Circunstancias acaecidas en el Centro Penintenciario de Teixeiro

Traballo fin de grao (UDC.DER). Dereito. Curso 2018/201

Photophysics and photochemistry of singlet oxygen precursor chromophores: insights from static calculations and molecular dynamics

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química. Fecha de lectura: 14-11-2014Aunque especies reactivas oxigenadas (oxígeno singlete (1O2) y ROS) han sido identificadas como las principales responsables del proceso de fotoxidación de la piel, sus propiedades oxidativas se han usado también con fines terapéuticos en tratamientos contra el cáncer. Por ello, muchos esfuerzos se han centrado en el descubrimiento de cromóforos capaces de producir 1O2 después de ser tratados con luz y así eliminar las células tumorales. Entender el mecanismo por el cual estos cromóforos producen 1O2 y ROS es fundamental para el diseño de nuevos sistemas capaces de maximizar las propiedades beneficiosas y eliminar sus efectos nocivos para la salud. Dos tipos de cromóforos han sido estudiados durante esta tesis perimiendo obtener mayor información a cerca de su mecanismo de acción. Bases de ADN en las que un carbonilo a sido sustituido por un azufre, tiobases, han sido usadas como fotosensibilizadores durante décadas pero los efectos nocivos descubiertos en pacientes tratados con estas bases a largo plazo (alta incidencia de cáncer) han abierto la búsqueda de nuevas generaciones de fotosensibilizadores. Se conoce que estas tiobases son capaces de generar 1O2 cuando son activadas con luz y en presencia de oxígeno molecular en la zona a tratar. El segundo tipo de sistemas estudiados son los endoperoxidos, sistemas aromáticos con un puente O-O. Este tipo de sistemas han sido propuestos como eficientes fotosensibilizadores bajo su excitación con luz incluso en ausencia de oxígeno molecular en el medio. Es en el contexto arriba descrito en el que se enmarca esta tesis cuyo principal objetivo es el estudio de dichos mecanismos desde un punto de vista estático y también dinámico. Los mecanismos elucidados en la primera parte de esta tesis se comprobarán mediante estudios dinámicos que permiten una resolución temporal de los mismos así como obtener rendimientos para los distintos fotoproductos, en otras palabras, permiten obtener información acerca de los tiempos y la eficiencia de dichos fotosensibilizadores para obtener 1O2. Finalmente, las propiedades fotofísicas de la base libre purina han sido investigadas tratando de revelar como los diferentes sustituyentes alteran dichas propiedades y como pueden cambiar la fotoestabilidad de las bases de ADN hacia la fototoxicidad de algunos derivados.Despite reactive oxygen species (ROS and 1O2) have been identified as responsible for the skin photo-oxidation processes, their oxidative properties have been also used with therapeutically anticancer effects. Thereby, tons of efforts have been done towards finding chromophores able to produce 1O2 after being treated with light and then destroy tumoral cells. Understanding, the mechanism by which this chromophores produce 1O2 and ROS is fundamental for the design of new systems that ideally will only present beneficial properties but not detrimental effects. Two types of chromophores have been studied along this thesis providing important information about their mechanism of action. DNA bases where a carbonyl oxygen atom has been substituted by a sulfur, thiobases, have been used as therapeutical photosensitizers during decades. However, detrimental effects have been discovered in patients after years of treatment with this bases (high skin cancer incidence) and have led to the search of new generation of photosensitizers. These thiobases generate 1O2 after being activated with light and in presence of molecular oxygen in the media. The second type of studied systems is endoperoxides, aromatic systems carrying an O-O bridge. These systems have been proposed as prototype of effective photosensitizers, which are able to produce 1O2 even in the absence of molecular oxygen in the media. In the above context this Thesis aims to elucidate the photodeactivation mechanism of the mentioned systems both from static high-level multiconfigurational calculations and semiclassical dynamics. This approach allows knowing at molecular level all energetically possible competing relaxation mechanism and evaluating their relative importance according to the outcome of the time resolved picture provided by the dynamics Moreover, the combined static and dynamic analysis allows a more reliable interpretation of the experimental results od the systems considered in this thesis by estimating photoproduct yields and time scales for different processes. Finally, the photophysical and photochemistry of purine free base have also been investigated aiming to provide insight on how the nature and position of different substituents affect the absorption properties and the photostability of these system

Subphthalocyaninato boron(III) hydride: synthesis, structure and reactivity

Subphthalocyanine (SubPc) chemistry has been limited so far by their high sensitivity toward strong nucleophiles. In particular, the substitution of the axial chlorine atom by a nucleophilic group in the case of less-reactive SubPcs, such as those bearing electron-withdrawing peripheral substituents, presents some limitations and requires harsh conditions. By taking advantage of the electrophilic character of DIBAL-H, it has been possible to prepare for the first time SubPc-hydride derivatives that exhibit high reactivity as hydroboration reagents of aldehydes. This hydride transfer requires using a typical carbonyl activator (trimethylsilyl triflate) and only one equivalent of aldehyde, affording SubPcs with an axial benzyloxy group in good yield. This transformation has proven to be a useful alternative method for the axial functionalisation of dodecafluoroSubPc, a paradigmatic SubPc derivative, by using electrophiles for the first time. Considering the increasing interest in SubPcs as electron-acceptor semiconductors with remarkable absorption in the visible range to replace fullerene in organic photovoltaic (OPV) devices, it is of the utmost importance to develop new synthetic methodologies for their axial functionalisationFinancial support from Spanish MINECO and MICINN (CTQ2017- 85393-P, PGC2018-094644-B-C21, PDI2019-110091GB-I00) is acknowledged. IMDEA Nanociencia acknowledges support from the “Severo Ochoa” Programme for Centres of Excellence in R&D (MINECO, grant SEV2016-0686). J.L. and L.T. acknowledge MECD, Spain, for a F.P.U. fellowship. I.C. and L.M

Electron holes in G-Quadruplexes: The role of adenine ending groups

The study deals with four-stranded DNA structures (G-Quadruplexes), known to undergo ionization upon direct absorption of low-energy UV photons. Combining quantum chemistry calculations and time-resolved absorption spectroscopy with 266 nm excitation, it focuses on the electron holes generated in tetramolecular systems with adenine groups at the ends. Our computations show that the electron hole is placed in a single guanine site, whose location depends on the position of the adenines at the 3′ or 5′ ends. This position also affects significantly the electronic absorption spectrum of (G+ )• radical cations. Their decay is highly anisotropic, composed of a fast process (<2 µs), followed by a slower one occurring in ~20 µs. On the one hand, they undergo deprotonation to (G-H2)• radicals and, on the other, they give rise to a reaction product absorbing in the 300–500 nm spectral domai

Molecular identification of the transient species mediating the deactivation dynamics of solvated guanosine and deazaguanosine

Small structural alterations of the purine/pyrimidine core have been related to important photophysical changes, such as the loss of photostability. Similarly to canonical nucleobases, solute-solvent interactions can lead to a change in the excited state lifetimes and/or to the interplay of different states in the photophysics of these modified nucleobases. To shed light on both effects, we here report a complete picture of the absorption spectra and excited state deactivation of deoxyguanosine and its closely related derivative, deoxydeazaguanosine, in water and methanol through the mapping of the excited state potential energy surfaces and molecular dynamics simulations at the TD-DFT level of theory. We show that the N by CH exchange in the imidazole ring of deoxyguanosine translates into a small red-shift of the bright states and slightly faster dynamics. In contrast, changing solvent from water to methanol implies the opposite, i.e., that the deactivation of both systems to the ground state is significantly hindered

Posttraumatic carotid-cavernous fistula: pathogenetic mechanisms, diagnostic management and proper treatment. A case report

Carotid-cavernous fistulas are an uncommon diseases characterized by abnormal communications between arteries and veins located in the cavernous sinus. According with Barrow´s classification they could be divided in two groups: direct and indirect. The typical symptoms showed by theses pathologies are: pulsating exophthalmos and orbital blow. The present study describes a case of direct posttraumatic carotid-cavernous fistula in a 26 years old man. Furthermore, we present the images that we used to make the diagnosis. In this light, we decided to treat this case with endovascular approach after considering several therapeutic options. The aim of the present report is twofold. First, we examine the importance of the proper management of the direct posttraumatic carotid-cavernous fistula. Second, we describe this rare syndrome with the goal of proposing suitable treatments

A new small supernumerary marker chromosome, generating mosaic pure trisomy 16q11.1–q12.1 in a healthy man

Here we report on a healthy and fertile 30 years old man, who was carrier of a small supernumerary marker chromosome (sSMC). The application of molecular techniques such as fluorescence in situ hybridisation (FISH), microdissection and reverse painting, helped to characterize the sSMC which resulted to be derived from chromosome 16. In fact, the presence of euchromatin material from the long arm (16q) in the sSMC was demonstrated, and the karyotype can be written as mos 47, XY,+min(16)(:p11.1->q12.1:)[20]/46, XY [10]

Ultrafast excited state dynamics of silver ion-mediated cytosine–cytosine base pairs in metallo-DNA

The following article appeared in The Journal of Chemical Physics 153.10 (2020): 105104 and may be found at ttps://doi.org/10.1063/5.0020463To better understand the nexus between structure and photophysics in metallo-DNA assemblies, the parallel-stranded duplex formed by the all-cytosine oligonucleotide, dC20, and silver nitrate was studied by circular dichroism (CD), femtosecond transient absorption spectroscopy, and time-dependent-density functional theory calculations. Silver(I) ions mediate Cytosine–Cytosine (CC) base pairs by coordinating to the N3 atoms of two cytosines. Although these silver(I) mediated CC base pairs resemble the proton-mediated CC base pairs found in i-motif DNA at first glance, a comparison of experimental and calculated CD spectra reveals that silver ion-mediated i-motif structures do not form. Instead, the parallel-stranded duplex formed between dC20 and silver ions is proposed to contain consecutive silver-mediated base pairs with high propeller twist-like ones seen in a recent crystal structure of an emissive, DNA-templated silver cluster. Femtosecond transient absorption measurements with broadband probing from the near UV to the near IR reveal an unusually long-lived (>10 ns) excited state in the dC20 silver ion complex that is not seen in dC20 in single-stranded or i-motif forms. This state is also absent in a concentrated solution of cytosine–silver ion complexes that are thought to assemble into planar ribbons or sheets that lack stacked silver(I) mediated CC base pairs. The large propeller twist angle present in metal-mediated base pairs may promote the formation of long-lived charged separated or triplet states in this metallo-DNAThe work at The Ohio State University was supported by a grant from the U.S. National Science Foundation (Grant No. CHE1800471). L.M.-F. thanks the MINECO project (No. CTQ2016- 76061-P) for financial support and the Centro de Computación Científica, CCC-UAM, for generous allocation of computational time. The authors declare no competing financial interes

Direct Access to Axially Substituted Subphthalocyanines from Trimethylsilyl-Protected Nucleophiles

A new synthetic one-step approach to perform the axial ligand exchange reaction in subphthalocyanines that employs trimethylsilyl-protected nucleophiles as starting materials is reported. Theoretical calculations indicate that the exchange reaction proceeds through a similar 4-centered σ-bond metathesis transition state as the substitution with phenols. This direct method allowed us to synthesize new axial derivatives of singular importance within the chemistry of subphthalocyanines, for which the reactivity and X-ray crystalline structure were studiedFinancial support from the MINECO, Spain (CTQ-2014-52869-P, T.T.; CTQ2014-57729-P, D.G.-R.), and the Comunidad de Madrid (S2013/MIT-2841 FOTOCARBON, T.T.) is acknowledged. M.Y. thank the MICINN (Spain) for the Project No.CTQ2012-35513-C02-0

Some histopathological and clinical correlations in oral squamous cell carcinoma

Oral squamous cell carcinoma (SCC) is an important health problem that causes high mortality and morbidity. Correlations between some clinical and histopathological parameters were studied in 37 oral SCC. Some interesting aspects in oral SCC arising from precancerous lesions were found such as smaller size and a lower TNM stage at the moment of diagnosis. Histological and clinical differences were also found between tumors invading deep tissues by little groups of dissociated malignant cells and those invading by big masses of malignant cells. The possible significance of the intensity of peritumoral eosinophilic infiltrate was also studied.Le carcinome squameux de la cavité orale constitue un problème important de santé, qui est responsable d’une mortalité et d’une morbidité élevées. Nous avons étudié 37 carcinomes squameux de la cavité orale à travers un suivi clinique et une étude des corrélations entre les variables cliniques et histopathologiques. Nous avons relevé différents aspects intéressants en ce qui concerne les carcinomes squameux de la cavité orale qui procédaient de lésions précancéreuses comme leur petite dimention et le bas stade TNM au moment du diagnostic. Nous avons également trouvé des différences cliniques et histopathologiques entre les tumeurs qui envahissent les tissus adjecents en petits groupes et ceux qui le font en grandes masses de cellules malignes. Finalement, nous avons étudié la signification possible de l’intensité de l’infiltrat à eosinophiles peritumoral