indicaram que as colunas supramoleculares desta classe que contêm Zn(II) apresentam anticooperatividade, exibindo energias de Gibbs de formação para o vácuo a 298 K positivas do dímero ao decâmero. Os resultados de solvatação contínua indicaram que a formação de um dímero deste composto é termodinamicamente favorável de 278 K para água e 267 K para o MCH, enquanto que para o vácuo a temperatura na qual a energia de Gibbs de dimerização é negativa ocorre em 246 K. Tal resultado aponta que o principal efeito de formação de colunas baseadas neste composto em altas temperaturas é primariamente um efeito solvofóbico que depende da polaridade do solvente. Observou-se a cooperatividade em vácuo e em ambos os solventes das colunas de derivados de OPE que contêm Pd(II) e Pt(II). Além destes fatos, as distâncias entre os centros metálicos diminuíram conforme monômeros eram adicionados à coluna, o que indica a existência de interações metalofílicas no sistema. Este resultado é corroborado experimentalmente por um artigo de Albuquerque el al. no caso do sistema de derivado de OPE que contém Pd(II). Para os sistemas cujos ligantes eram a 2,6-bis(1H-1,2,4-triazol-5-il)piridina, houve cooperatividade para ambas as colunas baseadas em Pd(II) e Pt(II), e houve para o sistema cujos centros metálicos são o Pt(II) uma transição não observada para todos os outros sistemas estudados; houve comportamento distinto das mudanças de distâncias entre monômeros no sistema triazol pridínico baseado em Pd(II) em relação àquele baseado em Pd(II) derivado de OPE. Este resultado indica a soma de dois efeitos no sistema OPE baseado em Pd(II): o de interações metalofílicas e de empilhamentos π-π. Como um todo, os resultados indicam que as principais interações envolvidas nas formações das colunas supramoleculares são interações de empilhamento π-π e metalofílicas para quatros compostos em graus diversos, exceto para o derivado de OPE baseado em Zn(II), que tem como principal força-motriz de agregação interações solvofóbicas. Perspectivas para este projeto: continuação da modelagem dos sistemas estudados por dinâmica molecular, com a simulação das interações de várias colunas formadas pelos monômeros estudados através do CP2K e publicação de um artigo com os resultados obtidos. / The study of aggregation reactions in self-assembled systems is of great scientific interest due to the wide range of applications which such resulting columns can play. Herein, we had the objective of investigating the general properties of supramolecular columns formed coordination complexes which contain platinum, palladium and zinc. This investigation was carried through the semiempirical method PM7. The investigated supramolecular aggregates were optimized, and their optimized geometries were subjected to thermochemical calculations. In this sense we could probe the influences of metals and ligands onto the general mechanisms and columnar properties, once were herein used two different ligands. The two ligands were 2,6-bis(1H-1,2,4-triazol-5-il)pyridine and oligophenyleneethynediyl (OPE) pyridine derivatives. COSMO solvation model -based calculations in water and methylcyclohexane (MCH) were performed in order to evaluate solvents effects on dimerization Gibbs energies of the studied systems. The results obtained for the OPE derivative based on Zn(II) pointed an anticooperative process in vacuum at 298K, exhibiting positive Gibbs energies of formation from the dimer to the decamer. The results from continuum solvation calculations indicate the formation of a dimer based on this Zn(II) molecule to be thermodynamically favorable at 278 K for water and at 267 K for MCH, while in vaccum this point lies at 246 K. This results indicates the formation of supramolecular columns based on this compound are formed in higher temperatures primarily due to solvophobic effects, and the intensity of this effect depends on the solvent polarity. The columns of OPE derviatives which contained Pd(II) and Pt(II) both showed cooperativity in the aggregation process. Besides these thermodynamic results, both of those columns showed monotonic distance shortening due to columns increasing process. This is an indicative of metallophilic interactions taking place in these aggregates. This result for Pd(II) is experimentally supported by a paper od Albuquerque et al. for the columns containing 2,6-bis(1H-1,2,4-triazol-5-il)pyridine cooperativity was observed for both the columns--those which contain Pd(II) and Pt(II)--, and for the Pt(II)-based columns of this class it was observed a transition not of most eneregetically favoured mechanisms not observed for all the other systems studied. A difference on the behavior of average monomer distances took place in the triazol pyridine Pd(II) compound when compared to its metal-related OPE derivative. This result indicates the summation of effects in the OPE-based Pd(II) system: the one of metallophilic interactions and π-π stacking interactions. As a whole, the results indicate π-π stacking and metallophilic interactions to be responsible for aggregation processes in diverse intensities for four of the compounds, except for that in the Zn(II)-based OPE derivative, which has the main aggregation effect as solvophobic interactions. The main perspectives for this project are the continuation of the modelling of the herein studied systems by molecular dynamics, simulating the interactions of many columns by the CP2K program, and the publication of a paper which contains the results obtained and presented in this dissertation.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-04-27T17:37:56Z No. of bitstreams: 1 stefanosleitegeorgopoulos.pdf: 4197342 bytes, checksum: 2974d92b3639af53c51f602c3cd7723f (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-13T13:03:11Z (GMT) No. of bitstreams: 1 stefanosleitegeorgopoulos.pdf: 4197342 bytes, checksum: 2974d92b3639af53c51f602c3cd7723f (MD5) / Made available in DSpace on 2017-05-13T13:03:11Z (GMT). No. of bitstreams: 1 stefanosleitegeorgopoulos.pdf: 4197342 bytes, checksum: 2974d92b3639af53c51f602c3cd7723f (MD5) Previous issue date: 2014-08-25 / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / A investigação das soluções de ácido esquárico (H2SQ), diprótico, em dimetilsulfóxido, utilizando a espectroscopia Raman, com o auxílio do cálculo dos métodos numéricos, possibilitou identificar e determinar quantitativamente diversas espécies formadas em solução, distinguindo também as possíveis interações entre o solvente e o soluto e, ainda, a interação entre os solutos vizinhos. A identificação destas interações permitiu tanto a descoberta de espécies químicas na solução, como o H2SQ não-dissociado, formando complexo e não formando complexo, como a fração de H2SQ que se dissociou, formando o ânion monovalente hidrogeno-esquarato (HSQ-) e o ânion divalente esquarato (SQ2-). Também se fez a determinação do tipo de interação predominante que ocorre entre os H2SQ, explicando-se a razão de surgir a cor rosa nas soluções que contêm o H2SQ como soluto, através da interação π-π entre os anéis vizinhos. A formação de sistemas cristalinos através dos sais contendo os cátions tetraalquilamônio e os ânions originados dos oxocarbonos, tais como o íon SQ2-, o ânion divalente croconato e o íon HSQ-, fornece condições de investigar como a variação do volume do cátion influencia na forma da dissociação iônica sofrida pelo H2SQ. Ao compararmos os diferentes sais de tetraalquilamônio, podemos perceber a avidez do ânion divalente croconato, por moléculas de água, e a preferência dos ânions derivados do H2SQ e do próprio H2SQ por realizar ligações de hidrogênio entre si, em solução aquosa. Estes sistemas cristalinos mostram claramente a maior “maciez” da nuvem eletrônica dos íons originados a partir da dissociação iônica do H2SQ do que a daqueles originados no íon croconato. A formação exclusiva do íon SQ2-, ligado, por ponte de hidrogênio, a outros dois H2SQ, no esquarato de tetrabutilamônio, enquanto no sal de tetrapropilamônio há apenas dois íons HSQ-, ligados por pontes de hidrogênio entre si, mostram o quanto o volume do cátion influencia na quantidade de dissociação iônica sofrida pelo H2SQ. / Investigations of the diprotic squaric acid (H2SQ) solutions in dimethylsulfoxide using Raman spectroscopy supported by numerical method calculation, were able to identifying and measure the amounts of the several species present in solutions, taking into account the interactions between solvent and solute, as well as the neighbouring solutes. The identification of such interactions allowed the discover of the chemical species present in the solution, as for instance the complex and non-complex H2SQ associated species, and the dissociated H2SQ, as a fraction of the hydrogen squarate anion (HSQ-) and divalent anion squarate (SQ2-). In addition, the type of interaction between neighbors H2SQ has also been determined, justifying the reason of an emerging pink color for the H2SQ solutions, probably generated by π-π interaction between neighbor rings of H2SQ species. The synthesis of a crystaline system originated by tetraalkylammonium cations and oxocarbon anions, as a SQ2- ion, croconate divalent anion and HSQ- ion was able to investigate how the variation of the cationic volume can influence the type of ionic dissociation presented by the different H2SQ species. When comparing different tetraalkylammonium salts, it can be noticed a great affinity by water molecules from croconate divalent anion, and the preference of the anions derived from H2SQ to perform hydrogen bonds between them, in aqueous solution. This crystalline system shows more “softly” electronic clouds of the ions originated from ionic dissociation of the H2SQ than croconate ion. Exclusive formation of the SQ2- ion, bonded by htdrogen bonds, for two H2SQ species, in the tetrabutylammonium squarate salts, while in the tetrapropylammonium salts have only two HSQ- ions, bonded by hydrogen bonds between them, has also showed how the cation volume can be an important influence for the ionic dissociation quantities suffered by H2SQ.

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No. of bitstreams: 1 elgteelminborgesdepaula.pdf: 3380575 bytes, checksum: 18f97b33fbd0bd8930a6495505ebf65e (MD5) Previous issue date: 2009-07-30 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Este trabalho consiste na síntese e caracterização de complexos inéditos envolvendo as espécies oxocarbônicas ácido esquárico e croconato, o pseudo-oxocarbono croconato violeta, bem como os ligantes nitrogenados derivados piridínicos 4,4’-dimetil-2,2’-bipiridina (MBP), 1,3-bis(4-piridil)propano (BPP) e 2,3,5,6-tetraquis(α-piridil)pirazina (TPP) e os sítios metálicos de Co(II), Ni(II) e Cu(II). Adicionalmente realizou-se sínteses envolvendo o sítio metálico de Mn(II). Utilizou-se diversas técnicas analíticas e espectroscópicas para a caracterização dos compostos sintetizados, tais como, análise elementar (CHN), análise térmica (TG/DTA) e espectroscopia vibracional (IV e Raman). Foram obtidos seis complexos envolvendo a espécie esquarato, dos quais três contêm o ligante 4,4’-dimetil-2,2’-bipiridina (MBP), denominados: [Co(MBP)2(C4O4)] (1), [Ni(MBP)3](C4O4).3H2O (2) e {[Cu2(MBP)2(C4O4)2(H2O)4]}n (3) e três o ligante 2,3,5,6-tetraquis(α-piridil)pirazina (TPP): [Co2(TPP)(C4O4)2(H2O)2)]2H2O (4), [Ni2(TPP)(C4O4)(H2O)2Cl2]7H2O (5) e [Cu2(TPP) (H2O)2Cl2)] (C4O4)2H2O (6). Os complexos (2), (3) e (6) tiveram suas estruturas determinadas por difração de raios X de monocristal. O composto (3) apresentou-se como um polímero de coordenação que se estende em uma dimensão através do ligante esquarato, coordenado em ponte entre dois sítios de Cu(II) pelo modo µ-1,2-bis(monodentado). O referido ligante oxocarbônico apresentou-se nos compostos (2) e (6) como contra-íon. As sínteses envolvendo a espécie oxocarbônica croconato de potássio levaram à obtenção de sete compostos inéditos denominados: {[Co(MBP)2(NO3)]2+.[Co(C5O5)2(H2O)4]2-} .6H2O (7), [Ni(MBP)2(C5O5)] (8), [Cu(MBP)(C5O5)(H2O)] (9), {[Mn2(BPP)2(C5O5)2(H2O)4].3H2O}n (10), {[Co2(BPP)2(C5O5)2(H2O)4].2H2O}n (11), {[Ni2(BPP)3(C5O5)2(H2O)4].5H2O}n (12) e {[Cu(BPP)(C5O5)(H2O)3]}n (13), em que MBP consiste no ligante nitrogenado 4,4’-dimetil-2,2’-bipiridina e BPP no 1,3-bis(4-piridil)propano. Os compostos (7), (8) e (10) tiveram suas estruturas determinadas por difração de raios X de monocristal. O complexo (7) apresentou-se dinuclear, sendo constituído por uma porção catiônica e outra aniônica que apresenta dois íons croconato coordenados pelo modo monodentado, enquanto que (8) é mononuclear com o diânion croconato coordenado ao Ni(II) pelo modo 1,2-bidentado, tais complexos apresentaram arranjos supramoleculares, sendo que em (7) a presença de interações de hidrogênio estendem o arranjo em duas dimensões e em (8) interações do tipo empacotamento π estende o arranjo supramolecular em uma dimensão. O composto (10) apresentou-se como um polímero de coordenação bidimensional em que tanto o ligante nitrogenado BPP, numa conformação TG (trans-gauche), quanto um dos diânions croconato, apresentaram-se coordenados em ponte entre dois sítios metálicos de Mn(II). Tal rede polimérica apresenta caminhos fechados cuja topologia estrutural é (6,3). O referido polímero apresenta dois íons croconato com modos de coordenação distintos, um deles se coordena ao sítio de Mn(II) pelo modo 1,2-bidentado e outro em ponte pelo inusitado modo µ-1,2-bis(monodentado), o qual não apresenta relatos na literatura. Observou-se que a folha bidimensional apresentou-se entrelaçada paralelamente à outra folha equivalente, gerando uma estrutura interpenetrada. Através das sínteses envolvendo o pseudo-oxocarbono croconato violeta obteve-se dois compostos denominados: [Co(MBP)2(CV)] (14) que envolve o ligante nitrogenado 4,4’-dimetil-2,2’-bipiridina (MBP) e {[Mn(BPP)2(H2O)2](CV)2-.2H2O}n (15) que envolve o ligante 1,3-bis(4-piridil)propano (BPP). O composto (15) teve sua estrutura determinada por difração de raios X de monocristal, a qual apresenta dois ligantes BPP, numa conformação TG (trans-gauche), coordenados em ponte entre dois sítios de Mn(II) gerando um arranjo polimérico unidimensional em que os diânions croconato violeta atuam como contra-íons. Observou-se a presença de interações de hidrogênio na estrutura, as quais foram responsáveis pelos arranjos supramoleculares bi e tridimensional. / This work presents the synthesis and characterization of novel complexes of Co(II), Ni(II) and Cu(II) involving the oxocarbons species, squaric acid and croconate ion, the pseudo-oxocarbon croconate violet dianion as well as the nitrogen ligands derived from pyridine 4,4’-dimethyl-2,2'-bipyridine (MBP), 2,3,5,6-tetrakis(α-pyridyl)pyrazine (TPP) and 1,3-bis(4-pyridyl)propane (BPP). Additionally, some syntheses involving the Mn(II) metal ion were realized. We used various analytical and spectroscopic techniques for characterization of the compounds such as elemental analysis (CHN), thermal analysis (TG/DTA) and vibrational spectroscopy (IR and Raman). We obtained six complexes involving the species squarate. Three of them contain the ligand 4,4’-dimethyl-2,2'-bipyridine (MBP), named: [Co(MBP)2 (C4O4)] (1), [Ni(MBP)3](C4O4).3H2O (2) and {[Cu2(MBP)2(C4O4)2(H2O)4]}n (3) and the other three contain the ligand 2,3,5,6 tetrakis(α-pyridyl)pyrazine (TPP): [Co2(TPP)(C4O4)2(H2O)2)]2H2O (4), [Ni2(TPP)(C4O4)(H2O)2Cl2]7H2O (5) and [Cu2(TPP)(H2O)2Cl2)](C4O4)2H2O (6). The complexes (2), (3) and (6) had their structures determined by single crystal X-ray diffraction analysis. The compound (3) is an one-dimensional coordination polymer extended through squarate ion coordinated to the Cu(II) sites in the µ-1,2-bis(monodentate) bridging mode. The oxocarbon ligand acts as counter-ion in compounds (2) and (6). The synthesis involving the croconate ion led to the taking of seven novel compounds named: {[Co(MBP)2(NO3)]2+[Co(C5O5)2(H2O)4]2-}.6H2O (7), [Ni(MBP)2(C5O5)] (8), [Cu(MBP)(C5O5)(H2O)] (9), {[Mn2(BPP)2(C5O5)2(H2O)4].3H2O}n (10), {[Co2(BPP)2(C5O5)2(H2O)4].2H2O}n (11), {[Ni2(BPP)3(C5O5)2(H2O)4].5H2O}n (12) and {[Cu(BPP)(C5O5)(H2O)3]}n (13). The compounds (7), (8) and (10) had their structures determined by single crystal X-ray diffraction analysis. The complex (7) is dinuclear, consisting of one cationic and one anionic portion that has two croconate ions coordinated to the metal center in a monodentate fashion, while compound (8) is mononuclear with croconate dianion coordinated to Ni(II) in the 1,2-bidentate mode. In compound (7) it can be noticed the presence of hydrogen interactions extending the arrangement into two dimensions, while in (8), π-π stacking interactions extend the supramolecular arrangement in one dimension. Compound (10) is a two-dimensional coordination polymer where both BPP nitrogen ligands adopt a TG (trans-gauche) conformation. The polymer has two croconate ions with different coordination modes, one adopts the 1,2-bidentate mode and the other acts in an unusual -1,2-bis(monodentate) bridging mode, which has no reports in the literature. This 2-D polymer network presents (6,3) structural topology. Two 2-D sheets interlocked each other in a parallel way generating an interpenetrated structure. Through the synthesis involving the croconate violet dianion was obtained two compounds, named: [Co(MBP)2(CV)] (14) and {[Mn(BPP)2(H2O)2](CV).2H2O)]}n (15). Compound (15) had its structure determined by single crystal X-ray diffraction analysis. It has two BPP ligands, in the TG (trans-gauche) conformation, bridging two sites of Mn(II) generating a one-dimensional polymeric array in which the croconato violet dianions act as counter-ions. There is the presence of hydrogen bonding interactions in the structure which are responsible for the extension of the supramolecular arrangements into two and three dimensions.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-07-20T17:37:01Z No. of bitstreams: 1 humbertocostagarcia.pdf: 7846659 bytes, checksum: 34217a22d6ed991eb248916aa4a1c452 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-08-09T12:51:50Z (GMT) No. of bitstreams: 1 humbertocostagarcia.pdf: 7846659 bytes, checksum: 34217a22d6ed991eb248916aa4a1c452 (MD5) / Made available in DSpace on 2017-08-09T12:51:50Z (GMT). No. of bitstreams: 1 humbertocostagarcia.pdf: 7846659 bytes, checksum: 34217a22d6ed991eb248916aa4a1c452 (MD5) Previous issue date: 2009-03-30 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Este trabalho descreve a síntese e caracterização de cinco novos complexos de metais de transição de fórmula geral MB2Bipi . 10H2O (onde M = Fe2+, Co2+, Ni2+, Cu2+ e Zn2+, B refere-se ao ânion barbiturato e Bipi a 4,4’-Bipiridina). Para caracterização dos compostos foram utilizadas as técnicas de análise elementar (CHN), análise térmica (TG/DTA), espectroscopia vibracional (Raman e infravermelho) e eletrônica (visível/Reflectância) e difração de raios X de monocristal. Os complexos FeB2Bipi . 10H2O (1), CoB2Bipi . 10H2O (2), NiB2Bipi . 10H2O (3), CuB2Bipi . 10H2O (4) e ZnB2Bipi . 10H2O (5) formam uma unidade básica polimérica, onde Fe(II), Co(II) e Zn(II) são isomorfos com grupo espacial P6422, diferentes de Ni(II) e Cu(II) também isomorfos, mas pertencentes ao grupo espacial P6522; no entanto todos os compostos apresentam a mesma estrutura molecular. O sítio metálico encontra-se em uma geometria octaédrica levemente distorcida, coordenado por dois átomos de nitrogênio do anel piridil e outros quatro átomos de oxigênio provenientes das moléculas de água. Cada estrutura exibe uma cadeia covalente linear [M(Bipi)(H2O)4]2+ unidimensional, a qual interage por interações de hidrogênio com o ânion barbiturato e moléculas de água de cristalização resultando em um arranjo tridimensional. A análise das estruturas dos complexos de Ni2+ e Cu2+ mostram uma interação de hidrogênio bidimensional formada por quatro ânions barbituratos e duas moléculas de água de cristalização, que pode ser considerada um hóspede enquanto a cadeia [M(bipi)(H2O)4]2+ unidimensional pode ser considerada o hospedeiro em uma intrigante e interessante estrutura. Os espectros vibracionais dos compostos são muito similares, e estão de acordo como os dados do cristal. Em todos os espectros na região do infravermelho, uma banda em torno de 1690 cm-1 é observada, atribuída ao estiramento CO [νCO] do ânion barbiturato. No espectro Raman as mais importantes bandas referentes ao ligante 4,4’bipiridina estão localizados em 1616, 1290 e 1020 cm-1, atribuídas aos modos νCC/CN, νring + δCH e νring respectivamente. Para caracterização do ânion barbiturato uma banda Raman de média intensidade é observada em torno de 680 cm-1, atribuído ao modo de respiração do anel. O sucesso na síntese dos compostos (1), (2), (3), (4) e (5) demonstra que a mistura de ligantes pode fornecer múltiplas forças de ligação, como covalente, eletrostática e as interações de hidrogênio, favorecendo a ordenação de uma arquitetura supramolecular multidimensional. Além disto, o uso do ânion barbiturato, o qual atua como doador de hidrogênio pelos grupos NH e CH, e aceptor pelo grupo CO, contribui com uma nova característica para expandir rapidamente a área da química supramolecular no nosso grupo de pesquisa. / This work describes the synthesis and characterization of five new transition metal complexes of general formula MB2Bipy.10H2O (where M = Fe2+, Co2+, Ni2+, Cu2+ and Zn2+, B is barbiturate anion and Bipy is 4,4’-bipyridine) . Several physical and spectroscopical techniques were used to characterize the compounds, such as elemental analysis (CHN), thermal analysis (TG/DTA), vibrational (Raman and infrared) and electronic (absorption and reflectance in the visible region) spectroscopy as well as single crystal X ray diffraction analysis. The FeB2Bipi . 10H2O (1), CoB2Bipi . 10H2O (2), NiB2Bipi . 10H2O (3), CuB2Bipi . 10H2O (4) and ZnB2Bipi . 10H2O (5) complexes give rise to polymeic basic units, where Fe(II), Co(II) and Zn(II) compounds are isomorphous belonging to P6422 space group, different from the Ni(II) and Cu(II) compounds which are also isomorphous, belonging to P6522 space group; however, all compounds present the same molecular structure. In each compound the metal site appears in a distorted octahedral geometry, coordinated by two pyridine nitrogen atoms and also to four oxygen atoms from the coordinated water molecules. Each structure shows a covalent linear [M(Bipy)(H2O)4]2+ one-dimensional chain , which interacts by hydrogen bond with the barbiturate anion and the crystallization waters, resulting in a tridimensional arrangement. The analysis of the Ni2+ and Cu2+ complexes structures shows flexible bidimensional hydrogen bonds networks being constructed by the four barbiturate anions and the two crystallization water molecules; this structure may be deemed to be the host, while the robust 1D [M(bipy)(H2O)4]2+ chains may be deemed to be the guest, in a very intriguing and interesting structure. The vibrational spectra of the compounds are very similar, in agreement to the crystallographic data. In all infrared spectra a medium intensity band at 1690 cm-1 has been observed, assigned to the CO stretch of the barbiturate anion. In the Raman spectra the most important bands referring to 4,4’-bipyridine ligand are the ones at 1616, 1290 and 1020 cm-1, assigned to νCC/CN, νring + δCH and νring modes, respectively. For characterization of barbiturate anion one medium Raman signal is observed around 680 cm-1 assigned to the ring breathing mode. The successful synthesis of the new (1), (2), (3), (4) and (5) compounds demonstrates that the introduction of mixed ligands may provide multiple binding forces such as coordinated covalent, electrostatic and hydrogen bonding interactions, which may endow an enormous potential for assembling multidimensional supramolecular architectures. Furthermore, the use of the barbiturate species, which act as H-donors by the NH and CH moieties, and H-acceptors by the CO groups, can contribute through new features and arrays to the rapidly expanding area of supramolecular chemistry by our research group.

Ce projet consiste à fabriquer et à étudier des micelles à la fois biocompatibles et capables de relarguer des molécules volatiles bioactives à partir d’une solution aqueuse sous l’influence de stimuli extérieurs tel que le pH, la température ou la concentration. Pour atteindre ce but, nous avons étudiés un nouveau type d’objets micellaires qui sont formés par l’auto-assemblage d’amphiphiles covalents dynamiques (DCAs), des surfactants peu onéreux formés de l’association moléculaire réversible d’un bloc hydrophile et d’un bloc hydrophobe. Ces systèmes peuvent relarger une large gamme de fragrances à partir d’une solution, que cela soit à partir du coeur hydrophobe de la micelle ou alors à partir de l’amphiphile (profragrance). Ils ont aussi été capables de stabiliser en solution des aldéhydes sensibles à l’hydrolyse. / This project relies on the simple design and the study of biocompatible responsive micelles, capable of releasing a hydrophobic bioactive volatile from an aqueous solution and that, depending on the modulation of external factors such as pH, temperature, and concentration. To reach this goal, we have taken advantages of a new kind of micellar objects that are formed by the efficient self-assembly of biodegradable Dynamic Covalent Amphiphiles (DCAs), low cost surfactants that are made by the reversible molecular association of one hydrophilic and one hydrophobic block. These systems can release a broad variety of fragrances from solution, both from the hydrophobic micellar core or directly from the amphiphile (profragrance). It also proved able to stabilise some sensitive aldehydes in solution.