Dipolar and quadripolar ruthenium nitrosyl complexes with enhanced two-photon absorption for nitric oxide delivery : syntheses and mechanism

Dipolar and quadripolar ruthenium nitrosyl complexes with enhanced two-photon absorption for nitric oxide delivery: syntheses and mechanism Nitric oxide (NO•) is important for its biological functions. In this context, photoreactive ruthenium nitrosyl complexes are of special interest because they can release nitric oxide under controlled excitation. In our group, Two Photon Absorption (TPA) materials are considered because it circumvents the main shortcomings that the nitric oxide is released out of the therapeutic window (700 - 1100 nm). The analyses presented in this thesis represent our current understanding and progress in TPA and photokinetic on RuNO compounds. Chapter I delves into how NO• has therapeutic potential, emphasis is placed on Photodynamic Therapy (PDT) and Photoactivated Chemotherapy (PACT) as innovative solutions against cancer and microbial infections. Additionally, the work explores nonlinear optics, focusing on conjugation, dipolar structures, and quadrupolar structures, elucidating their importance in TPA processes. In Chapter II, two types of molecular design containing [Fluorene-Terpyridine-Ru(bipyridine)(NO)] (RuNO-1) as the benchmark reference are synthetized and characterized: dipolar structures (RuNO-1 and 2) where the "push-pull" effect determines the ability to get a good TPA response and quadrupolar structures (RuNO-3 to 5). The Z-scan analysis at different wavelengths of the comparative dipolar and multipolar chromophores is presented. Chapter III explores the release capacities of NO• from RuNO complexes upon irradiation. Also, it is examining the photoresponse of these complexes at a different wavelength of irradiation. Through various analyses, it is observed that monometallic complexes show direct conversion following A→C mechanism, while bimetallic complexes have a two-step photodissociation A→B→C. With synthesis of one intermediate B and final photoproduct C it was possible to extract the nitric oxide quantum yield (φNO). In Chapter IV we discussed on how RuNO-3 complex is one of the most appealing compounds for PACT, but modifications are required for in vitro testing due to the instability in aqueous environments. As a solution, the synthesis of trans, trans-Ru(NO)Cl(OH)-3 is suggested.Photolibération de NO et absorption à deux photons remarquable dans des complexes dipolaires et quadripolaires de ruthénium à ligand nitrosyle : synthèses et mécanismes Le monoxyde d'azote (NO•) est important pour ses fonctions biologiques. Dans ce contexte, les complexes de ruthénium à ligand nitrosyle (RuNO) photoréactifs suscitent un intérêt particulier car ils peuvent libérer du monoxyde d'azote sous une excitation contrôlée. Dans notre groupe, les matériaux à Absorption Biphotonique (TPA) sont considérés car ils contournent les principaux inconvénients liés à la libération du NO• en dehors de la fenêtre thérapeutique (700 - 1100 nm). Les analyses présentées dans cette thèse font état de notre compréhension actuelle et de notre progression dans le domaine de l'absorption à deux photons et de la photocinétique des complexes RuNO. Le Chapitre I explore le potentiel thérapeutique du NO• sur la Thérapie Photodynamique (PDT) et la Chimiothérapie Photoactivée (PACT) comme solutions innovantes contre le cancer et les infections microbiennes. De plus, le travail explore l'optique non linéaire, la conjugaison, les structures dipolaires et quadrupolaires, élucidant leur importance dans les processus TPA. Dans le Chapitre II, deux complexes moléculaires contenant le fragment [Fluorène-Terpyridine-Ru(bipyridine)(NO)] (RuNO-1) sont synthétisés et caractérisés : Les structures dipolaires (RuNO-1 et 2) où l'effet "push-pull" détermine la capacité à obtenir une bonne réponse TPA et les structures quadrupolaires (RuNO-3 à 5). L'analyse par Z-scan à différentes longueurs d'onde est présentée. Le Chapitre III explore les capacités de libération du NO• à partir des complexes RuNO lors de l'irradiation. Il examine également la photo-réponse de ces complexes à différentes longueurs d'onde d'irradiation. À travers diverses analyses, on observe que les complexes monométalliques montrent une conversion directe suivant le mécanisme A→C, tandis que les complexes bimétalliques ont une photodissociation en deux étapes A→B→C. Avec la synthèse d'un intermédiaire B et les photoproduits finaux C, il a été possible d'extraire le rendement quantique du monoxyde d'azote (φNO). Dans le Chapitre IV, nous nous focalisons sur le complexe RuNO-3 qui est l'un des composés les plus prometteurs en PACT mais des modifications sont nécessaires pour les tests in vitro en raison de l'instabilité dans les environnements aqueux. Le complexe trans, trans-Ru(NO)Cl(OH)-3 est obtenu et ses propriétés étudiées

Crystal structures and conformational effects in bis-fluorenyl based ligands and related ruthenium nitrosyl complexes

International audienceFour crystal structures (two ruthenium complexes and two ligands) are presented containing a bis-fluorene fragment on which alkyl chains (methyl and hexyl) are grafted. The possibility to get both cisoid and transoid conformations in the bis-fluorene units is discussed. A computational investigation using the density functional theory indicates a tendency for a gradual stabilization of the cisoid form, as the length of the chains increases. The effect of the conformation on the charge transfer electronic properties of bis-fluorene based materials is discussed computationally at one-photon absorption (OPA) level and tentatively at two-photon absorption (TPA) levels, but it is found to be modest

Bimetallic Ruthenium Nitrosyl Complexes with Enhanced Two‐Photon Absorption Properties for Nitric Oxide Delivery

International audienceOne monometallic and three bimetallic ruthenium nitrosyl (RuNO) complexes are presented and fully characterized in reference to a parent monometallic complex of formula [FTRu(bpy)(NO)]3+, where FT is a fluorenyl-substituted terpyridine ligand, and bpy the 2,2’-bipyridine. These new complexes are built with the new ligands FFT, TFT, TFFT, and TF-CC-TF (where an alkyne C≡C group is inserted between two fluorenes). The crystal structures of the bis-RuNO2 and bis-RuNO complexes built from the TFT ligand are presented. The evolution of the spectroscopic features (intensities and energies) along the series, at one-photon absorption (OPA) correlates well with the TD-DFT computations. A spectacular effect is observed at two-photon absorption (TPA) with a large enhancement of the molecular cross-section (σTPA), in the bimetallic species. In the best case, σTPA is equal to 1523±98 GM at 700 nm, in the therapeutic window of transparency of biological tissues. All compounds are capable of releasing NO⋅ under irradiation, which leads to promising applications in TPA-based drug delivery