PhD in Sustainable Chemistry, 2012/2016, Faculty of Sciences and Technology, New University of Lisbon and Faculty of Sciences, University of Porto
Thesis: Design of novel 3-hydroxy-4-pyridinone iron chelators to fight mycobacterium infection
Area of scientific activity
The area of scientific activity is Bioinorganic Chemistry, interfacing with the Medicinal Inorganic Chemistry and Biophysical Chemistry. Particular interests are the design of molecules with a therapeutic effect in order to regulate metal ion levels in living organisms, and the application of spectroscopic techniques to investigate drug-membrane interactions and their relation with the biological activity of the drugs.
Domain of specialization
The domains of specialization are Biochemistry, Biophysical Chemistry and Microbiology.
In the BSc Degree, expertise on the synthesis of 3-hydroxy-4-pyrone and 3-hydroxy-4-pyridinone ligands and their respective Zn(II) and VO(II) complexes was acquired. She has developed a theoretical and experimental expertise on UV-Vis absorption, fluorescence emission, NMR and EPR Spectroscopy and a good experience with other methods such as: Mass Spectrometry and Elemental Analysis, which have been used mostly as characterization techniques for the synthetized compounds. She has also gained advanced knowledge on in vivo studies like the evaluation of the insulin-mimetic activity of Zn(II) and VO(II) complexes, which was performed in STZ-induced diabetic rats. During this work, sustainable methodologies have been considered in order to perform more clean and efficient synthetic routes, namely with the employment of microwave heating in spite of conventional heating methods.
In the MSc course, she has developed a solid expertise on the synthesis of 3-hydroxy-4-pyridinone ligands functionalized with different fluorophores. The compounds have been characterized by the methods described above in which she has a good expertise. She also acquired strong expertise on in vitro studies, as the evaluation of the antibacterial activity of the chelators in the inhibition of Mycobacterium avium growth has been performed.
During the PhD project she developed expertise on the preparation of membrane models of liposomes and on studies concerning the investigation of drug-membrane interactions by different spectroscopic methods such as: NMR, EPR and Fluorescence emission. She acquired experience in the visualization of chelator’s distribution within cells from the immune system by Fluorescence Confocal Microscopy, and she also performed toxicological safety studies for diverse compounds in cell lines of hepatocytes.
Present research interest
The present research interests are centred in Bioinorganic Chemistry, in particular in the design of molecules that may be used as novel therapeutic strategies, namely to fight Infection caused by different bacterial species. The main interest is related with the Iron Biology, but the study of the importance of other metals such as Copper, Zinc and Vanadium, for biological processes, is also of a great interest. The design of metal ion chelators or metal ion complexes and their administration with therapeutic effect by means of the regulation of metal ions levels in living organisms is another point of interest. Additionally, the study of the structure-activity relationships of the drugs which will impact their biological effect, and also the study of the interaction of the drugs with biological membranes are other topics with particular interest. The design of fluorescent chelators is also of great importance, as these ligands can be visualized by several techniques and may allow the improvement of the knowledge concerning their cellular uptake and distribution.
Moniz, T.*, Cunha-Silva, L., Mesquita, R. B. R., Miranda, J. A., Silva, A. M. N., Silva, A. M. G., Rangel, A. O. S. S., de Castro, B. and Rangel, M.*, New hydrophilic 3-hydroxy-4-pyridinone chelators with ether-derived substituents: synthesis and evaluation of analytical performance in the determination of iron in waters, Polyhedron, 2019, 160, 145-156.
Rangel, M.*, Moniz, T., Silva, A.M.N. and Leite, A., Tuning the anti(myco)bacterial Activity of 3-Hydroxy-4-pyridinone Chelators through fluorophores, Pharmaceuticals, 2018, 11, 110-133.
Moniz, T., Leite, A., Silva, T., Gameiro, P., Gomes, M.S., de Castro, B., Rangel, M.*, The influence of functional groups on the permeation and distribution of antimycobacterial rhodamine chelators, Journal of Inorganic Biochemistry, 2017, 175, 138-147.
Santos, C.S., Carvalho, S.M.P., Leite, A., Moniz, T., Roriz, M., Rangel, A.O.S.S., Rangel, M.* and Vasconcelos*, M.W., Effect of tris(3-hydroxy-4-pyridinonate) iron(III) complexes on iron uptake and storage in soybean (Glycine max L.), Plant Physiology and Biochemistry, 2016, 106, 91-100.
Moniz, T., Queirós, C., Ferreira, R., Leite, A., Gameiro, P., Silva, A.M.G.*, and Rangel, M.*, Design of a water soluble 1,8-naphthalimide/3-hydroxy-4-pyridinone conjugate: investigation of its spectroscopic properties at variable pH and in the presence of Fe3+, Cu2+ and Zn2+”, Dyes and Pigments, 2013, 98, 201-211.
Moniz, T., Amorim, M.J., Ferreira, R., Nunes, A., Silva, A.M.G., Queirós, C., Leite, A., Gameiro, P., Sarmento, B., Remião, F., Yoshikawa, Y., Sakurai, H. and Rangel, M., Investigation of the insulin-enhancing properties of Zinc(II) 3-hydroxy-4-pyridinone complexes: identification of a new compound with a hypoglycemic effect in type I-like diabetic animals, Journal of Inorganic Biochemistry, 2011, 105, 1675–1682. http://dx.doi.org/10.1016/j.jinorgbio.2011.09.005