Supramolecular assembly of pentamidine and polymeric cyclodextrin bimetallic core-shell nanoarchitectures.

Advanced nanoscale antimicrobials, originated from the combination of noble metal nanoparticles (NPs) with conventional antimicrobial drugs, are considered the next generation of antimicrobial agents. Therefore, there is an increasing demand for rapid, eco-friendly, and relatively inexpensive synthetic approaches for the preparation of nontoxic metallic nanostructures endowed with unique physicochemical properties. Recently, we have proposed a straightforward synthetic strategy that exploits the properties of polymeric ß-cyclodextrin (PolyCD) to act as both the reducing and stabilizing agent to produce monodispersed and stable gold-based NPs either as monometallic (nanoG) structures or core-shell bimetallic (nanoGS) architectures with an external silver layer. Here, we describe the preparation of a supramolecular assembly between nanoGS and pentamidine, an antileishmanial drug endowed with a wide range of therapeutic properties (i.e., antimicrobial, anti-inflammatory, and anticancer). The physicochemical characterization of the supramolecular assembly (nanoGSP) in terms of size and colloidal stability was investigated by complementary spectroscopic techniques, such as UV-vis, ζ-potential, and dynamic light scattering (DLS). Furthermore, the role of PolyCD during the reduction/stabilization of metal NPs was investigated for the first time by NMR spectroscopy.

Study on Metronidazole Acid-Base Behavior and Speciation with Ca2+ for Potential Applications in Natural Waters.

Metronidazole (MNZ) is an antibiotic widely used for the treatment of various infectious diseases and as an effective pesticide agent for the cultivation of chickens and fish. Its high resistance to purification processes and biological activity has led to the classification of MNZ as an emerging contaminant. A speciation study, aimed to define the acid-base properties of MNZ and its interaction with Ca2+, commonly present in natural waters, is reported. The protonation constants of MNZ, as well as the formation constant value of Ca2+-MNZ species, were obtained by potentiometric titrations in an aqueous solution, using NaCl as background salt at different ionic strengths (0.15, 0.5, 1 mol L-1) and temperature (15, 25 and 37 °C) conditions. The acid-base behavior and the complexation with Ca2+ were also investigated by 1H NMR and UV-Vis titrations, with results in very good agreement with the potentiometric ones. The dependence of the formation constants on the ionic strength and temperature was also determined. The sequestering ability of MNZ towards Ca2+ was defined by the empirical parameter pL0.5 at different pH and temperature values. The speciation of MNZ simulating sea water conditions was calculated.

Synthesis and Photophysics Characterization of Boronic Styril and Distyryl BODIPYs for Water-Based Dye-Sensitized Solar Cells.

In this study, two boronic acid BODIPYs are obtained through a microwave-assisted Knoevenagel reaction. The aim is to use them for the first time as dyes in a photosensitized solar cell (DSSC) to mimic chlorophyll photosynthesis, harvesting solar light and converting it into electricity. The microwave-assisted Knoevenagel reaction is a straightforward approach to extending the molecular conjugation of the dye and is applied for the first time to synthesize BODIPY's boronic acid derivatives. These derivatives have proved to be very useful for covalent deposition on titania. This work studies the photo-physical and electrochemical properties. Moreover, the photovoltaic performances of these two new dyes as sensitizers for DSSC are discussed. Experimental data show that both dyes exhibit photosensitizing activities in acetonitrile and water. In particular, in all the experiments, distyryl BODIPY was more efficient than styryl BODIPY. In this study, demonstrating the use of a natural component as a water-based electrolyte for boronic BODIPY sensitizers, we open new possibilities for the development of water-based solar cells.

Speciation Study on O-Phosphorylethanolamine and O-Phosphorylcholine: Acid-Base Behavior and Mg2+ Interaction.

In the present study, the acid-base behavior of compounds constituting the headgroups of biomembranes, O-phosphorylethanolamine (PEA), and O-phosphorylcholine (PPC) was investigated by potentiometric titrations in NaCl aqueous solutions at different temperatures (15 ≤ t/°C ≤ 37) and ionic strength (0.15 ≤ I/mol L-1 ≤ 1) values. The complexation properties and the speciation of these ligands with Mg2+ were defined under different temperatures (15 ≤ t/°C ≤ 37) and I = 0.15 mol L-1. The results evidenced the formation of three species for PEA, namely, MLH2, MLH, and ML and two species for PPC, namely, MLH and ML. 1H-NMR titrations were performed on solutions containing ligand and metal-ligand solutions at t = 25°C and I = 0.15 mol L-1. The estimated values of ligand protonation and complex formation constants and the speciation model are in accordance with the potentiometric data. The enthalpy changes were also determined at t = 25°C and I = 0.15 mol L-1 by the dependence of formation constants on the temperature, confirming the electrostatic nature of the interactions. Matrix-assisted laser desorption mass spectrometry (MALDI-MS) was applied for the characterization of Mg2+-L systems (L = PEA or PCC). MS/MS spectra of free ligands and of Mg2+-L species were obtained. The observed fragmentation patterns of both Mg2+-L systems allowed elucidating the interaction mechanism that occurs via the phosphate group generating a four-membered cycle.

State of the Art on Green Route Synthesis of Gold/Silver Bimetallic Nanoparticles.

Recently, bimetallic nanoparticles (BMNPs) blending the properties of two metals in one nanostructured system have generated enormous interest due to their potential applications in various fields including biosensing, imaging, nanomedicine, and catalysis. BMNPs have been developed later with respect to the monometallic nanoparticles (MNPs) and their physicochemical and biological properties have not yet been comprehensively explored. The manuscript aims at collecting the main design criteria used to synthetize BMNPs focusing on green route synthesis. The influence of experimental parameters such as temperature, time, reagent concentrations, capping agents on the particle growth and colloidal stability are examined. Finally, an overview of their nanotechnological applications and biological profile are presented.

Supramolecular BODIPY based dimers: synthesis, computational and spectroscopic studies.

The synthetic procedures for the preparation of supramolecular BODIPY dimers decorated with complementary patterns able to induce the formation of a triple hydrogen bond through mutual interactions are here reported. The BODIPY and styryl-equipped BODIPY species have been suitably functionalized in meso position with 2,6-diacetamido-4-pyridyl and 1-butyl-6-uracyl moieties. Dimers and monomers have been subjected to computational and photophysical investigations in solvent media. Various peculiarities concerning the effects of the interaction geometry on the stability of the H-bonded systems have also been investigated. The combination of modelling and experimental data provides a paradigm for improving and refining the BODIPY synthetic pathway to have chromophoric architectures with a programmable supramolecular identity. Furthermore, the possibility of assembling dimers of different dyes through H-bonds could be appealing for a systematic investigation of the principal factors affecting the dynamics of the energy migration and possibly driving coherent transfer mechanisms. Our work highlights how the chemical versatility of these dyes can be exploited to design new BODIPY-based supramolecular architectures.

Ca2+ Complexation With Relevant Bioligands in Aqueous Solution: A Speciation Study With Implications for Biological Fluids.

A speciation study on the interaction between Ca2+ and ligands of biological interest in aqueous solution is reported. The ligands under study are l-cysteine (Cys), d-penicillamine (PSH), reduced glutathione (GSH), and oxidized glutathione (GSSG). From the elaboration of the potentiometric experimental data the most likely speciation patterns obtained are characterized by only protonated species with a 1:1 metal to ligand ratio. In detail, two species, CaLH2 and CaLH, for systems containing Cys, PSH, and GSH, and five species, CaLH5, CaLH4, CaLH3, CaLH2, and CaLH, for system containing GSSG, were observed. The potentiometric titrations were performed at different temperatures (15 ≤ t/°C ≤ 37, at I = 0.15 mol L-1). The enthalpy and entropy change values were calculated for all systems, and the dependence of the formation constants of the complex species on the temperature was evaluated. 1H NMR spectroscopy, MALDI mass spectrometry, and tandem mass spectrometry (MS/MS) investigations on Ca2+-ligand solutions were also employed, confirming the interactions and underlining characteristic complexing behaviors of Cys, PSH, GSH, and GSSG toward Ca2+. The results of the analysis of 1H NMR experimental data are in full agreement with potentiometric ones in terms of speciation models and stability constants of the species. MALDI mass spectrometry and tandem mass spectrometry (MS/MS) analyses confirm the formation of Ca2+-L complex species and elucidate the mechanism of interaction. On the basis of speciation models, simulations of species formation under conditions of some biological fluids were reported. The sequestering ability of Cys, PSH, GSH, and GSSG toward Ca2+ was evaluated under different conditions of pH and temperature and under physiological condition.

The effect of hydrogen bonds on the ultrafast relaxation dynamics of a BODIPY dimer.

The influence of hydrogen bonds (H-bonds) in the structure, dynamics, and functionality of biological and artificial complex systems is the subject of intense investigation. In this broad context, particular attention has recently been focused on the ultrafast H-bond dependent dynamical properties in the electronic excited state because of their potentially dramatic consequences on the mechanism, dynamics, and efficiency of photochemical reactions and photophysical processes of crucial importance for life and technology. Excited-state H-bond dynamics generally occur on ultrafast time scales of hundreds of femtoseconds or less, making the characterization of associated mechanisms particularly challenging with conventional time-resolved techniques. Here, 2D electronic spectroscopy is exploited to shed light on this still largely unexplored dynamic mechanism. An H-bonded molecular dimer prepared by self-assembly of two boron-dipyrromethene dyes has been specifically designed and synthesized for this aim. The obtained results confirm that upon formation of H-bonds and the dimer, a new ultrafast relaxation channel is activated in the ultrafast dynamics, mediated by the vibrational motions of the hydrogen donor and acceptor groups. This relaxation channel also involves, beyond intra-molecular relaxations, an inter-molecular transfer process. This is particularly significant considering the long distance between the centers of mass of the two molecules. These findings suggest that the design of H-bonded structures is a particularly powerful tool to drive the ultrafast dynamics in complex materials.

Do Secondary Electrostatic Interactions Influence Multiple Dihydrogen Bonds? AA-DD Array on an Amine-Borane Aza-Coronand: Theoretical Studies and Synthesis.

Hydrogen bond plays a key role in a wide range of inorganic, organic, as well as biological systems. The understanding on how the chemical environment can affect this kind of interaction is crucial to predict its binding strength and consequently the robustness and the dynamic properties of many supramolecular systems. In this paper a new donor-acceptor complex was synthesized and characterized by SCXRD, showing for the first time in an organic system an AA-DD pattern of a particular hydrogen interaction, called dihydrogen bond. Over 250 functionals were computationally evaluated to select the best method to reproduce the binding interaction geometry of this new pattern. Moreover, a new vector force model was used to split the contribution of primary and secondary electrostatic interactions (SEIs), in order to evaluate how the latter one can modify the binding strength of this unusual hydrogen-hydrogen interaction.

High-Efficiency FRET Processes in BODIPY-Functionalized Quantum Dot Architectures.

Efficient FRET systems are developed combining colloidal CdSe quantum dots (QDs) donors and BODIPY acceptors. To promote effective energy transfer in FRET architectures, the distance between the organic fluorophore and the QDs needs to be optimized by a careful system engineering. In this context, BODIPY dyes bearing amino-terminated functionalities are used in virtue of the high affinity of amine groups in coordinating the QD surface. A preliminary QD surface treatment with a short amine ligand is performed to favor the interaction with the organic fluorophores in solution. The successful coordination of the dye to the QD surface, accomplishing a short donor-acceptor distance, provides effective energy transfer already in solution, with efficiency of 76 %. The efficiency further increases in the solid state where the QDs and the dye are deposited as single coordinated units from solution, with a distance between the fluorophores down to 2.2 nm, demonstrating the effectiveness of the coupling strategy.

Development of Polymeric Membranes Based on Quaternized Polysulfones for AMFC Applications.

A series of quaternary ammonium-functionalized polysulfones were successfully synthesized using a chloromethylation two-step method. In particular, triethylammonium and trimethylammonium polysulfone derivatives with different functionalization degrees from 60% to 150% were investigated. NMR spectroscopic techniques were used to determine the degree of functionalization of the polymers. The possibility to predict the functionalization degree by a reaction tool based on a linear regression was highlighted. Anionic membranes with a good homogeneity of thickness were prepared using a doctor-blade casting method of functionalized polymers. The chemical-physical data showed that ion exchange capacity, water content, and wettability increase with the increase of functionalization degree. A higher wettability was found for membranes prepared by the trimethylamine (TMA) quaternary ammonium group. A degree of functionalization of 100% was chosen for an electrochemical test as the best compromise between chemical-physical properties and mechanical stability. From anionic conductivity measurement a better stability was found for the triethylamine (TEA)-based membrane due to a lower swelling effect. A power density of about 300 mW/cm2 for the TEA-based sample at 60 °C in a H2/O2 fuel cell was found.

Two-Dimensional Electronic Spectroscopy Reveals Dynamics and Mechanisms of Solvent-Driven Inertial Relaxation in Polar BODIPY Dyes.

In this work, we demonstrate the use of two-dimensional electronic spectroscopy (2DES) to study the mechanism and time scale of the femtosecond Stokes shift dynamics in molecules characterized by intramolecular charge transfer, such as distyryl-functionalized boron dipyrromethene (BODIPY) molecules. The obtained results demonstrate that 2DES allows clear and direct visualization of the phenomenon. The analysis of the 2D data in terms of 2D frequency-frequency decay associated maps provides indeed not only the time scale of the relaxation process but also the starting and the final point of the energy flow and the associated reorganization energy, identified by looking at the coordinates of a negative signature below the diagonal. The sensitivity of the 2DES technique to vibrational coherence dynamics also allowed the identification of a possible relaxation mechanism involving specific interaction between a vibrational mode of the dye and the solvent.

Metal Complexes as Self-Indicating Titrants for Acid-Base Reactions in Chloroform.

The paper reports an unprecedented spectrophotometric determination of amines in chloroform, in which amines are not transformed into colored derivatives. This result has been achieved by exploiting the acid-base properties of the tight-ion-paired metal complexes [(HR2DTO)Pt(H2R2DTO)][Cl], which are able to donate a HCl molecule to an amine, giving rise to an ammonium salt and to the neutral complexes [(HR2DTO)2Pt]. The circumstance that [(HR2DTO)Pt(H2R2DTO)][Cl] and [(HR2DTO)2Pt] species show different absorptions in the visible region of the electromagnetic spectrum enables the aforementioned platinum complexes to behave as self-indicating titrants in the spectrophotometric determination of aliphatic amines, which are known to be UV-vis transparent. The new method has been tested by determining a series of fatty amines in the bulk and gave excellent results. The limits of applicability of this method (pKa > 4) were found by testing a series of benzodiazepines.

A functionalized, ethynyl-decorated, tetracobalt(III) cubane molecular catalyst for photoinduced water oxidation.

A new tetracobalt(III) cubane 1, carrying functionalized peripheral ethynyl groups, was prepared. Cubane 1 catalyses photoinduced water oxidation, indicating that the ethynyl groups do not negatively affect the catalytic properties of the Co cubane assembly. In contrast, the quantum yield for water oxidation (0.36) is significantly increased with respect to the prototype, simplest species.

Direct synthesis of C3-mono-functionalized oxindoles from N-unprotected 2-oxindole and their antileishmanial activity.

A novel approach for the synthesis of unprecedented C3-mono-functionalized indolin-2-ones is reported, starting from 2-oxindole and chalcones. The reactions proceed regioselectively under mild conditions, without di- and tri-alkylated side products. The new compounds have been evaluated in vitro for their antiproliferative effects against the protozoan Leishmania infantum. Interestingly, they appear able to kill L. infantum promastigotes and amastigotes, without significant cytotoxic effects.

Fast transport of HCl across a hydrophobic layer over macroscopic distances by using a Pt(II) compound as the transporter.

[Pt(H-(ethyl)2-dithiooxamidate)2] plays the role of a HCl symporter, allowing fast HCl transport over macroscopic distances (cm scale) across a hydrophobic layer made of a chloroform solution, without any stirring. The process is limited by interfacial transfer, whereas HCl is transported within the hydrophobic phase at extremely high rates.

Aldol-type compounds from water-soluble indole-3,4-diones: synthesis, kinetics, and antiviral properties.

A straightforward transformation of indole-3,4-diones is reported. The reaction feasibility is evidenced by kinetic studies on a model substrate, revealing a double phase process with a first faster pseudo-first-order step (i.e., deprotonation of the dione and self-nucleophilic attack of the anion) and a subsequent slower dehydration of the intermediate. The overall process is faster at pH higher than the pK value of the investigated substrate. The biological relevance of new compounds has been assessed in vitro against herpes simplex virus type-1 (HSV-1), showing a more promising biological profile with respect to their precursors.

Self-catalyzed Mannich-type reaction of enolizable cyclic 1,3-dicarbonyls to acyclic nitrones: an entry to functionalized ß-enamino diones.

A new method for the preparation of highly functionalized ß-enamino diones has been developed. The protocol involves an initial self-catalyzed Mannich-type reaction of enolizable cyclic 1,3-dicarbonyls to nitrones, followed by a spontaneous intramolecular reorganization of the resulting nonisolated hydroxylamine to enamino derivatives. These compounds retain the features of unnatural α-amino acids. The ease of preparation makes them attractive intermediates for the synthesis of peptidomimetics, polyheterocycles, and other multifunctional compounds. All experimental results have been efficiently rationalized by in silico studies at the M06-2X level of theory, and a valid mechanistic pathway has been proposed.

Diastereoselective multicomponent synthesis and anti-HSV-1 evaluation of dihydrofuran-fused derivatives.

Enolizable 6-membered cyclic 1,3-dicarbonyls undergo an efficient and diastereoselective domino condensation/addition/heterocyclization reaction with arylaldehydes and phenacyl chloride, producing highly substituted dihydrofuran-fused derivatives. Ring size of the cyclic 1,3-dicarbonyls and the presence of at least one keto group are crucial to the reaction's success. The new compounds were evaluated in vitro for antiviral activity against herpes simplex virus type-1 (HSV-1). Interestingly, some of them appeared able to interfere with HSV-1 replication, without detection of cytotoxic effects.

A functionalized enol lactone containing a protected α-amino acid.

The crystal structure of N-(3,9-dimethyl-4-phenyl-2,5-dioxo-3,4-dihydro-2H,5H-pyrano[3,2-c]chromen-3-yl)-N-methylbenzamide methanol monosolvate, C(28)H(23)NO(5)·CH(3)OH, has been determined at room temperature by X-ray diffraction. Structural parameters are discussed with reference to ab initio calculations.