[Show abstract][Hide abstract] ABSTRACT: A novel lipophilic fluorescent small-molecule 2,1,3-benzothiadiazole derivative (named here as BTD-AO) was designed, synthesized, characterized and applied as a live cell-imaging probe. Its cellular uptake and cellular dynamics at low temperature (4 °C) using MDA-MB-237 were investigated. Confocal bioimages revealed that the new bioprobe was capable of easily transposing the cell-membrane at low temperatures and also revealed the dynamics of BTD-AO over time. BTD-AO had a high affinity for vesicles (lipid droplets) and had its subcellular location precisely determined during its migration in the cells.
[Show abstract][Hide abstract] ABSTRACT: A novel Pd-complex with a charge tag (imidazolium cation) was applied for online monitoring of the neutral Heck reaction by electrospray ionization (tandem) mass spectrometry – ESI-MS(/MS). The results shed light on the mechanism of the reaction, whereas the charge-tagged ligand also allowed the unprecedented MS monitoring of Pd2+ reduction to Pd0. Key reaction intermediates associated with Pd catalysis could also be detected and characterized due to the presence of the charge tag on the Pd-complex. DFT calculations supported the proposed mechanism. The new charge-tagged Pd-complex is also shown to function as an active catalyst “on water” with the advantage of using cheaper and less reactive aryl chloride substrates in a phosphine-free version of the Heck reaction.
New Journal of Chemistry 06/2014; 38(7). · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Using a set of diﬀerent techniques, which included single crystal X-ray, NMR, UV−vis, conductivity measurements, SAXS (small angle X-rays), ESI-MS(/MS) (electrospray (tandem) mass spectrometry), and theoretical calculations, an ample study of the structural organization and supramolecular interaction of the task-speciﬁc ionic liquid 1-methyl-3-carboxymethylimidazolium chloride (named MAI.Cl) was conducted. All techniques allowed for comprehensive investigation in the solid state, solution, and gas-phase behavior of MAI.Cl. Most relevant interactions are demonstrated showing the importance of hydrogen bonding to supramolecular organization of MAI.Cl in diﬀerent states and its tendency to aggregate in aqueous solutions.
The Journal of Physical Chemistry C 06/2014; 118:17878−17889. · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two new benzothiadiazole-triazole-linked lapachone derivatives were designed, synthesized and characterized by 1D and 2D NMR spectroscopy. Their photophysical properties were also investigated. Theoretical calculations (DFT), based on the molecular design of the new compounds, allowed a better understanding of the derivatives' stability and behaviour, especially in the excited state. This manuscript also describes a discussion on the molecular architecture which is based on two substitutions at positions 4- and 7- of the important 2,1,3-benzothiadiazole (BTD) core. One side is replaced by a group capable of performing an ESIPT (excited-state intramolecular proton transfer) stabilizing process, and the other side is substituted by a triazole-containing group. This triazole ring acts as the linker between the BTD core and a group of known antitumoral activity i.e. a nor-β-lapachone derivative. These novel fluorescent compounds had their biological activities evaluated against twenty cancer cell lines and three normal cells with promising results. Finally, due to their interesting photophysical properties and good fluorescence, bioimaging experiments were conducted, and these dyes were tested as fluorescent cell-imaging probes, thus showing their preferable cellular location in MDA-MB-231 cancer cells (a breast-invasive cancer-cell lineage).
New Journal of Chemistry 05/2014; 38(6). · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of a charge-tagged acrylate derivative bearing an imidazolium tag to study the Morita-Baylis-Hillman reaction via ESI-MS(/MS) monitoring and the effect of such tag (imidazolium cations and ion pairs) over TS is described. The ionic nature of the substrate was meant to facilitate ESI transfer to the gas phase for direct mass spectrometric analysis. The detection and characterization of charged intermediates has suggested major reaction pathways. DFT calculations considering the effect of a polar and protic solvent (methanol), polar and aprotic solvent (acetonitrile) and of no-solvent (gas phase) were used to predict possible TS through a common accepted intermediate. The controversial proton transfer step, which may proceed via Aggarwal's or McQuade's proposals, was evaluated. Calculations predicted the formation of electrostatic intermediate complexes with both the cation and anion when charge-tagged reagents are used. These complexes contribute to the positive ionic liquid effect and, based on the formation of these unique complexes, a rationale for the ionic liquid effect is proposed. Moreover, it pointed to a plausible explanation for the positive ionic liquid effect observed in several reactions that are difficult to be carried out in organic solvents but have shown a beneficial effect when performed in ionic liquids.
The Journal of Organic Chemistry 05/2014; · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The current manuscript describes the role and importance of catalysis and solvent effects for the Biginelli multicomponent reaction. The overwhelming number of new catalysts and conditions recently published for the Biginelli synthesis, including in some manuscripts entitled "catalyst-free" and/or "solvent-free" have incentivized controversies and hot debates regarding the importance of developing new catalysts and reaction conditions to perform this very important multicomponent reaction. These so-called "catalyst-free" reports have generated much confusion in the field, therefore requiring urgent elucidations. In this manuscript, we exemplify, demystify and discuss the crucial role of catalysis, solvent effects, mechanisms, kinetics, facts, presumptions and myths associated with the Biginelli reaction aiming to avoid current and future confusions; and to stimulate new approaches.
The Journal of Organic Chemistry 03/2014; · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mechanism of the Ugi four-component reaction has been investigated by electrospray ionization (tandem) mass spectrometry using charge-tagged reagents (a carboxylic acid or an amine) to favour detection. Key intermediates were transferred directly via ESI(+) from the reaction solution to the gas phase and characterized by MS measurements and MS/MS collision induced dissociation. The Mumm rearrangement (final step) was also investigated by both travelling wave ion mobility mass spectrometry and DFT calculations. The data seem to consolidate the amazingly selective mechanism of this intricate four-component reaction.
Chemical Communications 11/2013; · 6.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This article describes a straightforward and simple synthesis of ionically tagged water-soluble Eu(3+) and Tb(3+) complexes (with ionophilic ligands) applied for bioimaging of invasive mammal cancer cells (MDA-MB-231). Use of the task-specific ionic liquid 1-methyl-3-carboxymethyl-imidazolium chloride (MAI·Cl) as the ionophilic ligand (ionically tagged) proved to be a simple, elegant, and efficient strategy to obtain highly fluorescent water-soluble Eu(3+) (EuMAI) and Tb(3+) (TbMAI) complexes. TbMAI showed an intense bright green fluorescence emission selectively staining endoplasmic reticulum of MDA-MB-231 cells.
[Show abstract][Hide abstract] ABSTRACT: We describe the synthesis of novel mononuclear and dinuclear copper complexes and an investigation of their behaviour in solution using mass spectrometry (ESI-MS and ESI-MS/MS) and in the solid state using X-ray crystallography. The complexes were synthesized from two widely used diacetylpryridine (dap) ligands, i.e. 2,6-diacetylpyridinebis(benzoic acid hydrazone) and 2,6-diacetylpyridinebis(2-aminobenzoic acid hydrazone). Theoretical calculations (DFT) were used to predict the complex geometries of these new structures, their equilibrium in solution and energies associated with the transformations.
[Show abstract][Hide abstract] ABSTRACT: Bronsted and Lewis acid catalysts with ionic tags under homogeneous and heterogeneous conditions have been tested to perform the Biginelli synthesis of 3,4-dihydropyrimidin-2(1H)-one (DHPMs). Metal-containing ionic liquids were evaluated as the catalysts with reasonable results (homogeneous systems). Heterogeneous catalysts (zeolite β and H3PW12O40 supported on zeolite β) have been tested, as well, with good to excellent results. The use of a functionalized acid ionic liquid with a heteropolyacid in the anion moiety (homogeneous system) gave the best results using no excess of the three reagents. The preferred mechanistic pathway was investigated by electrospray ionization (tandem) mass spectrometry in both positive and negative ion modes with very elucidative results. The ionic liquid effect and its origin were also investigated using mass spectrometry and DFT calculations.
[Show abstract][Hide abstract] ABSTRACT: In the present manuscript, a novel fluorescent chalcone derivative is synthesized and its photophysical properties are fully characterized. The designed fluorophore is applied as a probe to study protein-dye interactions with bovine serum albumin. Circular dichroism gave interesting results on the thermodynamics of the interaction. NMR spectroscopy, especially relaxation measurements, revealed the atoms in the chalcone derivative that interacts with the protein upon binding. Molecular docking calculations indicate that the most favourable binding sites are near the two tryptophan residues. Furthermore, ab initio and DFT calculations offer insights into the reactivity and physicochemical properties of this novel fluorophore.
[Show abstract][Hide abstract] ABSTRACT: The present manuscript describes the importance of small mitochondrion-specific fluorescent markers to study mitochondrial dynamics and related processes. The importance of mitochondria, their dynamic cellular processes, the use of fluorescent selective probes, limitations of selected commercially available fluorescent systems and recent developments on the synthesis and applications of small fluorescent probes and trends are discussed.
[Show abstract][Hide abstract] ABSTRACT: The present work describes the synthesis, characterization, and application of a new ion-tagged iron catalyst. The catalyst was employed in the Biginelli reaction with impressive performance. High yields have been achieved when the reaction was carried out in imidazolium-based ionic liquids (BMI⋅PF6 , BMI⋅NTf2 , and BMI⋅BF4 ), thus showing that the ionic-liquid effects play a role in the reaction. Moreover, the ion-tagged catalyst could be recovered and reused up to eight times without any noticeable loss in activity. Mechanistic studies performed by using high-resolution electrospray-ionization quadrupole-time-of-flight mass (HR-EI-QTOF) spectrometry and kinetic experiments indicate only one reaction pathway and rule out the other two possibilities under the development conditions. The theoretical calculations are in accordance with the proposed mechanism of action of the iron catalyst. Finally, the 37 dihydropyrimidinone derivatives, products of the Biginelli reaction, had their cytotoxicity evaluated in assays against MCF-7 cancer cell linages with encouraging results of some derivatives, which were virtually non-toxic against healthy cell linages (fibroblasts).
[Show abstract][Hide abstract] ABSTRACT: 2,1,3-Benzothiadiazole (BTD) is one of the most important nuclei used in the chemistry of photoluminescent compounds and applicable for light technology. The understanding of its properties and reactions is fundamental for the design and application of these derivatives in molecular organic electronic devices and for other technologies. As a result of their potential as constituents of organic light-emitting diodes, solar cells, liquid crystals, dyes, photovoltaic cells, and many others, attention has been focused on BTD π-extended derivatives with potential use in this exciting area. Herein, we describe their syntheses, properties, reactions, and selected examples of applications in light technology using by BTD (small molecules) as the core.
Annalen der Chemie und Pharmacie 01/2013; 2013(2). · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The species involved in the distillation of aprotic ionic liquids are discussed in light of recent simulations and mass spectrometric data obtained by various techniques. New mass spectrometric data collected via laser-induced acoustic desorption and the thermal desorption of ionic liquids are also presented as well as additional DFT calculations. The available evidence of theoretical simulations and mass spectrometric data suggests that the distillation of ionic liquids occurs mainly via neutral ion pairs of composition C n A n [C + = cation and A − = anion], followed by gas-phase dissociation to lower order ion pairs and then dissociation of hot CA to C + and A − , followed by ion/molecule association events to give [C n A n−1 ] + or [C n−1 A n ] − ions to a degree that depends on the amount of internal energy deposited into the neutral C n A n clusters upon evaporation. SECTION: Molecular Structure, Quantum Chemistry, and General Theory I onic liquids (IL) were long thought to be completely nonvolatile with negligible vapor pressures, as are also displayed by classical molten salts. 1 But room-temperature IL, especially those based on imidazolium cations, such as 1 (see below), are unique chemical entities due to a 3D cooperative network with H bonds between cations and anions. 2 This 3D preorganized H-bonded structures provide structural direction-ality via an entropic effect 3 whereas classical salts form aggregates only through simple ionic bonds. As a consequence, comparatively weak supramolecular interactions control the structures of IL, whereas the charges rigidly control the structure within classical salts. IL are better described, therefore, as H-bonded polymeric "zwitterionic supramolecules" of the type [(C) n (A) n−y) ] y+ [(C) m−y (A) m)] y− , where C + = cation and A − = anion. This structural description applies to the condensed phase and is apparently maintained to a large extent in the gas phase; 4 hence, the supramolecular interactions of IL should govern their main and unique properties, including their volatility and the species generated in the process of volatilization. The recent observation that both protic and most particularly aprotic IL can be distilled without degradation 5 was a major paradigm change in IL chemistry and one of the most intriguing findings about these exotic but very useful chemical species. Note that protic ionic liquids are volatile by their nature because proton-transfer equilibrium between both the cation [C−H] + and the anion A − allows for the formation of neutral molecular species C and A−H that readily evaporate and recombine restoring the protic ionic liquid upon condensation. Soon after that report, different proposals were made regarding the nature of the species present in the vapor of aprotic IL and whether isolated ions or neutral supramolecular aggregates were present. 6 Although it seemed that a consensus was reached about the prevalence of the CA neutral ion pair in the vapor of IL, 7 the matter is still under debate. Recently, Chaban and Prezhdo 8 reported detailed atomistic simulations of the vapor phase of IL in equilibrium with the liquid that seem to provide crucial insights into the debate. Interestingly, the simulations predicted that the saturated vapor of IL, at relatively high temperatures in the range of 1000−1075 K,
[Show abstract][Hide abstract] ABSTRACT: An iron(III) complex with ionic tags was applied to the reduction of alkenes in imidazolium-based ionic liquids (ILs) under oxidative conditions. The catalyst is very efficient to promote reactions of biomass derivatives. At least ten recycling reactions were performed without any loss of catalytic activity. Some important mechanistic insights for this new reaction are also provided based mostly on electrospray ionization quadrupole-time of flight mass spectrometry (ESI-QTOF-MS).
[Show abstract][Hide abstract] ABSTRACT: This paper describes the use of common Lewis acids supported in imidazolium-based ionic liquids as the catalysts to promote the Biginelli reaction. The ionic liquid effect and the reaction mechanism are discussed on the basis of nuclear magnetic resonance (NMR), electrospray ionization mass spectrometry (ESI-MS), and theoretical calculations. Indeed, the results showed that the ionic medium plays a fundamental role in the synthesis of biologically active dihydropyrimidinones due to the stabilization of the charged intermediates proposed in the mechanism. When conducted in an ionic liquid as solvent, the reaction mechanism is more complex than in other Lewis acid catalyzed Biginelli reactions.
The Journal of Organic Chemistry 10/2012; · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ̀This paper reports on the advancement of magnetic ionic liquids (MILs) as stable dispersions of surface-modified γ-Fe(2)O(3), Fe(3)O(4), and CoFe(2)O(4) magnetic nanoparticles (MNPs) in a hydrophobic ionic liquid, 1-n-butyl 3-methylimidazolium bis(trifluoromethanesulfonyl)imide (BMI.NTf(2)). The MNPs were obtained via coprecipitation and were characterized using powder X-ray diffraction, transmission electron microscopy, Raman spectroscopy and Fourier transform near-infrared (FT-NIR) spectroscopy, and magnetic measurements. The surface-modified MNPs (SM-MNPs) were obtained via the silanization of the MNPs with the aid of 1-butyl-3-[3-(trimethoxysilyl)propyl]imidazolium chloride (BMSPI.Cl). The SM-MNPs were characterized by Raman spectroscopy and Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy and by magnetic measurements. The FTIR-ATR spectra of the SM-MNPs exhibited characteristic absorptions of the imidazolium and those of the Fe-O-Si-C moieties, confirming the presence of BMSPI.Cl on the MNP surface. Thermogravimetric analysis (TGA) showed that the SM-MNPs were modified by at least one BMSPI.Cl monolayer. The MILs were characterized using Raman spectroscopy, differential scanning calorimetry (DSC), and magnetic measurements. The Raman and DSC results indicated an interaction between the SM-MNPs and the IL. This interaction promotes the formation of a supramolecular structure close to the MNP surface that mimics the IL structure and is responsible for the stability of the MIL. Magnetic measurements of the MILs indicated no hysteresis. Superparamagnetic behavior and a saturation magnetization of ∼22 emu/g could be inferred from the magnetic measurements of a sample containing 50% w/w γ-Fe(2)O(3) SM-MNP/BMI.NTf(2).