Luca Fusaro

A polyhedral oligomeric silsesquioxane-based catalyst for the efficient synthesis of cyclic carbonates

Polyhedral oligomeric silsesquioxane functionalized with imidazolium chloride peripheries (POSS-Imi) was successfully synthesized through a novel synthesis protocol. The solid was extensively characterized via1H NMR, 13C NMR and IR spectroscopy as well as combustion chemical analysis, mass spectrometry and transmission electron microscopy. Moreover, an in-depth investigation through 29Si NMR was performed. POSS-Imi was used for the first time as a catalyst for the conversion of CO2 and epoxides into cyclic carbonates with excellent results in terms of both yield and selectivity. The catalyst displayed improved catalytic performance with respect to unsupported 1-butyl-3-methylimidazolium chloride. The enhanced activity was ascribed to the proximity effect generated by the increased local concentration of imidazolium species surrounding the inorganic silsesquioxane core.

NMR study of the reversible trapping of SF6 by cucurbit[6]uril in aqueous solution.

The complexation of sulfur hexafluoride (SF(6)), a highly potent greenhouse gas, by cucurbit[6]uril (CB) was studied at various temperatures in Na(2)SO(4) aqueous solutions by (19)F and (1)H NMR. CB shows a remarkable affinity for SF(6), suggesting that it is a suitable molecular container for the design of materials tailored for SF(6) trapping. At 298 K, the equilibrium constant characterizing the inclusion of SF(6) by CB is 3.1 x 10(4) M(-1) and the residence time of SF(6) within the CB cavity is estimated to be of the order of a few seconds. The enthalpic and entropic contributions to the free energy of encapsulation were determined and are discussed. This work also reports on the interest of SF(6) in the framework of the spin-spy methodology. The advantages and drawbacks of solution-state (19)F NMR of SF(6) with respect to (129)Xe NMR are discussed. SF(6) comes forward as a versatile and informative spin-spy molecule for probing systems in solution because its detection limit by (19)F NMR reaches the micromolar range with standard equipment and because quantitative integral measurements, relaxation time measurements, and demanding experiments, such as translational diffusion coefficient measurements, are easily carried out in addition to chemical shift measurements. Solution-state (19)F NMR of SF(6) emerges as a promising alternative to (129)Xe NMR for probing cavities and for other applications relying on the encapsulation of an NMR active gaseous probe.

Translocation-coupled transmetalation at the origin of a dinuclear lead porphyrin complex: implication of a hanging-atop coordination mode

Translocation of a lead cation from the N-core of a porphyrin to a hanging carboxylate group is coupled to a transmetalation process with a second lead cation, leading to a dinuclear species. A novel hanging-atop coordination mode is responsible for the dynamic and stereocontrolled binding of lead to the porphyrin core.

Acid–Base‐Controlled Stereoselective Metalation of Overhanging Carboxylic Acid Porphyrins: Consequences for the Formation of Heterobimetallic Complexes

Overhanging carboxylic acid porphyrins have revealed promising ditopic ligands offering a new entry in the field of supramolecular coordination chemistry of porphyrinoids. Notably, the adjunction of a so-called hanging-atop (HAT) Pb(II) cation to regular Pb(II) porphyrin complexes allowed a stereoselective incorporation of the N-core bound cation, and an allosterically controlled Newtons cradle-like motion of the two Pb(II) ions also emerged from such bimetallic complexes. In this contribution, we have extended this work to other ligands and metal ions, aiming at understanding the parameters that control the HAT Pb(II) coordination. The nature of the N-core bound metal ion (Zn(II), Cd(II)), the influence of the deprotonation state of the overhanging COOH group and the presence of a neutral ligand on the opposite side (exogenous or intramolecular), have been examined through (1)H NMR spectroscopic experiments with the help of radiocrystallographic structures and DFT calculations. Single and bis-strap ligands have been considered. They all incorporate a COOH group hung over the N-core on one side. For the bis-strap ligands, either an ester or an amide group has been introduced on the other side. In the presence of a base, the mononuclear Zn(II) or Cd(II) complexes incorporate the carbonyl of the overhanging carboxylate as apical ligand, decreasing its availability for the binding of a HAT Pb(II). An allosteric effector (e.g., 4-dimethylaminopyridine (DMAP), in the case of a single-strap ligand) or an intramolecular ligand (e.g., an amide group), strong enough to compete with the carbonyl of the hung COO(-), is required to switch the N-core bound cation to the opposite side with concomitant release of the COO(-), thereby allowing HAT Pb(II) complexation. In the absence of a base, Zn(II) or Cd(II) binds preferentially the carbonyl of the intramolecular ester or amide groups in apical position rather than that of the COOH. This better preorganization, with the overhanging COOH fully available, is responsible for a stronger binding of the HAT Pb(II). Thus, either allosteric or acid-base control is achieved through stereoselective metalation of Zn(II) or Cd(II). In the latter case, according to the deprotonation state of the COOH group, the best electron-donating ligand is located on one or the other side of the porphyrin (COO(-)>CONHR>COOR>COOH): the lower affinity of COOH for Zn(II) and Cd(II), the higher for a HAT Pb(II). These insights provide new opportunities for the elaboration of innovative bimetallic molecular switches.

High-Yield Synthesis of Ethyl Lactate with Mesoporous Tin Silicate Catalysts Prepared by an Aerosol-Assisted Sol-Gel Process

An aerosol‐assisted sol–gel method is used to prepare mesoporous tin silicate catalysts that exhibit a record activity in the synthesis of ethyl lactate from dihydroxyacetone and ethanol. The method is based on the formation of an aerosol from a solution of precursors and surfactant. During the fast drying of the droplets, the surfactant self‐assembles and the Sn‐silica matrix is formed by polycondensation reactions. After calcination, the resulting material is composed of a true tin‐silicon mixed oxide in the form of spherical microparticles with calibrated mesopores of 5–6 nm. Sn species are incorporated in the silica network, mainly in the form of single sites. This makes these catalysts highly active for the targeted reaction, as shown by record turnover numbers. The catalyst is recyclable and truly heterogeneous as it can be reused for several cycles and it does not leach.

Insight into the dynamics of lanthanide-DTPA complexes as revealed by oxygen-17 NMR.

DTPA chelates of various diamagnetic and paramagnetic lanthanide(III) metal ions, as well as the chemically similar DTPA chelate of Y(3+), were studied in aqueous solution by variable temperature (17)O NMR with the aim of characterizing their internal dynamics. As a consequence of poor chemical shift dispersion and fast quadrupole relaxation, no dynamic exchange process could be detected for the diamagnetic complexes nor for the Sm-DTPA complex. In contrast, the spectra recorded for the Eu-DTPA complex show chemical exchange due to the well-known racemization process and, at high temperature, feature signal broadening that reveals a fluxional process involving the interchange of the coordinated and noncoordinated oxygen atoms of the carboxylate groups. The spectra recorded for the Pr-DTPA complex feature coalescence events due to such a fluxional process, which is ascribable to the rotation of the carboxylate groups. The activation free energy barriers determined experimentally are remarkably lower than the calculated activation barriers recently reported for the rotation of the carboxylate groups of various Ln-DOTA complexes. Furthermore, the smallest activation free energy measured for the Pr-DTPA complex, about 45 kJ mol(-1), is significantly lower than the activation free energy characterizing the racemization process. The fluxional behavior of the carboxylate groups is, however, not expected to significantly affect the residence time of the water molecule coordinated to the metal ion.

Supramolecular Assistance for the Selective Monofunctionalization of a Calix[6]arene Tris-carboxylic Acid-Based Receptor

The selective functionalization of macrocyclic receptors remains extremely challenging because it generally requires the transformation of one and only one functional group among several identical groups. Recently, some of us described that the host-guest properties of a calix[6]arene-based Zn complex could be exploited for its selective monofunctionalization. Herein, we report on the extension of this synthetic strategy to a calix[6]arene-based receptor displaying a different recognition pattern with its guest. More precisely, a calix[6]arene tris-carboxylic acid-based receptor bearing three azido groups at the large rim was selectively monofunctionalized through an intramolecular thermal Huisgen reaction with a hexynNH3(+) ion accommodated into the cavity. This work shows that the monofunctionalization methodology can also be performed efficiently with host-guest systems involving ionic/H-bonding interactions, and it is thus not limited only to the use of metal-ligand interactions. In other words, this supramolecular methodology can be used as a general tool for the selective functionalization of molecular receptors.

Development of controlled-release cisplatin dry powders for inhalation against lung cancers.

The present study focuses on the development of dry powders for inhalation as adjuvant chemotherapy in lung cancer treatment. Cisplatin was chosen as a potential candidate for a local treatment as it remains the main platinum component used in conventional chemotherapies, despite its high and cumulative systemic toxicities. Bulk cisplatin was reduced to submicron sizes using high-pressure homogenization, mixed with a solubilized lipid and/or PEGylated component and then spray-dried to produce controlled-release dry powder formulations. The obtained formulations were characterized for their physicochemical properties (particle size and morphology), aerodynamic performance and release profiles. Cisplatin content and integrity were assessed by electrothermal atomic absorption spectrometry and 195Pt nuclear magnetic resonance spectroscopy. DPI formulations with cisplatin contents ranging from 48.5 to 101.0% w/w exhibited high fine particle fractions ranging from 37.3% to 51.5% of the nominal dose. Formulations containing cisplatin microcrystals dispersed in solid lipid microparticles based on acceptable triglycerides for inhalation and PEGylated excipients showed a controlled-release for more than 24h and a limited burst effect. These new formulations could provide an interesting approach to increasing and prolonging drug exposure in the lung while minimizing systemic toxicities.

Sunlight‐Driven Formation and Dissociation of a Dynamic Mixed‐Valence Thallium(III)/Thallium(I) Porphyrin Complex

Inspired by a Newtons cradle device and interested in the development of redox-controllable bimetallic molecular switches, a mixed-valence thallium(III)/thallium(I) bis-strap porphyrin complex, with Tl(III) bound out of the plane of the N core and Tl(I) hung to a strap on the opposite side, was formed by the addition of TlOAc to the free base and exposure to indirect sunlight. In this process, oxygen photosensitization by the porphyrin allows the oxidation of Tl(I) to Tl(III). The bimetallic complex is dynamic as the metals exchange their positions symmetrically to the porphyrin plane with Tl(III) funneling through the macrocycle. Further exposure of the complex to direct sunlight leads to thallium dissociation and to total recovery of the free base. Hence, the porphyrin plays a key role at all stages of the cycle of the complex: It hosts two metal ions, and by absorbing light, it allows the formation and dissociation of Tl(III). These results constitute the basis for the further design of innovative light-driven bimetallic molecular devices.

Dynamic NMR of low-sensitivity fast-relaxing nuclei: 17O NMR and DFT study of acetoxysilanes

17O NMR is not routinely used for structure characterization, and kinetic studies of fluxional organic compounds are seldom undertaken because poor sensitivity and fast quadrupole relaxation are frequently regarded as intractable issues. This work shows how, nowadays, quantitative 17O dynamic NMR studies on small organic molecules are feasible without enrichment being needed. It reports on acetoxysilanes, a class of fluxional compounds whose structure and dynamics were to be clarified. Natural abundance 17O NMR spectra were recorded over a wide range of temperatures using standard instrumentation. The analysis relies on simple linewidth measurements and directly provides the activation parameters. The activation enthalpy is found to decrease with increasing number of acetoxy groups bound to silicon. Density functional theory calculations properly predict this trend and show that a single oxygen atom of the acetoxy group is bound to silicon, excluding chelation as binding mode, and that the dynamic process involves the shift of the silicon atom between the two oxygen atoms of the acetoxy group. Copyright