Molecularly Imprinted Methyl-Modified Hollow TiO2 Microspheres.

The possibility of generating organically modified hollow TiO2 microspheres via a simple sol-gel synthesis was demonstrated for the first time in this work. A mixture of titania precursors, including an organically modified precursor, was used to obtain methyl-modified hollow TiO2 microspheres selective for bilirubin by the molecular imprinting technique (Methyl-HTM-MIM). Methyl-HTM-MIM were prepared by a sol-gel method using titanium (IV) isopropoxide (TTIP), and methyltitanium triisopropoxide (MTTIP) as precursors. Two ratios of titania precursors were tested (1/6 and 1/30 molMTTIP/molTTIP). With the characterization results obtained by the SEM and ATR-FTIR techniques, it was possible to establish that only the 1/30 molMTTIP/molTTIP ratio allowed for the preparation of hollow spheres with a reasonably homogeneous methylated-TiO2 shell. It was possible to obtain a certain degree of organization of the hybrid network, which increased with calcination temperatures. By adjusting isothermal adsorption models, imprinting parameters were determined, indicating that the new methylated microspheres presented greater selectivity for bilirubin than the totally inorganic hollow TiO2 microspheres. The effectiveness of the molecular imprinting technique was proven for the first time in an organically modified titania material, with imprinting factor values greater than 1.4, corresponding to a significant increase in the maximum adsorption capacity of the template represented by the molecularly imprinted microspheres. In summary, the results obtained with the new methyl-HTM-MIM open the possibility of exploring the application of these microspheres for selective sorption (separation or sensing, for example) or perhaps even for selective photocatalysis, particularly for the degradation of organic compounds.

Unveiling the Surface and the Ultrastructure of Palladized Fungal Biotemplates.

In this paper, two biosystems based on filamentous fungi and Pd nanoparticles (NPs) were synthesized and structurally characterized. In the first case, results concerning the integration and distribution of Pd-NPs on Phialomyces macrosporus revealed that nanoparticles are accumulated on the cell wall, keeping the cytoplasm isolated from abiotic particles. However, the Penicillium sp. species showed an unexpected internalization of Pd-NPs in the fungal cytosol, becoming a promising biosystem to further studies of in vivo catalytic reactions. Next, we report a new solution-based strategy to prepare palladized biohybrids through sequential reduction of Pd2+ ions over previously harvested fungus/Au-NP composites. The chemical composition and the morphology of the biohybrid surface were characterized using a combination of scanning electron microscopy, transmission electron microscopy, and photoelectron spectroscopy. The deposition of Pd0 over the fungal surface produced biohybrids with a combination of Au and Pd in the NPs. Interestingly, other chemical species such as Au+ and Pd2+ are also observed on the outermost wall of microorganisms. Finally, the application of A. niger/AuPd-NP biohybrids in the 3-methyl-2-buten-1-ol hydrogenation reaction is presented for the first time. Biohybrids with a high fraction of Pd0 are active for this catalytic reaction.

Photoluminescent organisms: how to make fungi glow through biointegration with lanthanide metal-organic frameworks.

We show that filamentous fungi can emit green or red light after the accumulation of particulate lanthanide metal-organic frameworks over the cell wall. These new biohybrids present photoluminescence properties that are unaffected by the components of the cell wall. In addition, the fungal cells internalise lanthanide metal-organic framework particles, storing them into organelles, thereby making these materials promising for applications in living imaging studies.

Electrochemical Behavior of a Mitochondria-Targeted Antioxidant at an Interface between Two Immiscible Electrolyte Solutions: An Alternative Approach to Study Lipophilicity.

In this work, we report for the first time the accumulation activity by energized rat heart mitochondria and the ionic transfer process at a liquid-liquid interface of a novel mitochondria-targeted antioxidant, named as AntiOxCIN4, which is structurally based on a hydroxycinnamic acid. Lipophilicity studies conducted at the water/1,6-dichlorohexane (DCH) interface allowed the building up of an ionic partition diagram of AntiOxCIN4 in accordance with the electrochemical data obtained. The partition coefficients of both positively charged (-2.3) and zwitterionic (0.2) forms of the antioxidant were determined. This study contributed to gaining an insight about the ability of the synthesized antioxidants to cross biomembrane barriers by using an interface between two immiscible electrolyte solutions (ITIES) as a model system.

Edible Chitosan Films and Their Nanosized Counterparts Exhibit Antimicrobial Activity and Enhanced Mechanical and Barrier Properties.

Chitosan and chitosan-nanoparticles were combined to prepare biobased and unplasticized film blends displaying antimicrobial activity. Nanosized chitosans obtained by sonication for 5, 15, or 30 min were combined with chitosan at 3:7, 1:1, and 7:3 ratios, in order to adjust blend film mechanical properties and permeability. The incorporation of nanosized chitosans led to improvements in the interfacial interaction with chitosan microfibers, positively affecting film mechanical strength and stiffness, evidenced by scanning electron microscopy. Nanosized or blend chitosan film sensitivity to moisture was significantly decreased with the drop in biocomposite molecular masses, evidenced by increased water solubility and decreased water vapor permeability. Nanosized and chitosan interactions gave rise to light biobased films presenting discrete opacity and color changes, since red-green and yellow-blue colorations were affected. All chitosan blend films exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria. The performance of green unplasticized chitosan blend films displaying diverse morphologies has, thus, been proven as a potential step towards the design of nontoxic food packaging biobased films, protecting against spoilage microorganisms, while also minimizing environmental impacts.

Development of a Mitochondriotropic Antioxidant Based on Caffeic Acid: Proof of Concept on Cellular and Mitochondrial Oxidative Stress Models.

Targeting mitochondrial oxidative stress is an effective therapeutic strategy. In this context, a rational design of mitochondriotropic antioxidants (compounds 22-27) based on a dietary antioxidant (caffeic acid) was performed. Jointly named as AntiOxCINs, these molecules take advantage of the known ability of the triphenylphosphonium cation to target active molecules to mitochondria. The study was guided by structure-activity-toxicity-property relationships, and we demonstrate in this work that the novel AntiOxCINs act as mitochondriotropic antioxidants. In general, AntiOxCINs derivatives prevented lipid peroxidation and acted as inhibitors of the mitochondrial permeability transition pore. AntiOxCINs toxicity profile was found to be dependent on the structural modifications performed on the dietary antioxidant. On the basis of mitochondrial and cytotoxicity/antioxidant cellular data, compound 25 emerged as a potential candidate for the development of a drug candidate with therapeutic application in mitochondrial oxidative stress-related diseases. Compound 25 increased GSH intracellular levels and showed no toxicity on mitochondrial morphology and function.

Development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria.

Oxidative stress and mitochondrial dysfunction have been associated with metabolic and age-related diseases. Thus, the prevention of mitochondrial oxidative damage is nowadays a recognized pharmacological strategy to delay disease progression. Epidemiological studies suggested an association between the consumption of polyphenol-rich diet and the prevention of different pathologies, including diseases with a mitochondrial etiology. The development of mitochondrial-targeted antioxidants based on dietary antioxidants may decrease mitochondrial oxidative damage. Herein, we report the design and synthesis of two new mitochondriotropic antioxidants based on hydroxybenzoic acids (AntiOxBENs). The results obtained showed that the novel antioxidants are accumulated inside rat liver mitochondria driven by the organelle transmembrane electric potential and prevented lipid peroxidation, exhibiting low toxicity. Some of the observed effects on mitochondrial bioenergetics resulted from an increase of proton leakage through the mitochondrial inner membrane. The new derivatives present a higher lipophilicity than the parent compounds (protocatechuic and gallic acids) and similar antioxidant and iron chelating properties. AntiOxBENs are valid mitochondriotropic antioxidant prototypes, which can be optimized and used in a next future as drug candidates to prevent or slow mitochondrial oxidative stress associated to several pathologies.

Reduced graphene oxide-nickel nanoparticles/biopolymer composite films for the sub-millimolar detection of glucose.

Hybrid conjugates of graphene with metallic/semiconducting nanostructures can improve the sensitivity of electrochemical sensors due to their combination of well-balanced electrical/electrocatalytic properties and superior surface-to-volume ratio. In this study, the synthesis and physical characterization of a hybrid conjugate of reduced graphene oxide and nickel nanoparticles (rGO-Ni NPs) is presented. The conjugate was further deposited onto a glassy carbon electrode as a nanocomposite film of chitosan and glucose oxidase. The electrochemical response and morphology of the films were investigated using SEM, CV, and EIS, and their applications as a glucose biosensor explored for the first time in proof-of-concept tests. The low operating potential along with the good linearity and sensitivity (up to 129 µA cm(-2) mM(-1)) found in the sub-millimolar range suggest potential applications in the self-management of hypoglycemia from blood samples or in the development of non-invasive assays for body fluids such as saliva, tears or breath.

Aminoglutethimide-imprinted xerogels in bulk and spherical formats, based on a multifunctional organo-alkoxysilane precursor.

The multifunctional alkoxysilane precursor, 2,6-bis(propyl-trimethoxysilylurelene)pyridine (DPS) was designed and synthesized, envisaging a multiple hydrogen-bond interaction in the molecular imprinting of the drug aminoglutethimide (AGT). Imprinted xerogels were obtained in bulk and spherical formats. The spherical format was achieved by pore-filling onto spherical mesoporous silica, as a straightforward technique to generate the spherical format. The bulk gels presented better selectivity for the template against its glutarimide (GLU) analogue (selectivity factor: bulk 13.4; spherical 4.6), and good capacity (bulk 5521µmol/L; spherical 2679µmol/L) and imprinting factor parameters (bulk 11.3; spherical 1.4). On the other hand, the microspherical format exhibited better dynamic properties associated to chromatographic efficiency (theoretical plates: bulk 6.8; spherical 75) and mass transfer, due mainly to the existence of a mesoporous network, lacking in the bulk material. The performance of the imprinted xerogels was not as remarkable as that of their acrylic counterparts, previously described. Overall it was demonstrated that the use of designed new "breeds" of organo-alkoxysilanes may be a strategy to achieve satisfactory imprints by the sol-gel processes. DPS may in principle be applied even more effectively to other templates bearing better-matching spatially compatible acceptor-donor-acceptor arrays.

Recognitive nano-thin-film composite beads for the enantiomeric resolution of the metastatic breast cancer drug aminoglutethimide.

Straightforward crushing and sieving bulk polymeric R-aminoglutethimide-imprinted materials were prepared by classical free radical polymerization, whereas nano thin walled grafted imprinted materials were prepared using RAFT mediated control polymerization technique. A stoichiometric non-covalent approach based on a triply hydrogen bonding functional monomer-template 1:1 complex (K=599mol(-1)L(-1)) led to chiral selectors far outperforming previously used selectors for resolving this racemate. The recognitive materials produced here (enantioselectivity factors, α∼10) also have no match within the previously reported enantioselective imprinted polymers (α 1.2-4.5). We here demonstrate a potentially generic solution to produce good quality grafted MIPs for templates interacting by hydrogen bonding alone, relying on solvent polarity tuning, significantly extending the range of templates compatible with this format.

Bio-inspired gold microtubes based on the morphology of filamentous fungi.

This communication describes a general method for templating fungal filaments with gold nanoparticles that results in a gold replica of filaments after calcination of the biological template.

Haplotype analysis of the CAG and CCG repeats in 21 Brazilian families with Huntington's disease.

We studied the allelic profile of CAG and CCG repeats in 61 Brazilian individuals in 21 independent families affected by Huntington's disease (HD). Thirteen individuals had two normal alleles for HD, two had one mutable normal allele and no HD phenotype, and forty-six patients carried at least one expanded CAG repeat allele. Forty-five of these individuals had one expanded allele and one individual had one mutable normal allele (27 CAG repeats) and one expanded allele (48 CAG repeats). Eleven of these forty-five subjects had a mutant allele with reduced penetrance, and thirty-four patients had a mutant allele with complete penetrance. Inter- and intragenerational investigations of CAG repeats were also performed. We found a negative correlation between the number of CAG repeats and the age of disease onset (r=-0.84; P<0.001) and no correlation between the number of CCG repeats and the age of disease onset (r=0.06). We found 40 different haplotypes and the analysis showed that (CCG)(10) was linked to a CAG normal allele in 19 haplotypes and to expanded alleles in two haplotypes. We found that (CCG)(7) was linked to expanded CAG repeats in 40 haplotypes (95.24%) and (CCG)(10) was linked to expanded CAG repeats in only two haplotypes (4.76%). Therefore, (CCG)(7) was the most common allele in HD chromosomes in this Brazilian sample. It was also observed that there was a significant association of (CCG)(7) with the expanded CAG alleles (χ(2)=6.97, P=0.0084). Worldwide, the most common CCG alleles have 7 or 10 repeats. In Western Europe, (CCG)(7) is the most frequent allele, similarly to our findings.

Amperometric tape ion sensors for cadmium(II) ion analysis.

This paper describes a novel tape platform ion sensing methodology specific to the detection of cadmium(II) ions in aqueous solution based on assisted ion transfer reactions across a polarized water/organic gel micro-interface. The tape ion sensors were constructed to incorporate the micro-water/polyvinylchloride-2-nitrophenylethyl ether (PVC-NPOE) gel interfaces referred to as ionodes. The sensors have overall thicknesses less than 300 microm, allowing their packaging in a disposable tape format. The detection methodology is based on the selective assisted transfer of the cadmium ion in aqueous phase by ETH 1062 present in the PVC-NPOE gel layer and was first investigated using cyclic voltammetry. Quantitative analysis of cadmium(II) ions in aqueous solution using the tape sensors was then conducted under stop-flow conditions. Detection limits as low as 20 ppb (178 nM) for Cd(II) ions in very small volumes as low as a single 20 microl droplet without any sample preconcentration was achieved in an analysis time of approximately 20s, which could be easily employed for the direct measurement of Cd(II) ion levels in various field applications. The tape ion sensor can also be used in a flow-cell geometry to preconcentrate Cd(II) ions from aqueous samples and further improve the detection limit.

Development of a biodegradable bioadhesive containing urethane groups.

Surgical adhesives consist on an attractive alternative to suturing or stapling since they can accomplish other tasks, such as haemostasis and the ability to seal air leakages. The application of adhesives would also reduce the surgeries procedure time since they represent an easier and faster method to establish tissue adhesion. The aim of this work was the development of a biodegradable urethane pre-polymer that presents the capacity of reacting with the amino groups present in the biological molecules. Urethanes based on polycaprolactone diol (PCL) were synthesized by reaction of the molecule either with isophorone diisocyanate (IPD-isocyanate) or hexamethylene diisocyanate (HDI-isocyanate). The characterization of the materials was accomplished by: ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared), determination of swelling capacity, stability of NCO groups in the presence of humidity conditions, reaction with aminated substrates (as a simulation of the living tissues) and determination of surface energy by contact angle measurement. The haemocompatibility of the PU was also evaluated by thrombosis and haemolysis tests.

Modification of the biopolymer castor oil with free isocyanate groups to be applied as bioadhesive.

Surgical adhesives have been used for several applications, including haemostasis, sealing air leakages and tissue adhesion. The aim of this work was to develop a biodegradable urethane-based bioadhesive containing free isocyanate groups. This material presents the advantage of being biodegradable, biocompatible and having the capacity of reacting with amino groups present in the biological molecules. A urethane based on castor oil (CO) was synthesized by reaction of the molecule with isophorone diisocyanate (IPD). The characterization of the material was accomplished by different techniques: ATR-FT-IR (attenuated transmittance reflection-Fourier transform infrared), swelling capacity determination, evaluation of the moisture curing kinetics, reaction with aminated substrates and determination of surface energy by contact angle measurement. The study of the urethane thermal properties was performed by DMTA (dynamical mechanical thermal analysis) and TGA (thermogravimetric analysis). The haemocompatibility of the urethane was also evaluated by thrombosis and haemolysis tests.