Research

Research Interests

Our group is focused on the application and development of nuclear magnetic resonance (NMR) spectroscopy to study molecular interaction processes in systems of interest in chemistry and biology. 

Among our currently on going projects are the application of NMR to the rationalization of drug/protein interactions and to the study of how protein ligand interactions affect protein structure and dynamics.

We have also been applying NMR to study solvation in alternative solvents, namely ionic liquids and super critical carbon dioxide (scCO2). We have developed a system to perform High Pressure NMR to study solvation in supercritical CO2.

We are currently working on a project to explore the potentiality of using ionic liquids to capture CO2.

Projects and collaborations

Carbohydrate binding modules

(CBMs) are non-catalytic proteins that are part of a multienzymatic complex termed cellulosome. They bind to a wide range of poly- and oligosaccharides, being the most common specificity towards cellulose, which is the most abundant polysaccharide on Earth. The 3D solution structure of CBMs is being determined and the ligand specificity studied by STD-NMR and NMR titrations. Protein backbone dynamics in the presence and absence of ligand is being studied through measurement of longitudinal relaxation rates R1, transverse relaxation rates, R2, and the 15N{1H} NOE of the backbone amide 15N nuclei.
Collaboration with: 
Maria João Romão, Ana Luisa Carvalho - Xtal group at FCT-UNL 
Carlos Fontes, José Prates - Faculdade de Medicina Veterinária - UTL

Ovine Doppel protein

The prion-like Doppel (Dpl) protein is a homologue related to the prion protein (PrP). Dpl is expressed in the brain of sheeps that do not express PrP, and Dpl is known to be toxic to neurons. The three-dimensional solution structure associated with DHPC micelles was determined by NMR for ovine Dpl (1-30). The structure is mainly constituted by α-helix. Further studies are ongoing to understand  the toxicity of these proteins. 
Collaboration with: 
Carlos Fontes, José Prates - Faculdade de Medicina Veterinária - UTL
Jorge Pimenta, Rosa Lino Pereira - Unidade de Recursos Genéticos, Reprodução e Melhoramento Animal, Instituto Nacional dos Recursos Biológicos (INRB) L-INIA 

Interaction with Zinc finger proteins

Zinc finger proteins are important targets for antiviral and anticancer drug interventions with the zinc finger motif representing 1-3 % of the human genome. The interaction between a platinated oligonucleotide, {Pt(dien)d(5’-TACGCC-3’)}, and the (34‑52)HIVNCp7 protein of human immunodeficiency virus type I was studied by NMR spectroscopy giving insight into the nature of the specific oligonucleotide/zing finger interactions and showing how platination of the oligonucleotide affects this interaction 
Collaboration with: 
Stefan Erhardt - Molecular Modelling group FCT-UNL
Nicholas P Farrel - Department of Chemistry, Virginia Commonwealth University, USA

Development of selective COX-2 inhibitors 

STD-NMR is being used to characterize the binding anti-inflammatory drugs to COX-1 and COX-2. Using well-studied COX inhibitors and by comparing STD signals with crystallographic structures, we have shown that there is a relation between the orientations of ibuprofen and diclofenac in the COX-2 active site and the relative STD responses detected in the NMR experiments. On the basis of this analysis, we have proposed a binding mode for ketorolac to the COX-2 active site. The combination of STD-NMR with docking  studies is being used to direct the synthesis of new anti-inflamatory compounds.
Collaboration with: 
Maria Manuel Marques - Organic Chemistry group FCT-UNL
Stefan Erhardt - Molecular Modelling group FCT-UNL
Eduarda Fernandes - Faculdade de Farmácia UPorto

NMR in ionic liquids

To extend the actual molecular understanding of ILs properties a protocol based on liquid and SSNMR to study IL structure and solute/solvent interactions has been developed. This is being achieved by: (i) comparing the intra and intermolecular ion pair interactions for different families of ILs and combinations of ion pairs; (ii) using SSNMR to compare IL nanostructure in the liquid and solid state; (iii) applying a NMR protocol to study the solvation of selected model molecules in different ILs; (iv) rationalizing the interactions based on molecular modelling studies (v) performing studies of simple dynamic processes in ILs (conformational equilibria, keto-enol equilibria, etc).
Collaboration with: 
Jairton Dupont - Univ Federal Rio Grande do Sul, Brazil
Sandra Einloft, Marcus Seferin - Pontificia Universidade do Rio Grande do Sul, Brazil
Sonia Cabral - CENPES, PETROBRAS, Brazil
Luis Mafra - CICECO, Univ. Aveiro
Teresa Casimiro - Polymer synthesis and processing in scCO2, FCT/UNL
A. Gil Santos - Molecular Modelling group FCT-UNL


High Pressure NMR and NMR in scCO2

High Pressure NMR is being used to extend the actual understanding of the molecular properties of scCO2 as a solvent. This is being achieved by: (i) performing HP-NMR studies with selected “CO2-philic” model molecules in order to establish a relation between “CO2-philicity” and specific types of intermolecular interactions (ii) the rationalization of the nature of these interactions with the aid of molecular modelling studies (iii) the application of the previous data to the study of micelle-solute-scCO2 interactions.
Collaboration with: 
Jairton Dupont - Univ Federal Rio Grande do Sul, Brazil
Sandra Einloft, Marcus Seferin - Pontificia Universidade do Rio Grande do Sul, Brazil
Sonia Cabral - CENPES, PETROBRAS, Brazil
Teresa Casimiro and Ana Aguiar Ricardo - Polymer synthesis and processing in scCO2, FCT/UNL
A. Gil Santos - Molecular Modelling group FCT-UNL


Currently Funded Projects

01-01-2010 to 31-12-2012 – “Study of intermolecular interactions in alternative solvents: A NMR based contribution to sustainable chemistry” - PTDC/QUI-QUI/098892/2008 (coordinator) – Total Funding: 198.111,00 €

01-01-2010 to 31-12-2012 – Development of Ion jelly® thin film printable batteries for smart devices - PTDC/CTM/100244/2008 (team member) - Total Funding: 175.000,00 €.

01-01-2010 to 31-12-2012 – “The Development and Rationalization of Stereoselective Reactions in Some Chiral Systems. A mixed experimental and theoretical approach” - PTDC/QUI-QUI/104056/2008 (team member) - Total Funding: 140.014,00 €.

30-09-2009 to 30-09-2011 - "Studies of Ionic Liquids for the capture and storage of CO2" - Thematic Network Technologies for climate change mitigation - REQUIMTE/CENPES-PETROBRAS/UFRGS/PUCRGS – Funded by PETROBRAS  (coordinator of the Portuguese team) 

01-01-2009 to 31-12-2011 - "Sol-gel entrapped cutinase: Understanding enzyme/matrix interactions via fluorescence, NMR and DRIFT spectroscopies, and site-directed mutagenesis" - PTDC/QUI/64744/2006 (team member) - Total Funding: 150.000,00 €.