Correction to "N-Heterocyclic Carbene-Carbodiimide (NHC-CDI) Betaines as Organocatalysts for ß-Butyrolactone Polymerization: Synthesis of Green PHB Plasticizers with Tailored Molecular Weights".

[This corrects the article DOI: 10.1021/acscatal.3c05357.].

Alkali metal⋯methyl short contacts in aluminates: more than agostic interactions.

Knowing the nature and strength of noncovalent interactions is key to enhancing the synthetic methods and catalytic processes in which they are involved. We present herein the synthesis and characterization of a novel aluminium sodium oximate compound, followed by a comprehensive computational study of the sodium⋯methyl interaction that appears in its crystal structure. Our experimental results have been compared to a large set of structural data retrieved from the Cambridge Structural Database in order to assess the main geometrical preferences of these interactions. Moreover, representative model systems have been studied at the DFT level and the topology of their electron density analysed by means of QTAIM. Although alkali metal⋯methyl short contacts have been traditionally considered as agostic interactions, we have demonstrated here that the physical origin of the attraction relies on the electron-rich carbon atom bound to aluminium and its interaction with the cation.

Synthesis and applications of the sulfur containing analogues of cyclic carbonates.

Cyclic thiocarbonates are the sulfur containing analogues of the well-studied cyclic carbonates and are relatively poorly explored despite their potential applications and intriguing reactivities. To date, application of these organosulfur compounds has included their use as monomers for polythiocarbonate synthesis (their ring-opening is more readily achieved and more selective than the corresponding cyclic carbonates) and as reactive intermediates for the preparation of a range of higher-value sulfur containing compounds. Despite these uses, the synthesis of these compounds is far less explored and developed than their non-sulfur analogues. Here, we provide an overview of the state-of-the-art, both recent and historical, for the synthesis of a range of cyclic mono-, di- and tri-thiocarbonates (both five and six-membered rings), with selected examples of their reported applications also highlighted.

Pyridine-4-thiol as halogen-bond (HaB) acceptor: influence of the noncovalent interaction in its reactivity.

The study of pyridine-4-thiol as a halogen-bond (HaB) acceptor has allowed the isolation of its cocrystal with the HaB donor IC6F4I, namely, 1,2,4,5-tetrafluoro-3,6-diiodobenzene bis(pyridin-1-ium-4-ylsulfanide), C6F4I2·2C5H5NS (1), where the S atom is the HaB acceptor, while the pyridine position is blocked by the proton. Furthermore, the S atom acts a dual acceptor and also establishes an interaction with the pyridinium proton from an adjacent molecule. The presence of these interactions in 1 contributes to the stabilization of the zwitterionic form. This pre-organization seems to have an influence on the reactivity of the compound since when left in dichloromethane solution, an unusual activation of the C-Cl bond is observed that leads to the formation of the bis[(pyridin-1-ium-4-yl)sulfanyl]methane dication, while the Cl atoms are still present as chloride counter-ions, i.e. 4,4'-[methanediyldi(sulfanediyl)]dipyridinium dichloride, C11H12N2S22+·2Cl- (2). In the crystal structure of 2 it is observed that the S atom is now acting as the donor part of a chalcogenide bond with the chloride anions.

Group 13 salphen compounds (In, Ga and Al): a comparison of their structural features and activities as catalysts for cyclic carbonate synthesis.

Many complexes based on group 13 elements have been successfully applied as catalysts for the synthesis of cyclic carbonates from epoxides and CO2 and to date these have provided some of the most active catalysts developed. It is notable that most reports have focused on the use of aluminium-based compounds likely because of the well-established Lewis acidity of this element and its cost. In comparison, relatively little attention has been paid to the development of catalysts based on the heavier group 13 elements, despite their known Lewis acidic properties. This study describes the synthesis of aluminium, gallium and indium compounds supported by a readily prepared salphen ligand and explores both their comparative structures and also their potential as catalysts for the synthesis of cyclic carbonates. In addition, the halide ligand which forms a key part of the compound has been systematically varied and the effect of this change on the structure and catalytic activity is also discussed. It is demonstrated that the indium compounds are actually, and unexpectedly, the most active for cyclic carbonate synthesis, despite their lower Lewis acidity when compared to their aluminium congeners. The experimental observations from this work are fully supported by a Density Functional Theory (DFT) study, which provides important insights into the reasons as to why the indium catalyst with bromide, [InBr(salphen)], is most active.

σ-Hole triel bonds in aluminium derivatives.

This communication reports the synthesis and X-ray characterization of a new mononuclear aluminium compound exhibiting an intramolecular σ-hole triel bonding interaction. It is compared with a dinuclear aluminium compound, previously reported by us, where the aluminium atoms participate in two concurrent σ-hole triel bonding interactions. To our knowledge, such behaviour has not been previously described in the literature.

Chemoselective cycloadditions to epoxide derivatives of erucic acid with CO2 and CS2: controlled access to value-added bio-derived compounds.

The potential for application of bio-derived molecules in our everyday lives is attracting vast interest as attention moves towards development of a truly circular and sustainable economy. Whilst a large number of molecules are naturally available and contain a variety of functional groups, few of these compounds are able to be immediately transferred to applications where they can directly replace established oil-derived species. This issue presents both a challenge and an opportunity for the synthetic chemistry community. This study demonstrates how erucic acid, a molecule containing an olefin and a carboxylic acid, which is readily available from commonly cultivated rapeseed oils, can be used as a platform to be chemoselectively converted into a range of value-added compounds using established and high yielding synthetic procedures. In particular, the work showcases approaches towards the chemoselective (and in cases regioselective) oxidation with m-CPBA and incorporation of cyclic carbonate and cyclic dithiocarbonate functionalities which have potential to be employed in a range of applications. Expedient routes to unusual derivatives containing both cyclic carbonate and cyclic dithiocarbonates are also presented taking advantage of the distinct reactivities of the two different epoxides in the intermediate compounds. This work also provides a rare example of the synthesis of internal cyclic dithiocarbonates. These new products have potential to be applied as monomers in the growing field of bio-based non-isocyanate polyurethane synthesis.

Ring-Opening Polymerization of L-Lactide Catalyzed by Potassium-Based Complexes: Mechanistic Studies.

Two non-toxic potassium compounds, 1 and 2, with a commercial oximate ligand have been prepared and fully spectroscopically characterized. Their activity as catalysts for the ring-opening polymerization (ROP) process of LLA has been studied, showing that they are extremely active and able to polymerize the monomer in a few minutes. For derivative 2, the presence of a crown ether in the potassium coordination sphere affects the nuclearity of the compound and consequently its solubility, with both aspects having an influence in the polymerization process. Detailed studies of the polymerization mechanism have been performed, and an unusual anionic mechanism was observed in absence of a co-initiator. Indeed, the monomer deprotonation generates a lactide enolate, which initiates the polymerization propagation. On the contrary, when a 1:1 ratio of cat:BnOH is used, a mixture of mechanisms is observed, the anionic mechanism and the activated monomer one, while from a cat:BnOH ratio of 1:2 and over, only the activated monomer mechanism is observed.

Abrogation of Notch Signaling in Embryonic TECs Impacts Postnatal mTEC Homeostasis and Thymic Involution.

Notch signaling is crucial for fate specification and maturation of thymus-seeding progenitors along the T-cell lineage. Recent studies have extended the role of Notch signaling to thymic epithelial cells (TECs), showing that Notch regulates TEC progenitor maintenance and emergence of medullary TECs (mTECs) in fetal thymopoiesis. Based on immunohistochemistry studies of spatiotemporal regulation of Notch activation in the postnatal thymus, we show that in vivo Notch activation is not confined to fetal TECs. Rather, Notch signaling, likely mediated through the Notch1 receptor, is induced in postnatal cortical and medullary TECs, and increases significantly with age in the latter, in both humans and mice, suggesting a conserved role for Notch signaling in TEC homeostasis during thymus aging. To investigate the functional impact of Notch activation in postnatal TEC biology, we used a mouse model in which RPBJκ, the transcriptional effector of canonical Notch signaling, is deleted in epithelial cells, including TECs, under the control of the transcription factor Foxn1. Immunohistochemistry and flow cytometry analyses revealed no significant differences in TEC composition in mutant (RPBJκ-KOTEC) and wild-type (WT) littermate mice at early postnatal ages. However, a significant reduction of the medullary region was observed in mutant compared to WT older thymi, which was accompanied by an accelerated decrease of postnatal mTEC numbers. Also, we found that organization and integrity of the postnatal thymic medulla critically depends on activation of the canonical Notch signaling pathway, as abrogation of Notch signaling in TECs led to the disruption of the medullary thymic microenvironment and to an accelerated thymus atrophy. These features paralleled a significant increase in the proportion of intrathymic non-T lineage cells, mostly B cells, and a slight decrease of DP thymocyte numbers compatible with a compromised thymic function in mutant mice. Therefore, impaired Notch signaling induced in embryonic development impacts postnatal TECs and leads to an accelerated mTEC degeneration and a premature thymus involution. Collectively, our data have uncovered a new role for Notch1 signaling in the control of adult mTEC homeostasis, and point toward Notch signaling manipulation as a novel strategy for thymus regeneration and functional recovery from immunosenescence.

Rheology of Poly(glycidyl methacrylate) Macromolecular Nano Assemblies.

A recently reported combined polymerization process of glycidyl methacrylate, mediated by homometallic and heterobimetallic aluminium complexes, naturally produces nano-sized macromolecular assemblies. In this work, the morphological features and the rheological properties of these novel nanoassemblies are studied. The hydrodynamic sizes of the nanoparticles in the solution range from 10 to 40 nm (in numbers), but on a flat surface they adopt a characteristic thin disk shape. The dynamic moduli have been determined in a broad range of temperatures, and the time-temperature superposition applied to obtain master curves of the whole viscoelastic response from the glassy to the terminal regions. The fragility values obtained from the temperature dependence are of m ~40, typical of van de Waals liquids, suggesting a very effective packing of the macromolecular assemblies. The rheological master curves feature a characteristic viscoelastic relaxation with the absence of elastic intermediate plateau, indicating that the systems behaved as un-entangled polymers. The analysis of the linear viscoelastic fingerprint reveals a Zimm-like dynamics at intermediate frequencies typical of unentangled systems. This behaviour resembles that observed in highly functionalized stars, dendrimers, soft colloids and microgels.

NHC-CDI Betaine Adducts and Their Cationic Derivatives as Catalyst Precursors for Dichloromethane Valorization.

Zwitterionic adducts of N-heterocyclic carbene and carbodiimide (NHC-CDI) are an emerging class of organic compounds with promising properties for applications in various fields. Herein, we report the use of the ICyCDI(p-Tol) betaine adduct (1a) and its cationic derivatives 2a and 3a as catalyst precursors for the dichloromethane valorization via transformation into high added value products CH2Z2 (Z = OR, SR or NR2). This process implies selective chloride substitution of dichloromethane by a range of nucleophiles Na+Z- (preformed or generated in situ from HZ and an inorganic base) to yield formaldehyde-derived acetals, dithioacetals, or aminals with full selectivity. The reactions are conducted in a multigram-scale under very mild conditions, using dichloromethane both as a reagent and solvent, and very low catalyst loading (0.01 mol %). The CH2Z2 derivatives were isolated in quantitative yields after filtration and evaporation, which facilitates recycling the dichloromethane excess. Mechanistic studies for the synthesis of methylal CH2(OMe)2 rule out organocatalysis as being responsible for the CH2 transfer, and a phase-transfer catalysis mechanism is proposed instead. Furthermore, we observed that 1a and 2a react with NaOMe to form unusual isoureate ethers, which are the actual phase-transfer catalysts, with a strong preference for sodium over other alkali metal nucleophiles.

Poly(glycidyl methacrylate) macromolecular assemblies as biocompatible nanocarrier for the antimicrobial lysozyme.

The antimicrobial lysozyme (Lys) was electrostatically incorporated to negatively charged crosslinked poly(glycidyl methacrylate) (c-PGMA) macromolecular assemblies. The resulting material was characterized by AFM, infrared spectra, water contact angle measurements and the staining with the primary amino specific dye fluorescamine. c-PGMA nanoparticles were successfully loaded with Lys reaching ratios of 27.3 ± 4.0 and 22.5 ± 1.7 mg Lys/g polymer for c-PGMA suspensions and functionalized glass substrates, respectively. Lys-loaded c-PGMA caused clear inhibition zones on S. aureus and E. coli in comparison to neat c-PGMA. c-PGMA functionalized surfaces were intrinsically resistant to colonization, but the incorporation of Lys added resistance to bacterial attachment and allowed keeping surfaces clean of bacterial cells for both strains. A relatively rapid release (24 h) of Lys was observed at physiological pH (7.4). In addition, c-PGMA functionalized substrates could be reloaded several times without losing capacity. c-PGMA macromolecular assemblies did not display cytotoxicity to human dermal fibroblasts as shown in 24 h MTT assays. This work demonstrated that c-PGMA assemblies display durable antibacterial activity, biocompatibility, and full reloading capacity with antimicrobial peptides. c-PGMA functionalized materials have potential application as nanocarriers for anti-infective uses.

Conjugated polymer nanostructures displaying highly photoactivated antimicrobial and antibiofilm functionalities.

This work reports the use of conjugated polymer nanostructures (CPNs) as photoactivated antimicrobial compounds against Gram-positive and Gram-negative microorganisms. Two representative CPNs of polythiophene (PEDOT) and polyaniline (PANI) were prepared as nanofibres with an average diameter of 40 nm and length in the micrometer range. Both CPNs exhibited strong antimicrobial activity under UVA irradiation with the same fluence rate as the UVA component of the solar spectrum. The effect was tested using the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli. The reduction of colony forming units (CFUs) reached >6 log for PEDOT concentrations as low as 33 ng mL-1. For PEDOT nanofibers, a complete inhibition of S. aureus and E. coli growth was reached at 883 ng mL-1 and 333 ng mL-1 respectively. The photoactivation effect of PANI nanofibres on S. aureus and E. coli was also high, with a CFU reduction of about 7 log and 4 log respectively for an exposure concentration of 33 ng mL-1. The antimicrobial activity was only high under light irradiation and was almost negligible for bulk PEDOT and PANI. The effect of polymeric nanofibers could be attributed to the photoinduced generation of reactive oxygen species, which may induce cell membrane damage, eventually leading to bacterial impairment and inhibition of their biofilm forming capacity. CPN PEDOT and PANI coatings were able to keep surfaces free of bacterial attachment and growth even after 20 h of previous contact with exponentially growing cultures in the dark. PEDOT and PANI CPNs demonstrated good cytocompatibility with human fibroblasts and the absence of hemolytic activity. The materials demonstrated advantages in terms of broad antibacterial spectrum, biofilm inhibition, and the absence of acute toxicity for biomedical applications.

Polymeric ruthenium precursor as a photoactivated antimicrobial agent.

Ruthenium coordination compounds have demonstrated a promising anticancer and antibacterial activity, but their poor water solubility and low stability under physiological conditions may limit their therapeutic applications. Physical encapsulation or covalent conjugation with polymers may overcome these drawbacks, but generally involve multistep reactions and purification processes. In this work, the antibacterial activity of the polymeric precursor dicarbonyldichlororuthenium (II) [Ru(CO)2Cl2]n has been studied against Escherichia coli and Staphylococcus aureus. This Ru-carbonyl precursor shows minimum inhibitory concentration at nanogram per millilitre, which renders it a novel antimicrobial polymer without any organic ligands. Besides, [Ru(CO)2Cl2]n antimicrobial activity is markedly boosted under photoirradiation, which can be ascribed to the enhanced generation of reactive oxygen species under UV irradiation. [Ru(CO)2Cl2]n has been able to inhibit bacterial growth via the disruption of bacterial membranes and triggering upregulation of stress responses as shown in microscopic measurements. The activity of polymeric ruthenium as an antibacterial material is significant even at 6.6 ng/mL while remaining biocompatible to the mammalian cells at much higher concentrations. This study proves that this simple precursor, [Ru(CO)2Cl2]n, can be used as an antimicrobial compound with high activity and a low toxicity profile in the context of need for new antimicrobial agents to fight bacterial infections.

Conducting Polymer-Based Nanohybrids for Fuel Cell Application.

Carbon materials such as carbon graphitic structures, carbon nanotubes, and graphene nanosheets are extensively used as supports for electrocatalysts in fuel cells. Alternatively, conducting polymers displayed ultrahigh electrical conductivity and high chemical stability havegenerated an intense research interest as catalysts support for polymer electrolyte membrane fuel cells (PEMFCs) as well as microbial fuel cells (MFCs). Moreover, metal or metal oxides catalysts can be immobilized on the pure polymer or the functionalized polymer surface to generate conducting polymer-based nanohybrids (CPNHs) with improved catalytic performance and stability. Metal oxides generally have large surface area and/or porous structures and showed unique synergistic effects with CPs. Therefore, a stable, environmentally friendly bio/electro-catalyst can be obtained with CPNHs along with better catalytic activity and enhanced electron-transfer rate. The mass activity of Pd/polypyrrole (PPy) CPNHs as an anode material for ethanol oxidation is 7.5 and 78 times higher than that of commercial Pd/C and bulk Pd/PPy. The Pd rich multimetallic alloys incorporated on PPy nanofibers exhibited an excellent electrocatalytic activity which is approximately 5.5 times higher than monometallic counter parts. Similarly, binary and ternary Pt-rich electrocatalysts demonstrated superior catalytic activity for the methanol oxidation, and the catalytic activity of Pt24Pd26Au50/PPy significantly improved up to 12.5 A per mg Pt, which is approximately15 times higher than commercial Pt/C (0.85 A per mg Pt). The recent progress on CPNH materials as anode/cathode and membranes for fuel cell has been systematically reviewed, with detailed understandings into the characteristics, modifications, and performances of the electrode materials.

IL-7R is essential for leukemia-initiating cell activity of T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy resulting from the dysregulation of signaling pathways that control intrathymic T-cell development. Relapse rates are still significant, and prognosis is particularly bleak for relapsed patients. Therefore, development of novel therapies specifically targeting pathways controlling leukemia-initiating cell (LIC) activity is mandatory for fighting refractory T-ALL. The interleukin-7 receptor (IL-7R) is a crucial T-cell developmental pathway that is commonly expressed in T-ALL and has been implicated in leukemia progression; however, the significance of IL-7R/IL-7 signaling in T-ALL pathogenesis and its contribution to disease relapse remain unknown. To directly explore whether IL-7R targeting may be therapeutically efficient against T-ALL relapse, we focused on a known Notch1-induced T-ALL model, because a majority of T-ALL patients harbor activating mutations in NOTCH1, which is a transcriptional regulator of IL-7R expression. Using loss-of-function approaches, we show that Il7r-deficient, but not wild-type, mouse hematopoietic progenitors transduced with constitutively active Notch1 failed to generate leukemia upon transplantation into immunodeficient mice, thus providing formal evidence that IL-7R function is essential for Notch1-induced T-cell leukemogenesis. Moreover, we demonstrate that IL-7R expression is an early functional biomarker of T-ALL cells with LIC potential and report that impaired IL-7R signaling hampers engraftment and progression of patient-derived T-ALL xenografts. Notably, we show that IL-7R-dependent LIC activity and leukemia progression can be extended to human B-cell acute lymphoblastic leukemia (B-ALL). These results have important therapeutic implications, highlighting the relevance that targeting normal IL-7R signaling may have in future therapeutic interventions, particularly for preventing T-ALL (and B-ALL) relapse.

Heterobimetallic aluminate derivatives with bulky phenoxide ligands: a catalyst for selective vinyl polymerization.

New aluminium-alkali metal heterometallic compounds using the bulky ligand OAr = 2,6-bis(diphenylmethyl)-4-tert-butylphenoxide have been synthesized and characterized. The species obtained, [MAlMe3(OAr)] (M = Li(2a), Na(2b), K(2c)) and [MAlMe2(OAr)2] (M = Li(3a), Na(3b), K(3c)), include some of the few heterobimetallic examples of aluminate complexes with O-donor ligands described so far. Their activity in polymerization towards a difunctional monomer, such as Glycidyl Methacrylate (GMA), was evaluated. The compounds were revealed to be able to polymerize the acrylate groups via vinyl polymerization. Interestingly, the homometallic counterparts [AlXMe(OAr)] (X = Cl, Me), previously described by us, are very active in ROP processes of GMA. The combined polymerization process using both catalysts has also been explored to obtain a polymeric material with an exciting macromolecular architecture.

Aluminates with Fluorinated Schiff Bases: Influence of the Alkali Metal⁻Fluorine Interactions in Structure Stabilization.

New heterometallic aluminium-alkali metal compounds have been prepared using Schiff bases with electron withdrawing substituents as ligands. The synthesis of these new species was achieved via the reaction of AlMe3 with the freshly prepared alkali-metallated ligand. The derivatives formed were characterized by NMR in solution and by single crystal X-ray diffraction in the solid state. Aluminate derivatives with lithium and sodium were prepared and a clear influence of the alkali metal in the final outcome is observed. The presence of a Na···F interaction in the solid state has a stabilization effect and the species [NaAlMe3L]2 can de isolated for the first time, which was not possible when using Schiff bases without electron withdrawing substituents as ligands.

Interaction of an imidazolium-2-amidinate (NHC-CDI) zwitterion with zinc dichloride in dichloromethane: role as ligands and C-Cl activation promoters.

Adducts of imidazolium carbenes and carbodiimides (NHC-CDI) are emerging as a new class of thermally stable and modular zwitterions with many potential applications. Our study of the interaction of a representative NHC-CDI zwitterion with ZnCl2 in dichloromethane led to the serendipitous discovery of a highly selective, double activation of dichloromethane C-Cl bonds.