The nitrate radical (NO3·) was first identified as early as the 1881, but its role in atmospheric oxidation has only been identified within recent decades. Due to its high one-electron reduction potential and its reactivity toward a diverse set of substrates, it dominates nighttime atmospheric oxidation and has since been the subject of much work. Despite this, studies on NO3· hydrogen atom transfer reactions have been somewhat neglected in favor of its more reactive oxidative pathways. The first section of the dissertation will highlight the role of substrate structure, solvent effects, and the presence of a polar transition state on NO3· hydrogen abstractions from alcohols, alkanes, and ethers. In this work the acquisition of absolute rate constants from previously unexamined substrates was analyzed alongside a curated list of common organic pollutants degraded through hydrogen atom abstraction. It was found that NO3· reacts with low selectivity through an early polarized transition state with a modest degree of charge transfer. Compared to the gas-phase, condensed-phase reactions experience rate enhancement—consistent with Kirkwood theory—as a result of the polarized transition state. These insights are then applied to abstractions by NO3· from carboxylic acids in the next section. It was found that the rate constants for abstraction of α-carbons were diminished through induction by the adjacent carbonyl compared to the activation seen for the aforementioned substrates. The deactivation of abstraction by the carbonyl was found to be dramatically reduced as the substrate's alkyl chain was lengthened and/or branched. This apparent change in mechanism coincides with hydrogen abstraction of the alkyl chain for sufficiently large carboxylic acids and rules out the possibility of concerted bond breaking elsewhere in the molecule. Finally, the dissertation will cover some additional projects related to the overall nature of the work including examination of the kinetics of radical clock systems when complexed with metal ions and the examination of a highly oxidative biosourced monomer. / Doctor of Philosophy / The nitrate radical (NO3·) was first identified as early as the 1881, but its role in the breakdown of atmospheric pollutants has only been identified within recent decades. Operating primarily at night, NO3· serves as a major atmospheric oxidant—it breaks down pollutants by reactions that involve the removal of electrons from those substrates. This chemistry is particularly important in understanding the consequences of an increasingly industrialized world and the subsequent short-term health and environmental implications. Geographically, these reactions will occur in large concentrations near locations that contribute greatly to atmospheric pollution, such as above coal-powered plants, heavily industrialized areas, above the canopy of large forests, and immediately behind the engines of airplanes as they move through the sky. The proximity of these locations to large population centers has caused the pollutants to greatly impact human health. These contaminants have been linked to several of the leading global causes of death, such as ischemic heart disease, stroke, and respiratory illnesses. The first section of the dissertation will focus on the role of pollutant structure, the medium in which the reaction occurs, and the development of a charged complex when NO3· reacts with alcohols, alkanes, and ethers. These substrates are often found as the result of incomplete combustion when burning fuel or as products of even more sustainable biodiesels. In this work the exact rate constants were found for substrates that were previously unexamined and compared with similar known reaction rates. It was found that NO3· has a low preference for what it reacts with and passes through a modestly charged complex early in the reaction. Compared to gaseous reactions, reactions in a liquid environment proceed faster due to the formation of a charged complex. This was then applied to reactions with carboxylic acids in the next section. Carboxylic acids are often found in large concentrations above the canopy of large forests resulting from the oxidation of isoprenes that are naturally released from broad-leaf trees. It was found that these reactions were slower than reactions with alkanes as the development of the charged complex was inhibited due to the presence of an adjacent dipole. When the carboxylic acid was longer and/or more branched, the formation of the charged complex was no longer inhibited as the reaction site moved further from the dipole. A change in reaction pathway was observed when the acids were sufficiently large. This ruled out the possibility of the reaction occurring simultaneously with a fracturing and rearrangement elsewhere. Finally, the dissertation will cover some additional projects that share some overlap with the work already described including the study of the rates of radical clock systems in the presence of metal ions and the study of naturally sourced monomers that are prone to losing electrons.

[EN] Bile acids are a family of amphiphilic steroids that play a pivotal role in physiological functions such as elimination of cholesterol or solubilization of lipids. Chemically, they share a steroidal skeleton with an unusual cis fusion between rings A and B, a short lateral chain ending in a carboxylic acid moiety and different number of hydroxyl groups on the alpha-face. Hence, bile acids offer a versatile architecture that can be used to investigate photophysical processes of interest such as hydrogen atom transfer, through-bond energy trasfer, through-bond exciplex formation and DNA photodamage-related reactions. First, unmodified bile acids have been used to evaluate hydrogen atom trasfer to benzophenone-like triplet carbonyls. Dehydrogenation of bile acids at positions C-3 and/or C-7 by a radical-mediated mechanism from the excited state of benzophenone has been demonstrated. Moreover, synthesized lithocholic acid derivatives including benzophenone or carbazole as donors and a naphthalene, biphenyl or thymine as acceptors have been employed to investigate through-bond energy transfer and exciplex formation processes. Thus, energy transfer from benzophenone to naphthalene or biphenyl and extended through-bond exciplex formation in benzophenone/naphthalene and benzophenone/biphenyl linked systems has been demostrated by laser flash photolysis. Finally, bile acid derivatives incorporating one benzophenone and two thymine units with different degrees of freedom have been prepared to investigate the photochemical formation of oxetanes or thymine dimers. Photosensitized formation of cyclobutane pyrimidine dimers through the generation of a delocalized triplet excited state has been demonstrated in intermolecular systems, while oxetane formation is observed when the degrees of freedom are reduced. / [ES] Los ácidos biliares son una familia de esteroides anfifílicos que juegan un papel clave en diferentes funciones fisiológicas tales como la eliminación del colesterol o la solubilización de lípidos. Su estructura química está constituida por un esqueleto esteroideo con una fusión cis poco común entre los anillos A y B, una cadena lateral corta que termina con una función ácida y un número variable de grupos hidroxilo en la cara alfa. Por tanto, los ácidos biliares ofrecen una estructura versátil que puede ser utilizada para investigar procesos fotofísicos de interés como abstracción de hidrógeno, transferencia de energía y formación de exciplejos a larga distancia o reacciones relacionadas con el daño fotoinducido al ADN. En esta Tesis, en primer lugar, los ácidos biliares naturales se han utilizado para evaluar la abstracción de hidrógeno a carbonilos triplete en compuestos derivados de la benzofenona, demostrándose la deshidrogenación de los ácidos biliares en las posiciones C-3 y/o C-7 por un mecanismo radicalario desde el mencionado triplete de la benzofenona. En segundo lugar, se han preparado derivados de ácido litocólico que incluyen los dadores benzofenona o carbazol y los aceptores naftaleno, bifenilo o timina, que a continuación se han utilizado para investigar los procesos de transferencia de energía y formación de exciplejo intramolecular a larga distancia. De hecho, en los sistemas benzofenona/naftaleno y benzofenona/bifenilo, se demostró por fotólisis de destello láser la transferencia de energía desde benzofenona a naftaleno o bifenilo y la formación de exciplejo a larga distancia. Por último, se han preparado derivados de ácidos bliares que incorporan una unidad de benzofenona y dos de timina en diferentes posiciones del esqueleto para investigar la influencia de los diferentes grados de libertad en la formación fotosensibilizada de oxetanos o dímeros de timina. Gracias a ellos, se ha demostrado la formación fotosensibilizada de dímeros ciclobutánicos pirimidínicos a través de la generación de estados excitados triplete deslocalizados en sistemas en los que la benzofenona es intermolecular, mientras que se observa formación de oxetanos cuando los grados de libertad se ven reducidos. / [CA] Els àcids biliars són una família d'esteroides anfifílics que juguen un paper clau en funcions fisiològiques com l'eliminació del colesterol o la solubilització de lípids. La seua estructura química està constituïda per un esquelet esteroïdal amb una fusió cis entre els anells A i B poc comuna, una cadena lateral curta que acaba amb una funció àcida i un nombre diferent de grups hidroxil en la cara alfa. D'aquesta manera, els àcids biliars ofereixen una estructura versàtil que pot ser utilitzada per investigar processos fotofísics d'interès com abstracció d'hidrogen, transferència d'energia i formació de exciplexes a llarga distància o reaccions relacionades amb el dany a l'ADN induït per llum. En primer lloc, els àcids biliars naturals s'han utilitzat per avaluar la abstracció d'hidrogen a carbonils triplets derivats de la benzofenona, demostrant-se la deshidrogenació dels àcids biliars en les posicions C-3 i/o C-7 per un mecanisme radicalari des de l'estat excitat de la benzofenona. A més, derivats d'àcid litocòlic que inclouen els donadors benzofenona o carbazol i els acceptors naftalé, bifenil o timina s'han utilitzat per investigar els processos de transferència d'energia i formació de exciplexe a llarga distància. En els sistemes benzofenona /naftalé i benzofenona/bifenil la fotòlisis làser va demostrar la transferència d'energia des de benzofenona a naftalé o bifenil i la formació d'exciplexe a llarga distància. Finalment, per tal d'investigar la formació fotosensibilitzada d'oxetans o dímers de timina, s'han preparat derivats d'àcids bliars que incorporen una unitat de benzofenona i dues de timina amb diferents graus de llibertat. La formació fotosensibilitzada de dímers ciclobutànics pirimidínics mitjançant la generació d'estats excitats triplet deslocalitzats ha estat demostrada en sistemes intermoleculars, mentre que la formació d'oxetans s'observa quan els graus de llibertat es veuen reduïts. / Miró Richart, P. (2016). Hydrogen-Abstraction, Energy Transfer and Exciplex Formation in Photoactive Systems Based on Bile Acids [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/64084

It has been observed that in certain cases the exposure of dyed fibres to aging techniques results in the strengthening of fibres. This thesis explores the hypothesis that the strengthening is due to radical cross-coupling reactions that could be initiated through metal ion mediated photodecarboxylation. The approaches taken in this research include kinetic experiments (using flash photolysis), examination of possible cross-coupling experiments (using species of opposite charge), and the design and examination of small molecule model systems. A flash photolysis system was developed and used in attempts to determine the rates of photochemical product formation for cobalt(III) amino acid complexes. Lower limits have been established for the rate of product formation in these systems. The lower limits are: 2 x 10⁷ s⁻¹ for [Co(bpy)2(gly)]²⁺; 2 x 10⁷ s⁻¹ for [Co(tpa)(gly)]²⁺; and 5 x 10⁶ s⁻¹ for [Co(tpa)(aib)]²⁺, where bpy is 2,2'-bipyridine; gly is glycinate; tpa is tris(2-pyridylmethyl)amine; and aib is aminoisobutyrate. In past studies, the rates of a series of cobalt(III) amino acid complexes were reported as being the same, and much slower. It is thought that in these cases it may not be the rate of the formation of product that was being measured, but rather the response time of the electronics that was being observed. In this thesis the results obtained for the rate for the aib complex were somewhat lower than those of the gly complexes. This may imply, for the aib complex at least, the rate of the formation of the metallocycle is being observed (and not the response times of the electronics or other limitations of the instrumentation), but the data is poor and there is considerable doubt about this. The steady state photolysis of opposite charged species [Co(bpy)2(gly)]²⁺ and [Co(EDTA)]⁻ is reported. The reactions were carried out on a small scale in deuterated solvent for NMR spectrometry analysis and also on a large scale for the possible isolation and characterisation of the products. Evidence was found for a different reaction occurring when both complexes were present. The exact nature of the product remains elusive. A model system was designed in which a dinuclear ligand would bind to two metal centres and a fibre mimic would be later added. Eight ligands are discussed that could potentially bind two octahedral metal centres. They all had a xylene spacing group linking the two polydentate sites together. Five of the ligands have two bidentate binding sites. The other three had two tridentate sites. The binding sites in three of the bis(bidentate) ligands were based on ethane-1,2- diamine (en). Two of these ligands produced hypodentate monocobalt and sundentate dicobalt complexes. The other two bidentate ligands were based on 2- aminomethylpyridine (ampy). Both of these ligands degraded in the complexation reaction conditions. The binding sites in the tridentate ligands were all based on tacn. Once again, the principal products isolated were hypodentate systems in which only one metal ion was coordinated by the ligands. There is a distinct pattern observed in the xylene spaced ligands to form hypodentate complexes with cobalt(III) metal centred complexes. There is evidence of the di-nuclear species from a reaction with a charcoal catalyst in the bis(bidentate) system. ¹H NMR spectrometry, ¹³C NMR spectrometry, elemental analysis, X-ray crystallography and UV-vis spectroscopy were used to study and characterise the complexes and ligands that were prepared in this project.

It has been observed that in certain cases the exposure of dyed fibres to aging techniques results in the strengthening of fibres. This thesis explores the hypothesis that the strengthening is due to radical cross-coupling reactions that could be initiated through metal ion mediated photodecarboxylation. The approaches taken in this research include kinetic experiments (using flash photolysis), examination of possible cross-coupling experiments (using species of opposite charge), and the design and examination of small molecule model systems. A flash photolysis system was developed and used in attempts to determine the rates of photochemical product formation for cobalt(III) amino acid complexes. Lower limits have been established for the rate of product formation in these systems. The lower limits are: 2 x 10⁷ s⁻¹ for [Co(bpy)2(gly)]²⁺; 2 x 10⁷ s⁻¹ for [Co(tpa)(gly)]²⁺; and 5 x 10⁶ s⁻¹ for [Co(tpa)(aib)]²⁺, where bpy is 2,2'-bipyridine; gly is glycinate; tpa is tris(2-pyridylmethyl)amine; and aib is aminoisobutyrate. In past studies, the rates of a series of cobalt(III) amino acid complexes were reported as being the same, and much slower. It is thought that in these cases it may not be the rate of the formation of product that was being measured, but rather the response time of the electronics that was being observed. In this thesis the results obtained for the rate for the aib complex were somewhat lower than those of the gly complexes. This may imply, for the aib complex at least, the rate of the formation of the metallocycle is being observed (and not the response times of the electronics or other limitations of the instrumentation), but the data is poor and there is considerable doubt about this. The steady state photolysis of opposite charged species [Co(bpy)2(gly)]²⁺ and [Co(EDTA)]⁻ is reported. The reactions were carried out on a small scale in deuterated solvent for NMR spectrometry analysis and also on a large scale for the possible isolation and characterisation of the products. Evidence was found for a different reaction occurring when both complexes were present. The exact nature of the product remains elusive. A model system was designed in which a dinuclear ligand would bind to two metal centres and a fibre mimic would be later added. Eight ligands are discussed that could potentially bind two octahedral metal centres. They all had a xylene spacing group linking the two polydentate sites together. Five of the ligands have two bidentate binding sites. The other three had two tridentate sites. The binding sites in three of the bis(bidentate) ligands were based on ethane-1,2- diamine (en). Two of these ligands produced hypodentate monocobalt and sundentate dicobalt complexes. The other two bidentate ligands were based on 2- aminomethylpyridine (ampy). Both of these ligands degraded in the complexation reaction conditions. The binding sites in the tridentate ligands were all based on tacn. Once again, the principal products isolated were hypodentate systems in which only one metal ion was coordinated by the ligands. There is a distinct pattern observed in the xylene spaced ligands to form hypodentate complexes with cobalt(III) metal centred complexes. There is evidence of the di-nuclear species from a reaction with a charcoal catalyst in the bis(bidentate) system. ¹H NMR spectrometry, ¹³C NMR spectrometry, elemental analysis, X-ray crystallography and UV-vis spectroscopy were used to study and characterise the complexes and ligands that were prepared in this project.

No description available.

[ES] La luz solar puede producir daños en el ADN por absorción directa de luz UVB, o por fotosensibilización tras la absorción de luz UVA por parte de fármacos, que pueden actuar como fotosensibilizadores (PS). La benzofenona (BP), presente en la estructura química de una amplia variedad de fármacos, tiene el potencial de fotosensibilizar daño al ADN, especialmente hacia la base de timina (Thy). Este daño puede dar lugar a dímeros de pirimidina de tipo ciclobutano (CPD) y a fotoproductos (6-4) pirimidina-pirimidona ((6-4)PPs), los cuales pueden causar mutaciones graves, melanomas o incluso la muerte celular. En algunos organismos, los (6-4)PPs pueden repararse de manera eficiente por las fotoliasas, en lo que se podría entender como una reacción Paternò-Büchi (PB) inversa a través de un intermedio de oxetano altamente inestable. Con el fin de profundizar en la fotorreactividad de los derivados BP-Thy y en la ruptura fotoinducida de oxetanos, se sintetizaron por primera vez una variedad de diadas en las que Thy y BP están covalentemente unidas por un espaciador lineal de diferente longitud y naturaleza. La fotorreactividad de los diferentes derivados se investigó por fotólisis de destello láser (LFP) y espectroscopía de absorción transitoria a escala de femtosegundo; además, se aislaron y caracterizaron los principales fotoproductos (PPs) derivados de la irradiación en estado estacionario. Los resultados mostraron un alto grado de quimioselectividad en la longitud y conformación del espaciador. En cuanto a la reactividad fotoquímica, se formaron PPs derivados de la PB y de la abstracción formal de hidrógeno; así, las diadas con el espaciador más largo dieron lugar a la formación de oxetanos y de PPs de abstracción de hidrógeno. Por el contrario, las diadas con espaciadores más cortos formaron un fotoproducto de abstracción formal de hidrógeno y/o polimerización. Por tanto, la fotorreactividad se vio influida por la longitud del espaciador, correlacionándose bien con los tiempos de 3BP*, observándose los tiempos más cortos para las diadas de espaciadores largos. En relación con la fotoapertura de oxetanos, la irradiación de los diferentes regio- y estereoisoméros condujo a la formación de la típica banda de absorción triplete-triplete de BP; por tanto, dicho proceso opera de forma adiabática. La fotólisis del oxetano que resulta de la irradiación de la diada con el espaciador más largo mostró una banda de absorción transitoria sobre 400 nm, atribuida a la formación del exciplejo triplete entre BP y Thy covalentemente unidos. Por otro lado, se investigó la reacción PB y la cicloreversión de oxetanos que surgen de la interacción entre Thy o derivados de uracilo (Ura) y BP. Así, se sintetizó una amplia gama de oxetanos Thy-BP y Ura-BP con diferentes sustituyentes en las posiciones 1 y 5 de la nucleobase, incluyéndose los regioisómeros cabeza-cabeza (HH) y cabeza-cola (HT). Los estudios espectroscópicos (absorción transitoria ultrarrápida y LFP), junto con el análisis teórico, coinciden en que la cicloreversión fotoinducida para los isómeros HH y HT implica la formación de un exciplejo en el estado excitado triplete antes de la ruptura. Generalmente, se observó que la reacción fue completamente adiabática para los regioisómeros HH. En el caso del oxetano HH que surge de la interacción entre 1,3-dimetiltimina (DMT) y BP, se observó la formación de una banda ~400 nm, que se atribuyó al exciplejo triplete 3[DMT···BP]*. Su formación fue altamente regioselectiva, siendo más rápida y eficiente para el isómero HH que para HT. Estos resultados fueron confirmados por análisis computacional. En general, se observó adiabaticidad en el proceso de fotorreversión para todos los oxetanos investigados, con un alto grado de regioselectividad y con la participación de exciplejos triplete. / [CA] La llum solar pot produir danys a l'ADN per absorció directa de llum UVB, o per fotosensibilització després de l'absorció de llum UVA per part de fàrmacs, que poden actuar com fotosensibilitzadors (PS). La benzofenona (BP), present en l'estructura química d'una àmplia varietat de fàrmacs, té el potencial de fotosensibilitzar dany a l'ADN, especialment a la base de timina (Thy). Aquest dany pot donar lloc a dímers de pirimidina de tipus ciclobutà (CPD) i a fotoproductes (6-4) pirimidina-pirimidona ((6-4)PPs), els quals poden causar mutacions greus, melanomes o fins i tot la mort cel·lular. En alguns organismes, els (6-4)PPs poden reparar-se de manera eficient per les fotoliases, en el que es podria entendre com una reacció Paternò-Büchi (PB) inversa a través d'un intermedi d'oxetà altament inestable. Amb la finalitat d'aprofundir en la fotoreactivitat dels derivats BP-Thy i en la ruptura fotoinduïda d'oxetans, es van sintetitzar per primera vegada una varietat de diades en les quals Thy i BP estan covalentment unides per un espaiador lineal de diferent longitud i naturalesa. La fotoreactivitat dels diferents derivats es va investigar per fotòlisi de centelleig làser (LFP) i espectroscopía d'absorció transitòria a escala de femtosegons; a més, es van aïllar i caracteritzar els principals fotoproductes (PPs) derivats de la irradiació en estat estacionari. Els resultats van mostrar un alt grau de quimioselectivitat en la longitud i conformació de l'espaiador. Quant a la reactivitat fotoquímica, es van formar PPs derivats de la PB i de l'abstracció formal d'hidrogen; així, les diades amb l'espaiador més llarg van donar lloc a la formació d'oxetans i de PPs d'abstracció d'hidrogen. Per contra, les diades amb espaiadors més curts van formar un fotoproducte d'abstracció formal d'hidrogen i/o polimerització. Per tant, la fotoreactivitat es va veure influïda per la longitud de l'espaiador, correlacionant-se bé amb els temps de 3BP*, observant-se els temps més curts per a les diades amb espaiadors llargs. En relació amb la fotoapertura d'oxetans, la irradiació dels diferents regi- i estereoisòmers va conduir a la formació de la típica banda d'absorció triplet-triplet de BP; per tant, aquest procés opera de manera adiabàtica. La fotòlisi de l'oxetà que resulta de la irradiació de la diada amb l'espaiador més llarg va mostrar una banda d'absorció transitòria sobre 400 nm, atribuïda a la formació de l'exciplex triplet entre BP i Thy covalentment units. D'altra banda, es va investigar la reacció PB i la cicloreversió d'oxetans que sorgeixen de la interacció entre Thy o derivats d'uracil (Ura) i BP. Així, es va sintetitzar una àmplia gamma d'oxetans Thy-BP i Ura-BP amb diferents substituents en les posicions 1 i 5 de la nucleobase, incloent-se els regioisòmers cap-cap (HH) i cap-cua (HT). Els estudis espectroscòpics (absorció transitòria ultraràpida i LFP), juntament amb l'anàlisi teòric, coincideixen en que la cicloreversió fotoinduïda per als isòmers HH i HT implica la formació d'un exciplex en l'estat excitat triplet abans de la ruptura. Generalment, es va observar que la reacció va ser completament adiabàtica per als regioisòmers HH. En el cas de l'oxetà HH que sorgeix de la interacció entre 1,3-dimetiltimina (DMT) i BP, es va observar la formació d'una banda ~400 nm, que es va atribuir a l'exciplex triplet 3[DMT···BP]*. La seua formació va ser altament regioselectiva, sent més ràpida i eficient per a l'isòmer HH que per a HT. Aquests resultats van ser confirmats per anàlisi computacional. En general, es va observar adiabaticitat en el procés de fotoreversió per a tots els oxetans investigats, amb un alt grau de regioselectivitat i amb la participació d'exciplexes triplet. / [EN] Sunlight light can produce damage to DNA through direct absorption of UVB or, more commonly, by photosensitization upon absorption of UVA light by drugs, that act as a photosensitizer (PS). Benzophenone (BP) as a building-block is present in a wide variety of drugs, and have the potential to photosensitize damage to DNA, specially towards the thymine (Thy) nucleobase. The resulting DNA damage can give rise to bulky dimers, i.e. cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts ((6-4)PPs), which can cause severe mutations, melanomas, or even be fatal for the cell. In some organisms, (6-4)PP can be efficiently repaired by photolyase enzymes, in what could be a reverse Paternò-Büchi (PB) reaction through an unstable oxetane intermediate. With the aim of getting deeper insight into the photoreactivity of BP-Thy derivatives and in the photoinduced cleavage of oxetanes, a variety of dyads where Thy and BP are covalently linked by a linear spacer of different lengths and nature were first synthesized. The photochemical reactivity and the photophysical properties of the different derivatives were investigated by means of laser flash photolysis (LFP) and femtosecond transient absorption spectroscopy; besides, the main photoproducts (PPs) arising from steady-state irradiation were also isolated and characterized. The results showed a high degree of chemoselectivity on the linking bridge length and conformation. Concerning the photochemical reactivity, PPs arising from the PB and from formal hydrogen abstraction were formed. In this context, the PB reaction took place for the dyads with the longest spacer with complete regio- and stereoselectivity, along with a hydrogen abstraction process. Finally, the dyads with shorter spacers gave rise to a formal hydrogen abstraction photoproduct and/or polymerization. Accordingly, the overall photoreactivity was proportional to the spacer length and was well correlated with the 3BP* lifetimes, the longer spacers giving rise to shorter lifetimes. In connection to the oxetane photocleavage, irradiation of the different regio- and stereoisomeric oxetanes led to the formation of the typical triplet-triplet absorption band of BP. Accordingly, the photoinduced cycloreversion also operates as an adiabatic process. Photolysis of the oxetane that results from irradiation of the dyad with the longest spacer showed a transient absorption at ~400 nm, which is ascribed to formation of the purported triplet exciplex between BP and Thy covalently linked. Additionally, the PB reaction and the cycloreversion of oxetanes arising from the interaction between Thy or uracil (Ura) derivatives and BP were also investigated. Thus, a wide range of Thy-BP and Ura-BP oxetanes with varying substituents at positions 1 and 5 of the nucleobase were synthesized, including both the head-to-head (HH) and head-to-tail (HT) regioisomers. Spectroscopic studies, including femtosecond transient absorption and LFP results, as well as theoretical multiconfigurational quantum chemistry analysis, agree that the photoinduced cycloreversion for the HH and HT isomers involved the formation of a triplet excited exciplex before the cleavage takes place. Generally, the photochemical reaction was fully adiabatic for the HH regioisomers. In the case of the HH-oxetane arising from the interaction between 1,3-dimethylthymine (DMT) and BP, an absorption band at ca. 400 nm was formed, and was attributed to the triplet exciplex 3[DMT···BP]*. Its formation was highly regioselective towards the HH regioisomer, being faster and more efficient than for the HT isomer. These results were confirmed by computational analysis. In general, adiabaticity was observed in the photoreversion process for all oxetanes, with a high degree of regioselectivity, which falls in line with the theory of the involvement of a triplet exciplex in the process. / Thanks to the Generalitat Valenciana for the finantial support through the Santiago Grisolía grant. / Blasco Brusola, A. (2021). Mechanistic Studies on the Photochemical Formation and Cleavage of Oxetanes Derived from Pyrimidine Bases [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/165256

[ES] Los inhibidores de la tirosina quinasa (TKIs) son fármacos anticancerígenos que actúan atacando selectivamente a las células cancerosas, inhibiendo su crecimiento descontrolado y, por tanto, la consiguiente aparición de tumores. Sin embargo, muchos TKIs presentan un cromóforo en su estructura que les permite interaccionar con luz solar y, consecuentemente, pueden generar reacciones de fotosensibilización. A pesar de ello, existen pocos estudios sobre el mecanismo de reacción asociado a estos eventos. En este sentido, conocer la fotorreactividad de un fármaco en medio biológico es clave para entender dichos mecanismos y correlacionar el comportamiento fotofísico del fármaco con el daño fotobiológico que genera. La espectroscopía de fluorescencia y de absorción transitoria son técnicas altamente sensibles que permiten estudiar las especies transitorias generadas tras la absorción de luz por parte de un fármaco, las cuales podrían ser las responsables de las reacciones de fotosensibilización inducidas por éste. Habiendo estudiado recientemente la foto(geno)toxicidad asociada al TKI gefitinib (GFT) y a sus principales metabolitos fenólicos (GFT-M1 y GFT-M2), se ha llevado a cabo un estudio completo de la fotorreactividad de éstos tanto en disolución orgánica, utilizando disolventes de distintas polaridades, como en medio biológico, utilizando las proteínas transportadoras de origen humano albúmina sérica (HSA) y ¿1-glicoproteína ácida (HAG). Para ello, se han utilizado las técnicas espectroscópicas de absorción, fluorescencia y absorción transitoria, entre otras. Adicionalmente, se han llevado a cabo estudios teóricos de modelización molecular para investigar la unión ligando@proteína, así como las interacciones que tienen lugar en el complejo supramolecular tras la absorción de luz UV-A. Con este trabajo, se ha conseguido establecer una buena correlación entre el comportamiento fotofísico observado para gefitinib y sus dos metabolitos fenólicos con su potencial fototóxico. / [CA] Els inhibidors de la tirosina quinasa (TKIs) són fàrmacs anticancerígens que actuen atacant selectivament a les cèl·lules canceroses, inhibint el seu creixement descontrolat i, per tant, la consegüent aparició de tumors. No obstant això, molts TKIs presenten un cromòfor en la seua estructura que els permet interaccionar amb llum solar i, conseqüentment, poden generar reaccions de fotosensibilització. Malgrat això, existixen pocs estudis sobre el mecanisme de reacció associat a estos esdeveniments. En este sentit, conéixer la fotorreactivitat d'un fàrmac al mig biològic és clau per a entendre estos mecanismes i correlacionar el comportament fotofísic del fàrmac amb el dany fotobiològic que genera. La espectroscopia de fluorescència i d'absorció transitòria són tècniques altament sensibles que permeten estudiar les espècies transitòries generades després de l'absorció de llum per part d'un fàrmac, les quals podrien ser les responsables de les reaccions de fotosensibilització induïdes per aquest. Havent estudiat recentment la foto(geno)toxicitat associada al TKI gefitinib (GFT) i d'els seus principals metabòlits fenòlics (GFT-M1 i GFT-M2), s'ha dut a terme un estudi complet de la fotorreactivitat d'estos tant en dissolució orgànica, utilitzant dissolvents de diferents polaritats, com al mig biològic, utilitzant les proteïnes transportadores d'origen humà albúmina sèrica (HSA) i ¿1-glicoproteïna àcida (HAG). Per a això, s'han utilitzat les tècniques espectroscòpiques d'absorció, fluorescència i absorció transitòria, entre altres. Addicionalment, s'han dut a terme estudis teòrics de modelització molecular per a investigar la unió lligant@proteína, així com les interaccions que tenen lloc en el complex supramolecular després de l'absorció de llum UV-A. Amb este treball, s'ha aconseguit establir una bona correlació entre el comportament fotofísic observat per a gefitinib i els seu dos metabòlits fenòlics amb el seu potencial fototòxic. / [EN] Tyrosine kinase inhibitors (TKIs) are anticancer drugs that target cancer cells, inhibiting their uncontrolled growth and thus the subsequent development of tumours. However, many TKIs contain a chromophore in their structure that allows them to interact with sunlight and, consequently, to induce photosensitivity reactions. Despite this, there are few studies on the reaction mechanism associated with these events. In this regard, a better understanding on the photoreactivity of a drug in a biological environment is key to correlate the photophysical behaviour of the drug with the photoinduced damage it can induce to biomolecules. Fluorescence and transient absorption spectroscopies are very sensitive techniques that allow the study of the transient species generated after drug excitation, which could be responsible for drug-induced photosensitivity reactions. Having recently studied the photo(geno)toxicity associated with the TKI gefitinib (GFT) and its main phenolic metabolites (GFT-M1 and GFT-M2), a complete study of their photoreactivity has been carried out both in organic medium, using solvents of different polarities, and in a biological environment, using transport proteins such as human serum albumin (HSA) and human ¿1-acid glycoprotein (HAG). For this purpose, absorption, fluorescence and transient absorption techniques, among others, have been used. In addition, molecular dynamics simulation studies have been carried out to investigate the ligand@protein binding, as well as the interactions arising in the supramolecular complex after absorption of UV-A light. Therefore, a good correlation between the photophysical behaviour of gefitinib and its two phenolic metabolites and their phototoxic potential has been established in this research work. / Tamarit Mayo, L. (2024). Fotorreactividad de gefitinib y sus metabolitos fenólicos en disolución y en proteínas transportadoras [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/204145

Artificial photosynthesis is often considered to have great potential to provide alternative, renewable fuels by harvesting, conversion and storage of solar energy. One promising approach is the development of modular molecular photocatalysts inspired by natural photosynthetic enzymes. The first part of this thesis deals with artificial mimics of the water oxidizing photosystem II composed of a chromophore and an electron relay as synthetic counterpart of the P680-TyrZ/His190 ensemble of photosystem II. Three ruthenium polypyridyl - imidazole - phenol complexes with varying position of a methyl group on the phenol ring (Ru-xMe) were synthesized and characterized by electrochemical and photophysical methods. As an improvement compared to earlier complexes the increased redox potential (~0.9 V vs. Ferrocene) of the phenol groups makes their function as an electron relay in a photocatalytic system for water oxidation thermodynamically possible. Time-resolved absorption studies revealed fast intramolecular electron transfer (<5-10 µs in aprotic solvent and <100 ns in water) despite the low driving force and the importance of the hydrogen bond between the phenol and the imidazole group was put in evidence. Slight differences between the three Ru-xMe complexes and investigation of the effect of external bases allowed to derive a mechanistic picture in which the imidazole is involved in a "proton domino" reaction. Accepting the phenolic proton upon ligand oxidation (within the H-bond) renders its second nitrogen site more acidic and only deprotonation of this site pulls the overall equilibrium completely towards oxidation of the ligand. Another part of this thesis comprises a chromophore-tryptophan construct synthesized using a click chemistry approach. Light-induced oxidation of Trp in this Ru-tryptophan complex was shown to follow ETPT mechanism. Depending on the pH conditions tryptophan radicals, either Trp* or TrpH*⁺ were detected and spectral measurement at different time showed the transition between the two forms. Deprotonation of the radical was dependent on the concentration of water as proton acceptor. Later part of the thesis deals with efforts to covalently bind a catalytic unit to the previously characterized chromophore-electron relay module. The click chemistry approach was not successful to obtain the final photocatalytic assembly. Therefore bimolecular activation of a Mn salen catalyst was performed and formation of Mn(IV) species was observed. As a step towards utilization of these types of photocatalysts in a photoelectrochemical cell a [Ru(bpy)₃]²⁺ chromophore with phosphonate anchoring groups (Ru-Phosphonate) was synthesized and grafted on the surface of a TiO₂ mesoporous semiconductor surface anode to perform photocurrent measurements.

Les processus d'oxydation avancés à base du radical sulfate (SO4•- -) ont prouvé leur efficacité pour l'élimination de nombreux contaminants. Dans ce travail de thèse, nous avons étudié les processus d'oxydation et de dégradation par le radical sulfate activé à partir du persulfate (PS) pour les molécules suivantes : le diatrizoate, molécule utilisée comme produit de contraste radiologique iodé (DTZ), le salbutamol (SAL) et la terbutaline (TBL), agonistes des récepteurs ß2-adrénergiques. En outre, la réactivité de SO4•- avec la matière organique naturelle (NOM) a également été déterminée. Plus précisément, pour déterminer la réactivité de SO4•- avec NOM, une technique de photolyse laser couplée à la spectroscopie (LFP) a été appliquée pour étudier l'évolution de SO4 • ainsi que la formation d'espèces transitoires à partir de la matière organique. Des constantes de vitesses comprises entre 1530 et 3500 s-1 mgC-1 L ont été obtenues par analyse numérique des équations différentielles et des valeurs moyennes de coefficient d'absorption molaires comprises entre 400 et 800 M-1 cm-1 ont été déterminées pour les espèces transitoires générées de la matière organique.Dans le processus de décomposition de DTZ par PS activé par UV, les principales voies d'oxydation sont la dé-iodination-hydroxylation, la dé-carboxylation-hydroxylation et le clivage de la chaîne latérale. Les résultats ont également indiqué que la vitesse de dégradation du DTZ augmentait avec l'augmentation de la concentration en PS. La présence de NOM a inhibé la dégradation de DTZ, tandis que le bicarbonate l'a amélioré. Pour les ions chlorure un effet négatif a été observé pour des concentrations supérieures à 500 mM.Pour la dégradation du SAL et du TBL, il a été montré que les radicaux phénoxy jouaient un rôle majeur en début de réaction. Par ailleurs, le chlorure n'a pas eu d'effet tangible sur l'efficacité d'oxydation de la SAL et du TBL, tandis que les ions bromures, bicarbonates et le NOM présentaient des effets inhibiteurs / Sulfate radical (SO4•-) based advanced oxidation processes (AOPs) has been proved to be effective for the removal of many contaminants. In this thesis, we investigated the oxidation processes of iodinated X-ray contrast media diatrizoate (DTZ), ß2-adrenoceptor agonists salbutamol (SAL) and terbutaline (TBL) by reaction with SO4•- generated from the activation of persulfate (PS); in addition, the reactivity of SO4•- with natural organic matter (NOM) was also estimated.Specifically, to determine the reactivity of SO4•- with NOM, laser flash photolysis (LFP) technique was applied to monitor the SO4•- decay and the formation of the transients from organic matters. Reaction rate constants comprised between 1530 and 3500 s-1 mgC-1 L were obtained by numerical analysis of differential equations and the weighted average of the extinction coefficient of the generated organic matters radicals between 400 and 800 M-1 cm-1.In the decomposition process of DTZ by UV-activated PS, major oxidation pathways include deiodination-hydroxylation, decarboxylation- hydroxylation and side chain cleavage. Results also indicated that DTZ degradation rate increased with increasing PS concentration. The presence of NOM inhibited DTZ removal rate, while, bicarbonate enhanced it, and chloride ions induced a negative effect above 500 mM. For the degradation of SAL and TBL, phenoxyl radicals were proven to play a very important role from the initial step. Chloride exhibited no effect on the oxidation efficiencies of SAL and TBL, while bromide, bicarbonate and NOM all showed inhibitory effects

L'atmosphère est un milieu hautement hétérogène contenant de la matière condensée : les aérosols. Ceux-ci sont des composants importants de l'atmosphère car ils impactent le bilan radiatif planétaire mais aussi la qualité de l'air. En particulier les aérosols organiques secondaires (AOS), produits par la transformation chimique dans l'air de nombreux composés organiques, plus ou moins volatils, représentent une fraction conséquente dans le budget global des aérosols atmosphériques pour laquelle de nombreuses incertitudes persistent. En particulier, leurs voies de formation et de transformation dans la troposphère restent très mal décrites. C'est pourquoi, cette thèse décrit principalement l'étude de trois aspects de la croissance et du vieillissement (transformation) des aérosols : caractérisation de la croissance des AOS par des processus photosensibilisés ; investigations mécanistiques du vieillissement des AOS et de la photochimie des photosensibilisateurs ; analyse chimique des composés issus du vieillissement des AOS / Aerosols are important constituents of the atmosphere and secondary organic aerosols (SOA) represent a main fraction of the organic aerosols in the total budget. This thesis mainly reports the investigation of three aspects of the growth and aging of SOA: the photosensitized SOA growth ; the mechanistic investigation of SOA aging and of the photochemistry of photosensitizers ; the analysis of the chemical composition of aged SOA. The photosensitized growth and aging processes of SOA were investigated using an aerosol flow tube coupled with various aerosol and gas sensing instruments. For further analysis of the aerosol composition and a better understanding of the formation and growth of SOA in these experiments the aerosols produced in the dark and in the light were sampled on filters at the exit of the flow tube