Supramolecular chemistry is an emerging field of chemistry which has attracted much attention in recent years as a result of its broad applicability in many areas. Thus, the design of functional supramolecular systems is strongly in demand in this field. For this purpose, we have developed ratiometric fluorescent chemosensors for ion sensing and mechanically interlocked structures for their application in molecular logic. In the first part, we report a novel dimeric boradiazaindacene dye which can be converted in one step to an efficient resonance energy transfer (RET) dyad. In addition, if this modification is done with appropriate ligands, RET can be coupled to ion sensing. The utility of this approach is demonstrated in a highly selective, emission ratiometric chemosensor for Ag(I). In the second part, boradiazaindacene dyads designed as energy transfer casettes were modified to signal cation concentrations ratiometrically. If the energy transfer efficiency is increased by changing spectral overlap on cation binding, an enhancement of emission signal ratios can be obtained. A larger range of ratios results in highly improved sensitivity to analyte concentrations. We demonstrate this approach in a de novo design of a novel and highly selective ratiometric chemosensor for Hg(II) ions. In the last part, we synthesized a two-station [2]catenane composed of an &amp / #960 / -electron rich bis-1,5-dihydroxynapthalene[38]-crown-10 (1/5DNPC10) ring interlocked with a second macrocycle containing two &amp / #960 / -electron deficient unit, namely, napthodiimide (NpI) and bipyridinium (BIPY)2+ unit using the Cu(I)-catalyzed Huisgen 1,3-cycloaddition reaction. The resulting bistable [2]catenane is isolated as a single co-conformation which is comprised of the 1/5DNP[38]C10 ring around the NpI unit. Thermal activation of the pure NpI-isomer at 70&amp / #730 / C for 60 h leads to the formation of the BIPY2+-isomer by virtue of the circumrotation of the crown-ether ring along the backbone of the other macrocycle over the steric barrier of the tetra-aryl methane units. The energy barrier for the circumrotation is 28.5&plusmn / 0.3 kcal/mol. Electrochemistry of a 1:1 mixture of the two possible isomers shows that the [2]catenane cannot be switched mechanically on account of the large steric barriers presented by the tetra-aryl methane groups on the electron-accepting ring.

ABSTRACT TOWARDS PRACTICAL APPLICATIONS FOR MOLECULAR LOGIC GATES: &ldquo / AND&rdquo / LOGIC AS AN ADDITIONAL LAYER OF SELECTIVITY IN SINGLET OXYGEN RELEASE FOR PHOTODYNAMIC THERAPY &Ouml / zlem, Suriye M.S., Department of Chemistry Supervisor: Prof. Dr. Engin Umut Akkaya June 2008, 54 pages There have been many examples of individual molecular logic gates and molecular equivalents of more complex digital designs in recent years such as half adder, half subtractor, multiplexer. Neverethless, the unresolved issues of addressability and lack of communication between logic gates remain to be the Achille&rsquo / s heel for molecular logic gates. A few years ago we have demonstrated that appropriately decorated bodipy dyes can be very efficient generators for singlet oxygen, thus act as a satisfactory photodynamic agents. As a bonus, these dyes absorb very strongly at 660 nm which is considered to be within the therapeutic window of mammalian tissue. So, combining our earlier experience in molecular logic gates and rational design of photodynamic agents, we proposed a photodynamic therapy agent that would release singlet oxygen at a much larger rate when the cancer related cellular parameters are above a threshold value at the same location. Following the survey of the relevant literature for cancer related parameters, we decided that sodium ion concentration and pH (H+ concentration) could be very promising targets. In the tumor regions the pH can drop below 6 and the Na+ concentration is also significantly higher then normal tissues. As a result, in the proposed logic system the chemical inputs could be Na+ and H+. The system in fact is an automaton which is to seek higher concentration of both hydrogen and sodium ions, and release the toxic agent (singlet oxygen) only when both concentrations are high. Thus, the proposed logic gate is an AND logic gate, the output of which is singlet oxygen. Keywords: Photodynamic therapy, singlet oxygen, molecular logic gates, AND logic operation

Nesse trabalho, foram obtidos bis-azofenóis (HO-(Azo-R)2) pela reação de sais de diazônio estáveis e fenol. As condições dessas reações foram analisadas, sendo que, pela primeira vez, a influência da temperatura foi investigada. Temperaturas mais altas aumentam o rendimento dos bis-azofenóis, o que reforça o modelo Droplet, e indicam um aumento na velocidade de reação da segunda reação de acoplamento. As propriedades espectroscópicas e fotoquímicas de HO-(Azo-Me)2 são essencialmente governadas pelo estabelecimento de uma ligação de hidrogênio intramolecular assistida por ressonância. Os rendimentos quânticos de fotoisomerização E-Z são baixos em decorrência, provavelmente, da formação de tautômeros no estado excitado, que desativam a isomerização. Foi obtida uma díade (Azo1-X-Azo2) contendo um azobenzeno da classe espectroscópica \"azobenzeno\" (Azo 1) e outro da classe \"aminoazobenzeno\'\' (Azo 2) conectados através de um espaçador (X). Não existe interação apreciável entre Azo 1 e Azo 2, sendo a separação entre os máximos de absorção dessas subunidades de mais de 60 nm. Observou-se que não foi possível fotoisomerizar (E-Z) seletivamente Azo 1, seja na região de seu isosbéstico, seja na região de seu máximo de absorção, sendo sempre observada a isomerização concomitante de Azo 2. O rendimento quântico de Azo 1 (0,22) é idêntico ao obtido para o modelo M-Azo 1, indicando que sua incorporação na díade não altera essa propriedade fotoquímica. A unidade Azo 2 pode ser fotoisomerizada (E-Z) seletivamente na região de seu máximo de absorção, não sendo observada isomerização significativa de Azo 1. É obtido um rendimento quântico (0,34) também idêntico ao do modelo M-Azo 2. Entretanto, na díade existe uma dependência do rendimento quântico de Azo 2 em função da região de excitação, sendo observado um rendimento quântico (0,54) quando excitado na região de 370 nm, que difere consideravelmente do rendimento quântico de M-Azo 2, que é independente do comprimento de onda (0,33). Um comportamento interessante foi observado ao se irradiar a díade na região de 370 nm, que corresponde ao ponto isosbéstico de Azo 2 e uma região de alta absorção da banda pi-pi* de Azo 1. Apesar da menor fração de luz absorvida por Azo 2 (44%), não se observa isomerização de Azo 1 até ser obtido o estado fotoestacionário (PSS) de Azo 2, indicando que existe um período de indução para que seja obtida a isomerização de Azo 1. Esse comportamento corresponde a um sistema do tipo neural, em que existe um estímulo durante um período de indução até que seja atingido um limiar para que ocorra uma determinada função. Considerando também os processos de isomerização Z-E, é possível realizar várias combinações a partir de estímulos luminosos diferentes e estados iniciais diferentes, que podem ser correlacionados com a lógica binária (byte [x,y]; x e y = 0 ou 1). Devido à combinação conveniente de grupos azo, essa díade é a primeira em que é possível uma caracterização fotoquímica dos processos fotoquímicos E-Z e Z-E e que se obtém uma seletividade, ao menos parcial, no controle desses processos. / In the studies herein proposed, bis-azophenols (HO-(Azo-R)2) were synthesized by the coupling reaction of stable diazonium salts and phenol. The reaction conditions were assessed and, for the first time, the influence of temperature was investigated in this type of reaction. Higher temperatures lead to increased yields of bis-azophenol, reinforcing the Droplet Model, and indicate an increase in the reaction rate for the second coupling step. Spectroscopic and photochemical properties of HO-(Azo-Me)2 are essentially directed by the establishment of a Resonance-Assisted Hydrogen Bond. The E-Z photoisomerization quantum yield is low, probably due to the formation of tautomers in the excited state that deactivate the isomerization process. A dyad (Azo1-X-Azo2) containing an azobenzene of the \"azobenzene\" spectroscopic group (Azo 1) and another azobenzene of the \"aminoazobenzene\" spectroscopic group (Azo 2), connected through a spacer (X), has been obtained. There is no appreciable interaction between Azo 1 and Azo 2 and the separation of the corresponding absorption maxima of these subunits is 60 nm. It was observed that selectively photoisomerization (E-Z) of Azo 1, either in the region of its isosbestic or in the region of its absorption maximum, was not feasible, being always observed the concomitant isomerization of Azo 2. The quantum yield of Azo 1 (0.22) is identical to that obtained for M-Azo 2, indicating that its incorporation into the dyad does not modify this photochemical property. The Azo 2 unit can be selectively photoisomerized (E-Z) in the region of its absorption maximum, without Azo 1 isomerization. A quantum yield of 0.34 was obtained, also the same to M-Azo 2 model. However, the dyad presents a dependence on the quantum yield of Azo 2 as a function of the excitation region , and a quantum yield of (0.54) was observed when excited in the region of 370 nm, which differs considerably from the quantum yield of M-Azo 2 since it is independent of the wavelength of excitation. An interesting behavior was observed by irradiating the dyad in the region of 370 nm, which corresponds to the isosbestic point of Azo 2 and a region of high absorption of the pi-pi* band of Azo 1. Despite the smaller fraction of light absorbed by Azo 2 (44%), isomerization of Azo 1 isn\'t observed until the photostationary state of Azo 2 is achieved, indicating that there is an induction period to obtain Azo 1 isomerization. This behavior corresponds to a neural type system, in which there is a stimulus during an induction period until a threshold is reached for a given function to occur. Considering also the Z-E isomerization processes, it is possible to perform several combinations from different light stimuli and different initial states that can be correlated with binary logic (byte [x, y] x and y = 0 or 1). Due to the convenient combination of azo groups, this dyad is the first in which a photochemical characterization of the photochemical processes E-Z and Z-E is obtained, and a partial selectivity is achieved in the control of these processes.

L'imagerie de fluorescence s'est particulièrement développée au fil de ces dernières décennies notamment pour l'exploration des systèmes biologiques. De nombreux développements portant à la fois sur les instruments d'analyse et les agents de contraste (sondes) ont été entrepris pour améliorer cette technique de bioanalyse. Mes travaux de thèse avaient pour but d'explorer diverses plateformes moléculaires pro-fluorescentes pouvant générer, sous l'effet d'un stimulus biologique / chimique, un fluorophore organique. Cette approche de synthèse chimique in-situ met en jeu des réactions domino caractérisées par la formation et la rupture de liaisons covalentes. Ce processus devrait ouvrir la voie à des sondes fluorogéniques possédant des rapports signal sur bruit élevés. Cette étude avait aussi pour but d'étudier la synthèse in-situ de fluorophores déclenchée par plusieurs stimuli afin de concevoir des portes logiques moléculaires de type "AND", dans un but de détection "multi-analytes". Pour établir la preuve de principe, la formation d'un coeur 7-hydroxy-2-iminocoumarine fluorescent déclenchée par divers couples d'enzymes (hydrolase / nitroréductase) a été étudiée. L'ensemble de ces travaux sont décrits dans le chapitre I de ce manuscrit. Par la suite et comme présenté dans les chapitres II et III, notre intérêt s'est porté sur le développement des plateformes fluorogéniques libérant des fluorophores ayant des maxima d'absorption / émission décalés vers le rouge en comparaison de ceux des coumarines. Une première réalisation a concerné la conception d'un précurseur "cagé" agissant comme sonde à peptidases ou nitroréductase par libération d'un dérivé pyronine. Des travaux portant sur la formation in-situ d'une benzophénoxazine sont également en cours et sont présentés au chapitre III. Un dernier aspect de ce travail a concerné la chimie d'une nouvelle famille de fluorophores proche-IR (les hybrides dihydroxanthène-hémicyanine) dont la formation in-situ pourra être envisagée pour des applications in-vivo. / Fluorescence imaging is a growing field of biology over the past decades. Intensive works mainly focused on instrumental developments and chemistry of contrast agents (probes), were already done to improve such bioanalytical technique. The main goal of this Ph. D. thesis was to explore various fluorogenic molecular platforms responsive to various (bio)chemical stimuli and capable of releasing organic fluorophores in the biological medium to analyze. This approach named "in-situsynthesis" is based on domino reactions belonging to the repertoire of "covalent chemistry", triggered by the target (bio)analyte. This kind of process should provide advanced fluorogenic probes with high signal-to-noise ratio. Another purpose of this work was to investigate some dualtriggering events to access to fluorogenic molecules acting as "AND-type" molecular logic gates for dual-analytes detection applications. To establish this approach, the formation of highly fluorescent7-hydroxy-2-iminocoumarin scaffolds triggered by several enzyme pairs (hydrolase and nitroreductase) was studied and now described in the first chapter of this manuscript. The second part of this work, described in chapters II and III, was devoted to the development of original "caged" precursors able to release fluorophores whose absorption / emission maxima are dramatically redshifted compared to those of coumarin derivatives. The first achievement concerned the detection of protease or nitroreductase activities through in-situ formation of a pyronin scaffold. Further works, currently in progress, are focused on "caged" precursors whose the dual reaction with a model protease should lead to the release of a benzophenoxazine derivative. Finally, some chemistry aspects related to an emerging and promising class of NIR fluorophores (dihydroxanthene-hemicyanine hybrids) are presented and the opportunity to form them in biological media, upon enzymatic triggering is also discussed.