Three novel tetracationic bis‐triarylboranes with 3,4‐ethylenedioxythiophene (EDOT) linkers, and their neutral precursors, showed significant red‐shifted absorption and emission compared to their thiophene‐containing analogues, with one of the EDOT‐derivatives emitting in the NIR region. Only the EDOT‐linked trixylylborane tetracation was stable in aqueous solution, indicating that direct attachment of a thiophene or even 3‐methylthiophene to the boron atom is insufficient to provide hydrolytic stability in aqueous solution. Further comparative analysis of the EDOT‐linked trixylylborane tetracation and its bis‐thiophene analogue revealed efficient photo‐induced singlet oxygen production, with the consequent biological implications. Thus, both analogues bind strongly to ds‐DNA and BSA, very efficiently enter living human cells, accumulate in several different cytoplasmic organelles with no toxic effect but, under intense visible light irradiation, they exhibit almost instantaneous and very strong cytotoxic effects, presumably attributed to singlet oxygen production. Thus, both compounds are intriguing theranostic agents, whose intracellular and probably intra‐tissue location can be monitored by strong fluorescence, allowing switching on of the strong bioactivity by well‐focused visible light.

Diese Arbeit beschäftigt sich mit der Synthese, Charakterisierung und Eigeschaften neuer Monopentafluorethylborat-Anionen der Form [C2F5BH2X]- (X= F, Cl, Br), [C2F5BH2(CN)]-, [C2F5BH(CN)2]-, [C2F5BH(CN)X]- (X= F, Cl, Br) und [C2F5B(CN)X2]- (X= Cl, Br)sowie den Bis-pentafluorethylborat-Anionen [(C2F5)2B(OMe)(CN)]-, [(C2F5)2BF(CN)]- und [(C2F5)2B(CN)2]-. Von einigen dieser Verbindungen wurden Ionische Flüssigkeiten basierend auf dem 1-Ethyl-3-methylimidazolium-Kation synthetisiert und deren physikalischen Parameter ausführlich untersucht. Zudem wurden Pentafluorethylboran-Addukte mit verschiedenen Lewis-Basen der Form C2F5BH2-L (L= THF, SMe2, CH3CN, Pyridin, PPh3, CAAC, IDipp, SIDipp, Me4Im, (iPr)2Me2Im, tBu2Im) hergestellt welche zum Teil als Startmaterialien für die Synthese von Monopentafluorethylboraten verwendet wurden.

This thesis reports on synthesis and reactivity of new NHC- and cAAC-stabilized Lewis-acid/Lewis-base adducts of group 14 and group 15 element compounds.

After implementing a reliable mass spectrometry based kinetic study the indole conjugation with different organometallic indoles led to questions about the electronical and sterical influences on reactivity. The substitution pattern of the ferrocene functionalized indoles at the six-membered ring determines the electron density on the C3 atom, which reacts with the formed Schiff base. Since the experimental results showed the exact opposite trend, covalent docking studies were performed elucidating the importance of surface interactions. These studies were in harmony with the experimental results and determined lysine 33 as most preferable conjugation site as well as substitution in 6-position as most favourable pattern. The amine motif in compounds 6, 7 and 8 proofed to be easily fragmented by the ESI method used. The amide linker in 10 remains intact but shows a lower conversion. Those two inherent characteristics are however preferable for well-defined and site-specific bioconjugation. The synthesis and evaluation of piano stool complex derivatives with manganese and rhenium metal centre 15, 16, 18 and 22 gave additional guidance by the interpretation of applicable structural motifs. The electron-withdrawing carbonyl groups lead to the hindrance of fulvene formation and thus to no fragmentation as seen with the ferrocene group. The total conversion is low compared to 8, only 22 shows a good enough conversion to mainly monoconjugate of 45% and a possible radio-labelling application as 99mTc analogue. As consequence manganese complexes with a stable facial tricarbonyl unit and a tridentate chelator with 4-, 5- and 6-substituted aminomethylindole conjugated through an amide bond were synthesized and consecutively evaluated. The resulting organometallic indole derivatives 29, 30 and 31 all showed a total conversion around 40% similar to 16, but at the same time a rate constant in the range of 10-4 s-1 like the organic indole. Besides the similar conversion, the rate constants followed the trend of the 6-substituted derivative as fastest and then 5- and 4- substituted derivative with decreasing reactivity. For underlining the usage as technetium label for the best out of the series 31, a rhenium analogue was prepared. The resulting compound 32 was especially interesting, because the conversion was even higher than the 70% of 8 with a total of 88%. Additionally, the rate constant was a tenfold higher as well. This rendered compound 32 as best possible 99mTc analogue for further application as radio-label. After the success of 32 and realizing the sterical benefits resulting from the flexible tridentate ligand-system, substitution at the five-membered ring was explored. The complexes 33, 34 and 35 are based on indole-2-carboxylic acid and with the difference of the length of the alkyl spacer between amide and complex to probe for the influence and sterical hindrance, but all three derivatives showed no conjugation which excludes functionalization in 2-position. As the C3 is used for the actual bioconjugation, the last possible derivatization was realized on the indole-N1 by using 1-(3-bromopropyl)indole as building block during the synthesis of the ligand-system. The corresponding manganese 36 and rhenium 37 complexes both showed similar properties of a moderate conversion like 22 and a rate constant in the range of 10-5 s-1. In conclusion the rhenium complex 32 with the 6-substitution pattern at the tridentate indole-bearing ligand remains the most promising structure. The here developed liquid chromatography coupled mass spectrometry-based assay for the determination of inhibitory activity of drug candidates against the 3CLpro of the sever acute respiratory syndrome coronavirus type 2 was successfully implemented and especially designed to give, due to the available absorption spectra and corresponding mass traces, further insight in the otherwise through fluorescence resonance energy transfer-based assays neglected influences on the inhibition results. Starting with a literature-known quinolone containing covalent inhibitor 42 an N1-methylated derivative 43 and their analogues 44 and 45 in which the benzoic acid was exchanged for ferrocene carboxylic acid were synthesized. The inhibition of 3CLpro was evaluated by the concentration of initial 15mer peptide left after incubation and for that purpose the for 280 nm defined molar attenuation coefficient of (26.41±0.59) L*mol-1*cm-1 determined and used. The results showed a reaction of DL dithiothreitol with the less stable benzoic acid esters leading to a moderate inhibitory effect. The methylation in N1-position showed an increase in stability. The methylated and with ferrocene carboxylic acid functionalized derivative showed a complete inhibition during the timeframe of the assay. In search of a fluorescent and therefore traceable inhibitor, 4 hydroxycoumarin was used to synthesize the analogue with benzoic acid 49 and ferrocene carboxylic acid 50. Both derivatives were less stable than their analogues but exhibited the same trend of a more stable ferrocene-derived compound, which exerted a higher inhibition as well. After preparing and testing the model thioester 53 and showing an inactivation of the established inhibitor ebselen, it was concluded that the reaction with DL dithiothreitol reduces the concentration of active intact inhibitor and therefore decreases the inhibition rate during the assay. The next step was proofing the reducing agent as non-essential for the fast assay conducted in a timeframe of 5 min to circumvent the negative influence of DL dithiothreitol. By excluding every inhibition-altering part, the resulting method is the perfect tool for precise statements in relation of inhibitory activity. Then the inhibition assay was repeated for ebselen and the best out of the here introduced organometallic inhibitors 45. Both give equivalent results of a complete inhibition during the measurement. The implemented liquid chromatography coupled mass spectrometry-based assay has many advantages over the fluorescence resonance energy transfer-based assays in which all the information and insight accumulated by the evaluation of uv/vis traces and mass spectra are not available leading to wrong or deviating results regarding the inhibitory capacity of inhibitor candidates.

Die Vorliegende Arbeit befasst sich mit der Darstellung und Reaktivität von Aluminolen, als auch Aluminafluorenen. Die Aluminole gehen eine Ringerweiterungsreaktion mit organischen Aziden ein, welche zur Bildung von sechsgliedrigen Aluminium-Stickstoff-Heterocyclen, den ersten nicht annulierten 1,2 Azaaluminabenzolen führt. Weiterhin findet die Ringerweiterung des Aluminols mit einem Nitron, einem Iminoboran und einem Amin-N-Oxid statt, wodurch neue sechs-, sieben- und achtgliedrige cyclische Spezies mit hohem Heteroatomgehalt entstehen. Insgesamt wurden fünf neue Aluminafluorene hergestellt, die je nach Substituent am Aluminiumzentrum unterschiedliche Strukturen aufweisen. Ihre relativer Lewis-Säure-Stärke wurde mit der Gutmann-Beckett-Methode ermittelt. Neben der Bildung von Addukten mit NHCs, CAAC und DMAP, wurde in das Bromaluminiumfluoren auch (tert-Butylimino)mesitylboran insertiert, welches zur Bildung eines siebengliedrigen Aluminacyclus führte.