Desenvolvimento de fármacos: melhoria do desempenho de princípios farmacologicamente ativos por síntese supramolecular

Dissertação para obtenção do Grau de Mestre em Bioorgânica

Multiresponsive supramolecular systems for information processing at the molecular level

Dissertação para obtenção do Grau de Doutor em Química Sustentável

Supercomplexes of Prokaryotic Aerobic Respiratory Chains-Escherichia coli and Bacillus subtilis supramolecular assemblies

Dissertation presented to obtain the Ph.D degree in Biochemistry.

Synthesis and characterization of C3-symmetric 1,3,5 - Benzenetricarboxamide derived supramolecular systems

The aim of this work was to study the self-assembly process of C3-symmetric molecules. To accomplish this objective 1,3,5 – benzentricarboxamides (BTA) derivatives were obtained. Five C3-symmetric molecules were synthesized in moderate to good yields (39-72%) using azo-benzene, aniline, benzylamine, tryptophan and tyrosine. The aggregation behavior of the BTA derivatives was probed with 1H-NMR spectroscopy, 1H-1H 2D Nuclear Overhauser Effect Spectroscopy (NOESY) and Diffusion Ordered Spectroscopy (DOSY). These experiments allowed to study the influence of H-bonding groups, aromatic rings, unsaturated bonds and the overall geometry in the molecular self-assembly associated with the different structural patterns present on these molecules. The stacking and large molecule behavior where observed in BTA 1, aniline derivative, BTA 4, tyrosine derivative or BTA 5, tryptophan derivative, with several of those discussed functional groups such as unsaturated bonds and H-bonding groups. BTA 5 was used in a few preliminary interaction studies with glucose and ammonium chloride showing interaction with the ammonium ion.

Chemical reaction network of flavylium ions in heterogeneous media

Dissertação apresentada para a obtenção do Grau de Doutor em Química, especialidade em Química-Física, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Ditopic molecular architectures for the recognition of anionic species

Dissertation presented to obtain the Ph.D degree in Chemistry

The two-component system of a novel copper resistant operon of Marinobacter hydrocarbonoclasticus

Dissertation for the Master’s Degree in Structural and Functional Biochemistry

Novel ready-to-eat mango product using gellan gum as gelling agent: physico-chemical, microbial and sensory characteristics

Este trabalho foi efectuado com o apoio da Universidade de Lisboa, Instituto Superior de Agronomia com o Centro de Engenharia dos Biossistemas (CEER

Soft biomaterials as a substitute for the Nucleus Pulposus

One of the largest health problems faced worldwide, when evaluated by direct (clinical) as well indirect cost (absenteeism), is the degeneration of the intervertebral disc (IVD) that leads to back pain and, potentially disability and individual´s quality of life decreasing. The intervertebral disc is a mechanical and biological complex structure, formed by a tough outer layer of fibrocartilage called Annulus Fibrosus (AF),which surrounds a soft, elastic and gelatinous core called Nucleus Pulposus (NP). These two structures are completed by two upper and lower encasing layer called Vertebral Endplates (VEP). The degeneration of the IVD is marked by the dehydration of the Nucleus Pulposus, reducing the hydrostatic pressure inside the nucleus, resulting in a loss of capability to support compressive forces, during the active period, and to regain height during the resting period. This situation will compromise the role of shock absorber by the NP and transfers these forces to the AF. This transfer will result in cracks on the AF, deteriorating the IVD, allowing the ingrowth of vessels and nerves. This project was based on the developing a protocol to test suitable NP replacements, in hope to future assessment of discrete mechanical values and characteristics for an NP replacement. For this, Nucleus pulposus samples from goat, encapsulated Hydromed gel denominated “Raviolis” and Chitosan gels, produced via wet route using an ammonium environment, were confined compressed. Chitosan was rheologically tested and swelling capability of all the three type of materials was assessed. Results showed that the Nucleus Pulposus and “Raviolis” have similar mechanical behavior, being able to swell and “build up” hydrostatic pressure after a compression stage, while the Chitosan gel did not showed that ability. Therefore, “Raviolis” are a more suitable candidate to replace the NP than Chitosan gels. It was also observed that confined compression is the key test to perform on any possible candidate to replace the NP.

Development and application of NMR techniques to study water-in-CO2 microemulsions

Self-assembly is a phenomenon that occurs frequently throughout the universe. In this work, two self-assembling systems were studied: the formation of reverse micelles in isooctane and in supercritical CO2 (scCO2), and the formation of gels in organic solvents. The goal was the physicochemical study of these systems and the development of an NMR methodology to study them. In this work, AOT was used as a model molecule both to comprehensively study a widely researched system water/AOT/isooctane at different water concentrations and to assess its aggregation in supercritical carbon dioxide at different pressures. In order to do so an NMR methodology was devised, in which it was possible to accurately determine hydrodynamic radius of the micelle (in agreement with DLS measurements) using diffusion ordered spectroscopy (DOSY), the micellar stability and its dynamics. This was mostly assessed by 1H NMR relaxation studies, which allowed to determine correlation times and size of correlating water molecules, which are in agreement with the size of the shell that interacts with the micellar layer. The encapsulation of differently-sized carbohydrates was also studied and allowed to understand the dynamics and stability of the aggregates in such conditions. A W/CO2 microemulsion was prepared using AOT and water in scCO2, with ethanol as cosurfactant. The behaviour of the components of the system at different pressures was assessed and it is likely that above 130 bar reverse microemulsions were achieved. The homogeneity of the system was also determined by NMR. The formation of the gel network by two small molecular organogelators in toluene-d8 was studied by DOSY. A methodology using One-shot DOSY to perform the spectra was designed and applied with success. This yielded an understanding about the role of the solvent and gelator in the aggregation process, as an estimation of the time of gelation.