Collision Studies with Electro-Sprayed Biomolecules

In this PhD thesis, the fragmentation of prototype radiosensitizer molecules for cance radio- and chemo-therapy is investigated through gas-phase collision experiments. The main goal is to extend the current knowledge on the radiosensitization mechanism by assessing the formation of reactive species, ions and neutral radicals, which may lead to DNA damage during the early stages of radiation damage. In the first part, a collision-induced dissociation study with protonated ronidazole carried out with a home-built electrospray ionization source coupled to a double-focusing mass spectrometer is presented. The main fragmentation pathway results from an intramolecular proton transfer reaction followed by release of neutral – NH2CO2H fragment. This reaction was demonstrated in low- and high-energy CID experiments with partially deuterated ronidazole supported by DFT quantum chemical calculations. The second part of the thesis focuses on low-energy electron interactions with 5-trifluoromethanesulfonyluracil (OTfU), a modified pyrimidine, and benzaldehyde, a compound used in anti-cancer clinical trials. Crossed electron-molecular beam setups coupled with a quadrupole mass spectrometer were employed to identify the formed fragment anions, and to measure anion efficiency curves as function of the incident electron energy. In dissociative electron attachment (DEA) to OTfU, the triflate anion (OTF-), along with the reactive uracil-5-yl radical was identified as the dominant anionic fragment. The efficient decomposition of OTfU into reactive species upon electron attachment endorses its potential as a radiosensitizer. For benzaldehyde, in addition to the molecular anion detection, further nine fragment anions were observed with modest DEA cross sections of about 10−24 − 10−23 m2. The study with partially deuterated benzaldehyde showed that the dehydrogenation of benzaldehyde is selective with respect to the incident electron energy. The formation of resonances was also theoretically investigated by electron scattering calculations, and a quantum chemical study predicted the thermochemical thresholds for the observed fragments. The insights gained in this PhD thesis may contribute for a better understanding on radiation damage, which is of paramount importance for the design of new radiosensitizer drugs, as well as for the development of more efficient cancer treatments

Reactions in Tirapazamine Induced by the Attachment of Low-Energy Electrons: Dissociation Versus Roaming of OH

Vienna (P30332) PD/BD/114447/2016 PTDC/FIS-AQM/31215/2017 PD/00193/2012 UID/Multi/ 04378/2019 UID/FIS/00068/2019Tirapazamine (TPZ) has been tested in clinical trials on radio-chemotherapy due to its potential highly selective toxicity towards hypoxic tumor cells. It was suggested that either the hydroxyl radical or benzotriazinyl radical may form as bioactive radical after the initial reduction of TPZ in solution. In the present work, we studied low-energy electron attachment to TPZ in the gas phase and investigated the decomposition of the formed TPZ− anion by mass spectrometry. We observed the formation of the (TPZ–OH)− anion accompanied by the dissociation of the hydroxyl radical as by far the most abundant reaction pathway upon attachment of a low-energy electron. Quantum chemical calculations suggest that NH2 pyramidalization is the key reaction coordinate for the reaction dynamics upon electron attachment. We propose an OH roaming mechanism for other reaction channels observed, in competition with the OH dissociation.publishersversionpublishe

Excited states of bromopyrimidines probed by vuv photoabsorption spectroscopy and theoretical calculations

Funding Information: Funding: J.P.‐d.‐S. acknowledges the Portuguese National Funding Agency FCT‐MCTES through PhD grant PD/BD/142768/2018, together with R.R., J.A., M.M. and F.F.d.S. through the researcher grant PTDC/FIS‐AQM/31215/2017 and AIL through the researcher grant PTDC/FIS‐ AQM/31281/2017. This work was also supported by Radiation Biology and Biophysics Doctoral Training Programme (RaBBiT, PD/00193/2012); UIDB/04378/2020 (UCIBIO); and UIDB/00068/2020 (CEFITEC). The research leading to this result has been supported by the project CALIPSOplus under the Grant Agreement 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020.We report absolute photoabsorption cross sections for gas‐phase 2‐ and 5‐ bromopyrimidine in the 3.7–10.8 eV energy range, in a joint theoretical and experimental study. The measurements were carried out using high‐resolution vacuum ultraviolet synchrotron radiation, with quantum chemical calculations performed through the nuclear ensemble approach in combination with time‐dependent density functional theory, along with additional Franck–Condon Herzberg–Teller calculations for the first absorption band (3.7–4.6 eV). The cross sections of both bromopyrimidines are very similar below 7.3 eV, deviating more substantially from each other at higher energies. In the 7.3–9.0 eV range where the maximum cross‐section is found, a single and broad band is observed for 5‐bromopyrimidine, while more discernible features appear in the case of 2‐bromopyrimidine. Several π* ← π transitions account for the most intense bands, while weaker ones are assigned to transitions involving the nitrogen and bromine lone pairs, the antibonding σ*Br orbital, and the lower‐lying Rydberg states. A detailed comparison with the available photo‐absorption data of bromobenzene is also reported. We have found significant differences regarding the main absorption band, which is more peaked in bromobenzene, becoming broader and shifting to higher energies in both bromopyrimidines. In addition, there is a significant suppression of vibrational structures and of Rydberg states in the pair of isomers, most noticeably for 2‐bromopyrimidine.publishersversionpublishe

Formation of Temporary Negative Ions and Their Subsequent Fragmentation upon Electron Attachment to CoQ0 and CoQ0H2

P30332 153377/2016‐0 304571/2018‐0 PTDC/FIS‐AQM/31215/2017 PD/00193/2012 UID/FIS/00068/2020 PD/BD/142768/2018Ubiquinone molecules have a high biological relevance due to their action as electron carriers in the mitochondrial electron transport chain. Here, we studied the dissociative interaction of free electrons with CoQ0, the smallest ubiquinone derivative with no isoprenyl units, and its fully reduced form, 2,3-dimethoxy-5-methylhydroquinone (CoQ0H2), an ubiquinol derivative. The anionic products produced upon dissociative electron attachment (DEA) were detected by quadrupole mass spectrometry and studied theoretically through quantum chemical and electron scattering calculations. Despite the structural similarity of the two studied molecules, remarkably only a few DEA reactions are present for both compounds, such as abstraction of a neutral hydrogen atom or the release of a negatively charged methyl group. While the loss of a neutral methyl group represents the most abundant reaction observed in DEA to CoQ0, this pathway is not observed for CoQ0H2. Instead, the loss of a neutral OH radical from the CoQ0H2 temporary negative ion is observed as the most abundant reaction channel. Overall, this study gives insights into electron attachment properties of simple derivatives of more complex molecules found in biochemical pathways.publishersversionpublishe

Formation of Temporary Negative Ions and Their Subsequent Fragmentation upon Electron Attachment to CoQ0 and CoQ0 H2

Publisher Copyright: © 2022 Wiley-VCH GmbH.The front cover artwork is provided by Prof. Stephan Denifl's group at the University of Innsbruck, Austria, in collaboration with Prof. Filipe Ferreira da Silva's group at NOVA University Lisbon, Portugal, and Prof. Dr. Márcio Varella's group at University of São Paulo, Brazil, as well as with Prof. Dr. Martin Beyer and Prof. Dr. Milan Ončak also at the University of Innsbruck, Austria. The image shows the main fragmentation pathways of both coenzyme Q0 (CoQ0 ) and CoQ0 H2 upon electron attachment in the gas phase. Read the full text of the Research Article at 10.1002/cphc.202100834.publishersversionpublishe

An intense source for cold cluster ions of a specific composition

Funding Information: This work was supported by EFRE (K-Regio project FAENOMENAL, Grant No. EFRE 2016-4) and the Austrian Science Fund FWF (Project No. P31149, I4130). This work was also supported by Fundação para a Ciência e a Tecnologia (FCT-MCTES), Radiation Biology and Biophysics Doctoral Training Programme (RaBBiT, PD/00193/2012); Applied Molecular Biosciences Unit - UCIBIO (UIDB/04378/2020) and CEFITEC Unit (UIDB/00068/2020); and scholarship Grant No. PD/BD/114447/2016 to J.A., F. Zappa acknowledges support from the Brazilian agency CNPq. K.v.H. kindly acknowledges the award of a LFUI guest professorship.The demand for nanoscale materials of ultra-high purity and narrow size distribution is addressed. Clusters of Au, C60, H2O, and serine are produced inside helium nanodroplets using a combination of ionization, mass filtering, collisions with atomic or molecular vapor, and electrostatic extraction, in a specific and novel sequence. The helium droplets are produced in an expansion of cold helium gas through a nozzle into vacuum. The droplets are ionized by electron bombardment and subjected to a mass filter. The ionic and mass-selected helium droplets are then guided through a vacuum chamber filled with atomic or molecular vapor where they collide and "pick up" the vapor. The dopants then agglomerate inside the helium droplets around charge centers to singly charged clusters. Evaporation of the helium droplets is induced by collisions in a helium-filled radio frequency (RF)-hexapole, which liberates the cluster ions from the host droplets. The clusters are analyzed with a time-of-flight mass spectrometer. It is demonstrated that using this sequence, the size distribution of the dopant cluster ions is distinctly narrower compared to ionization after pickup. Likewise, the ion cluster beam is more intense. The mass spectra show, as well, that ion clusters of the dopants can be produced with only few helium atoms attached, which will be important for messenger spectroscopy. All these findings are important for the scientific research of clusters and nanoscale materials in general.publishersversionpublishe

Reaktionen in Tirapazamin induziert durch die Anlagerung von niederenergetischen Elektronen: Dissoziation versus Roaming von OH

P30332 PD/BD/114447/2016 PTDC/FIS‐AQM/31215/2017 PD/00193/2012 UID/Multi/ 04378/2019 UID/FIS/00068/2019Tirapazamin (TPZ) wurde aufgrund seiner potenziell hochselektiven Toxizität gegenüber hypoxischen Tumorzellen in klinischen Studien zur Radio‐Chemotherapie getestet. Dabei wurde vorgeschlagen, dass sich entweder das Hydroxyl‐Radikal oder das Benzotriazinyl‐Radikal nach der anfänglichen Reduktion von TPZ als bioaktives Radikal bildet. In dieser Arbeit beschäftigten wir uns mit der niederenergetischen Elektronenanlagerung an TPZ in der Gasphase und untersuchten die Zersetzung des gebildeten TPZ‐Anions mittels Massenspektrometrie. Wir beobachteten die Bildung des (TPZ‐OH)− Anions, begleitet von der Abspaltung des Hydroxyl‐radikals als dem bei weitem häufigsten Reaktionsweg. Quanten‐chemische Berechnungen legen nahe, dass die NH2‐Pyramidalisierung die Schlüsselkoordinate für die Reaktions‐dynamik bei Elektronenanlagerung ist. Für andere beobachtete Reaktionskanäle schlagen wir einen OH‐Roaming‐Mechanismus vor, der in Konkurrenz zur OH‐Dissoziation steht.publishersversionpublishe

práticas artísticas no ensino básico e secundário

Para este número 18 da Revista Matéria-Prima reuniram-se 16 artigos que permitem colocar em perspetiva diversas dimensões da Educação Artística. Entre a consciência patrimonial e a emancipação, entre o domínio da técnica e do género, entre a integração e a maturação criadora, há um espaço a ser pesquisado, feito de história, de identidade, de ensaio e de inclusividadeinfo:eu-repo/semantics/publishedVersio

Práticas artísticas no ensino básico e secundário

A mediação entre os conteúdos culturais e a Educação Artística formal tem emergido como uma distinta área de inovação e de intervenção, como o mostram os 18 artigos selecionados nesta nona edição da revista Matéria-Prima.Entre a identidade, fundada nos focos de conhecimento local, e uma inserção integrada nos problemas e conteúdos globais joga-se a problematização da Educação Artística. As propostas articulam quer discursos curatoriais (museu, bienal, exposição), como ações de mediação visando uma expansão das atividades, a que se juntam as reflexões sobre a realidade da formação de professores, nas suas diversas modalidades, em diversas realidades sociais.Propiciam-se oportunidades de ações de intervenção, concertadas ou não, entre os agentes artísticos e os educadores. O resultado pode ser potenciado se se conseguir uma perspetiva informada e integrada das realidades artísticas: pede-se a todos os intervenientes mais integração e disponibilidade para um conhecimento mútuo consequente.info:eu-repo/semantics/publishedVersio