Alessandro Di Michele

Nickel Catalysts Supported Over TiO2, SiO2 and ZrO2 for the Steam Reforming of Glycerol

Ni‐based catalysts supported on TiO2, ZrO2 and SiO2 (in the form of mesoporous Santa Barbara Amorphous 15 (SBA‐15) and amorphous dense nanoparticles), were employed in the steam reforming of glycerol. Each sample was prepared by liquid phase synthesis of the support followed by impregnation with the active phase and calcination at 800 °C or by direct synthesis through flame pyrolysis. Many techniques have been used to assess the physical chemical properties of both the fresh and spent catalysts, such as atomic absorption, N2 adsorption/desorption, XRD, SEM, TEM, temperature‐programmed reduction (TPR), X‐ray photoelectron spectroscopy (XPS), Micro‐Raman and FTIR spectroscopy. The samples showed different textural, structural and morphological properties, as well as different reducibility and thermal resistance depending on the preparation method and support. Some of these properties were tightly bound to catalyst performance, in terms of H2 productivity and stability towards coking and sintering. A key parameter was the metal–support interaction, which strongly depended on the preparation procedure. In particular, the stronger the interaction, the more stable the metallic Ni clusters, which in turn lead to a higher catalytic activity and stability. Surface acidity was also taken into account, in which the nature of the acid sites was differentiated (silanols, titanols or Lewis acid sites). The characterisation of the spent catalysts also allowed us to interpret the deactivation process. The formation of multi‐walled nanotubes was observed for every sample, though it was only in some cases that this led to severe deactivation.

Effect of head group size, temperature and counterion specificity on cationic micelles.

The critical micelle concentration (cmc) and ionisation degree (α), of micelles of cetyltrimethylammonium bromide (CTABr), cetyltrimethylammonium chloride (CTACl), cetyltripropylammonium bromide (CTPABr) and cetyltripropylammonium chloride (CTPACl) have been measured over a narrow temperature range at 2 degree intervals using electrical conductivity. CTPACl and CTPABr are very soluble in water and were measured in the temperature range 275.15-323.15K. The Krafft temperatures for CTABr and for CTACl are 293.15K and 284.15K, respectively and established a lower temperature limit for our studies on these two surfactants. The cmc vs temperature curves have a smooth minimum near room temperature and α linearly increases with temperature. The changes of cmc and α with temperature are smaller than those associated with the modification of head group size or counterion nature. Using these results, basic thermodynamic quantities associated with the phenomena of micellization have been evaluated. Thermodynamic properties of the surfactant solutions were discussed in terms of temperature dependence of the free energy, enthalpy and entropy of micellization. A close similarity between the effects of change in temperature on protein folding and micellization process appears from the data.

Determination of bile salt critical micellization concentration on the road to drug discovery.

With the discovery of the bile acid (BA)-activated nuclear and membrane receptors, the role of BAs as signalling molecules in important paracrine and endocrine networks has been fully documented in the last decade. Besides regulating their own synthesis and transport, BAs have been demonstrated being involved in triggering the adaptive response to cholestasis and other insults to liver. More to the point, their recognized ability to control the general energy-related metabolism and inflammation processes has contributed to justify the renewed interest towards this class of amphiphilic steroidal compounds. All these evidences feed a continuing interest in the BA research aimed at designing and synthesizing new side chain- and body-modified derivatives endowed with improved biological and physico-chemical profiles, as well as with proper ADMET behaviour. In this context, the micellar aggregation of BAs, and the respective critical micellization concentration (CMC) value (determined on the BA sodium salt, BS), is considered a key parameter that needs to be determined in the preliminary phase of compound characterization, being implicated in cytotoxicity issues. An extraordinary variety of different analytical techniques and methods have been proposed along the years with the aim of better identifying the start of the self-aggregation process of BS monomers. The unicity of the physico-chemical nature of such class of compounds can be invoked to explain this unusual interest. Accordingly, a number of both invasive and non-invasive approaches have been developed along with a limited number of indirect chromatographic-based estimation strategies. Worth to be mentioned among the non-invasive determination methods are those based on potentiometry, freezing point depression, surface tension, nuclear magnetic resonance, viscosimetry, turbidimetry, microcalorimetry, refractometry, conductimetry, spectrophotometry, cholesterol solubilization, and monoglucuronide solubilization. Dye solubilization- and fluorescence-based methods deserve instead credit among the invasive methodological approaches. Indirect chromatographic methods based on capillary electrophoresis and high performance liquid chromatography analysis also demonstrated to be profitably exploited for the CMC estimation, especially when a small amount of sample is available. The collection of literature data reveals that the CMC value of a given BS is markedly related to the method selected for determining it as well as to the experimental conditions applied during the analysis.

Lipid nanoparticles for brain targeting II. Technological characterization.

The aim of this work was to characterize lipid nanoparticles from a rheological point of view, intended for drug delivery after parenteral administration. The conditions to obtain a re-dispersible powder using freeze-drying and spray-drying have also been investigated. Lipid nanoparticles (179.9±6.2nm) were prepared with the high pressure homogenization technique, using previously established optimal conditions (lipid volume fraction of 0.121), though particle size increased (285.9±4.3nm) in suspensions produced with higher lipid volume fractions (0.255). Rheology evidenced an expected increase of viscosity with the volume fraction and Newtonian behaviour was observed for volume fractions up to 0.161, while higher volume fractions showed shear thinning and shear thickening. In the suspension with a volume fraction of 0.255, a change of the complex modulus was observed at low shear stress. Freeze-drying and nano spray-drying were suitable only when trehalose was employed as an additive. In the former case, particle size was increased by 18% (198.7±1.1nm) using 20 fold water dilution. With spray-drying, the use of 20 fold dilution in water:ethanol (8:2) led to particle dimensions of 207.7 ±10.0 (Δsize 20%). In conclusion, cetylpalmitate nanoparticles seem to be suitable for parenteral application, up to volume fractions of 0.16, and pharmaceutical operations, which submit suspensions to shear stress, should not be a critical issue.

Stem cells from human amniotic fluid exert immunoregulatory function via secreted indoleamine 2,3-dioxygenase1

Although human amniotic fluid does contain different populations of foetal‐derived stem cells, scanty information is available on the stemness and the potential immunomodulatory activity of in vitro expanded, amniotic fluid stem cells. By means of a methodology unrequiring immune selection, we isolated and characterized different stem cell types from second‐trimester human amniotic fluid samples (human amniotic fluid stem cells, HASCs). Of those populations, one was characterized by a fast doubling time, and cells were thus designated as fHASCs. Cells maintained their original phenotype under prolonged in vitro passaging, and they were able to originate embryoid bodies. Moreover, fHASCs exhibited regulatory properties when treated with interferon (IFN)‐γ, including induction of the immunomodulatory enzyme indoleamine 2,3‐dioxygenase 1 (IDO1). On coculture with human peripheral blood mononuclear cells, IFN‐γ–treated fHASCs caused significantly decreased T‐cell proliferation and increased frequency in CD4+ CD25+ FOXP3+ regulatory T cells. Both effects required an intact IDO1 function and were cell contact‐independent. An unprecedented finding in our study was that purified vesicles from IFN‐γ–treated fHASCs abundantly expressed the functional IDO1 protein, and those vesicles were endowed with an fHASC‐like regulatory function. In vivo, fHASCs were capable of immunoregulatory function, promoting allograft survival in a mouse model of allogeneic skin transplantation. This was concurrent with the expansion of CD4+ CD25+ Foxp3+ T cells in graft‐draining lymph nodes from recipient mice. Thus fHASCs, or vesicles thereof, may represent a novel opportunity for immunoregulatory maneuvers both in vitro and in vivo.

Diastereo- and enantioseparation of a Nα-Boc amino acid with a zwitterionic quinine-based stationary phase: Focus on the stereorecognition mechanism

A chiral chromatography method enabling the simultaneous diastereo- and enantioseparation of N(α)-Boc-N(4)-(hydroorotyl)-4-aminophenylalanine [Boc-Aph(Hor)-OH, 1] was optimized with a quinine-based zwitterionic stationary phase. The polar-ionic eluent system consisting of ACN:MeOH:water-49.7:49.7:0.6 (v/v/v) with formic acid (4.0mM) and diethylamine (2.5mM), allowed the successful separation of the four acid stereoisomers: αd,d-/d,l-1=1.08; αd,l-/l,d-1=1.08; αl,d-/l,l-1=1.40. According to the in-house developed synthetic procedure and the recorded electronic circular dichroism spectra, the following stereoisomeric elution order was readily established in the optimal chromatographic conditions: d,d-1<d,l-1<l,d-1<l,l-1. With the aim of better understanding the molecular basis of the retention behaviour of the four stereoisomers in the employed chromatographic system and conditions, a computational protocol consisting in molecular dynamics simulations was applied. The use of the three descriptors INTER (in kcalmol(-1), encoding for the interaction energy between the selector SO unit and the whole system), INTER_SA (in kcalmol(-1), encoding for the interaction energy between SO and the sole selectand SA), and SELF (in kcalmol(-1), encoding for the conformational energy of SA relative to its minimum energy registered by the collected snapshots) revealed the active role of achiral sub-structural elements of the chiral stationary phase and eluent components in the overall stereorecognition mechanism.

Flame-pyrolysis-prepared catalysts for the steam reforming of ethanol

An innovative flame pyrolysis method was employed for the preparation of Ni-based catalysts for the steam reforming of ethanol. Titania and lanthana supports, characterised by variable acidity and Ni loading, were compared as well as the different procedures to add the Ni active phase to the support, thus affecting the metal dispersion. Samples characterisation provided evidence that the one-pot preparation of the catalyst by flame pyrolysis (FP) resulted in the formation of a mixed oxide phase and, thus, in a higher Ni dispersion, even at the highest loading. The metal–support interaction was also strengthened when preparing the samples by FP rather than by conventional impregnation. Steam reforming at 750 °C resulted in full ethanol conversion without by-products, such that a fuel processor able to feed a 5 kWe + 5 kWt fuel cell may operate with ca. 1.35 kg of catalyst. Tests at lower temperature were also carried out, focusing on the optimization of the resistance to coking. The best results at 500 °C were achieved for the FP-prepared sample supported over La2O3 and containing 15 wt% Ni as the active phase.

Bimetallic Ni–Cu Catalysts for the Low-Temperature Ethanol Steam Reforming: Importance of Metal–Support Interactions

The activity of bimetallic Ni–Cu catalysts in ethanol steam reforming was evaluated and compared to the activity of the corresponding monometallic Ni catalyst. Copper addition positively affected the catalytic activity only if the proper metal–support interactions, as well as the proper ratio between the different reducible species, were maintained. This target can be pursued by tuning the synthesis conditions.Graphical Abstract.

Metal Dispersion and Interaction with the Supports in the Coke Production Over Ethanol Steam Reforming Catalysts

Two families of Ni/TiO2 catalysts were prepared for use in the steam reforming of ethanol. The catalytic performances, in terms of both H2 productivity and stability towards coking and sintering, were related to the physico-chemical properties of the catalysts.

The “racemic approach” in the evaluation of the enantiomeric NorA efflux pump inhibition activity of 2-phenylquinoline derivatives

Among the mechanisms adopted by bacteria, efflux pumps (EPs) have been recognized as being significantly involved in contributing to resistance to commonly used antibacterial agents. However, little is known about their three-dimensional structures or the steric requirements for their inhibition. Lack of such knowledge includes NorA, one of the most studied Staphylococcus aureus EPs. In the present study, the use of two commercialized Cinchona alkaloid-based zwitterionic chiral stationary phases allowed the enantioseparation of four 2-((2-(4-propoxyphenyl)quinolin-4-yl)oxy)alkylamines 1-4 previously found to be potent S. aureus NorA efflux pump inhibitors when tested as racemates. In the identified optimal polar-ionic conditions (MeOH/THF/H2O-49/49/2 (v/v/v)+25mM formic acid, 12.5mM diethylamine), repeated consecutive injections of 1 allowed the isolation of sufficient amount of its enantiomers (2.6mg and 2.8mg, for (R)-1 and (S)-1, respectively) and then to evaluate their ability to inhibit the S. aureus NorA efflux pump. The biological evaluation highlighted the main contribution of the (R)-1 enantiomer to both the EtBr efflux inhibition and synergistic effect with against SA-1199B (norA+/A116E GrlA) respect to the racemate activity. The comparison between the experimental electronic circular dichroism and the time-dependent density functional theory calculations spectra of the two isolated enantiomeric fractions allowed for all compounds a clear and easy assignment of the enantiomeric elution order.