Cette thèse s’inscrit dans le développement et l’évaluation de nouvelles plateformesmoléculaires pour une application en imagerie optique par fluorescence. Nous avons cherché àdévelopper de nouveaux outils multifonctionnels et modifiables à façon. Cette approche estnécessaire car l’introduction d’un fluorophore peut fortement influencer les propriétés ducomposé final. Cela signifie que l’introduction du fluorophore sur l’agent sélectionné doit avoirêtre réalisé dès le départ. Pour cela deux axes principaux ont été étudiés; le premier consiste àutiliser des BODIPY pour le développement d’agents thérapeutiques traçables pour uneapplication principalement in vitro; le deuxième cible sur la conception de plateformes à based’AzaBODIPY compatibles avec l’imagerie in vivo.Dans la première partie deux fluorophores à base de 3,5-dichloro-BODIPY ont été identifiéscomme plateformes prometteurs. Ils ont été fonctionnalisés sélectivement par un agent or(I)-phosphine, un thiosucre et un phosphonium afin de pouvoir étudier l’influence du positionnementde chaque substituant sur les propriétés finales. Nous avons pu démontrer qu’unefonctionnalisation sélective et spécifique est possible avec ces substituants fragiles ; cela nous apermis de développer 12 agents théranostiques à base d’or(I). Les propriétés photophysiques etbiologiques ont ensuite été évaluées; pour cela nous avons déterminé leurs propriétés antiprolifératives (3 lignés cellulaires), la balance hydrophile, l’accumulation d’or dans les cellules etla localisation des composés des composés par microscopie confocale. Cette stratégie deplateforme multifonctionnelle nous a permis de développer un panel de composés traçables ayantdes activités mixtes ainsi que des distributions cellulaires distinctes. Cette étude a permisl’identification et la sélection de trois ou quatre composés qui feront l’objet d’une étudeapprofondie.Dans la deuxième partie de cette thèse nous avons développé des plateformes multifonctionnellescompatibles avec l’imagerie in vivo; pour cela nous avons poursuivi deux approches différentes.La première était l’utilisation de 1,7-di(phenol)3,5-di(phenyl)-azaBODIPY, suivi par safonctionnalisation sur les groupements OH afin de développer un traceur bioconjugablefluorescent dans le proche infrarouge (NIR-I). Malheureusement ce traceur possède despropriétés optiques très défavorables. Nous avons alors développé une approche innovante baséesur la fonctionnalisation de l’atome de bore. En s’appuyant sur cette approche deux traceursfortement fluorescents dans le proche infrarouge et solubles dans l’eau ont été développés. Cesfluorophores ont été conjugués sur un anticorps innovateur afin de permettre l’imagerie optiquedu ligand PD-L1. Les traceurs se sont montrés stables pour au moins 48h dans le plasma murin etpossèdent de très bonnes propriétés optiques. Comme preuve de concept nous avons conduitune étude préclinique in vivo. Cette étude a montré que les traceurs sont fortement fluorescents(NIR-I) et ne possèdent pas de toxicité imminente.La méthodologie développée pendant cette thèse présente un grand potentiel pour des étudesallant plus loin et des futures applications ; il est possible d’appliquer les principes et outilsdéveloppés sur d’autre fluorophores ; la méthodologie permet une fonctionnalisation très richeavec une grande variété de substituants d’intérêt. Son utilisation n’est pas limitée aux applicationsbiologiques, biochimiques et médicinales. / The objective of this thesis was the development and evaluation of new molecular platformsfor optical fluorescence imaging applications. This work sought to develop new tools that caneasily be modified and adapted to the specific needs of the intended use. This is required asthe fluorophore will influence the final properties and should thus be incorporated beforestructural optimization of the selected agent rather than at the very end. Two main axes wereexplored; the use of BODIPYs for the development of trackable therapeutic agents that areprimarily intended for in vitro applications and the use of azaBODIPYs for the design of an invivo compatible fluorescent platform.In the first part two fluorophores on the basis of a 3,5-dichloro-BODIPY were identified aspromising platforms. These platform molecules were selectively functionalized using a gold(I)-phosphine moiety, a thiosugar and a phosphonium to explore their selective functionalizationand investigate the influence of each substitutents position on the final properties. Weshowed that a site-specific, selective functionalization with these fragile substituents ispossible and developed 12 gold(I)-bearing therapeutic agents. We evaluated thephotophysical properties of all obtained compounds which was followed by a characterizationof their biological properties (antiproliferative properties on 3 cancer cell lines, lipophilicbalance and cellular gold accumulation as well as fluorescence imaging on 3 cell lines for upto 24h). We succeeded in developing a panel of closely related trackable compounds thatdisplay mixed activity in cells and distinct cellular localization. This investigation permitted theselection of three to four hits that will be studied further.In the second part we developed an in vivo-compatible multifunctional platform following twostrategies: the first was the use of 1,7-di(phenol)-3,5-di(phenyl)-azaBODIPY and thefunctionalization of the hydroxy groups for the development of a bioconjugable NIR-I probe.Unfortunately the developed probe displayed very unfavourable optical properties; wetherefore developed a new strategy that is entirely based on the functionalization of the boronatom. Using this approach we successfully synthesized 2 watersoluble, strongly fluorescent(NIR-I) molecular platforms that were conjugated to an innovative antibody to image the PD-L1 ligand. The developed probes displayed excellent optical properties, are stable for at least48h in mice plasma and were validated in a preclinical study on mice. The developed probesdisplayed strong fluorescence in vivo and showed no acute toxicity.The developed methodology shows great potential for further investigations and futurestudies; it can be transposed onto other closely related fluorophores and permits versatilefunctionalization with a large variety of compounds of interest. Its use is thus not limited tobiological, biochemical and medical applications.

Artificial photosynthesis, for the purpose of converting solar energy into fuel, is one of the most viable and promising alternative approaches to solve the current global energy and environmental issues. Among the challenges faced in artificial photosynthesis is in building photosystems that can effectively and efficiently perform light absorption and charge separation in broad-band capturing donor-acceptor systems. While having a broad-band capturing antenna system that can harness incoming photons is crucial, another equally important task is to successfully couple the antenna system, while maintaining its optical properties, to an energy or electron acceptor which serves as the reaction center for the generation of charged species of useful potential energy. The stored potential energy will be utilized in different applications such as driving electrons in solar cells or in splitting water for the generation of fuel. Hence, the particular endeavor of this thesis is to study and synthesize molecular/supramolecular systems with wide-band capturing capabilities to generate long-lived charge separated states. The sensitizer used in building these systems in the present study is 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, for short, BF2 chelated Azaboron dipyrromenthene or AzaBODIPY. A handful of novel donor-acceptor systems based on AzaBODIPY have been successfully designed, synthesized and their photochemistry have been investigated using various techniques. In these systems, Azabodipy has been covalently attached to several donors like porphyrin, bodipy, subphthalocyanine, phenothiazine, ferrocene, bithiophene and effectively coupled to an electron acceptor, C60. These systems have been fully characterized by NMR, Mass, optical absorption and emission, X-ray crystallographic, computational, electrochemical, and photochemical studies. It has been possible to demonstrate occurrence of efficient electron and energy transfer events and long-lived charge separated states upon photoexcitation in these model compounds. By changing the arrangements of the donor and acceptor entities, it has also been possible to show directional, through-space and through-bond electron transfer processes. The present study brings out the importance of utilizing near-IR sensitizers in building solar energy harvesting model systems.

Donor-acceptor systems exhibit distinctive attributes rendering them highly promising for the emulation of natural photosynthesis and the efficient capture of solar energy. This dissertation is primarily devoted to the investigation of these unique features within diverse donor-acceptor system typologies, encompassing categories such as closely covalently linked, push-pull, supramolecular, and multi-modular donor- acceptor conjugates. The research encompasses an examination of photosynthetic analogs involving compounds such as chelated azadipyromethene (AzaBODIPY), N,N-dimethylaminophenyl (NND), phenothiazine (PTZ), triphenylamine (TPA), phenothiazine sulfone (PTZSO2), tetracyanobutadiene (TCBD), and expanded tetracyanobutadiene (exTCBD). The strategic configuration of the donor (D), acceptor (A), and spacer elements within these constructs serves to promote intramolecular charge transfer (ICT), which are crucial for efficient charge and electron transfer. The employment of cutting-edge analytical techniques, such as ultrafast transient absorption spectroscopy, is integral to the study. Furthermore, a comprehensive suite of analytical methodologies including steady-state UV-visible absorption spectroscopy, fluorescence and phosphorescence spectroscopies, electrochemical techniques (including cyclic voltammetry and differential pulse voltammetry), spectroelectrochemistry, and density functional theory calculation (DFT), collectively contribute to the comprehensive characterization of push-pull donor-acceptor systems, with a particular emphasis on their potential as highly effective solar energy harvesting application.