Raquel Viveiros

Development of 2-(dimethylamino)ethyl methacrylate-based molecular recognition devices for controlled drug delivery using supercritical fluid technology.

This work reports the development of a novel potential body-friendly oral drug delivery system, which consists of a biocompatible molecularly imprinted polymer (MIP), with pH sensitive character and low cross-linking degree (20.2wt%), synthesized and processed in supercritical carbon dioxide. The MIP is synthesized using 2-(dimethylamino)ethyl methacrylate (DMAEMA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as cross-linker, and ibuprofen as molecular recognition template. The imprinted matrix was able to show a higher affinity towards ibuprofen than its corresponding non-imprinted polymer (NIP) meaning that the molecular imprinting in scCO(2) was efficient even using a low crosslinking degree. MIP showed a significant molecular recognition towards the template, presenting higher drug uptake ability in the supercritical impregnation step, loading 33.1wt% of ibuprofen compared to only 10.2wt% for the NIP polymer. In vitro drug release experiments, simulating an oral administration, showed different release profiles at pH 2.2 and pH 7.4. Zeta potential measurements were performed to both MIP and NIP showing that the imprinting process has a significant influence on the charge of the polymeric particles. Cytotoxicity assays performed with human colorectal carcinoma-derived Caco-2 cells demonstrated that the polymers are biocompatible and could be potentially used in drug delivery applications.

Natural melanin: a potential pH-responsive drug release device.

This work proposes melanin as a new nanocarrier for pH-responsive drug release. Melanin is an abundant natural polymer that can be easily extracted from cuttlefish as nanoparticles with a suitable size range for drug delivery. However, despite its high potentiality, the application of this biopolymer in the pharmaceutical and biomedical fields is yet to be explored. Herein, melanin nanoparticles were impregnated with metronidazole, chosen as model antibiotic drug, using supercritical carbon dioxide. The drug release profile was investigated at acidic and physiologic pH, and the dominant mechanism was found to follow a non-Fickian transport. Drug release from melanin shows a strong pH dependency, which allied to its biocompatibility and lack of cytotoxicity envisages its potential application as nanocarrier in formulations for colon and intestine targeted drug delivery.

Supercritical fluid technology as a new strategy for the development of semi-covalent molecularly imprinted materials

Molecularly imprinted polymeric particles with molecular recognition towards Bisphenol A (BPA) were synthesized for the first time using the semi-covalent imprinting approach in supercritical carbon dioxide (scCO2). The materials affinity to BPA was achieved by co-polymerizing ethylene glycol dimethacrylate (EGDMA) with a template-containing monomer, Bisphenol A dimethacrylate (BPADM) in scCO2. Bisphenol A is then cleaved from the polymeric matrix by hydrolysis with tetrabutylammonium hydroxide (n-Bu4OH) also in a supercritical environment, taking advantage of the high diffusivity of scCO2. The selectivity of the molecular imprinted polymer (MIP) was assessed by evaluating its capability to bind BPA in comparison with progesterone and α-ethinylestradiol. In addition, the cross-linked particles were used to prepare a PMMA-based hybrid imprinted membrane by a scCO2-assisted phase inversion method. Results show that the incorporation of MIP particles was able to confer molecular affinity to BPA to the membrane and that at dynamic conditions of filtration, this imprinted porous structure was able to adsorb a higher amount of BPA than the corresponding non-imprinted hybrid membrane. Our work represents a valuable greener alternative to conventional methods, for the synthesis of affinity materials which are able to maintain molecular recognition properties in water.

Integrated desulfurization of diesel by combination of metal-free oxidation and product removal by molecularly imprinted polymers

The production of ultra-low-sulfur diesel is an important worldwide demand. In this work a novel integrated method for desulfurization of diesel is proposed based on the combination of Bronsted acid catalyzed oxidation and the selective removal of the oxidized products using a molecularly imprinted polymer (MIP) produced in supercritical carbon dioxide (scCO2). The biphasic oxidation reaction of dibenzothiophene sulfone (DBT), as model substrate, and H2O2 as oxidant, was optimized by testing different acid catalysts, and also different phase transfer catalysts (PTC), including two different ionic liquids (ILs) trihexyl(tetradecyl)phosphoniumchloride [P6,6,6,14]Cl and Aliquat®. The products of the efficient oxidation of DBT, dibenzothiophene sulfoxide (DBTSO) and dibenzothiophene sulfone (DBTSO2), were then selectively removed from real diesel using the MIP.

Supercritical CO2-assisted synthesis of an ultrasensitive amphibious quantum dot-molecularly imprinted sensor

Molecularly imprinted polymers are simple and robust materials for the selective binding of analytes with affinities and selectivities similar to biological probes. A green supercritical CO2-assisted molecular imprinting protocol enabled the production of smart sensory particles, incorporating quantum dots, with molecular recognition to bisphenol A at very low concentrations (4 nM). The protocol uses amphibious vinyl-coated quantum dots and enables the design of sensors for a wide range of molecules through a simple, low cost and clean technology.

Bioactivity, mechanical properties and drug delivery ability of bioactive glass-ceramic scaffolds coated with a natural-derived polymer

In this work, hybrid melanin-coated bioactive glass-ceramic multifunctional scaffolds were developed and characterized in terms of mechanical strength, in vitro bioactivity in simulated body fluid (SBF) and ability to load ibuprofen. The coated scaffolds exhibited an accelerated bioactivity in comparison with the uncoated ones, being able of developing hydroxyapatite-like crystals after 7days soaking in simulated body fluid (SBF). Besides its positive influence on the scaffolds bioactivity, the melanin coating was able to enhance their mechanical properties, increasing the initial compressive strength by a factor of >2.5. Furthermore, ibuprofen was successfully loaded on this coating, allowing a controlled drug release of the anti-inflammatory agent.

Green Strategies for Molecularly Imprinted Polymer Development

Molecular imprinting is a powerful technology to create artificial receptors within polymeric matrices. Although it was reported for the first time by Polyakov, eighty-four years ago, it remains, nowadays, a very challenging research area. Molecularly imprinted polymers (MIPs) have been successfully used in several applications where selective binding is a requirement, such as immunoassays, affinity separation, sensors, and catalysis. Conventional methods used on MIP production still use large amounts of organic solvents which, allied with stricter legislation on the use and release of chemicals to the environment and the presence of impurities on final materials, will boost, in our opinion, the use of new cleaner synthetic strategies, in particular, with the application of the principles of green chemistry and engineering. Supercritical carbon dioxide, microwave, ionic liquids, and ultrasound technology are some of the green strategies which have already been applied in MIP production. These strategies can improve MIP properties, such as controlled morphology, homogeneity of the binding sites, and the absence of organic solvents. This review intends to give examples reported in literature on green approaches to MIP development, from nano- to micron-scale applications.

Development of itaconic acid-based molecular imprinted polymers using supercritical fluid technology for pH-triggered drug delivery

&NA; A novel pH‐responsive molecularly imprinted polymer (MIP) based on Itaconic acid:Ethylene glycol dimethacrylate was developed as a potential body‐friendly oral drug delivery system for metronidazole (MZ), a pH‐independent drug. MIP performance was evaluated in a simulated oral administration situation, at pHs 2.2 and 7.4. Itaconic acid‐based copolymers were synthesized using two different molar ratios of template:monomer:crosslinker (T:M:C), 1:5:25 and 1:5:50, in supercritical carbon dioxide (scCO2) in high yields. Further, impregnation of MZ was performed in scCO2 environment. Morphological and chemical properties of the copolymers produced were assessed by SEM, Morphologi G3 and FTIR analyses. Non‐molecularly imprinted polymer (NIP) matrices presented swelling over time in opposition to the molecularly imprinted ones. In the scCO2‐impregnation process, MIPs showed a significant molecular recognition towards MZ, presenting higher drug uptake ability with MZ loading of 18‐61 wt% in MIPs, compared to 7–20 wt% in NIPs. In vitro drug release experiments presented different release profiles at the different pHs, where MZ‐MIPs could release higher amounts of MZ at the lowest pH than at pH 7.4.

Green design of lock-and-key affinity devices to address API purification challenges

B is a clean, renewable and abundant resource that can be converted to bio-char, bio-oil and fuel gas through various thermochemical processes. Conversion of biomass for high value products is an important development direction for biomass utilization, which has attracted more attention. In this study, a new method of biomass pyrolysis with exogenous nitrogen introduced was proposed. The influence of NH3 on the property of bamboo pyrolysis process and products characteristics was investigated with variant approaches (e.g. elemental analysis, automatic adsorption equipment, X-ray photoelectron spectroscopy and CHI760 electrochemical workstation) and as well as the influence of KOH (as activator). The results showed that, the specific surface area, the content of nitrogen and nitrogen-containing functional groups of bio-char increased significantly with NH3 introduced in. On the other hand, with the addition of KOH, the yield of bio-char increased obviously and it increased gradually with increasing KOH amount, and the specific surface area increased dramatically to 1873.17 m2 g-1. The content of nitrogen in bio-char increased greatly with KOH introduced in, especially the content of pyridinic-N and pyrrolic/pyridone-N, while it decreased slightly with increasing KOH amount, but nitrogen content was still relative high (9.1-10.4 wt.%). The formation mechanism of nitrogen-containing functional groups was proposed. Besides, electrochemical analysis showed that the specific capacitance of bio-char electrodes increased with increasing KOH content, and the largest specific capacitance could reach to 187 F g-1 at 1 A g-1 with good cycling stability. Therefore, it could be concluded that biomass nitrogen-enriched pyrolysis was a promising method for more efficient utilization of biomass resources.A insoluble palladium catalyst (Pd-pol) was obtained by copolymerization of the metal containing monomer Pd(AAEMA)2 [AAEMA− = deprotonated form of 2-(acetoacetoxy)ethyl methacrylate] with ethyl methacrylate (co-monomer) and ethylene glycol dimethacrylate (cross-linker), followed by in situ reduction of Pd(II) to Pd(0), to give polymer stabilized metal nanoparticles. The good swellability in water exhibited by Pd-pol rendered it an ideal potential catalyst for reactions carried out in a green solvent, such as water, since the migration of the reagents to the active sites would not be hampered by the solid support. With the aim to develop innovative catalytic processes that enable chemical transformations to be performed under mild and sustainable conditions with high efficiency, we decided to evaluate the catalytic activity of Pd-pol for several important organic reactions using water as solvent. Pd-pol resulted highly active and selective in catalyzing (figure 1): the Suzuki-Miyaura coupling between aryl bromides or activated aryl chlorides and phenylboronic acid; the oxidation of benzyl alcohols to aldehydes; the reduction of quinolines and nitroarenes by H2 or NaBH4. Pd-pol was recyclable for several consecutive runs (for example, at least 12 times in the nitroarene reduction). TEM analyses carried out on the catalyst showed that the active species were supported palladium nanoparticles having a mean size of 4 nm, which did not aggregate with the recycles. Recently, due to their low cost, Ni catalysts have been employed in several organic reactions (mainly hydrogenations). In this context, we synthetized a Ni catalyst similar to Pd-pol, starting from Ni(AAEMA)2 and we employed it as active and recyclable, insoluble catalyst for the reduction of different nitroarenes to give the corresponding anilines, under sustainable conditions. All these results proved that the proposed Pd or Ni based composite materials are excellent hybrid structures as efficient and reusable catalysts.A amino acids are versatile structures readily available by a number of methods and are accessible using very few transformations from economical starting materials. They can be functionalized by many chemical functions and offer a wide range of possible transformations. Particularly, unsaturated α-amino acids give access to many synthetic applications in all fields of chemistry. Among them, metal catalyzed cross-coupling reactions and cross metathesis are commonly used to generate peptide modifications and cyclization. They are very interesting and useful tools for “Click” Chemistry in peptidomimetic drug design or covalent modification of proteins. They can also be incorporated in compounds as beta-turn inducer to promote secondary structures. Finally they can be used for the preparation of stapled peptides. Some such amino acids are commercially attainable in enantiomerically pure form. Here, we present a stereoselective approach to synthesize unsaturated α-amino acids in optically active form. As a starting amino acid synthon for the asymmetric synthesis of amino acids NiII square-planar complexes of Schiff ’s bases of propargylglycine with chiral auxiliary (S)-2-N-(N`-benzyl-prolyl)aminobenzophenone (BPB) (1) was taken. As a result effective methods of asymmetric synthesis for novel enantiomerically enriched derivatives of (S)-propargylglycine (S)-propargylglycine (ee > 80%) was developed.

Development of Switchable “Smart” Biomaterials Using an Environmental Friendly Technology

The possibility of using three dimensional porous networks as microreactors for synthesizing thermoresponsive polymers and hydrogels in a CO 2 environment is an important breakthrough in the strategies to prepare smart films, membranes and porous bulky devices that undergo fast reversible changes in surface properties triggered by external stimuli. In situ synthesis of thermoresponsive polymers namely, poly(N-isopropylacrylamide) (PNIPAAm) and poly (N,N-diethylacrylamide) (PDEAAm) within chitosan (CHT), collagen (CLG) and chitosan-collagen (CHT:CLG) blended scaffolds were performed in order to further impregnate with model drugs. The performance of these switchable release devices was evaluated through the study of drug release kinetics as a function of temperature and pH. The same methodology was successfully applied to produce thermoresponsive polysulfone-based membranes.