The present study aimed to investigate the influence of albumin structure and gold speciation on the synthesis of gold nanoparticles (GNPs). The strategy of synthesis was the addition of HAuCl4 solutions at different pH values (3–12) to solutions of human and bovine serum albumins (HSA and BSA) at the same corresponding pH values. Different pH values influence the GNP synthesis due to gold speciation. Besides the inherent effect of pH on the native structure of albumins, the use N-ethylmaleimide (NEM)-treated and heat-denaturated forms of HSA and BSA provided additional insights about the influence of protein structure, net charge, and thiol group approachability on the GNP synthesis. NEM treatment, heating, and the extreme values of pH promoted loss of the native albumin structure. The formation of GNPs indicated by the appearance of surface plasmon resonance (SPR) bands became detectable from 15 days of the synthesis processes that were carried out with native, NEM-treated and heat-denaturated forms of HSA and BSA, exclusively at pH 6 and 7. After 2 months of incubation, SPR band was also detected for all synthesis carried out at pH 8.0. The mean values of the hydrodynamic radius (RH) were 24 and 34 nm for GNPs synthesized with native HSA and BSA, respectively. X-ray diffraction (XRD) revealed crystallites of 13 nm. RH, XRD, and zeta potential values were consistent with GNP capping by the albumins. However, the GNPs produced with NEM-treated and heat-denaturated albumins exhibited loss of protein capping by lowering the ionic strength. This result suggests a significant contribution of non-electrostatic interactions of albumins with the GNP surface, in these conditions. The denaturation of proteins exposes hydrophobic groups to the solvent, and these groups could interact with the gold surface. In these conditions, the thiol blockage or oxidation, the latter probably favored upon heating, impaired the formation of a stable capping by thiol coordination with the gold surface. Therefore, the cysteine side chain of albumins is important for the colloidal stabilization of GNPs rather than as the reducing agent for the synthesis. Despite the presence of more reactive gold species at more acidic pH values, i.e., below 6.0, in these conditions the loss of native albumin structure impaired GNP synthesis. Alkaline pH values (9–12) combined the unfavorable conditions of denaturated protein structure with less reactive gold species. Therefore, an optimal condition for the synthesis of GNPs using serum albumins involves more reactive gold salt species combined with a reducing and negatively charged form of the protein, all favored at pH 6–7.

Ca 2+-overload contributes to the oxidation of mitochondrial membrane lipids and associated events such as the permeability transition pore (MPTP) opening. Numerous experimental studies about the Ca 2+ /cardiolipin (CL) interaction are reported in the literature, but there are few studies in conjunction with theoretical approaches based on ab initio calculations. In the present study, the lipid fraction of the inner mitochondrial membrane was modeled as POPC/CL large unilamellar vesicles (LUVs). POPC/CL and, comparatively, POPC, and CL LUVs were challenged by singlet molecular oxygen using the anionic porphyrin TPPS4 as a photosensitizer and by free radicals produced by Fe 2+-citrate. Calcium ion favored both types of lipid oxidation in a lipid composition-dependent manner. In membranes containing predominantly or exclusively POPC, Ca 2+ increased the oxidation at later reaction times while the oxidation of CL membranes was exacerbated at the early times of reaction. Considering that Ca 2+ interaction affects the lipid structure and packing, density functional theory (DFT) calculations were applied to the Ca 2+ association with totally and partially protonated and deprotonated CL, in the presence of water. The interaction of totally and partially protonated CL head groups with Ca 2+ decreased the intramolecular P-P distance and increased the hydrophobic volume of the acyl chains. Consistently with the theoretically predicted effect of Ca 2+ on CL, in the absence of pro-oxidants, giant unilamellar vesicles (GUVs) challenged by Ca 2+ formed buds and many internal vesicles. Therefore, Ca 2+ induces changes in CL packing and increases the susceptibility of CL to the oxidation promoted by free radicals and excited species.

Aerobic organisms are afforded with an antioxidant enzymatic apparatus that more recently has been recognized to include cytochrome c, as it is able to prevent hydrogen peroxide generation by returning electrons from the superoxide ion back to the respiratory chain. The present study investigated the glutathione peroxidase (GPx), superoxide dismutase (SOD) and cytochrome c-like antioxidant activities of para Mn(III)TMPyP in isolated rat liver mitochondria (RLM) and mitoplasts. In RLM, Mn TMPyP is expected to be produced at the expense of NADPH/GSH oxidation. The present results suggest GPx-like activity to be the principal antioxidant mechanism of Mn III TMPyP, whose efficiency is dependent on the NADPH/GSH content in cells.

The photodynamic effects of the cationic TMPyP (meso-tetrakis [N-methyl-4-pyridyl]porphyrin) and the anionic TPPS4 (meso-tetrakis[4-sulfonatophenyl]porphyrin) against PC/CL phosphatidylcholine/cardiolipin (85/15%) membranes were probed to address the influence of phorphyrin binding on lipid damage. Electronic absorption spectroscopy and zeta potential measurements demonstrated that only TMPyP binds to PC/CL large unilamellar vesicles (LUVs). The photodamage after irradiation with visible light was analyzed by dosages of lipid peroxides (LOOH) and thiobarbituric reactive substance and by a contrast phase image of the giant unilamellar vesicles (GUVs). Damage to LUVs and GUVs promoted by TMPyP and TPPS4 were qualitatively and quantitatively different. The cationic porphyrin promoted damage more extensive and faster. The increase in LOOH was higher in the presence of D2O, and was impaired by sodium azide and sorbic acid. The effect of D2O was higher for TPPS4 as the photosensitizer. The use of DCFH demonstrated that liposomes prevent the photobleaching of TMPyP. The results are consistent with a more stable TMPyP that generates long-lived singlet oxygen preferentially partitioned in the bilayer. Conversely, TPPS4 generates singlet oxygen in the bulk whose lifetime is increased in D2O. Therefore, the affinity of the porphyrin to the membrane modulates the rate, type and degree of lipid damage.

Liposomes containing magnetic nanoparticles (magnetoliposomes) have been extensively explored for targeted drug delivery. However, the magnetic effect of nanoparticles movement is also an attractive choice for the conduction of signals in communication systems at the nanoscale level because of the simple manipulation and efficient control. Here, we propose a model for the transmission of electrical and luminous signals taking advantage of magnetophoresis. The study involved three steps. Firstly, magnetite was synthesized and incorporated into fusogenic large unilamellar vesicles (LUVs) previously associated with a fluorescent label. Secondly, the fluorescent magnetite-containing LUVs delivered their contents to the giant unilamellar vesicles (GUVs), which were corroborated by magnetophoresis and fluorescence microscopy. In the third step, magnetophoresis of magnetic vesicles was used for the conduction of the luminous signal from a capillary to an optical fibre connected to a fluorescence detector. Also, the magnetophoresis effects on subsequent transmission of the electrochemical signal were demonstrated using magnetite associated with CTAB micelles modified with ferrocene. We glimpse that these magnetic supramolecular systems can be applied in micro- and nanoscale communication systems.

In this minireview, the more recent findings about the effects of peculiar reactive thiol drugs on mitochondria are presented. These include the following compounds: metallo meso-tetrakis porphyrins, palladacycles, telluranes and phenothiazines. Metallo meso-tetrakis porphyrins can exhibit both beneficial and deleterious effects on mitochodria that are modulated by the central metal, cell location, and availability of axial ligands. Therefore, these compounds have the versatility to be used for cell and mitochondria protection and death. The antioxidant activity of manganese porphyrins is related to a glutathione peroxidase-like activity. By attacking exclusively the membrane protein thiol groups without glutathione depletion, palladacycles are able to induce mitochondrial permeability transition (MPT) and cytochrome c release in the absence of oxidative stress. In hepatoma cells, the mitochondrial action of palladacycles was able to induce apoptotic death. As opposed to palladacycles, telluranes and phenothiazines are able to conjugate the capacity to promote the MPT in a dose-dependent manner in association with efficient antioxidant activity toward lipids. These studies demonstrated that the action of drugs on mitochondrial bioenergetics can be modulated by peculiar reactivity with thiol groups. Therefore, they contribute to studies of toxicity as well as the design of new drugs.

The vital role played by porphyrins in cells and their use in therapeutic processes are well known. More recently, the technological applications of porphyrins have attracted the attention of researchers. Porphyrins have the property of half-metallic material, i.e., molecules that can host transition metals making feasible the production of spin-polarized electronic states at different channels. Therefore, porphyrins and hemeproteins are among the materials that have spin-filtering property to be applied in spintronics. Molecular spintronics is an emerging and highly relevant field due to their applications to the development of high-capacity informationstorage devices and quantum computers. The catalytic properties of porphyrins and related compounds such as the hemeproteins are also applicable in the fabrication of micro-/nanomotors (MNMs). In this chapter, we describe the advances and future perspectives in the technological applications of porphyrins and related compounds in spintronic devices and micro-/nanomotors.

In the present study, the binding of the cationic Mn III TMPyP [meso-tetrakis (4-N-methyl pyridinium) porphyrin] to negatively charged membrane models containing phosphatidylcholine (PC)/ phosphatidylserine (PS) and the porphyrin reactivity with PS-derived peroxides (LOOH) were evaluated. This investigation is relevant due to the participation of PS in cell signaling and apoptosis. Addition of PC/PS liposomes to Mn III TMPyP solutions led to spectral changes of the porphyrin electronic absorption spectrum suggestive of electrostatic interactions with the negatively charged interface provided by PS. The binding of Mn III TMPyP to PC/PS liposomes was corroborated by the quenching of the fluorophore merocyanine 540. In addition total energy calculations of saturated and unsaturated PS based on the spinpolarized variant of KS-DFT were used to support some experimental data. Cyclic voltammetry analysis revealed that the association to PC/PS liposomes shifted the redox potential of the Mn II /Mn III (+87 mV vs NHE, in aqueous buffered solution) couple to a more positive value to (+110 mV vs NHE). This event favors the oxidation of O 2-• to O 2 by the porphyrin. Mn III TMPyP was able to react with the lipid-derived peroxides as evidenced by spectral changes of the porphyrin consistent with the generation of a high valence state (Mn IV =O) of the catalyst. The spectral changes were not observed when biological lipids containing unsaturated PC and PS were replaced by the corresponding dipalmitoyl (DP)derived: DPPC/DPPS.