Circadian oscillators or clocks are a widespread, endogenous class of oscillatory mechanisms that control the ~24h temporal pattern of diverse organism functions. In cyanobacteria this mechanism is formed by three proteins, KaiA, KaiB and KaiC. KaiA is shown here to be a two domain protein that directly interacts with KaiC and enhances the KaiC autokinase activity. The amino-terminal domain of KaiA can be structurally categorized as a pseudo-receiver, a class of proteins used in signaling cascades and activated by direct protein??protein interactions. The carboxy-terminal domain interacts directly with KaiC, is sufficient to enhance the KaiC autokinase activity in a manner similar to full-length KaiA, and adopts a unique, all α-helical dimeric fold. The structure of this domain raises interesting probabilities regarding the mode of KaiA??KaiC interaction. The two KaiA domains are shown to directly interact with each other, which suggests a possible mechanism of signal transfer from the amino to carboxy-terminal domain. Hydrogen bonds are of paramount importance in nucleic acid structure and function. Here we show that changes in the width and anharmonicity of vibrational potential energy wells of hydrogen bonded groups can be measured in nucleic acids and can possibly be correlated to structural properties, such as length. Deuterium/protium fractionation factors, which are sensitive to the vibrational potential well width, were measured for the imino sites of thymidine residues involved in A:T base pairs or free in solution, and a correlation was established between decreasing fractionation factors and increasing imino proton chemical shift, δH3. Similarly, a correlation was observed between δH3and deuterium isotope effects (DIE) on chemical shift of thymidine carbon atoms. Combined these results indicate that as hydrogen-bond strength increases the vibrational potential wells of imino protons widen with a corresponding increase in anharmonicity. However, trans-hydrogen bond DIE on carbon chemical shifts of A:T base-paired adenosine residues do not correlate with those measured on thymidine residues. We propose that this lack of correlation is due to DIE dependence on base-pair geometry, which is not easily measured by traditional NMR experiments.

S,S-diphenyl sulfimide (Ph2SNH) has been employed in current investigations divided in three different directions, concerning hydrogen bonding motifs of new sulfimide systems, polymorphism of trans- Cu(Ph2SNH)2Cl2 as well as carboxylations of Ph2SNH. The isomorphic analogues of [Mn(Ph2SNH)6]Cl2 and [Co(Ph2SNH)6]Cl2 were synthesised as parent systems, with their derivatisations by metathesis to give BF4 and PF6 salts. The BF4 daughter systems displayed face on and snug fit hydrogen bonding motifs in the Mn(II) and Co(II) variants respectively. The PF6 analogues were the first examples to have spectator sulfimide units not participating in hydrogen bonds, rationalised as means to relief steric constrains. [Co(Ph2SNH)4]SO4 was observed to be stabilised by the formation of l-D hydrogen bond array between the unsaturated complex centres with SO4 anions. The square planar polymorph of trans- Cu(Ph2SNH)2Cl2 has recently been observed to display reversible mechanochromism when ground. The yielding of a green ground collective was reasoned as the formation of an amorphous conformer closely related to the green pseudotetrahedral polymorph. The concomitant crystallisation of both forms has also been revisited. Internal voids, ether partial pressure and volume of mother liquor have been proposed as contributing factors concerning the crystallisation outcomes. The reaction between Ph2SNH and CO2 led to the formation of [Ph2SNH2]HCO3, Ph2SN(H)COO as well as Ph2SNCOOH, depending on reaction conditions. The zwitterion of Ph2SN(H)COO is expected to be the principle product of Ph2SNH/CO2 reactions, while [Ph2SNH2]HCO3 was deduced as a hydrolysis product of Ph2SN(H)COO. The isolation of Ph2SNCOOH was only possible when CO2 fixation was carried out in DMSO, rationalised as a unique proton transfer equilibrium only attainable in the protophilic solvent.

Poly (Ethylene Oxide) (PEO, with a general formula (CH₂-CH₂-O)[subscript pi] ) is completely soluble in water at room temperature over an extremely wide molecular weight range and has been widely studied by experiment and theory. The objective of our work is to study the solubility behavior by the method of Monte Carlo simulation. The insertion factor lnB, which is equivalent to the infinite dilute Henry's Law Constant, is used to represent the solubility of various molecules in water. Our research started with simple fluid and aqueous solutions of small molecules including hard spheres, inert gases, hydrocarbons and dimethyl ether (DME, as a precursor for PEO). Solubility consists of a favorable energy term and an unfavorable entropy term. Against the common belief of entropy-dominating-hydrophobicity effect, it is actually the ability of the solute to interact with solvent (or the energetic factor) that dominates solubility. The solubility minimum appearing for both hydrophobic and hydrophilic solutes along the water coexistence curve is the result of competition between the favorable energy contribution and the unfavorable entropy contribution. Normal alkanes with carbon number from 1 to 20 have been modeled by LJ chains to study the solubility of non-polar polymer chains in water. Various constraints have been put on the LJ model to evaluate their effect on solubility. No significant difference was observed for LJ chain with or without fixed bond angles, but torsional interaction changed the chain solubility dramatically. The temperature and chain-length effect on chain solubility has been examined and it can be explained by the balancing between the intra-chain interaction and entropy penalty. By choosing the right torsional interaction parameters we may be able to reproduce by simulations the solubility minimum of normal alkanes at C₁₁. PEO was modeled by united atom chains with length up to 30. The most probable distance between two nearest ether oxygens in both vacuum and aqueous solutions matches the hydrogen bond length in bulk water. Hydrogen bonding plays an important role in the unique water solubility behavior of PEO since the water-PEO interaction effectively increases the total number of hydrogen bonds and results in a favorable change in energy. A trans-gauche-trans conformation along the O-C-C-O bonds does enable hydrogen bond formation between one water molecule and two nearest or next nearest ether oxygens. A helix structure is not required for the PEO to have favorable interactions with water. Two polymers with similar structure as PEO but are insoluble in water: Poly (methylene oxide) (PMO) and Poly (propylene oxide) (PPO) have been studied to compare with PEO. Their difference in structure from PEO, though slight, reduces the chance of hydrogen bond forming between water and chains so as to decrease the solubility. / text

Molecular dynamics simulations were performed on the influenza A non-structural protein 1 (NS1) RNA binding domain (RBD), a homodimer. Fourteen simulations were performed at 298K, nine ionized with 0.1M KCl and five with no ions. Several analysis techniques were employed to study RBD residue flexibility. The focus of the study was the RNA binding cavity formed by side chains of helix 2 (chain A) and helix 2’ (chain B) and cavity intermonomeric salt bridges. Opening of the salt bridges D29–R46’ and D29’–R46 was observed in several of the trajectories. The RNA binding cavity has large flexibility, where the dimension and shape change during the dynamics. One pair of residues surrounding the cavity and necessary for RNA binding, residues R38 and R38’, have motions during the simulations which cover the top of the cavity. There is correlation between the salt bridge breaking, flexibility of R38 and R38’, and the cavity size and shape changes. Possible RBD small molecule drug targets are these two salt bridges and the pair R38 and R38’. Disrupting the events that occur around these areas could possibly inactivate RNA binding function of the domain. These results could have implications in searching for potential molecules that effectively treat influenza A.

Supramolecular polymer networks are prepared basing on two different supramolecular interactions, ionic interaction and hydrogen bonds interaction. Ionic interaction was introduced in P(BMA-co-MA) with CaCO3 as a filler. The presence of Ca2+ is confirmed with X-ray diffraction by the apperence of specific ionic peak. The hydrogen bond interaction was introduced by two approaches. One is to first prepare a supramolecular monomer bearing DA moiety then supramolecular polymer P(MAAM-co-St) and P(MAP-co-St) are prepared by polyaddition. In the other approach, the supramolecular polymer is synthesized by one-step PUU polycodensation from the reagent containing multiple-hydrogen-bond sequence. The presence of intermolecular hydrogen bonds is detected by FTIR qualitatively, and the strengh, quantified as Kass, is calculated by 1H-NMR for different moieties respectively. Solubility tests indicate that the introduction of supramolecular interaction in the traditional polymers leads to the crosslinking in different extents. Consequently, materials are strengthened showing better thermo-endurence property and higher modulus when the content of supramolecular moiety is increased. Furthermore, rheological analysis is performed to investigate the viscoelasticity and to track the thermo reversibility

O propósito deste trabalho é aumentar o conhecimento existente sobre as interações dielétricas da água confinada em materiais hidrofílicos, no regime de baixas temperaturas. Os materiais hidrofílicos (sílica gel, gesso, colágeno e álcool polivinílico - PVA) foram analisados com os recursos disponíveis na técnica de Espectroscopia de Impedância - permissividade dielétrica e impedância elétrica. Como objetivo especifico procurou-se estabelecer experimentalmente o papel das ligações hidrogênio nos processos de condução observados na água confinada e verificar a existência da transição dinâmica da água super-resfriada em T = -45ºC (228K). As substâncias examinadas possuem redes ou cadeias moleculares, com grupos polares superficiais capazes de se ligarem às moléculas de água por meio de ligações hidrogênio. Em espaços restritos de natureza hidrofílica, a água pode ser super-resfriada além do ponto de nucleação homogênea, permanecendo líquida para temperaturas inferiores a 0ºC. O entendimento de sistemas envolvendo materiais hidrofílicos - tais como sólidos, géis e macromoléculas - e a água, contribui para o desenvolvimento de novos materiais e para o entendimento dos sistemas vivos. De acordo com os resultados obtidos a condução dos íons na água confinada se dá por meio da rede formada, via ligações hidrogênio, entre as moléculas de água e a cadeia dos materiais. O espectro elétrico dos materiais estudados exibe dois processos de condução, comuns a todas as substâncias. O primeiro, é influenciado pelo nível de hidratação das amostras e está relacionado as moléculas de água distantes das superfícies. O segundo, é próprio da água confinada e possui tempos de relaxação elétricos com transições observadas em -60ºC (210K) na sílica gel, e -45ºC nos outros materiais. Também constatou-se que o tamanho da cadeia polimérica do PVA altera a dinâmica do confinamento de água: cadeias de menor peso molecular não são capazes de gerar sítios que propiciem o confinamento da água. / This work aims to increase the existing knowledge on the dielectric interactions of water confined in hydrophilic materials at low temperatures. The hydrophilic materials (silica gel, gypsum, collagen and polyvinyl alcohol - PVA) were studied with the available functions of Impedance Spectroscopy - dielectric permittivity and electrical impedance. The specific goal of this thesis is to establish the role of hydrogen bonds in the conduction processes observed in confined water and to verify the existence of the supercooled water dynamic crossover at T = -45 ºC (228K). The chosen substances have molecular chains or networks with polar surface groups connected to water molecules through hydrogen bonds. When confined in small geometries, water does not crystallize and can be supercooled bellow its homogeneous nucleation temperature. This allows the indirect investigation of supercooled confined water. The studies of systems involving hydrophilic materials - such as solids, gels and macromolecules - and water, contributes to the development of new materials and to the understanding of living systems. This study demonstrated that the conduction in the confined water occurs through the network formed by hydrogen bonds between water molecules and the chain materials. The impedance spectra of all material exhibits two conduction processes common to all the analyzed samples. While the level of hydration of the samples can influence the process of higher frequencies, the one found in lower frequencies is independent of the amount of water in the samples. The first was associated to bulk water molecules and the second is related to confined water and show the expected dynamic crossover. In addition, the size of the PVA polymeric chain alters the dynamics of water: lower molecular weight polymers are not capable of displaying the supercooled dynamic crossover.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / In this work six aqua complexes of the transition metals Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Cd2+ containing the dithionate ion were synthesized and characterized through metathesis reactions in aqueous solution between BaS2O6·2H2O and the sulfate of the metal. Single crystals suitable for X-ray diffraction were obtained from the filtrates of the reactions and the structures of four complex salts, hexaaquairon(2+) dithionate hydrate, [Fe(H2O)6](S2O6)·H2O 1, hexaaquacobalt(2+) dithionate, [Co(H2O)6](S2O6) 2, hexaaquanickel(2+) dithionate, [Ni(H2O)6](S2O6) 3 and hexaaquazinc(2+) dithionate [Zn(H2O)6](S2O6) 5, and of two coordination polymers, catena-poli-[trans-tetraaquacopper-μ-dithionato-κ2O,O ] ([Cu(H2O)4(S2O6)]) 4 and catena-poli-[trans-tetraaquacadmium-μ-dithionato-κ2O,O ] ([Cd(H2O)4(S2O6)]) 6, all in triclinic system, space group P1 ‾ . The products were characterized by infrared spectroscopic, thermogravimetric, single crystal X-ray diffraction and powder Xray diffraction analyses. The Hirshfeld surface and the electron density were mapped with a cutoff 0.002 e− au−3 and basis 6-31G** for 1 to 5 and basis 3-21G* to 6, both basis in the Hartree-Fock method, revealing 79% and 75% of the contacts O···H, 19% and 11% of contacts H···H and 2% and 9% of the contacts O···O, for salts and complex coordination polymers, respectively. With the Hirshfeld surface, it was also possible to determine the volume of the molecules, determining the distorted cubic packing, according to the rules of Pauling. / Neste trabalho foram sintetizados e caracterizados seis aquacomplexos dos metais de transição Fe2+, Co2+, Ni2+, Cu2+, Zn2+ e Cd2+, contendo o íon ditionato, através de reações de metátese em solução aquosa entre BaS2O6·2H2O e o sulfato do metal. Monocristais apropriados para a difração de raios X foram obtidos a partir dos filtrados das reações, sendo as estruturas de quatro sais complexos, ditionato de hexaaquaferro(2+) hidrato, [Fe(H2O)6](S2O6)·H2O 1, ditionato de hexaaquacobalto(2+), [Co(H2O)6](S2O6) 2, ditionato de hexaaquaníquel(2+), [Ni(H2O)6](S2O6) 3 e ditionato de hexaaquazinco(2+), [Zn(H2O)6](S2O6) 5 e de dois polímeros de coordenação, catena-poli-[trans-tetraaquacobre-μ-ditionato-κ2O,O ] ([Cu(H2O)4(S2O6)]) 4 e catena-poli-[trans-tetraaquacádmio-μ-ditionato-κ2O,O ] ([Cd(H2O)4(S2O6)]) 6, todos resolvidos em sistema triclínico, grupo espacial P1 ‾ . Os produtos foram caracterizados por espectroscopia de infravermelho, análise termogravimétrica, difração de raios X de monocristal e difração de raios X em pó. A superfície de Hirshfeld e a densidade eletrônica foram mapeadas com ponto de corte 0,002 e− au−3 e bases 6-31G** para 1 a 5 e bases 3-21G* para 6, ambas as bases em nível Hartree-Fock, revelando 79% e 75% de contatos O···H, 19% e 11% de contatos H···H e 2% e 9% de contatos O···O, para os sais complexos e polímeros de coordenação, respectivamente. Com a superfície de Hirshfeld também foi possível determinar o volume das moléculas, determinando o empacotamento cúbico distorcido, segundo as regras de Pauling.

Doctor Of Philosophy / Department of Chemistry / Christer Aakeröy / Crystal engineering, or non-covalent synthesis in the solid state, requires an understanding of intermolecular forces, and the hydrogen bond has become a reliable non-covalent tool in the construction of supramolecular architectures. In the same way that synthetic chemists refer to a “yield” to quantify a desired product, crystal engineers typically determine the successful formation of a supramolecular product according to the frequency or occurrence of preferred intermolecular interactions between molecules under certain reaction conditions, thus, the supramolecular yield. These non-covalent reactions can be effectively carried out using supramolecular reagents (SR’s). A family of ditopic bis-imidazol-1-yl/benzimidazol-1-yl compounds were synthesized and used as SR’s in combination with a variety of dicarboxylic acids to produce binary solids in 100% yield through the primary acid···imidazol-1-yl/benzimidazol-1-yl synthons even in the presence of potentially disruptive intermolecular interactions. We furthermore noted that secondary C–H···O interactions within and between 1-D chains were of equal structural importance based upon an analysis of the metrics displayed by these interactions. The use of these SR’s as ligands with neutrally charged metal complexes was also investigated. SR’s containing benzimidazol-1-yl and carboxamide moieties were synthesized and combined with two different carboxylic acids to make ternary solids through acid···benzimidazol-1-yl and carboxamide···acid hydrogen bonds using a hierarchical approach – the best donor-best acceptor, second best donor-second best acceptor guidelines. These SR’s were also employed as ligands for high-yielding syntheses of linear metal complexes where neighboring complexes are linked via carboxamide···carboxamide hydrogen bonds. Asymmetric SR’s possessing two different N-heterocycles were synthesized and employed in the construction of ternary supermolecules with a high degree of structural selectivity and specificity when introduced to two different carboxylic acids. The stronger acid interacts at the more basic site, while the weaker acid hydrogen-bonds with the less basic nitrogen atom. Finally, an SR containing three different binding sites was designed and synthesized with the aim of producing quaternary co-crystals.

Ce travail de thèse traite de la synthèse de porphyrines à une ou deux anses (6, 11, 8i and 14i) greffées sur les positions méso adjacentes 5,10 et 15,20 et portant une fonction acide carboxylique suspendue avec ou sans un autre groupement fonctionnel (cyano, pyridine) en position alpha. Cette conformation génère une flexibilité de l'anse avec deux positions clairement identifiées de l'acide carboxylique (intérieure/extérieure). Ainsi la synthèse et la caractérisation des composés sont discutées en détails puis la coordination des ligands 6, 11, et 8i avec les métaux Zn(II), Hg(II), Pb(II) et Bi(III) est décrite. Dans le cas du zinc, cation penta-coordiné en géométrie pyramidale à base carrée, ce dernier est stabilisé soit par le groupement acide carboxylique intramoléculaire soit par une molécule de solvant exogène (DMSO ou H2O). Dans le cas du mercure, des complexes des deux types, monométalliques et bimétalliques, sont obtenus alors que pour le plomb, deux espèces monométalliques sont formées dans lesquelles le cation est soit du même côté, soit du côté opposé à l'anse, mais dans des proportions différentes. Enfin, le cation Bi(III) induit une seconde sphère de coordination inédite, responsable de l'insertion stéréosélective du métal. Qui plus est, un processus de transmétallation augmente la cinétique d'insertion du bismuth. Également, la présence d'un groupement cyano en position alpha de l'acide carboxylique génère une gêne stérique en coordination dans le cas du plomb, l'obligeant à coordiner la porphyrine sur sa face nue. / This thesis work concerns the synthesis of 5,10 single and bis-strapped porphyrin ligands (6, 11, 8i and 14i) bearing an overhung carboxylic acid group with/without an additional functional group (cyano and pyridine). The 5,10 meso linkage promotes a flexibility of the strap which allows the carboxylic acid group to be in two identified positions (in/out). The synthesis and characterization of the compounds are discussed in details, and the coordination of the ligands (6, 11, and 8i) with metals Zn(II), Hg(II), Pb(II) and Bi(III) have been investigated. In the case of Zn(II), five-coordinated metal in a square pyramidal geometry, the metal was stabilized by either an intramolecular carboxylic acid group or an exogenous molecule (DMSO or H2O). In the case of Hg(II), both monometallic and bimetallic species were obtained where for lead, two monometallic species were formed in which Pb(II) is coordinated from the same / opposite side of the strap with different ratios. Finally, Bi(III) promotes a new second sphere of coordination which is responsible for the side selective insertion of the metal. Beside, a transmetalation process speeds up the kinetic insertion of bismuth. In addition, the presence of a cyano group in the α position of the carboxylic acid group creates a steric effect on coordination (in case of Pb(II)) which forces the metal to coordinate from the opposite side of the strap.

Four new ternary crystalline molecular complexes have been synthesised from a common 3,5-dinitrobenzoic acid (3,5-dnda) and 4,4'-bipyridine (bipy) pairing with a series of amino-substituted aromatic compounds (4-aminobenzoic acid (4-aba), 4-(N,N-dimethylamino)benzoic acid (4-dmaba), 4-aminosalicylic acid (4-asa) and sulfanilamide (saa)). The ternary crystals were created through the application of complementary charge transfer and hydrogen-bonding interactions. For these systems a dimer was created through a charge-transfer interaction between two of the components, while hydrogen bonding between the third molecule and this dimer completed the construction of the ternary co-crystal. All resulting structures display the same acidpyridine interaction between 3,5-dnba and bipy. However, changing the third component causes the proton of this bond to shift from neutral OHN to a salt form, O(-) HN(+) , as the nature of the group hydrogen bonding to the carboxylic acid was changed. This highlights the role of the crystal environment on the level of proton transfer and the utility of ternary systems for the study of this process.