Imaging nuclear motion during the photofragmentation of halomethane molecules triggered by ultraviolet light

Doctor of PhilosophyDepartment of PhysicsArtem RudenkoDaniel RollesUnderstanding the photoexcitation of molecules and visualizing the ensuing dynamics on their natural time scale is essential for our ability to describe and exploit many fundamental processes in different areas of science and technology. Prominent examples of such processes include, among many others, the adverse impacts of different classes of molecules on the ozone layer in atmospheric chemistry, light conversion into electricity through photovoltaics, photocatalysis, and some essential biological processes like vision and photosynthesis. Studies of molecular dynamics triggered by photon-molecule interaction underpin our understanding of many of these phenomena by adding the intermediate state to the “before-and-after” view of such photochemical or photobiological reactions. While identifying the initial molecular structure at equilibrium and determining the final products are crucial steps for the reaction characterization, understanding the dynamics connecting these initial and final states is essential for comprehending how the reaction really happens and potentially controlling its outcome. In other words, besides the “static” view of photo-induced reactions, identifying all intermediate states involved and mapping their spatio-temporal evolution are of great interest and importance. Since photoexcitation often induces coupled electron and nuclear motion on Angström spatial and femtosecond time scales, resolving such dynamics in space and time represents a significant scientific and technological challenge. Experimental tools to address this challenge have recently become available with the development of femtosecond lasers and imaging techniques capable of visualizing the evolving molecular structure. The present thesis aims to investigate the photodissociation dynamics of halomethane molecules triggered by ultraviolet (UV) light using coincidence ion momentum imaging as a primary structural characterization tool. Halomethanes are often considered as prototypical systems for molecular photodissociation in the UV domain. Due to the complicated excited-state structure driving the photochemistry of these molecules, they exhibit rich dynamics while being small enough to still allow for a detailed theoretical treatment. The primary goal of this work is to disentangle the photo-induced reaction channels, including direct and indirect dissociation pathways, and to visualize the motion of the individual molecular fragments in each of these channels. The photofragmentation reactions considered here include two- and three-body dissociation, transient isomerization and molecular halogen formation. The experiments are carried out at two different excitation wavelengths, 263 nm and 198 nm, which enables varying the dominant reaction pathways. To carry out these measurements, the 3rd and 4th harmonics of a 790 nm Ti: Sa femtosecond laser are used to initiate the dynamics of interest, which are then probed by multiple ionization and Coulomb explosion induced by an intense 790 nm pulse arriving after a variable time delay. The ions created in such pump-probe experiments are detected employing COLd Target Recoil Ion Momentum Spectroscopy (COLTRIMS). To facilitate interpreting the experimental results, they are compared to an extensive set of Coulomb explosion simulations. More specifically, this thesis describes three major studies. The first one is a set of time-resolved measurements on iodomethane (CH3I) photodissociation in the A-band, one of the best-studied reactions in ultrafast photochemistry. Here, the focus is on a detailed characterization of direct dissociation dynamics by Coulomb explosion imaging (CEI) and disentangling the competing reaction pathways involving single- and multi-photon excitations. The coincident measurement mode and an improved time resolution of 40-45 fs allowed us to observe a new feature in the two-body CEI pattern of this well-studied reaction, which was predicted theoretically but not yet observed experimentally, and to identify signatures of two- and three-photon processes populating Rydberg and ionic states. The second part of this work focuses on time-resolved studies of bromoiodomethane (CH2BrI) and chloroiodomethane (CH2ICl) photofragmentation in the A-band at 263 nm and, in particular, on imaging the co-fragment rotation. Here, the main objectives are to evaluate the effects of halogen-atom substitution on molecular dynamics and map the time evolution of individual photodissociation pathways. For these molecules, photoabsorption in the A-band predominantly breaks the C-I bond, with weaker but non-negligible contribution from the C-Br (or C-Cl) bond cleavage. Coincident two-body CEI analysis is used to map both of these channels, as well as a minor contribution from molecular halogen (IBr or ICl) formation. Three-body CEI patterns offer a deeper insight into the dynamics of these reactions and, in addition, reveal clear signatures of the three-body dissociation, which – at this wavelength – is most likely driven by the two-photon absorption. The three-body analysis also suggests that some fragmentation pathways pass through a transient linearized configuration, which is reached within ~100 fs from the initial photoabsorption and decays on a comparably fast time scale. One of the interesting aspects of dihalomethanes photodissociation in the A-band is that, unlike CH3I, where the excess energy is primarily channeled into translational motion, a significant portion of the available energy is partitioned into rotational excitation. Carbon-halogen bond cleavage results in the rotation of the molecular co-fragment, which can be unambiguously traced in the coincident three-body CEI maps for the corresponding dissociation channel. In this work, such rotational motion is directly imaged for the dissociation of either halogen atom, resulting in a “molecular movie” of the dissociating and rotating molecule. The third group of experiments described in this thesis includes time-resolved studies of bromoiodomethane and diiodomethane (CH2I2) photofragmentation in the B-band at 198 nm. In this part, the main goal is to trace the wavelength dependence of the photochemical reaction pathways. For CH2BrI, we observe a reversal of the branching ratio of C-I and C-Br bond cleavage compared to the 263 nm data, in agreement with earlier spectroscopic and theoretical studies. However, at 198 nm, three-body dissociation and molecular halogen formation become dominant photofragmentation channels for both molecules. Finally, the CH3I photodissociation is also studied in the B-band at 198 nm, where the excitation of the lowest-lying Rydberg states is expected to trigger pre-dissociation dynamics. Although no in-depth data analysis and modeling for this reaction have been carried out, the two-body CEI results clearly demonstrate the pre-dissociation nature of CH3I fragmentation at this wavelength, reflected in a broad, diffuse dissociation band, which is very different from distinct dissociation features observed for direct dissociation processes. Moreover, the data exhibit a pronounced oscillatory structure with a periodicity of 130-140 fs, which is visible only within the pre-dissociation lifetime of the excited state (~1.5 ps). While the exact origin of this structure remains unclear and will be a subject of further analysis and theoretical work, it most likely reflects the bound-state vibrational motion, which lasts until it pre-dissociates. The work presented in this thesis represents a significant step towards a better understanding of the UV-driven photochemistry of halomethanes and contains several examples of direct visualization of the atomic motion during these photochemical reactions. Our experimental approach enabled us to identify and disentangle different dissociation pathways and track their time evolution. The experimental methodology described here can be directly applied to investigate the light-driven nuclear motion in other molecular systems with different light sources

Evaluation of an arterial blood sampling device and its function in accelerating and facilitating blood sampling

Background: Arterial blood sampling is among the basic standards in critically ill patients. The aim of this study was to examine an inventive sampling device in facilitating arterial blood sampling in comparison to the conventional method using an insulin syringe.Methods and materials: This randomized interventional clinical trial was performed on 100 patients admitted to Qaem and Imam Reza Hospitals in Mashhad in 2016 for whom two arterial blood gas (ABG) samples were indicated. The patients were randomly selected by the visiting operator on a daily basis. The operator visited the hospital on certain days and took two samples from the selected patients.Results: The patients' mean age was 45.31±16.15 years. In the insulin syringe group, venous blood gas sampling was in 24% and arterial sample in 76%. In the designed device group, same figures were 12.1% and 87.9%, respectively. Sampling score (p=0.01), unsuccessful attempts with and without needle removal from the skin (p=0.01), and need for vertical and horizontal needle displacement for sampling (p=0.01) were significantly differed between the two groups. Localized swelling score and its size, localized bruising, palpable arterial spasm and the spasm duration was significantly less for the inventive device (p<0.05). Satisfaction score of patients and operator were significantly higher in the device group (p=0.01).Conclusion: The study device had desirable function in facilitating and accelerating arterial blood sampling. Its application can be further approved by future studies.Keywords: Arterial blood sampling, Facilitated sampling, Accelerated sampling, Intensive Care Uni

Neurologic complications in percutaneous nephrolithotomy

Percutaneous nephrolithotomy (PCNL) has been the preferred procedure for the removal of large renal stones in Iran since 1990. Recently, we encountered a series of devastating neurologic complications during PCNL, including paraplegia and hemiplegia. There are several reports of neurologic complications following PCNL owing to paradoxical air emboli, but there are no reports of paraplegia following PCNL. Materials and Methods: We retrospectively reviewed the medical records of patients who had undergone PCNL in 13 different endourologic centers and retrieved data related to neurologic complications after PCNL, including coma, paraplegia, hemiplegia, and quadriplegia. Results: The total number of PCNL procedures in these 13 centers was 30,666. Among these procedures, 11 cases were complicated by neurologic events, and four of these cases experienced paraplegia. All events happened with the patient in the prone position with the use of general anesthesia and in the presence of air injection. There were no reports of neurologic complications in PCNL procedures performed with the patient under general anesthesia and in the prone position and with contrast injection. Conclusions: It can be assumed that using room air to opacify the collecting system played a major role in the occurrence of these complications. Likewise, the prone position and general anesthesia may predispose to these events in the presence of air injectio

Time-resolved site-selective imaging of predissociation and charge transfer dynamics: The CH3I B-band

The predissociation dynamics of the 6s (B2E) Rydberg state of gas-phase CH3I were investigated by time-resolved Coulomb-explosion imaging using extreme ultraviolet (XUV) free-electron laser pulses. Inner-shell ionization at the iodine 4d edge was utilized to provide a site-specific probe of the ensuing dynamics. The combination of a velocity-map imaging (VMI) spectrometer coupled with the pixel imaging mass spectrometry (PImMS) camera permitted three-dimensional ionic fragment momenta to be recorded simultaneously for a wide range of iodine charge states. In accord with previous studies, initial excitation at 201.2 nm results in internal conversion and subsequent dissociation on the lower-lying A-state surface on a picosecond time scale. Examination of the time-dependent yield of low kinetic energy iodine fragments yields mechanistic insights into the predissociation and subsequent charge transfer following multiple ionization of the iodine products. The effect of charge transfer was observed through differing delay-dependencies of the various iodine charge states, from which critical internuclear distances for charge transfer could be inferred and compared to a classical over-the-barrier model. Time-dependent photofragment angular anisotropy parameters were extracted from the central slice of the Newton sphere, without Abel inversion, and highlight the effect of rotation of the parent molecule before dissociation, as observed in previous © 2020 The Author(s). Published by IOP Publishing Ltd Printed in the U

Solo Sonographically Guided PCNL under Spinal Anesthesia: Defining Predictors of Success

Aim. Sonography has been brought in percutaneous nephrolithotripsy (PCNL) as an adjunct to or substitute for X-ray to restrict radiation exposure. Tis study was designed to investigate the possible predictors for the success of the solo sonographically guided PCNL. Methods. 148 consecutive cases were prospectively enrolled. All steps of PCNL were performed solely with sonography guidance under spinal anesthesia. Residual stones were evaluated the day afer surgery using sonography and plain radiography. Results. Te mean age was 46 ± 15 years; 40% of kidneys had hydronephrosis. Te mean stone burden was 504 ± 350 mm2. Te mean duration of surgery was 43 ± 21 minutes. Te early stone-free rate was 92% in inferior or middle calyceal stones, 89.5% in single pelvic stones, 81.5% in partial staghorn stones, and 61.9% in staghorn stones. Te mean residual stone size was 13 ± 8 mm. Logistic regression showed that a lower age and a larger stone burden signifcantly predicted positive residual stones. Fifeen percent of patients presented with grade I or II and six percent showed grade III complication based on Clavien classifcation. Tere was no cases of organ injury or death. Conclusion. Solo ultrasonographically guided PCNL under spinal anesthesia is feasible with an acceptable stone-free rate and complication rate

Multi-channel photodissociation and XUV-induced charge transfer dynamics in strong-field-ionized methyl iodide studied with time-resolved recoil-frame covariance imaging

The photodissociation dynamics of strong-field ionized methyl iodide (CH3I) were probed using intense extreme ultraviolet (XUV) radiation produced by the SPring-8 Angstrom Compact free electron LAser (SACLA). Strong-field ionization and subsequent fragmentation of CH3I was initiated by an intense femtosecond infrared (IR) pulse. The ensuing fragmentation and charge transfer processes following multiple ionization by the XUV pulse at a range of pump–probe delays were followed in a multi-mass ion velocity-map imaging (VMI) experiment. Simultaneous imaging of a wide range of resultant ions allowed for additional insight into the complex dynamics by elucidating correlations between the momenta of different fragment ions using time-resolved recoil-frame covariance imaging analysis. The comprehensive picture of the photodynamics that can be extracted provides promising evidence that the techniques described here could be applied to study ultrafast photochemistry in a range of molecular systems at high count rates using state-of-the-art advanced light sources.</p

Novel Synthesis of <i>N</i>-Acetylcysteine Medicine Using an Effective Method

N-acetylcysteine (NAC) is mainly administrated as a mucolytic medication, antioxidant supplement, antidote in paracetamol overdose, and a drug for the prevention of diabetic kidney disease. Its effect has been investigated for the treatment of several diseases such as COVID-19. In this work, an effective method for high-yield synthesis of N-acetylcysteine is proposed. This drug can be synthesized in a single-batch step instead of using a multi-stage process. The proposed method has shown the potential to be considered as an alternative method for producing NAC. The purification process was carried out using suitable solvents to reach a high level of purity. The characterization of the synthesized drug was undertaken through Elemental analysis, Proton Nuclear Magnetic Resonance (1H NMR), High Performance Liquid Chromatography (HPLC), Fourier Transform Infrared Spectroscopy (FT-IR), and melting point analyses

Engineering self-assembling peptide hydrogels for pluripotent stem cell and cardiac organoid culture

Human pluripotent stem cells (hPSCs) hold enormous potential in cell biology research, drug discovery, and regenerative medicine due to their unique characteristics, such as self-renewal and differentiation into multiple cell lineages. Additionally, over the past decade, stem cell-derived organoids have gained extensive attention as promising models for organ development, disease modelling, and drug discovery. However, the current hPSCs expansion and differentiation, and organoid generation protocols rely on feeder cells or complex and poorly-defined animal-derived matrices. These matrices have hindered the applicability of hPSCs and stem cell-derived organoids in pre-clinical and clinical applications, which is one of the most pressing challenges in stem cell research. Thus, there is an urgent need to develop fully-defined and xeno-free substrates for stem cell expansion and differentiation. This work aims to design a biomaterial platform that supports human embryonic stem cells and cardiac organoid cultures. Moreover, we aim to develop a strategy to investigate the biochemical and biophysical cues required for stem cell-matrix interactions. To accomplish this, a novel library of short self-assembling peptides containing a range of integrin-binding ligands inspired by fibronectin, collagen, and laminin was developed. This class of biomimetic material has great potential for chemical and physical modifications aiming to better mimic the extracellular matrix (ECM). The chemical verification and physical characterisation of peptide sequences were performed, followed by morphology assessment resulting in nanofibrous networks resembling the ECM. Next, the role of peptide sequences in human embryonic stem cell (hESCs) behaviour in maintenance culture was explored. Cell adhesion, viability, and morphology were examined in 2D and 3D cultures. Even though these peptide matrices could not be employed for long-term hESCs maintenance culture, the results enhanced our understanding of integrin-ligand interactions in human embryonic stem cell culture. Furthermore, the developed self-assembling peptide hydrogels were screened as a potential matrix for cardiac organoid generation, growth, and function. The obtained data revealed that the fibronectin-derived and laminin-derived composite hydrogel resulted in greater human cardiac organoids development and function across all compositions. In conclusion, this study contributed to our knowledge about the complex stem cell-matrix interactions by employing self-assembling peptides with the incorporation of one or more inherent bioactive motifs of a native protein. In this study, the fibronectin and laminin motifs, RGD and YIGSR, respectively, contributed more to support human embryonic stem cells in maintenance culture as well as cardiac organoid formation, growth, and function. This biomaterial development strategy is promising for the next generation of well-defined and tailored matrices for stem cell and organoid technology

Collagen as Adherent Substratum and Inducer of Dorsal Root Ganglia Outgrowth

ABSTRACT Neurite outgrowth from dorsal root ganglion (DRG) explants is a method of evaluating neurotrophic activity of growth factors. When complete medium containing collagen was supplemented with nerve growth factor (NGF) DRG outgrowth was observed after 18 h. In the absence of NGF and in the presence of collagen, the DRG outgrowth took place after 72 h. In wells not supplemented with collagen gel in substratum, no DRG outgrowth was observed. Partially, DRG differentiation was observed in the presence of NGF. In the absence of NGF and collagen, there was no DRG outgrowth detected. It seems that, in some circumstances, cells degenerated by DRG may be an indication of an apoptosis phenomenon. Therefore, we suggested that collagen as a substratum is more effective than NGF