[Show abstract][Hide abstract] ABSTRACT: A series of new rationale designed 2,1,3-benzothiadiazole (BTD) fluorescent derivatives has been synthesized and applied for cellular selective staining of cancer cells in cell-imaging experiments. Four new synthesized BTD derivatives showed only poor or reasonable cellular selection, but with excellent fluorescence intensity and almost no background signal emitting at the blue or green channels. The knowledge gained by analysing their molecular architecture, however, allowed the planning and synthesis of a fluorescent BTD, which was then successfully tested and showed superior mitochondrial selection with outstanding results in bioimaging experiments in living cells. The new marker (named Splendor) was then compared with the commercially available MitoTracker Red (also through co-staining experiments) and showed far better mitochondrial selection, fluorescence intensity and chemical stability. Mitochondrial imaging and tracking (dynamic changes) was possible using Splendor during the whole cellular division cycle. DFT calculations were performed to offer insights into the origin of the chemical- and photostability of BTD derivatives. In addition, molecular docking calculations hint at a potential molecular target for the BTD derivatives in the mitochondrial protein adenine nucleotide translocase, which may explain the mitochondrial selectivity of Splendor versus the other four BTD derivatives.
Chemistry - A European Journal 10/2014; · 5.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The current manuscript describes the importance, mechanism propositions, evidence and controversies associated with multicomponent reactions (MCRs). The following multicomponent reactions are presented and critically evaluated: The Biginelli, Hantzsch, Mannich, Passerini and Ugi reactions. THE AIM OF THIS REVIEW IS TO HIGHLIGHT WHAT WE ALREADY KNOW ABOUT THE MECHANISMS ASSOCIATED WITH THESE MCRS AND THE EVIDENCE SUPPORTING THE PROPOSED REACTION PATHWAYS. CONTROVERSIES AND PROSPECTS ARE ALSO DISCUSSED HEREIN.
[Show abstract][Hide abstract] ABSTRACT: The bioactive 3,4-dihydropyrimidin-2(1H)-thione derivative known as Monastrol was synthesized under catalyzed and non-catalyzed
conditions through the Biginelli multicomponent reaction under solvent-free conditions. The use of two Lewis acids (FeCl 3 and
CuCl 2 ) and two Brønsted acids (HCl and CF 3 COOH) as catalysts improved the reaction yields of the transformation compared with
the non-catalyzed reaction. The experiments investigated catalysis and its role, the importance of multicomponent reactions and their
green features, and the application of these concepts to the synthesis of a biologically important structure.
Química Nova 09/2014; 37(10):1713. · 0.66 Impact Factor
[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). · 3.16 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). · 3.16 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; · 4.64 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; · 4.64 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