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A multivariate approach allows the treatment of coordination structural data of complexes [Fe(bpp-R)2](X)2·solvent into unified models that take into account the crystal packing effects on the modulation of the magnetic features in the solid state.

Immobilization of redox active complexes as electrodes modifier is appealing for a large set of applications such as sensing, electrolysers or fuel cell. In this work iron based N-heterocyclic carbene complexes bearing an 3,4‑Ethylene dioxythiophene (EDOT) moiety in the side chain have been prepared following two different synthetic approaches determined by the length of the lateral chain. The approaches exploit carbonyldiimidazole (CDI) as the coupling agent between the –CH2OH moiety of the hydroxymethyl-EDOT and the –OH functionalized N-heterocyclic carbene iron complex or the imidazolium salt precursor. In both cases, the syntheses allow to obtain functional monomers suitable for electrochemical polymerization in the form of thin films on conducting substrates. The modified electrodes have been characterized by ATR-IR, showing successful copolymerisation to functionalized poly(3,4‑ethylene dioxythiophene) (PEDOT), by cyclic voltammetry (CV), demonstrating the dominant and reversible redox response of NHC-iron complexes, and by SEM-EDS, which provides the average copolymerisation ratio. The capability of the NHC-iron complex to act as a redox mediator has been assessed by using the functionalized device for glucose detection.

Accepted Manuscript version. The Published Journal Article is available on Biochimica et Biophysica Acta (BBA) - Biomembranes, Volume 1863, Issue 9, Article number 183641 (DOI: https://doi.org/10.1016/j.bbamem.2021.183641). Supplementary Material available free of charge on the article webpage. © 2021. This Manuscript version is made available under the CC-BY-NC-ND 4.0 license. https://creativecommons.org/licenses/by-nc-nd/4.0/ ABSTRACT The ability of styrene–maleic acid (SMAc) co-polymers to spontaneously insert into biological membranes can be exploited to extract G protein-coupled receptors (GPCRs) embedded in styrene–maleic acid lipid particles (SMALPs), preserving the native environment around the protein and thus enhancing the feasibility 20 of functional studies. So far, the SMALP technology has been primarily employed on non-mammalian cells and protocols are not optimized for adherent human cell lines, which cannot be harvested in large amounts. In this work, a fine investigation of key parameters affecting the formation of SMALPs was undertaken with the purpose of maximizing the yield of extraction of a recombinant form of human β2-adrenergic receptor (rhβ2AR) from HEK293T cells. The study highlighted an important influence of ionic strength on the 25 membrane solubilization efficiency and GPCR purification yield of SMAc co-polymers: by lowering the salt concentration of all buffers used in previously published SMALP protocols, the water solubility and extraction efficiency of the selected SMAc co-polymer (commercially supplied as a potassium salt) were enhanced. In-line combination of size-exclusion chromatography (SEC) with immobilized metal affinity chromatography (IMAC) allowed further improvement of the final rhβ2AR yield by reducing the loss of 30 SMALP-embedded GPCRs during the fractionation and purification of SMALPs. The overall findings of this study show that the available SMALP protocols can be significantly optimized in several aspects in order to increase the efficiency of GPCR solubilization and isolation from low-yielding expression systems.

The ability of styrene–maleic acid (SMAc) co-polymers to spontaneously insert into biological membranes can be exploited to extract G protein-coupled receptors (GPCRs) embedded in styrene–maleic acid lipid particles (SMALPs), preserving the native environment around the protein and thus enhancing the feasibility of functional studies. So far, the SMALP technology has been primarily employed on non-mammalian cells and protocols are not optimized for adherent human cell lines, which cannot be harvested in large amounts. In this work, a fine investigation of key parameters affecting the formation of SMALPs was undertaken with the purpose of maximizing the yield of extraction of a recombinant form of human β2-adrenergic receptor (rhβ2AR) from HEK293T cells. The study highlighted an important influence of ionic strength on the membrane solubilization efficiency and GPCR purification yield of SMAc co-polymers: by lowering the salt concentration of all buffers used in previously published SMALP protocols, the water solubility and extraction efficiency of the selected SMAc co-polymer (commercially supplied as a potassium salt) were enhanced. In-line combination of size-exclusion chromatography (SEC) with immobilized metal affinity chromatography (IMAC) allowed further improvement of the final rhβ2AR yield by reducing the loss of SMALP-embedded GPCRs during the fractionation and purification of SMALPs. The overall findings of this study show that the available SMALP protocols can be significantly optimized in several aspects in order to increase the efficiency of GPCR solubilization and isolation from low-yielding expression systems.HighlightsThe SMALP technology enables a direct solubilization of GPCRs from cell membranes.The isolation of GPCRs from mammalian cells is usually a low-yield procedure.SMALPs embedding the β2-adrenergic receptor were prepared from a HEK293T cell line.The ionic strength of buffers plays a key role in SMALP formation and isolation.Standard SMALP protocols can be finely optimized to increase purification yields.Graphical abstract

The reactivity of the dinuclear complex dicarbonyl[η4-3,4-bis(4-methoxyphenyl)-2,5-diphenylcyclopenta-2,4-dienone] (2) with imidazolium salts has been studied using a library of variously functionalized imidazolium salts, and leading to a class of ruthenium anionic complexes of the type [dicarbonylη4-3,4-bis(4-methoxyphenyl)-2,5-diphenylcyclopenta-2,4-dienone (halide)Ru][1,3-disubsittuted-imidazolium] (4) in the form of ion pair with imidazolium. The reaction is clean, general and quantitative and the complexes formed are stable to air and moisture both in the solid state and in solution. The ionic complexes 4 show affinity for ionic liquids and represent stable precursors of a catalytic active species, likely similar to those generated from Shvo catalyst, a well-established homogeneous bifunctional catalyst for hydrogen transfer. Our approach allows the use of green ionic liquids (IL) as solvents, providing better control of catalytic reactions involving 4, and easier catalyst recycle. IL-supported ionic pair catalysts exhibit interesting catalytic activity (up to > 99 % of conversion) in the transfer hydrogenation of a model compound such as 4-fluoroacetophenone. The IL-supported redox catalysts can be also recycled exploiting the biphasic nature of the system. The synthetic method here discussed represents a novelty within the field of IL-supportation and is potentially useful for the heterogenization of the catalysts.

The peculiar reactivity of catechol carbonate (CC) with amines and polyamines in both solvent and catalyst free conditions is herein described. In all the tests performed at room temperature, CC conversion reached 100% in few seconds leading to the selective formation of the corresponding 2-hydroxyphenylcarbamate. This compound is furtherly rapidly converted to the di-substituted urea by the consecutive nucleophilic attack of another amine. Noteworthy, the application of this approach can be successfully extended to the one-pot bio-amine based synthesis of polyurea as herein proposed for the first time in literature. The reaction is of general purpose for primary amines and catechol can be easily recovered by sublimation as pure crystals ready to be recycled for the synthesis of new CC. An exception is related to the reactivity of secondary amine, which leads anyway to the selective formation of substituted phenolic carbamates (e.g. 2-hydroxyphenyl diethylcarbamate), suitable as intermediates in medicinal chemistry.

The design of new flame retardants (FR) that avoid the use of halogen and phosphorus additives is challenging and urgent. Herein we report on the synthesis of bis-amino functionalized N-heterocyclic carbene cyclopentadienone iron complexes aimed at promoting the production of iron containing epoxy resins. Iron complexes are successfully employed to obtain high Tg thermosets with as low as 5% hardener content. Moreover the obtained resins display an impressive charring ability that paves the way to the application of such systems for material with improved flame behavior.

A large number of catalysts for hydrogen evolution reaction (HER) that are related (structurally and/or functionally) to the active site of [FeFe]-hydrogenases (H-cluster) has been proposed in the past few decades. Very recently, a novel recipe for HER catalysts has been added to the list. This consists in the combination of a diiron core, a ligand that can act as an intramolecular weak base to support protonation (both features that are common to the H-cluster), and a peculiar carbyne ligand that bridges the two metal centers. For instance, complex [Fe2{μ-CNMe2}(μ-CO)(CO)(CN)Cp2] (4) proved to be catalytically active towards HER. The novelty related to this family of biomimicry is not only structural, but also mechanistic. Indeed, an unprecedented (in the context of hydrogenase mimicry) ligand-based mechanism of HER, which avoids protonation at metal, has been dissected by DFT. In order to increase catalytic activity of this “non dithiolate based” system, a systematic search of ligand modification is therefore desirable. In this regard, herein we present results of replacing CN− (the proton shuttle in 4) by other ligands such as CNCH2Ph (5), PPh3 (6) or azide (7). The redox behavior of these compounds has been tested, in the absence and presence of a proton source. CV experiments combined with DFT calculations have revealed and rationalized critical points entailed by modifications of stereo-electronic features of 4. However, understanding the key factors underlying the absence of catalytic activity of these new compounds can be beneficial for the design of future improved biomimicry related to HER. As an example, properly tailored hydrocarbyl complexes replacing dithiolates at the Fe2 core might allow recovering the fruitful electronic properties of cyanides, when coordinated to metal centers.

The synthesis of a bis-amino-functionalized iron cyclopentadienone N-heterocyclic carbene complex (1) has been fine tuned to develop an hardener for the production of a novel hybrid epoxy resin (EP) with the aim of also reducing fire hazard. The synthesized organometallic complex well performs as curing agent both with DGEBA, preliminary employed, and the commercial pre-polymer Elan-tron® EC 157 in different formulations (loading range 5, 7.5, 10%wt). Thermogravimetric analyses revealed that curing temperature shows a significant intumescent char residual (yield 25%), possibly to due iron presence. DSC indicated that reaction rate and glass transition increase with complex 1 content, and under isothermal conditions the best performances have been identified at 170 °C and 7.5%wt of 1. The latter conditions has been finally employed for tests in cone calorimeter displaying a charring action of the complex included in the resins, together with an early ignition that has to be addressed playing on the formulation and chemical structure of the hardener.

In the structure of title borohydride pincer complex, [Co(BH4)(C16H37NP2)(CO)], the cobalt(I) metal exhibits a distorted square-pyramidal coordination geometry with the basal positions occupied by the P and N atoms of the tridentate ligand and by the C atom of the carbon monoxide ligand. In the crystal, molecules interact only by van der Waals forces.

DFT has been used to investigate viable mechanisms of the hydrogen evolution reaction (HER) electrocatalyzed by [Fe

A selection of cobalt(I) and cobalt(II) pincer type complexes with different substitution patterns was tested in the catalytic reduction of carboxylic acid esters to alcohols. The cobalt pincer type complex 4 is suitable for the hydrogenation of aromatic as well as aliphatic and cyclic esters. Mechanistic investigation indicated a metal ligand cooperated reaction pathway.

DFT has been used to investigate viable mechanisms of the hydrogen evolution reaction (HER) electrocatalyzed by [Fe2(CN){μ-CN(Me)2}(μ-CO)(CO)(Cp)2] (1) in AcOH. Molecular details underlying the proposed ECEC electrochemical sequence have been studied, and the key functionalities of CN- and amino-carbyne ligands have been elucidated. After the first reduction, CN- works as a relay for the first proton from AcOH to the carbyne, with this ligand serving as the main electron acceptor for both reduction steps. After the second reduction, a second protonation occurs at CN- that forms a Fe(CNH) moiety: i.e., the acidic source for the H2 generation. The hydride (formally 2e/H+), necessary to the heterocoupling with H+ is thus provided by the μ-CN(Me)2 ligand and not by Fe centers, as occurs in typical L6Fe2S2 derivatives modeling the hydrogenase active site. It is remarkable, in this regard, that CN- plays a role more subtle than that previously expected (increasing electron density at Fe atoms). In addition, the role of AcOH in shuttling protons from CN- to CN(Me)2 is highlighted. The incompetence for the HER of the related species [Fe2{μ-CN(Me)2}(μ-CO)(CO)2(Cp)2]+ (2+) has been investigated and attributed to the loss of proton responsiveness caused by CN- replacement with CO. In the context of hydrogenase mimicry, an implication of this study is that the dithiolate strap, normally present in all synthetic models, can be removed from the Fe2 core without loss of HER, but the redox and acid-base processes underlying turnover switch from a metal-based to a ligand-based chemistry. The versatile nature of the carbyne, once incorporated in the Fe2 scaffold, could be exploited to develop more active and robust catalysts for the HER.

Pediatric hospitals usually need their pharmacy departments to prepare drug formulations that are not available commercially, especially dosages for pediatric patients, which are often not manufactured at industrial scale. Once compounded, most of these formulations must be used on the day of

Novel iron complexes bearing both cyclopentadienone and N-heterocyclic carbene ancillary ligands were obtained by a straightforward synthesis from Fe2(CO)9. The preparation represents a rare example of silver transmetallation involving iron. The reaction is general and occurs in the presence of variously functionalized NHC and cyclopentadienones.

A series of novel cationic hydroxycyclopentadienyl and methoxycyclopentadienyl N-heterocyclic carbene ruthenium(II) complexes have been synthesized from the corresponding neutral ruthenium(0) complexes containing both the non-innocent cyclopentadienone ligand and variously functionalized N-heterocyclic carbenes (NHCs). In particular an NHC derivative containing a pyridine group in the side chain has been designed and developed in order to evaluate the influence of a basic, potentially cooperative substituent in the catalytic activity of these complexes. All the prepared complexes were employed as selective catalysts for transfer hydrogenation reactions employing refluxing iPrOH as a hydrogen source and several ketones and aldehydes as substrates. We found that while the presence of oxidizing additives such as CAN and benzoquinone is mandatory to activate the neutral ruthenium(0) complexes, no activation is needed for the cationic Ru(II) catalysts. The catalytic activity of the latter is also influenced by the coordinating ability of the counterion, and indeed the cationic complexes having a pyridine-functionalized NHC ligand and CF3SO3− as counterion, present the best conversion (>99%) thus demonstrating the fundamental role played by the basic pyridine in the catalytic activity. With regard to the hydrogenation reaction mechanism, the release of the CO ligand was demonstrated to be the key step and the presence of hydride species has been detected at the end of the reaction.

This study was conducted to compare the bioavailability of two prolonged-release pharmaceutical forms containing 300 mg of diltiazem. The test formulation is a new design of tablets with a hydrophilic matrix, and the reference formulation is capsules containing prolonged liberation microgranules, in the same dose, that are commercially available in the pharmaceutical market. Diltiazem plasma concentrations were analyzed by high-performance liquid chromatography (HPLC), which involves solid-phase extraction for plasma sample preparation. Twelve healthy volunteers participated in the study, which had a single-dose, two-treatment, two-sequence-crossover, randomized design. The preparations were compared using pharmacokinetic parameters such as the area under the plasma concentration-time curve AUC(0-36), peak plasma concentration Cmax, and Cmax/AUC(0-36) ratio as a measure for the absorption rate. No statistically significant difference was observed for any of the parameters, and the 90% confidence intervals calculated for the ratio of the logarithmically transformed AUC(0-36) and Cmax/AUC(0-36) values of both formulations were within the bioequivalence limit of 0.80-1.25. Moreover, an in vitro study of dissolution according to USP 23 was conducted, and the in vitro parameters were calculated.