Replacement of thymidine in DNA by halopyrimidines, such as bromodeoxyuridine (BrdU) and iododeoxyuridine (IdU), has long been known to enhance DNA damage and cell death induced by ionizing/UV radiation, but the mechanism of action of halopyrimidines at the molecular level is poorly understood. We have applied advanced time-resolved femtosecond laser spectroscopy to this molecular system of biological, chemical and medical significance. We obtained the first real-time observations of the transition states of the ultrafast electron transfer (UET) reactions of halopyrimidines with the ultrashort-lived precursor to the hydrated electron, which is a general product in ionizing/UV radiation. Our results provide a mechanistic understanding of these photo-/radiosensitizing drugs at the molecular level. We found that the UET reaction of BrdU is completed within 0.2 picosecond (ps) after the electronic exciataion, leading to the formation of the transition state BrdU* with a lifetime of ~1.5 ps that then dissociates into Br and a high reactive radical dU•. We have also demonstrated that the reaction efficiency for the formation of the reactive radical dU• to cause DNA damage and cell death is in the order of IdU>>BrdU>CldU>>FdU. This is due to the availability of two precursor states of ~0.2 ps and ~ 0.54 ps lifetimes for dissociative electron attachment (DEA) to IdU, of one precursor state of ~0.2 ps lifetime for DEAs to BrdU and CldU, and no precursors for DEA to FdU. This explains why BrdU and IdU were found to be effective radio-/photosensitizers and indicates that IdU should be explored as the most effective radiosensitizer among halopyrimidines. Moreover, as a by-product of this project, these halopyrimidines have been employed as quantum-state-specific molecular probes to resolve a long-standing controversy about the nature and lifetimes of prehydrated electrons. These findings also have a broader significance as they indicated that nonequilibrium precursor electrons may play an important role in electron-initiated reactions in many biological, chemical and environmental systems. We have also demonstrated UET reactions of nucleotides with the precursor to the hydrated electrons. Our results indicate that among DNA bases, adenine is the most efficient electron trapper and an effective electron transfer promoter, while guanine is the most effective in dissociative electron attachment. These results not only primarily explain the sequence selectivity of duplex DNA containing BrdU/IdU, but imply that the DEA of guanine is an important mechanism for radiation-induced DNA damage in ionizing radiation and radiotherapy of cancer.

Replacement of thymidine in DNA by halopyrimidines, such as bromodeoxyuridine (BrdU) and iododeoxyuridine (IdU), has long been known to enhance DNA damage and cell death induced by ionizing/UV radiation, but the mechanism of action of halopyrimidines at the molecular level is poorly understood. We have applied advanced time-resolved femtosecond laser spectroscopy to this molecular system of biological, chemical and medical significance. We obtained the first real-time observations of the transition states of the ultrafast electron transfer (UET) reactions of halopyrimidines with the ultrashort-lived precursor to the hydrated electron, which is a general product in ionizing/UV radiation. Our results provide a mechanistic understanding of these photo-/radiosensitizing drugs at the molecular level. We found that the UET reaction of BrdU is completed within 0.2 picosecond (ps) after the electronic exciataion, leading to the formation of the transition state BrdU* with a lifetime of ~1.5 ps that then dissociates into Br and a high reactive radical dU•. We have also demonstrated that the reaction efficiency for the formation of the reactive radical dU• to cause DNA damage and cell death is in the order of IdU>>BrdU>CldU>>FdU. This is due to the availability of two precursor states of ~0.2 ps and ~ 0.54 ps lifetimes for dissociative electron attachment (DEA) to IdU, of one precursor state of ~0.2 ps lifetime for DEAs to BrdU and CldU, and no precursors for DEA to FdU. This explains why BrdU and IdU were found to be effective radio-/photosensitizers and indicates that IdU should be explored as the most effective radiosensitizer among halopyrimidines. Moreover, as a by-product of this project, these halopyrimidines have been employed as quantum-state-specific molecular probes to resolve a long-standing controversy about the nature and lifetimes of prehydrated electrons. These findings also have a broader significance as they indicated that nonequilibrium precursor electrons may play an important role in electron-initiated reactions in many biological, chemical and environmental systems. We have also demonstrated UET reactions of nucleotides with the precursor to the hydrated electrons. Our results indicate that among DNA bases, adenine is the most efficient electron trapper and an effective electron transfer promoter, while guanine is the most effective in dissociative electron attachment. These results not only primarily explain the sequence selectivity of duplex DNA containing BrdU/IdU, but imply that the DEA of guanine is an important mechanism for radiation-induced DNA damage in ionizing radiation and radiotherapy of cancer.

La recombinaison dissociative (RD) est le processus dans lequel un ion moléculaire positif se recombine avec un électron et se dissocie après en fragments neutres. Parmi les différents types de réactions entre ions moléculaires et électrons, la RD mérite une attention particulière à cause du rôle important qu'elle joue dans les plasmas à basse température et de faible densité, telles que celles rencontrées dans les ionosphères planétaires et les nuages interstellaires. En dépit de l'apparente simplicité de la RD, son étude s'est avéré difficile aussi bien du point de vue expérimental que théorique. Afin d'apporter plus de lumière sur ce processus, la technique de la post-décharge en écoulement a été introduite et a été largement utilisée ces dernières décennies. La présente thèse est dédiée aux études expérimentales de la réaction RD, à l'aide du spectromètre de masse à sonde Langmuir (FALP-MS) en post-décharge en écoulement, à l'Université de Rennes 1, à Rennes, en France. Nous avons étudié la réaction RD à température ambiante a été étudiée pour les ions moléculaires d'acétone ( ) et les cations de diméthylamine cations ( ainsi que les vitesses de réaction des cations de triméthylamine ( cations, et nous avons obtenu des valeurs avec des incertitudes de of ± 30 %. De plus, nous avons étudié l'attachement électronique à la diméthylamine neutre et nous avons trouvé une constante de vitesse de = 4.81 x 10-10 cm3 s-1. Un nouveau système d'injection pour l'anneau de stockage électrostatique de KACST a été conçu et construit dans le laboratoire de l'IPR à Rennes. Le couplage de la source d'ions avec un analyseur de masse quadripolaire et l'utilisation d'un système de vannes pulsées assurant un pompage différentiel entre différentes régions de la ligne d'injection constitue une méthode nouvelle dans le contexte d'un anneau de stockage. Le but final de ce projet est l'étude des réactions à ions lourds tels que les ions moléculaires biologiques. / Dissociative recombination (DR) is a process in which a positive molecular ion recombines with an electron and subsequently dissociates into neutral fragments. Among the different types of molecular ion-electron reactions DR deserves particular attention due to the important role it plays in low-temperature and low-density plasmas such as those encountered in planetary ionospheres and interstellar clouds. Despite the apparent simplicity of the DR reaction, its investigation has proven to be a difficult task from both experimental and theoretical perspectives. In order to shed more light upon this process the flowing afterglow technique has been introduced and utilised extensively for the last few decades. This thesis is devoted to experimental studies into the DR reaction using the flowing afterglow Langmuir probe mass spectrometer FALP-MS at the University of Rennes 1, in Rennes, France. The DR reaction at room temperature has been investigated for the acetone molecular ions ( ) and dimethylamine cations ( as well as the reaction rates of trimethylamine ( cations, and the obtained values were with uncertainties of ± 30 %. In addition, the electronic attachment to neutral dimethylamine was also studied and the rate constant was determined to be = 4.81 x 10-10 cm3 s-1. A new ion injection system system for the KACST electrostatic storage ring has been designed and built in the IPR laboratory in Rennes. The coupling of an ion source with a quadrupole mass analyzer and the use of a gas pulsing system to maintain the differential pumping between different regions of the injection line, is a novel technique for use with a storage ring. The final goal of this system is to study the reactivity of heavy ions such as biological molecular ions.

In the presented thesis we study analytical behavior of vibrational excitation cross sections and probability flux density in nonlocal resonance model. An analytical formula for determining the shape of Wigner cusps from three complex parameters is derived. The results of this formula are compared to numerical calculations with complex scaling method and interpreted within Feynman approach to quantum mechanics. Furthermore, we derive nonlocal continuity equation and show how it implies the multichannel optical theorem. Detail analysis of fluxes in the nonlocal resonance model is used to accelerate the convergence of formula for the dissociative attachment cross section and we present a simple model describing boomerang oscillations. A program in Fortran language is attached to this work. The program allows calculation of vibrational excitation and dissociative attachment cross sections, flux divergences and other quantities specified in this text.

A two-dimensional model of the resonant electron-molecule collision processes with one nuclear and one electronic degree of freedom introduced by Houfek, Rescigno and McCurdy [Phys. Rev. A 73, 032721 (2006)] and a similar two- dimensional model of the dissociative recombination with potential proposed by Hamilton [Ph.D. thesis, University of Colorado, (2003)] are formulated within the time-dependent framework and solved numerically using the finite-element method with the discrete variable representation basis, the exterior complex scaling method and the generalized Crank-Nicolson method. On the model of electron-molecule collisions we illustrate how the time-dependent calculations can provide a deep insight into the origin of oscillatory structures in the vibrational excitation cross sections if one evaluates the cross sections not only at sufficiently large time to obtain the final cross sections, but rather at several characteristic times which are given by the evolution of the system. With use of the time- dependent calculations we demonstrate the complex nature of the dissociative recombination model dynamics and we propose the interpretation of the recom- bination process mechanism. We also propose few techniques for the explanation of the sharp structures in the dissociative recombination cross sections...