Search

The synthesis and characterization of two homoleptic Zn(II)- and Mg(II)-complexes based on a simple tridentate {NNO} ligand are reported. The production of biocompatible atactic poly(lactic acid) (PLA) under industrially relevant melt conditions is demonstrated, noting high activity for Zn(1) 2at room temperature in CH 2Cl 2(TOF = 184 h -1). Mg(1) 2and Zn(1) 2were shown to facilitate rapid PLA methanolysis into methyl lactate (Me-LA) under mild conditions, achieving up to 85% Me-LA yield within 30 min at 50 °C in THF. Further kinetic analysis found Mg(1) 2and Zn(1) 2to exhibitk appvalues of 0.23 ± 0.0076 and 0.15 ± 0.0029 min -1, respectively {8 wt % cat. loading}, among the highest reported thus far. Zn(1) 2retained excellent activity for both poly(ethylene terephthalate) (PET) and poly(ε-caprolactone) (PCL) degradations, demonstrating catalyst versatility. Various upcycling strategies (e.g., methanolysis, glycolysis, and aminolysis) were employed to achieve a broad substrate scope, which included bis(2-hydroxyethyl) terephthalate (BHET), high value terephthalamides, and methyl 6-hydroxyhexanoate. Optimal glycolysis conditions using Zn(1) 2enabled 64% BHET yield within 1 h at 180 °C, a rare example of PET glycolysis mediated by a discrete homogeneous metal-based catalyst. The application of such catalysts for PET aminolysis and PCL methanolysis has been reported for the first time.

The concept of Molecular Crowding depicts the high density of diverse molecules present in the cellular interior. Here, we determine the impact of low molecular weight and larger molecules on binding capacity of single-stranded DNA (ssDNA) to the cold shock protein B (CspB). Whereas structural features of ssDNA-bound CspB are fully conserved in crowded environments as probed by high-resolution NMR spectroscopy, intrinsic fluorescence quenching experiments reveal subtle changes in equilibrium affinity. Kinetic stopped-flow data showed that DNA-to-protein association is significantly retarded independent of choice of the molecule that is added to the solution, but dissociation depends in a nontrivial way on its size and chemical characteristics. Thus, for this DNA–protein interaction, excluded volume effect does not play the dominant role but instead observed effects are dictated by the chemical properties of the crowder. We propose that surrounding molecules are capable of specific modification of the protein’s hydration shell via soft interactions that, in turn, tune protein–ligand binding dynamics and affinity.

Glandularia is one of the genera that has few published phytochemical studies and, for many years, it was considered to be within the genus Verbena. Verbena is known to be rich in iridoids, flavonoids, and phenylpropanoids. Three iridoid glucosides, 6β-hydroxyipolamiide, phlomiol, and pulchelloside I (3-5) were isolated from the methanolic extract of the whole plant of Glandularia gooddingii (Briq.) Solbrig and elucidated by extensive analysis of the 1D- and 2D-NMR as well as by HR-ESI-QTOF mass spectra. Identification of these iridoids and determining their chemical nature supports the chemotaxonomic classification of the genus Glandularia and defines certain members belonging to it. This is the first report of the X-ray crystal structure of 6β-hydroxyipolamiide (3).

The through-space 1H NMR effect of steric compression by the lone-pair electrons of O- and N-atoms is shown in synthetic [3.3.1]oxa- and azabicycles. The electrons of the compressed proton bond are pushed away by the repulsive force generated by the lone-pair electrons of the heteroatom. There is a corresponding significant increase in the chemical shift of the compressed proton. The intensity of this deshielding effect is related to the proximity and overlap of the lone-pair or compressing atom. The steric compression decreases when the lone-pair electrons of the heteroatom and the compressed proton are not directly overlapped, for example, in [4.3.1]- and [3.2.1]azabicycles. Steric compression is also caused by a proton, deuterium, or an ethyl group close in space to the compressed proton. The protonated [3.3.1]azabicycle adopts a true-boat/true-chair conformation in its crystal lattice, but in solution the conformation is true-chair/true-chair.

Three new main group ferrocenyldithiocarbamate complexes, viz., {Pb[(FcCH2)(CH2CH2OH)(NCS2)]2}·(FcCH2-3-oxazolidine-2-thione)·(H2O) (1), {Sb[(FcCH2)(CH2CH2OH)(NCS2)]3} (2) and {Bi[(FcCH2)(CH2CH2OH)(NCS2)]3} (3), (Fc = ferrocenyl) have been synthesized and characterized by elemental analyses and IR, 1H and 13C NMR spectroscopy as well as X-ray crystallography. The X-ray analysis of 1 indicates distorted trigonal bipyramidal geometry around Pb(II) and a cyclised product, 3-ferrocenylmethyl-oxazolidine-2-thione (4), co-crystallizes with 1. The geometry around Sb(III) in 2 is pseudo-octahedral, while 3 forms a dimer, displaying distorted square antiprism geometry around the Bi(III) center. Several attempts to synthesize the pure cyclised product 3-ferrocenylmethyl-oxazolidine-2-thione (4) using Pb(II) salts failed but 4 was fortuitously obtained in an attempt to synthesize the Cu(I) cluster by the comproportionation of {Cu[(FcCH2)(CH2CH2OH)(NCS2)]2} using copper powder. Interestingly, varying the reaction time yielded another completely desulfurized cyclised product 3-ferrocenylmethyl-oxazolidine-2-one (5). Both 4 and 5 have been characterized using spectroscopic techniques and X-ray crystallography, and the possible mechanism for the conversion of {Cu[(FcCH2)(CH2CH2OH)(NCS2)]2} to 3-ferrocenylmethyl-oxazolidine-2-thione (4) has been explained with the help of periodic UV-Vis and ESI-MS experiments. This investigation will pave a new pathway for the synthesis of similar cyclised products using similar safe and sustainable reaction conditions.

Over the past decade, porphyrin derivatives have emerged as invaluable synthetic building blocks and theranostic kits for the delivery of cellular fluorescence imaging and photodynamic therapy. Tetraphenylporphyrin (TPP), its metal complexes, and related derivatives have been investigated for their use as dyes in histology and as components of multimodal imaging probes. The photophysical properties of porphyrin-metal complexes featuring radiometals have been a focus of our attention for the realization of fluorescence imaging probes coupled with radioimaging capabilities and therapeutic potential having "true" theranostic promise. We report hereby on the synthesis, radiochemistry, structural investigations, and preliminary in vitro and in vivo uptake studies on a range of functionalized porphyrin-based derivatives. In pursuit of developing new porphyrin-based probes for multimodality imaging applications, we report new functionalized neutral, polycationic, and polyanionic porphyrins incorporating nitroimidazole and sulfonamide moieties, which were used as targeting groups to improve the notoriously poor pharmacokinetics of porphyrin tags. The resulting functional metalloporphyrin species were stable under serum challenges and the nitroimidazole and sulfonamide derivatives remained fluorescent, allowing in vitro confocal studies and visualization of the lysosomal uptake in a gallium(III) sulfonamide derivative. The molecular structures of selected porphyrin derivatives were determined by single crystal X-ray diffraction using synchrotron radiation. We also investigated the nature of the emission/excitation behavior of model functional porphyrins using in silico approaches such as TD DFT in simple solvation models. The conjugation of porphyrins with the [7-13] and [7-14] fragments of bombesin was also achieved, to provide targeting of the gastrin releasing peptide receptor (GRPR). Depending on the metal, probe conjugates of relevance for single photon emission computed tomography (SPECT) or positron emission tomography (PET) probes have been designed and tested hereby, using TPP and related functional free base porphyrins as the bifunctional chelator synthetic scaffold and 111In[In] or 68Ga[Ga], respectively, as the central metal ions. Interestingly, for simple porphyrin conjugates good radiochemical incorporation was obtained for both radiometals, but the presence of peptides significantly diminished the radio-incorporation yields. Although the gallium-68 radiochemistry of the bombesin conjugates did not show radiochemical incorporation suitable for in vivo studies, likely because the presence of the peptide changed the behavior of the TPP-NH2 synthon taken alone, the optical imaging assays indicated that the conjugated peptide tags do mediate uptake of the porphyrin units into cells.

Recently we reported a series of highly active Al(III)-complexes bearing a catalen ligand support for lactide polymerisation, observing unprecedented activity in the melt. Herein we report diversification of the metal to furnish a series of well-defined dimeric Zn(II)- and Mg(II)-complexes, which were fully characterised by X-ray crystallography and NMR spectroscopy. The production of biocompatible atactic PLA from rac-LA in solution and under industrially preferred solvent-free conditions was demonstrated, typically observing good activity and Mn control with a broad range of dispersities (Đ = 1.08–2.04). Mg(II)-Complexes were shown to facilitate the relatively mild methanolysis of PLA, achieving up to 64% conversion to Me-LA within 8 h at 80 °C in THF. Further kinetic analysis found [Mg(1,3)]2 to have kapp values of 0.628 ± 0.0536 {4 wt% cat. loading} and 0.265 ± 0.0193 h−1 {8 wt% cat. loading} respectively for the rate of consumption of PLA. Preliminary work extended polymer scope to PET from various sources, demonstrating catalyst versatility.

Three new one dimensional ferrocene decorated Hg(II) based coordination polymers with the general formula of (FcCH2N(C2H4OH)NCS2HgX)n {X = Cl (FcHgCl); Br (FcHgBr); I (FcHgI)} have been synthesized using a functionalized dithiocarbamate ligand with a redox active ferrocene pendant and –C2H4OH and have been characterized by microanalyses, FTIR, 1H, 13C, and 199Hg NMR, electronic absorption and photoluminescence spectroscopy. The redox properties of these compounds have been assessed by cyclic voltammtery which suggested their quasi-reversible redox behaviour. Single crystal X-ray diffraction studies suggested that the geometries around all three Hg(II) polymers are square pyramidal and two such square-pyramids fuse in an antiparallel mode in FcHgCl and FcHgI and in an orthogonal mode in FcHgBr to generate a ferrocene decorated 1D polymeric framework. The adjacent 1D polymeric chains in all three compounds are held by different intermolecular interactions which provide stability to these compounds in the solid state. Also, these compounds exhibit interesting Hg⋯X (X = Cl, Br and I) spodium bonding interactions. The nature of all these interactions have been studied by Hirshfeld surface analyses, density functional theory and quantum theory of atoms in molecules (QTAIM). The QTAIM results indicated that Hg⋯X interactions are moderately strong with interaction energies of 9.32, 44.37 and 19.56 kJ mol−1 for chloro, bromo and iodo derivatives, respectively. Further bond order calculations also suggest the presence of spodium bonding interaction in all three polymers.

Two series of N-methyliminodiacetic acid (MIDA) boronates were prepared and their mesomorphic properties were investigated. MIDA-substituted benzoic acid esters were synthesized via the Mitsunobu reaction. The second series of MIDA benzyl ether derivatives was prepared via Williamson etherification and subsequent borylation. Both series exhibit smectic A (SmA) phases. In the case of MIDA boronate esters, a substitution with perfluorinated side chains led to increased transition temperatures and broadening of the SmA phases. The phase geometries of the mesophases were determined by X-ray diffraction. Quantum-chemical calculations provided further insight into the packing model.

The phosphatases PP1 and PP2A are responsible for the majority of dephosphorylation reactions on phosphoserine (pSer) and phosphothreonine (pThr), and are involved in virtually all cellular processes and numerous diseases. The catalytic subunits exist in cells in form of holoenzymes, which impart substrate specificity. The contribution of the catalytic subunits to the recognition of substrates is unclear. By developing a phosphopeptide library approach and a phosphoproteomic assay, we demonstrate that the specificity of PP1 and PP2A holoenzymes towards pThr and of PP1 for basic motifs adjacent to the phosphorylation site are due to intrinsic properties of the catalytic subunits. Thus, we dissect this amino acid specificity of the catalytic subunits from the contribution of regulatory proteins. Furthermore, our approach enables discovering a role for PP1 as regulator of the GRB-associated-binding protein 2 (GAB2)/14-3-3 complex. Beyond this, we expect that this approach is broadly applicable to detect enzyme-substrate recognition preferences., The substrate specificity of phosphoprotein phosphatases PP1 and PP2A depends on their catalytic and regulatory subunits. Using proteomics approaches, the authors here provide insights into the sequence specificity of the catalytic subunits and their distinct contributions to PP1 and PP2A selectivity.

A novel set of linear α-olefin trimerisation pre-catalysts is presented. The R3TACCr(OTf)3 (R3TAC = 1,3,5-trialkyl-1,3,5-triazacyclohexane) complexes produce an active system after facile activation with less than 10 equivalents of trialkylaluminium. Isomerisation was observed in many cases, which is proposed to occur via the π-allyl complex mechanism, though this was minimised by optimisation of the reaction conditions. The pre-catalysts can be synthesised from R3TACCrCl3 in neat TfOH or by addition of R3TAC to Cr(OTf)3 or better Cr(OTf)3(THF)3, the synthesis and structure of which is presented here. The use of this highly defined system allowed the identification of 2-methyl-1-hexene as a side product of activation with AlMe3, in agreement with the proposed metallacyclic mechanism. Isomer distribution of the trimer product is similar to R3TACCrCl3/MAO activated systems and depends mostly on the ligand substituent R. ESI mass spectrometry of an ortho-difluorobenzene solution of the activated catalyst was analysed at different stages of reaction. A series of signals was observed that matched those expected for cationic chromium species predicted by the metallacyclic mechanism. In particular, [R3TACCrMe2]+ was observed to form immediately after alkylation with AlMe3, while [R3TACCr(olefin)n]+ (n = 0, 1, 2, 3, 4 and olefin = 1-hexene or 1-octene) formed after addition of 1-hexene. Absence of any detected tetramer and observation of [R3TACCr(olefin)4]+ leads to the conclusion that a metallacycloheptane-olefin complex may lead to β-H abstraction rather than insertion and may even be required to avoid formation of [R3TACCr(olefin)1]+ which is observed in only very small amounts indicating a low stability. Chromium(I) complexes [R3TACCr(arene)]+ with the arene solvent can also be observed and their signal intensity indicate a relative stability of o-C6H4F2 < cymene < benzene < PhF, toluene < p-xylene.

The receptor-linked protein tyrosine phosphatases (RPTPs) are key regulators of cell-cell communication through the control of cellular phosphotyrosine levels. Most human RPTPs possess an extracellular receptor domain and tandem intracellular phosphatase domains: comprising an active membrane proximal (D1) domain and an inactive distal (D2) pseudophosphatase domain. Here we demonstrate that PTPRU is unique amongst the RPTPs in possessing two pseudophosphatase domains. The PTPRU-D1 displays no detectable catalytic activity against a range of phosphorylated substrates and we show that this is due to multiple structural rearrangements that destabilise the active site pocket and block the catalytic cysteine. Upon oxidation, this cysteine forms an intramolecular disulphide bond with a vicinal “backdoor” cysteine, a process thought to reversibly inactivate related phosphatases. Importantly, despite the absence of catalytic activity, PTPRU binds substrates of related phosphatases strongly suggesting that this pseudophosphatase functions in tyrosine phosphorylation by competing with active phosphatases for the binding of substrates., Receptor-linked protein tyrosine phosphatases (RPTPs) usually contain an active membrane proximal domain and an inactive pseudophosphatase domain. Here, the authors characterize an RPTP with two pseudophosphatase domains, providing evidence that it may act as a decoy receptor for substrate sequestration.

AzuFluor® 435-DPA-Zn, an azulene fluorophore bearing two zinc(ii)-dipicolylamine receptor motifs, exhibits fluorescence enhancement in the presence of adenosine diphosphate. Selectivity for ADP over ATP, AMP and PPi results from appropriate positioning of the receptor motifs, since an isomeric sensor cannot discriminate between ADP and ATP.

Steel surfaces have been coated with Co-based tungsten carbide (WC) in an additive printing process. This process leads to compact and extremely mechanically stable surfaces. We performed tribological measurements using WC counter bodies under dry conditions and severe mechanical load. Low coefficients of friction, even for rough surfaces, were found and the resulting wear rates were extraordinarily small, even when compared to high-quality PVD film with a similar composition. These findings suggest a wide field of application for this novel preparation process for wear-resistive surfaces.

The natural product (+)‐grandifloracin is a potent “anti‐austerity” agent, able to suppress the ability of various pancreatic cancer cell lines to tolerate conditions of nutrient deprivation. Such anti‐austerity agents represent a promising approach to cancer chemotherapy. Here we report the synthesis and biological evaluation of racemic analogues of grandifloracin bearing diverse sidechains, of which two show enhanced potency in comparison with the natural product. Additionally, several unexpected by‐products containing modifications of the grandifloracin core were isolated, identified and similarly evaluated for biological activity., Austerity measures: Grandifloracin is a natural product that is known to exhibit anti‐austerity activity, i. e. it is able to abolish the ability of pancreatic cancer cells to survive under “austere” conditions of nutrient deprivation. Herein we report the synthesis and biological evaluation of analogues of grandifloracin, as well as our findings on rearrangement and fragmentation reactions of the dimeric grandifloracin core. Live imaging, fluorescence microscopy and colony formation experiments with the most active analogue are described.

Thermotropic ionic liquid crystals based on the flavylium scaffold have been synthesized and studied for their structure‐properties relationship for the first time. The mesogens were probed by differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and X‐ray diffraction (XRD). Low numbers of alkoxy side chains resulted in smectic (SmA) and lamello‐columnar (LamCol) phases, whereas higher substituted flavylium salts showed Colro as well as ordered and disordered columnar (Colho, Colhd) mesophases. Mesophase width ranged from 13 K to 220 K, giving access to room temperature liquid crystals. The optical properties of the synthesized compounds were probed towards absorption and emission properties. Strong absorption with maxima between 444 and 507 nm was observed, and some chromophores were highly emissive with quantum yields up to 99 %. Ultimately, mesogenic and dye properties were examined by temperature‐dependent emissive experiments in the solid state., Flower power: In the search for new mesogenic cores for ionic liquid crystals, the authors were inspired by anthocyanidins, which are responsible for the bright red to blue colors in many plants. The new flavylium triflates were examined for their liquid crystalline and dye properties.

A dual seven-membered cyclic carbonate/olefin monomer was synthesized from CO2 and cis-1,4-butenediol and polymerized. The properties of the polymer were controlled using divergent catalytic strategies toward the stereochemistry of the olefin. Ring-opening polymerization of the cyclic carbonate using an organocatalytic approach retained the cis-stereoconfiguration of the olefin and yielded a hard semicrystalline polymer (Tm 115 °C). Ring-opening metathesis polymerization using Grubbs’ catalyst proceeded with high trans-stereoregularity (95%) and produced a soft amorphous polymer (Tg −22 °C). Cis to trans isomerization of the polymer was possible using Cu(I) salts under UV light. In all polymers, the C═C double bond remained available for postpolymerization modification and thermoset resins were formed by cross-linking. From this single monomer, cis-trans-cis triblock copolymers, with potential applications as thermoplastic elastomers, were synthesized by combining both strategies using cis-1,4-butenediol as a chain transfer agent.

The study presents a rational synthesis of new dimethyltin carboxylates, Me2Sn(H2btec) (1), Me2Sn(btec)0.5(2), [Me2Sn(H2O)2(btec)0.5]·H2O (3), and [{Me2SnOSn(OH)Me2}(Me2SnOH)(btec)0.5]·H2O (4), derived from tetratopic 1,2,4,5-benzenetetracarboxylic acid (H4btec). The method relies upon hydrothermal reaction (130 °C, 72 h) of dimethyltin dichloride and H4btec under optimized pH (2 < pH < 8) conditions that allow control over dimethyltin speciation in aqueous medium as well as degree of deprotonation of the tetrafuntional carboxylic acid. The formation of a three-dimensional assembly in 1 is assisted by the bridging bidentate (μ2) mode of the carboxylate and O–H···O hydrogen bonds involving −COOH groups. The structure represents a unique example of the diorganotin framework derived from a partially deprotonated polyfuntional carboxylic acid. The structure of 2 adopts a three-dimensional motif wherein each pair of μ2-carboxylate groups (designated by C1 and C4) of the tetraanionic ligand form different spati...

Autophagy mediates the degradation of damaged proteins, organelles and pathogens, and plays a key role in health and disease. Thus, the identification of new mechanisms involved in the regulation of autophagy is of major interest. In particular, little is known about the role of lipids and lipid-binding proteins in the early steps of autophagosome biogenesis. Using target-agnostic, high-content, image-based identification of indicative phenotypic changes induced by small molecules, we have identified autogramins as a new class of autophagy inhibitor. Autogramins selectively target the recently discovered cholesterol transfer protein GRAM domain-containing protein 1A (GRAMD1A, which had not previously been implicated in autophagy), and directly compete with cholesterol binding to the GRAMD1A StART domain. GRAMD1A accumulates at sites of autophagosome initiation, affects cholesterol distribution in response to starvation and is required for autophagosome biogenesis. These findings identify a new biological function of GRAMD1A and a new role for cholesterol in autophagy.

Phosphorylation, which is mediated by protein kinases and opposed by protein phosphatases, is an important post-translational modification that regulates many cellular processes, including cellular metabolism, cell migration, and cell division. Due to its essential role in cellular physiology, a great deal of attention has been devoted to identifying sites of phosphorylation on cellular proteins and understanding how modification of these sites affects their cellular functions. This has led to the development of several computational methods designed to predict sites of phosphorylation based on a protein’s primary amino acid sequence. In contrast, much less attention has been paid to dephosphorylation and its role in regulating the phosphorylation status of proteins inside cells. Indeed, to date, dephosphorylation site prediction tools have been restricted to a few tyrosine phosphatases. To fill this knowledge gap, we have employed a transfer learning strategy to develop a deep learning-based model to predict sites that are likely to be dephosphorylated. Based on independent test results, our model, which we termed DTL-DephosSite, achieved efficiency scores for phosphoserine/phosphothreonine residues of 84%, 84% and 0.68 with respect to sensitivity (SN), specificity (SP) and Matthew’s correlation coefficient (MCC). Similarly, DTL-DephosSite exhibited efficiency scores of 75%, 88% and 0.64 for phosphotyrosine residues with respect to SN, SP, and MCC.

Small water bodies including (former) drainage ditches can be hotspots for methane (CH4) emissions from peatlands. We assessed the CH4 emissions of a drained and a rewetted temperate fen including emissions of active and former drainage ditches over the course of 2.5 years, covering three vegetation periods. Ditch CH4 emissions in the rewetted fen were significantly higher than in the drained fen. In the rewetted fen ditches contributed up to 91 % of the annual CH4 budget, despite covering only 1.5 % of the area. In the drained fen CH4 emissions were solely made up of ditch emissions. When including CH4 uptake by the peat soil, the CH4 balance of the drained fen was neutral. Dissolved organic carbon concentrations likely had an enhancing effect on CH4 emissions while nitrate and sulphate in the ditch water seem to have had an inhibitory effect. Air and water temperature controlled seasonal variability of ebullitive as well as diffusive CH4 emissions. Ebullition contributed less than 10 % to the overall CH4 budget in the ditches. Drainage ditches represent a hotspot of CH4 emissions and need therefore be taken into account when assessing the success of rewetting projects of peatlands.

We report herein the first all-donor aromatic [2]catenane formed through dynamic combinatorial chemistry, using single component libraries. The building block is a benzo[1,2-b:4,5-b′]dithiophene derivative, a π-donor molecule, with cysteine appendages that allow for disulfide exchange. The hydrophobic effect plays an essential role in the formation of the all-donor [2]catenane. The design of the building block allows the formation of a quasi-fused pentacyclic core, which enhances the stacking interactions between the cores. The [2]catenane has chiro-optical and fluorescent properties, being also the first known DCC-disulphide-based interlocked molecule to be fluorescent., An all-donor [2]catenane has been synthesised via dynamic combinatorial chemistry. It features stacked benzodithiophenes which are quasi-pentacyclic through hydrogen bonding.

Tree stems can be a source of the greenhouse gas methane (CH4) and locally as regionally important to the overall GHG budget. Stem emissions even hold the potential of narrowing down knowledge gap in the global methane budget. However, assessments of the global importance of stem CH4 emissions are complicated by a lack of research and high variability between individual ecosystems. Here, we determined the contribution of emissions from stems of mature black alder (Alnus glutinosa (L.) Gaertn.) to overall CH4 exchange in two temperate peatlands. We measured emissions from stems and soils using closed chambers in a drained and an undrained alder forest over 2 years. Furthermore, we studied the importance of alder leaves as substrate for methanogenesis in an incubation experiment. Stem CH4 emissions at the undrained alder forest were very variable in time and only persisted for a few weeks during the year. Generally the drained alder forest did not soil nor stem CH4 emissions. Different upscaling approaches were assessed and all approaches showed that stem CH4 emissions contributed less than 0.3 % to the total ecosystem CH4 budget. However, stem CH4 seem to depend strongly on the hydrological regime and therefore vary strongly between ecosystems. Hence, every ecosystem must be consdidered attentively with respect to their stem CH4 emissions.

Palmitic acid (PA) is a major fatty acid, derived from diet and endogenous production, which is being linked to inflammation. While such actions of PA at the level of the testis remain difficult to examine, we reasoned that studies in human testicular cells may be instructive. Human testicular peritubular cells (HTPCs) can be isolated from men and cultured. They have contractile properties but also produce Interleukin 6 (IL6), express the inflammasome member NLRP3, and via glia cell line derived neurotrophic factor (GDNF), they contribute to the spermatogonial stem cell niche. We found that PA at 100 &micro, M significantly increased the levels of IL6, while NLRP3 or the related Interleukin 1 beta (IL1beta) were not affected. The contractility marker calponin (CNN1) and the growth factor GDNF were likewise not affected. ELISA studies confirmed the stimulatory PA actions on IL6. Hence, PA derived from diet and/or endogenous sources may be able to foster a pro-inflammatory milieu in the testis. A possible link of these results to diet and high fat intake and obesity is indicated by the about 12-fold elevated testicular levels of IL6 in testes of obese rhesus monkeys (n = 3), fed with a Western Style diet. They had elevated 2&ndash, 5-fold increased body fat and increased circulating triglyceride levels. Further consequences of PA and obesity for testicular functions remain to be evaluated.

In all intracellular processes, protein structure and dynamics are subject to the influence of macromolecular crowding (MC). Here, the impact of MC agents of different types and sizes on the model protein Bacillus subtilis Cold shock protein B (BsCspB) during both thermal and chemical denaturation have been comprehensively investigated. We consistently reveal a distinct stabilization of BsCspB in a manner dependent on the MC concentration but not on viscosity, polarity, or size of the MC agent used. This general stabilization has been decoded by use of NMR spectroscopy, through monitoring of chemical shift (CS) perturbations and the intramolecular hydrogen‐bonding networks, as well as local protection of amide protons against exchange with solvent protons. Whereas CSs and hydrogen‐bonding networks are not systematically affected in the presence of MC, we detected a pronounced reduction in exchange in loop regions of BsCspB. We conclude that this reduced accessibility of solvent protons is a key parameter for the increases in protein stability seen under MC.

Herein, we report a series of highly active Al(III)-complexes based on a novel hybrid ligand: the catalen. Their application in the production of polylactide under both solution, and industrially preferred melt conditions, is demonstrated. Potential structural diversification to broaden initiator scope is discussed.

The formation of the spherical self-assembly of gold nanoparticles (AuNPs) of 200 ± 20 nm size at the water–chloroform interface is achieved by employing the cyclotetrasiloxane [RSCH2CH2SiMeO]4 (R = CH2CH2OH) as the stabilizing ligand. The interfacially stabilized AuNPs act as a versatile catalyst for selective hydrolytic oxidation of only one of the Si–H bonds in secondary organosilanes, RR1SiH2 (R, R1 = alkyl, aryl, and sila-alkyl), to afford the high yield synthesis of 1,1,3,3-tetraorganodisiloxanes, (HRR1Si)2O. The study unravels for the first time the role of the photothermal effect arising from the excitation of the surface plasmon resonance of the AuNPs under visible light irradiation in enhancing the catalytic activity at ambient temperature.

The study describes the synthesis of new hybrid zinc phosphonates, {Zn(O3PMe)(4,4′-bipy)0.5}·2H2O (2), {Zn(O3PMe)(1,2-bpe)0.5}·H2O (3) and Zn(O3PMe)(Im) (4) [4,4′-bipyridine (4,4′-bipy), 1,2-bis(4-pyridyl)ethane (1,2-bpe) and imidazole (Im)] by hydro(solvo)thermal reaction (140–150 °C, 3 days) of a preformed coordination polymer, zinc bis(O-methyl methylphosphonate), Zn{OP(O)(OMe)Me}2 (1) with an appropriate N-donor ligand. X-ray crystallographic studies reveal structural transformation of a linear chain zinc-phosphonate framework in 1 to a ladder motif in 2–4 which is constructed by corner sharing of ZnO3N and CPO3 tetrahedra. For 2 and 3, the bifunctional N-donor ligands act as linkers to afford the formation of a layered structure. The lattice water molecules in 2 form an infinite array of cyclic tetramers via O–H⋯O2(P) hydrogen bonding interactions and occupy the interlayer region.

Background Disruption of Ca2+ homeostasis is a key pathomechanism in heart failure. CaMKII-dependent hyperphosphorylation of ryanodine receptors in the sarcoplasmic reticulum (SR) increases the arrhythmogenic SR Ca2+ leak and depletes SR Ca2+ stores. The contribution of conversely acting serine/threonine phosphatases [protein phosphatase 1 (PP1) and 2A (PP2A)] is largely unknown. Methods and results Human myocardium from three groups of patients was investigated: (i) healthy controls (non-failing, NF, n = 8), (ii) compensated hypertrophy (Hy, n = 16), and (iii) end-stage heart failure (HF, n = 52). Expression of PP1 was unchanged in Hy but greater in HF compared to NF while its endogenous inhibitor-1 (I-1) was markedly lower expressed in both compared to NF, suggesting increased total PP1 activity. In contrast, PP2A expression was lower in Hy and HF compared to NF. Ca2+ homeostasis was severely disturbed in HF compared to Hy signified by a higher SR Ca2+ leak, lower systolic Ca2+ transients as well as a decreased SR Ca2+ load. Inhibition of PP1/PP2A by okadaic acid increased SR Ca2+ load and systolic Ca2+ transients but severely aggravated diastolic SR Ca2+ leak and cellular arrhythmias in Hy. Conversely, selective activation of PP1 by a PP1-disrupting peptide (PDP3) in HF potently reduced SR Ca2+ leak as well as cellular arrhythmias and, importantly, did not compromise systolic Ca2+ release and SR Ca2+ load. Conclusion This study is the first to functionally investigate the role of PP1/PP2A for Ca2+ homeostasis in diseased human myocardium. Our data indicate that a modulation of phosphatase activity potently impacts Ca2+ cycling properties. An activation of PP1 counteracts increased kinase activity in heart failure and successfully seals the arrhythmogenic SR Ca2+ leak. It may thus represent a promising future antiarrhythmic therapeutic approach.

Two extensively conjugated asymmetric ferrocene appended compounds with azine spacers, and phenolic and nitro groups as terminal groups with the following formulas Fc-CH=N-N=CH-p-C6H4-OH (Fc-OH) and Fc-CH=N-N=CH-p-C6H4-NO2 (Fc-NO2) (Fc= ferrocene) have been synthesized and characterized using micro-analyses, FTIR, 1H and 13C NMR, UV-Vis and for Fc-NO2 single crystal X-ray diffraction. The structural studies reveal that Fc-NO2 possess an extensively conjugated system where C5H4(Cp)-CH=N-N=CH-p-C6H4-NO2 is nearly planar which suggest strong electron communication from the ferrocene moiety to the p-C6H4-NO2 group via a -CH=N-N=CH- spacer. Both compounds have been used as sensitizers in titanium oxid based dye-sensitized solar cells (DSSCs) which indicate that amongst both sensitizers the Fc-OH one exhibited a better cell performance with Jsc 12.91 mA·cm−2, Voc 0.710 V, η 5.88% and incident photon to a current conversion efficiency of 53%. Electron injection in the conduction band of the titanium oxide semiconductor have been authenticated with the help of density of states calculations.

Thin films of wear-resistant tungsten carbide were deposited on steel substrates by sputtering of WC with magnetron sputtering in a mixed argon/acetylene atmosphere. Variation of the acetylene supply during the deposition led to the growth of the tungsten carbide films with different excesses of carbon with respect to the stoichiometric WC. Variation of bias voltage influences mainly the [C]/([C]+[W]) ratio and secondary the mechanical properties hardness and Young's modulus. The films are supposed to combine good wear-resistant properties with a low friction under dry conditions. A tribometric analysis of friction and wear shows that an excess of carbon in the hard material layer can reduce the coefficient of friction by up to 40%. However, the volume of wear increased with increasing amount of carbon, while the nanoindentation measurements revealed higher hardness and lower elastic modulus.

Semiconductor charge transfer (CT) cocrystals are an emerging class of molecular materials which combines the characteristics of the constituent molecules in order to tune physical properties. Cocrystals can exhibit polymorphism, but different stoichiometries of the donor-acceptor (DA) pair can also give different structures. In addition, the structures of the donor and acceptor as pristine compounds can influence the resulting cocrystal forms. We report a structural study on several CT cocrystals obtained by combining the polyaromatic hydrocarbon perylene with 7,7,8,8-tetracyanoquinodimethane (TCNQ) and its fluorinated derivatives having increasing electronegativity. This is achieved by varying the amount of fluorine substitution on the aromatic ring, with TCNQ-F2 and TCNQ-F4. We find structures with different stoichiometries. Namely, the system perylene:TCNQ-F0 is found with ratios 1:1 and 3:1, while the systems perylene:TCNQ-Fx (x = 2, 4) are found with ratios 1:1 and 3:2. We discuss the structures on the basis of the polymorphism of perylene as pure compound, and show that by a judicious choice of growth temperature the crystal structure can be in principle designed a priori. We also analyze the structural motifs taking into account the degree of charge transfer between the perylene donor and the TCNQ-Fx acceptors and the optical gap determined from infrared (IR) spectroscopy. This family of materials exhibits tunable optical gaps in the near-IR (NIR), promising applications in organic optoelectronics.

Resonant soft X-ray reflectivity at the carbon K-edge was applied to a trigonal tetracene single crystal. The angular resolved reflectivity was quantitatively simulated describing the tetracene crystal in terms of its dielectric tensor, which was derived from the anisotropic absorption cross section of the single molecule, as calculated by density functional theory. A good agreement was found between the experimental and theoretically predicted reflectivity. This allows us to assess the anisotropic optical constants of the organic material, probed at the carbon K-edge, in relation to the bulk/surface structural and electronic properties of the crystal, through empty energy levels.

We report two hitherto unknown polymorphs of the charge transfer (CT) cocrystal perylene:tetracyanoquinodimethane (TCNQ) grown by physical vapor transport (PVT) in argon atmosphere. One of the polymorphs, named β, has stoichiometry 1:1 and adds to the three known structures with stoichiometry 1:1 (α), 2:1, and 3:1. Interestingly, below (280 ± 10) K the β structure undergoes a phase transition to what we refer to as the γ polymorph, with halving of the unit cell and reduction of symmetry from monoclinic to triclinic. Both new crystal structures present two alternating stacks with different intermolecular and intramolecular geometries. In stack S–I the perylene molecules show substantial deviations from planarity, with the angle between the naphthalene intramolecular moieties of 6.69°, and with the perylene and TCNQ molecular centroids shifted by 1.95 Å. In the second stack, S-II, the perylene is planar, and the centroids almost coincident. Structural investigations on bond length complemented by vibrational IR spectroscopy indicate that in the new polymorphs the degree of charge transfer, ρ, can be 0 or 0.12. The higher value of ionicity to be due to donor–acceptor pairs in the S-II, while molecules in S-I are closer to neutrality. Thus, the ionicity of the donor–acceptor pair depends on the stack and is comparable to that of the α polymorph which we redetermined as ρ = 0.15 ± 0.05.

In this work, four heteroleptic Ni(II)dppe dithiolates complexes, [Ni(NED)(dppe)] (Ni-NED), [Ni(ecda)(dppe)] (Ni-ecda), [Ni(i-mnt)(dppe)] (Ni-i-mnt) and [Ni(cdc)(dppe)] (Ni-cdc) (dppe = 1,2-bis(diphenylphosphino)ethane; NED = 1-nitroethylene-2,2-dithiolate; ecda = 1-ethoxycarbonyl-1-cyanoethyelene-2,2-dithiolate; i-mnt = 1,1-dicyanoethylene-2,2-dithiolate and cdc = cyanodithioimidocarbonate), have been synthesized and characterized by analytical and spectroscopic techniques (Elemental analysis, vibrational, electronic absorption and multinuclear NMR spectroscopy). Structural characterization of all the four complexes by single crystal X-ray diffraction study suggests distortion in regular square planar geometry at Ni(II) center by coordination with two phosphorus of the dppe and two sulfur of the dithiolate ligands, respectively. The decomposition of all four complexes have been done to produce nickel sulfides and the resulting nickel sulfides have been utilized for electrocatalytic oxygen evolution reaction (OER). The nickel sulfide obtained by decomposing Ni-cdc shows best activity with overpotential η = 222 mV at j = 10 mA cm−2 and a Tafel slope of 44.2 mV dec−1 while other catalysts shows η > 470 mV at j = 5 mA cm−2 and η > 600 mV at j = 10 mA cm−2 at loading of 1.3 mg cm−2.

Tumor cells—even if nonauxotrophic—are often highly sensitive to arginine deficiency. We hypothesized that arginine deprivation therapy (ADT) if combined with irradiation could be a new treatment strategy for glioblastoma (GBM) patients because systemic ADT is independent of local penetration and diffusion limitations. A proof-of-principle in vitro study was performed with ADT being mimicked by application of recombinant human arginase or arginine-free diets. ADT inhibited two-dimensional (2-D) growth and cell-cycle progression, and reduced growth recovery after completion of treatment in four different GBM cell line models. Cells were less susceptible to ADT alone in the presence of citrulline and in a three-dimensional (3-D) environment. Migration and 3-D invasion were not unfavorably affected. However, ADT caused a significant radiosensitization that was more pronounced in a GBM cell model with p53 loss of function as compared with its p53-wildtype counterpart. The synergistic effect was independent of basic and induced argininosuccinate synthase or argininosuccinate lyase protein expression and not abrogated by the presence of citrulline. The radiosensitizing potential was maintained or even more distinguishable in a 3-D environment as verified in p53-knockdown and p53-wildtype U87-MG cells via a 60-day spheroid control probability assay. Although the underlying mechanism is still ambiguous, the observation of ADT-induced radiosensitization is of great clinical interest, in particular for patients with GBM showing high radioresistance and/or p53 loss of function. Mol Cancer Ther; 17(2); 393–406. ©2017 AACR. See all articles in this MCT Focus section, “Developmental Therapeutics in Radiation Oncology.”

SnO is a rare example of a stable p-type semiconductor material. Here, we describe the synthesis and characterisation of a family of Sn(ii) pyrrolide complexes for future application in the MOCVD and ALD of tin containing thin films. Reaction of the Sn(ii) amide complex, [{(Me3Si)2N}2Sn], with the N,N-bidentate pyrrole pro-ligand, L1H, forms the hetero- and homoleptic complexes [{L1}Sn{N(SiMe3)2}] (1) and [{L1}2Sn] (2), respectively, bearing the 2-dimethylaminomethyl-pyrrolide ligand (L1). Reaction of [{(Me3Si)2N)}2Sn] with the pyrrole-aldimine pro-ligands, L2H-L7H, results in the exclusive formation of the homoleptic bis-pyrrolide complexes [{L2-7}2Sn] (3-8). All complexes have been characterised by elemental analysis and NMR spectroscopy, and the molecular structures of complexes 1-5 and 8 are determined by single crystal X-ray diffraction. TG analysis and isothermal TG analysis have been used to evaluate the potential utility of these systems as MOCVD and ALD precursors.

Three isomeric bis-(triphenylphosphine)copper(I) complexes comprising xanthate ligands derived from 2- (1), 3- (2), and 4-methanol pyridine (3) have been synthesized and characterized using microanalyses, IR, multinuclear NMR, UV-Vis and fluorescence spectroscopic methods as well as single crystal X-ray diffraction. The single crystal X-ray diffraction results indicated that the immediate geometry around Cu(I) in the complexes is distorted tetrahedral, which is satisfied by the two sulfur centers of the xanthate ligands and two phosphorus centers of the two PPh3 moieties. Additionally, thermogravimetric analysis (TGA) under an inert atmosphere was performed, and the results indicated that the complexes decompose to copper sulfide. The complexes were decomposed under an inert atmosphere to obtain copper sulfides, which were characterized by PXRD and SEM. Additionally, their electrocatalytic properties were investigated in the oxygen evolution reaction (OER). The OER results indicate that the copper sulfide (CuxS-3) obtained from 3 exhibited the best activity with an onset potential of 475 mV.

Herein, two new Ni(dppf)dithiolates in which dithiolate ligands comprise 2,2-diacetyl (D-1) and 2-nitro (D-2) anchors have been synthesized and characterized using microanalyses, FTIR, 1H and 13C NMR spectroscopy, as well as single-crystal X-ray diffraction. The X-ray crystallographic studies indicate that in both compounds, the geometry around the Ni(II) center can be described as distorted square planar, which is defined by the two sulfur centers of the dinegative dithiolate ligands and two phosphorus centers of the neutral dppf ligand. The electronic absorption spectra for both sensitizers display a blue shift when compared with the characteristic electronic absorption spectrum of the dppf ligand in a similar wavelength region. The photovoltaic performances and charge transport properties (EIS spectra) were studied to evaluate the performance of the synthesized dye in DSSCs. Upon comparing both dyes, it was found that the dye with the nitro anchor (D-2) showed better photovoltaic performance than the dye with the ketonic anchor (D-1). The superior performance of D-2 suggests better anchorage and superior dye loading capability on the TiO2 surface, which suppresses charge recombination, prolongs electron lifetime, and decreases the total resistance of DSSCs. The assembly fabricated using D-2 showed best performance with an overall conversion efficiency, η, of 3.21%, Jsc of 7.96 mA cm−2, and Voc of −0.654 V. The obtained efficiency is ∼46% that of today's state-of-the-art N719 dye under similar conditions. The probable reasons for the poor performance of both dyes have been addressed with the help of theoretical calculations.

Two series of ligands based on diaminocyclohexane (DACH) have been prepared and successfully complexed to Al(III) and Zn(II) metal centres. Solution and solid-state studies reveal a tendency to form mono- or bis-ligated forms depending on the steric bulk of the ligand. These complexes have been tested for their ability to ring open rac-lactide. Al(III) based complexes generally gave atactic PLA after a polymerization time of 1-2 days. The Zn(II) complexes, were found to be more active and furnished PLA with a slight heterotactic bias.

A 2D-TiO2 nanosheet material (as a film deposit of approximately 1 μm thickness on glassy carbon) is employed to host ferroceneboronic acid receptor molecules. It is suggested that the negative surface charge on 2D-TiO2 nanosheets allows weak binding of ferroceneboronic acid, which can then be employed to detect fluoride, glucose, or fructose. The nature of the aqueous electrolyte is shown to strongly affect the ferroceneboronic acid – host interaction. In the presence of di-sodium sulfate stable reversible voltammetric responses are observed. In the presence of fluoride loss of the ferroceneboronic acid occurs probably due to weakening of the boron-titanate interaction. For glucose and for fructose “bound” and “unbound” states of the ferroceneboronic acid are observed as long as fast square wave voltammetry is employed to capture the “bound” state before decomplexation can occur. It is shown that this kinetic selectivity is highly biassed towards fructose and essentially insensitive to glucose.

In this paper a series of Mg(II), Li(I) and Zn(II) complexes based on two families of amine bis(phenolate)s have been prepared and structurally characterised. In the solid-state the Li(I) complexes form common Li4O4 cubes and there are subtle differences in coordination mode between the two salan ligands employed. We also have prepared a Li3Mg1O4 cube structure, by the reaction of 1 eq. of ligand 2H2, with 1 eq. of both nBuLi and MgnBu2. Upon addition of the ligands with Zn(II) either a trimetallic or tetrametallic structure was isolated. With 2H2 a complex with an –OMe was observed, this arises from the insertion of oxygen into the Zn-Me bond. Upon reaction with MgnBu2 dimeric complexes were isolated. All complexes were tested for the ROP of rac-lactide in solution. High molecular weight polylactide was isolated with narrow molecular weight distributions being observed. In most cases PLA with a very slight heterotactic bias was formed.

A series of rigidified dyes with either dodecyloxy or piperidyl donors in combination with either malononitrile or barbiturate acceptors were synthesized. To analyze the influence of varying donor (piperidyl vs dodecyloxy), chromophore (mono-, bis- or tricyclic system) and acceptor moiety (methyl barbiturate vs malononitrile) to the ground state polarity, a combination of several methods was employed: UV/Vis absorption and emission, quantum chemical computations, 1H as well as 13C NMR and cyclic voltammetry measurements. Depending on acceptor and donor moieties, the ground state was shifted from a neutral form to the cyanine limit and further to a zwitterionic structure. By using strong piperidyl donor and barbiturate acceptor substituents, the ground state was close to the cyanine limit, which resulted in strong cyanine-like absorption properties having a dominant 0-0 transition. When combining a weak dodecyloxy donor with a malononitrile or barbiturate acceptor, the neutral resonance form significantly contributed to the ground state leading to weaker but broader absorption spectra featuring transitions to higher vibronic states.

Many cell signaling pathways are activated or deactivated by protein tyrosine phosphorylation and dephosphorylation, catalyzed by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), respectively. Even though PTPs are as important as PTKs in this process, their role has been neglected for a long time. Multiple myeloma (MM) is a cancer of plasma cells, which is characterized by production of monoclonal immunoglobulin, anemia and destruction of bone. MM is still incurable with high relapse frequency after treatment. In this review, we highlight the PTPs that were previously described in MM or have a role that can be relevant in a myeloma context. Our purpose is to show that despite the importance of PTPs in MM pathogenesis, many unanswered questions in this field need to be addressed. This might help to detect novel treatment strategies for MM patients. 0304-3835/© 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

The skeletal conformations of naturally occurring norditerpenoid alkaloids fix their substituent functional groups in space, thereby directing their bioactivities. Solution conformations of the A-rings of 4 selected norditerpenoid alkaloid free bases: mesaconitine, karacoline (karakoline), condelphine, and neoline (bullatine B), were analysed by NMR spectroscopy and single-crystal X-ray crystallography. They adopt twisted-chair, twisted-boat, twisted-boat, twisted-boat conformations, respectively. That the A-ring is stabilised in a boat conformer by an intramolecular H-bond from 1α-OH to the N-ethyl tertiary amine is also confirmed in the condelphine single crystal data. The conformations are a result of through-space repulsion between 12-He′ and atoms attached to C1 (in the equatorial positions). This causes the A-rings with 1α-OR always to be twisted whether in a chair or a boat conformation. The impact of these studies is in providing a detailed understanding of the shape of the A-ring of these important biologically active natural product alkaloids.

The 3:2 Charge Transfer (CT) co-crystal (Perylene)3(TCNQF1)2 is grown by the Physical Vapor Transport (PVT) method, and characterized structurally and spectroscopically. Infrared analysis of the charge sensitive modes reveals a low degree of charge transfer (less than 0.1) between donor and acceptor molecules. The crystal is isostructural to the other 3:2 CT crystals formed by Perylene with TCNQF2 and TCNQF4, whereas such stoichiometry and packing is not known for the CT crystals with non-fluorinated TCNQ. The analysis of the isostructural family of 3:2 Perylene–TCNQFx (x = 1,2,4) co-crystal put in evidence the role of weak F…HC bonding in stabilizing this type of structure, The work has been supported by the local research funds of Bologna and Parma Universities.

Microbial arene oxidation of benzoic acid with Ralstonia eutropha B9 provides a chiral highly functionalized cyclohexadiene, suitable for further structural diversification. Subjecting this scaffold to a palladium-catalyzed Heck reaction effects a regioselective and stereoselective arylation of the cyclohexadiene ring. The arylation proceeds with a highly selective 1,3-chirality transfer of stereogenic information installed in the microbial arene oxidation. Quantum chemical calculations have provided insightinto the mechanism of the palladium catalyzed arylation. The high selectivity can be explained both by a kinetic preference for the observed arylation position and, interestingly, by reversible carbopalladation in competing positions. Functional groups that were well tolerated on the diene substrate included a range of esters, amides and a Weinreb amide, affording a total of 23 different productsin good yields. These products, which can be considered as latent enolic nucleophiles, also possess a unique three dimensional structure which can be utilized in further stereoselective transformations. This was demonstrated by subjecting one of the products, which contained a protected aldehyde, to a tandem deprotection – cyclization sequence. The reaction proceeded with complete stereoselectivityand afforded a tricyclic ketone product possessing four stereogenic centers. This demonstrates the capability of the method to introduce stereochemical complexity from a planar molecule such as benzoic acid in just a few steps.