Hydrocarbon oxidation catalyzed by iron and manganese porphyrins anchored on aminofunctionalized supports

The second-generation metalloporphyrins (MePs) [5,10,15,20-tetrakis(pentafluorophenyl)porphyrin iron(III)] chloride, FeP, and [5,10,15,20-tetrakis(pentafluorophenyl)porphyrin manganese(III)] chloride, MnP, were covalently attached to aminofunctionalized supports, with a view to preparing selective solid catalysts for the oxidation of organic compounds. Montmorillonite K10 functionalized with 3-aminopropyltriethoxysilane (Mont1) or modified with 3-chloropropyltriethoxysilane followed by reaction with 1,6-diaminohexane (Mont2), and silica gel functionalized with 3-aminopropyltriethoxysilane (Sil1) or modified with 3-chloropropyltriethoxysilane followed by reaction with 1,6-diaminohexane (Sil2) were synthesized and characterized by UV-Vis and IR spectroscopies, EPR, TGA, and X-ray diffractometry. The catalytic activities of the MePs immobilized on these supports were investigated for the oxidation of (Z)-cyclooctene, cyclohexane and styrene by PhIO or H2O2. The studied systems were efficient catalysts for the oxidation of all substrates, especially when PhIO was the oxidant. There was no MeP leaching from the supports, indicating that covalent binding is a very efficient method for catalyst immobilization. The immobilized FePs were more efficient catalysts than the corresponding MnPs, even when imidazole was employed as a cocatalyst for the supported MnPs. Although the yields of oxidized products obtained with H2O2 were lower than those achieved with PhIO, some heterogeneous MeP systems were more efficient than the parent MePs in solution, both in terms of product yield and selectivity.As metaloporfirinas de segunda geração (MePs), cloreto de [5,10,15,20-tetraquis(pentafluorofenil)porfirinaferro(III)], FeP, e cloreto de [5,10,15,20-tetraquis(pentafluorofenil)porfirinamanganês(III)], MnP, foram covalentemente ancoradas em suportes aminofuncionalizados, com o objetivo de preparar catalisadores sólidos seletivos para a oxidação de compostos orgânicos. Montmorillonita K10 funcionalizada com 3-aminopropiltrietoxissilano (Mont1) ou com 3-cloropropiltrietoxissilano seguida por reação com 1,6-diaminoexano (Mont2), e sílica gel funcionalizada com 3-aminopropiltrietoxissilano (Sil1) ou modificada com 3-cloropropiltrietoxissilano seguida por reação com 1,6-diaminoexano (Sil2) foram preparadas e caracterizadas por UV-Vis, IR, EPR, TGA e difratometria de raios X. As atividades catalíticas das MePs imobilizadas nestes suportes foram investigadas na oxidação de (Z)-cicloocteno, cicloexano e estireno por iodosilbenzeno (PhIO) ou H2O2. Os sistemas estudados foram catalisadores eficientes da oxidação de todos os substratos, especialmente utilizando PhIO como oxidante. Não se observou lixiviamento das MePs dos suportes, indicando que a ligação covalente é um método muito eficiente para a imobilização de catalisadores. As FePs imobilizadas foram catalisadores mais eficientes que as correspondentes MnPs, mesmo quando imidazol foi empregado como um co-catalisador para as MnPs ancoradas. Embora os rendimentos de produtos oxidados utilizando H2O2 tenham sido mais baixos que aqueles obtidos com PhIO, alguns sistemas heterogêneos envolvendo MePs foram mais eficientes que as correspondentes MePs em solução, tanto em termos de rendimento de produto quanto de seletividade.FAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CNP

Robotic implantation of intracerebral electrodes for deep brain stimulation

This dissertation objective is to contribute for the development of a robotic system towards neurosurgery assistance in Deep Brain Stimulation (DBS) stereotactic procedures. Being DBS neurosurgery typically a long, physically and cognitively demanding procedure; the introduction of a robotic assistant to hold, manipulate and position instrumentation would improve the medical team working conditions and lead to better surgery outcomes. Upon understanding how could the robot be used and what robotic systems were adequate to the task, we implemented a simulation environment to emulate several industrial robot manipulators and the operating room. It was also developed each robot geometric and differential kinematic equations, and control algorithms specifically oriented for DBS neurosurgery assistance. Taking into account the operating room arrangement, the robot characteristics and task requirements, we selected the most apt industrial robotic manipulator and further elaborated on its placement and orientation to achieve utmost performance.This work has been partially financed by projects FP7 Marie Curie ITN - NETT (project no289146), FCT FCOMP-01-0124-FEDER-022674, Pest-C/MAT-UI0013/2011 (FCT grant ref. UMINHO/BIC/8/2012) and FCT PhD grant (ref. SFRH/BD/86499/2012)

Tuning graphitic carbon nitride (g-C3N4) electrocatalysts for efficient oxygen evolution reaction (OER)

Nowadays, energy conversion and storage technologies are essential research topics due to the necessity of more sustainable processes. Specifically, water splitting is highly affected by slow kinetics and limited knowledge of the oxygen evolution reaction (OER). This work envisages the preparation of graphitic carbon nitride (g-C3N4) electrocatalysts for efficient OER by a facile one-pot method. The impact of the preparation temperature (450–650 ◦C) of g-C3N4 was assessed for the first time on water splitting processes and explained by different characterisation techniques. The unique crystal structure, surface chemistry, and electronic properties of the material prepared at 550 ◦C lead to a remarkable OER efficiency, with an overpotential of 355 mV at 10 mA cm− 2 and a Tafel slope of 46.8 mV dec− 1. Interestingly, three major differences were observed when comparing the material prepared at 550 ◦C with those obtained at other temperatures: the reduced structural distortion, the superior composition in oxygen and the presence of terminal functional groups. Also, compared to other metalfree g-C3N4 electrocatalysts reported in the literature, we achieved lower Tafel slope values without additional post-treatments or co-catalysts. Hence, for the first time a metal-free catalyst defeats benchmark IrO2. The prepared electrodes were stable for up to 45 h, even when increasing the applied current density to 100 mA cm− 2 for 15 h. Thus, this work provides a simple route for the fabrication of highly-efficient and long-lasting electrocatalysts for a remarkable OER performance.Agencia Estatal de Investigación | Ref. PID2020-113667 GB-I00Fundação para a Ciência e a Tecnologia | Ref. UIDB/50020/2020Fundação para a Ciência e a Tecnologia | Ref. UIDP/50020/2020Xunta de Galicia | Ref. ED481D-2023/015Universidade de Vigo/CISU

REGULATION OF BETA-ADRENOCEPTORS ACTIVITYUSING SYNTHETIC LIGHT-REGULATED MOLECULES

Beta-adrenoceptors (ß-AR) are prototypical G proteincoupled receptors and important pharmacological targets for many diseases. Indeed, a number of approved drugs target these receptors due to their key role on many physiological functions. Among other examples, we encounter ß1-AR antagonists (ß- Blockers), which constitute the first-line therapy for the treatment of heart diseases, and ß2-AR agonists, which act as bronchodilators for the treatment of breathing pathologies. Considering the relevance of these receptors, achieving a reversible and localised control of their activity would provide a powerful tool, both for its research applications and its clinical potential. In this context, photopharmacology arises as a potent approach. Photopharmacology is an emerging field based on the use of synthetic light-regulated molecules to allow reversible spatiotemporal control of target receptors in native tissues. These ligands have the potential to provide a precise and controllable therapeutic action with increased efficacy and reduced side effects. Moreover, the fine regulation on demand of the receptor activation state is of great interest for their study in non-modified cells, tissues and organisms. The present project provides the first proof of concept for beta-adrenoceptor photopharmacology. We first designed and synthesised libraries of lightregulated compounds in order to regulate ß-AR activity with spatiotemporal precision. Subsequent testing highlighted the successful development of compounds with promising pharmacological properties which can be reversibly and irreversibly controlled by light. The discovered molecules enable a fine control of ß-AR in their native environment that will certainly open the door to innovative research procedures and may inspire future personalized therapies targeting these receptors

In vitro and in vivo regulation of ß-Adrenoceptors signaling using synthetic light-regulated molecules

Beta-adrenoceptors (ß-AR) are prototypical G protein-coupled receptors (GPCR) and important pharmacological targets for numerous diseases. Indeed, a number of approved drugs target ß-AR, which are key regulators of many physiological functions. Among other examples, ß1-AR antagonists (known as ß-Blockers) are first-line therapies for the treatment of heart failure, and ß2-AR agonists, which act as bronchodilators, are widely used for the treatment of breathing pathologies. Considering the medical relevance of these receptors, achieving a reversible and localized control of their activity would provide a powerful research and clinical tool. GPCR signaling is currently recognized as a multidimensional process governed by molecular, spatial and temporal components. Uncovering the role of each of these dimensions is crucial to improve our knowledge on cell communication, to understand how different pathways give rise to cellular and physiological effects, and to know how can we interact with biological systems with precision using drugs. Photopharmacology is an emerging field in which light-sensitive molecules are used to control the function of a given target protein in native tissues. The modulation of the target activity is achieved by small, drug-like, photoregulated ligands. By the use of light, both spatial and temporal control of the compound activity can be achieved in unprecedented manners compared to conventional pharmacology. These ligands have the potential to provide highly precise and controllable therapeutic actions that may result in increased efficacies and reduced side effects. Importantly, photopharmacology may allow to gain mechanistic insight on the interplay between the activation time and the receptor location during signaling processes in non-modified cells, tissues and whole organisms. Our research focused on the generation of new molecular tools for beta-adrenoceptors photopharmacology will be presented in this communication. First, several libraries of light-sensitive compounds with the aim to regulate ß-AR activity with spatiotemporal precision were designed and synthesized. Subsequent testing in cell preparations demonstrated the successful development of compounds with promising pharmacological properties, which can be reversibly and irreversibly controlled by light. Among those, several hit compounds were identified as ligands for beta-1 and beta-2 adrenoceptors with low nanomolar activities. These libraries compounds were found to be active enough to become useful photopharmacological tools, so we also performed in vivo experiments to determine their research potential in physiological environments. Indeed, the discovered molecules enabled a fine control of ß-AR in their native environment. We believe that the results of these studies will certainly open the door to innovative research procedures and may inspire future therapies targeting ß-AR

Enzyme classification with peptide programs: a comparative study

<p>Abstract</p> <p>Background</p> <p>Efficient and accurate prediction of protein function from sequence is one of the standing problems in Biology. The generalised use of sequence alignments for inferring function promotes the propagation of errors, and there are limits to its applicability. Several machine learning methods have been applied to predict protein function, but they lose much of the information encoded by protein sequences because they need to transform them to obtain data of fixed length.</p> <p>Results</p> <p>We have developed a machine learning methodology, called peptide programs (PPs), to deal directly with protein sequences and compared its performance with that of Support Vector Machines (SVMs) and BLAST in detailed enzyme classification tasks. Overall, the PPs and SVMs had a similar performance in terms of Matthews Correlation Coefficient, but the PPs had generally a higher precision. BLAST performed globally better than both methodologies, but the PPs had better results than BLAST and SVMs for the smaller datasets.</p> <p>Conclusion</p> <p>The higher precision of the PPs in comparison to the SVMs suggests that dealing with sequences is advantageous for detailed protein classification, as precision is essential to avoid annotation errors. The fact that the PPs performed better than BLAST for the smaller datasets demonstrates the potential of the methodology, but the drop in performance observed for the larger datasets indicates that further development is required.</p> <p>Possible strategies to address this issue include partitioning the datasets into smaller subsets and training individual PPs for each subset, or training several PPs for each dataset and combining them using a bagging strategy.</p

Iron(III) porphyrin covalently supported onto magnetic amino-functionalized nanospheres as catalyst for hydrocarbon and herbicide oxidations

This work describes the covalent immobilization of an ironporphyrin, 5,10,15,20- tetrakis(pentafluorophenyl)porphyrin iron(III) chloride (FeTFPP), onto maghemite/silica magnetic nanospheres covered with aminofunctionalized silica. The resulting material (&#947;-Fe2O3/SiO2-NHFeP) was characterized by diffuse reflectance infrared spectroscopy (DRIFTS) and UV-Vis absorption spectroscopy. The catalytic activity of this magnetic ironporphyrin was investigated in the oxidation of hydrocarbons (styrene, (Z)-cyclooctene and R-(+)-limonene) and an herbicide (simazine) by hydrogen peroxide or 3-chloroperoxybenzoic acid. Hydrocarbon and simazine oxidation reaction products were analyzed by gas chromatography (GC) and high performance liquid chromatography (HPLC), respectively. This catalytic system proved to be efficient and selective for hydrocarbon oxidation, leading to high product yields from styrene (89%), cyclooctene (71%) and R-(+)-limonene (86%). Simazine oxidation was attained with 100% selectivity for a dechlorinated product (OEAT), while several oxidation products were obtained for the same catalyst in homogeneous media. The catalyst can be easily recovered through application of an external magnetic field and washed after reaction. Catalyst reuse experiments for R-(+)-limonene oxidation have shown that the catalytic activity is kept at 90% after 10 consecutive reactions

Hepatitis C virus infection protein network

A proteome-wide mapping of interactions between hepatitis C virus (HCV) and human proteins was performed to provide a comprehensive view of the cellular infection. A total of 314 protein–protein interactions between HCV and human proteins was identified by yeast two-hybrid and 170 by literature mining. Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HCV are enriched in highly central and interconnected proteins. A global analysis on the basis of functional annotation highlighted the enrichment of cellular pathways targeted by HCV. A network of proteins associated with frequent clinical disorders of chronically infected patients was constructed by connecting the insulin, Jak/STAT and TGFβ pathways with cellular proteins targeted by HCV. CORE protein appeared as a major perturbator of this network. Focal adhesion was identified as a new function affected by HCV, mainly by NS3 and NS5A proteins

Metrics for GO based protein semantic similarity: a systematic evaluation

<p>Abstract</p> <p>Background</p> <p>Several semantic similarity measures have been applied to gene products annotated with Gene Ontology terms, providing a basis for their functional comparison. However, it is still unclear which is the best approach to semantic similarity in this context, since there is no conclusive evaluation of the various measures. Another issue, is whether electronic annotations should or not be used in semantic similarity calculations.</p> <p>Results</p> <p>We conducted a systematic evaluation of GO-based semantic similarity measures using the relationship with sequence similarity as a means to quantify their performance, and assessed the influence of electronic annotations by testing the measures in the presence and absence of these annotations. We verified that the relationship between semantic and sequence similarity is not linear, but can be well approximated by a rescaled Normal cumulative distribution function. Given that the majority of the semantic similarity measures capture an identical behaviour, but differ in resolution, we used the latter as the main criterion of evaluation.</p> <p>Conclusions</p> <p>This work has provided a basis for the comparison of several semantic similarity measures, and can aid researchers in choosing the most adequate measure for their work. We have found that the hybrid <it>simGIC</it> was the measure with the best overall performance, followed by Resnik's measure using a best-match average combination approach. We have also found that the average and maximum combination approaches are problematic since both are inherently influenced by the number of terms being combined. We suspect that there may be a direct influence of data circularity in the behaviour of the results including electronic annotations, as a result of functional inference from sequence similarity.</p