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Pivotal degradation pathways of the most active non-heme iron epoxidation catalyst to date are investigated in detail. In-depth HR-ESI-MS and NMR spectroscopy decomposition studies and comparative catalytic experiments exclude the generally accepted literature paths of μ2-oxo bridged FeIII–O–FeIII dimer formation and methylene bridge oxidation. Instead, the Fe–NHC bond has been identified as the “weak spot”. It is shown that direct oxidation of one of the carbenes (ImCO) results in its de-coordination and induces protonation of the other NHC moieties, thus completely deactivating the catalyst. Evidence for protonation prior to carbene oxidation has not been found in this study.

The first diiron(III,IV)-μ2-oxo tetracarbene complex is isolated and characterized by SC-XRD, UV/Vis, EPR, Evans’ NMR and elemental analysis. CV indicates the presence of a transient high-valent diiron(IV)-μ2-oxo species. Its formation and decay is investigated via UV/Vis kinetics and NMR.

A straightforward modification route to obtain mono‐ and di‐substituted anthroyl ester bridge functionalized dinuclear Au(I) bis‐N‐heterocyclic carbene complexes is presented. The functionalization can be achieved starting from a hydroxyl‐functionalized ligand precursor followed by transmetallation of the corresponding Ag complex or via esterification of the hydroxyl‐functionalized gold complex. The compounds are characterized by NMR‐spectroscopy, ESI‐MS, elemental analysis and SC‐XRD. The mono‐ester Au complex shows quantum yields around 18%. In contrast, the corresponding syn‐di‐ester Au complex, exhibits significantly lower quantum yields of around 8%. Due to insufficient water solubility of the di‐ester, only the mono‐ester complex has been tested regarding its antiproliferative activity against HeLa‐ (cervix) and MCF‐7‐ (breast) cancer cell lines and a healthy fibroblast cell line (V79). IC50 values of 7.26 μM in the HeLa cell line and 7.92 μM in the MCF‐7 cell line along with selectivity indices of 8.8 (HeLa) and 8.0 (MCF‐7) are obtained. These selectivity indices are significantly higher than those obtained for the reference drugs cisplatin or auranofin., A simple modification route of hydroxyl functionalized bis‐NHC dinuclear Au(I) complexes with anthracene is presented, which leads to a significant improvement of the antiproliferative activity and quantum yields up to 18%. By controlling the reaction parameters, one hydroxyl group remains, allowing for further potential bioconjugation to obtain a selective theranostic metal complex.

A series of histidine derived Au(I) bis‐NHC complexes bearing different ester, amide and carboxylic acid functionalities as well as wingtip substituents is synthesized and characterized. The stability in aqueous media, in vitro cytotoxicity in a set of cancer cell lines (MCF7, PC3 and A2780/A2780cisR) along with the cellular uptake are evaluated. Stability tests suggest hydrolysis of the ester within 8 h, which might lead to deactivation. Furthermore, the bis‐NHC system shows a sufficient stability against cysteine and the thiol containing peptide GSH. The benzyl ester and amide show the highest activity comparable to the benchmark compound cisplatin, with the ester only displaying a slightly lower cytotoxicity than the amide. A cellular uptake study revealed that the benzyl ester and the amide could have different intracellular distribution profiles but both complexes induce perturbations of the cellular physiological processes. The simple modifiability and high stability of the complexes provides a promising system for upcoming post modifications to enable targeted cancer therapy., Novel histidine‐derived Au(I) bis‐NHCs with different functional groups (ester, amide and carboxylic acid) show antiproliferative activity in MCF7, PC3 and A2780/A2780cisR cancer cell lines. A cellular uptake study revealed that the ester and the amide could have different intracellular distribution profiles but both complexes induce perturbations of the cellular physiological processes.

A novel N,N’‐allyl‐bridged bisimidazolium salt and a novel dinuclear Ag(I) and a Au(I) NHC complex are reported. Both metallacyclic complexes have a twisted structural shape due to the rigid allylic system and form two different isomers relating to the position of the double bonds. The allyl‐group shows photoisomerisation, but no reactivity towards bases for the additional coordination of Pd(II)., Building bridges: A novel N,N’‐allyl‐bridged bisimidazolium salt and a novel dinuclear Ag(I) and a Au(I) NHC complex are reported. Both metallacyclic complexes have a twisted structural shape due to the rigid allylic system and form two different isomers relating to the position of the double bonds. The allyl‐group shows photoisomerisation, but no reactivity towards bases for the additional coordination of Pd(II).

Two bio-inspired non-heme iron complexes bearing mixed tetradentate N-heterocyclic carbene/1,2,3-triazole ligands with cis labile coordination sites are reported. The compounds are studied in olefin epoxidation catalysis using H2O2 as oxidant. Sc(OTf)3, HClO4 and HOAc are applied as additives resulting in significant improvement of catalytic performance. Under optimized conditions the most active catalyst exhibits activities of 76,000 turnovers per hour, which is the highest reported value for an iron(II) catalyst. The complexes reveal comparably high stability and enable the challenging epoxidation of functionalized olefins. These results prove 1,2,3-triazoles to be promising and tunable ligands for iron catalyzed oxidation reactions.

The synthesis and antiproliferative activity of Mes- and iPr-substituted gold(I) bis(1,2,3-triazol-5-ylidene) complexes in various cancer cell lines are reported, showing nanomolar IC50 values of 50 nM (lymphoma cells) and 500 nM (leukemia cells), respectively (Mes < iPr). The compounds exclusively induce apoptosis (50 nM to 5 μM) instead of necrosis in common malignant blood cells (leukemia cells) and do not affect non-malignant leucocytes. Remarkably, the complexes not only overcome resistances against the well-established cytostatic etoposide, cytarabine, daunorubicin, and cisplatin but also promote a synergistic effect of up to 182% when used with daunorubicin. The present results demonstrate that gold(I) bis(1,2,3-triazol-5-ylidene) complexes are highly promising and easily modifiable anticancer metallodrugs.

The first diiron(iii,iv)-μ2-oxo tetracarbene complex is isolated and characterized by SC-XRD, UV/Vis, EPR, Evans' NMR and elemental analysis. CV indicates the presence of a transient high-valent diiron(iv)-μ2-oxo species. Its formation and decay is investigated via UV/Vis kinetics and NMR.

Fluorescent Pd(II) and Pt(II) complexes bearing 4-methylene-7-methoxycoumarin (MMC) and 2,6-diispropylphenyl (Dipp) substituted NHC/1,2,3-triazole hybrid ligands are described. Depending on the reaction conditions two different ligand coordination modes are observed, i.e., bidentate solely coordinating via NHCs or tetradentate coordinating via NHCs and 1,2,3-triazoles. All Dipp substituted complexes show antiproliferative activity against cervix (HeLa) and breast (MCF-7) human carcinoma cells. The activity significantly depends on the coordination mode, with the tetradentate motif being notably more effective (HeLa: IC50 = 3.9 μM to 4.7 μM; MCF-7: IC50 = 2.07 μM to 2.35 μM). Amongst the MMC series, only the Pd(II) complex featuring the bidentate coordination mode is active against HeLa (IC50 = 6.1 μM). In contrast to its structurally related Dipp derivative (SI = 0.6), it shows a high selectivity for HeLa (SI > 16) compared to healthy skin cells (HaCaT). According to fluorescence microscopy, this compound is presumably located in late endosomes or lysosomes.

Synthesis and characterisation of the first macrocyclic Cu(I), Ag(I) and Au(I) tricarbene/urea N-heterocyclic carbene (NHC) complexes is described and their fluorescence properties are compared to related tetracarbene complexes. The newly described silver and gold complexes show luminescence with emission maxima at λem,max = 481 nm and λem,max = 334 nm, respectively. Moreover, their ability to inhibit the growth of bacteria (S. aureus and E. coli) and cancer cells (HeLa and MCF7) is investigated. A strong influence of the metal is observed. While the copper and gold complexes are inactive against bacteria, the silver complex depicts a moderate activity (MIC ≈ 30 µM). The copper and silver complexes exhibit antiproliferative activity in both cell lines, ranging from 25.1 µM to 3.03 µM.

The syn- and anti-isomers of dinuclear Au(I) complexes of the type Au2(RLOH)(PF6)2 (R = isopropyl or mesityl) bearing 2-hydroxyethane-1,1-diyl-bridged bisimidazolylidene ligands were separated by reversed phase high performance liquid chromatography (HPLC) and characterized by NMR spectroscopy, elemental analysis, ESI mass spectrometry as well as single crystal X-ray diffraction analysis. Evaluation of the antiproliferative activity of the isolated isomers has shown very small difference in their cytotoxic behavior in various cancer cell lines. Additional counter-anion exchange (hexafluorophosphate to chloride) allows to increase the water solubility of synAu2(MesLOH)(PF6)2 and leads to higher antiproliferative activity when compared to the hexafluorophosphate-complex. Both isomers were treated with l -cysteine as nucleophilic thiol source and only the anti-isomer shows dissociation of one bisimidazolylidene ligand after 24 h. In the case of the syn-isomer, density functional theory calculations indicate a lower reactivity due to the higher steric hindrance of the N-substituents and additional hydrogen bond interaction, which prevents a nucleophilic attack. When the N-substituent is replaced by the bulkier mesityl group, both conformations remain unreactive and result to be the most cytotoxic complexes in the above-mentioned cancer cell lines. Interestingly, synAu2(MesLOH)(PF6)2 exhibits a high selectivity in the MCF-7 cell line with a selectivity index (SI) of 19, which is superior to auranofin (SI

The use of extracorporeal support systems in cardiac and/or pulmonary failure is an established treatment option. Although scientific evidence is limited there is an increasing amount of data from individual studies, e.g. Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial 2010, suggesting that extracorporeal membrane oxygenation (ECMO) as a veno-venous pump-driven system is a life-saving procedure in severe respiratory failure. Initially established as a rescue option for postcardiotomy cardiac failure extracorporeal life support (ECLS) as a pump-driven veno-arterial cardiovascular support system is increasingly being used in cardiogenic shock after myocardial infarction, as bridging to transplantation or as part of extended cardiopulmonary resuscitation. The pumpless extracorporeal lung assist (pECLA) as an arterio-venous pumpless system is technically easier to handle but only ensures sufficient decarboxylation and not oxygenation. Therefore, this method is mainly applied in primarily hypercapnic respiratory failure to allow lung protective ventilation. Enormous technical improvements, e.g. extreme miniaturization of the extracorporeal assist devices must not obscure the fact that this therapeutic option represents an invasive procedure frequently associated with major complications. With this in mind a widespread use of this technology cannot be recommended and the use of extracorporeal systems should be restricted to centers with high levels of expertise and experience.

Serum procalcitonin (PCT), an accurate marker of severe infection, is moderately increased in chronic kidney disease (CKD), peritoneal dialysis (PD) and haemodialysis (HD). We studied the extent of PCT elevation and factors accounting for elevated PCT in CKD and dialysis, and whether peripheral blood mononuclear cells (PBMC) contribute to increased PCT. In 37 controls, 281 CKD, 31 PD, and 65 HD patients without infection, PCT was measured and correlated with CKD stage, PD, HD, C-reactive protein (CRP), cardiovascular disease (CVD) and other clinical parameters. PCT release by PBMC from controls, advanced CKD, PD and HD patients (12 subjects each) was measured. PCT increased in parallel to the deterioration of CKD. Oliguria, advanced CKD, PD, HD, CVD and elevated CRP were independently associated with PCT elevation. PCT release from PBMC significantly increased in advanced CKD, PD and HD. PCT release from PBMC correlated closely with the corresponding serum PCT values (r=0.76, P

Endovascular stent-graft placement is emerging as a novel therapeutic option in patients with disease of the descending thoracic aorta. Quality standards for performing stent-graft procedures as well as for pre- and postoperative patient management are lacking, so far. It was the aim of this present survey to assess the current therapeutic standard of thoracic aortic stent-graft placement in Germany.In a nationwide survey, a total of 206 vascular surgical, radiologic, cardiologic, and cardiothoracic surgical departments were contacted. Data concerning preoperative procedure planning, logistics, practical/technical issues of stent-graft placement, and postoperative patient management were evaluated using a standardized questionnaire comprising 29 items. Data analysis was performed using univariate analysis.184 (89.3 %) of the 206 departments participated in the survey. Of these, 71 centers reported intending to perform or having performed thoracic aortic stent-graft placement. The survey overall represents 2267 endovascular stent-graft procedures performed in Germany between 1997/98 and 2003. On average, 7.4 stent-graft procedures/year were performed by each center, with half the centers performing fewer than 5 procedures/year. Thoracic aortic aneurysms was the main indication for endovascular stent-graft placement, followed by aortic dissection. There were significant differences between the different medical specialties which perform stent-graft procedures with respect to indications, choice of preoperative and intraoperative imaging methods, and technical equipment. There was strong agreement between the different centers concerning the necessity of a life-long follow-up after stent-graft placement, with computed tomography being the preferred imaging technique (90 % of centers).The present survey documents an increasing use of endovascular stent-graft placement in patients with disease of the descending thoracic aorta. There were differences regarding the technical execution of this procedures between specialties with respect to indication, procedure planning, and practical-technical aspects of stent-graft placement.

In a randomized, prospective clinical trial, 50 patients undergoing elective coronary artery bypass grafting (CABG) were divided into two groups of 25 each. Group I had a centrifugal pump (CP, Biomedicus) and Group II a roller pump (RP, Stöckert) as the arterial line. Neither group differed significantly, and variables during surgery were kept to a minimum. The parameters studied included the cellular blood elements and their components, such as PMN-elastase (PMN-E), plasma hemoglobin (pHb), beta-thromboglobulin (beta-TG), and D-dimer (D-D) and thrombin-antithrombin III complex (TAT) as indicators for activated coagulation. Blood and urine samples were taken at induction of anesthesia, every 15 minutes throughout extracorporeal circulation (ECC), at arrival in the ICU, and 1, 3, 6, 12, and 24 hours thereafter. No difference between the groups was found in bypass time, ECC flow or volume, or fluid balance. Significant differences in favor of Group I were found in pHb (p less than 0.05), beta-TG (p less than 0.01), D-D (p less than 0.05), and platelet counts (p less than 0.05). These differences were clearly ECC time dependent, became significant after 90 minutes of bypass, but disappeared within hours after surgery. No difference in patient outcome, ICU time, or need for volume substitution was seen. It is concluded that the RP can be safely used for routine ECC, but should be supplied with a CP in complex and prolonged cardiosurgical procedures to avoid severe postperfusion syndrome.