Among the various metal ions which play a vital role in biology, we have been devoting a special attention to iron. Iron is an essential element to life, being involved in fundamental processes such as ribonucleotide reduction, oxidative respiration and oxygen transport. This transition metal has been chosen by evolution due to its natural abundance and the versatility of its chemical properties, namely the multitude of oxidation states and the tunability of reduction potentials. However, its role as a catalyst in redox reactions presents a sour side, and the excess of iron or its mismanagement by the organism are intrinsically related with increased oxidative damage. Maintaining a critical balance of iron levels is, thus for, one of the main aims of living organisms.
Taking this in mind, in the last few years, our research has been focusing in different objectives such as developing approaches to tackle TB infection by limiting bacteria from accessing this nutrient, or contrariwise creating strategies to feed plants which suffer from chlorosis (iron deficiency). Furthermore, we are using our knowledge to develop innovative ways to quantify this essential micronutrient, either in water ecosystems or biological fluids.
Iron imbalance and particularly iron overload is related with several clinical conditions, such as hemochromatosis, thalassemias, diabetes and neurodegeneration. We aim thus for to develop innovative strategies to quantify iron in the blood serum. We are particularly interested in developing reliable methodologies to quantify toxic non-transferrin-bound iron (NTBI). In healthy individuals, virtually all the blood plasma iron is bound to the iron-transport protein transferrin. However, NTBI has been detected in the blood plasma of individuals suffering from several diseases and has been related to clinical outcome. The chemical nature of these iron species is still uncertain, which hampers its reliable quantification.
Aiming to surpass this key difficulty we have been dedicated to:
Study the chemical identity of NTBI;
Understand how modifications occurring to key serum proteins contribute to unbalance serum iron transport;
Develop new molecules/materials that will allow the selective and reliable quantification of NTBI.
The (Bio)Chemistry of Non-Transferrin-Bound Iron. Molecules, Silva AMN, Rangel M, Molecules 2022, 27, 1784. DOI: 10.3390/molecules27061784
Human transferrin: a bioinorganic chemistry perspective, Silva AMN, Moniz T, de Castro B, Rangel M. Coord. Chem. Rev. 2021, 449, 214186. DOI: 10.1016/j.ccr.2021.214186
Determining the glycation site specificity of human holo-transferrin, Silva, AMN,, Coimbra, JTS., Castro, MM., Oliveira, A,, Brás, NF., Fernandes, PA., Ramos, MJ., Rangel, M., J. Inorg. Biochem. 2018, 186, 95-102; DOI: 10.1016/j.jinorgbio.2018.05.016.
The glycation site specificity of human serum transferrin is a determinant for transferrin's functional impairment under elevated glycaemic conditions, Silva, AMN., Sousa, PRH., Coimbra, JTS., Brás, NF., Vitorino, R., Fernandes, PA., Ramos, MJ., Rangel, M., Domingues, P., Biochem. J., 2014, 461(1), 33-42: DOI: 10.1042/BJ20140133.