Emilia Bertolo

Steady-State and Time-Resolved Investigations on Pyrene-Based Chemosensors

Two novel fluorescent probes bearing a single (P) and two (a podand-like structure, L) pyrene units derived from 1,5-bis(2-aminophenoxy)-3-oxopentane have been synthesized and investigated in dioxane using UV-vis absorption, and steady-state and time-resolved (in a picosecond time scale) emission spectroscopy; in the gas phase, matrix-assisted laser desorption ionization mass spectrometry was employed. In dioxane, the absorption and emission spectra of P present a unique band with maxima at 361 and 392 nm, which have been associated with the monomer absorption and emission bands, respectively. In dioxane, for compound L, an additional band with a maximum at ∼525 nm is observed; upon the addition of water, an emissive band (with maxima varying from 405 to 490 nm) appears in both P and L spectra; this is discussed in terms of the emission of a species with charge character. Upon metal addition (Cu(2+), Zn(2+), and Ag(+)) to P, a gradual quenching effect of the monomer emission is observed and found to be more pronounced with Cu(2+). In the case of L, upon the addition of metal cations, the long emission band (∼550 nm) decreases and the monomer emission band increases (with an isoemissive point at ∼450 nm) and no evidence for the intermediate band (at ∼405-490 nm) now exists. Time-resolved data in dioxane/water mixtures showed that for P and L these two fit double- and triple-exponential decay laws, respectively. With P, this has been attributed to a two-state system, which involves the monomer and a charged species, with its emission maxima varying with the polarity of the media (here mirrored by its dielectric constant), which can potentially be addressed to an exciplex-like species, whereas with L, it has been attributed to a three-state system involving, in addition to these two species, an excimer. From absorption and fluorescence excitation and time-resolved data, evidence is given for the presence of intramolecular dimer formation in the ground state.

Green and Red Fluorescent Dyes for Translational Applications in Imaging and Sensing Analytes: A Dual-Color Flag

Abstract Invited for this months cover picture is the BIOSCOPE group of Professors Carlos Lodeiro and José Luis Capelo at the REQUIMTE/UCIBIO‐LAQv‐FCT University NOVA of Lisbon (Portugal), and their collaborators. The cover picture is devoted to Translational Research, and shows the Portuguese Flag represented by the interaction between cells and Janus gold/silver nanoparticles functionalized with rhodamine (red) and Fluorescein (green) dyes as tools for biomedical translational research. Read the full text of their Review at 10.1002/open.201700135.

Winter Aconite (Eranthis hyemalis) Lectin as a cytotoxic effector in the lifecycle of Caenorhabditis elegans

The lectin found in the tubers of the Winter Aconite (Eranthis hyemalis) plant is an N-acetyl-D-galactosamine specific Type II Ribosome Inactivating Protein (RIP); Type II RIPs have shown anti-cancer properties, and hence have potential as therapeutic agents. Here we present a modified protocol for the extraction and purification of the E. hyemalis lectin (EHL) using affinity chromatography. De novo amino acid sequencing of EHL confirms its classification as a Type II Ribosome Inactivating Protein. The biocidal properties of EHL have been investigated against the nematode Caenorhabditis elegans. Arrested first stage larvae treated with EHL have shown some direct mortality, with surviving larvae subsequently showing a range of phenotypes including food avoidance, reduced fecundity, developmental delay and constitutive dauer larvae formation. Both inappropriate dauer larvae development and failure to locate to bacterial food source are consistent with the disruption of chemosensory function and the ablation of amphid neurons. Further investigation indicates that mutations that disrupt normal amphid formation can block the EHL-induced dauer larvae formation. In combination, these phenotypes indicate that EHL is cytotoxic and suggest a cell specific activity against the amphid neurons of C. elegans.

Unraveling the organotellurium chemistry applied to the synthesis of gold nanomaterials

Long-term preservation of the properties of gold nanoparticles in both solution and the dry powder form can be difficult. We have overcome this challenge by using organotellurium derivatives as both reducing agents and stabilizers in the synthesis of gold nanoparticles. This new synthetic protocol takes advantage of the photochemical and oxidative properties of diphenyl ditelluride (Ph2Te2), which, so far, have never been exploited in the synthesis of gold nanoparticles. The Au/Te core/shell (inorganic/organic) hybrid nanomaterial can be obtained in a one-step reaction, using only Ph2Te2 and HAuCl4. By modifying the reaction conditions, different resonance conditions of the gold core are achieved due to the formation of external shells with different thicknesses. The organotellurium shell can be easily removed by resuspension of the nanoparticles in environmentally friendly solvents, such as water or ethanol, making the Au core available for subsequent applications. A mechanism for the formation of core/shell nanoparticles has also been discussed.

Synthesis of four novel pendant armed macrocyclic ligands and their interaction with lanthanide(III) cations

The ability of La3+ ions to form stable complexes with four novel pendant-armed NxOy-macrocycles derived from 2,6-bis(2-formylphenoxymethyl)pyridine, L1, L2, L3, and L4, has been studied. The corresponding (unsubstituted) parent ligands were prepared by the reaction between 2,6-bis(2-formylphenoxymethyl)pyridine and three different amines: 1,2-bis(2-aminophenoxy)propane (L1), diethylenetriamine (L2), and 3,6-dioxa-1,8-octanediamine (L3 and L4). This was followed for the parent ligands of L1, L3, and L4 by in situ reduction with sodium borohydride. The pendant-armed ligands were then synthesized by the alkylation of the free-NH groups with p-(L1 and L3) and o-nitrobenzyl bromide (L4), and 2-chloromethylpyridine chlorohydrate (L2). A series of Ln(III) complexes were prepared for the four ligands by the direct synthesis between the corresponding macrocycle and Ln(III) hydrated nitrates and perchlorates. The number of complexes obtained from the pendant-armed macrocycles is lower than that of the (unsubstituted) parent ones, suggesting that the introduction of pendant arms in the macrocyclic skeletons increases the selectivity of the ligands. More complexes were synthesized when using nitrate as the counterion, showing the important role of the counterion in the complexation reaction.

Four novel N3O4 donor macrocycles and their Lanthanide(III) complexes

Abstract A new series of lanthanide(III) complexes with two novel Schiff-base macrocycles, L1 and L2, containing a N3O4 donor set have been prepared by cyclocondensation of 2,6-bis(2-formylphen-oxymethyl)pyridine and l,2-bis(2-aminophenoxy)ethane or 1,3-bis(2-aminophenoxy)propane, respectively, in the presence of the appropriate metal salt as a template agent. In the absence of the metal salt the macrocycles are not formed. The diamine macrocycles L3 and L4 are also formed by reaction of the corresponding diamine and dicarbonyl precursors followed by an in situ reduction with NaBH4. Their complexation potential towards Ln(III) ions were also investigated.

Synthesis of Gold Functionalised Nanoparticles with the Eranthis hyemalis Lectin and Preliminary Toxicological Studies on Caenorhabditis elegans

The lectin found in the tubers of the Winter Aconite (Eranthis hyemalis) plant (EHL) is a Type II Ribosome Inactivating Protein (RIP). Type II RIPs have shown anti-cancer properties and have great potential as therapeutic agents. Similarly, colloidal gold nanoparticles are successfully used in biomedical applications as they can be functionalised with ligands with high affinity and specificity for target cells to create therapeutic and imaging agents. Here we present the synthesis and characterization of gold nanoparticles conjugated with EHL and the results of a set of initial assays to establish whether the biological effect of EHL is altered by the conjugation. Gold nanoparticles functionalised with EHL (AuNPs@EHL) were successfully synthesised by bioconjugation with citrate gold nanoparticles (AuNPs@Citrate). The conjugates were analysed by UV-Vis spectroscopy, Dynamic Light Scattering (DLS), Zeta Potential analysis, and Transmission Electron Microscopy (TEM). Results indicate that an optimal functionalisation was achieved with the addition of 100 µL of EHL (concentration 1090 ± 40 µg/mL) over 5 mL of AuNPs (concentration [Au0] = 0.8 mM). Biological assays on the effect of AuNPs@EHL were undertaken on Caenorhabditis elegans, a free-living nematode commonly used for toxicological studies, that has previously been shown to be strongly affected by EHL. Citrate gold nanoparticles did not have any obvious effect on the nematodes. For first larval stage (L1) nematodes, AuNPs@EHL showed a lower biological effect than EHL. For L4 stage, pre-adult nematodes, both EHL alone and AuNPs@EHL delayed the onset of reproduction and reduced fecundity. These assays indicate that EHL can be conjugated to gold nanoparticles and retain elements of biocidal activity.

N1-((1H-Indazol-5-yl)methylene)-N2-(2-((2-((2-(((1H-indazol-6-yl)methylene)amino)ethyl)amino)ethyl)amino)ethyl)ethane-1,2-diamine

Abstract: One novel molecular emissive probe L has been synthesized by classical Schiff-base reaction between 1H-indazole-6-carboxaldehyde and tetraethylenepentamine. The structure of compound L was confirmed by melting point, elemental analysis, ESI-MS spectrometry and by IR and 13 C-NMR and 1 H-NMR spectroscopy. Keywords: imine compounds; amine compounds; indazol Indazole ring systems have an interesting chemistry, which has been used in biology, catalysis, and medicinal chemistry [1]. Although rare in nature [2], indazoles exhibit a variety of biological activities such as HIV protease inhibition [3–5], antiarrhythmic and analgesic activities [6], antitumor activity [7,8], and antihypertensive properties [9]. Furthermore, antimicrobial and antineoplastic activities have also been shown to be associated with certain indazole derivatives [10]. As a part of our ongoing research into the design and synthesis of novel organic molecular probes, luminescent materials and MALDI-TOF-MS matrices [11–14], here we report the synthesis and

N1-Benzylidene-N2-(2-((2-((2-(benzylideneamino)ethyl)amino) ethyl)amino)ethyl)ethane-1,2-diamine

A tetraethylene pentamine-diamine (L4), the biggest compound in the family of dibenzylated diimine-polyamines (L1–L4) has been synthesized by classical Schiff-base reaction between benzaldehyde and the diamine tetraethylenepentamine, and the structure was confirmed by elemental analysis, ESI-MS spectrometry and by IR and 1H-NMR spectroscopy.

N1-(Benzo[b]thiophen-3-ylmethylidene)-N2-(2-((2-((2-(benzo[b]thiophen-3-ylmethylidene)amino)ethyl)amino)ethyl)amino)ethyl)ethane-1,2-diamine

A novel probe L has been synthesized by classical Schiff-base reaction between 1-benzothiophene-3-carbaldehyde and tetraethylenepentamine as diamine. The structure of compound L was confirmed by melting point, elemental analysis, ESI-MS spectrometry, IR and 13C-NMR and 1H-NMR spectroscopy.