Feasibility of new polymeric matrices in the production of ferrous sulphate dosimeters.

External beam radiotherapy is a treatment modality that employs high doses for curative or palliative purposes. Safety in such treatments, particularly with high-precision equipment, necessitates strict adherence to quality control protocols to ensure the efficacy of oncological treatments. In this context, chemical dosimeters, particularly the Fricke gel, have emerged as valuable tools for quantitatively analysing absorbed radiation doses. These dosimeters can be applied both as tissue-equivalent phantoms and as radiation detectors in radiotherapy centers. The objective of this study was to evaluate the feasibility of new gelling matrices, comprising common materials such as CMC, GGU, and PVA, for producing ferrous sulphate dosimeters aimed at the relative quantification of radiation dose. A rheological study was conducted for different Fricke gel dosimetric formulations. Initially, the performance of these dosimeters, produced at various gel concentrations, was evaluated in terms of their consistency at room temperature. This was achieved through the straightforward process of humidification the gels with glycerine. These matrices consist of both natural and synthetic polymers that are readily accessible, easy to handle, and can be easily incorporated into the acidic ferrous sulphate solution. Parameters such as the influence of gelling matrix concentration, linearity, and stability were assessed and correlated with those previously investigated for Fricke gel produced with bloom 300 pig skin gelatine (GEL). Ferrous sulphate dosimeters fabricated with sodium carboxymethylcellulose (CMC), guar gum (GGU), and polyvinyl alcohol (PVA) exhibited a coefficient of variation of less than 1% relative to the dose response evaluated in this study. By using readily available and easily manageable materials, it is possible to replicate dosimeters with a favourable dosimetric response for high-dose measurements.

Computational 3D Models of Fe2+/3+-Aß1-42 Complexes Associated with Alzheimer's Disease.

The interaction between iron and amyloid-beta (Aß) peptides has received significant attention in Alzheimer's disease (AD) research due to its potential implications in developing this pathology. However, the coordination preferences of iron and Aß1-42 have not been thoroughly investigated or remain unknown. This study employs a computational protocol that combines homology modeling techniques with quantum mechanics (DTF-xTB) calculations to build and evaluate several 3D models of Fe2+/3+-Aß1-42. Our results reveal well-defined complexes for both the metal and peptide moieties, and we discuss the molecular interactions stabilizing these complexes by elucidating the coordinating environments and binding preferences. These proposed models offer valuable insights into the role of iron in Alzheimer's disease (AD) pathology.

Multifunctional Organometallic Compounds Active against Infective Trypanosomes: Ru(II) Ferrocenyl Derivatives with Two Different Bioactive Ligands.

Human African trypanosomiasis (HAT, sleeping sickness) and American trypanosomiasis (Chagas disease) are endemic zoonotic diseases caused by genomically related trypanosomatid protozoan parasites (Trypanosoma brucei and Trypanosoma cruzi, respectively). Just a few old drugs are available for their treatment, with most of them sharing poor safety, efficacy, and pharmacokinetic profiles. Only fexinidazole has been recently incorporated into the arsenal for the treatment of HAT. In this work, new multifunctional Ru(II) ferrocenyl compounds were rationally designed as potential agents against these pathogens by including in a single molecule 1,1'-bis(diphenylphosphino)ferrocene (dppf) and two bioactive bidentate ligands: pyridine-2-thiolato-1-oxide ligand (mpo) and polypyridyl ligands (NN). Three [Ru(mpo)(dppf)(NN)](PF6) compounds and their derivatives with chloride as a counterion were synthesized and fully characterized in solid state and solution. They showed in vitro activity on bloodstream T. brucei (EC50 = 31-160 nM) and on T. cruzi trypomastigotes (EC50 = 190-410 nM). Compounds showed the lowest EC50 values on T. brucei when compared to the whole set of metal-based compounds previously developed by us. In addition, several of the Ru compounds showed good selectivity toward the parasites, particularly against the highly proliferative bloodstream form of T. brucei. Interaction with DNA and generation of reactive oxygen species (ROS) were ruled out as potential targets and modes of action of the Ru compounds. Biochemical assays and in silico analysis led to the insight that they are able to inhibit the NADH-dependent fumarate reductase from T. cruzi. One representative hit induced a mild oxidation of low molecular weight thiols in T. brucei. The compounds were stable for at least 72 h in two different media and more lipophilic than both bioactive ligands, mpo and NN. An initial assessment of the therapeutic efficacy of one of the most potent and selective candidates, [Ru(mpo)(dppf)(bipy)]Cl, was performed using a murine infection model of acute African trypanosomiasis. This hit compound lacks acute toxicity when applied to animals in the dose/regimen described, but was unable to control parasite proliferation in vivo, probably because of its rapid clearance or low biodistribution in the extracellular fluids. Future studies should investigate the pharmacokinetics of this compound in vivo and involve further research to gain deeper insight into the mechanism of action of the compounds.

Bis(benzimidazole)amino thio- and selenoether Iron(II) complexes as proton reduction electrocatalysts.

Two novel Iron (II) complexes featuring tetrapodal bis(benzimidazole)amino thio- and selenoether ligands (LS and LSe) were synthesized, characterized, and tested as electrocatalysts for the hydrogen evolution reaction. The bromide complexes [Fe(LS,LSe)Br2] (1-2) are highly insoluble, but their DMSO solvates were characterized by single crystal X-ray diffraction, revealing an octahedral coordination environment that does not feature coordination of the chalcogen atoms. The corresponding triflate derivatives [Fe(LS,LSe)(MeCN)3]OTf2 (1c-2c) were employed for electrocatalytic proton reduction, with 1c exhibiting higher activity, thus suggesting that the thioether may participate as a more competent pendant ligand for proton transfer.

Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-N-acyl Hydrazones as Immunomodulatory Agents.

Immunomodulatory agents are widely used for the treatment of immune-mediated diseases, but the range of side effects of the available drugs makes necessary the search for new immunomodulatory drugs. Here, we investigated the immunomodulatory activity of new ferrocenyl-N-acyl hydrazones derivatives (SintMed(141−156). The evaluated N-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC50 values greater than 50 µM. In addition, all ferrocenyl-N-acyl hydrazones modulated nitrite production in immortalized macrophages, showing inhibition values between 14.4% and 74.2%. By presenting a better activity profile, the ferrocenyl-N-acyl hydrazones SintMed149 and SintMed150 also had their cytotoxicity and anti-inflammatory effect evaluated in cultures of peritoneal macrophages. The molecules were not cytotoxic at any of the concentrations tested in peritoneal macrophages and were able to significantly reduce (p < 0.05) the production of nitrite, TNF-α, and IL-1ß. Interestingly, both molecules significantly reduced the production of IL-2 and IFN-γ in cultured splenocytes activated with concanavalin A. Moreover, SintMed150 did not show signs of acute toxicity in animals treated with 50 or 100 mg/kg. Finally, we observed that ferrocenyl-N-acyl hydrazone SintMed150 at 100 mg/kg reduced the migration of neutrophils (44.6%) in an acute peritonitis model and increased animal survival by 20% in an LPS-induced endotoxic shock model. These findings suggest that such compounds have therapeutic potential to be used to treat diseases of inflammatory origin.

Mechanisms of chromium(VI) removal from solution by zeolite and vermiculite modified with iron(II).

Mechanisms of Cr(VI) reduction by Fe(II) modified zeolite (clinoptilolite/mordenite) and vermiculite were evaluated. Adsorbents were treated with Fe(SO4)·7H2O to saturate their exchange sites with Fe(II). However, this treatment decreased their CEC and pHPZC, probably due to the dealumination process. Vermiculite (V-Fe) adsorbed more Fe(II) (21.8 mg g-1) than zeolite (Z-Fe) (15.1 mg g-1). Z-Fe and V-Fe were used to remove Cr(VI) from solution in a batch test to evaluate the effect of contact time and the initial concentration of Cr(VI). The Cr(VI) was 100% reduced to Cr(III) by Z-Fe and V-Fe in solution at 18 mg L-1 Cr(VI) after 1 min. Considering that 3 mol of Fe(II) are required to reduce 1 mol of Cr(VI) (3Fe+2 + Cr+6 → 3Fe+3 + Cr+3), the iron content released from Z-Fe and V-Fe was sufficient to reduce 100% of the Cr(VI) in solutions up to 46.8 mg L-1 Cr(VI) and about 90% (V-Fe) and 95% (Z-Fe) at 95.3 mg L-1 Cr(VI). The Fe(II), Cr(III), Cr(VI), and K+ contents of the adsorbents and solutions after the batch tests indicated that the K+ ions from the [Formula: see text] solution were the main cation adsorbed by Z-Fe, while vermiculite did not absorb any of these cations. The H+ of the acidic solution (pH around 5) may have been adsorbed by V-Fe. The release of Fe(II) from Z-Fe and V-Fe involved cation exchange between K+ and H+ ions from solution, respectively. The reduction of Cr(VI) by Fe(II) resulted in the precipitation of Cr(III) and Fe(III) and a decrease in the pH of the solution to < 5. As acidity limits the precipitation of Cr(III) ions, they remained in solution and were not adsorbed by either adsorbent (since they prefer to adsorb K+ and H+). To avoid oxidation, Cr(III) can be removed by precipitation or the adsorption by untreated minerals.

Synthesis, docking, machine learning and antiproliferative activity of the 6-ferrocene/heterocycle-2-aminopyrimidine and 5-ferrocene-1H-Pyrazole derivatives obtained by microwave-assisted Atwal reaction as potential anticancer agents.

A simple and fast methodology under microwave irradiation for the synthesis of 2-aminopyrimidine and pyrazole derivatives using Atwal reaction is reported. After the optimization of the reaction conditions, eight 2-aminolpyrimidines containing ferrocene and heterocycles and three ferrocene pyrazoles were synthesized from the respective chalcones in good yields. Eight compounds had their structure determined by X-ray diffraction. The molecular hybrid 6a-h and 9a-c were tested on four cancer cell lines - HCT116, PC3, HL60 and SNB19 - where four pyrimidine 6a, 6f-h and one pyrazole 9c derivatives show promising antiproliferative activity. In addition, docking simulation and machine learning methods were carried out to explain the biological activity achieved by the synthetized compounds.

Solid-phase synthesis and evaluation of linear and cyclic ferrocenoyl/ruthenocenoyl water-soluble hexapeptides as potential antibacterial compounds.

A series of novel water-soluble short peptide-bioconjugates containing a ferrocenoyl (Fc) or ruthenocenoyl (Rc) unit was synthesized and characterized to combine the unique activity of ferrocene and the isoelectronic ruthenocene with precisely designed peptide structures. We aim at evaluating these bioconjugates as a new class of OrganoMetallic Short AntiMicrobial Peptides (OM-SAMPs). The series of OM-SAMPs was designed with a set of linear and "head-to-tail" cyclic metallocene-based hexapeptides derived from the homo-sequence H-KKKKKK-NH2 by substitution of lysine (K) by tryptophan (W) and by orthogonal derivatization of the ε-N-amine group of lysine by a metallocene moiety. Peptide conjugates were characterized by RP-HPLC, mass spectrometry (ESI and MALDI-TOF) and circular dichroism (CD) spectroscopy. Gram-positive and Gram-negative antibacterial activity testings were carried out to explore the role of insertion of the metallocene fragment into the peptide, and the effect of the modification of the cationic charge and aromatic residues on the physiochemical properties of these OM-SAMPs. These results show that the insertion of two tryptophan residues and ferrocenoyl/ruthenocenoyl moieties into a linear homo-sequence peptides increase significantly their antibacterial activity with minimum inhibitory concentration values as low as 5 µM for the most active compounds. However, "head-to-tail" cyclic metallocene-based hexapeptides were not active against Gram-negative bacteria up to concentrations of 50 µM. These studies provide a better understanding of the role of structural modifications to enhance antibacterial peptide activity, which is promising for their therapeutic application.

Evaluation of the environmental impact of magnetic nanostructured materials at different trophic levels.

Safety on the use of magnetic nanomaterials (MNMs) has become an active topic of research given all the recent applications of these materials in various fields. It is known that the toxicity of MNMs depends on size, shape, and surface functionalization. In this study, we evaluate the biocompatibility with different aquatic organisms of engineered MNMs-CIT with excellent aqueous dispersion and long-term colloidal stability. Primary producers (the alga Pseudokirchneriella subcapitata), primary consumers (the rotifer Lecane papuana), and predators (the fish, Danio rerio) interacted with these materials in acute and sub-chronic toxicity tests. Our results indicate that P. subcaptita was the most sensitive taxon to MNMs-CIT. Inhibition of their population growth (IC50 = 22.84 mg L-1) elicited cell malformations and increased the content of photosynthetic pigments, likely due to inhibition of cell division (as demonstrated in AFM analysis). For L. papuana, the acute exposure to MNMs shows no significant mortality. However, adverse effects such as decreased rate of population and altered swimming patterns arise after chronic interaction with MNMs. For D. rerio organisms on early life stages, their exposure to MNMs results in delayed hatching of eggs, diminished survival of larvae, altered energy resources allocation (measured as the content of total carbohydrates, lipids, and protein), and increased glucose demand. As to our knowledge, this is the first study that includes three different trophic levels to assess the effect of MNMs in aquatic organisms; furthermore, we demonstrated that these MNMs pose hazards on aquatic food webs at low concentrations (few mgL-1).

New Pd-Fe ferrocenyl antiparasitic compounds with bioactive 8-hydroxyquinoline ligands: a comparative study with their Pt-Fe analogues.

In the search for a more effective chemotherapy for the treatment of Human African Trypanosomiasis, a disease caused by the parasite Trypanosoma brucei, the development of ferrocenyl compounds has arisen as a promising strategy. In this work, five new Pd-Fe heterobimetallic [PdII(L)(dppf)](PF6) compounds, including 8-hydroxyquinolyl derivatives HL1-HL5 as bioactive ligands and dppf = 1,1'-bis(diphenylphosphino)ferrocene as the organometallic co-ligand, were synthesized and fully characterized in the solid state and in solution. Molecular structures of three compounds were solved by single crystal X-ray diffraction methods. The compounds displayed submicromolar or micromolar IC50 values against bloodstream T. brucei (IC50: 0.33-1.2 µM), and good selectivity towards the pathogen (SI: 4-102) with respect to mammalian macrophages (cell line J774). The new Pd complexes proved to be 2-fold to 45-fold more potent than the drug nifurtimox but most of them are less active than their Pt analogues. Potential molecular targets were studied. The complexes interact with DNA but they do not alter the intracellular thiol-redox homeostasis of the parasite. In order to understand and predict the main structural determinants on the anti-T. brucei activity, a search of quantitative structure-activity relationships (QSAR) was performed including all the [M(L)(dppf)](PF6) complexes, where M = Pd(ii) or Pt(ii), currently and previously developed by us. The correlation obtained shows the relevance of the electronic effects, the lipophilicity and the type of metal. According to the QSAR study, compounds with electron-withdrawing ligands, higher lipophilicity and harboring Pt would result in higher T. brucei cytotoxicity. From the whole series of [M(L)(dppf)](PF6) compounds developed, where M = Pt(ii) or Pd(ii) and HL = 8-hydroxyquinolyl derivatives, Pt-dppf-L4 (IC50 = 0.14 µM, SI = 48) was selected to perform an exploratory pre-clinical study in infected mice. This hit compound lacks acute toxicity when applied to animals in the dose/regimen described and exerts an anti-proliferative effect on parasites, which extends animal survival but is not curative.

Nanostructured functional peptide films and their application in C-reactive protein immunosensors.

Peptides with an active redox molecule are incorporated into nanostructured films for electrochemical biosensors with stable and controllable physicochemical properties. In this study, we synthesized three ferrocene (Fc)-containing peptides with the sequence Fc-Glu-(Ala)n-Cys-NH2, which could form self-assembled monolayers on gold and be attached to antibodies. The peptide with two alanines (n = 2) yielded the immunosensor with the highest performance in detecting C-reactive protein (CRP), a biomarker of inflammation. Using electrochemical impedance-derived capacitive spectroscopy, the limit of detection was 240 pM with a dynamic range that included clinically relevant CRP concentrations. With a combination of electrochemical methods and polarization-modulated infrared reflection-absorption spectroscopy, we identified the chemical groups involved in the antibody-CRP interaction, and were able to relate the highest performance for the peptide with n = 2 to chain length and efficient packing in the organized films. These strategies to design peptides and methods to fabricate the immunosensors are generic, and can be applied to other types of biosensors, including in low cost platforms for point-of-care diagnostics.

In vitro nematicidal activity of two ferrocenyl chalcones against larvae of Haemonchus contortus (L3) and Nacobbus aberrans (J2).

The main goal of this work was to evaluate the in vitro biological activity of two ferrocenyl chalcones (FcC-1 and FcC-2) against Haemonchus contortus (third-stage larvae (L3)) and Nacobbus aberrans (second-stage juveniles (J2)). Both compounds were synthesized and characterized by usual spectroscopic methods and their molecular structures were confirmed by single-crystal X-ray diffractometry. Nematode strains were examined in terms of percentage mortality of H. contortus (L3) by the action of FcC-1, which showed an effectivity of 100% at a concentration of 342 µM in 24 h, with EC50 = 20.33 µM and EC90 = 162.76 µM, whereas FcC-2 had an effectivity of 72% at a concentration of 342 µM in 24 h, with EC50 = 167.39 µM and EC90 = 316.21 µM. The effect of FcC-1 against nematode phytoparasite N. aberrans showed a better percentage of 95% at a concentration of 342 µM, with EC50 = 7.18 µM and EC90 = 79.25 µM, whereas the effect of FcC-2 was 87% at 342 µM, with EC50 = 168 µM and EC90 = 319.56 µM at 36 h. After treatment, the scanning electron micrographs revealed deformities in the dorsal flank and posterior part close to the tail of H. contortus L3. They showed moderate in vitro nematicidal activity against H. contortus L3 and N. aberrans J2.

The solar photo-Fenton process at neutral pH applied to microcystin-LR degradation: Fe2+, H2O2 and reaction matrix effects.

Microcystins are a group of cyanotoxins with known hepatotoxic effects, and their presence in drinking water represents a public health concern all over the world. The main objective of this work was to evaluate the solar photo-Fenton process at near-neutral pH in the degradation of microcystin-LR (MC-LR) under conditions close to those found in bloom episodes, with a high concentration of cell debris and natural organic matter (NOM). The influence of experimental parameters such as Fe2+ and H2O2 concentrations, reaction matrix, and the presence of scavenger ions, as well as ecotoxicity before and after treatment, was also evaluated. The reaction matrix was obtained from Microcystis aeruginosa cultivated in ASM-1 medium (ACE1 and ACE2 extracts). H2O2 and Fe2+ concentrations were optimized by 22 factorial design with the central point in a bench-scale solar reactor, using ACE1 extract, and the improved condition was applied in a compound parabolic collector (CPC) reactor, for the ACE2, natural water (RVW) and natural water with M. aeruginosa crude extract (RVCE). Matrix effect assays indicated that radical scavengers present in the medium were responsible for the decrease in the mineralization rates. The solar photo-Fenton process in the CPC reactor achieved COD (75%) and MC-LR (70%) reduction after 120 min at pH = 7.8, [H2O2]/COD = 3.18 and [H2O2]/[Fe2+] = 10 for the ACE2 sample. When the same conditions were applied to the RVCE sample, the process removed 77% of DOC and up to 99% of MC-LR after 45 min of the reaction. Sinapis alba bioassays showed that there was no increase in ecotoxicity after the solar photo-Fenton treatment. These results demonstrate the potential of the solar photo-Fenton process at neutral pH as an additional step in the treatment of natural matrices contaminated with microcystins. In addition, the work reinforces the importance of bioassays in treatment process monitoring.

Eugenia umbelliflora mediated reduction of silver nanoparticles incorporated into O-carboxymethylchitosan/y-Fe2O3: Synthesis, antimicrobial activity and toxicity.

The purpose of this study was to synthesize a new magnetic material with antimicrobial properties, incorporated into a biopolymer and containing silver nanoparticles (Ag NP) prepared extract of Eugenia umbelliflora as a reducing agent. Silver nanoparticles incorporated into magnetic nanocomposite O-carboxymethylchitosan/y-Fe2O3/Ag0 (CMAgE) composite were synthesized using an extract of E. umbelliflora. The antimicrobial activity of the pathogenic microorganism is reported here. The synthesized nanoparticles were also characterized, and quantified by Ag analysis. The minimum inhibitory concentrations (MIC) of CMAgE against Staphylococcus aureus, Escherichia coli, and Candida albicans were 16.5, 1000 and 500 µg/mL, respectively. The results show that these materials have significant synergistic effect on each other. The potential phytotoxic effect of the nanocomposites was evaluated using Cucumis sativus seeds. The positive values for seedling elongation inhibition (SEI) show that CMAgE and methanol extract of Eugenia umbelliflora (Eug) cause growth inhibition at a concentration of 1000 mg/L. The germination index (GI) values of 40% and 80% at 1000 mg/L, for CMAgE and Eug, respectively, showed inhibition of germination. CMAgE and Eug showed cytotoxic effects against Artemia salina nauplii, with LC50 values of 72.5 µL/mL and < 5.0 µL/mL respectively, after 48 h.

Antimicrobial activity of RP-1 peptide conjugate with ferrocene group.

Parasitic diseases are a neglected and serious problem, especially in underdeveloped countries. Among the major parasitic diseases, Leishmaniasis figures as an urgent challenge due to its high incidence and severity. At the same time, the indiscriminate use of antibiotics by the population is increasing together with resistance to medicines. To address this problem, new antibiotic-like molecules that directly kill or inhibit the growth of microorganisms are necessary, where antimicrobial peptides (AMPs) can be of great help. In this work, the ferrocene molecule, one active compound with low levels of in vivo toxicity, was coupled to the N-terminus of the RP1 peptide (derived from the human chemokine CXCL4), aiming to evaluate how this change modifies the structure, biological activity, and toxicity of the peptide. The peptide and the conjugate were synthesized using the solid phase peptide synthesis (SPPS). Circular dichroism assays in PBS showed that the RP1 peptide and its conjugate had a typical spectrum for disordered structures. The Fc-RP1 presented anti-amastigote activity against Leishmania amazonensis (IC50 = 0.25 µmol L-1). In comparison with amphotericin B, a second-line drug approved for leishmaniasis treatment, (IC50 = 0.63 µmol L-1), Fc-RP1 was more active and showed a 2.5-fold higher selectivity index. The RP1 peptide presented a MIC of 4.3 µmol L-1 against S. agalactiae, whilst Fc-RP1 was four times more active (MIC = 0.96 µmol L-1), indicating that ferrocene improved the antimicrobial activity against Gram-positive bacteria. The Fc-RP1 peptide also decreased the minimum inhibitory concentration (MIC) in the assays against E. faecalis (MIC = 7.9 µmol L-1), E. coli (MIC = 3.9 µmol L-1) and S. aureus (MIC = 3.9 µmol L-1). The cytotoxicity of the compounds was tested against HaCaT cells, and no significant activity at the highest concentration tested (500 µg. mL-1) was observed, showing the high potential of this new compound as a possible new drug. The coupling of ferrocene also increased the vesicle permeabilization of the peptide, showing a direct relation between high peptide concentration and high carboxyfluorescein release, which indicates the action mechanism by pore formation on the vesicles. Several studies have shown that ferrocene destabilizes cell membranes through lipid peroxidation, leading to cell lysis. It is noteworthy that the Fc-RP1 peptide synthesized here is a prototype of a bioconjugation strategy, but it still is a compound with great biological activity against neglected and fish diseases.

C-H Amination via Nitrene Transfer Catalyzed by Mononuclear Non-Heme Iron-Dependent Enzymes.

Expanding the reaction scope of natural metalloenzymes can provide new opportunities for biocatalysis. Mononuclear non-heme iron-dependent enzymes represent a large class of biological catalysts involved in the biosynthesis of natural products and catabolism of xenobiotics, among other processes. Here, we report that several members of this enzyme family, including Rieske dioxygenases as well as α-ketoglutarate-dependent dioxygenases and halogenases, are able to catalyze the intramolecular C-H amination of a sulfonyl azide substrate, thereby exhibiting a promiscuous nitrene transfer reactivity. One of these enzymes, naphthalene dioxygenase (NDO), was further engineered resulting in several active site variants that function as C-H aminases. Furthermore, this enzyme could be applied to execute this non-native transformation on a gram scale in a bioreactor, thus demonstrating its potential for synthetic applications. These studies highlight the functional versatility of non-heme iron-dependent enzymes and pave the way to their further investigation and development as promising biocatalysts for non-native metal-catalyzed transformations.

Microencapsulation performance of Fe-peptide complexes and stability monitoring.

Iron supplementation presents several challenges, such as low bioavailability, high reactivity and a metallic taste. Iron absorption is enhanced by complexing with organic compounds such as peptides, while microencapsulation is an alternative to protect the mineral and mask undesirable flavors. Fe-peptide complexes were obtained by reacting small whey peptides (< 5 kDa) with iron (from ferrous sulfate) under controlled conditions. Maltodextrin (MD) and polydextrose (PD) were used as the wall materials and spray dried to form particles containing the active Fe-peptide. The conditions of enzymatic hydrolysis with the bacterial endopeptidase produced from Bacillus licheniformis were optimized to achieve a high degree of cleavage (~20% degree of hydrolysis). The physicochemical and structural properties of the microparticles were evaluated during storage (365 days). The encapsulation process showed high efficiency (84%) and process yield (≥90%). The iron dialyzability and uptake by Caco-2 cells from microparticles were at least 3-fold higher than the ferrous sulfate. The water content and water activity varied from 3.0 to 5.7% and from 0.29 to 0.44, respectively, after 365 days. SEM revealed morphological stability during storage and EDX showed the presence of iron ions at the surface of the microparticles, which could be free or complexed. The microparticles can be an alternative of higher bioavailable iron besides the further protection and iron stability which the microparticles may present when compared with the Fe-peptide complexes. Future studies could demonstrate the feasibility of applying these microparticles in formulation for food supplementation, concerning bioavailability and sensory aspects.

Increased whitening efficacy and reduced cytotoxicity are achieved by the chemical activation of a highly concentrated hydrogen peroxide bleaching gel.

OBJECTIVE: This study was designed for the chemical activation of a 35% hydrogen peroxide (H2O2) bleaching gel to increase its whitening effectiveness and reduce its toxicity. METHODOLOGY: First, the bleaching gel - associated or not with ferrous sulfate (FS), manganese chloride (MC), peroxidase (PR), or catalase (CT) - was applied (3x 15 min) to enamel/dentin discs adapted to artificial pulp chambers. Then, odontoblast-like MDPC-23 cells were exposed for 1 h to the extracts (culture medium + components released from the product), for the assessment of viability (MTT assay) and oxidative stress (H2DCFDA). Residual H2O2 and bleaching effectiveness (DE) were also evaluated. Data were analyzed with one-way ANOVA complemented with Tukey's test (n=8. p<0.05). RESULTS: All chemically activated groups minimized MDPC-23 oxidative stress generation; however, significantly higher cell viability was detected for MC, PR, and CT than for plain 35% H2O2 gel. Nevertheless, FS, MC, PR, and CT reduced the amount of residual H2O2 and increased bleaching effectiveness. CONCLUSION: Chemical activation of 35% H2O2 gel with MC, PR, and CT minimized residual H2O2 and pulp cell toxicity; but PR duplicated the whitening potential of the bleaching gel after a single 45-minute session.

Pt-Fe ferrocenyl compounds with hydroxyquinoline ligands show selective cytotoxicity on highly proliferative cells.

Searching for a more effective chemotherapy for the treatment of Human African trypanosomiasis, the disease caused by the parasite Trypanosoma brucei, and cancer, in the current work five new [PtII(L)(dppf)](PF6) compounds, with HL = 8-hydroxyquinoline derivatives and dppf = 1,1'-bis(diphenylphosphino)ferrocene, were synthesized and fully characterized. Crystal structures of three compounds were solved by XRD. The compounds displayed fairly good activity against bloodstream T. brucei, with IC50 values in the submicromolar range (IC50: 0.14-0.93 µM), and good selectivity towards the pathogen (SI: 11 - 48) with respect to mammalian macrophages (cell line J774). Coordination to the {Pt-dppf} moiety led, in most cases, to an enhancement of the activity in respect to the bioactive ligands (11 to 41 fold). Cytotoxicity was assessed against wildtype (A2780) and cisplatin-resistance (A2780cisR) ovarian cancer cell lines. Four [PtII(L)(dppf)](PF6) compounds were more active (IC50: 1.2-4.4 µM) than cisplatin (IC50: 26.0 µM) on A2780 cells and showed far superior activity than the reference drug against A2780cisR cells. Platinum levels in A2780 cells showed poor correlation between cellular uptake and the cytotoxic activity. All the complexes interacted with DNA and the most active ones induced reactive oxygen species (ROS) formation which suggested that the mechanism of action for these complexes may be mediated by oxidative stress and interaction with DNA that could act as a potential molecular target for this type of complexes. Some complexes of this series could be considered new hits for the development of prospective agents against trypanosomatid parasites and ovarian cancer.

Exploring the metallochromic behavior of pentacyanidoferrates in visual, electronic and Raman spot tests.

Pentacyanidoferrate(II) complexes of aromatic N-heterocycles, such as 4-cyanopyridine, exhibit characteristic colors and strong metallochromism associated with the donor-acceptor interactions of the metal ions with the cyanide ligands. In the presence of transition metal ions insoluble polymeric complexes are formed, displaying bright yellow, red, brown and green colors with zinc(II), nickel(II), copper(II) and iron(III) ions, respectively. Such metallochromic response is better observed on filter paper, allowing applications in analytical spot tests. The effects can be explored visually and probed by means of modern instrumental facilities, including spectrophotometric and resonance Raman techniques. In this way, by using the cyanopyridinepentacyanidoferrates, the Prussian Blue test for ferric ions can be extended to the entire row of transition metal elements, providing a new and modern insight of such classical Feigl's spot tests.