Tiago A. Matias

Encapsulation of metalloporphyrins improves their capacity to block the viability of the human malaria parasite Plasmodium falciparum

UNLABELLED Several synthetic metallated protoporphyrins (M-PPIX) were tested for their ability to block the cell cycle of the lethal human malaria parasite Plasmodium falciparum. After encapsulating the porphyrin derivatives in micro- and nanocapsules of marine atelocollagen, their effects on cultures of red blood cells infected (RBC) with P. falciparum were verified. RBCs infected with synchronized P. falciparum incubated for 48 h showed a toxic effect over a micromolar range. Strikingly, the IC50 of encapsulated metalloporphyrins reached nanomolar concentrations, where Zn-PPIX showed the best antimalarial effect, with an IC50=330 nM. This value is an 80-fold increase in the antimalarial activity compared to the antimalarial effect of non-encapsulated Zn-PPIX. These findings reveal that the incubation of P. falciparum infected-RBCs with 20 μM Zn-PPIX reduced the size of hemozoin crystal by 34%, whereas a 28% reduction was noticed with chloroquine, confirming the importance of heme detoxification pathway in drug therapy. FROM THE CLINICAL EDITOR In this study, synthetic metalloporphyrins were tested as therapeutics that target Plasmodium falciparum. The IC50 of encapsulated metalloporphyrins was found to be in the nanomolar concentration range, with encapsulated Zn-PPIX showing an 80-fold increase in its antimalarial activity compared to the non-encapsulated form.

Design, syntheses, characterization, and cytotoxicity studies of novel heterobinuclear oxindolimine copper(II)-platinum(II) complexes

Herein, the design and syntheses of two new mononuclear oxindolimine-copper(II) (1 and 2) and corresponding heterobinuclear oxindolimine Cu(II)Pt(II) complexes (3 and 4), are described. All the isolated complexes were characterized by spectroscopic techniques (UV/Vis, IR, EPR), in addition to elemental analysis and mass spectrometry. Cyclic voltammetry (CV) measurements showed that in all cases, one-electron quasi-reversible waves were observed, and ascribed to the formation of corresponding copper(I) complexes. Additionally, waves related to oxindolimine ligand reduction was verified, and confirmed using analogous oxindolimine-Zn(II) complexes. The Pt(IV/II) reduction, and corresponding oxidation, for complexes 3 and 4 occurred at very close values to those observed for cisplatin. By complementary fluorescence studies, it was shown that glutathione (GSH) cannot reduce any of these complexes, under the experimental conditions (room temperature, phosphate buffer 50mM, pH7.4), using an excess of 20-fold [GSH]. All these complexes showed characteristic EPR spectral profile, with parameters values gǁ>g⊥ suggesting an axially distorted environment around the copper(II) center. Interactions with calf thymus-DNA, monitored by circular dichroism (CD), indicated different effects modulated by the ligands. Finally, the cytotoxicity of each complex was tested toward different tumor cells, in comparison to cisplatin, and low values of IC50 in the range 0.6 to 4.0μM were obtained, after 24 or 48h incubation at 37°C. The obtained results indicate that such complexes can be promising alternative antitumor agents.

Supramolecular Hybrid Organic/Inorganic Nanomaterials Based on Metalloporphyrins and Phthalocyanines

Metalloporphyrins and phthalocyanines have remarkable electrocatalytic properties, generally associated with the ring coordinated transition metal ion, which can be further improved based on supramolecular approach, by combination with suitable molecular ancillary groups. Among the possibilities, transition metal complexes such as ferrocene and ruthenium polypyridine complexes, as well as bisthiophene, dendrimers, and other macrocycles. For example, the electrochemical and photoinduced electron transfer properties of metalloporphyrin-dendrimer based systems (metalloporphyrin in dendrimer core, branches or periphery) are affected by dendrimer structure. The dendrimers at higher generations are globular structures providing many possibilities to arrange electroactive groups in different microenvironments giving rise to new properties and functionalities. Phenylazomethine dendrimers with a cobalt porphyrin core was applied for catalytic CO2 reduction in the presence of Lewis acid at relatively low overpotentials, due to the synergetic effect of the assembled metal ions and the porphyrin core involving a multielectron transfer process. That strategy has been extended by associating them with nanoparticles opening broad new perspectives in porphyrin and phthalocyanine chemistry. In fact, the combination with carbon, metals, sulfides, and oxides-based nanoparticles, as well as lamellar materials, is generating a whole new series of hybrid organic/inorganic nanomaterials with enhanced electrochemical, electrocatalytic, and photocatalytic properties. For example, porphyrin nanocomposites with lamellar materials such as vanadium pentoxide xerogels were explored as chemical vapor sensors. Ethinyl metalloporphyrin derivatives have been anchored to carbon nanotubes by electropolymerization, and the hybrid nanomaterial was shown to exhibit enhanced electroanalytic activity for tetraelectronic reduction of dioxygen. The electropolymerization of meso-tetra(4-sulfonatophenyl)porphyrinate manganese(III) in the presence of minute amounts of AgCl in alkaline solution was performed generating nanoflakes of MnTPPS decorated with MnO2 and silver nanoparticles, showing high electrocatalytic activity and sensitivity in hydrazine amperometric sensors. Also, porphyrins have been bond to carbon nanotubes, carbon nanohorns, graphene and graphene oxide, as well as fullerenes, generating interesting material for electrochemical and light-harvesting devices. The previous account (2006) was focused on the electrochemical modulation of electrocatalytic, as well as interaction and conduction properties, by electronic effects induced by ancillary groups, more specifically transition metal complexes. Now, a clear tendency of incorporating porphyrins and other macrocycles in nanosystems generating hybrid organic/inorganic nanomaterials is observed, widening the scope and perspectives in the porphyrin and phthalocyanine chemistry, as well as their electrochemical applications.

Thiosemicarbazone@Gold nanoparticle hybrid as selective SERS substrate for Hg 2+ ions

The Raman spectral profile of p-methylcarbohydrazonethioamide (MCHT) is completely changed due to strong SERS effects upon bonding onto gold nanoparticles surface, but some vibrational modes are further enhanced in the presence of Hg(II) ions. The lack of SERS response for most common metal ions indicates that the coordinating groups are interacting with the gold nanoparticles surface and not available for binding metal ions in solution, except for mercury ions. The selective enhancement of some vibrational modes is consistent with significant conformational changes upon binding of Hg(II) ion onto the AuNP@MCHT hybrid, as confirmed by TEM/EDS measurements, demonstrating its potentiality as a highly selective and sensitive SERS substrate.

REPLY to Nanomedicine: NMB, 2015; 11:1035

The observations raised by Somsri Wiwanitkit and Viroj Wiwanitkit concerning our recent report about the encapsulation of metalloporphyrins and their effect on human malaria parasite Plasmodium falciparum highlighted the increasing concern in finding new and safe antimalarial therapies and allow an opportunity to better clarify some aspects of our work. It is well known that one of the effects of chloroquine treatment is to impair the hemozoin formation. In our experiments comparing the hemozoin area in living red blood cells (RBC) infected with P. falciparum, we have confirmed that 20 μM of Zn-PPIX had a similar effect as 1 μM chloroquine on hemozoin growth inhibition after 2 hours incubation. Under these conditions, no relevant differences were observed between Zn-PPIX and chloroquine, however both treatments induced a statistically significant (P b 0.05) decrease on hemozoin area when those groups are compared with a control group treated with DMSO only, as shown in figure and methods section (a full comparison between all groups for this experiment is shown on Table 1). In fact, our work confirmed the results previously obtained by Martiney et al listed as reference 8 of the article. The decrease of hemozoin activity by Zn-PPIX reported by

Non-innocent behavior of 1-(2′-pyridylazo)-2-naphtholate coordinated to polypyridine ruthenium(II) complexes

The study of non-innocent redox behavior of ligands is important for the development of new catalysts and to comprehend the function of bioinorganic molecules in biochemical processes. In this work, we present a description of the non-innocent behavior of 1-(2′-pyridylazo)-2-naphtholate (pan) coordinated to ruthenium complexes. The synthesis and characterization of a series of [Ru(pan)(PPh3)(L)]PF6 complexes [where L = 2,2′-bipyridine (bpy), 4,4′-dimethyl-2,2′-bipyridine (dmbpy), and 1,10-phenanthroline (phen)] are presented. UV–vis analyses of the studied ruthenium complexes show intense absorptions from intraligand π–π* and metal-to-ligand charge-transfer transitions bands in the visible region. This observation shows a significant contribution of the pan ligand in all electronic transitions and is the indicative of non-innocent behavior. Theoretical calculations were carried out to support the UV–vis spectral assignments. Non-innocent behavior of pan was observed and confirmed using the electrochemical parameter EL(L) and by electrochemical studies. The pan ligand is non-innocent and can be modulated by donor and acceptor character of the other ligands present in the coordination sphere of the complex. Graphical Abstract