Physical and chemical aspects of the interaction of molecules with external surface and structural cavities of nanomaterials.

The research work carried out during this PhD project has been aimed to the investigation of molecular surface events relevant for the catalytic formation, in mild conditions, of amide/peptide bonds from non-activated reagents adsorbed on nanomaterials. The formation of C-N bonds is among the topics of high interest in modern research in chemistry, addressing issues ranging from fine to prebiotic chemistry. The implementation of this project required the selection of both catalyst and reactants. As for the nanomaterials, the criteria of choice were simplicity, availability and low cost for possible future applications and, on the other hand, reasonable representativeness of minerals possibly present on the early Earth, and active as catalyst towards adsorbed organic molecules. On this basis the following nanoparticles of silica and titania are selected as well as a zeolite of the ZSM-10 type, with a MOZ framework. This latter material was intended as a porous host for future studies of the high pressure induced oligomerization of amino acids. This part of the work belongs to a very recent project, and then the work carried out in this respect in this PhD thesis is focused on the synthesis of zeolite particles with proper framework features. The choice of reactants was driven, on one hand, on the suitability to be studied in depth by both experimental methods and theoretical modelling, and on the other hand, by the possibility to adsorb them on surfaces of nanomaterials from the vapour phase, i.e. in highly controlled conditions. Thus, the simplest carboxylic acid, HCOOH was selected, as well as two simple primary amines (methylamine and 1-pentanamine). One of the surface reaction investigated was the oligomerization of amino acids on the nanomaterials and for this glycine, alanine, histidine, serine were selected because of the possibility to adsorb them on catalyst via a chemical vapour deposition method. In summary, in Chapter One, the study targeting the elucidation of the mechanism of the amide bond formation between non-activated carboxylic acids and amines at the surface of amorphous silica is reported. The results prepare the ground to address the occurrence of this reaction and of the oligomerization of amino acids (glycine and alanine) at the surface of \u3b1-quartz sub-micrometric particles (Chapter Two). The study of the C-N bond formation at the surface of titania nanoparticles is the object of Chapters Three to Five. In particular, Chapter Three is devoted to the investigation the structural requirements of sites expose at the surface of titania nanoparticles in order they can act as catalytic sites towards amino acid oligomerization. In Chapter Four, insights on basic aspects of the interaction of formic acid and methylamine with the 101 anatase titania surface are presented. The possibility to prepare Ser-His dipeptides starting from non-activated amino acids by using titania nanoparticle as catalyst and the possible hydrolytic activity of the obtained peptides is the object of Chapter Five. Finally, in Chapter Six, challenges, successes and problems still to be solved for and effective synthesis of large ZSM-10 particles, required for multitechniques investigations, including single crystal X-ray diffraction

Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma.

TBX15 is a gene involved in the development of mesodermal derivatives. As the ovaries and the female reproductive system are of mesodermal origin, the aim of the present study was to determine the methylation status of the TBX15 gene promoter and the expression levels of TBX15 in ovarian carcinoma, which is the most lethal and aggressive type of gynecological tumor, in order to determine the role of TBX15 in the pathogenesis of ovarian carcinoma. This alteration could be used to predict tumor development, progression, recurrence and therapeutic effects. The study was conducted on 80 epithelial ovarian carcinoma and 17 control cases (normal ovarian and tubal tissues). TBX15 promoter methylation was first determined by pyrosequencing following bisulfite modification, then by cloning and sequencing, in order to obtain information about the epigenetic haplotype. Immunohistochemical analysis was performed to evaluate the correlation between the methylation and protein expression levels. Data revealed a statistically significant increase of the TBX15 promoter region methylation in 82% of the tumor samples and in various histological subtypes. Immunohistochemistry showed an inverse correlation between methylation levels and the expression of the TBX15 protein. Furthermore, numerous tumor samples displayed varying degrees of intratumor heterogeneity. Thus, the present study determined that ovarian carcinoma typically expresses low levels of TBX15 protein, predominantly due to an epigenetic mechanism. This may have a role in the pathogenesis of ovarian carcinoma independent of the histological subtype

Changing and challenging times for service crystallography

Crystallography is no longer solely the preserve of the specialist, a situation that has implications for the operation of crystallographic service facilities. This mini-review provides an overview of the challenges in operating a crystallographic facility from the perspective and experience of the UK National Crystallography Service – a modern mid-range facility. Examples of chemical research generating the greatest challenges for the modern crystallography service and the state-of-the-art tools, hardware, facilities and expertise that are required to address them are highlighted. An overview of current research trends in single crystal diffraction research, which will ensure the future development of the technique, is presented. The remit of the service crystallographer is examined, together with proposed examples of best practice.<br/

Redetermination and invariom refinement of 1-cyclo­propyl-6-fluoro-4-oxo-7-(piperazin-4-ium-1-yl)-1,4-dihydro­quinoline-3-carboxyl­ate hexa­hydrate at 120 K

The structure of the title compound, C17H18FN3O3·6H2O, has been redetermined at 120 K. An invariom refinement, a structural refinement using aspherical scattering factors from theoretically predicted multipole population parameters, yields accurate geometry and anisotropic displacement parameters, including hydrogen-bonding parameters. All potential hydrogen-bond donors and acceptors are involved in hydrogen bonding, forming an intricate three-dimensional network of N—H⋯O and O—H⋯O bonds

Alerta Farmacovigilancia: Actualización de los controles hematológicos en pacientes tratados con clozapina

El Comité para la Evaluación de Riesgos en Farmacovigilancia (PRAC, por sus siglas en inglés) ha revisado la evidencia disponible sobre el riesgo de neutropenia y agranulocitosis asociado al tratamiento con clozapina. En base a ello, recomienda que se reduzca la frecuencia de los controles hematológicos en los pacientes tratados con este antipsicótico