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Modified Iron Chelators Permeating Plasmatic Membrane
Tomášková, Alena ; Kotek, Jan (advisor) ; Schulz, Jiří (referee)
The effort to find a cure for cancer is a big topic nowadays. Some types of cancer cells contain more iron than healthy cells. Iron is a biogenic element that is important for cell proliferation and growth. Since the main site of iron metabolism is in the mitochondria, one way to induce cell death in cancer cells is to reduce the bioavailability of iron in the mitochondria. There are several currently registered therapeutics, some of which contain a hydroxypyridone group as an iron chelating unit, but none of the drugs in use are designed to target the mitochondria. For the chelating unit able to bind iron localized in the mitochondria, it needs to cross the outer and inner membranes of the mitochondria, which can be achieved by coupling the chelating unit with the triphenylphosphonium cation, which is a known membrane transporter, via a lipophilic chain. Triphenylphosphonium should be able to transport the hydrophilic chelating unit into the mitochondria due to its positive charge. The chelator will complex the ferric cations, thereby reducing their availability for other biochemical processes. In this work, two hydroxypyridone derivatives were prepared differing in the length of the spacer between the chelating unit and triphenylphosphine cation. Keywords Iron-binding ligands, mitochondrial...
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Synthesis and coordination behaviour of diphenylphosphinoferrocifen
Křelinová, Magda ; Schulz, Jiří (advisor) ; Kubíček, Vojtěch (referee)
Title: Synthesis and coordination behaviour of diphenylphosphinoferrocifen Author: Bc. Magda Křelinová Department: Department of Inorganic Chemistry Supervisor: RNDr. Jiří Schulz, Ph.D. Abstract: Ferrocifen, as a ferrocene analog of a commonly used drug - tamoxifen, showed promising activity against breast cancer cells - both the hormone-dependent type and the hormone-independent one. The treatment of the latter is a struggle for today's medicine and a new effective treatment is urgently needed. One of the goals of this thesis was to optimize the synthesis of 1-{1-[bis(4-hydroxyphenyl)methylene]propyl}-1'-(diphenylphosphino) ferrocene (compound 4), which will provide a way of conjugating the ferrocifenol moiety to metal complexes, that are also studied as anticancer agents. The combination of those effects could provide some interesting results against cancer cells. In this thesis, 8 complexes of compound 4 as a ligand were prepared. All of these compounds were subsequently tested on cancerous (MDA-MB-231, and A549) as well as non-cancerous (MCF10A) cell lines to assess their biological activity and potential selectivity towards cancerous cells. Ru Cl Cl P Ph2 Fe HO OH 6 Ru Cl Cl P Ph2 Fe HO OH 7 Ru Cl Cl P Ph2 Fe HO OH 8 Ru Cl Cl P Ph2 Fe HO OH 9 Ir Cl Cl P Ph2 Fe HO OH 10 Rh Cl Cl P Ph2 Fe HO OH 11 Fe P...
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Zirconium ternary complexes with fluoride anions
Zach, Kamil - Lukáš ; Kubíček, Vojtěch (advisor) ; Schulz, Jiří (referee)
Modern medicine uses non-invasive imaging methods for diagnostic purposes. Positron emission tomography is one of them. During the examination, the patient is injected with a radiopharmaceutical that is accumulated in tissue abnormalities and emits detectable radiation during its nuclear decay. The world's most commonly used radionuclide for these purposes is the radioisotope 18 F. The biodistribution of the fluoride ion itself is not very specific, so the radioisotope is usually bound to the structure of bioactive molecules. The actual preparation of these molecules is very challenging, so new labeling methods are currently being sought. One of the new possibilities is the preparation of labeled ternary complexes. In this work, the preparation of two polyazamacrocyclic ligands, H3NOTA and H3PCTA, which have acetate arms attached to their skeleton via aliphatic nitrogen atoms, is described. Zirconium complexes were prepared with these ligands. Subsequently, coordination and dissociation studies of fluoride ions to the prepared complexes were carried out. The measurements were monitored with a fluoride ion selective electrode. Both kinetic and thermodynamic aspects of coordination and decoordination were investigated in the measurements. Furthermore, characterization of the prepared ternary...
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Synthesis of ligands and reductive coupling catalysts
Žáková, Andrea ; Hulla, Martin (advisor) ; Schulz, Jiří (referee)
This thesis investigates Frustrated Lewis pair hydrogenation catalysts for the use in reductive amination reactions. A series of tin complexes using Schiff base ligands was synthetized. Their ability to act as Lewis acids in Frustrated Lewis pair catalysis was disclosed by series of experiment including Gutmann Beckett method, H2 activation using high pressure NMR measurements and hydrogenation catalytic testing. Synthetized ditriflate and monotriflate complexes were proven to reversibly activate H2 at room temperature and 60 řC respectively. All of the synthetized compounds successfully mediated imine hydrogenation confirming Frustrated Lewis pairs catalysis.
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Ternary macrocyclic complexes of metals with fluoride anions
Kuncová, Lucie ; Kubíček, Vojtěch (advisor) ; Schulz, Jiří (referee)
The aim of this thesis was to synthesize three ligands derived from mackrocycle TACN, which were previously investigated in our laboratory group, and subsequently prepare gallium and aluminum complexes with these ligands for the study of coordination properties. The complexes were characterized by NMR, HPLC-MS and EA. For the complexes that were prepared, data on the ability to bind fluoride anions (i.e. the formation of ternary macrocyclic complexes) were measured using fluoride ion-selective electrode. Dissociation equilibria at pH = 8-10 were also studied for the complex [Ga(L1)] that had the highest percentage of bound fluorine anions (~ 95%).
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Synthesis of phosphine derivatives of ferrocifen
Křelinová, Magda ; Schulz, Jiří (advisor) ; Pinkas, Jiří (referee)
Title: Synthesis of phosphine derivates of ferrocifen Author: Magda Křelinová Department: Department of Inorganic Chemistry Supervisor: RNDr. Jiří Schulz, PhD. Abstract: The goal of this bachelor thesis was to synthesize and characterize 1-{1-[bis(4-hydroxyphenyl)methylene]propyl}-1'-(diphenylphosphino)ferrocene (compound 7). As a ferrociphenol derivative, this compound should possess significant biological activity against breast cancer cells of both types (hormone-dependent and hormone-independent). Such treatment is currently not available and it is urgently needed. The diphenylphosphine moiety could serve as a linker to form conjugates with other organometallic pharmacophores. This could result in a better targetting or may otherwise enrich the effect of the compound 7. Thioketone 2 was prepared from 1,1'-dibromoferrocene by lithiation and reaction with Weinreb amide which afforded ketone 1 that was treated with Lawesson's reagent. Thiirane 3 was then synthesized by reaction of 2 with 1,1'-(diazomethylene)bis[4-methoxybenzene]. Its desulfurization afforded bromoderivative of methoxyferrociphene 4. Phosphinylation of compound 4 gave phosphinomethoxyferrociphene 5. Reaction with boronium tribromide formed aduct 6, which was deprotected by DABCO to give compound 7. All new compounds were characterized by...
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Preparation of P,N-donor ferrocene ligands by coupling reactions
Rezazgui, David ; Schulz, Jiří (advisor) ; Gyepes, Róbert (referee)
Title: Preparation of P,N-donor ferrocene ligands by coupling reactions Author: Bc. David Rezazgui Department: Department of Inorganic Chemistry Supervisor: RNDr. Jiří Schulz, Ph.D. Abstract: P,N-donor ligands form a varied group of compounds with wide utilization in homogeneous gold catalysis. This group of ligands uses geometrical features of moieties to which the donors are attached and the difference in hardness of the donor groups resulting in their unique coordination behavior. Ferrocene moiety offers unique geometrical features and flexibility. The chemical stability of ferrocene makes it possible to use various synthetic methods like cross- coupling reactions which are commonly used in organic synthesis. This work describes the preparation of six P,N-donor ferrocene ligands via Negishi cross-coupling reaction and their gold complexes which were further tested in catalytic cyclization of N-(prop-2-yn-1- yl)benzamide and oxidative cyclization of phenylacetylene. The electron richness of the phosphine donor moieties was assessed by measuring of 1 JSeP interaction constant of the corresponding selenides. In this work a general synthetic route to hetero- and homoannularly substituted P,N-donor ferrocene ligands of catalytically active complexes was introduced. Keywords: ferrocen, hybrid ligand, gold...
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Coordinatively unsaturated complexes with potential nucleasic activity
Willimetz, Robert ; Kotek, Jan (advisor) ; Schulz, Jiří (referee)
Biofilms are bacterial colonies attached to the surfaces through matrix of the biopolymer substances they produce. These biofilms can also form on medical implants, where they are responsible for difficult-to-treat chronic infections. One approach to prevent biofilm formation may be using of coordination compounds with nuclease activity. These compounds contain a hydrolytically active metal ion that is able to actively cleave extracellular DNA to prevent matrix and biofilm formation. The aim of this diploma thesis was to prepare a series of Cu(II) complexes of 1,4,7-triazacyclononane derivatives and to observe their potential nuclease activity. One of the complexes was a 1,4,7-triazacyclononane derivative with a thiazole anchor. Prepared complex can be incorporated through this anchor into polymers to a surface with potential ability to prevent biofilm formation.
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Synthesis and characterization of bidentate P,N-donor ferrocene ligand
Rezazgui, David ; Schulz, Jiří (advisor) ; Hulla, Martin (referee)
Title: Synthesis and characterization of bidentate P,N-donor ferrocene ligand Author: Bc. David Rezazgui Department: Department of Inorganic chemistry Supervisor: RNDr. Jiří Schulz, Ph.D. The main goal of this thesis was the preparation and characterization of ferrocene ligand 4-[1'-(diphenylphosphino)ferrocen-1-yl]morpholine (compound 3). Compared to structurally similar compounds, compound 3 offers greater geometrical flexibility which might have a positive effect in some applications, for example in catalysis by transition metal complexes. Two new compounds were synthesized along the synthetic route of phosphinoamine 3, the protected amine 1 and morpholine derivate 2. Selenide 4 was prepared in order to determine the basicity of compound 3 via the direct scalar interaction of 77 Se with 31 P. The synthesis comprised phosphinylation of 1,1'-dibromoferrocene, protection of the obtained 1-bromo-1'- (diphenylphosphino)ferrocene with sulfur, azidation and immediate reduction to protected amine 1. Morpholine derivate 2 was subsequently synthesized by cyclization reaction with bis(2-chloroethyl)ether. Phosphinoamine 3 was obtained by deprotection of compound 2 with Raney nickel. Finally, selenide 4 was obtained by the reaction of 3 with KSeCN. All newly prepared compounds were analyzed by NMR and transmission...
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