Impact of Halogen Termination and Chain Length on π-Electron Conjugation and Vibrational Properties of Halogen-Terminated Polyynes.

We explored the optoelectronic and vibrational properties of a new class of halogen-terminated carbon atomic wires in the form of polyynes using UV-vis, infrared absorption, Raman spectroscopy, X-ray single-crystal diffraction, and DFT calculations. These polyynes terminate on one side with a cyanophenyl group and on the other side, with a halogen atom X (X = Cl, Br, I). We focus on the effect of different halogen terminations and increasing lengths (i.e., 4, 6, and 8 sp-carbon atoms) on the π-electron conjugation and the electronic structure of these systems. The variation in the sp-carbon chain length is more effective in tuning these features than changing the halogen end group, which instead leads to a variety of solid-state architectures. Shifts between the vibrational frequencies of samples in crystalline powders and in solution reflect intermolecular interactions. In particular, the presence of head-to-tail dimers in the crystals is responsible for the modulation of the charge density associated with the π-electron system, and this phenomenon is particularly important when strong I··· N halogen bonds occur.

Molecular Mechanism of the Piezoelectric Response in the ß-Phase PVDF Crystals Interpreted by Periodic Boundary Conditions DFT Calculations.

A theoretical approach based on Periodic Boundary Conditions (PBC) and a Linear Combination of Atomic Orbitals (LCAO) in the framework of the density functional theory (DFT) is used to investigate the molecular mechanism that rules the piezoelectric behavior of poly(vinylidene fluoride) (PVDF) polymer in the crystalline ß-phase. We present several computational tests highlighting the peculiar electrostatic potential energy landscape the polymer chains feel when they change their orientation by a rigid rotation in the lattice cell. We demonstrate that a rotation of the permanent dipole through chain rotation has a rather low energy cost and leads to a lattice relaxation. This justifies the macroscopic strain observed when the material is subjected to an electric field. Moreover, we investigate the effect on the molecular geometry of the expansion of the lattice parameters in the (a, b) plane, proving that the rotation of the dipole can take place spontaneously under mechanical deformation. By band deconvolution of the IR and Raman spectra of a PVDF film with a high content of ß-phase, we provide the experimental phonon wavenumbers and relative band intensities, which we compare against the predictions from DFT calculations. This analysis shows the reliability of the LCAO approach, as implemented in the CRYSTAL software, for calculating the vibrational spectra. Finally, we investigate how the IR/Raman spectra evolve as a function of inter-chain distance, moving towards the isolated chain limit and to the limit of a single crystal slab. The results show the relevance of the inter-molecular interactions on the vibrational dynamics and on the electro-optical features ruling the intensity pattern of the vibrational spectra.

Insights into the Safety and Versatility of 4D Printed Intravesical Drug Delivery Systems.

This paper focuses on recent advancements in the development of 4D printed drug delivery systems (DDSs) for the intravesical administration of drugs. By coupling the effectiveness of local treatments with major compliance and long-lasting performance, they would represent a promising innovation for the current treatment of bladder pathologies. Being based on a shape-memory pharmaceutical-grade polyvinyl alcohol (PVA), these DDSs are manufactured in a bulky shape, can be programmed to take on a collapsed one suitable for insertion into a catheter and re-expand inside the target organ, following exposure to biological fluids at body temperature, while releasing their content. The biocompatibility of prototypes made of PVAs of different molecular weight, either uncoated or coated with Eudragit®-based formulations, was assessed by excluding relevant in vitro toxicity and inflammatory response using bladder cancer and human monocytic cell lines. Moreover, the feasibility of a novel configuration was preliminarily investigated, targeting the development of prototypes provided with inner reservoirs to be filled with different drug-containing formulations. Samples entailing two cavities, filled during the printing process, were successfully fabricated and showed, in simulated urine at body temperature, potential for controlled release, while maintaining the ability to recover about 70% of their original shape within 3 min.

A Combined Raman Spectroscopy and Atomic Force Microscopy System for In Situ and Real-Time Measures in Electrochemical Cells.

An innovative and versatile set-up for in situ and real time measures in an electrochemical cell is described. An original coupling between micro-Raman spectroscopy and atomic force microscopy enables one to collect data on opaque electrodes. This system allows for the correlation of topographic images with chemical maps during the charge exchange occurring in oxidation/reduction processes. The proposed set-up plays a crucial role when reactions, both reversible and non-reversible, are studied step by step during electrochemical reactions and/or when local chemical analysis is required.

Development of Tailored Graphene Nanoparticles: Preparation, Sorting and Structure Assessment by Complementary Techniques.

We present a thorough structural characterization of Graphene Nano Particles (GNPs) prepared by means of physical procedures, i.e., ball milling and ultra-sonication of high-purity synthetic graphite. UV-vis absorption/extinction spectroscopy, Dynamic Light Scattering, Transmission Electron Microscopy, IR and Raman spectroscopies were performed. Particles with small size were obtained, with an average lateral size = 70−120 nm, formed by few = 1−10 stacked layers, and with a small number of carboxylic groups on the edges. GNPs relatively more functionalized were separated by centrifugation, which formed stable water dispersions without the need for any surfactant. A critical reading and unified interpretation of a wide set of spectroscopic data was provided, which demonstrated the potential of Specular Reflectance Infrared Spectroscopy for the diagnosis and quantification of chemical functionalization of GNPs. Raman parameters commonly adopted for the characterization of graphitic materials do not always follow a monotonic trend, e.g., with the particle size and shape, thus unveiling some limitations of the available spectroscopic metrics. This issue was overcome thanks to a comparative spectra analysis, including spectra deconvolution by means of curve fitting procedures, experiments on reference materials and the exploitation of complementary characterization techniques.

Conducting Electrospun Nanofibres: Monitoring of Iodine Doping of P3HT through Infrared (IRAV) and Raman (RaAV) Polaron Spectroscopic Features.

Aligned polymer nanofibres are prepared by means of the electrospinning of a chlorobenzene solution containing regioregular poly(3-hexyltiophene-2,5-diyl), P3HT, and poly(ethylene oxide), PEO. The PEO scaffold is easily dissolved with acetonitrile, leaving pure P3HT fibres, which do not show structural modification. Polymer fibres, either with or without the PEO supporting polymer, are effectively doped by exposure to iodine vapours. Doping is monitored following the changes in the doping-induced vibrational bands (IRAVs) observed in the infrared spectra and by means of Raman spectroscopy. Molecular orientation inside the fibres has been assessed by means of IR experiments in polarised light, clearly demonstrating that electrospinning induces the orientation of the polymer chains along the fibre axis as well as of the defects introduced by doping. This work illustrates a case study that contributes to the fundamental knowledge of the vibrational properties of the doping-induced defects-charged polarons-of P3HT. Moreover, it provides experimental protocols for a thorough spectroscopic characterisation of the P3HT nanofibres, and of doped conjugated polymers in general, opening the way for the control of the material structure when the doped polymer is confined in a one-dimensional architecture.

Morphology and Intramolecular Interactions in P(VDF-TrFE) Electrospun Nanofibers Doped with Disperse Orange 3 Dye: A Joint Infrared Spectroscopy and Electron Microscopy Study.

In this study, we describe a host-guest system consisting of a push-pull dye, the 4-amino-4'-nitroazobenzene (Disperse Orange 3, DO3), mixed with the copolymer poly(vinylidene fluoride-co-trifluoroethylene) [P(VDF-TrFE)] as a potential candidate for nonlinear optics (NLO) applications. We developed electrospun nanofibers of the polymer/dye blend, showing a highly anisotropic molecular structure, where DO3 molecules are mostly oriented parallel to the polymer chain, running in the fiber axis direction. The technique opens a way for obtaining non-centrosymmetric ordering of the NLO chromophore without requiring further poling. The supramolecular architecture is deeply investigated through infrared vibrational spectroscopy, which allows detecting a new phase involving DO3 molecules linked together by strong directional H-bonds. Electron microscopies highlight peculiar nanofiber morphologies with a preferred localization of DO3 at the surface layers.

Non-destructive Monitoring of Dye Depth Profile in Mesoporous TiO2 Electrodes of Solar Cells with Micro-SORS.

The dye distribution within a photo-electrode is a key parameter in determining the performances of dye-sensitized photon-to-electron conversion devices, such as dye-sensitized solar cells (DSSCs). A traditional, depth profiling investigation by destructive means including cross-sectional sampling is unsuitable for large quality control applications in manufacturing processes. Therefore, a non-destructive monitoring of the dye depth profile is required, which is the first step toward a non-destructive evaluation of the internal degradation of the device in the field. Here, we present a conceptual demonstration of the ability to monitor the dye depth profile within the light active layer of DSSCs by non-destructive means with high chemical specificity using a recently developed non-destructive/non-invasive Raman method, micro-spatially offset Raman spectroscopy (micro-SORS). Micro-SORS is able to probe through turbid materials, providing the molecular identification of compounds located under the surface, without the need of resorting to a cross-sectional analysis. The study was performed on the photo-electrode of DSSCs. This represents the first demonstration of the micro-SORS concept in the solar cell area as well as, more generally, the application of micro-SORS to the thinnest layer to date. A sample set has been prepared with varying concentrations of the dye and the thickness of the matrix consisting of a titanium dioxide layer. The results showed that micro-SORS can unequivocally discriminate between the homogeneous and inhomogeneous dye depth profiles. Moreover, micro-SORS outcomes have been compared with the results obtained with destructive time-of-flight secondary ion mass spectrometry measurements. The results of the two techniques are in good agreement, confirming the reliability of micro-SORS analysis. Therefore, this study is expected to pave the way for establishing a wider and more effective monitoring capability in this important field.

Real-World Evidence on Disease Burden and Economic Impact of Sickle Cell Disease in Italy.

A real-world analysis was conducted in Italy among sickle cell disease (SCD) patients to evaluate the epidemiology of SCD, describe patients' characteristics and the therapeutic and economic burden. A retrospective analysis of administrative databases of various Italian entities was carried out. All patients with ≥1 hospitalization with SCD diagnosis were included from 01/2010-12/2017 (up to 12/2018 for epidemiologic analysis). The index date corresponded to the first SCD diagnosis. In 2018, SCD incidence rate was 0.93/100,000, the prevalence was estimated at 13.1/100,000. Overall, 1816 patients were included. During the 1st year of follow-up, 50.7% of patients had one all-cause hospitalization, 27.8% had 2, 10.4% had 3, and 11.1% had ≥4. Over follow-up, 6.1-7.2% of patients were treated with SCD-specific, 58.4-69.4% with SCD-related, 60.7-71.3% with SCD-complications-related drugs. Mean annual number per patient of overall treatments was 14.9 ± 13.9, hospitalizations 1.1 ± 1.1, and out-patient services 5.3 ± 7.6. The total mean direct cost per patient was EUR 7918/year (EUR 2201 drugs, EUR 3320 hospitalizations, and EUR 2397 out-patient services). The results from this real-world analysis showed a high disease burden for SCD patients with multiple hospitalizations during the follow-up. High healthcare resource utilization and costs were associated with patient' management and were most likely underestimated since indirect costs and Emergency Room admissions were not included.

Driving Organic Nanocrystals Dissolution Through Electrochemistry.

We have recently discussed how organic nanocrystal dissolution appears in different morphologies and the role of the solution pH in the crystal detriment process. We also highlighted the role of the local molecular chemistry in porphyrin nanocrystals having comparable structures: in water-based acid solutions, protonation of free-base porphyrin molecules is the driving force for crystal dissolution, whereas metal (ZnII ) porphyrin nanocrystals remain unperturbed. However, all porphyrin types, having an electron rich π-structure, can be electrochemically oxidized. In this scenario, a key question is: does electrochemistry represent a viable strategy to drive the dissolution of both free-base and metal porphyrin nanocrystals? In this work, by exploiting electrochemical atomic force microscopy (EC-AFM), we monitor in situ and in real time the dissolution of both free-base and metal porphyrin nanocrystals, as soon as molecules reach the oxidation potential, showing different regimes according to the applied EC potential.

Tuning the Solubility Parameters of Carbon Nanotubes by Means of Their Adducts with Janus Pyrrole Compounds.

The solubility parameters of multiwalled carbon nanotubes (CNTs) was tuned via their chemical modification with pyrrole compounds (PyCs), by means of a simple and sustainable methodology. PyCs were synthesized with high atom efficiency through the Paal-Knorr reaction of primary amines with 2,5-hexanedione, in the absence of solvents and catalysts. Methylamine, 1-dodecylamine, 2-amino-1,3-propanediol, and 3-(triethoxysilyl)propan-1-amine were selected. PyCs are characterized by two moieties, the pyrrole ring and the substituent of the nitrogen atom, and can be considered as Janus molecules. The functionalization of CNTs occurred with a high yield by simply heating CNTs and PyC. The whole reaction pathway did not produce any waste and was characterized by a carbon efficiency up to almost 100%. Thanks to the variety of PyC chemical structures, the CNT solubility parameter was modified in a pretty broad range of values, in the expected direction. Stable CNT dispersions were prepared in different solvents. From the aqueous dispersion, coating layers were prepared with high electrical conductivity, larger with respect to a top commercial product. The "pyrrole methodology" reported here is based on one reaction and allows almost infinite variations of the CNT solubility parameter, thus promoting their compatibility with target matrices and allowing the preparation of nanocomposite materials with improved properties. This work thus paves the way for a highly efficient exploitation of CNTs.

Color polymorphism in organic crystals.

Color polymorphism is an interesting property of chemical systems which present crystal polymorphs of different colors. It is a rare phenomenon, with only a few examples reported in the literature hitherto. Nevertheless, systems exhibiting color polymorphism have many potential applications in different domains, such as pigment, sensor, and technology industries. Here, known representative chemical systems showing color polymorphism are reviewed, and the reasons for them to present such property discussed. Also, since some of the concepts related to color polymorphism have been frequently used imprecisely in the scientific literature, this article provides concise, systematic definitions for these concepts.

P(VDF-TrFE) nanofibers: structure of the ferroelectric and paraelectric phases through IR and Raman spectroscopies.

This study elucidates the complex morphology and the related spectroscopic response of poly(vinylidene fluoride-co-trifluoroethylene) copolymer, with 80% molar VDF content, namely P(VDF-TrFE) (80/20). We investigate the molecular structure, the morphology and the thermal behaviour of P(VDF-TrFE) samples obtained as electrospun nanofibers; we discuss their thermal evolution crossing the Curie temperature and the structure resulting after annealing, giving a comparison with P(VDF-TrFE) films. The new experimental data here obtained, combined with previous spectroscopic studies carried out on piezoelectric fluorinated polymers and copolymers, allow identifying spectroscopic markers sensitive to the molecular structure, the molecular orientation, the conformational defects and the kind of crystalline phase. We assign the vibrational modes localized on TrFE units by combining experimental observation and density functional calculations carried out on suitable molecular models. This work provides a sound set of diagnostic tools, which can be exploited for the assessment of structure/property relationships aimed at clarifying the molecular mechanisms leading to the piezoelectric performance of fluorinated copolymers.

Stone/Coating Interaction and Durability of Si-Based Photocatalytic Nanocomposites Applied to Porous Lithotypes.

The use of hybrid nanocoatings for the protection of natural stones has received increasing attention over the last years. However, the interaction of these materials with stones and, in particular, its modification resulting from the blending of nanoparticles and matrices, are yet little explored. In this work, the interaction of two nanocomposite coatings (based on alkylalkoxysilane matrices and TiO2 nanoparticles in water and 2-propanol) with two different porous stones is examined in detail by comparing their absorption behaviour and protection performance with those of the respective TiO2-free matrices. It is shown that the protective effectiveness of both matrices is not negatively affected by the presence of TiO2, as the desired water barrier effect is retained, while a significant photocatalytic activity is achieved. The addition of titania leads to a partial aggregation of the water-based matrix and accordingly reduces the product penetration into stones. On the positive side, a chemical interaction between titania and this matrix is observed, probably resulting in a greater stability of nanoparticles inside the protective coating. Moreover, although an effect of TiO2 on the chemical stability of matrices is observed upon UV light exposure, the protective performance of coatings is substantially maintained after ageing, while the interaction between matrices and nanoparticles results in a good retention of the latter upon in-lab simulated rain wash-out.

Domino Reaction for the Sustainable Functionalization of Few-Layer Graphene.

The mechanism for the functionalization of graphene layers with pyrrole compounds was investigated. Liquid 1,2,5-trimethylpyrrole (TMP) was heated in air in the presence of a high surface area nanosized graphite (HSAG), at temperatures between 80 °C and 180 °C. After the thermal treatments solid and liquid samples, separated by centrifugation, were analysed by means of Raman, Fourier Transform Infrared (FT-IR) spectroscopy, X-Rays Photoelectron Spectroscopy (XPS) and ¹H-Nuclear Magnetic Resonance (¹H NMR) spectroscopy and High Resolution Transmission Electron Microscopy (HRTEM). FT-IR spectra were interpreted with the support of Density Functional Theory (DFT) quantum chemical modelling. Raman findings suggested that the bulk structure of HSAG remained substantially unaltered, without intercalation products. FT-IR and XPS spectra showed the presence of oxidized TMP derivatives on the solid adducts, in a much larger amount than in the liquid. For thermal treatments at T ≥ 150 °C, IR spectral features revealed not only the presence of oxidized products but also the reaction of intra-annular double bond of TMP with HSAG. XPS spectroscopy showed the increase of the ratio between C(sp²)N bonds involved in the aromatic system and C(sp³)N bonds, resulting from reaction of the pyrrole moiety, observed while increasing the temperature from 130 °C to 180 °C. All these findings, supported by modeling, led to hypothesize a cascade reaction involving a carbocatalyzed oxidation of the pyrrole compound followed by Diels-Alder cycloaddition. Graphene layers play a twofold role: at the early stages of the reaction, they behave as a catalyst for the oxidation of TMP and then they become the substrate for the cycloaddition reaction. Such sustainable functionalization, which does not produce by-products, allows us to use the pyrrole compounds for decorating sp² carbon allotropes without altering their bulk structure and smooths the path for their wider application.

Combining Static and Dynamical Approaches for Infrared Spectra Calculations of Gas Phase Molecules and Clusters.

Four models for the calculation of the IR spectrum of gas phase molecules and clusters from molecular dynamics simulations are presented with the aim to reduce the computational cost of the usual Fourier transform (FT) of the time correlation function of the dipole moment. These models are based on the VDOS, FT of time correlation function of velocities, and atomic polar tensors (APT). The models differ from each other by the number of APTs inserted into the velocities correlation function. Excellent accuracy is achieved by the model adopting a weighted linear combination of a few selected APTs adapted for the rotation of the molecule (model D). The achieved accuracy relates to band positions, band shapes, and band intensities. Depending on the degree of actual dynamics of the molecule, rotational motion, conformational isomerization, and large amplitude motions that can be seen during the finite temperature trajectory, one could also apply one of the other models (models A, B, or C), but with caution. Model D is therefore found simple and accurate, with appealing computational cost and should be systematically applied. Its generalization to condensed phase systems should be straightforward.

Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers.

A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra®) after single-dose administration to 53 healthy male volunteers (aged 18-51 years) in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax) and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0-t) of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration-time profiles up to 24 h after single-dose administration of sildenafil 100 mg orodispersible film and film-coated tablet were nearly superimposable. The bioequivalence test was fully satisfied for sildenafil and N-desmethyl-sildenafil in terms of rate and extent of bioavailability. Adverse events occurred at similar rates for the two formulations and were of mild-to-moderate severity. The results suggest that the new orodispersible film formulation can be used interchangeably with the conventional film-coated formulation.

Static vs dynamic DFT prediction of IR spectra of flexible molecules in the condensed phase: The (ClCF2CF(CF3)OCF2CH3) liquid as a test case.

First-principles molecular dynamics (FPMD) simulations in the framework of Density Functional Theory (DFT) are carried out for the prediction of the infrared spectrum of the fluorinated molecule ClCF2CF(CF3)OCF2CH3 in liquid and gas phase. This molecule is characterized by a flexible structure, allowing the co-existence of several stable conformers, that differ by values of the torsional angles. FPMD computed spectra are compared to the experimental ones, and to Boltzmann weighted IR spectra based on gas phase calculations.

Intermolecular modulation of IR intensities in the solid state. The role of weak interactions in polyethylene crystal: A computational DFT study.

Density functional theory calculations with periodic boundary conditions are exploited to study the infrared spectrum of crystalline polyethylene. Spectral changes lead by the intermolecular packing in the orthorhombic three-dimensional crystal are discussed by means of a careful comparison with calculations carried out for an isolated polymer chain in the all-trans conformation, described as an ideal one-dimensional crystal. The results are analyzed in the framework of the "oligomer approach" through the modelling of the IR spectrum of n-alkanes of different lengths. The study demonstrates that a relevant absorption intensity modulation of CH2 deformation transitions takes place in the solid state. This finding suggests a new interpretation for the experimental evidences collected in the past by means of IR intensity measurement during thermal treatment. Moreover, the comparison between calculations for 3-D crystal and for the isolated polyethylene chain (1-D crystal) allows to put in evidence the effect of the local electric field on the computed infrared intensities. This observation provides guidelines for the comparison between infrared absorption intensities predicted for an isolated unit and for a molecule belonging to a crystal, through the introduction of suitable correction factors based on the refraction index of the material and depending on the dimensionality of such units (0D-molecule; 1D-polymer; 2D-slab).