Multifunctional Cyclopentadienes as a Scaffold for Combinatorial Bioorganometallics in [(η5-C5H2R1R2R3)M(CO)3] (M=Re, 99mTc) Piano-Stool Complexes

Multifunctional cyclopentadiene (Cp) ligands and their rhenium and 99mTc complexes were prepared by a versatile synthetic route. The properties of these Cp ligands can be tuned on demand, either during their synthesis (variation of R1) or through post-synthetic functionalization with two equal or different vectors (V1 and V2). Variation of these groups enables a combinatorial approach in the synthesis of bioorganometallic complexes. This is demonstrated by the preparation of Cp ligands containing both electron-donating and electron-withdrawing groups at the R1 position and their subsequent homo- or heterofunctionalization with biovector models (benzylamine and phenylalanine) under standard amide bond-formation conditions. All ligands can be coordinated to the fac-[Re(CO)3]+ and fac-[99mTc(CO)3]+ cores to give tetrafunctional complexes in straightforward and functional-group-tolerant procedures. The 99mTc complexes were prepared in one step, in 30 min, and under aqueous conditions from generator-eluted [99mTcO4]-

Derivatives of Sodium Boranocarbonate as Novel CO-Releasing Molecules (CO-RMs)

Despite the apparent and well-known toxic effects of carbon monoxide (CO), studies on the intriguing biological roles of this molecule are rapidly emerging. Recent investigations have brought to the limelight various physiological effects of CO which include, among others, vasorelaxation and inhibition of organ rejection after transplantation. The importance of CO in biology can be compared with another gas, nitric oxide (NO), an essential and ubiquitous signalling molecule. This parallelism led to the tantalising concept of using CO for therapeutic purposes wherein compounds that transport and deliver this gas to a target tissue would clearly facilitate both the clinical feasibility and the specificity of CO therapy. Sodium boranocarbonate, Na[H3 BCO2H] (1) was the first water-soluble and non-transition metal containing CO-releasing molecule (CO-RM) to be identified. In order to tune the rate of CO release, we modified 1 and synthesised and characterized various derivatives which release CO under physiological conditions but at rates different from the parent compound 1. The synthesis, structure and CO-releasing properties of ester and amide derivatives of 1 will be presented together with some biological studies carried out with a selection of the compounds

SensorCloud: Towards the Interdisciplinary Development of a Trustworthy Platform for Globally Interconnected Sensors and Actuators

Although Cloud Computing promises to lower IT costs and increase users' productivity in everyday life, the unattractive aspect of this new technology is that the user no longer owns all the devices which process personal data. To lower scepticism, the project SensorCloud investigates techniques to understand and compensate these adoption barriers in a scenario consisting of cloud applications that utilize sensors and actuators placed in private places. This work provides an interdisciplinary overview of the social and technical core research challenges for the trustworthy integration of sensor and actuator devices with the Cloud Computing paradigm. Most importantly, these challenges include i) ease of development, ii) security and privacy, and iii) social dimensions of a cloud-based system which integrates into private life. When these challenges are tackled in the development of future cloud systems, the attractiveness of new use cases in a sensor-enabled world will considerably be increased for users who currently do not trust the Cloud.Comment: 14 pages, 3 figures, published as technical report of the Department of Computer Science of RWTH Aachen Universit

Polar Substituents Enable Efficient Catalysis for a Class of Cobalt Polypyridyl Hydrogen Evolving Catalysts

A series of structurally related, acyclic cobalt tetrapyridyl hydrogen evolving catalysts (HEC) were prepared and characterized. The common motif, di(2,2′-bipyridin-6-yl)-methane, was derivatized at the bridging methylene to include a carbonyl group (L1), a hydroxy (L2), a methyl and a hydroxy (L3), a 1,1′-biphenyl-2,2′-diyl (L4), a hydroxy and a phenyl (L5) or a hydroxy and a pyrid-6-yl group. These catalysts were compared with the known HEC [Co(appy)Br]Br. Photo- and electrochemistry showed a distinct influence of the bridging position on rates and stabilities of the hydrogen evolution reaction (HER). Apolar ligands resulted in inferior catalytic performance as compared to HECs with polar substituents. Electrochemically, [Co(L1)Br2] was shown to be converted to [Co(L2)Br2] in catalysis. The best catalyst made more than 10’000 turnovers, albeit at an overpotential of 600 mV. Additional pH dependent mechanistic aspects were elucidated by cyclic voltammetry

Antibacterial mechanisms identified through structural systems pharmacology

Background: The growing discipline of structural systems pharmacology is applied prospectively in this study to predict pharmacological outcomes of antibacterial compounds in Escherichia coli K12. This work builds upon previously established methods for structural prediction of ligand binding pockets on protein molecules and utilizes and expands upon the previously developed genome scale model of metabolism integrated with protein structures (GEM-PRO) for E. coli, structurally accounting for protein complexes. Carefully selected case studies are demonstrated to display the potential for this structural systems pharmacology framework in discovery and development of antibacterial compounds. Results: The prediction framework for antibacterial activity of compounds was validated for a control set of well-studied compounds, recapitulating experimentally-determined protein binding interactions and deleterious growth phenotypes resulting from these interactions. The antibacterial activity of fosfomycin, sulfathiazole, and trimethoprim were accurately predicted, and as a negative control glucose was found to have no predicted antibacterial activity. Previously uncharacterized mechanisms of action were predicted for compounds with known antibacterial properties, including (1-hydroxyheptane-1,1-diyl)bis(phosphonic acid) and cholesteryl oleate. Five candidate inhibitors were predicted for a desirable target protein without any known inhibitors, tryptophan synthase β subunit (TrpB). In addition to the predictions presented, this effort also included significant expansion of the previously developed GEM-PRO to account for physiological assemblies of protein complex structures with activities included in the E. coli K12 metabolic network. Conclusions: The structural systems pharmacology framework presented in this study was shown to be effective in the prediction of molecular mechanisms of antibacterial compounds. The study provides a promising proof of principle for such an approach to antibacterial development and raises specific molecular and systemic hypotheses about antibacterials that are amenable to experimental testing. This framework, and perhaps also the specific predictions of antibacterials, is extensible to developing antibacterial treatments for pathogenic E. coli and other bacterial pathogens

User-driven Privacy Enforcement for Cloud-based Services in the Internet of Things

Internet of Things devices are envisioned to penetrate essentially all aspects of life, including homes and urbanspaces, in use cases such as health care, assisted living, and smart cities. One often proposed solution for dealing with the massive amount of data collected by these devices and offering services on top of them is the federation of the Internet of Things and cloud computing. However, user acceptance of such systems is a critical factor that hinders the adoption of this promising approach due to severe privacy concerns. We present UPECSI, an approach for user-driven privacy enforcement for cloud-based services in the Internet of Things to address this critical factor. UPECSI enables enforcement of all privacy requirements of the user once her sensitive data leaves the border of her network, provides a novel approach for the integration of privacy functionality into the development process of cloud-based services, and offers the user an adaptable and transparent configuration of her privacy requirements. Hence, UPECSI demonstrates an approach for realizing user-accepted cloud services in the Internet of Things.Comment: 6 pages, 2 figures, 1 listing. The 2nd International Conference on Future Internet of Things and Cloud (FiCloud-2014

Synthesis and Photophysical Evaluation of 3,3’‐Nitrogen Bis‐Substituted <i>fac</i>‐[Re(CO)₃(Diimine)Br] Complexes

The preparations, photophysical and electrochemical properties of a series of fac‐[Re(CO)$_{3}$(diimine)Br] complexes are presented. The bipyridine (bpy) based diimine ligands feature symmetrical and asymmetrical 3,3’‐diamino‐2,2’‐bipyridine substitution patterns. Photophysical and electrochemical properties of these complexes are tunable, depending on their organic diimine framework. Introduction of a distal urea bridge via the 3,3’‐substitution pattern led to prolonged phosphorescence lifetimes without a significant change in absorbance and phosphorescence emission wavelengths. Reversible electrochemical bipyridine reduction remained largely unchanged by this derivatization

Syntheses and characterization of vitamin B12-Pt(II) conjugates and their adenosylation in an enzymatic assay

Aiming at the use of vitamin B12 as a drug delivery carrier for cytotoxic agents, we have reacted vitaminB12 with trans-[PtCl(NH3)2(H2O)]+, [PtCl3(NH3)]− and [PtCl4]2−. These Pt(II) precursors coordinated directly to the Co(III)-bound cyanide, giving the conjugates [{Co}-CN-{trans-PtCl(NH3)2}]+ (5), [{Co}-CN-{trans-PtCl2(NH3)}] (6), [{Co}-CN-{cis-PtCl2(NH3)}] (7) and [{Co}-CN-{PtCl3}]− (8) in good yields. Spectroscopic analyses for all compounds and X-ray structure elucidation for 5 and 7 confirmed their authenticity and the presence of the central "Co-CN-Pt” motif. Applicability of these heterodinuclear conjugates depends primarily on serum stability. Whereas 6 and 8 transmetallated rapidly to bovine serum albumin proteins, compounds 5 and 7 were reasonably stable. Around 20% of cyanocobalamin could be detected after 48h, while the remaining 80% was still the respective vitaminB12 conjugates. Release of the platinum complexes from vitaminB12 is driven by intracellular reduction of Co(III) to Co(II) to Co(I) and subsequent adenosylation by the adenosyltransferase CobA. Despite bearing a rather large metal complex on the β-axial position, the cobamides in 5 and 7 are recognized by the corrinoid adenosyltransferase enzyme that catalyzes the formation of the organometallic C-Co bond present in adenosylcobalamin after release of the Pt(II) complexes. Thus, vitamin B12 can potentially be used for delivering metal-containing compounds into cell

Binding Small Molecules to a cis-Dicarbonyl 99^{\text{99}}TcITc^{\text{I}}-PNP Complex via Metal–Ligand Cooperativity

Metal–ligand cooperativity is a powerful tool for the activation of various bonds but has rarely, if ever, been studied with the radioactive transition metal $^{\text{99}}$Tc. In this work, we explore this bond activation pathway with the dearomatized PNP complex cis-[99TcI(PyrPNPtBu*)(CO)2] (4), which was synthesized by deprotonation of trans-[99TcI(PyrPNPtBu)(CO)2Cl] with KOtBu. Analogous to its rhenium congener, the dearomatized compound reacts with CO2 to form the carboxy complex cis-[99TcI(PyrPNPtBu–COO)(CO)2] and with H2 to form the mono-hydride complex cis-[99TcI(PyrPNPtBu)(CO)2H] (7). Substrates with weakly acidic protons are deprotonated by the Brønsted basic pincer backbone of 4, yielding a variety of intriguing complexes. Reactions with terminal alkynes enable the isolation of acetylide complexes. The deprotonation of an imidazolium salt results in the in situ formation and coordination of a carbene ligand. Furthermore, a study with heterocyclic substrates allowed for the isolation of pyrrolide and pyrazolide complexes, which is uncommon for Tc. The spectroscopic analyses and their solid-state structures are reported