Browsing by Author "Leite, Andreia"
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- Novel 3-hydroxy-4-pyridinonato oxidovanadium(IV) complexes to investigate structure/activity relationshipsPublication . Rangel, Maria; João Amorim, M.; Nunes, Ana; Leite, Andreia; Pereira, Eulalia; De Castro, Baltazar; Silva, Carla Sousa e; Yoshikawa, Yutaka; Sakurai, HiromuA previous evaluation of the insulin-like activity of three 3-hydroxy-4-pyridinonato oxidovanadium(IV) complexes raised questions about structure/activity relationships, namely the influence of the hydrophilic/lipophilic balance of the complex and the capacity of the ligand to stabilize the +4 oxidation state of vanadium ion, on achieving an positive effect. To address these questions, we synthesized six new oxidovanadium(IV) complexes with variable hydrophilic/lipophilic balance, obtained by introducing different substituents on the nitrogen atom, and used two 3-hydroxy-4-pyrones as starting reagents to provide methyl and ethyl groups in the ortho position of the ring. For the new and previously reported complexes, we studied the oxidation–reduction properties and insulin-like activity in terms of inhibitory effect on Free fatty acid (FFA) release in isolated rat adipocytes. The results obtained show that only one of the complexes, Bis(3-hydroxy-1(H)-2-methyl-4-pyridonato)oxidovanadium(IV), VO(mpp)2, exhibits a significantly greater capacity to inhibit FFA release than VOSO4 and consequently is worthy to be considered for further studies. The establishment of structure activity relationships was not attainable but this study brings new information about the influence of some properties of the compounds on the achievement of an insulin-like effect. The results reveal that: (i) the oxidation–reduction cycles of the complexes are identical; (ii) the presence of more lipophilic substituents on the nitrogen atom does not enhance insulin-like properties; (iii) a high solubility in water proved to be not sufficient for a positive activity in inhibiting FFA release; (iv) a small molecular size may be an important property for reaching the right targets.
- Novel tetradentate chelators derived from 3-hydroxy-4-pyridinone units: synthesis, characterization and aqueous solution propertiesPublication . Leite, Andreia; Silva, Ana M.G.; Nunes, Ana; Andrade, Mariana; Sousa, Carla; Cunha-Silva, Luís; Gameiro, Paula; de Castro, Baltazar; Rangel, MariaThe synthesis and characterization of three novel tetradentate ligands (T1, T2 and T3) based on 3-hydroxy-4-pyridinone chelating units are described. The three ligands exhibit different flexibility due to the use of two different anchor molecules, piperazine and 1,2-diaminobenzene, and to the diverse length of the 3-hydroxy-4-pyridinone arms. All reactions were performed using both conventional heating and microwave irradiation in order to evaluate the possibility of using greener methods in these synthetic procedures. The results showed that, in all cases, microwave irradiation provides the desired ligands reducing reaction time in ca. 97%. The structure of ligand T3 was resolved by X-ray crystallography, showing significant hydrogen bonding and interesting pep interaction between the benzene and pyridinone rings. The use of potentiometric and spectroscopic methods allowed determination of acidity constants and unequivocal assignment of proton loss for each pKa value. Interaction of the ligands with divalent metal ions was assessed by spectroscopic methods.