[Show abstract][Hide abstract] ABSTRACT: Photoluminescent Lanthanide-Organic Frameworks (Ln-MOFs) were printed onto plastic and paper foils with a conventional Inkjet printer. Ln-MOF inks were used to reproduce color images that can be only observed under a UV light irradiation. This approach opens up a new window to explore Ln-MOF materials in technological applications, such as optical devices (e.g. lab-on-a-chip), proof of authenticity for official documents.
[Show abstract][Hide abstract] ABSTRACT: A joint experimental and theoretical investigation on the mechanism of the Petasis Borono-Mannich reaction is described. Using the charge-tag strategy for mass spectrometry ion monitoring in solution, unprecedented key intermediates were intercepted and characterized. A key intermediate was also isolated from the reaction solution and its structure could be deduced from single crystal X-ray diffraction. A mechanism further consolidated by DFT calculations that reconciles the present and all available data on this important multicomponent reaction is presented.
[Show abstract][Hide abstract] ABSTRACT: Two novel coordination polymers (CPs) have been synthesized, characterized and successfully applied as robust heterogeneous catalysts for the Biginelli multicomponent reaction to obtain 3,4-dihydropyrimidin-2(1H)-one or thione (DHPMs) derivatives. The reaction was initially developed using both CPs and the Zn-based material showed much better catalytic activity. After the reaction optimization under batch conditions, a continuous flow protocol was developed and applied with impressive results. Four bioactive DHPMs were successfully synthesized with high yields. The mechanism of the transformation was also investigated by electrospray (tandem) mass spectrometry (ESI-MS(/MS)) analyses. Online monitoring of the reaction indicated under the developed conditions that the iminium mechanism is preferred over the enamine- and Knoevenagel-based mechanisms. Nine DHPMs had their antitumoral activities evaluated against MCF-7 (human breast cancer cells), A549 (human alveolar basal epithelial cells) and Caco-2 (human epithelial colorectal cells) cancer cell lineages. Fibroblasts (healthy cells) were not affected by the tested DHPMs showing an excellent selectivity for tumour cells. Three DHPMs returned impressive results, being capable of inhibiting tumour cell proliferation in 72 h.
[Show abstract][Hide abstract] ABSTRACT: This Account describes the origins, features, importance, and trends of the use of fluorescent small-molecule 2,1,3-benzothiadiazole (BTD) derivatives as a new class of bioprobes applied to bioimaging analyses of several (live and fixed) cell types. BTDs have been successfully used as probes for a plethora of biological analyses for only a few years, and the impressive responses obtained by using this important class of heterocycle are fostering the development of new fluorescent BTDs and expanding the biological applications of such derivatives. The first use of a fluorescent small-molecule BTD derivative as a selective cellular probe dates back to 2010, and since then impressive advances have been described by us and others. The well-known limitations of classical scaffolds urged the development of new classes of bioprobes. Although great developments have been achieved by using classical scaffolds such as coumarins, BODIPYs, fluoresceins, rhodamines, cyanines, and phenoxazines, there is still much to be done, and BTDs aim to succeed where these dyes have shown their limitations.
Accounts of Chemical Research 05/2015; 48(6). DOI:10.1021/ar500468p · 22.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this paper, we describe a novel synthesized ionically-tagged water-soluble artificial enzyme (PI) that can efficiently cleave phosphate esters, with enhanced ionic liquid effect through cooperative effects for the substrate activation and further nucleophilic reaction. Dephosphorylation reaction with PI was evaluated in the presence and absence of 2-methyl-4(5)-nitroimidazole, showing impressive rate enhancements up to 2x106-fold, accounted for by the imidazolide species known as excellent nucleophiles, and formed favorably at lower pH values in the presence of PI.
The Journal of Organic Chemistry 05/2015; 80(11). DOI:10.1021/acs.joc.5b00750 · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fluorescent naphthoxazoles and their boron derivatives have been synthesized and applied as superior and selective probes for endocytic pathway tracking in live cancer cells. The best fluorophores were compared with the commercially available acridine orange (co-staining experiments), showing far better selectivity.
Chemical Communications 04/2015; 51(44). DOI:10.1039/C5CC02383A · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Breast cancer is a complex heterogeneous disease and is one of the leading causes of death among women. In addressing the need for treatments of this life-threatening illness, we studied 3,4-dihydropyrimidin-2(1H)-one (or thione) derivatives (DHPMs), a class of inhibitor molecules of the Eg5 motor spindle protein that shows pronounced antitumor activity against several cancer cell lines.
An in vitro screening was performed for identification of DHPMs with potent antitumor effects on MCF-7 and MDA-MB-231 cells and the selected DHPMs were evaluated for their inhibitory activity on Eg5 both in silico, using Molecular dynamics, and in vitro Eg5 inhibition assays. Analysis of cell death induction, proliferation, cell cycle and cancer stem cells (CSC) profile were performed by flow cytometry to assess the influence of the selected DPHMs on these important tumor features. Finally, the effects of DHPM treatment on tube formation were evaluated in vitro using HUVEC cells, and in vivo using a model on chorioallantoic membrane (CAM) of fertilized eggs.
We identified five DHPMs with pronounced inhibitory activity on Eg5 motor protein interfering with the proper mitotic spindle assembly during cell division. These compounds impair the correct conclusion of cell cycle of the breast cancer cells and showed to be selective for tumor cells. Moreover, DHPMs modulate the CD44(+)/CD24(-) phenotype leading to a decrease in the CSC population in MDA-MB-231 cells, an important effect since CSC are resistant to many conventional cancer therapies and play a pivotal role in tumor initiation and maintenance. This observation was confirmed by the results which demonstrated that DHPM treated cells had impaired proliferation and were unable to sustain angiogenesis events. Finally, the DHMP treated cells were induced to apoptosis, which is one of the most pursued goals in drug development.
The results of our study strongly suggest that DHPMs inhibit important tumorigenic features of breast cancer cells leading them to death by apoptosis. These findings firmly point to DHPM molecular architecture as a promising alternative against breast cancer.
BMC Cancer 04/2015; 15(1):283. DOI:10.1186/s12885-015-1274-1 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Iron-containing imidazolium-based ionic liquids were successfully applied as catalysts in the styrene polymerization. Solventless conditions, organic solvents and different imidazolium-based ionic liquid catalysts were tested to evaluate the best reaction conditions. The ionic liquids BMI.FeCl4 and BMI.Fe2Cl7 showed very distinct catalytic activities. Schulz–Flory distributions indicate two or three active catalytic species in different distributions. Via on-line direct infusion electrospray (tandem) mass spectrometry (ESI-MS(/MS)) reaction monitoring, both active catalytic species in accordance with the Schulz–Flory distributions were intercepted and characterized, providing important mechanistic insights that allowed us to propose a rationale for the origin of the superior catalytic efficiency.
[Show abstract][Hide abstract] ABSTRACT: 2,1,3-Benzothiadiazola (BTD) derivatives have been successfully applied in different scientific and technological areas. The possibility of combining the BTD core with several other organic molecules renders this nucleus the status of outstanding fluorophore. Computational methods such as Density Functional Theory (DFT) allowed for a rational design of new fluorescent compounds, as well as a better understanding of their electronic processes. The current revision describes a step-by-step methodology based on DFT calculations aiming at a theoretical prediction of the photophysical properties of an important oleic acid derivative tagged with a fluorescent BTD probe.
Revista Virtual de Quimica 01/2015; 7(1). DOI:10.5935/1984-6835.20150018
[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; 20(47). DOI:10.1002/chem.201404039 · 5.73 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. DOI:10.5935/0100-4042.20140266 · 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.
Chemical Science 07/2014; 5(10). DOI:10.1039/C4SC01785D · 9.21 Impact Factor
[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). DOI:10.1039/C4NJ00285G · 3.09 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(31):17878−17889. DOI:10.1021/jp506363h · 4.77 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). DOI:10.1039/C3NJ01499A · 3.09 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; 79(11). DOI:10.1021/jo500799j · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A task-specific ionic liquid with a Bronsted acid (1-(3-sulfopropyI)-3-methylimidazolium hydrogen sulfate, namely MSI) bearing an anionic heteropolyacid derivative ([PW12O40](3-), namely PW) were used as an efficient catalyst for the three-component Mannich and Hantzsch reactions. Using (MSI)(3)PW as the catalyst supported in imidazolium-based ionic liquids allowed these multicomponent reactions to take place in good to excellent yields. The Mannich reaction, performed at room temperature, was also evaluated by means of electrospray (tandem) mass spectrometry ESI-MS(/MS). ESI-MS data pointed to the origin of the ionic liquid effect, i.e., formation of ion pairs with the charged reaction intermediates and furthers association into larger supramolecular aggregates. DFT calculations revealed the strength of the supramolecular interactions between the charged species detected by ESI-MS and the spontaneity association of these ion pairs affording larger supramolecular aggregates.
[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; 79(8). DOI:10.1021/jo5001498 · 4.72 Impact Factor