Thesis title: Physicochemical Properties, In Vitro Experiments and Potentialities as Bimodal Anticancer Drugs of Novel Porphyrazine Macrocycles and Related Coordination Studies on Cis and Trans Bis-(m-Carborane-1-Thiolate) Pd(II) and Pt(II) N-Base Adducts
During the PhD course in Chemistry, my research work has concerned the synthesis and characterization of mono- and pentanuclear porphyrazine macrocycles of formulae [Py8PzM], [(PdCl2)4Py8PzM] and [{Pd(CBT)2}4Py8PzM] (M = MgII(H2O), ZnII, PdII). These species can find an important application as photosensitizers for the generation of singlet oxygen, 1O2, one the most active cytotoxic agent in PhotoDynamic Therapy (PDT). This is a well-known anticancer therapy in which 1O2 is used to destroy malignant cells, where the photosensitizer is preferentially localized. Furthermore, among the studied porphyrazine macrocycles, those carrying external Pd(CBT)2 units can find application in another anticancer treatment, the Boron Neutron Capture Therapy (BNCT), that requires species with a high content of boron atoms.
In parallel with the investigation on porphyrazine macrocycles, coordination studies have been carried out on the bidentate ligand 2,2’-bipirydil (bipy), by preparation of its bis-carboranthiolate derivatives of PdII and PtII, in order to achieve a deeper knowledge about the UV-visible spectral behavior observed for the related octacarboranthiolate porphyrazines [{Pd(CBT)2}4Py8PzM] (M = MgII(H2O), ZnII).
During the period spent abroad and thanks to the kind hospitality and collaboration of Dr. Nikolitsa Nomikou and Dr. Fabiola Sciscione at the Royal Free Hospital (London, UK), in-vitro tests have been developed on the squamous cell carcinoma (OSCC) verifying the photodynamic activity of the already known octacationic porphyrazines [(2-Mepy)8PzM](I)8 (M = MgII(H2O), ZnII).
Besides, another important study has been the investigation of the coordination properties of the multiple N-donor ligand 2,3-di-(2-pyridyl)-5,6-dihydropyrazine (dhdpp) with particular interest to define the type of coordination of the metal center in the complexes of formula [(dhdpp)MCl2] (PtII, PdII).