Reactive Aromatic Molecules on Metal Surfaces: Syntheses, Reactions and Structures

The interaction of organic molecules with metal contacts and the reactivity of those molecules are of high technological interest, especially in the field of organic electronics and surface-assisted catalysis. The presented work comprises the investigation of several reactive aromatic compounds on coinage metal surfaces. Although all systems raise their own scientific questions, all discussions concern either the on-surface synthesis, possible reactions or the formation of two-dimensional structures. In the studies, the methods of scanning tunneling microscopy (STM), X-ray and ultraviolet photoelectron spectroscopy (XPS, UPS) as well as near-edge X-ray absorption fine structure (NEXAFS) spectroscopy were employed. The experimental results are substantiated with insights from density functional theory (DFT) calculations. The first experimental topic is focused on the structures and reactions of tetrapyrrole macrocycles on diverse surfaces. Corroles exhibit a slightly different chemical structure than porphyrins. In the investigations of hexaethyldimethylcorrole (3H-HEDMC) monolayers on Ag(111), an enhanced surface reactivity was observed. Furthermore, superstructures of 2H-HEDMC are formed at this temperature. The metalation of 3H-HEDMC with iron, cobalt and nickel was studied on Ag(111). The resulting organometallic complexes were investigated regarding the electronic state of the metal center. The investigation of tetraphenylporphyrin with co-adsorbed lead revealed a possible metalation and a transmetalation at increased temperatures. A bromine substituted nickel-tetraphenylporphyrin was studied concerning its reactive coupling and thus a resulting formation of covalent C–C bonds due to an Ullmann coupling. The investigations on aromatic dicarbonitriles are dedicated to the influence of functional groups in reactively formed or self-assembled structures. An annulated naphthalenedicarbonitrile serves as precursor for the synthesis of an extended iron-naphthalocyanine. The precursor molecules self-assemble in locally ordered phases. The tetramerization was observed after post-deposition of iron onto a monolayer of the corresponding precursor and a subsequent annealing. While dicarbonitriles can be reactively linked in this fashion, the functional groups are also responsible for self-assembled nanostructures. Large acenes are promising novel organic semiconductors, whose properties, e.g., the HOMO-LUMO gap or the reactivity, scale with the length of the annulated aromatic backbone. A diketone-bridged precursor was used in a surface-assisted synthesis of heptacene. The transition is achieved by thermal didecarbonylation. The precursor and heptacene molecules were furthermore investigated concerning the influence of the surface on the molecules

Increasing the oxidation power of TCNQ by coordination of B(C6F5)3

The oxidation power of the cyanocarbon TCNQ (tetracyano-quinodimethane) can be significantly increased to approximately E = +0.9 V vs. Cp2Fe by coordination of up to four equivalents of the strong fluorinated Lewis acid B(C6F5)3, resulting in a highly reactive but easy-to-use oxidation system. Thianthrene and tris(4-bromophenyl)amine were oxidized to the corresponding radical cations. Dianionic [TCNQ·4 B(C6F5)3]2− was formed upon reduction with two equivalents of ferrocene or decamethylcobaltocene. [TCNQ·4 B(C6F5)3]− and [TCNQ·4 B(C6F5)3]2− are rare cases of redox-active weakly-coordinating anions

Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study

Background: Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far. Methods: This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications. Results: A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P 18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular ([less than or equal to]18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with overall survival were high CRP ([greater than or equal to]2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258 CI (0.077 to 0.862)), model of end stage liver disease (MELD) score [greater than or equal to]20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 1.047, CI (1.011 to 1.085)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)). Conclusions: In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis

Experimental tests on achieving equilibrium in synthetic fluid inclusions: Results for scheelite, molybdenite, and gold solubility at 800 °C and 200 MPa

Synthetic fluid inclusions formed in high P-T experiments, which are subsequently analyzed with LA-ICP-MS, enable us to collect thermodynamic data to constrain metal transport in aqueous fluids as well as partitioning of metals between coexisting phases. The most essential prerequisite for such studies is to ensure that equilibrium conditions between liquid and solid phases are reached prior to the formation of synthetic fluid inclusions in the host mineral. Various methods have been proposed by different authors to achieve this goal, but to this point our knowledge on the best approach to synthesize equilibrated fluid inclusions under constrained pressure, temperature, and compositional (P, T, and X) conditions remains poor. In addition, information on the time needed to reach equilibrium metal concentrations in the fluid as well as on the timing of the onset of fluid inclusion formation in the host mineral are scarce. The latter has been tested in a series of time-dependent experiments at 800 °C and 200 MPa using scheelite (CaWO4), molybdenite (MoS2) and metallic gold as dissolving phases and using different approaches to optimize the formation of equilibrated fluid inclusions. Both Embedded Image and Embedded Image were fixed during all experiments using the pyrite-pyrrhotite-magnetite buffer (PPM). As an intermediate in situ quenching of the sample charge plays an important role in the synthesis of fluid inclusions, we further tested the efficiency of such an intermediate quench for re-opening fluid inclusions formed at 600 °C and 200 MPa. Our results reveal that fluid inclusions start forming almost instantaneously and that equilibrium between fluid and solid phases occurs in the timescale of less than two hours for molybdenite and gold up to ca. 10 h for scheelite. The best approach to synthesize equilibrated fluid inclusions at 800 °C was obtained by using an intermediate quench on a previously unfractured quartz host. Experiments at 600 °C showed similar results and illustrate that this should be the method of choice down to this temperature. Below 600 °C pre-treatment of the quartz host (HF etching and/or thermal fracturing) becomes important to produce large enough fluid inclusions for the analyses via LA-ICP-MS and special care must be taken to prevent premature entrapment of the fluid. Fluids with 8 wt% NaCl in equilibrium with scheelite, molybdenite and gold at 800 °C and 200 MPa have concentrations of ca. 7300 ppm W, 1300 ppm Mo, and 300 ppm Au, respectively, which is in good agreement with results from other studies or extrapolation from lower temperatures. It can be concluded that the formation of synthetic fluid inclusions from an equilibrated fluid is possible, but different experimental designs are required, depending on the investigated temperature. In general, dissolution of solid phases seems to be much faster than previously assumed, so that experimental run durations can be designed considerably shorter, which is of great advantage when using fast-consuming mineral buffers.State of Lower SaxonyGraduate School GeoFluxesLeibniz Universität Hannove

Depletion of Macrophages Improves Therapeutic Response to Gemcitabine in Murine Pancreas Cancer.

BACKGROUND: The tumor microenvironment (TME) is composed of fibro-inflammatory cells and extracellular matrix (ECM) components. However, the exact contribution of the various TME compartments towards therapeutic response is unknown. Here, we aim to dissect the specific contribution of tumor-associated macrophages (TAMs) towards drug delivery and response in pancreatic ductal adenocarcinoma (PDAC). METHODS: The effect of gemcitabine was assessed in human and murine macrophages, human pancreatic stellate cells (hPSCs), and tumor cells (L3.6pl, BxPC3 and KPC) in vitro. The drug metabolism of gemcitabine was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Preclinical studies were conducted using KrasG12D;p48-Cre and KrasG12D;p53172H;Pdx-Cre mice to investigate gemcitabine delivery at different stages of tumor progression and upon pharmacological TAM depletion. RESULTS: Gemcitabine accumulation was significantly increased in murine PDAC tissue compared to pancreatic intraepithelial neoplasia (PanIN) lesions and healthy control pancreas tissue. In vitro, macrophages accumulated and rapidly metabolized gemcitabine resulting in a significant drug scavenging effect for gemcitabine. Finally, pharmacological TAM depletion enhanced therapeutic response to gemcitabine in tumor-bearing KPC mice. CONCLUSION: Macrophages rapidly metabolize gemcitabine in vitro, and pharmacological depletion improves the therapeutic response to gemcitabine in vivo. Our study supports the notion that TAMs might be a promising therapeutic target in PDAC

German S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" – long version of the update 2023

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was updated and expanded by the topics cutanepus squamous cell carcinoma in situ (Bowen’s disease) and actinic cheilitis. This guideline was developed at the highest evidence level (S3) and is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV