Salt forms of Amides: protonation and polymorphism of Carbamazepine and Cytenamide

In situ generation of HCl or HBr in alcohol leads to O-protonation of the amide group of carbamazepine. Six salt phases have been produced using this method and their crystal structures determined by single crystal diffraction. A new polymorph of carbamazepine hydrochloride is described as are two polymorphs of carbamazepine hydrobromide. All are protonated at the amide O atom to give RC(OH)NH2 cations. Prolonged exposure to air results in addition of water to the solid salt forms. Such hydration of carbamazepine hydrobromide simply gives a monohydrated phase, but similar treatment of the equivalent hydrochloride results in partial loss of HCl and the transfer of the remaining proton from the amide group to water to give [carbamazepine][H3O]0.5[Cl]0.5·H2O. A similar hydronium chloride species is the only product isolated after reaction of the carbamazepine analogue cytenamide with HCl generated in methanol.

Salt and ionic cocrystalline forms of amides: protonation of carbamazepine in aqueous media

The products of reactions of the pharmaceutical amide carbamazepine (CBZ) with strong acids under aqueous conditions were investigated by both powder and single crystal X-ray diffraction. Despite previous claims to the contrary, it was found that salt forms with CBZ protonated at the amide O atom could be isolated from reactions with both HCl and HBr. These forms include the newly identified hydrate phase [CBZ(H)][Cl]·H O. Reactions with other mineral acids (HI and HBF ) gave ionic cocrystalline (ICC) forms (CBZ· [acridinium][I ]·2.5I and CBZ·[H O ] [BF ] ·H O) as well as the salt form CBZ·[CBZ(H)][BF ]·0.5H O. Reaction 2 4 3 2 5 2 0.25 4 0.25 2 4 2 of CBZ with a series of sulfonic acids also gave salt forms, namely, [CBZ(H)][O SC H ], [CBZ(H)][O SC H (OH)]· 3 6 5 3 6 4 0.5H O, [CBZ(H)] [O SCH CH SO ], and [CBZ(H)][O SC H (OH) (COOH)]·H O. CBZ and protonated CBZ(H) 2 2 3 2 2 3 3 6 3 2 moieties can be differentiated in the solid state both by changes to molecular geometry and by differing packing preferences

Direct Observation of Tetragonal Distortion in Epitaxial Structures through Secondary Peak Split in a Synchrotron Radiation Renninger Scan

This paper reports a direct observation of an interesting split of the (022)(022) four-beam secondary peak into two (022) and (022) three-beam peaks, in a synchrotron radiation Renninger scan (phi-scan), as an evidence of the layer tetragonal distortion in two InGaP/GaAs (001) epitaxial structures with different thicknesses. The thickness, composition, (a perpendicular to) perpendicular lattice parameter, and (01) in-plane lattice parameter of the two epitaxial ternary layers were obtained from rocking curves (omega-scan) as well as from the simulation of the (022)(022) split, and then, it allowed for the determination of the perpendicular and parallel (in-plane) strains. Furthermore, (022)(022) omega:phi mappings were measured in order to exhibit the multiple diffraction condition of this four-beam case with their split measurement.

Crystallization of nordstrandite in ethylene glycol water solutions: electron microscopic studies

The present work shows the growth of nordstrandile microcrystals observed by transmission and scanning electron microscopy. Nordstrandite was synthesised from non-crystalline aluminium hydroxide reacted in 20% ethylene glycol/water solution, at room temperature. This material was characterized by TEM, SEM, SAED, XRD and EDS/TEM, during six month and revealed the formation and growth of nordstrandite. Fibrillar pseudoboehmite is the only aluminium hydroxide which could be identified during the first two weeks. The nuclei grow, from complete dissolution/recrystallization of pseudoboehmite fibrils, into platy rectangular microscrystals of nordstrandite. Some tabular microcrystals recrystallise, forming after six months only the mufti-point nordstrandite stars. This electron-optical study suggest that the star shape results from the overlapping of rectangular plates, and pseudoboehmite fibrils act as the precursor of nordstrandite crystallisation in ethylene glycol/water solution.

First evidence of crystalline KHSO(4):Mn grown by an aqueous solution method and the investigation of the effect of ionizing radiation exposure

In this work, KHSO(4):Mn crystals doped with Mn and K(2)SO(4) were synthesized using an aqueous solution method. The samples were exposed to ionizing radiation in order to observe the effects on their physical properties. Raman spectroscopy was used to identify the structure of the crystals by detecting the vibrational frequencies of the crystalline lattice. Electron paramagnetic resonance (EPR) was used to study the creation of paramagnetic centers arising from exposure to ionizing radiation. This new synthesis method produces high quality K(2)SO(4) and KHSO(4):Mn crystals and allows control of structural, morphological, optical and magnetic properties. (C) 2009 Elsevier B.V. All rights reserved,

Thickness and Annealing Temperature Effects on the Optical Properties and Surface Morphology of Layer-by-Layer Poly(p-phenyline vinylene) plus Dodecylbenzenesulfonate Films

The fabrication of controlled molecular architectures is essential for organic devices, as is the case of emission of polarized light for the information industry. In this study, we show that optimized conditions can be established to allow layer-by-layer (LbL) films of poly(p-phenylene vinylene) (PPV)+dodecylbenzenesulfonate (DBS) to be obtained with anisotropic properties. Films with five layers and converted at 110 degrees C had a dichroic ratio delta = 2.3 and order parameter r = 34%, as indicated in optical spectroscopy and emission ellipsometry data. This anisotropy was decreased with the number of layers deposited, with delta = 1.0 for a 75-layer LbL PPV + DBS film. The analysis with atomic force microscopy showed the formation of polymer clusters in a random growth process with the normalized height distribution being represented by a Gaussian function. In spite of this randomness in film growth, the self-covariance function pointed to a correlation between clusters, especially for thick films. In summary, the LbL method may be exploited to obtain both anisotropic films with polarized emission and regular, nanostructured surfaces. (c) 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 206-213, 2011

From Rational Design of Drug Crystals to Understanding of Nucleic Acid Structures: Lamivudine Duplex

A DNA-like duplex of nucleosides is probable to exist even without the 5`-phosphate groups needed to assemble the chain backbone. However, double-stranded helical structures of nucleosides are unknown. Here, we report a duplex of nucleoside analogs that is spontaneously assembled due to stacking of the neutral and protonated molecules of lamivudine, a nucleoside reverse transcriptase inhibitor (NTRI) widely used in anti-HIV drug combinatory medication. The left-handed lamivudine duplex has features similar to those of i-motif DNA, as the face-to-face base stacking and the helix rise per base pair. Furthermore, the protonation pattern on alternate bases expected for it DNA-like duplex stabilized by pairing of neutral and protonated cytosine fragments was observed for the first time in the lamivudine double-stranded helix. This structure demonstrates that hydrogen bonds can substitute for covalent phosphodiester linkage in the stabilization of the duplex backbone. This interesting example of spontaneous molecular self-organization indicates that the 5`-phosphate group could not be a requirement for duplex assembly.

Conformational Polymorphism in Racemic Crystals of the Diuretic Drug Chlortalidone

Chlortalidone (HIGROTON) is a diuretic drug widely used in antihypertensive therapy. Thus far, only two solid-state polymorphs of chlortalidone have been reported. We elucidated the structure of chlortalidone form I and a new polymorph. This new phase, namely, chlortalidone form III, was also entirely characterized. It was possible to conclude that it is a conformer with a different orientation of the chlorobenzenesulfonamide moiety. Compared to form I, it has a rotation of about 90 degrees on the axis of the C-C bond bridging the substituted phenyl and isoindolinyl rings. This conformational feature is related to the crystal packing patterns of the chlortalidone forms. Furthermore, certain intermolecular hydrogen bonds are present in both polymorphs, giving rise to ribbons with chlortalidone enantiomers alternately placed into them. The chlortalidone form I and form III crystallize in the triclinic space group P (1) over bar as racemic mixtures. Additional conformational details also differentiate the chlortalidone conformers. Slight twists on the isoindolinyl and sulfamyl groups exist. Considering all structural relationships, the fingerprint plots derived from the Hirshfeld surfaces exhibited the characteristics of the chlortalidone form I and form III crystal structures.

Triple Structural Transition below Room Temperature in the Antifilarial Drug Diethylcarbamazine Citrate

A very unusual triple structural transition pattern below room temperature was observed for the antifilarial drug diethylcarbamazine citrate. Besides the first thermal, crystallographic, and vibrational investigations of this first-line drug used in clinical treatment for lymphatic filariasis, a noteworthy behavior with three structural transformations as a function of temperature was demonstrated by differential scanning calorimetry, Raman spectroscopy, and single-crystal X-ray diffractometry. Our X-ray data on single crystals allow for a complete featuring and understanding of all transitions, since the four structures associated with the three solid-solid phase transformations were accurately determined. Two of three structural transitions show an order-disorder mechanism and temperature hysteresis with exothermic peaks at 224 K (T(1)`) and 213 K (T(2)`) upon cooling and endothermic ones at 248 K (T(1)) and 226 K (T(2)) upon heating. The other transition occurs at 108 K (T(3)) and it is temperature-rate sensitive. Molecular displacements onto the (010) plane and conformational changes of the diethylcarbamazine backbone as a consequence of the C-H center dot center dot center dot N hydrogen bonding formation/cleavage between drug molecules explain the mechanism of the transitions at T(1)`/T(2). However, such changes are observed only on alternate columns of the drug intercalated by citrate chains, which leads to a doubling of the lattice period along the a axis of the 235 K structure with respect to the 150 and 293 K structures. At T(2)`/T(1), these structural alterations occur in all columns of the drug. At T(3), there is a rotation on the axis of the N-C bond between the carbamoyl moiety and an ethyl group of one crystallographically independent diethylcarbamazine molecule besides molecular shifts and other conformational alterations. The impact of this study is based on the fascinating finding in which the versatile capability of structural adaptation dependent on the thermal history was observed for a relatively simple organic salt, diethylcarbamazine citrate.

Solvothermal Preparation of Drug Crystals: Didanosine

For the first time, crystals of suitable size for X-ray diffractometry structure determination (Dian important anti-HI V drug were prepared under solvothermal conditions. In this study, the crystal structure of didanosine (2`,3`-dideoxyinosine, ddI) in the form of a hydrate was determined using single-crystal X-ray diffractometry. Powder X-ray diffraction analysis revealed that the solid-state phase of the drug incorporated into pharmaceutical solid dosage forms is isostructural to the solvothermally prepared ddI material, even though they do not exhibit an identical chemical composition due to different water fractions occupying hydrophobic channels formed within the crystal lattice. Two ddI conformers are present in the structure, in agreement with a previous structure elucidation attempt. Concerning the keto enol equilibrium of ddI, our crystal data and vibrational characterizations by Fourier transform infrared (FTIR) and FT-Raman spectroscopy techniques were conclusive to state that both conformers exist in the keto form, contrary to solid-state NMR spectroscopic assignments that suggested ddI molecules occur as enol tautomers. In addition, characterizations by thermal (differential scanning calorimetry) and spectroscopic techniques allowed us to understand the structural similarities and the differences related to the hydration pattern of the nonstoichiometric hydrates.

A questão da autodidaxia em educação e seus fundamentos nas filosofias de Kant e de Heidegger

O livre arbítrio na forma de uma independência de que todo ser humano é capaz no processo formativo, não poderia permanecer restrito, também no campo da Educação, à afirmação vaga de uma autonomia relativa característica de todo processo social. A procura de seus fundamentos filosóficos, na esperança de poder encontrar determinações mais precisas de sua possibilidade, é dever irrecusável para quem pretende escapar a uma certa ambiguidade ideológica. Esta ambiguidade se manifesta, por um lado, na incorporação do determinismo dos fenômenos naturais ao campo social e, por outro, na valorização daquilo que pertence à essencia do homem: a capacidade de constituição de sua própria humanidade"junto ao processo de formação"do social. Kant e Heidegger. cada um de maneira própria, mas de modo algum excludentes entre si, permitem fundar filosoficamente a autonomia formativa, através da categoria transcendência. Em Kant, a liberdade, enquanto possibilidade inscrita no âmbito da humanidade do homem de inaugurar uma ação absolutamente nova, à revelia do mecanismo causa-efeito dos fenômenos naturais; e em Heidegger, a abertura da pré-sença - entidade ontológica do homem - que lhe permite constituir sua humanidade junto à constituição/revelação do mundo constróem a realidade daquilo que chamamos livre-arbítrio.

Stage level measurement of information and communication technology in organizations

Na moderna Economia do Conhecimento, na Era do Big Data, entender corretamente o uso e a gestão da Tecnologia de Informação e Comunicação (TIC) tendo como base o campo acadêmico de estudos de Sistemas de Informação (SI), torna-se cada vez mais relevante e estratégico para as organizações que pretendem: permanecer em atividade, estar aptas para atender novas demandas (internas e externas) e enfrentar as complexas mudanças na competição de mercado. Esta pesquisa utiliza a teoria dos estágios de crescimento, fundamentada pelos estudos de Richard L. Nolan nos anos 70. A literatura acadêmica relacionada com modelos de estágios de crescimento e o contexto do campo de estudo de SI, fornecem as bases conceituais deste estudo. A pesquisa identifica um modelo com seus construtos relacionados aos estágios de crescimento das iniciativas da TIC/SI organizacional, partindo das variáveis de benchmark de segundo nível de Nolan, e propõe sua operacionalização com a criação e desenvolvimento de uma escala. De caráter exploratório e descritivo, a pesquisa traz contribuição teórica ao paradigma da teoria dos estágios de crescimento, adicionando um novo processo de crescimento em sua estrutura conceitual. Como resultado, é disponibilizado além de um instrumento de escala bilíngue (português e inglês), recomendações e regras para aplicação de um instrumento de pesquisa do tipo survey, na continuidade deste estudo. Como implicação geral desta pesquisa, é esperado que seu uso e aplicação ao mensurar a avaliação do nível de estágio da TIC/SI em organizações, possam auxiliar dois perfis de indivíduos: acadêmicos que estudam essa temática, assim como, profissionais que buscam respostas de suas ações práticas nas organizações onde trabalham.

Comunidades tradicionais em áreas protegidas: convergências e lacunas da Política Urbana e Ambiental na Reserva de Desenvolvimento Sustentável Estadual Ponta do Tubarão/RN

This work presents a reflection on possibilities and boundaries of consolidation and expansion of human settlements characterized as traditional communities that are located within protected areas, using as study reference the State Sustainable Development Reserve Ponta do Tubarão, at Rio Grande do Norte state. The main topics highlight the conflict between the right to housing and the prevalence of fundamental rights of traditional populations, opposed to the diffuse right to environment, according to the regulatory framework of the Brazilian Urban and Environmental Policies. At the same time that these settlements, historically built, are substantiated by the principles of recognition of rights to traditional populations, they are in a condition of complexity to the resolution of conflicts in its urban dimension and lead to an impairment of natural sites. This work questions how the instruments of land use and occupation are defined and relate to environmental planning, especially considering that the settlements are located in Permanent Preservation Areas (APP). It aims to further the discussion of the urban dimension in settlements, characterizing its formation and growth process, to identify the gaps and convergences between the Urban and Environmental Policy, under the foundations of a socio-environmental approach. The results spotlights the conflicts between occupation and natural areas, inferring that the definition of Urban Policies instruments and its integration with Environmental Policies instruments account for essential and priority actions to the achievement to the rights to a sustainable city, as determined in the Cities Statute and environmental protection goals, defined for the Conservation Units

Exclusão social e projetos habitacionais. Um estudo sobre conjuntos habitacionais, segregação e exclusão social em Natal/RN

In Natal s urban growth process it is given that the performance period of the National Housing Bank (BNH, 1964-1986) was marked by the intense expansion of the urban grid and configuration of outskirts, through the construction of social housing developments. Implanted in segregated areas of the existing formal city, the population installed in these complexes was also excluded from their rights, considering that the housing defines itself not only by the physical dwelling, but also by its access to urban infrastructure, facilities, services, and others. From this reality and the verification of the city s exclusion and sociospatial segregation processes, we aimed to quantitatively demonstrate levels of social exclusion in Natal, based on the methodology developed by Sposati (2000) and adapted by Genovez (2002), which relates IBGE s (Brazilian Institute of Geography and Statistics) database underlying variables such as income, schooling and dwelling s quality. The research unveiled some spatial patterns promoted by the social housings: in these areas islands were developed with higher indicators than surrounding areas, revealing internal hierarchies in the city s outskirts

Direct Observation of Tetragonal Distortion in Epitaxial Structures through Secondary Peak Split in a Synchrotron Radiation Renninger Scan

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)