Showing papers by "Andreia Leite published in 2018"

Synthesis and coordination studies of 5-(4′-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)porphyrin and its pyrrolidine-fused chlorin derivative

Abstract: The introduction of a carboxylate function into porphyrins allows a variety of modifications, including coordination and conjugation, which are central to enhance the efficiency of macrocycles in photonic materials and biological applications Herein, a synthetic strategy to obtain 5-(4′-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)porphyrin and its pyrrolidine-fused chlorin derivative was developed by the 1,3-dipolar cycloaddition of a carbomethoxyphenyl substituted porphyrin with an azomethine ylide, followed by hydrolysis under thermal acidic conditions The 1,3-dipolar cycloaddition of the carbomethoxyphenyl porphyrin with N-methyl nitrone was also performed to give an isomeric mixture of isoxazolidine-fused chlorins, revealing lower selectivity and lower yields; in addition, retrocycloaddition of the isoxazolidine-fused chlorins was observed under the hydrolysis conditions The resulting carboxyphenyl macrocycles were characterized using 1H and 19F NMR, ESI-MS and SC-XRD for 5-(4′-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)porphyrin In order to study the influence of coordination to a metal ion on the electronic properties of carboxyphenyl substituted porphyrins, a series of metal complexes of 5-(4′-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)porphyrin and its pyrrolidine-fused chlorin derivative were synthesized by microwave-mediated metallation with Fe(III), Cu(II) and Zn(II) salts EPR spectroscopy was particularly relevant to the characterization of the Cu(II) complexes of both macrocycles and to study the coordination chemistry of these ligands with Cu(II) ions

Tuning the Anti(myco)bacterial Activity of 3-Hydroxy-4-pyridinone Chelators through Fluorophores.

Abstract: Controlling the sources of Fe available to pathogens is one of the possible strategies that can be successfully used by novel antibacterial drugs. We focused our interest on the design of chelators to address Mycobacterium avium infections. Taking into account the molecular structure of mycobacterial siderophores and considering that new chelators must be able to compete for Fe(III), we selected ligands of the 3-hydroxy-4-pyridinone class to achieve our purpose. After choosing the type of chelating unit it was also our objective to design chelators that could be monitored inside the cell and for that reason we designed chelators that could be functionalized with fluorophores. We didn’t realize at the time that the incorporation a fluorophore, to allow spectroscopic detection, would be so relevant for the antimycobacterial effect or to determine the affinity of the chelators towards biological membranes. From a biophysical perspective, this is a fascinating illustration of the fact that functionalization of a molecule with a particular label may lead to a change in its membrane permeation properties and result in a dramatic change in biological activity. For that reason we believe it is interesting to give a critical account of our entire work in this area and justify the statement “to label means to change”. New perspectives regarding combined therapeutic approaches and the use of rhodamine B conjugates to target closely related problems such as bacterial resistance and biofilm production are also discussed.

EPR and 51V NMR studies of prospective anti-diabetic bis(3-hydroxy-4-pyridinonato)oxidovanadium(IV) complexes in aqueous solution and liposome suspensions

Abstract: We report EPR and 51V NMR characterization of vanadium(IV/V) species originating from bis(3-hydroxy-4-pyridinonato)oxidovanadium(IV) complexes in aqueous solution at pH 74, under aerobic conditions and along time Since complexes possess variable hydrophilic/lipophilic balance and consequently different solubilities in water we also performed a parallel study in POPC liposome suspensions For less soluble complexes we used DMSO as a co-solvent We identified three groups of complexes with different solubilities in water Compounds 1 and 2 are soluble enough to produce 15 mM solutions in MOPS buffer Compounds 3 and 4 exhibit intermediate solubility but studies in MOPS buffer and POPC liposomes demonstrate that solubilisation is considerably enhanced in liposome suspensions Compounds 5 and 6 exhibit low water solubility, which is not sufficiently enhanced in liposome suspensions thus constraining the use of DMSO as a co-solvent Analysis of the EPR spectra of bis(3-hydroxy-4-pyridinonato)oxidovanadium(IV) complexes shows that upon dissolution a single species is present in solution, [VOL2] In the presence of air [VOL2] is oxidized to three species, [VO2L2]−, [VO2L] and V1 (H2VO4−) as characterized by the 51V NMR spectra Addition of sodium ascorbate reduces the V(V) species to the original [VOL2] complex The results demonstrate that the use of DMSO lowers the rate of oxidation of the [VOL2] complex For DMSO percentages higher than 10% two distinct EPR signals are observable and EPR spin-Hamiltonian parameters confirm the presence of [VOL2] in two different solvation environments, which confirms the participation of DMSO in the first solvation sphere of the complex