Browsing by Subject "Physical chemistry"
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Item Open Access A Covalent Modification Technique for Protein-Ligand Binding Analysis Using Mass Spectrometry-Based Proteomics Platforms(2009) West, Graham MeldahlCurrently there is a dearth of analytical techniques for studying protein-ligand interactions on the proteomic scale. Existing techniques, which rely on various calorimetry or spectroscopy methods, are limited in their application to the proteomic scale due to their need for large amounts of pure protein. Recently, several mass spectrometry-based methods have been developed to study protein-ligand interactions. These mass spectrometry-based methods overcome some of the limitations of existing techniques by enabling the analysis of unpurified protein samples. However, the existing mass spectrometry-based methodologies for the analysis of protein-ligand binding interactions are not directly compatible with current mass spectrometry-based proteomics platforms.
Described here is the development and application of a new technique designed to detect and quantify protein-ligand binding interactions with mass spectrometry-based proteomic platforms. This technique, termed SPROX (Stability of Proteins from Rates of Oxidation), uses an irreversible covalent oxidation labeling reaction to monitor the global unfolding reactions of proteins to measure protein thermodynamic stability. Two variations of the SPROX technique are established here, including one variation that utilizes chemical denaturant to induce protein unfolding and a second variation that utilizes temperature to denature proteins. The SPROX methodology is tested on five proteins including ubiquitin, ribonuclease A, bovine carbonic anhydrase II, cyclophilin A, and calmodulin. Results obtained on these model systems are used to determine the method's ability to measure the thermodynamic parameters associated with each protein's folding/unfolding reaction. Results obtained on calmodulin and cyclophilin A are used to determine the method's ability to quantify the dissociation constants of protein-ligand complexes.
The primary motivation for the development of the SPROX protocols in this work was to create a protein-ligand binding assay that could be interfaced with conventional mass spectrometry-based platforms. Two specific SPROX protocols, including a label-free approach and an oxygen-16/18 labeling approach, are developed and demonstrated using the thermal SPROX technique to analyze ligand binding in a model four-protein component mixture consisting of ubiquitin, ribonuclease A, bovine carbonic anhydrase, and cyclophilin A. The thermal SPROX technique's ability to detect cyclosporin A binding to cyclophilin A in the context of the model mixture is shown using both labeling approaches.
An application using the SPROX technique combined with a multi-dimensional protein identification technology (MudPIT)-based proteomics platform is also described. In this application, which utilized an isobaric mass tagging strategy, 325 proteins in a yeast cell lysate are simultaneously assayed for CsA-binding. This study was also used to investigate the protein targets of an already well-studied immunosuppressive drug, cyclosporin A. Two of the ten protein targets identified in this work are known to interact with CsA, one through a direct binding event and one through an indirect binding event. The eight newly discovered protein targets of CsA suggest a molecular basis for post-transplant diabetes mellitus, which is a side effect of CsA in humans.
Item Open Access Advances in Forces Fields for Small Molecules, Water and Proteins: from Polarization to Neural Network(2018) Wang, HaoMolecular dynamics (MD) simulations is an invaluable tool to investigate chemical and biological processes in atomic details. The accuracy of MD simulations strongly depends on underlying force fields. In conventional molecular mechanics (MM) force fields, the total energy is divided into bond energy, angle energy, dihedral energy, electrostatic interactions and van der Waals interactions. Each of these energy terms is parameterized by fitting to either experimental data or quantum mechanical (QM) calculations. In this dissertation, our aim is to develop accurate force fields for small molecules, water and proteins fully from QM calculations of small fragments. In the framework of conventional MM force fields, we calculated both transferable and molecule-specific atomic polarizabilities of small molecules by electrostatic potential fitting. Atomic polarizabilities are the key physical quantities in induced dipole polarization model. Molecular polarizabilities recovered from our atomic polarizabilities show good agreement with those obtained from QM calculations. We believe the main limitation of conventional MM force fields is the limited form of its Hamiltonian. Going beyond conventional MM force fields, we adopt the many-body expansion method and residue-based systematic molecular fragmentation (rSMF) method to start afresh building force fields for water and proteins, respectively. We used electrostatically embedded two-body expansion as the Hamiltonian of bulk water. QM reference of electrostatically embedded water monomer and dimer at the level of CCSD/aug-cc-pVDZ are parameterized by neural network (NN). Compared with experimental results, our water force fields show good structural and dynamical properties of bulk water. We developed rSMF to partition general proteins into twenty amino acid dipeptides and one peptide bond. The total energy of proteins is the combination of the energy of these small fragments. The QM reference energy of each fragment is parameterized by NN. Our protein force fields compare favorably with full QM calculations for both homogeneous and heterogeneous polypeptides in terms of energy and force errors.
Item Open Access Advances in Real-time 3D Single Particle Tracking Microscopy for Particle-by-Particle In-Situ Characterization of the Nanoparticle Protein Corona(2022) Tan, XiaochenSingle-molecule spectroscopic (SMS) measurements have revolutionized biological science due to their ability to directly observe exactly one molecule in the crowd. This single molecule observation removes the ensemble average, revealing molecular heterogeneities. However, traditional SMS techniques fail to study single molecules in the solution phase for a long observation time, because the molecules rapidly diffuse away from the small focal spot. Accordingly, it is typically required to isolate the molecules from the native solution to study time-dependent dynamical behaviors, by either tethering the molecules to a stationary surface or confining the molecules in a small space based on physical principles. This isolation of molecules barricades in-situ and in-vivo single-molecule research. To address this gap, real-time feedback single particle tracking (RT-3D-SPT) has been developed, with the ability to directly monitor individual freely diffusing particles in the solution phase less disruptively. Real-time tracking is realized by estimating the particle’s position using photon information and applying active feedback to keep the particle in a small detection center. This set of techniques is largely divided into two classes, each with its limitations. The first class of RT-3D-SPT techniques spatially separates the emission of the particle using a set of detectors. The signal variation detected by these detectors can be used to estimate the particle’s position in real-time. The second class of RT-3D-SPT uses a spatiotemporally patterned laser excitation to illuminate the particle. The detected photon arrivals can therefore be used to estimate the particle’s position within the dynamic laser excitation pattern. A feedback control actuator such as a scanning mirror or a piezoelectric stage is driven to compensate for the particle’s diffusion in real-time, keeping the particle in the focal volume. However, both methods have limited ability to track dim and fast diffusing objects, such as single molecules. Moreover, very few of these optical configurations provide simultaneous contextualization in three dimensions yet fail to observe rapid processes happening in the surrounding of the tracked objects.In this dissertation, we present a new real-time 3D tracking and imaging method to directly observe fast biological and chemical processes. These processes include the rapid protein adsorption onto nanoparticles when the nanoparticles are exposed to biological fluids. This adsorbed protein layer, called the protein corona, alters nanoparticles’ biological identity and their fate in vivo. Therefore, it is important to understand this critical roadblock in the biological application of engineered nanoparticles. Herein, we first introduce the construction of this microscope, called 3D real-time ultrafast local microscopy (3D-RULM), with its ability to track fast diffusing and lowly emitting objects while rapidly imaging the surroundings concurrently. Next, we show this RT-3D-SPT method can be applied to quantitatively characterize individual nanoparticle protein corona in situ particle by particle, with single protein sensitivity at signal-to-background ratios down to 1%. Finally, to expand this method to smaller NP-protein systems, we have further implemented a Galvo mirror as a control actuator with a response time five times faster than the currently used piezoelectric stage, opening the possibility to study transient NP-protein interactions and other fast biological phenomena in situ and in vivo.
Item Open Access Aqueous Desolvation and Molecular Recognition: Experimental and Computational Studies of a Novel Host-Guest System Based on Cucurbit[7]uril(2012) Wang, YiMolecular recognition is arguably the most elementary physical process essential for life that arises at the molecular scale. Molecular recognition drives events across virtually all length scales, from the folding of proteins and binding of ligands, to the organization of membranes and the function of muscles. Understanding such events at the molecular level is massively complicated by the unique medium in which life occurs: water. In contrast to recognition in non-aqueous solvents, which are driven largely by attractive interactions between binding partners, binding reactions in water are driven in large measure by the properties of the medium itself. Aqueous binding involves the loss of solute-solvent interactions (desolvation) and the concomitant formation of solute-solute interactions. Despite decades of research, aqueous binding remains poorly understood, a deficit that profoundly limits our ability to design effective pharmaceuticals and new enzymes. Particularly problematic is understanding the energetic consequences of aqueous desolvation, an area the Toone and Beratan groups have considered for many years.
In this dissertation, we embark on a quest to shed new light on aqueous desolvation from two perspectives. In one component of this research, we improve current computational tools to study aqueous desolvation, employing quantum mechanics (QM), molecular dynamics (MD) and Monte Carlo (MC) simulations to better understand the behavior of water near molecular surfaces. In the other, we use a synthetic host, cucurbit[7]uril (CB[7]), in conjunction with a de novo series of ligands to study the structure and thermodynamics of aqueous desolvation in the context of ligand binding with atomic precision, a feat hitherto impossible. A simple and rigid macrocycle, CB[7] alleviates the drawbacks of protein systems for the study of aqueous ligand binding, that arise from conformational heterogeneity and prohibitive computational costs to model.
We first constructed a novel host-guest system that facilitates internalization of the trimethylammonium (methonium) group from bulk water to the hydrophobic cavity of CB[7] with precise (atomic-scale) control over the position of the ligand with respect to the cavity. The process of internalization was investigated energetically using isothermal titration microcalorimetry and structurally by nuclear magnetic resonance (NMR) spectroscopy. We show that the transfer of methonium from bulk water to the CB[7] cavity is accompanied by an unfavorable desolvation enthalpy of just 0.49±0.27 kcal*mol-1, a value significantly less endothermic than those values suggested from previous gas-phase model studies. Our results offer a rationale for the wide distribution of methonium in biology and demonstrate important limitations to computational estimates of binding affinities based on simple solvent-accessible surface area approaches.
To better understand our experimental results, we developed a two-dimensional lattice model of water based on random cluster structures that successfully reproduces the temperature-density anomaly of water with minimum computational cost. Using reported well-characterized ligands of CB[7], we probed water structure within the CB[7] cavity and identified an energetically perturbed cluster of water. We offer both experimental and computational evidence that this unstable water cluster provides a significant portion of the driving force for encapsulation of hydrophobic guests.
The studies reported herein shed important light on the thermodynamic and structural nature of aqueous desolvation, and bring our previous understanding of the hydrophobic effect based on ordered water and buried surface area into question. Our approach provides new tools to quantify the thermodynamics of functional group desolvation in the context of ligand binding, which will be of tremendous value for future research on ligand/drug design.
Item Open Access Caging and Transport in Simple Disordered Systems(2021) Hu, YiRecent advances on the glass problem motivate reexamining classical models of caging and transport. In particular, seemingly incompatible percolation and mean-field caging descriptions on the localization transition call for better understanding both. In light of this fundamental inconsistency, we study the caging and transport of a series of simple disordered systems.
We first consider the dynamics of site percolation on hypercubic lattices. Using theory and simulations, we obtain that both caging and subdiffusion scale logarithmically for dimension d ≥ d_u, the upper critical dimension of percolation. The theoretical derivation on Bethe lattice and a random graph confirm that logarithmic scalings should persist in the limit d→∞. The computational validation evaluates directly the dynamical critical exponents below d_u as well as their logarithmic scaling above d_u. Our numerical results improve various earlier estimates and are fully consistent with our theoretical predictions.
Recent implementation of efficient simulation algorithms for high-dimensional systems also facilitates the study of dense packing lattices beyond the conventional hypercubic ones. Here, we consider the percolation problem on checkerboard D_d lattices and on E_8 relatives for d=6 to 9. Precise estimates for both site and bond percolation thresholds obtained from invasion percolation simulations are compared with dimensional series expansion based on lattice animal enumeration for D_d lattices. As expected, the bond percolation threshold rapidly approaches the Bethe lattice limit as d increases for these high-connectivity lattices. Corrections, however, exhibit clear yet unexplained trends.
The random Lorentz gas (RLG) is a minimal model for transport in disordered media. Despite the broad relevance of the model, theoretical grasp over its properties remains weak. Here, we first extend analytical expectations for asymptotic high-d bounds on the void percolation threshold, and then computationally evaluate both the threshold and its criticality in various d. A simple modification of the RLG is found to bring the mean-field-like caging down to d=3.
The RLG also provides a toy model of particle caging, which is known to be relevant for describing the discontinuous dynamical transition of glasses. Following the percolation studies, we consider its exact mean-field solution in the d→∞ limit and perform simulation in d=2...20. We find that for sufficiently high d the mean-field caging transition precedes and prevents the percolation transition, which only happens on timescales diverging with d. This perturbative correction is associated with the cage heterogeneity. We further show that activated processes related to rare cage escapes destroy the glass transition in finite dimensions, leading to a rich interplay between glassiness and percolation physics. This advance suggests that the RLG can be used as a toy model to develop a first-principle description of particle hopping in structural glasses.
While the cages in the RLG are formed by non-interacting obstacles, cage structure is important for the hopping process in three-dimensional glasses. As a final note and also a future direction, a study on the three-dimensional polydisperse hard spheres with modification, named as the Mari-Kurchan-Krzakala (MKK) model was proposed. This consideration provides a controllable way to interpolate between the mean-field and the real space glasses. These insights help chart a path toward a complete description of finite-dimensional glasses.
Item Open Access Computational Study of Low-friction Quasicrystalline Coatings via Simulations of Thin Film Growth of Hydrocarbons and Rare Gases(2008-04-25) Setyawan, WahyuQuasicrystalline compounds (QC) have been shown to have lower friction compared to other structures of the same constituents. The abscence of structural interlocking when two QC surfaces slide against one another yields the low friction. To use QC as low-friction coatings in combustion engines where hydrocarbon-based oil lubricant is commonly used, knowledge of how a film of lubricant forms on the coating is required. Any adsorbed films having non-quasicrystalline structure will reduce the self-lubricity of the coatings. In this manuscript, we report the results of simulations on thin films growth of selected hydrocarbons and rare gases on a decagonal Al$_{73}$Ni$_{10}$Co$_{17}$ quasicrystal (d-AlNiCo). Grand canonical Monte Carlo method is used to perform the simulations. We develop a set of classical interatomic many-body potentials which are based on the embedded-atom method to study the adsorption processes for hydrocarbons. Methane, propane, hexane, octane, and benzene are simulated and show complete wetting and layered films. Methane monolayer forms a pentagonal order commensurate with the d-AlNiCo. Propane forms disordered monolayer. Hexane and octane adsorb in a close-packed manner consistent with their bulk structure. The results of hexane and octane are expected to represent those of longer alkanes which constitute typical lubricants. Benzene monolayer has pentagonal order at low temperatures which transforms into triangular lattice at high temperatures. The effects of size mismatch and relative strength of the competing interactions (adsorbate-substrate and between adsorbates) on the film growth and structure are systematically studied using rare gases with Lennard-Jones pair potentials. It is found that the relative strength of the interactions determines the growth mode, while the structure of the film is affected mostly by the size mismatch between adsorbate and substrate's characteristic length. On d-AlNiCo, xenon monolayer undergoes a first-order structural transition from quasiperiodic pentagonal to periodic triangular. Smaller gases such as Ne, Ar, Kr do not show such transition. A simple rule is proposed to predict the existence of the transition which will be useful in the search of the appropriate quasicrystalline coatings for certain oil lubricants. Another part of this thesis is the calculation of phase diagram of Fe-Mo-C system under pressure for studying the effects of Mo on the thermodynamics of Fe:Mo nanoparticles as catalysts for growing single-walled carbon nanotubes (SWCNTs). Adding an appropriate amount of Mo to Fe particles avoids the formation of stable binary Fe$_3$C carbide that can terminate SWCNTs growth. Eventhough the formation of ternary carbides in Fe-Mo-C system might also reduce the activity of the catalyst, there are regions in the Fe:Mo which contain enough free Fe and excess carbon to yield nanotubes. Furthermore, the ternary carbides become stable at a smaller size of particle as compared to Fe$_3$C indicating that Fe:Mo particles can be used to grow smaller SWCNTs.Item Open Access Control and Characterization of Electron Transfer with Vibrational Excitations(2018) Ma, ZhengThe interactions between electronic dynamics and the molecular vibrations in a donor-‐‑bridge-‐‑acceptor (DBA) structure lie at the core of electron transfer (ET) reactions mechanisms. Aiming to control and characterize ET reactions via vibrational excitations of molecular modes, in this thesis, we discuss three aspects of the interplay between ET and nuclear vibrations and the charge transfer in transition metal complex compounds.
First, a theoretical framework is established to explore how transient infra-‐‑red (IR) excitation perturbs ET kinetics and dynamics in DBA systems. Recent experiments find that IR excitation can change ET rates and can even change the relative dominance of ET and competing reactions. A comprehensive theoretical framework is formulated to describe IR-‐‑perturbed nonadiabatic ET reactions, including the effects of IR-‐‑induced non-‐‑ equilibrium initial state populations and IR-‐‑perturbed bridge-‐‑mediated couplings. We find that these effects can produce either rate slowing or acceleration, depending on structural and energetic features of the bridge. The framework is used to interpret the origins of the observed rate slowing of charge separation and to predict rate acceleration for charge recombination in a DBA structure, and to describe the microscopic origins.
Second, a non-‐‑equilibrium molecular dynamics (NEqMD) computational methodology is employed to explore how the molecular underpinnings of how vibrational excitation may influence non-‐‑adiabatic electron-‐‑transfer. NEqMD combines classical molecular dynamics simulations with nonequilibrium semiclassical initial conditions to simulate the dynamics of vibrationally excited molecules. We combine NEqMD with electronic structure computations of bridge-‐‑mediated donor-‐‑acceptor couplings to probe IR effects on electron transfer in two molecular species: dimethylaniline-‐‑guanosine-‐‑cytidine-‐‑anthracene (DMA-‐‑GC-‐‑Anth) ensemble and 4-‐‑ (pyrrolidin-‐‑1-‐‑yl)phenyl-‐‑2,6,7-‐‑triazabicyclo[2,2,2]octatriene-‐‑10-‐‑cyanoanthracen-‐‑9-‐‑yl structure (PP-‐‑BCN-‐‑CA). In DMA-‐‑GC-‐‑Anth, the simulations find that IR excitation of NH2 scissoring motion, and subsequent intramolecular vibrational energy redistribution (IVR) do not significantly alter the mean-‐‑squared DA coupling interaction. This finding is consistent with earlier static system analysis. In PP-‐‑BCN-‐‑CA, IR excitation of the bridging C=N bond changes the bridge-‐‑mediated coupling for charge separation and recombination by ~ 30 -‐‑ 40%. These methods provide an approach to exploring out of equilibrium molecular dynamics may impact charge transfer processes at the molecular scale.
In addition, we explore the feasibility of using transient 2D-‐‑IR spectroscopy for examining elastic and inelastic ET pathway in DBA systems. Bridge-‐‑mediated electron transfer interactions depend upon the quantum interferences of amplitude propagating through the bridge. The nature of these interferences is different for elastic and inelastic electron transfer. Hence, it is of great interest to develop methods that may distinguish between elastic and inelastic transport mechanisms. We show that it is feasible to use 2D-‐‑IR spectroscopy to assess the contribution of inelastic tunneling channels to bridge-‐‑ mediated electron transfer. 2D-‐‑IR spectra were simulated using simple 3-‐‑state/2-‐‑mode models. We identified 2D-‐‑IR spectral features that distinguish elastic and inelastic charge transfer. DBA systems with ET time scales that are shorter than the vibrational relaxation time scale should allow detection of these features. We also propose to use the change of peak volumes [J. Phys. Chem. B 2006, 110, 19998-‐‑20013] caused by varying waiting-‐‑times between the second and third IR pulses in the 2D-‐‑IR pulse sequence to estimate the rates of electron transfer via elastic or inelastic mechanisms.
Finally, quantum chemistry characterization of charge transfer reactions in Rhenium complex compounds and the IR-‐‑induced rate modulation mechanism are discussed. Electronic structure calculations and normal mode analysis indicates that in rhenium-‐‑centered complex compounds, IR-‐‑induced donor-‐‑acceptor energy gap change modulates the charge transfer rates.
Item Open Access Control of Surface Plasmon Substrates and Analysis of Near field Structure(2011) Chen, Shiuan-YehThe electromagnetic properties of various plasmonic nanostructures are investigated. These nanostructures, which include random clusters, controlled clusters and particle-film hybrids are applied to surface-enhanced Raman scattering (SERS). A variety of techniques are utilized to fabricate, characterize, and model these SERS-active structures, including nanoparticle functionalization, thin film deposition, extinction spectroscopy, elastic scattering spectroscopy, Raman scattering spectroscopy, single-assembly scattering spectroscopy, transmission electron microscopy, generalized Mie theory, and finite element method.
Initially, the generalized Mie theory is applied to calculate the near-field of the small random clusters to explain their SERS signal distribution. The nonlinear trend of SERS intensity versus size of clusters is demonstrated in experiments and near-field simulations.
Subsequently, controlled nanoparticle clusters are fabricated for quantitative SERS. A 50 nm gold nanoparticle and 20nm gold nanoparticles are tethered to form several hot spots between them. The SERS signal from this assembly is compared with SERS signals from single particles and the relative intensities are found to be consistent with intensity ratios predicted by near-field calculation.
Finally, the nanoparticle/film hybrid structure is studied. The scattering properties and SERS activity are observed from gold nanoparticles on different substrates. The gold nanoparticle on gold film demonstrates high field enhancement. Raman blinking is observed and implies a single molecule signal. Furthermore, the doughnut shape of Raman images indicates that this hybrid structure serves as nano-antenna and modifies the direction of molecular emission.
In additional to the primary gap dipole utilized for SERS, high order modes supported by the nanoparticle/film hybrid also are investigated. In experiments, the HO mode show less symmetry compared to the gap dipole mode. The simulation indicates that the HO modes observed may be comprised of two gap modes. One is quadrupole-like and the other is dipole-like in terms of near-field profile. The analytical treatment of the coupled dipole is performed to mimic the imaging of the quadrupole radiation.
Item Open Access Density Functional and Ab Initio Study of Molecular Response(2014) Peng, DegaoQuantum chemistry methods nowadays reach its maturity with various robust ground state correlation methods. However, many problems related to response do not have satisfactory solutions. Chemical reactivity indexes are some static response to external fields and number of particle change. These chemical reactivity indexes have important chemical significance, while not all of them had analytical expressions for direct evaluations. By solving coupled perturbed self-consistent field equations, analytical expressions were obtained and verified numerically. In the particle-particle (pp) channel, the response to the pairing field can describe N±2 excitations, i.e. double ionization potentials and double electron affinities. The linear response time-dependent density-functional theory (DFT) with pairing fields is the response theory in the density-functional theory (DFT) framework to describe $N\pm 2$ excitations. Both adiabatic and dynamic kernels can be included in this response theory. The correlation energy based on this response, the correlation energy of the particle-particle random phase approximation (pp-RPA), can also be proved equivalent to the ladder approximation of the well-established coupled-cluster doubles. These connections between the response theory, ab initio methods, and Green's function theory would be beneficial for further development. Based on RPA and pp-RPA, the theory of second RPA and the second pp-RPA with restrictions can be used to capture single and double excitations efficiently. We also present a novel methods, variational fractional spin DFT, to calculate singlet-triplet energy gaps for diradicals, which are usually calculated through spin-flip response theories.
Item Open Access Deposition of Nano-scale Particles in Aqueous Environments --Influence of Particle Size, Surface Coating, and Aggregation State(2012) Lin, ShihongThis work considers the transport and attachment of nanoscale particles to surfaces and the associated phenomena that dictate particle-surface interactions. A consideration of the deposition of nano-scale particles on surfaces is a natural outgrowth of more than a century of research in the area of colloid science, and has taken on new pertinence in the context of understanding the fate and transport of engineered nanoparticles in aqueous environments. More specifically, the goal of this work is to better understand the effects of particle size, surface polymer coatings, and aggregation state on the kinetics of nanoparticle deposition. Theoretical tools such as those developed by Derjaguin-Landau-Verwey-Overbeek (DLVO) and Flory-Krigbaum , as well as the soft particle theory and surface element integration scaling methods are employed to address certain problems that were not considered with the existing theoretical frameworks for the conventional colloidal problems. Consequences of theoretical predictions are evaluated experimentally using column experiments or the quartz crystal microbalance techniques to monitor deposition kinetics. One of the key findings of this work is the observation that polymer coatings may stabilize nanoparticles against deposition or increase deposition, depending on whether the polymer coatings exist on both of the interacting surfaces and the interaction between the polymer and the collector surface. Both steric and bridging mechanisms are possible depending on whether contact between the polymer and collector surface can result in successful attachment. In addition, limitations in the use of conventional, equilibrium-based DLVO theory to describe the deposition of nano-scale particles at very low ionic strength are also identified and discussed. Moreover, it is demonstrated that the interaction between the aggregated nano-scale particles and environmental surfaces is controlled by the characteristic size of the primary particles rather than that of the aggregates. Thus despite an increase in hydrodynamic diameter, aggregation is predicted to reduce deposition only from the hydrodynamic aspects, but not from the colloidal interaction aspect. The affinity between aggregated nanoparticles and a surface may be increased at the initial stage of deposition while being unaffected by aggregation state during later stages of deposition. The results of this study lead to better understandings, at least on a qualitative level, of the factors that controlling the kinetics of deposition and, in a broader sense, the fate and transport of nanoscale particles in the aqueous environment.
Item Open Access Development and Application of Scaling Correction Methods in Density Functional Theory(2021) Mei, YuncaiDensity functional theory (DFT) has become the main working horse for performing electronic structure calculations for chemical and physical systems nowadays. The theory is exact in principle, however, a density functional approximation (DFA) to the unknown exchange-correction energy $E_{\rm{xc}}$ in DFT has to be used in practice. Conventional DFAs have gained much success, while they usually possess intrinsic error and fail to describe some critical physical properties. In this dissertation, we focus on the delocalization error, a key concept to understand the systematic error existing in conventional DFAs, and we present the scaling correction methods which are designed to systematically and effectively reduce the delocalization error. The applications and improvements of two recently developed scaling correction methods, namely the the global scaling correction (GSC) method and the localized orbital scaling correction (LOSC) method, are mainly discussed in this dissertation. First, we demonstrate that the scaling corrections is capable of accurately predicting the quasiparticle energies and photoemission spectra from the orbital energies of the (generalized) Kohn-Sham DFT calculations. Second, we present a new method called QE-DFT, which is developed based on the connection between the orbital energies and the quasiparticle energies, to describe the difficult excited-state problems, including the low-lying, Rydberg and charge transfer excitations and conical intersections. We further derive the analytical gradients of the QE-DFT method, and demonstrate the application of QE-DFT for describing the potential energy surface and geometry optimization of excited states. Third, we show the application of LOSC to describe the polymer polarizability, which is a challenging problem for conventional DFAs. Fourth, we present the recent development for both GSC and LOSC methods. Specifically, we developed the analytic and exact second-order correction under the framework of GSC and achieved much improved accuracy compared to the original work of GSC. We also developed a new and robust self-consistent approach for LOSC method to avoid the convergence difficulties in the original LOSC work, which comes from using the approximate LOSC effective Hamiltonian. Finally, we developed the implementation of the scaling correction methods as a library with the supports to multiple programming languages. In summary, we demonstrated with extensive results that the GSC and LOSC are powerful and effective scaling correction methods to conventional DFAs to largely reduce the delocalization error. With the further developments to GSC and LOSC, they should be of great potential for broad application to describing challenging electronic structure problems of complex systems with high accuracy in the future.
Item Open Access Development of Advanced MRI Methods for Improving Signal and Contrast in Biomedical Imaging Applications(2012) Stokes, Ashley MarieThis dissertation reports advances in magnetic resonance imaging (MRI), with the ultimate goal of improving signal and contrast in biomedical applications. More specifically, novel MRI pulse sequences have been designed to characterize microstructure, enhance signal and contrast in tissue, and image functional processes. Using these pulse sequences, intermolecular multiple quantum coherence (iMQC) signals that arise from the dipolar field over well-defined distances can be observed; these signals were used here to probe material microstructure. Using iMQCs, the restricted diffusion in uni- and multi-lamellar vesicles such as liposomes and polymersomes was characterized, with potential applications for monitoring drug transport and release; moreover, mesoscopic anisotropy in developing rat brains was studied, which required significant pulse sequence optimizations and corrections to the original dipolar field framework. We have also developed and applied modified multipulse echo sequences with optimized interpulse delays for tissue imaging. These sequences have enhanced the signal and may provide new contrast in various tissues, including normal, tumor, and fatty tissues. Finally, the use of MRI to study functional processes, including temperature and perfusion, is described.
Item Open Access Development of Novel Physical Methods to Enhance Contrast and Sensitivity in Magnetic Resonance Imaging(2010) Jenista, ElizabethThe purpose of this thesis is to report technological developments in contrast mechanisms for MRI. The search for new forms of contrast is on-going, with the hope that new contrast mechanisms and new contrast agents will provide unique insights into various molecular processes and disease states. In this thesis, we will describe new contrast mechanisms developed by manipulating the inherent physics of the system, as well as the development of exogenous contrast agents. More specifically, we will describe the application of iMQCs (intermolecular multiple quantum coherences) to thermometry and structural imaging, and the unique information provided from these studies. We will also describe methods for migrating iMQC-based pulse sequences from a Bruker research console onto a clinical GE console, thus enabling the application of iMQCs to humans. We will describe the development of hyperpolarized contrast agents which have the potential to provide an unprecedented level of molecular contrast to MRI and the development of techniques to enhance the lifetime of these hyperpolarized contrast agents. Finally, we will discuss a new type of T2 -weighted imaging which significantly improves the refocusing of CPMG-type sequences.
Item Open Access Electronic Structure Based Investigations of Hybrid Perovskites and Their Nanostructures(2023) Song, RuyiPerovskites are a category of semiconductors with outstanding optoelectronic properties. Especially in the last decades, three-dimensionally connected (“3D”) hybrid perovskites gained an important position as an innovative solar-cell material by including organic cations. Related molecularly engineered materials, for example, atomic-scale two-dimensionally connected (“2D”) layered crystals and nano-scale structures offer a wide range of compositional, structural, and electronic tunability. Based on quantum chemistry simulations (specifically, density functional theory), this dissertation aims to contribute to the understanding of the relationship between the components and structure of hybrid perovskites and their electronic properties, related to alloying, energy level alignment in quantum wells, impact of chiral organic constituents on the atomic structure of 2D perovskites and resulting spin character of the electronic levels, and on the structure of related perovskite nanostructures.First, to investigate the tunability of 2D hybrid perovskites, 1) the author simulated the Sn/Pb alloying at the central metal site and explained the corresponding “bowing effect” on the bandgap values with different contribution preferences towards the conduction bands versus valence bands from different elements; 2) taking the conjugation length in different oligothiophene cations and the inorganic layer thickness as two independent factors, the author confirmed a gradual change of quantum well types. Second, to gain an in-depth understanding of the spin properties of the energy bands (specifically, the spin-selectivity) in hybrid perovskites, 1) the author analyzed the frontier bands of the 2D hybrid perovskite S-1-(1-naphthyl)ethylammonium lead bromide and revealed a giant spin-splitting originated from the inorganic moiety; 2) the author (together with experimental collaborators) identified a difference in the inter-octahedron Pb-X-Pb (X stands for the halides) distortion angles as the crucial geometric descriptor for spin-splitting in 2D hybrid perovskites by a correlation analysis of 22 experimental and relaxed structures with various chiral or achiral organic cations; 3) for perovskite nano-crystals with chiral surface ligands, simulations by the author helped to attribute the chirality transfer between organic cations and inorganic substrate to the geometric distortions driven by hydrogen bonds. Third, the author investigated 2D hybrid perovskites containing oligoacene organic cations, validated the theoretical method for geometry evaluation and predicted the expected quantum well type, crystal symmetry, and detailed expected spin-splitting properties that determine the potential for spin-selective transport and optoelectronics Finally, driven by the computational needs of large-scale hybrid perovskites DFT simulations, the application of an innovative hardware, tensor processing units (designed by Google), to quantum chemistry calculations (specifically, to solve for the density matrix) was explored. The author removed the code bottleneck to facilitate the largest “end-to-end” O(N^3) DFT simulations ever reported and benchmarked the accuracy and performance of this new hardware with test cases from biomolecular systems to solid-state and nano-scale materials.
Item Open Access Energy Transduction By Electron Bifurcation(2021) Yuly, Jonathon LukeElectron bifurcation oxidizes a two-electron donor, using the two electrons to reduce high- and low-potential acceptors. Thus, one electron may move thermodynamically uphill, being kinetically coupled to the downhill flow of the other electron. Electron bifurcation in nature is often reversible (∆G ≈ 0) so minimal free energy is dissipated, and the reaction occurs at minimal overpotential. Thus, electron bifurcation is a compelling target for bioinspired catalysis and/or nanoscale device design.We formulate a general theory of the electron bifurcation process, using a many-electron hopping kinetics model with hopping rate constants estimated with thermally activated electron tunneling theory. We conclude that efficient and reversible electron bifurcation requires only a conserved redox potential (free energy) landscape, with steep redox potential gradients in the high- and low-potential branches (the reversible EB scheme). This energy landscape naturally builds up electron and hole populations near the bifurcating two-electron cofactor in the high- and low-potential branches, respectively, thus disfavoring short-circuiting electron-hole combination. The reversible EB scheme suppresses short-circuiting reactions by erecting a Boltzmann penalty against redox states of the enzyme that may short-circuit, and largely accounts for short-circuit insulation in complex III of the electron transport chain, although our model does not uniquely account for the slow short-circuit turnover with an inhibited low-potential branch. For electron bifurcating enzymes that reduce the low-potential substrate directly (such as bifurcating electron transfer flavoproteins), we hypothesize that a downward shift in redox potential of the low-potential substrate upon binding to the bifurcating enzyme (similar to the iron protein bound to nitrogenase) could explain how the requisite steep redox potential gradient is achieved without housing a series of redox cofactors in the low-potential branch. Electron bifurcating enzymes in nature are often found with bifurcating cofactors (for example quinones and flavins) with inverted reduction potentials (i.e., the first reduction potential lower than the second). We derive a free energy decomposition scheme for the half-reactions of a two electron species from quantum chemical calculations to find physical and chemical factors that determine whether the reduction potentials are inverted. Remarkably, two electron species such as quinones and flavins can exhibit normally-ordered or inverted reduction potentials depending on the protein environment. Using our energy decomposition scheme and an estimate of a quinone Pourbaix diagram under continuum mean-field environments with varying electrostatic permittivity, we conclude that the proton transfer events that often accompany reduction in addition to the electrostatic interactions of charged species may have a significant impact on the invertedness of two-electron compounds. Thus, we hypothesize that electrostatic interactions (including the self-interaction of a charged semiquinone) may principally explain the ability of flavins and quinones to change the order of their first and second reduction potentials so profoundly. Future studies will be required to test this hypothesis. In addition, we show that efficient and reversible electron bifurcation is possible with normally ordered potentials at the bifurcating cofactor, provided the absolute value of the difference between the first and second reduction potentials is large (on the order of the redox potential span of the high- and low-potential branches in the reversible EB scheme). This finding has implications for synthetic electron bifurcation, as engineering redox active catalytic sites with strongly normally ordered potentials seems more straightforward than sites with strongly inverted potentials. Finally, we describe kinetics schemes for thermodynamically irreversible electron bifurcation that rely on disequilibrium populations of electrons within the high potential branch (irreversible confurcation is possible with a disequilibrium population of holes within the low-potential branch). Although these schemes are yet only hypothesized, these schemes allow orders-of-magnitude regulation of the bifurcating turnover rate with the redox poise of the two-electron donor (including faster turnover than in the reversible EB scheme), with kinetics fit by a generalized Shockley ideal diode equation.
Item Open Access Equilibrium and Non-equilibrium Monte Carlo Simulations of Microphases and Cluster Crystals(2012) Zhang, KaiSoft matter systems exhibiting spatially modulated patterns on a mesoscale are characterized by many long-lived metastable phases for which relaxation to equilibrium is difficult and a satisfactory thermodynamic description is missing. Current dynamical theories suffer as well, because they mostly rely on an understanding of the underlying equilibrium behavior. This thesis relates the study of two canonical examples of modulated systems: microphase and cluster crystal formers. Microphases are the counterpart to gas-liquid phase separation in systems with competing short-range attractive and long-range repulsive interactions. Periodic lamellae, cylinders, clusters, etc., are thus observed in a wide variety of physical and chemical systems, such as multiblock copolymers, oil-water surfactant mixtures, charged colloidal suspensions, and magnetic materials. Cluster crystals in which each lattice site is occupied by multiple particles are formed in systems with steep soft-core repulsive interactions. Dendrimers have been proposed as a potential experimental realization. In order to access and understand the equilibrium properties of modulated systems, we here develop novel Monte Carlo simulation methods. A thermodynamic integration scheme allows us to calculate the free energy of specific modulated phases, while a [N]pT ensemble simulation approach, in which both particle number and lattice spacing fluctuate, allows us to explore their phase space more efficiently. With these two methods, we solve the equilibrium phase behavior of five schematic modulated-phase-forming spin and particle models, including the axial next-nearest-neighbor Ising (ANNNI) model, the Ising-Coulomb (IC) model, the square-well linear (SWL) model, the generalized exponential model of index 4 (GEM-4) and the penetrable sphere model (PSM). Interesting new physics ensues. In the ANNNI layered regime, simple phases are not found to play a particularly significant role in the devil's flowers and interfacial roughening plays at most a small role. With the help of generalized order parameters, the paramagnetic-modulated critical transition of the ANNNI model is also studied. We confirm the XY universality of the paramagnetic-modulated transition and its isotropic nature. With our development of novel free energy minimization schemes, the determination of a first phase diagram of a particle-based microphase former SWL is possible. We identify the low temperature GEM-4 phase diagram to be hybrid between the Gaussian core model (GCM) and the PSM. The system additionally exhibits S-shaped doubly reentrant phase sequences as well as critical isostructural transitions between face-centered cubic (FCC) cluster solids of different integer occupancy. The fluid-solid coexistence in the PSM phase diagram presents a crossover behavior around T~0.1, below which the system approaches the hard sphere limit. Studying this regime allows us to correct and reconcile prior DFT and cell theory work around this transition.
Item Open Access Excited State Dynamics of Conjugated Metalloporphyrins(2010) Cleveland, LauraThe goal of this review is to highlight the unique and interesting aspects of conjugated metalloporphyrins. I will show the fundamental importance of these conjugated porphyrin systems by reviewing the excited state dynamics of some of the key systems that have been studied to date. The spectroscopic aspects I will be focusing on are the electronic absorption and emission and the transient absorption and emission. It is necessary to compare the ground and excited states in order to understand the significance of the excited state dynamics. Also important to discuss are the EPR and electrochemical data to further elucidate the unique qualities of conjugated porphryin oligomers.
Item Open Access Exploration of Alkyne-bridged Multi[(Porphinato)metal] Oligomers for Charge Transport Applications and Spin-Spin Exchange Coupling Properties Using Synthetic, Spectroscopic, Potentiometric, and Magnetic Resonance Methods(2017) Wang, RuobingAs silicon-based microelectronics approaches its fundamental physical limit, molecular electronics is emerging as a promising candidate for future ultra-dense electronic devices with individual molecules as active device components. The emerging of molecular spintronics, which exploits the spin-dependent charge transport through organic materials, further demonstrate the promising future of molecular electronics. This dissertation describes the charge transport and spin-spin electronic coupling properties of an extraordinary class of molecular wires, alkyne-bridged porphyrin arrays. Chapter one provides a general background of molecular electronics and molecular wires, as well as the basics of electron paramagnetic resonance (EPR). Chapter two describes utilizing highly conjugated (porphinato)metal-based oligomers (PMn structures) as molecular wire components of nanotransfer printed (nTP) molecular junctions; electrical characterization of these “bulk” nTP devices highlights device resistances that depend on PMn wire length. This study demonstrates the ability to fabricate “bulk” and scalable electronic devices in which function derives from the electronic properties of discrete single molecules, and underscores how a critical device function—wire resistance—may be straightforwardly engineered by PMn molecular composition. Chapter three describe the electronic exchange coupling between two unpaired spin on Cu(II) ions in meso-meso alkyne-bridged multi[copper(II) porphyrin] (mmPCu2). Spin and conformational dynamics in symmetric mmPCu2 have been studied in toluene solution at variable temperature using EPR spectroscopy. Comparison of the dimer EPR spectra to those of Cu porphyrin monomers shows clear evidence of an isotropic exchange interaction (Javg) in these biradicaloid structures, manifested by a significant line broadening in the dimer spectra. Comparison of ethyne and butadiyne alkyne bridges reveals a remarkable sensitivity to orbital interactions between the spacer and the metal, which is reflected in measurements of Javg as a function of temperature. The results suggest that orbital symmetry relationships may be more important than previously recognized in the design of optimized molecular spintronic devices. Chapter four reports a study of β-β linked bis[(porphinato)copper(II)] complexes (ββPCu2), which exhibit very different electronic structures compared to their mm linked analogs. By using electron paramagnetic resonance (EPR) spectroscopy, this study exhibits that a wide range (3 orders of magnitude) of the average electronic spin-spin exchange coupling can be achieved by varying the length of bridges and points of connections between the porphyrin rings. The pathways for mmPCu2 and ββPCu2 complexes were also investigated, with the ββPCu2 complexes exhibiting a dominant σ-type pathway and the mmPCu2 complexes showing a dominant π-type pathway.
Item Open Access Ground and Electronic Excited States from Pairing Matrix Fluctuation and Particle-Particle Random Phase Approximation(2016) Yang, YangThe accurate description of ground and electronic excited states is an important and challenging topic in quantum chemistry. The pairing matrix fluctuation, as a counterpart of the density fluctuation, is applied to this topic. From the pairing matrix fluctuation, the exact electron correlation energy as well as two electron addition/removal energies can be extracted. Therefore, both ground state and excited states energies can be obtained and they are in principle exact with a complete knowledge of the pairing matrix fluctuation. In practice, considering the exact pairing matrix fluctuation is unknown, we adopt its simple approximation --- the particle-particle random phase approximation (pp-RPA) --- for ground and excited states calculations. The algorithms for accelerating the pp-RPA calculation, including spin separation, spin adaptation, as well as an iterative Davidson method, are developed. For ground states correlation descriptions, the results obtained from pp-RPA are usually comparable to and can be more accurate than those from traditional particle-hole random phase approximation (ph-RPA). For excited states, the pp-RPA is able to describe double, Rydberg, and charge transfer excitations, which are challenging for conventional time-dependent density functional theory (TDDFT). Although the pp-RPA intrinsically cannot describe those excitations excited from the orbitals below the highest occupied molecular orbital (HOMO), its performances on those single excitations that can be captured are comparable to TDDFT. The pp-RPA for excitation calculation is further applied to challenging diradical problems and is used to unveil the nature of the ground and electronic excited states of higher acenes. The pp-RPA and the corresponding Tamm-Dancoff approximation (pp-TDA) are also applied to conical intersections, an important concept in nonadiabatic dynamics. Their good description of the double-cone feature of conical intersections is in sharp contrast to the failure of TDDFT. All in all, the pairing matrix fluctuation opens up new channel of thinking for quantum chemistry, and the pp-RPA is a promising method in describing ground and electronic excited states.
Item Open Access Large Two-photon Absorption of Highly Conjugated Porphyrin Arrays and Their in vivo Applications(2015) Park, Jong KangTwo-photon excited fluorescence microscopy (TPM) has become a standard biological imaging tool due to its simplicity and versatility. The fundamental contrast mechanism is derived from fluorescence of intrinsic or extrinsic markers via simultaneous two-photon absorption which provides inherent optical sectioning capabilities. The NIR-II wavelength window (1000–1350 nm), a new biological imaging window, is promising for TPM because tissue components scatter and absorb less at longer wavelengths, resulting in deeper imaging depths and better contrasts, compared to the conventional NIR-I imaging window (700–1000 nm). However, the further enhancement of TPM has been hindered by a lack of good two-photon fluorescent imaging markers in the NIR-II.
In this dissertation, we design and characterize novel two-photon imaging markers, optimized for NIR-II excitation. More specifically, the work in this dissertation includes the investigation of two-photon excited fluorescence of various highly conjugated porphyrin arrays in the NIR-II excitation window and the utilization of nanoscale polymersomes that disperse these highly conjugated porphyrin arrays in their hydrophobic layer in aqueous environment. The NIR-emissive polymersomes, highly conjugated porphyrins-dispersed polymersomes, possess superb two-photon excited brightness. The synthetic nature of polymersomes enables us to formulate fully biodegradable, non-toxic and surface-functionalized polymersomes of varying diameters, making them a promising and fully customizable multimodal diagnostic nano-structured soft-material for deep tissue imaging at high resolutions. We demonstrated key proof-of-principle experiments using NIR-emissive polymersomes for in vivo two-photon excited fluorescence imaging in mice, allowing visualization of blood vessel structure and identification of localized tumor tissue. In addition to spectroscopic characterization of the two-photon imaging agents and their imaging capabilities/applications, the effect of the laser setup (e.g., repetition rate of the laser, peak intensity, system geometry) on two-photon excited fluorescence measurements is explored to accurately measure two-photon absorption (TPA) cross-sections. A simple pulse train shaping technique is demonstrated to separate pure nonlinear processes from linear background signals, which hinders accurate quantification of TPA cross-sections.
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