10 research outputs found
Recommended from our members
Radiation Induced Processes in Biomolecules and Clusters in Controlled Beams
The fundamental nanoscale processes that initiate radiation damage in biological material have not yet been fully elucidated. This represents a significant barrier to developing multidimensional simulations of radiation effects that can lead to advances in radiotherapy and radioprotection. This thesis explores UV- and electron-induced processes in DNA and RNA bases. Pure and hydrated clusters are studied in order to better understand the effects of the chemical environment on the radiation response of these important biomolecules.
Although extensive research has been carried out on the relaxation pathways of UV-excited nucleobases, no previous experiments have investigated bond breaking in neutral electronic excited states. This thesis reveals a new fragment ion from uracil (C3H4N2O+) that can be accessed by multi-photon ionization (MPI) but not by electron impact ionization (ElI). This provides the first experimental demonstration that neutral excited state dynamics in a nucleobase can lead to bond breaking in the aromatic ring, as predicted in recent theoretical studies. The specific excited state dynamics have not yet been identified definitively and are the subject of on-going ultrafast pump-probe experiments in collaboration with Townsend and co-workers (Heriot-Watt University). The time-resolved measurements provide new evidence supporting a theoretically predicted relaxation pathway into long-lived triplet states.
Dissociative ionization of hydrated nucleobases and uracil-adenine clusters has been studied experimentally for the first time. Evidence for deamination reactions is observed in hydrated adenine complexes. The production of C3H4N2O+ fragments from uracil is strongly suppressed by clustering with water whereas the channel remains open in uracil-adenine complexes. To unravel the specific cluster-mediated dynamics and reactions responsible for these effects, further experiments are required with greater control over the cluster targets. Indeed the range of monomers and cluster configurations in neutral beams currently limits interpretations and direct comparisons with calculations. In response to this challenge, a new experiment has been built that enables radiation effects to be studied on molecules and clusters in Stark-deflected beams (MPI, ElI, and future electron attachment measurements). Early results on nitromethane beams include a demonstration that studying ElI as a function of the Stark deflector voltage can be used to deduce whether certain product ions came from monomers or from clusters
Ultraviolet relaxation dynamics in uracil: Time-resolved photoion yield studies using a laser-based thermal desorption source
Wavelength-dependent measurements of the RNA base uracil, undertaken with nanosecond ultraviolet laser pulses, have previously identified a fragment at m/z = 84 (corresponding to the C3H4N2O+ ion) at excitation wavelengths ≤232 nm. This has been interpreted as a possible signature of a theoretically predicted ultrafast ring-opening occurring on a neutral excited state potential energy surface. To further investigate the dynamics of this mechanism, and also the non-adiabatic dynamics operating more generally in uracil, we have used a newly built ultra-high vacuum spectrometer incorporating a laser-based thermal desorption source to perform time-resolved ion-yield measurements at pump wavelengths of 267 nm, 220 nm, and 200 nm. We also report complementary data obtained for the related species 2-thiouracil following 267 nm excitation. Where direct comparisons can be made (267 nm), our findings are in good agreement with the previously reported measurements conducted on these systems using cold molecular beams, demonstrating that the role of initial internal energy on the excited state dynamics is negligible. Our 220 nm and 200 nm data also represent the first reported ultrafast study of uracil at pump wavelengths 3(1ππ*) state. These measurements do not, however, provide any evidence for the appearance of the m/z = 84 fragment within the first few hundred picoseconds following excitation. This key finding indicates that the detection of this specific species in previous nanosecond work is not directly related to an ultrafast ring-opening process. An alternative excited state process, operating on a more extended time scale, remains an open possibility
Stabilities of nanohydrated thymine radical cations: insights from multiphoton ionization experiments and ab initio calculations
Multi-photon ionization experiments have been carried out on thymine-water clusters in the gas phase. Metastable H2O loss from T+(H2O)n was observed at n ≥ 3 only. Ab initio quantum-chemical calculations of a large range of optimized T+(H2O)n conformers have been performed up to n = 4, enabling binding energies of water to be derived. These decrease smoothly with n, consistent with the general trend of increasing metastable H2O loss in the experimental data. The lowest-energy conformers of T+(H2O)3 and T+(H2O)4 feature intermolecular bonding via charge-dipole interactions, in contrast with the purely hydrogen-bonded neutrals. We found no evidence for a closed hydration shell at n = 4, also contrasting with studies of neutral clusters
Fragmentation processes of ionized 5-fluorouracil in the gas phase and within clusters
We have measured mass spectra for positive ions produced from neutral 5-fluorouracil by electron impact at energies from 0 to 100 eV. Fragment ion appearance energies of this (radio-)chemotherapy agent have been determined for the first time and we have identified several new fragment ions of low abundance. The main fragmentations are similar to uracil, involving HNCO loss and subsequent HCN loss, CO loss, or FCCO loss. The features adjacent to these prominent peaks in the mass spectra are attributed to tautomerization preceding the fragmentation and/or the loss of one or two additional hydrogen atoms. A few fragmentions are distinct for 5-fluorouracil compared to uracil, most notably the production of the reactive moiety CF+. Finally, multiphoton ionization mass spectra are compared for 5-fluorouracil from a laser thermal desorption source and from a supersonic expansion source. The detection of a new fragment ion at 114 u in the supersonic expansion experiments provides the first evidence for a clustering effect on the radiation response of 5-fluorouracil. By analogy with previous experiments and calculations on protonated uracil, this is assigned to NH3 loss from protonated 5-fluorouracil
Mapping the complex metastable fragmentation pathways of excited 3-aminophenol+
This work applies the technique of mapping ion detection using a reflectron mass spectrometer against flight-time and reflection voltage to elucidate the complex metastable fragmentation pattern of the biomolecular ion 3-aminophenol+ (3-AP+, C6H7NO+). Multiphoton ionization experiments revealed the excited ion's fragmentation routes for the first time and comparisons with calculated flight-times enabled 18 μs-timescale dissociations to be assigned. These included the rare observation of a double hydrogen loss channel from a fragment ion. Ab initio calculations provided further insights into the most prominent apparent fragmentation sequence: 3-AP+ (m/z 109) → HCO + C5H6N+ (m/z 80) → CNH + C4H5+ (m/z 53) → C2H2 + C2H3+ (m/z 27)
A velocity map imaging spectrometer for measuring absolute differential cross sections for ion-induced electron emission from molecules
International audienc
Multiple valence electron detachment following Auger decay of inner-shell vacancies in gas-phase DNA
International audienceWe have studied soft X-ray photoabsorption in the doubly deprotonated gas-phase oligonucleotide [dTGGGGT–2H]2−. The dominating decay mechanism of the X-ray induced inner shell vacancy was found to be Auger decay with detachment of at least three electrons, leading to charge reversal of the anionic precursor and the formation of positively charged photofragment ions. The same process is observed in heavy ion (12 MeV C4+) collisions with [dTGGGGT–2H]2− where inner shell vacancies are generated as well, but with smaller probability. Auger decay of a single K-vacancy in DNA, followed by detachment of three or more low energy electrons instead of a single high energy electron has profound implications for DNA damage and damage modelling. The production of three low kinetic energy electrons with short mean free path instead of one high kinetic energy electron with long mean free path implies that electron-induced DNA damage will be much more localized around the initial K-shell vacancy. The fragmentation channels, triggered by triple electron detachment Auger decay are predominantly related to protonated guanine base loss and even loss of protonated guanine dimers is tentatively observed. The fragmentation is not a consequence of the initial K-shell vacancy but purely due to multiple detachment of valence electrons, as a very similar positive ion fragmentation pattern is observed in femtosecond laser-induced dissociation experiment
Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study
Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general
anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use
of neuromuscular blocking agents is associated with postoperative pulmonary complications.
Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in
28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital
procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge
were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination
within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative
pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were
adjusted for surgical factors and patients’ preoperative physical status, providing adjusted odds ratios (ORadj) and
adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513.
Findings Between June 16, 2014, and April 29, 2015, data from 22803 patients were collected. The use of neuromuscular
blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who
had undergone general anaesthesia (1658 [7·6%] of 21694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj –4·4%, 95% CI
–5·5 to –3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised
without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49;
ARRadj –2·6%, 95% CI –3·9 to –1·4) and the administration of reversal agents (1·23, 1·07–1·41; –1·9%, –3·2 to –0·7)
were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex
instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj –0·3%, 95% CI –2·4 to 1·5) nor extubation at
a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; –0·4%, –3·5 to 2·2) was associated with better pulmonary outcomes.
Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an
increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of
neuromuscular blockade against the increased risk of postoperative pulmonary complications