Ce travail intitulé " Libération du monoxyde d'azote induite par deux photons à partir de complexes ruthénium-nitrosyle contenant des ligands de capacités push-pull différentes " a été consacré à l'étude des principaux facteurs qui déterminent l'efficacité des complexes ruthénium- nitrosyles (Ru(NO)) dans l'absorption à deux photons (ADP) et à l'amélioration de leur section efficace ADP par modification de la nature et de la structure de leurs ligands. A partir de complexes précédemment obtenus dans le groupe de recherche du Prof. I. Malfant, nous avons effectué diverses modifications structurales. Il a été montré que la substitution des ligands monodentes par la 2,2'-bipyridine dans les complexes de Ru(NO) conduit à une légère augmentation de la section efficace, mais cette modification diminue le rendement quantique du relargage du monoxyde d'azote NO. La partie synthétique du travail a principalement porté sur la modification du ligand. / The work "Two-photon induced photorelease of nitric oxide from ruthenium-nitrosyl complexes containing ligands of various push-pull capabilities" was devoted to the revealing of main factors that determine the efficiency of ruthenium-nitrosyl complexes in two-photon absorption (TPA) and the improvement of TPA cross-section through modification of the ligands nature and their structure. Starting from complexes previously obtained by the research group of Prof. I. Malfant, we have modified their structure in several directions. It was shown that substitution of monodentate ligands by 2,2'-bipyridine in ruthenium complexes with nitrosyl ligands leads to a slight increase of their TPA cross- section, however this modification decreases the quantum yield of the nitric oxide photo release. Synthetic part of the work was mainly aimed at the modification of the ligand.

Scorpionate and terpyridine ligands are of importance in inorganic chemistry for their metal-binding properties. Tris-pyrazolylborate (Scorpionate) ligands that show facial binding mode and steric protection have been extensively used to synthesize complexes modeling the active site structure and biological function of various metalloproteins and as catalysts in C-H and NO activation and carbine transfer reactions. Terpyridine and modified terpyridine ligands showing meridional binding mode have been used in bioinorganic chemistry where Pt-terpyridine complexes are known to inhibit the activity of thiordoxin reductase (TrxR) besides showing interaction with G-quadruplex. The thesis work stems from our interest to use these ligand systems to design and prepare new 3-d metal-based photodynamic therapeutic (PDT) agents to explore their visible light-induced DNA cleavage activity and photocytotoxicity. Efforts have been made in this thesis work to design and synthesize Co(II) and Cu(II) complexes having scorpionate (Tpph) abd terpyridine (tpy) ligands. Ternary 3d-metal complexes having Tpph and planar phenanthroline bases have been synthesized and structurally characterized. The steric encumbrance of Tpph has led to the reduction in chemical nuclease activity along with enhanced photo-induced DNA cleavage activity, particularly of the Cu(II) and Co(II) complexes. The Co(II), Cu(II) and Zn(II) complexes of Tpph and a pyridyl ligand having a photoactive naphthalilmide moiety show molecular light-switch effect on binding to calf thymus DNA or BSA protein. The complexes do not show any chemical nuclease activity. The Cu(II) complex shows significant DNA cleavage activity in red light. The Co(II) complex displays significant photocytotoxicity in UV-A light. Ternary Cu(II) complexes of ph-tpy and heterocycylic bases are prepared and their DNA binding and cleavage activity studied. The complexes are avid binders to CT-DNA. The dipyridoquinoxaline (dpq) and dipyridophenazine (dppz) complexes are photocleavers of DNA in visible light. A significant enhancement in cytotoxicity in HeLa cancer cells is observed on exposure of the dppz complex to light. The binary Cu(II) complexes are also prepared to reduce the dark toxicity using phenyl and pyrenyl substituted terpyridine ligands. The pyrenyl substituted complex shows DNA cleavage activity in the visible light, low dark toxicity and unprecedented photocytotoxicity in visible light. The copper(II) complexes generally show dark cellular toxicity due to the presence of reducing thiols. The present terpyridine copper(II) complex having pendant pyrenyl moiety shows significant PDT effect that is similar to that of the PDT drug Photofrin. Binary Co(II) complexes show efficient DNA cleavage activity in visible light, significant photocytotoxicity in visible light and cytosolic uptake behaviour. Considering the bio-essential nature of the cobalt and copper ions, the present study opens up new strategies for designing and developing 3d-metal-based photosensitizers for their potential applications in PDT.