Iridium and Ruthenium Complexes Bearing Perylene Ligands

The present review summarizes the work carried out mostly in the last decade on iridium and ruthenium complexes bearing various perylene ligands, of particular interest for bioimaging, photodynamic therapy, and solar energy conversion. In these complexes, the absorption spectra and the electrochemical properties are those of the perylene subunit plus those of the metal moiety. In contrast, the emissions are completely changed with respect to perylenes considered alone. Thus, fully organic perylenes are characterized by a strong fluorescence in the visible region, lifetimes of a few nanoseconds, and luminescence quantum yields approaching 100%, whereas perylene Ir and Ru complexes usually do not emit; however, in few cases, weak phosphorescent emissions, with lifetimes in the range of microseconds and relatively low quantum yields, are reported. This is due to a strong interaction between the perylene core and the heavy metal center, taking place after the excitation. Nevertheless, an important advantage deriving from the presence of the heavy metal center is represented by the ability to generate large amounts of singlet oxygen, which plays a key role in photodynamic therapy.     

Optical Anisotropy of Porphyrin Nanocrystals Modified by the Electrochemical Dissolution

Reflectance anisotropy spectroscopy (RAS) coupled to an electrochemical cell represents a powerful tool to correlate changes in the surface optical anisotropy to changes in the electrochemical currents related to electrochemical reactions. The high sensitivity of RAS in the range of the absorption bands of organic systems, such as porphyrins, allows us to directly correlate the variations of the optical anisotropy signal to modifications in the solid-state aggregation of the porphyrin molecules. By combining in situ RAS to electrochemical techniques, we studied the case of vacuum-deposited porphyrin nanocrystals, which have been recently observed dissolving through electrochemical oxidation in diluted sulfuric acid. Specifically, we could identify the first stages of the morphological modifications of the nanocrystals, which we could attribute to the single-electron transfers involved in the oxidation reaction; in this sense, the simultaneous variation of the optical anisotropy with the electron transfer acts as a precursor of the dissolution process of porphyrin nanocrystals.     

Biological Investigation and Chemical Study of Brassica villosa subsp. drepanensis (Brassicaeae) Leaves

Brassica villosa subsp. drepanensis (Caruel) Raimondo & Mazzola, belonging to the Brassica oleracea complex, is a wild edible plant endemic to western Sicily and a relative of modern cultivated Brassica crops. In this study, the antioxidant properties, anti-inflammatory activities, enzymatic inhibition, and cytotoxicity in cancer cells of B. villosa subsp. drepanensis leaf ethanolic extract were analysed for the first time. In addition, its chemical profile was investigated partitioning the total 70% ethanol extract among ethyl acetate, n-butanol, and water to obtain three residues that were subjected to chromatographic separation. Two flavonol glycosides, a phenol glucoside, two amino acids, and purine/pyrimidine bases were obtained. The presence of the glucosinolate glucoiberin was detected in the water extract by UHPLC-MS analysis. The total polyphenol and flavonoid content of the 70% ethanol extract showed good antioxidant capacities and anti-inflammatory properties by reducing nitric oxide release and reactive oxygen species levels and increasing glutathione in lipopolysaccharide-stimulated RAW 264.7 cells. The extract inhibited the enzymatic activity of α-amylase, α-glucosidase, and, significantly, of lipase. The MTT assay showed that the extract did not affect the viability of normal HFF-1 and RAW 264.7 cells. Among the cancer cell lines tested, an antiproliferative action was only observed in CaCo-2. The cytotoxicity of the extract was further confirmed by LDH release assay and by the destabilization of the oxidative balance. Results confirmed the antioxidant properties of the crude extract responsible for the anti-inflammatory effect on healthy cells and cytotoxicity in cancer cells.     

Development of Novel Polypropylene Syntactic Foams Containing Paraffin Microcapsules for Thermal Energy Storage Applications

polypropylene (PP) syntactic foams (SFs) containing hollow glass microspheres (HGMs) possess low density and elevated mechanical properties, which can be tuned according to the specific application. A possible way to improve their multifunctionality could be the incorporation of organic Phase Change Materials (PCMs), widely used for thermal energy storage (TES) applications. In the present work, a PCM constituted by encapsulated paraffin, having a melting temperature of 57 °C, was embedded in a compatibilized polypropylene SF by melt compounding and hot pressing at different relative amounts. The rheological, morphological, thermal, and mechanical properties of the prepared materials were systematically investigated. Rheological properties in the molten state were strongly affected by the introduction of both PCMs and HGMs. As expected, the introduction of HGMs reduced both the foam density and thermal conductivity, while the enthalpy of fusion (representing the TES capability) was proportional to the PCM concentration. The mechanical properties of these foams were improved by the incorporation of HGMs, while they were reduced by addition of PCMs. Therefore, the combination of PCMs and HGMs in a PP matrix generated multifunctional materials with tunable thermo-mechanical properties, with a wide range of applications in the automotive, oil, textile, electronics, and aerospace fields.     

Electrification of a Milstein-type catalyst for alcohol reformation

Novel energy and atom efficiency processes will be keys to develop the sustainable chemical industry of the future. Electrification could play an important role, by allowing to fine-tune energy input and using the ideal redox agent: the electron. Here we demonstrate that a commercially available Milstein ruthenium catalyst (1) can be used to promote the electrochemical oxidation of ethanol to ethyl acetate and acetate, thus demonstrating the four electron oxidation under preparative conditions. Cyclic voltammetry and DFT-calculations are used to devise a possible catalytic cycle based on a thermal chemical step generating the key hydride intermediate. Successful electrification of Milstein-type catalysts opens a pathway to use alcohols as a renewable feedstock for the generation of esters and other key building blocks in organic chemistry, thus contributing to increase energy efficiency in organic redox chemistry.

Electrification of the Milstein catalyst enabled successful molecular electrocatalytic oxidation of ethanol to the four-electron products acetate and ethyl acetate.

In order to achieve the goals of the Sustainable Development Scenario (SDS) of the International Energy Agency, the chemical industry''s emission should decline by around 10% before 2030.^1,2 This could be achieved by increasing energy efficiency and the usage of renewable feedstocks. In this respect, molecular electrocatalytic alcohol oxidation could be powerful tool by potentially providing energy and atom efficiency for organic synthesis and energy applications.^2–7 Besides the use of aminoxyl-derivatives,^8–13 especially the seminal work of Vizza, Bianchini and Grützmacher demonstrated that (transfer)-hydrogenation (TH) catalysts could be activated electrochemically and used in a so-called “organometallic fuel cell”.¹⁴ Other TH systems are however mostly limited to two electron oxidations of secondary or benzylic alcohols (Scheme 1A).^15–21Open in a separate windowScheme 1(A) Advantages/limitation of electrochemical homogeneous alcohol oxidation using well-defined catalysts. (B) Current efforts to electrify acceptor-less alcohol dehydrogenation (AAD) systems due to their large range of application in thermal catalysis.As an exception, Waymouth et al. recently reported an example of the intramolecular coupling of vicinal benzylic alcohols to the corresponding esters.^19,22 In order to extend the range of possible catalysts candidates, the Waymouth group recently also explored the possibility to use an iron-based acceptor-less alcohol dehydrogenation (AAD) catalysts²³ for electrocatalytic alcohol oxidation (Scheme 1B).²⁴ The stability under electrochemical conditions in this case is limited to <2 turnovers, but it opens the door to explore a wide range of AAD reactions under electrochemical conditions. Here, we demonstrate that a commercially available Milstein-type AAD catalyst (1)²⁵ is competent for the electrocatalytic alcohol oxidation of ethanol to ethyl acetate and acetate (Scheme 1B).The cyclic voltammogram (CV) of complex 1 (Fig. 1) shows a quasi-reversible diffusive one electron oxidation wave at 0.2 V (all potentials are referenced vs. Fc⁺/Fc⁰) in 0.2 M NaPF₆ THF/DFB (2 : 1) (DFB = 1,2 difluoro benzene) assigned to the Ru(ii)–Ru(iii) couple (see ESI, section 2.2^†). The addition of 1 to a 10 mM sodium ethoxide (NaOEt) solution in 200 mM ethanol (EtOH) in 0.1 M NaPF₆ (2 : 1 THF/DFB) gives rise to several waves at ca. −0.5, 0.0 and 0.2 V with currents significantly higher than in the absence of catalysts or substrate, indicative of possible catalytic turnover (Fig. 2). Gradual increase of the EtOH concentration from 200 mM to 1 M is accompanied by the disappearance of the first wave at −0.5 V, while a new oxidation wave appears at ca. −0.25 V (Fig. 2, light to dark green traces).Open in a separate windowFig. 1Scan rate dependence of a 1 mM solution of 1 in in 2 : 1 THF/DFB + 0.2 M NaPF6 (from light to dark green: 0.05, 0.1, 0.2, 0.3, 0.4 and 0.5 V s⁻¹, 3 mm GC electrode). Inset: evolution of the peak current as a function of the square root of the scan rate.Open in a separate windowFig. 2CVs of 10 mM NaOEt (grey) and of 5 mM 1 + 5 mM NaOEt with increasing concentrations of EtOH (from light to dark green: 200, 400, 600, 800 and 1000 mM) in 2 : 1 THF/DFB + 0.2 M NaPF₆. Scan rate 0.1 V s⁻¹, electrode: 3 mm diameter GC electrode.Increasing the base loading gradually from 5 to 20 mM yields a stark increase of current at this new wave at ca. −0.25 V (Fig. 3). Using (TBA)PF₆ instead of NaPF₆ (used to avoid Hofmann-elimination²⁶) gave similar results (see ESI, section 2.2–2.5 and section 4^†). In order to assess catalytic turnover under preparative conditions, controlled potential electrolysis (CPE) was performed. CPE experiments were run in pure ethanol (to reduce cell resistance) in the presence of 0.1 M electrolyte of well soluble bases (e.g. NaOEt, LiOH, see ESI section 4^†). CPE in 0.1 M LiOH with 1 mM 1 at E = 0 V vs. Fc^0/+ delivered ca. 15 mM of acetate and 6 mM of ethyl acetate, corresponding to 21 turnovers (per 4 electrons, or 42 turnovers per two electrons) and a faradaic efficiency (FE) of ca. 62% (see ESI section 4.3^†). In the absence of applied potential (OCP, open circuit potential), no ethyl acetate was formed (see ESI, section 4.4^†). Likewise, in the absence of catalyst, the passed charge was significantly lower (7C vs. 40C) with no detected formation of ethyl acetate. The low FE could be due to catalyst degradation, as Ru-nanoparticle formation is observed on the electrode post CPE (confirmed by SEM/Elemental mapping, see ESI section 5^†). Noteworthy, rinse-test CPE and a CPE using a simple Ru-precursor, RuCl₃, did not show any ethyl acetate formation and gave similar results to blank experiments, indicating that Ru-nanoparticles are probably not the active catalyst species and that catalyst instability could be responsible for low FE. Further studies are underway to fully understand catalyst speciation under preparative conditions (see ESI section 4.7^†) the observed catalytic activity of 1 compares well in terms of TON and product selectivity with other molecular homogeneous TH systems, with most systems being limited to the two-electron oxidation of secondary or benzylic alcohols. The Waymouth group reported a NNC ruthenium pincer for the oxidation of isopropanol to acetone with a TON of 4.¹⁸ The same group reported on the usage of phenoxy mediators with an iridium pincer complex, reaching a TON of 8 for the same reaction.²² Bonitatibus and co-workers demonstrated the activity of an iridium-based systems with a TON of 32 for the formation of p-benzaldehyde.¹⁷ Appel and co-workers reported on a nickel (TON = 3.1)¹⁵ and a cobalt triphos systems (TON = 19.9)¹⁶ for benzaldehyde formation from benzyl alcohol. To the best of our knowledge, there is only one acceptor-less alcohol dehydrogenation (AAD) catalyst that has been activated electrochemically so-far,²⁴ generating acetone with a TON <2. Only a handful of molecular systems are known to catalyze the electrochemical four electron alcohol reformation to esters, however at significantly higher potentials (1.15 V vs. Fc⁺/Fc⁰).^2,27,28 Thus, although not designed for electrochemical applications, 1 shows high activity for the challenging 4 electron oxidation of aliphatic substrates.Open in a separate windowFig. 3CV of 5 mM NaOEt (grey), 5 mM of 1 + 1 M EtOH with varying concentrations of base (5, 10, 15, and 20 mM NaOEt, light to dark green) in 2 : 1 THF/DFB + 0.2 M NaPF₆. Scan rate 0.1 V s⁻¹, electrode: 3 mm diameter GC electrode.To achieve the transposition from thermal to electrochemical TH, both Grützmacher et al. and Waymouth took advantage of a fast equilibrium between the alcohol substrate and a metal hydride intermediate that could be readily oxidized. The chemistry of ruthenium pincer AAD systems is well studied (Scheme 2)^25,29–33 and allows for a putative assignment of the observed CV-behavior. In the presence of excess base and alcohol (Fig. 2 and ​and3),3), 1 is expected to yield dearomatized complex 2,²⁵ as well as the alkoxide species 3.^25,32 We might therefore assign the first wave at −0.5 V to the oxidation of dearomatized complex 2 and the wave around 0 V to the oxidation of the alkoxide complex 3. Indeed, independently synthesized samples of 2 and 3 (in the presence of excess ethanol) give rise to oxidation half-waves at −0.45 V and −0.1 V respectively (see ESI, section 3 and 5.2^†). This is also in agreement with the observed behavior upon increasing the alcohol concentration with the expected consumption of dearomatized species 2 and concomitant disappearance of the first oxidation wave at −0.5 V. The equilibrium between 2, 3 and 4 has been reported³² and addition of excess ethanol to 2 is thus not only generating 3, but also is expected to deliver 4 (Scheme 2). The appearance of a new anodic wave at ca. −0.25 V (Fig. 2) is thus attributed to the increasing formation of 4 upon addition of larger amounts of EtOH. Complex 4 is relatively unstable in solution,^25,32,33 and decomposes in the presence of electrolyte (see ESI section 3.1^†). DFT calculations were thus used to predict its oxidation potential (see ESI, section 6^†), which was in reasonable agreement with the observed wave (−0.19 V). The DFT calculations also confirmed the assignment of the other waves related to the dearomatized complex 2 (−0.33 V) and the ethoxide species 3 (−0.1 V). A more detailed mechanistic analysis remains currently hampered by the chemical instability of 4 under the employed reaction conditions, as well as difficulties to isolate 3 in the solid state (limiting kinetic measurements). DFT calculations were thus used to get a better view on possible reaction pathways (Schemes 2, ​,33 and ESI section 6.3^†). The oxidation of 4 at −0.19 V (DFT) yields the radical cation 5, with a calculated pK_a in THF of 8.2. In the presence of NaOEt, 5 should thus deprotonate readily to give radical 6, which has an extremely negative oxidation potential of −2.1 V. At the potential it is generated, 6 should thus directly be oxidized to cationic complex 7. This cationic species 7 has a calculated pK_a of 22.7 in THF, which is in good agreement with experimental data from the Saouma group on a similar system.²⁶ The high pK_a of 7 in THF also validates the need for a strong base (e.g. NaOEt) to reform dearomatized 2. Both Grützmacher and co-workers,¹⁴ as well as Waymouth²⁴ have noted that the accelerating effect during electrocatalysis stems from the oxidation of a metal hydride intermediate that is generated by fast chemical steps. In order to verify this hypothesis and to exclude an electrochemical activation of this hydride formation step, transition state barriers were computed (Scheme 3). Taking the dearomatized complex 2 as a reference point, a first step will form the alkoxide species 3 (TS₀ = 21.2 kcal mol⁻¹). Oxidizing 2 to 8 slows down the formation of the alkoxide species (T_S0^ox = 27.5 kcal mol⁻¹), most-likely due to decreased basicity of the ligand. From the alkoxide species 3 dihydride 4 is formed via a linear, charge-separated transition state TS₁ (15.7 kcal mol⁻¹). The role of such linear transition states was highlighted recently in the case of ruthenium pincer catalysis for alcohol oxidation.^34–37 In principle, it might be envisioned that the oxidation of the metal center could be an additional driving force for this hydride abstraction step. However, after oxidation, the energy span^38,39 rises by about 11 kcal mol⁻¹ (TS₁^ox = 24.7 kcal mol⁻¹). Likewise, a beta-hydride elimination via side-arm opening is not accelerated either by oxidation (TS₂^ox = 37.5 kcal mol⁻¹, see ESI section 6.4^†). It thus seems that the generation of 4 is not accelerated by electron transfer steps and relies on a thermally activated chemical step. Importantly, alkoxide solutions were shown to be excellent hydride donors electrochemically, further corroborating that under the employed basic conditions, generation of 4 from 3 should be fast.⁴⁰ Oxidation of 4 to 5 also doesn''t accelerate thermal intramolecular release of H₂ (TS_3B^ox = 37.5 kcal mol⁻¹), which is significantly higher than neutral thermal H₂-releasing states (TS_3A and TS_3B). The experimentally observed acceleration via electron-transfer is thus proposed to follow a classical ECEC mechanism initiated by the oxidation of 4 to 5 (at roughly −0.19 V (DFT)), followed by deprotonation and re-oxidation as described above, finally delivering 2 at the electrode surface. Importantly, at the electrode surface 2 and 3 should be oxidized at the employed potentials, but based on DFT-calculations, these pathways are thought to be non-productive (Scheme 3) and could explain the low catalyst life-time and degradation under electrochemical conditions.Open in a separate windowScheme 2Reactivity of pyridine-based ruthenium complexes via dearomatization/aromatization, as well as DFT-based.Open in a separate windowScheme 3DFT-calculated energy landscape for the neutral (black dotted lines and bars) and cationic surface (blue dotted lines and bars) of ethanol dehydrogenation starting from 2 or its cationic analogue 8.     

Optimized Green Extraction of Polyphenols from Cassia javanica L. Petals for Their Application in Sunflower Oil: Anticancer and Antioxidant Properties

The total phenolic content (TPC) from Cassia javanica L. petals were extracted using ethanolic solvent extraction at concentrations ranging from 0 to 90% and an SCF-CO₂ co-solvent at various pressures. Ultrasound-assisted extraction parameters were optimized using response surface methodology (RSM). Antioxidant and anticancer properties of total phenols were assessed. An SCF-CO₂ co-solvent extract was nano-encapsulated and applied to sunflower oil without the addition of an antioxidant. The results indicated that the best treatment for retaining TPC and total flavonoids content (TFC) was SCF-CO₂ co-solvent followed by the ultrasound and ethanolic extraction procedures. Additionally, the best antioxidant activity by β-carotene/linoleic acid and DPPH free radical-scavenging test systems was observed by SCF-CO₂ co-solvent then ultrasound and ethanolic extraction methods. SCF-CO₂ co-solvent recorded the highest inhibition % for PC3 (76.20%) and MCF7 (98.70%) and the lowest IC₅₀ value for PC3 (145 µ/mL) and MCF7 (96 µ/mL). It was discovered that fortifying sunflower oil with SCF-CO₂ co-solvent nanoparticles had a beneficial effect on free fatty acids and peroxide levels. The SCF-CO₂ method was finally found to be superior and could be used in large-scale processing.     

Design,Synthesis and Evaluation of New Multifunctional Benzothiazoles as Photoprotective,Antioxidant and Antiproliferative Agents

A current trend of research in the health field is toward the discovery of multifunctional compounds, capable of interacting with multiple biological targets, thus simplifying multidrug therapies and improving patient compliance. The aim of this work was to synthesize new multifunctional chemical entities bearing a benzothiazole nucleus, a structure that has attracted increasing interest for the great variety of biological actions that it can perform, and already used as a scaffold in several multifunctional drugs. Compounds are reported, divided into two distinct series, synthetized and tested in vitro for the antioxidant, and include UV-filtering and antitumor activities. DPPH and FRAP tests were chosen to outline an antioxidant activity profile against different radical species. The UV-filtering activity was investigated, pre- and post-irradiation, through evaluation of a O/W sunscreen standard formulation containing 3% of the synthetic compounds. The antitumor activity was investigated both on human melanoma cells (Colo-38) and on immortalized human keratinocytes as a control (HaCat). A good antiproliferative profile in terms of IC₅₀ was chosen as a mandatory condition to further investigate apoptosis induction as a possible cytotoxicity mechanism through the Annexin V test. Compound BZTcin4 was endowed with excellent activity and a selectivity profile towards Colo-38, supported by a good antioxidant capacity and an excellent broad-spectrum photoprotective profile.     

From symmetry breaking to symmetry swapping: is Kasha's rule violated in multibranched phenyleneethynylenes?

The phenomenon of excited-state symmetry breaking is often observed in multipolar molecular systems, significantly affecting their photophysical and charge separation behavior. As a result of this phenomenon, the electronic excitation is partially localized in one of the molecular branches. However, the intrinsic structural and electronic factors that regulate excited-state symmetry breaking in multibranched systems have hardly been investigated. Herein, we explore these aspects by adopting a joint experimental and theoretical investigation for a class of phenyleneethynylenes, one of the most widely used molecular building blocks for optoelectronic applications. The large Stokes shifts observed for highly symmetric phenyleneethynylenes are explained by the presence of low-lying dark states, as also established by two-photon absorption measurements and TDDFT calculations. In spite of the presence of low-lying dark states, these systems show an intense fluorescence in striking contrast to Kasha''s rule. This intriguing behavior is explained in terms of a novel phenomenon, dubbed “symmetry swapping” that describes the inversion of the energy order of excited states, i.e., the swapping of excited states occurring as a consequence of symmetry breaking. Thus, symmetry swapping explains quite naturally the observation of an intense fluorescence emission in molecular systems whose lowest vertical excited state is a dark state. In short, symmetry swapping is observed in highly symmetric molecules having multiple degenerate or quasi-degenerate excited states that are prone to symmetry breaking.

Highly symmetric multibranched phenyleneethynylenes exhibit intense fluorescence despite the presence of low-lying dark states. The inversion of the energy order of excited states is explained in terms of a novel phenomenon dubbed “symmetry swapping”.     

Nitrogen-Doped Carbon Quantum Dots for Biosensing Applications: The Effect of the Thermal Treatments on Electrochemical and Optical Properties

The knowledge of the ways in which post-synthesis treatments may influence the properties of carbon quantum dots (CDs) is of paramount importance for their employment in biosensors. It enables the definition of the mechanism of sensing, which is essential for the application of the suited design strategy of the device. In the present work, we studied the ways in which post-synthesis thermal treatments influence the optical and electrochemical properties of Nitrogen-doped CDs (N-CDs). Blue-emitting, N-CDs for application in biosensors were synthesized through the hydrothermal route, starting from citric acid and urea as bio-synthesizable and low-cost precursors. The CDs samples were thermally post-treated and then characterized through a combination of spectroscopic, structural, and electrochemical techniques. We observed that the post-synthesis thermal treatments show an oxidative effect on CDs graphitic N-atoms. They cause their partially oxidation with the formation of mixed valence state systems, [CDs]⁰⁺, which could be further oxidized into the graphitic N-oxide forms. We also observed that thermal treatments cause the decomposition of the CDs external ammonium ions into ammonia and protons, which protonate their pyridinic N-atoms. Photoluminescence (PL) emission is quenched.     

Natural Formulations Based on Olea europaea L. Fruit Extract for the Topical Treatment of HSV-1 Infections

In the present study, a hydroxytyrosol-rich Olea europaea L. fruit extract (OFE) was added to three thoroughly green formulations—hydrogel, oleogel, and cream—in order to evaluate their antiviral activity against HSV-1. The extract was characterized by different analytical techniques, i.e., FT-IR, XPS, and TGA. HPLC analyses were carried out to monitor the content and release of hydroxytyrosol in the prepared formulations. The total polyphenol content and antioxidant activity were investigated through Folin–Ciocâlteu’s reagent, DPPH, and ABTS assays. The ability of the three formulations to convey active principles to the skin was evaluated using a Franz cell, showing that the number of permeated polyphenols in the hydrogel (272.1 ± 1.8 GAE/g) was significantly higher than those in the oleogel and cream (174 ± 10 and 179.6 ± 2 GAE/g, respectively), even if a negligible amount of hydroxytyrosol crossed the membrane for all the formulations. The cell viability assay indicated that the OFE and the three formulations were not toxic to cultured Vero cells. The antiviral activity tests highlighted that the OFE had a strong inhibitory effect against HSV-1 with a 50% inhibitory concentration (IC50) at 25 µg/mL, interfering directly with the viral particles. Among the three formulations, the hydrogel exhibited the highest antiviral activity also against the acyclovir-resistant strain.