Interdisciplinary approaches towards cooperation

Die Standard Ökonomie und im Besonderen das Konzept des „Homo Ökonomicus“ wird durch neue Ansätze aus anderen Forschungsgebieten herausgefordert. Diese Diplomarbeit stellt drei interdisziplinäre Ansätze vor. Die Verhaltensökonomie nutzt Wissen aus der Psychologie. Die Neuroökonomie kombiniert die Neurowissenschaften mit der Ökonomie und versucht so, Antworten auf neuronaler Ebene zu finden. Der dritte Ansatz, genannt Verhaltensgenetik der Ökonomie (genoeconomics), konzentriert sich auf die Rolle, die Gene bei für die Ökonomie interessanten Verhaltensweisen spielt. Um zu demonstrieren, wie diese Ansätze forschen, werden die jeweiligen Ergebnisse zum Thema Kooperation vorgestellt und die Chancen und Probleme der interdisziplinären Ansätze diskutiert. Die Verhaltensökonomie nutzte experimentelle Ansätze und konnte zeigen, dass Menschen nicht nur egoistisch sind. Sie zeigen soziale Präferenzen wie Reziprozität oder Aversion gegen Ungleichheit. Die Neuroökonomie konnte zeigen, dass der präfrontale Cortex, ein Vermittler zwischen Egoismus und Gemeinschaftsinteresse, und das Belohnungzentrum aktiv sind, wenn Kooperationsentscheidungen getroffen werden müssen. Die Verhaltensgenetik der Ökonomie konnte zeigen, dass kooperatives Verhalten eine genetische Komponente besitzt. Diese Diplomarbeit konnte zeigen, dass auch andere Wissenschaften Beiträge zur Ökonomie leisten können. Auch wenn es noch Probleme gibt, können diese interdisziplinären Ansätze die Ökonomie bereichern.Standard economic theory and especially the concept of the “homo oeconomicus” have been challenged by a number of new approaches from other scientific fields. This thesis will discuss three interdisciplinary approaches: Psychological knowledge of behavior is incorporated in the theory of behavioral economics. Neuroeconomics combines neuroscience with economics and tries to find answers on the neural level. The third approach of genoeconomics focuses on the role of genes related to economic behavior. To demonstrate how these approaches work, findings on cooperation were presented and chances and problems of the interdisciplinary approaches discussed. Behavioral economics uses experimental approaches and could show that people are not solely self-interested. They are also showing other-regarding preferences like reciprocity or inequity aversion. Neuroeconomic research found out that the prefrontal cortex, a mediator between social- and self-interest, and the reward system are activated when decisions concerning cooperation had to be made. Genoeconomics could prove that cooperative behavior has a genetic component. This thesis showed that other fields of science can contribute to economic questions. Although there are still problems to solve, interdisciplinary approaches can enrich economics

Solution Equilibrium Studies of Anticancer Ruthenium(II)-η6-p-cymene Complexes of Pyridinecarboxylic Acids

Stoichiometry and stability of antitumor ruthenium(II)-η6-p-cymene complexes of picolinic acid and its 6-methyl and 6-carboxylic acid derivatives were determined by pH-potentiometry, 1H NMR spectroscopy and UV–Vis spectrophotometry in aqueous solution in the presence or absence of coordinating chloride ions. The picolinates form exclusively mono-ligand complexes in which they can coordinate via the bidentate (O,N) mode and a chloride or a water molecule is found at the third binding site of the ruthenium(II)-η6-p-cymene moiety depending on the conditions. [Ru(η6-p-cymene)(L)(H2O/Cl)] species are predominant at physiological pH in all studied cases. Hydrolysis of the aqua complex or the chlorido/hydroxido co-ligand exchange results in the formation of the mixed-hydroxido species [Ru(η6-p-cymene)(L)(OH)] in the basic pH range. There is no indication for the decomposition of the mono-ligand complexes during 24 h in the ruthenium(II)-η6-p-cymene-picolinic acid system between pH 3 and 11; however, a slight dissociation with a low reaction rate was found in the other two systems leading to the appearance of the dinuclear trihydroxido-bridged species [Ru2(η6-p-cymene)2(OH)3]+ and free ligands at pH > 10. The replacement of the chlorido by an aqua ligand in [Ru(η6-p-cymene)(L)Cl] was also monitored and equilibrium constants for the exchange process were determined

Maltol-derived ruthenium(II)-cymene complexes with tumor inhibiting properties

Krebs ist die zweithäufigste Todesursache weltweit und in den letzten Jahrzehnten wurde nach immer neuen Behandlungsmöglichkeiten geforscht. Platinbasierende Zytostatika (Cis-platin, Carboplatin, Oxaliplatin) werden in ca. 50% aller Chemotherapien verwendet, aber wegen starker Nebenwirkungen (Nierenschädigung, Neurotoxizität, Übelkeit, Erbrechen, etc.) und Resistenzbildung werden neue Medikamente mit einer höheren Selektivität gegenüber der Krebszellen mit einer geringeren Toxizität bei normalen Zellen gesucht. Deswegen steigerte sich in den letzten Jahren das Interesse an Metallkomplexen mit anderen Zentralatomen als Platin, wie z. B. Ruthenium oder Gallium. Der Vorteil dieser neuen Verbindungen besteht in einer geringeren Toxizität und aus der Sicht des Chemikers in der höheren Koordinationszahl im Vergleich zu Platin. Eine Serie von Ru(III) und Ga(III) Komplexen (KP46, Trismaltolato-gallium, KP1019, NAMI-A) befindet sich derzeit in klinischen Studien mit sehr vielverspre-chenden Resultaten. Es wird vermutet, dass Ru(III) intrazellulär durch Glutathion zur aktiven Ru(II) Spezies reduziert wird („Activation by Reduction“ Hypothese). Seit einiger Zeit findet die Klasse der Ru(II) Aren Komplexe immer größer werdendes Inte-resse. Der aromatische Ligand stabilisiert das Ru(II) Zentralatom und bietet eine hydrophobe Stelle für den passiven Transport in die Zelle. Durch die Modifikation des Arens kann die Löslichkeit der Verbindung und die Affinität zu Nukleobasen stark beeinflusst werden. 4-Pyrone werden aufgrund ihrer starken Affinität zu Metallionen seit langem als Chelatligan-den verwendet. Maltol ist ein Vertreter dieser Substanzklasse der mit verschiedensten di- und trivalenten Metallionen, wie etwa Fe(III), Ga(III), Zn(II), Al(III), Ru(III), stabile und definierte Komplexe bildet und weiters eine hohe Biokompatibilität mit einem bevorzugten Toxizitäts-profil verbindet. Im Rahmen meiner Doktorarbeit wurde eine Serie neuer Ru(II)-Aren Komplexe, mit Pyron- und Thiopyronderivaten als Liganden, hergestellt und mittels 1D/2D NMR Spektroskopie, FT-IR Spektroskopie, Massenspektrometrie, Elementaranalyse und im Fall von Einkristallen mit Kristallstrukturanalyse charakterisiert. Die Stabilität in wässriger Lösung und der pKa Wert der reaktiven Aqua-Spezies wurden bestimmt und Untersuchungen bezüglich der Wech-selwirkungen mit kleinen Biomolekülen (z.B. 5’-GMP und diverse Aminosäuren) durchge-führt. Die IC50 Werte der Komplexe bezüglich der humanen Krebszelllinien CH1 (Eierstock-krebs), SW480 (Dickdarmkrebs) und A549 (Lungenkrebs) wurden bestimmt und Struk-tur/Aktivitäts-Beziehungen abgeleitet.Cancer is the second leading cause of death worldwide and has been over the last decades an area of intensive research. Platinum based chemotherapeutics as cisplatin, oxaliplatin or car-boplatin are used in approximately 50% of all cancer treatments. Due to severe side effects of these drugs (e.g. nephrotoxicity, neurotoxicity, nausea, vomiting etc.) and intrinsic or ac-quired resistance, there is an intensive search for novel drugs to overcome these limitations. In the last decade, complexes with metal ions other than platinum, like gallium and ruthenium, have been investigated for their anticancer properties. These compounds have a general lower toxicity and from the chemical point of view more coordination sites compared to platinum. Several ruthenium(III) and gallium(III) complexes (KP46, trismaltolate gallium, KP1019, NAMI-A) entered clinical trials and gave promising results. It is supposed, that the active species of the Ru(III) drugs are Ru(II) analogues which are obtained by reduction with glu-tathione inside the tumor cell (“Activation by Reduction”). During the last years, the novel class of “piano-stool” configurated Ru(II) arene complexes has found considerable interest. The arene ligand stabilizes the Ru(II) central atom and also provides an hydrophobic face for the passive transport inside the cell. By modifying the arene moiety, the solubility in water changes dramatically and the affinity to nucleobases can be tuned. 4-Pyrones have been used as chelating ligands for a long time, due to their high affinity to-wards metal ions. 3-Hydroxy-2-methyl-4-pyrone (maltol) is one of the best known com-pounds of this class, which forms stable and defined complexes with a high number of 2- and 3-valent metal ions, such as Fe(III), Ga(III), Zn(II), Al(III), Ru(III) etc. and based on of its well-studied biocompatibility a favorable toxicity profile is suggested. Within this Ph.D. thesis, a series of novel Ru(II) arene complexes, bearing a pyrone or thiopy-rone moiety as chelating ligand, were synthesized and characterized by 1D and 2D NMR spectroscopy, FT-IR spectroscopy, mass spectrometry, elemental analysis and, if single crys-tals were obtained, by X-ray diffraction analysis. The stability in aqueous solution, pKa values of the aqua species and the interactions with small biomolecules (e.g. 5’-GMP, and various amino acids) were determined. The cytotoxic activity of the complexes towards the human cancer cell lines CH1 (ovarian carcinoma), SW480 (colon carcinoma) and A549 (lung carci-noma) was investigated by using the colorimetric MTT assays, expressed as the IC50 values and structure–activity relationships have been derived

Solution Equilibria of Anticancer Ruthenium(II)-(η6-p-Cymene)-Hydroxy(thio)pyr(id)one Complexes: Impact of Sulfur vs. Oxygen Donor Systems on the Speciation and Bioactivity

Stoichiometry and stability of antitumor ruthenium(II)-eta(6)-p-cymene complexes of bidentate (0,0) hydroxypyrone and (O,S) hydroxythiopyr(id)one type ligands were determined by pH-potentiometry, H-1 NMR spectroscopy and UV-Vis spectrophotometry in aqueous solution and in dependence of chloride ion concentration. Formation of mono-ligand complexes with moderate stability was found in the case of the hydroxypyrone ligands (ethyl maltol and allomaltol) predominating at the physiological pH range. These complexes decompose to the dinuclear tri-hydroxido bridged species [(Ru-II(eta(6)-p-cymene)h(OH)(3)](+) and to the metal-free ligand at basic pH values. In addition, formation of a hydroxido [Ru-II(eta(6)-p-cymene)(L)(OH)] species was found. The hydroxythiopyr(id)one ligands (thiomaltol, thioallomaltol, 3-hydroxy-1,2-dimethyl-thiopyridone) form complexes of significantly higher stability compared with the hydroxypyrones; their complexes are biologically more active, the simultaneous bi- and monodentate coordination of the ligands in the bis complexes (ML2 and ML2H) was also demonstrated. In the case of thiomaltol, formation of tris complexes is also likely at high pH. The replacement of the chlorido by the aqua ligand in the [Ru-II(eta(6)-p-cymene)(L)(CI)] species was monitored, which is an important activation step in the course of the mode of action of the complexes, facilitating binding to biological targets

Antitumor Pentamethylcyclopentadienyl Rhodium Complexes of Maltol and Allomaltol: Synthesis, Solution Speciation and Bioactivity

The reaction of the dimer [RhIII(pentamethylcyclopentadienyl)(m-Cl)Cl]2 ([RhIII(Cp*)(m- Cl)Cl]2) with the hydroxypyrone ligands maltol and allomaltol affords complexes of the general formula [RhIII(Cp*)(L)Cl] under standard and microwave conditions. The organometallic compounds were characterized by standard analytical methods and in the case of the allomaltol derivative in the solid state by single-crystal X-ray diffraction analysis. The complexes showed similar cytotoxicity profiles and were proved to be moderately active against various human cancer cell lines. The stoichiometry and stability of these complexes were determined in aqueous solution by pH-potentiometry, 1H NMR spectroscopy and UVvisible spectrophotometry. Speciation was studied in the presence and in the absence of chloride ions. Hydrolysis of [RhIII(Cp*)(H2O)3]2+ gave dimeric mixed hydroxido species [(RhIII(Cp*))2(m-OH)3]+ and [(RhIII(Cp*))2(m-OH)2Z2] (Z = H2O/Cl‒). Formation of the mononuclear complexes [RhIII(Cp*)(L)Z] of maltol and allomaltol with similar and moderate stability was found. These species predominate at physiological pH and decompose only partially at micromolar concentrations. In addition, hydrolysis of the aqua complex or the chlorido/hydroxido co-ligand exchange resulted in the formation of the mixed-hydroxido species [RhIII(Cp*)(L)(OH)] in the basic pH range. Replacement of the chlorido by an aqua ligand in the complex [RhIII(Cp*)(L)Cl] was monitored and with the help of the equilibrium constants the extent of aquation at various chloride concentrations of the extra- and intracellular milieu can be predicted. Complexation of these RhIII complexes was compared to analogous [RuII(h6-p-cymene)] species and higher conditional stabilities were found in the case of the RhIII compounds at pH 7.4

Half-Sandwich Rhodium Complexes with Releasable N-Donor Monodentate Ligands: Solution Chemical Properties and the Possibility for Acidosis Activation

Cancer chemotherapeutics usually have serious side effects. Targeting the special properties of cancer and activation of the anticancer drug in the tumor microenvironment in situ may decrease the intensity of the side effects and improve the efficacy of therapy. In this study, half-sandwich Rh complexes are introduced, which may be activated at the acidic, extracellular pH of the tumor tissue. The synthesis and aqueous stability of mixed-ligand complexes with a general formula of [Rh(η5-Cp*)(N,N/O)(N)]2+/+ are reported, where (N,N/O) indicates bidentate 8-quinolate, ethylenediamine and 1,10-phenanthroline and (N) represents the releasable monodentate ligand with a nitrogen donor atom. UV-visible spectrophotometry, 1H NMR, and pH-potentiometry were used to determine the protonation constants of the monodentate ligands, the proton dissociation constants of the coordinated water molecules in the aqua complexes, and the formation constants of the mixed-ligand complexes. The obtained data were compared to those of the analogous Ru(η6-p-cymene) complexes. The developed mixed-ligand complexes were tested in drug-sensitive and resistant colon cancer cell lines (Colo205 and Colo320, respectively) and in four bacterial strains (Gram-positive and Gram-negative, drug-sensitive, and resistant) at different pH values (5–8). The mixed-ligand complexes with 1-methylimidazole displayed sufficient stability at pH 7.4, and their activation was found in cancer cells with decreasing pH; moreover, the mixed-ligand complexes demonstrated antimicrobial activity in Gram-positive and Gram-negative bacteria, including the resistant MRSA strain. This study proved the viability of incorporating releasable monodentate ligands into mixed-ligand half-sandwich complexes, which is supported by the biological assays

Heavy Metal Extraction under Environmentally Relevant Conditions Using 3-Hydroxy-2-Naphthoate- Based Ionic Liquids: Extraction Capabilities vs. Acute Algal Toxicity

We investigated the applicability of three task-specific ionic liquids (ILs) as heavy metal extracting agents by contrasting extraction capabilities with algal toxicity. The compounds tested were trihexyltetradecylphosphonium-, methyltrioctylphosphonium- and methyltrioctylammonium 3-hydroxy-2-naphthoates. Experiments were performed to assess if these ILs can provide environmentally safe residual concentrations of the target metals after extraction. Both pure water and natural mineral water samples were spiked with 20 mu g L-1 of Cu, Ag, Cd, Hg and Pb, respectively. Quantitative extraction (> 99%) of Hg and Ag was achieved. Cu and Hg were below the respective no-observed-effect-concentrations (NOECs) after extraction and Ag below 0.03 mu g L-1. Acute toxicity assays were conducted using two freshwater green algae Raphidocelis subcapitata and Tetradesmus obliquus. Growth inhibition and maximum photochemical quantum yield of photosystem II after 72 h were assessed. ILs were less toxic than similar compounds, but still must be classified as acute toxicants for algae. An inhibiting effect on both growth and chlorophyll fluorescence was observed. The leaching of the ILs into the samples remains a limitation regarding their environmental-friendly applicability. Nonetheless, the extremely efficient removal of Cu, Ag and Hg under environmentally relevant conditions calls for further research, which should focus on the immobilization of the ILs

Supplementary data for article: Mészáros, J. P.; Geisler, H.; Poljarević, J. M.; Roller, A.; Legina, M. S.; Hejl, M.; Jakupec, M. A.; Keppler, B. K.; Kandioller, W.; Enyedy, É. A. Naphthoquinones of Natural Origin: Aqueous Chemistry and Coordination to Half-Sandwich Organometallic Cations. Journal of Organometallic Chemistry 2020, 907. https://doi.org/10.1016/j.jorganchem.2019.121070

Supplementary material for: [https://doi.org/10.1016/j.jorganchem.2019.121070]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3804