Coulomb explosion imaging and covariance analysis of concurrent fragmentation mechanisms

This thesis uses Coulomb explosion imaging and covariance analysis to characterise concurrent fragmentation processes generating identical sets of products via different reaction pathways, highlighting the potential of extending these methods to study the photochemistry of larger, more chemically relevant species than those that have previously been studied. The photodissociation dynamics of CH2I2 at 202.5 nm were investigated using site-selective ionisation at the I 4d orbitals using photons of 95 eV. A concerted three-body dissociation process was assigned using charge transfer features and time-dependent covariance. Dynamic changes to the C-I internuclear distances and I-C-I bond angle were characterised, demonstrating the potential of Coulomb explosion imaging to simultaneously map potential energy surfaces of reaction dynamics along multiple degrees of freedom. Site-selective ionisation of 1- and 2-iodopropane at the I 4d orbitals was carried out using photons of 95 eV. Modified three-dimensional momentum covariance analysis techniques were used to disentangle fragmentation processes generating the same sets of products as well as the individual steps of multi-step fragmentation mechanisms. Observable isomeric differences demonstrated the sensitivity of individual fragmentation processes, and the corresponding nuclear dynamics, to the geometry and charge distribution of the parent polycation species. Iodobenzene was site-selectively ionised at the I 4d orbitals using photons of 120 eV, and valence-shell ionisation was also conducted using 800 nm laser pulses. Covariance analysis techniques were employed to analyse the range of products generated from stable and metastable phenyl cations and polycations, demonstrating how concurrent fragmentation processes generating long-lived species in lowly-charged cationic states can be characterised. Valence-shell ionisation could initially ionise more atomic sites than just iodine, leading to fragmentation channels that were not observed with site-selective, inner-shell ionisation. Both ionisation regimes generated similar sets of products but on different relative timescales due to initially populating different electronic excited states. Each ionisation regime results in many observable fragmentation processes, but photoelectron information is required to relate specific fragmentation channels to specific ionisation and charge generation/redistribution processes

Characterizing the multi-dimensional reaction dynamics of dihalomethanes using XUV-induced Coulomb explosion imaging

Site-selective probing of iodine 4d orbitals at 13.1 nm was used to characterize the photolysis of CH2I2 and CH2BrI initiated at 202.5 nm. Time-dependent fragment ion momenta were recorded using Coulomb explosion imaging mass spectrometry and used to determine the structural dynamics of the dissociating molecules. Correlations between these fragment momenta, as well as the onset times of electron transfer reactions between them, indicate that each molecule can undergo neutral three-body photolysis. For CH2I2, the structural evolution of the neutral molecule was simultaneously characterized along the C-I and I-C-I coordinates, demonstrating the sensitivity of these measurements to nuclear motion along multiple degrees of freedom

Disentangling sequential and concerted fragmentations of molecular polycations with covariant native frame analysis

Using covariance analysis methods, we study the fragmentation dynamics of multiply ionized 1- and 2-iodopropane. Signatures of isomer-specific nuclear motion occurring during sequential fragmentation pathways are identified.</jats:p

Direct momentum imaging of charge transfer following site-selective ionization

We study ultrafast charge rearrangement in dissociating 2-iodopropane (2−C3H7I) using site-selective core ionization at the iodine atom. Clear signatures of electron transfer between the neutral propyl fragment and multiply charged iodine ions are observed in the recorded delay-dependent ion momentum distributions. The detected charge-transfer pathway is only favorable within a small (few angstroms), charge-state-dependent spatial window located at C-I distances longer than that of the neutral ground-state molecule. These results offer insights into the physics underpinning charge transfer in isolated molecules and pave the way for a different class of time-resolved studies

Disentangling sequential and concerted fragmentations of molecular polycations with covariant native frame analysis

We present results from an experimental ion imaging study into the fragmentation dynamics of 1-iodopropane and 2-iodopropane following interaction with extreme ultraviolet intense femtosecond laser pulses with a photon energy of 95 eV. Using covariance imaging analysis, a range of observed fragmentation pathways of the resulting polycations can be isolated and interrogated in detail at relatively high ion count rates (∼12 ions shot−1). By incorporating the recently developed native frames analysis approach into the three-dimensional covariance imaging procedure, contributions from three-body concerted and sequential fragmentation mechanisms can be isolated. The angular distribution of the fragment ions is much more complex than in previously reported studies for triatomic polycations, and differs substantially between the two isomeric species. With support of simple simulations of the dissociation channels of interest, detailed physical insights into the fragmentation dynamics are obtained, including how the initial dissociation step in a sequential mechanism influences rovibrational dynamics in the metastable intermediate ion and how signatures of this nuclear motion manifest in the measured signals.</p

The role of momentum partitioning in covariance ion imaging analysis

We present results from a covariance ion imaging study, which employs extensive filtering, on the relationship between fragment momenta to gain deeper insight into photofragmentation dynamics. A new data analysis approach is introduced that considers the momentum partitioning between the fragments of the breakup of a molecular polycation to disentangle concurrent fragmentation channels, which yield the same ion species. We exploit this approach to examine the momentum exchange relationship between the products, which provides direct insight into the dynamics of molecular fragmentation. We apply these techniques to extensively characterize the dissociation of 1-iodopropane and 2-iodopropane dications prepared by site-selective ionization of the iodine atom using extreme ultraviolet intense femtosecond laser pulses with a photon energy of 95 eV. Our assignments are supported by classical simulations, using parameters largely obtained directly from the experimental data

The role of momentum partitioning in covariance ion imaging analysis

We present results from a covariance ion imaging study, which employs extensive filtering, on the relationship between fragment momenta to gain deeper insight into photofragmentation dynamics. A new data analysis approach is introduced that considers the momentum partitioning between the fragments of the breakup of a molecular polycation to disentangle concurrent fragmentation channels, which yield the same ion species. We exploit this approach to examine the momentum exchange relationship between the products, which provides direct insight into the dynamics of molecular fragmentation. We apply these techniques to extensively characterize the dissociation of 1-iodopropane and 2-iodopropane dications prepared by site-selective ionization of the iodine atom using extreme ultraviolet intense femtosecond laser pulses with a photon energy of 95 eV. Our assignments are supported by classical simulations, using parameters largely obtained directly from the experimental data

PTEN loss mediates clinical cross-resistance to CDK4/6 and PI3Kα inhibitors in breast cancer

The combination of CDK4/6 inhibitors with anti-estrogen therapies significantly improves clinical outcomes in ER-positive advanced breast cancer. To identify mechanisms of acquired resistance, we analyzed serial biopsies and rapid autopsies from patients treated with the combination of the CDK4/6 inhibitor ribociclib with letrozole. This study revealed that some resistant tumors acquired RB loss, whereas other tumors lost PTEN expression at the time of progression. In breast cancer cells ablation of PTEN, through increased AKT activation, was sufficient to promote resistance to CDK4/6 inhibition in vitro and in vivo. Mechanistically, PTEN loss resulted in exclusion of p27 from the nucleus, leading to increased activation of both CDK4 and CDK2. Since PTEN loss also causes resistance to PI3Kalpha-inhibitors, currently approved in the post-CDK4/6 setting, these findings provide critical insight into how this single genetic event may cause clinical cross-resistance to multiple targeted therapies in the same patient, with implications for optimal treatment sequencing strategies

Characterizing the multi-dimensional reaction dynamics of dihalomethanes using XUV-induced Coulomb explosion imaging

Site-selective probing of iodine 4d orbitals at 13.1 nm was used to characterize the photolysis of CH$_2$I$_2$ and CH$_2$BrI initiated at 202.5 nm. Time-dependent fragment ion momenta were recorded using Coulomb explosion imaging mass spectrometry and used to determine the structural dynamics of the dissociating molecules. Correlations between these fragment momenta, as well as the onset times of electron transfer reactions between them, indicate that each molecule can undergo neutral three-body photolysis. For CH$_2$I$_2$, the structural evolution of the neutral molecule was simultaneously characterized along the C–I and I–C–I coordinates, demonstrating the sensitivity of these measurements to nuclear motion along multiple degrees of freedom