Pd-Catalyzed Miyaura Borylation and Telescopic Borylation/Suzuki-Miyaura Cross-Coupling Processes in Deep-Eutectic Solvents.

We report an efficient procedure to carry out palladium-catalyzed Miyaura borylation reactions of (hetero)aromatic halides and triflates in choline chloride (ChCl)-based deep eutectic solvents (DESs). The procedure employs bis(pinacolato)diboron as a boron source and a catalyst prepared in situ from readily available Pd2(dba)3 and the phosphine ligand XPhos. Reactions proceed well in different ChCl-based DESs, among which the best results were provided by environmentally friendly and biodegradable mixtures with glycerol and glucose. The reaction tolerates both EDG and EWG substituents on the substrates and can be run on different halides (chloride, bromide, iodide) and pseudohalides (triflate). Furthermore, for several substrates, the catalyst loading can be reduced to 1 mol % Pd (0.5% mol Pd2(dba)3) without compromising the reaction yield. Moreover, we show that the Miyaura borylation protocol in DES can be combined with a subsequent Suzuki-Miyaura cross-coupling reaction in a one-pot procedure, allowing access to various biaryl products and demonstrating its synthetic utility by preparing the precursors of two compounds with reported applications in the photovoltaics sector. Finally, two green metrics (E-factor and EcoScale) of the new one-pot procedure in DES were calculated and compared with literature values to assess the potential advantages in terms of waste reduction, safety, and energy consumption.

Recent Advances in Organic Dyes for Application in Dye-Sensitized Solar Cells under Indoor Lighting Conditions.

Among the emerging photovoltaic (PV) technologies, Dye-Sensitized Solar Cells (DSSCs) appear especially interesting in view of their potential for unconventional PV applications. In particular, DSSCs have been proven to provide excellent performances under indoor illumination, opening the way to their use in the field of low-power devices, such as wearable electronics and wireless sensor networks, including those relevant for application to the rapidly growing Internet of Things technology. Considering the low intensity of indoor light sources, efficient light capture constitutes a pivotal factor in optimizing cell efficiency. Consequently, the development of novel dyes exhibiting intense absorption within the visible range and light-harvesting properties well-matched with the emission spectra of the various light sources becomes indispensable. In this review, we will discuss the current state-of-the-art in the design, synthesis, and application of organic dyes as sensitizers for indoor DSSCs, focusing on the most recent results. We will start by examining the various classes of individual dyes reported to date for this application, organized by their structural features, highlighting their strengths and weaknesses. On the basis of this discussion, we will then draft some potential guidelines in an effort to help the design of this kind of sensitizer. Subsequently, we will describe some alternative approaches investigated to improve the light-harvesting properties of the cells, such as the co-sensitization strategy and the use of concerted companion dyes. Finally, the issue of measurement standardization will be introduced, and some considerations regarding the proper characterization methods of indoor PV systems and their differences compared to (simulated) outdoor conditions will be provided.

Orange/Red Benzo[1,2-b:4,5-b']dithiophene 1,1,5,5-Tetraoxide-Based Emitters for Luminescent Solar Concentrators: Effect of Structures on Fluorescence Properties and Device Performances.

Luminescent solar concentrators (LSCs) are a class of optical devices able to harvest, downshift, and concentrate sunlight, thanks to the presence of emitting materials embedded in a polymer matrix. Use of LSCs in combination with silicon-based photovoltaic (PV) devices has been proposed as a viable strategy to enhance their ability to harvest diffuse light and facilitate their integration in the built environment. LSC performances can be improved by employing organic fluorophores with strong light absorption in the center of the solar spectrum and intense, red-shifted emission. In this work, we present the design, synthesis, characterization, and application in LSCs of a series of orange/red organic emitters featuring a benzo[1,2-b:4,5-b']dithiophene 1,1,5,5-tetraoxide central core as an acceptor (A) unit. The latter was connected to different donor (D) and acceptor (A') moieties by means of Pd-catalyzed direct arylation reactions, yielding compounds with either symmetric (D-A-D) or non-symmetric (D-A-A') structures. We found that upon light absorption, the compounds attained excited states with a strong intramolecular charge-transfer character, whose evolution was greatly influenced by the nature of the substituents. In general, symmetric structures showed better photophysical properties for the application in LSCs than their non-symmetric counterparts, and using a donor group of moderate strength such as triphenylamine was found preferable. The best LSC built with these compounds presented photonic (external quantum efficiency of 8.4 ± 0.1%) and PV (device efficiency of 0.94 ± 0.06%) performances close to the state-of-the-art, coupled with a sufficient stability in accelerated aging tests.

Synthesis and Spectroscopic Characterization of Thienopyrazine-Based Fluorophores for Application in Luminescent Solar Concentrators (LSCs).

Organic fluorophores have found broad application as emitters in luminescent solar concentrators (LSCs) for silicon photovoltaics. In particular, the preparation of organic conjugated systems with intense light-harvesting ability, emissions in the deep-red and NIR regions, and large Stokes shift values represent a very challenging undertaking. Here, we report a simple and easy way to prepare three symmetrical donor-acceptor-donor (DAD) organic-emitting materials based on a thienopyrazine core. The central core in the three dyes was modified with the introduction of aromatic substituents, aiming to affect their optical properties. The fluorophores were characterized by spectroscopic studies. In all cases, visible-NIR emissions with large Stokes shifts were found, highlighting these molecules as promising materials for the application in LSCs.

Synthesis and Characterization of New Organic Dyes Containing the Indigo Core.

A new series of symmetrical organic dyes containing an indigo central core decorated with different electron donor groups have been prepared, starting from Tyrian Purple and using the Pd-catalyzed Stille-Migita coupling process. The effect of substituents on the spectroscopic properties of the dyes has been investigated theoretically and experimentally. In general, all dyes presented intense light absorption bands, both in the blue and red regions of the visible spectrum, conferring them a bright green color in solution. Using the same approach, an asymmetrically substituted D-A-π-A green dye, bearing a triarylamine electron donor and the cyanoacrylate acceptor/anchoring group, has been synthesized for the first time and fully characterized, confirming that spectroscopic and electrochemical properties are consistent with a possible application in dye-sensitized solar cells (DSSC).

Combined LCA and Green Metrics Approach for the Sustainability Assessment of an Organic Dye Synthesis on Lab Scale.

New generation photovoltaic devices have attracted much attention in the last decades since they can be efficiently manufactured employing abundant raw materials and with less-energy intensive processes. In this context, the use of powerful environmental assessment is pivotal to support the fine-tuning of solar cells fabrication and hit the target of manufacturing effective sustainable technological devices. In this work, a mass-based green metrics and life cycle assessment combined approach is applied to analyze the environmental performances of an innovative synthetic protocol for the preparation of organic dye TTZ5, which has been successfully proposed as sensitizer for manufacturing dye sensitized solar cells. The new synthetic strategy, which is based on the C-H activation process, has been compared with the previously reported synthesis employing classic Suzuki-Miyaura cross-coupling chemistry. Results highlight the contribution of direct energy consumption and purification operations in organic syntheses at lab scale. Furthermore, they demonstrate the usefulness of the environmental multifaceted analytic tool and the power of life cycle assessment to overcome the intrinsic less comprehensive nature of green metrics for the evaluation of organic synthetic protocols.

New Blue Donor-Acceptor Pechmann Dyes: Synthesis, Spectroscopic, Electrochemical, and Computational Studies.

The design, synthesis, and characterization of a new class of blue-colored thiophene-substituted Pechmann dyes are reported. Due to a distinguishing blue coloration and the capability to absorb light in one of the most photon-dense regions of the solar spectrum, such compounds are of great interest for application as photoactive materials in organic optoelectronics, in particular, in dye-sensitized solar cells. To achieve fine tuning of the optical and electrochemical properties, the electron-poor thiophene-bis-lactone moiety has been decorated with donor (D) and acceptor groups (A), targeting fully conjugated D-A-π-A structures. The designed structures have been investigated by means of DFT and time-dependent DFT calculations, and the most promising dyes have been synthesized. These molecules represent the very first preparation of unsymmetrical Pechmann derivatives. Optical and electrochemical properties of the new dyes have been studied by cyclic voltammetry and UV-vis and fluorescence spectroscopy. In two cases, test cells were built proving that a photocurrent can indeed be generated when using electrolytes especially formulated for narrow-band-gap dyes, although with a very low efficiency.

Nonunion fracture healing: Evaluation of effectiveness of demineralized bone matrix and mesenchymal stem cells in a novel sheep bone nonunion model.

Nonunion treatment has a high rate of success, although recalcitrant nonunion may determine the need for amputation. Therefore, new treatment options are continuously investigated in order to further reduce the risk of nonunion recurrence. This study aimed to (a) develop a new large animal model for bone atrophic nonunion and (b) compare the efficacy of demineralized bone matrix (DBM) and DBM in combination with mesenchymal stem cells (MSC) in the new nonunion model. The new model consists of a noncritical, full-thickness segmental defect created in the sheep tibia, stabilized by an intramedullary nail, and involves the creation of a locally impaired blood supply achieved through periosteum excision and electrocauterization of the stump ends. Six weeks after defect creation, lack of hard tissue callus and established nonunion was observed in all operated tibiae both by radiographic and clinical evaluation. Nonunion was treated with allogeneic DBM or autologous MSC cultivated on DBM particles (DBM + MSC) for 1 day before implantation. Twelve weeks after treatment, radiographic, microtomographic, histologic, and histomorphometric analysis showed the formation of bone callus in DBM group, whereas the fracture healing appeared at an early stage in DBM + MSC group. Torsional strength and stiffness of the DBM group appeared higher than those of DBM + MSC group, although the differences were not statistically significant. In conclusion, a new sheep bone nonunion model resembling the complexity of the clinical condition was developed. DBM is an effective option for nonunion treatment, whereas MSC do not improve the healing process when cultivated on DBM particles before implantation.

Towards Sustainable H2 Production: Rational Design of Hydrophobic Triphenylamine-based Dyes for Sensitized Ethanol Photoreforming.

Donor-acceptor dyes are a well-established class of photosensitizers, used to enhance visible-light harvesting in solar cells and in direct photocatalytic reactions, such as H2 production by photoreforming of sacrificial electron donors (SEDs). Amines-typically triethanolamine (TEOA)-are commonly employed as SEDs in such reactions. Dye-sensitized photoreforming of more sustainable, biomass-derived alcohols, on the other hand, was only recently reported by using methanol as the electron donor. In this work, several rationally designed donor-acceptor dyes were used as sensitizers in H2 photocatalytic production, comparing the efficiency of TEOA and EtOH as SEDs. In particular, the effect of hydrophobic chains in the spacer and/or the donor unit of the dyes was systematically studied. The H2 production rates were higher when TEOA was used as SED, whereas the activity trends depended on the SED used. The best performance was obtained with TEOA by using a sensitizer with just one bulky hydrophobic moiety, propylenedioxythiophene, placed on the spacer unit. In the case of EtOH, the best-performing sensitizers were the ones featuring a thiazolo[5,4-d]thiazole internal unit, needed for enhancing light harvesting, and carrying alkyl chains on both the donor part and the spacer unit. The results are discussed in terms of reaction mechanism, interaction with the SED, and structural/electrochemical properties of the sensitizers.

Organic dye-sensitized solar cells containing alkaline iodide-based gel polymer electrolytes: influence of cation size.

The electrolyte used in dye-sensitized solar cells (DSSCs) plays a key role in the process of current generation, and hence the analysis of charge-transfer mechanisms both in its bulk and at its interfaces with other materials is of fundamental importance. Because of solvent confinement, gel polymer electrolytes are more practical and convenient to use with respect to liquid electrolytes, but in-depth studies are still necessary to optimize their performances. In this work, gel polymer electrolytes of general formulation polyacrylonitrile (PAN)/ethylene carbonate (EC)/propylene carbonate (PC)/MI, where M+ is a cation in the alkaline series Li-Cs, were prepared and used in DSSCs. Their ionic conductivities were determined by impedance analysis, and their temperature dependence showed Arrhenius behavior within the experimental window. FT-IR studies of the electrolytes confirmed the prevalence of EC coordination around the cations. Photo-anodes were prepared by adsorbing organic sensitizer D35 on nanocrystalline TiO2 thin films, and employed to build DSSCs with the gel electrolytes. Nanosecond transient spectroscopy results indicated a slightly faster dye regeneration process in the presence of large cations (Cs+, Rb+). Moreover, a negative shift of TiO2 flat-band potential with the decreasing charge density of the cations (increasing size) was observed through Mott-Schottky analysis. In general, results indicate that cell efficiencies are mostly governed by photocurrent values, in turn depending on the conductivity increase with cation size. Accordingly, the best result was obtained with the Cs+-containing cell, although in this case a slight reduction of photovoltage compared to Rb+ was observed.

Photoinduced excitation and charge transfer processes of organic dyes with siloxane anchoring groups: a combined spectroscopic and computational study.

Dye-sensitized solar cells (DSSCs) have attracted significant interest in the last few years as effective low-cost devices for solar energy conversion. We have analyzed the excited state dynamics of several organic dyes bearing both cyanoacrylic acid and siloxane anchoring groups. The spectroscopic properties of the dyes have been studied both in solution and when adsorbed on a TiO2 film using stationary and time-resolved techniques, probing the sub-picosecond to nanosecond time interval. The comparison between the spectra registered in solution and on the solid substrate evidences different pathways for energy and electron relaxation. The transient spectra of the TiO2-adsorbed dyes show the appearance of a long wavelength excited state absorption band, attributed to the cationic dye species, which is absent in the spectra measured in solution. Furthermore, the kinetic traces of the samples adsorbed on the TiO2 film show a long decay component not present in solution which constitutes indirect evidence of electron transfer between the dye and the semiconductor. The interpretation of the experimental results has been supported by theoretical DFT calculations of the excited state energies and by the analysis of molecular orbitals of the analyzed dye molecules.

The Stille Reaction: Applications in the Synthesis of Organic Dyes for DSSCs.

The cross-coupling reaction of organic electrophiles with organostannanes, traditionally known as the Stille reaction, has found renewed interest in the preparation of new organic materials such as conjugated polymers, organic semiconductors and photoactive molecules for use in organic photovoltaics. Moreover, a very recent field in which the Stille reaction has found successful application is that of the design and synthesis of new photosensitizers for dye-sensitized solar cells (DSSCs). DSSCs are considered a promising alternative for energy production from renewable sources. In such devices light harvesting is carried out by a dye which is generally a highly conjugated molecule. Due to the mild operating conditions and the high functional-group compatibility, the Stille reaction proved to be a powerful tool not only for the preparation of photosensitizers, but also to plan their chemical elaboration in order to tune and optimize their photophysical, electrochemical and photovoltaic properties. In this microreview some recent examples of the Stille reaction in the synthesis of organic dyes for DSSC are reported.

Discovery of 4,6-disubstituted pyrimidines as potent inhibitors of the heat shock factor 1 (HSF1) stress pathway and CDK9.

Heat shock factor 1 (HSF1) is a transcription factor that plays key roles in cancer, including providing a mechanism for cell survival under proteotoxic stress. Therefore, inhibition of the HSF1-stress pathway represents an exciting new opportunity in cancer treatment. We employed an unbiased phenotypic screen to discover inhibitors of the HSF1-stress pathway. Using this approach we identified an initial hit (1) based on a 4,6-pyrimidine scaffold (2.00 µM). Optimisation of cellular SAR led to an inhibitor with improved potency (25, 15 nM) in the HSF1 phenotypic assay. The 4,6-pyrimidine 25 was also shown to have high potency against the CDK9 enzyme (3 nM).

Strain distribution in the proximal Human femur during in vitro simulated sideways fall.

This study assessed: (i) how the magnitude and direction of principal strains vary for different sideways fall loading directions; (ii) how the principal strains for a sideways fall differ from physiological loading directions; (iii) the fracture mechanism during a sideways fall. Eleven human femurs were instrumented with 16 triaxial strain gauges each. The femurs were non-destructively subjected to: (a) six loading configurations covering the range of physiological loading directions; (b) 12 configurations simulating sideways falls. The femurs were eventually fractured in a sideways fall configuration while high-speed cameras recorded the event. When the same force magnitude was applied, strains were significantly larger in a sideways fall than for physiological loading directions (principal compressive strain was 70% larger in a sideways fall). Also the compressive-to-tensile strain ratio was different: for physiological loading the largest compressive strain was only 30% larger than the largest tensile strain; but for the sideways fall, compressive strains were twice as large as the tensile strains. Principal strains during a sideways fall were nearly perpendicular to the direction of principal strains for physiological loading. In the most critical regions (medial part of the head-neck) the direction of principal strain varied by less than 9° between the different physiological loading conditions, whereas it varied by up to 17° between the sideways fall loading conditions. This was associated with a specific fracture mechanism during sideways fall, where failure initiated on the superior-lateral side (compression) followed by later failure of the medially (tension), often exhibiting a two-peak force-displacement curve.

Suprapectoral biceps tenodesis: a biomechanical comparison of a new "soft anchor" tenodesis technique versus interference screw biceps tendon fixation.

BACKGROUND: The interference screw technique is commonly used in tenodesis of the long head of the biceps for its well-documented robust fixation strength. Some complications may occur after tenodesis with interference screw such as persistent pain, bone fracture and cyst formation. A new technique using a small "soft anchor" has been proposed to avoid the risk of occurrence of the above-mentioned complications associated with the use of the interference screw. However, the proposed technique must provide adequate fixation strength. This study investigated the mechanical performance of the new technique and compared it with interference screw fixation. METHODS: Fourteen human humeri and proximal biceps were tested after tenodesis using the two techniques. The fixation constructs were cycled 500 times between 20N and 100N at 1Hz to simulate some level of post-operative physical activity. Then, a tensile test to failure was performed to determine the strength of the two tenodesis constructs. FINDINGS: The ultimate strength was 238N (SD 96N) and 172N (SD 58N) for the "soft anchor" and the interference screw, respectively (P=0.14). In two out of seven repetitions in both groups, failure occurred at low load level due to inaccuracies in performing tenodesis. Considering these cases as outliers, the strength values increased up to 290N (SD 40N) and 202N (SD 32N) for the "soft anchor" and the interference screw, respectively (P=0.02). INTERPRETATION: The "soft anchor" technique provides a fixation strength comparable with the interference screw, but without using a screw. It could be considered as an alternative for suprapectoral biceps tenodesis.

Organic dyes with intense light absorption especially suitable for application in thin-layer dye-sensitized solar cells.

Three new thiazolo[5,4-d]thiazole-based organic dyes have been designed and synthesized for employment as DSSC sensitizers. Alternation of the electron poor thiazolothiazole unit with two propylenedioxythiophene (ProDOT) groups ensured very intense light absorption in the visible region (ε up to 9.41 × 10(4) M(-1) cm(-1) in THF solution). The dyes were particularly suitable for application in transparent and opaque thin-layer DSSCs (TiO2 thickness: 5.5-6.5 µm, efficiencies up to 7.71%), thus being good candidates for production of solar cells under simple fabrication conditions.

Stereoselective synthesis of polysubstituted piperazines and oxopiperazines. Useful building blocks in medicinal chemistry.

Many pharmaceutical agents include piperazines or oxopiperazines as part of their core structures. The presence of substituents on these heterocycles has a significant influence on the biological activity, thus the search for efficient routes to control the substitution at different ring positions might have a crucial impact, especially to promote the use of such scaffolds in SAR studies. Many research groups have been engaged in the stereoselective synthesis of polysubstituted piperazines and oxopiperazines and in the majority of cases the stereochemistry of the final compounds is dependent on the starting material configuration. In the present minireview we have summarized some of the most significant approaches towards the stereoselective synthesis and functionalization of substituted piperazines and oxopiperazines, with a particular focus on our own contributions mainly based on readily available natural amino-acids as "chiral pool" starting materials. An efficient and scalable route to orthogonally protected 2-oxopiperazines has been developed using the corresponding diamines as key intermediates: diastereoselective elaboration of the resulting heterocycles was possible by metalation and reaction with electrophiles, leading to anti 3,5-disubstituted-oxopiperazines, in agreement with the model for a conventional 1,3-asymmetric induction. Both piperazines and tetrahydropyrazines could be prepared via LiAlH4-mediated reduction of 2-oxopiperazines, depending on reaction conditions. Finally, the diastereoselective synthesis of cyclopropane- containing analogs 2,5-diaza-bicyclo[4.1.0]heptanes was demonstrated by application of the classic Simmons-Smith reaction on enantiomerically enriched dihydro-2H-pyrazines.

Excited State Geometries and Vertical Emission Energies of Solvated Dyes for DSSC: A PCM/TD-DFT Benchmark Study.

The ability of Time-Dependent Density Functional Theory (TD-DFT) to provide excited state geometries and reproduce emission energies of organic D-π-A dyes designed for DSSC applications is evaluated. The performance of six functionals (CAM-B3LYP, MPW1K, ωB97X-D, LC-BLYP, LC-ωPBE, and M06-HF) in combination with three basis sets (cc-pVDZ, 6-31+G(d,p), and 6-311+G(2d,p)) has been analyzed. Solvent effects have been taken into account by means of a Polarizable Continuum Model in both LR and SS formalisms. Our LR-PCM/TD-DFT results show that accurate emission energies are obtained only when solvent effects are included in the computation of excited state geometries and when a range separated hybrid functional is used. Vertical emission energies are reproduced with a mean absolute error of at most 0.2 eV. The accuracy is further improved using the SS-PCM formalism.

Reproducible reference frame for in vitro testing of the human vertebrae.

Definition of an anatomical reference frame is necessary for in vitro biomechanical testing. Nevertheless, there is neither a clear recommendation, nor consensus in the literature concerning an anatomical reference frame for in vitro testing of the human vertebrae. The scope of this work is to define a reference frame for the human vertebrae for in vitro applications. The proposed anatomical reference frame relies on alignment of well-defined points on the endplates, and on two landmarks on the posterior wall. The repeatability of the proposed alignment procedure has been tested in vitro by 5 operators, on 7 specimens. Furthermore, the feasibility and repeatability of the proposed procedure was assessed in silico, using CT-scans of the same specimens. Variations between operators were slightly larger than between repetitions by the same operator. The intra-operator in vitro repeatability was better than 3° for all angles. The inter-operator in vitro repeatability was better than 9° for all angles. The lateral tilt was the most repeatable angle, while anterior-posterior tilt was least repeatable. The repeatability when alignment was performed in silico on CT-scans was comparable to that obtained in vitro, on the physical specimens. This is the first time than an anatomical reference frame is formally defined and validated for the human vertebrae. The adoption of this reference frame will provide more reproducible alignment of the specimens and of the test load. This will enable better in vitro biomechanical tests, and comparisons with numerical models.

Accurate in vitro identification of fracture onset in bones: failure mechanism of the proximal human femur.

Bone fractures have extensively been investigated, especially for the proximal femur. While failure load can easily be recorded, and the fracture surface is readily accessible, identification of the point of fracture initiation is difficult. Accurate location of fracture initiation is extremely important to understand the multi-scale determinants of bone fracture. In this study, a recently developed technique based on electro-conductive lines was applied to the proximal femoral metaphysis to elucidate the fracture mechanism. Eight cadaveric femurs were prepared with 15-20 electro-conductive lines (crack-grid) covering the proximal region. The crack-grid was connected to a dedicated data-logger that monitored electrical continuity of each line at 700 kHz. High-speed videos (12,000 frames/s, 0.1-0.2 mm pixel size) of the destructive tests were acquired. Most crack-grid-lines failed in a time-span of 0.08-0.50 ms, which was comparable to that identified in the high-speed videos, and consistent with previous video recordings. However, on all specimens 1-3 crack-grid-lines failed significantly earlier (2-200 ms) than the majority of the crack-grid-lines. The first crack-grid-line to fail was always the closest one to the point of fracture initiation identified in the high-speed videos (superior-lateral neck region). Then the crack propagated simultaneously, at comparable velocity on the anterior and posterior sides of the neck. Such a failure pattern has never been observed before, as spatial resolution of the high-speed videos prevented from observing the initial opening of a crack. This mechanism (fracture onset, time-lag, followed by catastrophic failure) can be explained with a transfer of load to the internal trabecular structure caused by the initial fracture of the thin cortical shell. This study proves the suitability of the crack-grid method to investigate bone fractures associated to tensile stress. The crack-grid method enables significantly faster sampling than high-speed cameras. The present findings elucidate some aspects of the failure mechanism of the proximal human femoral metaphysis.