Untersuchungen zur Synthese und Hydrolyse von aminosäure- und peptidfunktionalisierten Organozinnsulfidclustern

Im Rahmen dieser Doktorarbeit wurde die Anbindung von Aminosäuren sowie Peptiden an Organozinnsulfidcluster über zwei verschiedene synthetische Ansätze untersucht. Ziel sollte es sein, die Löslichkeit dieser Cluster zu erhöhen und eine bessere Stabilität gegenüber Luftsauerstoff und Wasser zu erreic...

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Bibliographic Details
Main Author: Engel, Annikka
Contributors: Dehnen, Stefanie (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2019
Online Access:PDF Full Text
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Within the framework of this doctoral thesis, the attachment of amino acids and peptides to the surface of organotin sulfide clusters were investigated via two different synthetic approaches. The main goal was to improve clusters’ solubility and stability against air and moisture. The first approach followed a novel strategy for the synthesis of organo-functionalized tin sulfide clusters. Up to date, keto-functionalized clusters were prepared and post-functionalized with organic substituents. The presence of water, which arises during this functionalization, decomposition of the clusters took place in some cases. Therefore, is was decided to functionalize the less sensitive organotintrichloride reactant. This was realized with non-polar (L-alanine, L-valine, L-leucine, L-phenylalanine und L-methionine) as well as polar (L-tyrosine und L-serine) and basic (L-histidine) amino acids. To avoid an intramolecular condensation reaction, the amino group of the amino acid was protected with a boc protection group. Later on, we were also able to partially cleave this protection group off the ligands by addition of trifluoroacetic acid. The reaction of the functionalized organotintrichlorides with bistrimethylsilylsulfide led to the formation of defect-heterocubane-type organotin sulfide clusters. This was proven by 1H-NMR, 13C-NMR and 119Sn-NMR spectroscopy, and ESI(+) mass spectrometry. Reactions of the organotintrichlorides with sodium sulfide yielded the related “doppeldecker”-type clusters. Discrimination from the defect-heterocubane-type cluster was allowed by 119Sn-NMR spectroscopy, whereas 1H-NMR and 13C-NMR spectroscopy as well as ESI(+) mass spectrometry showed no significant differences. Moreover, the hydrolysis of keto- and phenylalanine-functionalized organotin sulfide clusters was investigated under acid conditions. Upon addition of hydrochloric acid, the organotintrichloride was re-constituted under the release of H2S without any further side products. This was demonstrated by means of 1H-NMR spectroscopy and mass spectrometry. The use of hydrobromic acid led to a mixture of chloride (X) and bromide substituted (Y) organotin compounds (RSnX3-nYn), as shown by ESI(–) mass spectrometry. Reaction with sulfuric acid caused complete decomposition of the clusters under formation of polysulfides and tin sulfide. The addition of acetic acid as well as ammonium chloride did not lead to decomposition of the clusters according to ESI(+) mass spectrometry and 1H-NMR spectroscopy. In the presence of an excess of acetic acid, a black solid precipitated, which was not further investigated due to low solubility. The second approach addressed the attachment of biomolecules. It was realized in cooperation with Jan-Philipp Berndt (Schreiner group). Jan-Philipp Berndt synthesized an adamantylazide moiety, which we were able to attach to the surface of organotin sulfide clusters. Subsequent reactions of the terminal azide group of the functionalized cluster with an alkyne via “click-chemistry” led to the desired product. In the case of an unsymmetrical alkyne containing a terminal amine function, a side reaction took place. By ring-closing during an intramolecular condensation reaction, two tin atoms were linked via an organic substituent. However, this structure may allow selective functionalization at one organic substituent. Through the attachment of tripeptides (by Jan-Philipp Berndt) at the side chain of the unsymmetrical and at another, symmetrical, alkyne, larger biomolecules were attached to the tin sulfide cluster. The target product was a threefold-substituted compound, which we were able to detect. For reactions with the symmetrical alkyne, the product could be characterized by means of ESI(+) mass spectrometry and 13C-NMR and 119Sn-NMR spectroscopy. This work showcased the attachment of large biomolecules to the surface of organotin sulfide clusters. This way, the clusters’ solubility in polar and donor solvents like dimethylformamide, methanol and acetonitrile, was improved considerably. This may be the base for potential biological applications in the future.