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Digital archive of theses discussed at the University of Pisa

 

Thesis etd-02142023-163425


Thesis type
Tesi di dottorato di ricerca
Author
GOBBO, ALBERTO
URN
etd-02142023-163425
Thesis title
Adding Diversity to the Ruthenium-Tris(pyrazolyl)methane Scaffold
Academic discipline
CHIM/03
Course of study
SCIENZE CHIMICHE E DEI MATERIALI
Supervisors
tutor Prof. Marchetti, Fabio
Keywords
  • bioinorganic
  • catalysis
  • ruthenium
Graduation session start date
20/02/2023
Availability
Full
Summary
Ruthenium(II) coordination compounds with an arene ligand have been intensively investigated for their applications in catalysis and in medicinal chemistry. The formal replacement of the arene ligand with the isoelectronic tridentate tris(pyrazolyl)methane (tpm) has been sparingly explored heretofore.
A straightforward route was developed to access a family of novel [RuCl(3-tpm)(PPh3)(L)]Cl complexes, differing from each other in one key ligand (L). In addition, a range of bioactive fragments was tethered to the Ru-tpm scaffold to prepare optimized tumour-targeting molecules. Most of these complexes display an appreciable solubility in water, where they undergo partial chloride/water exchange. In addition, the Ru-tpm-PPh3 assembly is usually stable in D2O and in biological medium.
The investigated complexes displayed a shared antiproliferative activity against human cancer cells, and the mechanism of their biological activity appears mainly mediated by disruption of calcium homeostasis. Experiments on the bio-functionalized complexes indicates that the antiproliferative activity is not closely linked to enzymes inhibition.
The complex bearing a nitrile ligand exhibited the highest activity in the transfer hydrogenation of a series of ketones with isopropanol as the hydrogen source. Extensive NMR experiments and DFT calculations suggest the crucial role played by the tpm ligand, reversibly switching from tri- to bidentate coordination during the catalytic cycle.
The wide scope of the proposed synthetic strategies is potentially useful for the future design and preparation of targeted ruthenium compounds with improved specific properties for advanced applications.

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