En route to coordination chemistry under confined conditions in a porous capsule: Pr3+ with different coordination shells

The highly charged nanocontainer capsule of the type [pentagon]12[linker]30 identical with [(Mo)Mo5O21(H2O)6]12[Mo2O4(SO4)]30 with 20 nanosized pores and channels allows the entrance of cations like Pr3+: the latter are positioned at two different sites and have two different coordination shells, corresponding to a coordination chemistry under confined conditions; a fascinating aspect is that capsule encapsulated water shells fixed by hydrogen bonds act formally as polydentate ligands.     

Micellar shape change and internal segregation induced by chemical modification of a tryptych block copolymer surfactant

We report the detailed characterization of micelles formed by two nonionic, amphiphilic ABC triblock copolymers. Poly(ethylene oxide)-b-poly(styrene)-b-1,2-poly(butadiene) (PEO-b-PS-b-PB) triblock copolymer "OSB" forms core-corona spherical micelles in aqueous solution, and the two hydrophobic blocks S and B are mixed homogeneously within the micelle core. PEO-b-PS-b-PB:C6F13I triblock copolymer "OSF" was prepared by selective fluorination of the B block in OSB with n-perfluorohexyl iodide. Fluorination of the B block induces internal segregation into an inner F core and an intermediate S shell. Furthermore, the strong incompatibility that results from fluorination drives a shape change into an oblate ellipsoid. These micellar morphologies are confirmed by combined light, neutron, and X-ray scattering measurements, as well as TEM imaging.     

Improved access to 19-nor-7β, 8β-methylene-taxoids and formation of a 7-membered C-ring analog of doxetaxel by electrochemistry

A new route to semisynthetic 19-nor-7β, 8β-methylene taxoids, such as compound 8, from the 7-O-trifluoromethanesulfonyl derivative 6 is reported. Evidence for a dissociation of the triflate to form a carbocation at C-7 under the reaction conditions is presented. Electrochemical reduction of the cyclopropane taxoid 8 gives, besides the expected 10-dehydroxy-cyclopropane analog 10, the 7-membered C-ring derivative 11.     

Observations of Bell Inequality Violations with Causal Isolation between Source and Detectors

We report the experimental observations of Bell inequality violations (BIV) in entangled photons causally separated by a rotating mirror. A Foucault mirror gating geometry is used to causally isolate the entangled photon source and detectors. We report an observed BIV of CHSH-S=2.30±0.07>2.00. This result rules out theories that explain correlations with traveling communication between source and detectors, including super-luminal and instantaneous communication.     

Supramolecular Protein-Polyelectrolyte Assembly at Near Physiological Conditions—Water Proton NMR,ITC, and DLS Study

The in vivo potency of polyphosphazene immunoadjuvants is inherently linked to the ability of these ionic macromolecules to assemble with antigenic proteins in aqueous solutions and form physiologically stable supramolecular complexes. Therefore, in-depth knowledge of interactions in this biologically relevant system is a prerequisite for a better understanding of mechanism of immunoadjuvant activity. Present study explores a self-assembly of polyphosphazene immunoadjuvant—PCPP and a model antigen—lysozyme in a physiologically relevant environment—saline solution and neutral pH. Three analytical techniques were employed to characterize reaction thermodynamics, water-solute structural organization, and supramolecular dimensions: isothermal titration calorimetry (ITC), water proton nuclear magnetic resonance (wNMR), and dynamic light scattering (DLS). The formation of lysozyme–PCPP complexes at near physiological conditions was detected by all methods and the avidity was modulated by a physical state and dimensions of the assemblies. Thermodynamic analysis revealed the dissociation constant in micromolar range and the dominance of enthalpy factor in interactions, which is in line with previously suggested model of protein charge anisotropy and small persistence length of the polymer favoring the formation of high affinity complexes. The paper reports advantageous use of wNMR method for studying protein-polymer interactions, especially for low protein-load complexes.     

Thiazole fused S,N-heteroacene step-ladder polymeric semiconductors for organic transistors

Ladder-type thiazole-fused S,N-heteroacenes with an extended π-conjugation consisting of six (SN6-Tz) and nine (SN9-Tz) fused aromatic rings have been synthesized and fully characterized. To date, the synthesis of well-defined fused building blocks and polymers of π-conjugated organic compounds based on the thiazole moiety is a considerable synthetic challenge, due to the difficulty in their synthesis. Acceptor–donor building blocks M1 and M2 were successfully polymerized into ladder homopolymers P1–P2 and further copolymerized with a diketopyrrolopyrrole unit to afford step-ladder copolymer P3. The optical, electronic, and thermal properties, in addition to their charge transport behavior in organic thin-film transistors (OTFTs), were investigated. The results showed an interesting effect on the molecular arrangement of the thiazole-based ladder-type heteroacene in the crystal structure revealing skewed π–π-stacking, and expected to possess better p-type semiconducting performance. The polymers all possess good molecular weights and excellent thermal properties. All the polymer-based OTFT devices exhibit annealing temperature dependent performance, and among the polymers P3 exhibits the highest mobility of 0.05 cm² V⁻¹ s⁻¹.

Ladder-type thiazole-fused S,N-heteroacenes with an extended π-conjugation consisting of six (SN6-Tz) and nine (SN9-Tz) fused aromatic rings have been synthesized and fully characterized.     

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.     

Folding Free Energy Determination of an RNA Three-Way Junction Using Fluctuation Theorems

Nonequilibrium work relations and fluctuation theorems permit us to extract equilibrium information from nonequilibrium measurements. They find application in single-molecule pulling experiments where molecular free energies can be determined from irreversible work measurements by using unidirectional (e.g., Jarzynski’s equality) and bidirectional (e.g., Crooks fluctuation theorem and Bennet’s acceptance ratio (BAR)) methods. However, irreversibility and the finite number of pulls limit their applicability: the higher the dissipation, the larger the number of pulls necessary to estimate ΔG within a few kBT. Here, we revisit pulling experiments on an RNA three-way junction (3WJ) that exhibits significant dissipation and work-distribution long tails upon mechanical unfolding. While bidirectional methods are more predictive, unidirectional methods are strongly biased. We also consider a cyclic protocol that combines the forward and reverse work values to increase the statistics of the measurements. For a fixed total experimental time, faster pulling rates permit us to efficiently sample rare events and reduce the bias, compensating for the increased dissipation. This analysis provides a more stringent test of the fluctuation theorem in the large irreversibility regime.     

Ziziphus nummularia: A Comprehensive Review of Its Phytochemical Constituents and Pharmacological Properties

Ziziphus nummularia, a small bush of the Rhamnaceae family, has been widely used in traditional folk medicine, is rich in bioactive molecules, and has many reported pharmacological and therapeutic properties. Objective: To gather the current knowledge related to the medicinal characteristics of Z. nummularia. Specifically, its phytochemical contents and pharmacological activities in the treatment of various diseases such as cancer, diabetes, and cardiovascular diseases, are discussed. Methods: Major scientific literature databases, including PubMed, Scopus, ScienceDirect, SciFinder, Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, Henriette’s Herbal Homepage, Dr. Duke’s Phytochemical and Ethnobotanical Databases, were searched to retrieve articles related to the review subject. General web searches using Google and Google scholar were also utilized. The search period covered articles published between 1980 and the end of October 2021.The search used the keywords ‘Ziziphus nummularia’, AND (‘phytochemical content’, ‘pharmacological properties, or activities, or effects, or roles’, ‘anti-inflammatory’, ‘anti-drought’, ‘anti-thermal’, ‘anthelmintic’, ‘antidiabetic’,’ anticancer’, ‘anticholinesterase’, ‘antimicrobial’, ‘sedative’, ‘antipyretic’, ‘analgesic’, or ‘gastrointestinal’). Results: This plant is rich in characteristic alkaloids, especially cyclopeptide alkaloids such as nummularine-M. Other phytochemicals, including flavonoids, saponins, glycosides, tannins, and phenolic compounds, are also present. These phytochemicals are responsible for the reported pharmacological properties of Z. nummularia, including anti-inflammatory, antioxidant, antimicrobial, anthelmintic, antidiabetic, anticancer, analgesic, and gastrointestinal activities. In addition, Z. nummularia has anti-drought and anti-thermal characteristics. Conclusion: Research into the phytochemical and pharmacological properties of Z. nummularia has demonstrated that this plant is a rich source of novel bioactive compounds. So far, Z. nummularia has shown a varied pharmacological profile (antioxidant, anticancer, anti-inflammatory, and cardioprotective), warranting further research to uncover the therapeutic potential of the bioactives of this plant. Taken together, Z. nummularia may represent a new potential target for the discovery of new drug leads.