Vasco D. B. Bonifácio

Solvent‐Free and Catalysts‐Free Chemistry: A Benign Pathway to Sustainability

In the past decade, alternative benign organic methodologies have become an imperative part of organic syntheses and chemical reactions. The various new and innovative sustainable organic reactions and methodologies using no solvents or catalysts and employing alternative energy inputs such as microwaves, sonication, conventional and room temperature heating conditions, mechanochemical mixing, and high-speed ball milling are discussed in detail. Environmentally benign and pharmaceutically important reactions such as multicomponent, condensation, and Michael addition reactions; ring opening of epoxides; and oxidation and other significant organic reactions are discussed. An overview of benign reactions through solvent- and catalyst-free (SF-CF) chemistry and a critical perspective on emerging synergies between SF-CF organic reactions are discussed.

Magnetically recyclable magnetite–ceria (Nanocat-Fe-Ce) nanocatalyst – applications in multicomponent reactions under benign conditions

A novel magnetite nanoparticle-supported ceria catalyst (Nanocat-Fe-Ce) has been successfully prepared by a simple impregnation method and was characterized by XRD, SIMS, FEG-SEM-EDS, and TEM. The exact nature of Nanocat-Fe-Ce was confirmed by X-ray photoelectron spectroscopy and it is noted that CeO2 nanoparticles are supported on magnetite, with evidence of secondary ion mass spectrometry. Catalytic activity of the nano-catalyst was explored for the synthesis of dihydropyridines under benign conditions; a greener protocol is described that provides a simple and efficient method for the synthesis of functionalized 1,4-dihydropyridines using a recyclable nanocatalyst. Notably, 5.22 mol% of the catalyst is sufficient to catalyze the multicomponent reaction in ethanolic medium at room temperature. Importantly, the catalyst could be easily separated from the reaction mixture by using an external magnet and recycled several times without loss of activity.

Biocompatible Polyurea Dendrimers with pH‐Dependent Fluorescence

dendrimers emerge as powerful nanotools.Herein, we describe the synthesis and properties (up tothe fourth generation in this report) of polyurea (PURE)dendrimers. PURE dendrimers are a new family of water-soluble blue photoluminescent biocompatible and biodegrad-able “green” bifunctional dendrimers. The synthesis wasperformed in supercritical carbon dioxide (scCO

Dehydroindigo, the Forgotten Indigo and Its Contribution to the Color of Maya Blue

A comprehensive investigation of the electronic spectral and photophysical properties of the oxidized form of indigo, dehydroindigo (DHI), has been carried out in solution at 293 K. It is shown that dehydroindigo readily converts into its neutral keto form, the blue indigo, in a process which depends on the solvent and water content of the medium. DHI was investigated in toluene, in benzene, and in methanol and it was found that both the oxidized and the keto indigo forms are present in solution. In marked contrast to what has been found for keto-indigo, where the internal conversion channel dominates >99% of the excited state deactivation, or with the fully reduced leuco-indigo, where fluorescence, internal conversion, and singlet-to-triplet intersystem crossing coexist, in the case of DHI in toluene and benzene, the dominant excited state deactivation channel involves the triplet state. Triplet state yields (phi(T)) of 70-80%, with negligible fluorescence (< or = 0.01%) are observed in these solvents. In methanol the phi(T) value decreases to approximately 15%, with an increase of the fluorescence quantum yield to 2%, which makes these processes competitive with the S(1) --> S(0) internal conversion deactivation process. The data are experimentally compatible with the existence of a lowest lying singlet excited state of n,pi* origin in toluene and of pi,pi* origin in methanol. A time-resolved investigation in the picosecond time domain suggests that the emission of DHI involves three interconnected species (involving rotational isomerism), with relative contributions depending on the emission wavelength. DFT calculations (B3LYP 6-31G** level) were performed in order to characterize the electronic ground (S(0)) and excited singlet (S(1)) and triplet (T(1)) states of DHI. The HOMO-LUMO transition was found to accompany an n --> pi* transition of the oxygen nonbonding orbitals to the central CC and adjacent C-N bonds. Calculations also revealed that in S(0) the two indole-like moieties deviate from planarity from ca. 20 degrees, whereas in S(1) and T(1) the predicted structure is basically planar; a gradual decrease of the carbon-carbon central bond distance is seen in the order S(0), S(1), T(1). An additional study on the blue pigment Maya Blue was made, and the comparison between the solid-state spectra of indigo, DHI, and Maya Blue suggests that, in line with recent investigations, DHI is present together with indigo in Maya Blue. These results are relevant to the discussion of the involvement of dehydroindigo in the palette of colors of the ancient Maya Blue pigment.

Green synthesis and anti-infective activities of fluorinated pyrazoline derivatives.

A new series of fluorinated pyrazoles, 4a-e, were synthesized in good to excellent overall yields (65-82%) from the corresponding chalcones, 3a-e, by ultrasonic irradiation. The newly synthesized compounds were characterized and screened for their in vitro anti-bacterial, anti-fungal, and anti-tubercular activities against Mycobacterium tuberculosis H(37)Rv.

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.

Oxazoline-Based Antimicrobial Oligomers: Synthesis by CROP Using Supercritical CO2

A method using supercritical CO(2) to obtain biocompatible 2-oxazoline-based oligomers quaternized with different amines is described. The synthesized oligo(2-oxazoline)s display partial carbamic-acid insertion at one end. The syntheses of quaternary oligo(2-bisoxazoline)s and linear oligoethylenimine hydrochlorides are reported. Oligo(2-methyl-2-oxazoline) and oligo(2-bisoxazoline) quaternized with N,N-dimethyldodecylamine are the most efficient biocidal agents showing fast killing rates against Staphylococcus aureus and Escherichia coli. Linear oligoethylenimine hydrochloride shows the lowest MIC values but higher killing times against both bacteria. Based on the antimicrobial activity studies, a cooperative action of carbamic acid with the ammonium end group is proposed.

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.

Ultrasensitive microchip sensor based on boron-containing polyfluorene nanofilms

A fluorene-based π-conjugated copolymer with on-chain dibenzoborole units was used in the development of a nanocoated gold interdigitated microelectrode array device which successfully detects fluoride in a broad range of concentrations (10(-11)-10(-4) M) in aqueous solution, upon impedance spectroscopy measurements. A calibration curve obtained over this range of concentrations and a new analytical method based on impedance spectroscopy measurements in aqueous solution is proposed. The sensor nanofilm was produced by spin-coating and diagnosed via spectroscopic ellipsometry, AFM, and electrically conductivity techniques. Changes in the conductivity due to the boron-fluoride complex formation seem to be the major mechanism behind the dependence of impedimetric results on the fluoride concentration.

Anti-biofouling 3D porous systems: the blend effect of oxazoline-based oligomers on chitosan scaffolds.

The production, characterization and anti-biofouling activity of 3D porous scaffolds combining different blends of chitosan and oxazoline-based antimicrobial oligomers is reported. The incorporation of ammonium quaternized oligo(2-oxazoline)s into the composition of the scaffold enhances the stability of the chitosan scaffold under physiological conditions as well as its ability to repel protein adsorption. The blended scaffolds showed mean pore sizes in the range of 18–32 μm, a good pore interconnectivity and high porosity, as well as a large surface area, ultimate key features for anti-biofouling applications. Bovine serum albumin (BSA) adhesion profiles showed that the composition of the scaffolds plays a critical role in the chitosan–oligooxazoline system. Oligobisoxazoline-enriched scaffolds (20% w/w, CB8020) decreased protein adsorption (BSA) by up to 70%. Moreover, 1 mg of CB8020 was able to kill 99.9% of Escherichia coli cells upon contact, demonstrating its potential as promising material for production of tailored non-fouling 3D structures to be used in the construction of novel devices with applications in the biomedical field and water treatment processes.