The redox-conversion reaction of metal-disulfide and metal-thiolate complexes are important, as they may shed light on electron-transfer reactions that often occur in Nature. Despite their... Show moreThe redox-conversion reaction of metal-disulfide and metal-thiolate complexes are important, as they may shed light on electron-transfer reactions that often occur in Nature. Despite their importance, very few examples have been reported. In addition to that, there is a limited understanding of how the coordination environment of the metal ion affects this reaction. In this thesis, our investigation was set based on the ligand-field theory to determine its correlation with the redox-conversion reactions in cobalt-based systems. Our experiments revealed that using an exogenous ligand with a strong ligand-field character may induce the redox conversion from cobalt(II)-disulfide complexes to cobalt(III)-thiolate complexes. Using this knowledge, the possibility of the redox-conversion reaction was also extended from cobalt(II)-diselenide to cobalt(III)-selenolate complexes.Finally, we have come up with several conclusions about the redox-conversion reactions of the cobalt(II)-dichalcogenide complexes. It was revealed that the conversion is affected by the ligand-field strength of the dichalcogenide ligand. The smaller ligand-field strength can be counterbalanced with the introduction of the strong auxiliary ligand. Lastly, the cleanliness of the conversion depends on the magnitude of the overall ligand-field splitting energy of the complex. Show less
The electrochemical oxygen reduction reaction (ORR) is an essential half-reaction for the utilization of hydrogen as a sustainable fuel, via the conversion of hydrogen to electrons and protons... Show moreThe electrochemical oxygen reduction reaction (ORR) is an essential half-reaction for the utilization of hydrogen as a sustainable fuel, via the conversion of hydrogen to electrons and protons facilitated by the ORR. In the most common fuel cells, the ORR is requires high loadings of non-abundant platinum based catalysts. Inspired by Laccase, a multicopper oxidase able to perform the ORR at a low overpotential, copper complexes have become interesting targets as non-precious metal catalysts for the ORR.In this thesis, the ORR performance of molecular copper catalysts and the involved catalytic mechanisms have been investigated. The previously undetermined electrocatalytic mechanism for the ORR by the Cu(tmpa) copper complex was elucidated. Hydrogen peroxide was shown to play an important role in the catalytic cycle as a reaction intermediate. This has interesting implications for the sustainable electrochemical production of hydrogen peroxide. Furthermore, the reduction of hydrogen peroxide shows striking similarities with Fenton-like reactions observed in copper containing enzymes. Finally, the performance of several different copper electrocatalysts for the reduction of oxygen and hydrogen peroxide was investigated and compared. Show less
Metal complexes and 2D materials like graphene were combined to produce structures that can function as sensors. Using spin crossover materials, both in bulk single crystal form and in thin layer... Show moreMetal complexes and 2D materials like graphene were combined to produce structures that can function as sensors. Using spin crossover materials, both in bulk single crystal form and in thin layer form, graphene-based electronic sensors were produced and characterized that can detect spin switches in the spin crossover materials. At the same time, the light-activatable ruthenium complexes were researched for their application in sensors that can monitor reactions that were triggered by light. We found that the photoreaction of a ruthenium complex with a nucleobase could be triggered in paper-based graphene devices. Moreover, we found that this ruthenium scaffold could also be used to increase the signal strength in a nanopore-based DNA detection system. Lastly, a ruthenium complex was designed that had a sensing function built in, as a dual-function molecule with a sensing and anticancer function. Overall, combining metal complexes with graphene was found to be a successful strategy to produce hybrid structures for sensing. Show less
The aim of the present study was to develop folic acid (FA) conjugates which can deliver the kinase inhibitor dactolisib to the kidneys via folate receptor-mediated uptake in tubular epithelial... Show moreThe aim of the present study was to develop folic acid (FA) conjugates which can deliver the kinase inhibitor dactolisib to the kidneys via folate receptor-mediated uptake in tubular epithelial cells. Dactolisib is a dual inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) and is considered an attractive agent for treatment of polycystic kidney disease. The ethylenediamine platinum(II) linker, herein called Lx, was employed to couple dactolisib via coordination chemistry to thiol-containing FA-spacer adducts to yield FA-Lx-dactolisib conjugates. The dye lissamine was coupled via similar linker chemistry to folate to yield fluorescent FA-Lx-lissamine conjugates. Three different spacers (PEG(5)-Cys, PEG(27)-Cys or an Asp-Arg-Asp-Asp-Cys peptide spacer) were used to compare the influence of hydrophilicity and charged groups in the spacer on interaction with target cells and in vivo organ distribution of the final conjugates. The purity and identity of the final products were confirmed by UPLC and LC-MS analysis, respectively. FA-Lx-dactolisib conjugates were stable in serum and culture medium, while dactolisib was released from the conjugates in the presence of glutathione. All three type of conjugates were internalized efficiently by HK-2 cells and uptake could be blocked by an excess of folic acid in the medium, demonstrating FR mediated uptake. FA-Lx-dactolisib conjugates showed nanomolar inhibition of the PI3K pathway (Akt phosphorylation) and mTOR pathway (S6 phosphorylation) in cultured kidney epithelial cells (HK-2 cells). After intraperitoneal administration, all three types conjugates accumulated extensively in kidneys of iKsp-Pkd1(del) mice with polycystic kidney disease. In conclusion, folate conjugates were successfully prepared by platinum(II) coordination chemistry and accumulated in a target-specific manner in kidney cells and polycystic kidneys. The folate conjugate of dactolisib thus may have potential for targeted therapy of polycystic kidney disease. Show less
Metal-based prodrugs based on ruthenium(II) polypyridyl complexes have proven to be very suitable for application in both photodynamic therapy (PDT) and photo-activated chemotherapy (PACT). As most... Show moreMetal-based prodrugs based on ruthenium(II) polypyridyl complexes have proven to be very suitable for application in both photodynamic therapy (PDT) and photo-activated chemotherapy (PACT). As most of these complexes unfortunately require poorly-penetrative, potentially-toxic blue light for their photo-activation, a lot of research effort has been dedicated to the development of prodrug systems that can be activated using near-infrared light, which is less harmful and penetrates deeper into human tissue. Thulium-doped upconverting nanoparticles (UCNPs) produce the desired blue light upon excitation with near-infrared light, allowing for the development of a drug delivery system in which ruthenium prodrugs are activated with near-infrared light. This thesis deals with the development of several new photo-activatable ruthenium polypyridyl complexes and the investigation of their photochemistry. Furthermore, a multicentre comparative study of the upconversion quantum efficiencies of LiYF4 UCNPs is reported. Finally, it describes the formation of water-dispersible UCNPs decorated with the newly-developed ruthenium complexes, as well as their stability in aqueous media and the successful photo-activation of the surface-bound ruthenium complexes using near-infrared light. The work has resulted in new insights into the design principles that are essential for the successful development of photo-activatable ruthenium-decorated upconverting nanoparticles. Show less
In the last decade, the redox interconversion between metal thiolate and disulfide compounds has been extensively investigated for copper, but not for other transition metal ions. In this... Show moreIn the last decade, the redox interconversion between metal thiolate and disulfide compounds has been extensively investigated for copper, but not for other transition metal ions. In this thesis, our investigations are described of the possibility to extend the metal thiolate/disulfide redox interconversion reactions to cobalt or iron compounds. A number of cobalt(II) disulfide and cobalt(III) thiolate compounds of different ligands and different anions are reported in this thesis. It was revealed that the anion of cobalt(II) salts, the structure of disulfide ligands, and the type of solvent influence the formation of either cobalt(II) disulfide or cobalt(III) thiolate compounds. However, a consistent trend cannot be provided to predict which of the species is generated. An important conclusion of this work is that the cobalt(II) disulfide to cobalt(III) thiolate interconversion reaction might be related to the ligand field strength of the ligand, and the binding strength and ligand field strength of the anions and solvent used. Apart from the cobalt compounds, two iron(II) disulfide compounds were reported in this thesis as well. However, so far we were not able to trigger the conversion of these compounds to their respective iron(III) thiolate compounds. Show less
The research described in this thesis focused on the preparation of S/N functionalized carbene ligands and their transition metal complexes, and the exploration of their application as... Show moreThe research described in this thesis focused on the preparation of S/N functionalized carbene ligands and their transition metal complexes, and the exploration of their application as electrocatalysts for proton reduction. Show less
Ording-Wenker, E.C.M.; Siegler, M.A.; Bouwman, E. 2015
The research described in this thesis is focused on the modeling of different aspects of biomimetic redox reactions between copper ions and sulfur-containing compounds.
