Reactivity studies on chromene derivatives

Dissertação de mestrado em Medicinal Chemistry

Analysis of output properties of the Peroxiredoxin/Thioredoxin/Thioredoxin reductase system

Dissertação de mestrado em Bioinformática

Perchlorate and chlorate reduction by the Crenarchaeon Aeropyrum pernix and two thermophilic Firmicutes

This study reports the ability of one hyperthermophile and two thermophilic microorganisms to grow anaerobically by the reduction of chlorate and perchlorate. Physiological, genomic and proteome analyses suggest that the Crenarchaeon Aeropyrum pernix reduces perchlorate with a periplasmic enzyme related to nitrate reductases, but that it lacks a functional chlorite-disproportionating enzyme (Cld) to complete the pathway. A. pernix, previously described as a strictly aerobic microorganism, seems to rely on the chemical reactivity of reduced sulfur compounds with chlorite, a mechanism previously reported for perchlorate-reducing Archaeoglobus fulgidus. The chemical oxidation of thiosulfate (in excessive amounts present in the medium) and the reduction of chlorite result in the release of sulfate and chloride, which are the products of a biotic-abiotic perchlorate reduction pathway in A. pernix. The apparent absence of Cld in two other perchlorate-reducing microorganisms, Carboxydothermus hydrogenoformans and Moorella glycerini strain NMP, and their dependence on sulfide for perchlorate reduction is consistent with observations made on A. fulgidus. Our findings suggest that microbial perchlorate reduction at high temperature differs notably from the physiology of perchlorate- and chlorate-reducing mesophiles and that it is characterized by the lack of a chlorite dismutase and is enabled by a combination of biotic and abiotic reactions.

Empatia no desenvolvimento típico: relação entre autorrelatos e comportamentos empáticos

Dissertação de mestrado integrado em Psicologia

Síntese de moléculas contendo a unidade de piperazina como potenciais agentes antipsicóticos

Tese de Doutoramente em Ciências (área de especialização em Química).

A novel and efficient approach to new N3-substituted-6,8-diaminopurines

[Excerpt] Purine nucleobases are fundamental biochemicals in living organisms. They have been a valuable inspiration for drug design once they play several key roles in the cell.1 To the best of our knowledge, reported routes to 8-aminopurines are still scarce due to the difficulty in introducing amino groups in this position of the purine ring. Here we report a novel, inexpensive and facile synthetic method to generate N3,N6-disubstituted-6,8-diaminopurines. In our research group, a number of substituted purines have been obtained from a common imidazole precursor, the 5-amino-4-cyanoformimidoyl imidazole 1. Recently, a comprehensive study on the reactivity of imidazoles 1 with nucleophiles under acidic conditions led us to develop experimental methods to incorporate primary amines into the cyanoformimidoyl group.2 (...)

Autoimmune diseases and pregnancy: analysis of a series of cases

BACKGROUND: An autoimmune disease is characterized by tissue damage, caused by self-reactivity of different effector mechanisms of the immune system, namely antibodies and T cells. All autoimmune diseases, to some extent, have implications for fertility and obstetrics. Currently, due to available treatments and specialised care for pregnant women with autoimmune disease, the prognosis for both mother and child has improved significantly. However these pregnancies are always high risk. The purpose of this study is to analyse the fertility/pregnancy process of women with systemic and organ-specific autoimmune diseases and assess pathological and treatment implications. METHODS: The authors performed an analysis of the clinical records and relevant obstetric history of five patients representing five distinct autoimmune pathological scenarios, selected from Autoimmune Disease Consultation at the Hospital of Braga, and reviewed the literature. RESULTS: The five clinical cases are the following: Case 1-28 years old with systemic lupus erythematosus, and clinical remission of the disease, under medication with hydroxychloroquine, prednisolone and acetylsalicylic acid, with incomplete miscarriage at 7 weeks of gestation without signs of thrombosis. Case 2-44 years old with history of two late miscarriages, a single preterm delivery (33 weeks) and multiple thrombotic events over the years, was diagnosed with antiphospholipid syndrome after acute myocardial infarction. Case 3-31 years old with polymyositis, treated with azathioprine for 3 years with complete remission of the disease, took the informed decision to get pregnant after medical consultation and full weaning from azathioprine, and gave birth to a healthy term new-born. Case 4-38 years old pregnant woman developed Behcet's syndrome during the final 15 weeks of gestation and with disease exacerbation after delivery. Case 5-36 years old with autoimmune thyroiditis diagnosed during her first pregnancy, with difficult control over the thyroid function over the years and first trimester miscarriage, suffered a second miscarriage despite clinical stability and antibody regression. CONCLUSIONS: As described in literature, the authors found a strong association between autoimmune disease and obstetric complications, especially with systemic lupus erythematosus, antiphospholipid syndrome and autoimmune thyroiditis.

Synthesis of polyhydroxylated compounds from Derythrose: enzymatic inhibition studies

Dissertação de mestrado em Química Medicinal

Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity

The relaxivity displayed by Gd3+ chelates immobilized onto gold nanoparticles is the result of complex interplay between nanoparticle size, water exchange rate and chelate structure. In this work we study the effect of the length of -thioalkyl linkers, anchoring fast water exchanging Gd3+ chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd3+ chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM-1s-1 (30 MHz, 25 ºC) were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles is determined mainly by size. Small nanoparticles (HD= 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD= 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggests that functionalized gold nanoparticles hold great potential for further investigation as MRI Contrast Agents. This study contributes to understand the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd3+ complexes. It is a relevant contribution towards “design rules” for nanostructures functionalized with Gd3+ chelates as Contrast Agents for MRI and multimodal imaging.

Síntese de derivados de adenina e guanina

Tese de Doutoramento em Ciências (Especialidade em Química)

Ligantes de baixo impacto ambiental e baixo custo, baseados na ativação química de escórias de aciaria

Dissertação de mestrado integrado em Engenharia Civil

A relação entre jornalistas e leitores no online: análise do feedback do público durante a experiência de estágio no P3

Relatório de estágio de mestrado em Ciências da Comunicação (área de especialização em Informação e Jornalismo)

Síntese de tetrahidroquinolinas a partir da D-eritrose

Dissertação de mestrado em Química Medicinal

Síntese e testes in vitro de novas pirimido[5,4-d] pirimidinas em células resistentes do cancro coloretal

Dissertação de mestrado em Química Medicinal

Production of whey protein-based aggregates under ohmic heating

Formation of whey protein isolate protein aggregates under the influence of moderate electric fields upon ohmic heating (OH) has been monitored through evaluation of molecular protein unfolding, loss of its solubility, and aggregation. To shed more light on the microstructure of the protein aggregates produced by OH, samples were assayed by transmission electron microscopy (TEM). Results show that during early steps of an OH thermal treatment, aggregation of whey proteins can be reduced with a concomitant reduction of the heating chargeby reducing the come-up time (CUT) needed to reach a target temperatureand increase of the electric field applied (from 6 to 12 V cm1). Exposure of reactive free thiol groups involved in molecular unfolding of -lactoglobulin (-lg) can be reduced from 10 to 20 %, when a CUT of 10 s is combined with an electric field of 12 V cm1. Kinetic and multivariate analysis evidenced that the presence of an electric field during heating contributes to a change in the amplitude of aggregation, as well as in the shape of the produced aggregates. TEM discloses the appearance of small fibrillar aggregates upon the influence of OH, which have recognized potential in the functionalization of food protein networks. This study demonstrated that OH technology can be used to tailor denaturation and aggregation behavior of whey proteins due to the presence of a constant electric field together with the ability to provide a very fast heating, thus overcoming heat transfer limitations that naturally occur during conventional thermal treatments.