Showing papers by "Carlos A. M. Afonso published in 2016"

Synthesis of Chiral Cyclopentenones.

Abstract: The cyclopentenone unit is a very powerful synthon for the synthesis of a variety of bioactive target molecules. This is due to the broad diversity of chemical modifications available for the enone structural motif. In particular, chiral cyclopentenones are important precursors in the asymmetric synthesis of target chiral molecules. This Review provides an overview of reported methods for enantioselective and asymmetric syntheses of cyclopentenones, including chemical and enzymatic resolution, asymmetric synthesis via Pauson-Khand reaction, Nazarov cyclization and organocatalyzed reactions, asymmetric functionalization of the existing cyclopentenone unit, and functionalization of chiral building blocks.

Basicity and stability of urea deep eutectic mixtures

Abstract: The stability and basicity origin of some common urea based deep eutectic mixtures/solvents (DES) were studied. We have observed an unexpected Hantzsch dihydropyridine reaction in sorbitol/urea DES, where the source of ammonia was found not to be originated from the individual ingredients of the DES. Our results showed that decomposition of urea occurs in DES at lower than expected temperatures, namely below 100 °C and is enhanced in diol DES by the formation of carbonates causing their unexplained basicity. Carbohydrates and choline chloride (ChCl) DES exhibit lower rates of decomposition, while no decomposition was observed from neat urea or MeOH and EtOH urea solutions.

Preparation and Characterization of Facilitated Transport Membranes Composed of Chitosan-Styrene and Chitosan-Acrylonitrile Copolymers Modified by Methylimidazolium Based Ionic Liquids for CO2 Separation from CH4 and N2

Abstract: CO2 separation was found to be facilitated by transport membranes based on novel chitosan (CS)–poly(styrene) (PS) and chitosan (CS)–poly(acrylonitrile) (PAN) copolymer matrices doped with methylimidazolium based ionic liquids: [bmim][BF4], [bmim][PF6], and [bmim][Tf2N] (IL). CS plays the role of biodegradable film former and selectivity promoter. Copolymers were prepared implementing the latest achievements in radical copolymerization with chosen monomers, which enabled the achievement of outstanding mechanical strength values for the CS-based membranes (75–104 MPa for CS-PAN and 69–75 MPa for CS-PS). Ionic liquid (IL) doping affected the surface and mechanical properties of the membranes as well as the gas separation properties. The highest CO2 permeability 400 Barrers belongs to CS-b-PS/[bmim][BF4]. The highest selectivity α (CO2/N2) = 15.5 was achieved for CS-b-PAN/[bmim][BF4]. The operational temperature of the membranes is under 220 °C.

Choline‐Based Ionic Liquids: Improvement of Antimicrobial Activity

Abstract: Antibiotic resistance is a global public health concern. The choline-based ionic liquids (ILs) have raised particular attention in the design of “greener” ILs and can exert a broad-spectrum of antimicrobial activity. To improve antimicrobial chemotherapy, we herein tested the antimicrobial activity and toxicity of a wide range of choline-based ILs. Two series of compounds were synthesized -dimethylethanolamine monoquaternary ammonium salts (Series A) and -methyl diethanolamine, diethanolamine and triethanolamine monoquaternary ammonium salts (Series B). The antimicrobial screening revealed that compounds N-(2-hydroxyethyl)-N,N-dimethyl-1-tetradecanaminium bromide ([N1,1,14,2(OH)]Br), N-(2-hydroxyethyl)-N,N-dimethyl-1-hexadecanaminium bromide ([N1,1,16,2(OH)]Br) and N-(2-hydroxyethyl)-N,N-dimethyl-1-octadecanaminium bromide ([N1,1,18,2(OH)]Br) are potent antimicrobial agents. The presence of a hydroxyethyl group and as mention previously in the literature, the C14 to C16 linker in a choline compound improves the antimicrobial activity and lowers the cytotoxic properties of this class of compounds.

Reactivity of Diterpenoid Quinones: Royleanones.

Abstract: Naturally occurring abietane diterpenoids have been studied over the years and have shown to display a wide range of biological activities. This review covers three main aspects of the abietane-type diterpenoids with hydroxy-p-quinone C ring, designated as royleanones. An overview of 1) the naturally occurrence, 2) chemical features and 3) the biological activities of this abietane group of compounds, including rearranged derivatives, is here explained. Likewise, hemisynthetic and total synthetic procedures to obtain royleanones will be reviewed. Thus, the chemistry of these bioactive compounds will be emphasized as well as their potential impact in the discovery of new macromolecular targets and novel therapeutic drugs. This review contains about 190 references covering the years from 1962 to 2014 on royleanone studies.

New low viscous cholinium-based magnetic ionic liquids

Abstract: Magnetic ionic liquids (MILs) are a type of ionic liquids (ILs) that have paramagnetic metal based anions, and thus they can respond to an external magnetic field. Owing to the high propensity of these anions to crystallize, there are only few reported MILs that are liquid at room temperature. This study describes a new family of cholinium based ILs containing two and three ethanol side chains, that are liquid at room temperature, even in combination with paramagnetic anions. In addition, these new family of ILs are prone to the generation of low toxicities on human cell lines.

Optimization of protein loaded PLGA nanoparticle manufacturing parameters following a quality-by-design approach

Abstract: This paper discusses the development of a multivariate-based regression model for estimating the critical attributes to establish a design-space for poly(lactic-co-glycolic acid) (PLGA) nanoparticles formulated by a double emulsion–solvent evaporation method A three-level, full factorial experimental design is used to assess the impact of three different manufacturing conditions (polymer viscosity, surfactant concentration and amount of model antigen ovalbumin) on five critical particle attributes (zeta potential, polydispersity index, hydrodynamic diameter, loading capacity and entrapment efficiency) The optimized formulation was achieved with a viscosity of 06 dl g−1, a surfactant concentration of 11% (w/v) in the internal phase and 25% (w/w) of ovalbumin The design-space that is satisfied for nanoparticles with the targeted attributes was obtained with a polymer viscosity between 04 and 09 dl g−1, a surfactant concentration ranging from 8 to 15% (w/v) and 25% (w/w) of ovalbumin The nanoparticles were spherical and homogenous and were extensively taken up by JAWS II murine immature dendritic cells without affecting the viability of these phagocytic cells Better understanding was achieved by multivariate regression to control process manufacturing to optimize PLGA nanoparticle formulation Utilization of multivariate regression with a defined control space is a good tool to meet product specifications, particularly over a narrow variation range

Synthesis of Chiral Cyclopentenones

Abstract: The cyclopentenone unit is a very powerful synthon for the synthesis of a variety of bioactive target molecules. This is due to the broad diversity of chemical modifications available for the enone structural motif. In particular, chiral cyclopentenones are important precursors in the asymmetric synthesis of target chiral molecules. This Review provides an overview of reported methods for enantioselective and asymmetric syntheses of cyclopentenones, including chemical and enzymatic resolution, asymmetric synthesis via Pauson-Khand reaction, Nazarov cyclization and organocatalyzed reactions, asymmetric functionalization of the existing cyclopentenone unit, and functionalization of chiral building blocks.

Synthesis of Symmetric Bis(N‐alkylaniline)triarylmethanes via Friedel—Crafts‐Catalyzed Reaction Between Secondary Anilines and Aldehydes.

Abstract: The first general protocol for the preparation of symmetric triarylmethanes bearing secondary anilines by ytterbium-catalyzed Friedel–Crafts reaction of hetero(aryl) aldehydes and secondary anilines is reported. Mechanistic studies indicated that the iminium ion intermediate is the electrophilic partner. The reaction is greatly accelerated by high pressure (9 kbar) and showed a broad substrate scope on the hetero(aryl) aldehyde. The new triarylmethanes exhibited activity against HT-29 cancer cell lines, with the best result scoring an IC50 of 1.74 μM.

Fármacos quirais em diferentes matrizes ambientais: ocorrência, remoção e toxicidade

Abstract: In recent decades, the occurrence of pharmaceuticals in the environment has been widely reported due to their high frequency and recalcitrance in many cases. Concerning the chiral pharmaceuticals (CPs) in environmental matrices, the stereochemistry is often neglected and enantiomers are determined together as unique molecules. However, it is well known that CPs might have enantioselective toxicity, rendering important to assess the occurrence and degradation processes of single enantiomers in the environment, namely during biological treatment in wastewater treatment plants (WWTPs). The development of analytical methods to qualitatively and quantitatively evaluate the enantiomers of CPs is crucial for determining enantiomeric fraction (EF). The EF is the most important parameter in studies involving enantiomers and enantioselective processes and fundamental in biodegradation studies and wastewater monitoring. This review summarizes the analytical methods used to determine EF of CPs in environmental matrices and/or during biodegradation processes. The occurrence of CPs in the environment and their biodegradation are reviewed and future trends in the area outlined.

Ring Opening of 6‐Azabicyclo[3.1.0]hex‐3‐en‐2‐ols in Water under Mild Conditions.

Abstract: The title process, investigated for the preparation of aminocyclopentitol units, becomes possible in the presence of nitrogen- and sulfur-containing nucleophiles under physiological conditions.

Chiral Derivatives of Xanthones: Investigation of Enantioselectivity as Inhibitors of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

Abstract: Searching for new enantiomerically pure chiral derivatives of xanthones (CDXs) with potential pharmacological properties has remained an area of interest of our group, namely those with anti-inflammatory activity [1,2]. Herein, we describe in silico studies and in vitro inhibitory assays of different enantiomeric pairs of CDXs. The evaluation of the inhibition of cyclooxygenases (COX-1 and COX-2) activities was performed by using the COX Inhibitor Screening Assay Kit. Docking simulations between the small molecules (CDXs, known ligands and decoys) and the enzyme targets were undertaken with AutoDock Vina embedded in PyRx – Virtual Screening Tool software. All the CDXs evaluated exhibited COX-1 and COX-2 inhibition potential as predicted. Considering that the (S)-(-)-enantiomer of the nonsteroidal anti-inflammatory drug Ketoprofen preferentially binds to albumin, resulting in lower free plasma concentration than (R)-(+)-enantiomer [3], protein binding affinity for CDXs was also evaluated by spectrofluorimetry. For some CDXs enantioselectivity was observed. [1] Fernandes, C., et al. Bioorg Med Chem. 2014, 22(3), 1049-1062. [2] Fernandes, C., et al. Eur. J. Med. Chem. 2012, 55, 1-11. [3] Evans, S. E. et al. Trends in Environmental Analytical Chemistry, 2014, 1(0), e34-e51. This research was partially supported by the Structured Program of R&D&I INNOVMAR –Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035, Research Line NOVELMAR), funded by the Northern Regional Operational Programme (NORTE2020) through the European Regional Development Fund (ERDF) and by Foundation for Science and Technology (FCT) and COMPETE under the projects PTDC/MAR-BIO/4694/2014 (POCI-01-0145-FEDER-016790) and COXANT–CESPU- 2016.