Master of Science / Department of Chemistry / Daniel A. Higgins / The potential-dependent reorientation dynamics of double stranded DNA (ds-DNA) covalently attached to planar glassy carbon electrode (GCE) surfaces were studied in this thesis. The orientation of ds-DNA was investigated via the distance-dependent quenching of fluorescence from a 6–carboxyfluorescein (FAM6) flurophore to the electrode surface. The fluorophore was covalently bound to the distal end of the DNA. Fluorescence microscopy was employed for optical detection of FAM6 fluorescence and hence the DNA dynamics. The variation of the fluorescence from the dye with electrode potential is attributed to distance-dependent dipole-electrode energy transfer. Application of positive potentials (i.e., +0.2 V vs. open circuit potential, OCP) to the GCE caused the ds-DNA to align approximately parallel to the surface, yielding strong FAM6-electrode energy transfer and low fluorescence intensity. With the switching of the potential towards negative values (i.e., -0.4 V vs. OCP) the ds-DNA realigned perpendicular to the GCE surface leading to a reduction in energy transfer and high fluorescence intensity. Initial DNA reorientation upon a change in electrode potential is very fast. These fast dynamics have been observed and characterized in a number of previous publications. We have observed subsequent slow dynamics that we attribute to slow orientational relaxation of the DNA. Our observations were first reported by Q. Li, et al., J. Am. Chem. Soc. 2012, 134, 14467. In this thesis, this prior work is extended to verify the reproducibility of these new dynamics and to eliminate the possibility of certain artifacts as their source. Specifically, the experiments are repeated using a new cell design and a different buffer. In the primary experiments performed in this thesis, the dependence of the DNA reorientation dynamics on surface coverage was investigated by observing the fluorescence modulation as a function of probe concentration in the functionalization bath. Concentrations of 0.25, 1.0 and 1.5 µM 35-mer ds-DNA were employed. Electrodes functionalized at these concentrations have ds-DNA surface coverages of 1.18 x 10[superscript]12, 3.24 x 10[superscript]12 and 4.26 x 10[superscript]12 cm[superscript]-2, respectively. With increasing concentration of the DNA probe, the reorientation time constant at positive applied bias (vs. OCP) increased, indicting reorientation was slowed. In contrast, the time constant decreased with the negative applied bias (vs. OCP) indicating faster orientational relaxation. The possible origins for the observed trends in the reorientation time constant are discussed.

Doctor of Philosophy / Department of Chemistry / Christine M. Aikens / This body of work describes a theoretical study of the growth mechanism of gold thiolate nanoparticles from Au(III) as synthesized in the Brust-Schiffrin method. The Au(III) salt can be reduced to form Au(I) by two thiols or a hydride. Depending on the polarity of the solvent, the Au(I) species will either yield rings and anionic chains, remain in isolation, or create an ionic complex with the phase transfer agent. No matter what form the Au(I) species takes, a second reduction must occur to yield Au(0). If the solvent is polar, such as methanol or water, and the Au(I) species is a ring or anionic chain, then a hydride can reduce the structure and create a gold-gold bond and dissociate a thiol from the structure. The gold atoms involved in the gold-gold bond would have a formal Au(0) oxidation state. However if the Au(I) species can be kept from forming rings or chains in the polar solvent or if the system is in a nonpolar solvent, then two Au(I) species in close proximity in the presence of hydride can react to yield a non-radical Au(0) species. The oxidation of bare gold nanoclusters by thiol will also be examined, such as in the case of SMAD-produced gold nanoparticles. In this process, the gold nanoclusters are initially in the Au(0) oxidation state. However the SR-Au-SR “staple” motifs that are known to passivate gold nanoparticles contain Au(I) species. The adsorption of thiol on various sizes of gold clusters in several charge states will be calculated and the mechanism for the oxidation of Au3 and three-dimensional Au12 will be modeled. The rate-limiting step is found to be the thiol hydrogen dissociation onto the gold cluster. Once this dissociation occurs, the hydrogen can move freely around the surface. Finally, Au25(SH)18- will be investigated as a catalyst for selective hydrogenation of α,β-unsaturated aldehyde. The dependence of the energetics of hydrogen gas dissociation on Au25(SH)18- on the functional and Grimme dispersion correction employed will also be examined.

Doctor of Philosophy / Department of Chemistry / Ryszard J. Jankowiak / The constituents of oxygen-evolving photosystem II core complexes—antenna proteins (CP43 and CP47) and reaction center (RC)—have been the subject of many studies over the years. However, the various issues related to electronic structure, including the origin/composition of the lowest-energy traps, origin of various emission bands, excitation energy transfer (EET), primary charge separation (CS) processes and pigment site energies remain yet to be fully resolved. Exploiting our state-of-the-art techniques such as low-T absorption, fluorescence, and hole burning (HB) spectroscopies, we resolved some of the issues particularly related to CP47 and isolated RC protein complexes. For example, we demonstrated that the fluorescence origin band maximum (~695 nm) originates from the lowest-energy state ~693 nm of intact CP47. In intact CP47 in contrast to destablished protein complexes, the band (~695 nm) does not shift in the temperature range of 5–77 K unless hole-burning takes place. We also studied a large number of isolated RC preparations from spinach, and wild-type Chlamydomonas reinhardtii (at different levels of intactness), as well as its mutant (D2-L209H), in which the active branch pheophytin (PheoD1) has been genetically replaced with chlorophyll a (Chl a). We showed that the Qx-/Qy-region site-energies of PheoD1 and PheoD2 are ~545/680 nm and ~541.5/670 nm, respectively, in good agreement with our previous assignment [Jankowiak et al. J. Phys. Chem. B 2002, 106, 8803]. Finally, we demonstrated that the primary electron donor in isolated algal RCs from C. reinhardtii (referred to as RC684) is PD1 and/or PD2 of the special Chl pair (analogous to PL and PM, the special BChl pair of the bacterial RC) and not ChlD1. However, the latter can also be the primary electron donor (minor pathway) in RC684 depending on the realization of the energetic disorder. We further demonstrate that transient HB spectra in RC684 are very similar to P+QA - PQA spectra measured in PSII core, providing the first evidence that RC684 represent intact isolated RC that also possesses the secondary electron acceptor, QA. In summary, a new insight into possible charge separation pathways in isolated PSII RCs has been provided.

Doctor of Philosophy / Department of Chemistry / Christine M. Aikens / Small silver and gold clusters (less than 2 nm) display a discrete absorption spectrum characteristic of molecular systems whereas larger particles display a strong, broad absorption band in the visible. The latter feature is due to the surface plasmon resonance, which is commonly explained by the collective dipolar motion of free electrons across the particle, creating charged surface states. The evolution between molecular properties and plasmon is investigated. Time-dependent density functional theory (TDDFT) calculations are performed to study the absorption spectrum of cluster-size silver and gold nanorods. The absorption spectrum of these silver nanorods exhibits high-intensity longitudinal and transverse modes (along the long and short axis of the nanorod respectively), similar to the plasmons observed experimentally for larger nanoparticles. These plasmon modes result from a constructive addition of the dipole moments of nearly degenerate single-particle excitations. The number of single-particle transitions involved increases with increasing system size, due to the growing density of states available. Gold nanorods exhibit a broader absorption spectrum than their silver counterpart due to enhanced relativistic effects, affecting the onset of the longitudinal plasmon mode. The high-energy, high-intensity beta-peak of acenes also results from a constructive addition of single-particle transitions and I show that it can be assigned to a plasmon. I also show that the plasmon modes of both acenes and metallic nanoparticles can be described with a simple configuration interaction (CI) interpretation. The evolution between molecular absorption spectrum and plasmon is also investigated by computing the density of states of spherical thiolate-protected gold clusters using a charge-perturbed particle-in-a-sphere model. The electronic structure obtained with this model gives good qualitative agreement with DFT calculations at a fraction of the cost. The progressive increase of the density of states with particle size observed is in accordance with the appearance of a plasmon peak. The optical properties of nanoparticles can be tuned by varying their composition. Therefore, the optical behavior of the bimetallic Au[subscript](25-n)Ag[subscript]n(SH)[subscript]18[superscript]- cluster for different values of n using TDDFT is analyzed. A large blue shift of the HOMO-LUMO absorption peak is observed with increasing silver content, in accordance with experimental results.

Doctor of Philosophy / Department of Chemistry / Christine M. Aikens / Water oxidation can be considered as the ‘holy grail’ of renewable energy research, where water is split into constituent molecular hydrogen and oxygen. Hydrogen is a very efficient energy source that is both clean and sustainable. The byproduct of hydrogen combustion is water, which in turn can be reused as the source for hydrogen generation. Natural water splitting is observed during photosynthesis in the oxygen-evolving complex of photosystem II, which consists of a CaMn₄O₄ cubane core. Herein, we report in silico approaches to understand bottom up catalytic design of model transition metal oxide complexes for water splitting. We have employed density functional theory to investigate model ligand-free architectures of cobalt and manganese oxide dimer (Mn₂(μ-OH)(μ-O)(H₂O)₃(OH)₅, Mn₂(μ-OH)₂(H₂O)₄(OH)₄, Mn₂(μ-OH)₂(H₂O)₂(OH)₂(O(CH)₃O)₂, Co₂(μ-OH)₂(H₂O)₄(OH)₄ and cubane (Co₄O₄(H₂O)₈(OH)₄, Mn₄O₄(H₂O)[subscript]x(OH)[subscript]y x = 4-8, y = 8-4) complexes. The thermodynamically lowest energy pathway on the cobalt dimer catalyst proceeds through a nucleophilic attack of a solvent water molecule to a Co(V)-O radical moiety whereas the pathway on the cubane catalyst involves a geminal coupling of a Co(V)-O radical oxo group with bridging oxo sites. The lowest energy pathway for the fully saturated Mn₂O₄•6H₂O (Mn₂(μ-OH)(μ-O)(H₂O)₃(OH)₅) and Mn₂O₃•7H₂O (Mn₂(μ-OH)₂(H₂O)₄(OH)₄) complexes occur through a nucleophilic attack of a solvent water molecule to Mn(IV½)O and Mn(V)O oxo moieties respectively. Out of all the oxidation state configurations studied for the manganese cubane, we observed that Mn₄(IV IV IV IV), Mn₄(III IV IV IV), and Mn₄(III III IV V) configurations are thermodynamically viable for water oxidation. All three of these reaction pathways proceed via nucleophilic attack of solvent water molecule to the manganese oxo species. The highest thermodynamic energy step in manganese dimer and cubane complexes corresponds to the formation of the manganese oxo species, which is a significant feature that reoccurred in all these reaction pathways. We have also employed multireference and multiconfigurational calculations to investigate the Mn₂(μ-OH)₂(H₂O)₂(OH)₂(O(CH)₃O)₂ system. The presence of Mn(IV)O[superscript]• radical moieties has been observed in this catalytic pathway. These simplest models of cobalt and manganese with water-derived ligands are essential to understand microscopic properties that can be used as descriptors in designing future catalysts.

Doctor of Philosophy / Department of Chemistry / Viktor Chikan / The research work in this thesis aims at investigating the basic physic-chemical properties of magnetic and metal nanoparticles (NPs) for biomedical applications such as magnetic hyperthermia and controlled drug release. Magneto-plasmonic properties of magnetic NPs are important to evaluate potential applications of these materials. Magnetic property can be used to control, monitor and deliver the particles using a magnetic field while plasmonic property allows the tracking of the position of the particles, but aggregation of NPs could pose a problem. Here, the aggregation of NPs is investigated via the Faraday rotation of gold coated Fe[subscript]2O[subscript]3 NPs in alternating magnetic fields. In addition, the Faraday rotation of the particles is measured in pulsed magnetic fields, which can generate stronger magnetic fields than traditional inductive heaters used in the previous experiments. In the second project, the formation of protein-NPs complexes is investigated for hyperthermia treatment. The interactions between gold and iron-platinum NPs with octameric mycobacterial porin A from Mycobacterium smegmatis (MspA) and MspA[superscript])cys protein molecules are examined to assemble a stable, geometrically suitable and amphiphilic proteins-NPs complex. Magnetic NPs show promising heating effects in magnetic hyperthermia to eliminate cancer cells selectively in the presence of alternating magnetic field. As a part of investigation, the heating capacity of a variety of magnetic NPs and the effects of solvent viscosity are investigated to obtain insight into the heating mechanism of these particles. Finally, the controlled drug release of magnetic NPs loaded liposomes by pulsed magnetic field is investigated. The preliminary data indicate about 5-10% release of drug after the application of 2 Tesla magnetic pulses. The preliminary experiments will serve as the initial stage of investigation for more effective magnetic hyperthermia treatment with the help of short magnetic pulses.

Doctor of Philosophy / Department of Chemistry / Paul E. Smith / The Kirkwood-Buff (KB) theory of solutions, published in 1951, established a route from integrals over radial (pair) distribution functions (RDFs) in the grand canonical ensemble to a set of thermodynamic quantities in an equivalent closed ensemble. These “KB integrals” (KBIs) can also be expressed in terms of the particle-particle (i.e., concentration or density) fluctuations within grand canonical ensemble regions. Contributions by Ben-Naim in 1977 provided the means to obtain the KBIs if one already knew the set of thermodynamic quantities for the mixture of interest; that is, he provided the inversion procedure. Thus, KB theory provides a two-way bridge between local (microscopic) and global (bulk/thermodynamic) properties. Due to its lack of approximations, its wide ranging applicability, and the absence of a competitive theory for rigorously understanding liquid mixtures, it has been used to understand solution microheterogeneity, solute solubility, cosolvent effects on biomolecules, preferential solvation, etc. Here, after using KB theory to test the accuracy of pair potentials, we present and illustrate two extensions of the theory, resulting in a general Fluctuation Solution Theory (FST). First, we generalize KB theory to include two-way relationships between the grand canonical ensemble’s particle-energy and energy-energy fluctuations and additional thermodynamic quantities. This extension allows for non-isothermal conditions to be considered, unlike traditional KB theory. We illustrate these new relationships using analyses of experimental data and molecular dynamics (MD) simulations for pure liquids and binary mixtures. Furthermore, we use it to obtain conformation-specific infinitely dilute partial molar volumes and compressibilities for proteins (other properties will follow) from MD simulations and compare the method to a non-FST method for obtaining the same properties. The second extension of KB theory involves moving beyond doublet particle fluctuations to additionally consider triplet and quadruplet particle fluctuations, which are related to derivatives of the thermodynamic properties involved in regular KB theory. We present these higher order fluctuations obtained from experiment and simulation for pure liquids and binary mixtures. Using the newfound experimental third and fourth cumulants of the distribution of particles in solution, which can be extracted from bulk thermodynamic data using this extension, we also probe particle distributions’ non-Gaussian nature.

Doctor of Philosophy / Department of Physics / Uwe Thumm / We study the dynamics of diatomic molecules (dimers) in intense IR and XUV laser fields theoretically and compare the results with measured data in collaboration with different experimental groups worldwide. The first three chapters of the thesis cover the introduction and the background on solving time-independent and time-dependent Schrödinger equation. The numerical results in this thesis are presented in four chapters, three of which are focused on diatomic molecules in IR fields. The last one concentrates on diatomic molecules in XUV pulses. The study of nuclear dynamics of H[subscript]2 or D[subscript]2 molecules in IR pulses is given in Chapter 4. First, we investigate the optimal laser parameters for observing field-induced bond softening and bond hardening in D[subscript]2[superscript]+. Next, the nuclear dynamics of H[subscript]2[superscript]+ molecular ions in intense laser fields are investigated by analyzing their fragment kinetic-energy release (KER) spectra as a function of the pump-probe delay τ. Lastly, the electron localization is studied for long circularly polarized laser pulses. Chapter 5 covers the dissociation dynamics of O[subscript]2[superscript]+ in an IR laser field. The fragment KER spectra are analyzed as a function of the pump-probe delay τ. Within the Born-Oppenheimer approximation, we calculate ab-initio adiabatic potential-energy curves and their electric dipole couplings, using the quantum chemistry code GAMESS. In Chapter 6, the dissociation dynamics of the noble gas dimer ions He[subscript]2[superscript]+, Ne[subscript]2[superscript]+, Ar[subscript]2[superscript]+, Kr[subscript]2[superscript]+, and Xe[subscript]2[superscript]+ is investigated in ultrashort pump and probe laser pulses of different wavelengths. We observe a striking ‘‘delay gap’’ in the pump-probe-delay-dependent KER spectrum only if the probe-pulse wavelength exceeds the pump-pulse wavelength. Comparing pump-probe-pulse-delay dependent KER spectra for different noble gas dimer cations, we quantitatively discuss quantum-mechanical versus classical aspects of the nuclear vibrational motion as a function of the nuclear mass. Chapter 7 focuses on diatomic molecules in XUV laser pulses. We trace the femtosecond nuclear-wave-packet dynamics in ionic states of oxygen and nitrogen diatomic molecules by comparing measured kinetic-energy-release spectra with classical and quantum-mechanical simulations. Experiments were done at the free-electron laser in Hamburg (FLASH) using 38-eV XUV-pump–XUV-probe. The summary and outlook of the work is discussed in Chapter 8.

Doctor of Philosophy / Department of Chemistry / Sundeep Rayat / Research in our laboratory has focused on designing photoactivated DNA cleaving agents based on tetrazolethione scaffolds. The key step in the activation of these involves conversion of tetrazolethione moiety to carbodiimides upon irradiation. However, the mechanism of this reaction was not previously reported. Therefore, we undertook a study to elucidate the mechanism of photodecomposition of tetrazolethione as to identify reactive intermediates involved, that may interfere or aid with the activity of our synthesized DNA cleaving agents under physiological conditions. In Part 1 of this dissertation, we present mechanistic studies on this photodecomposition. Our results indicate the clean photoconversion of tetrazolethiones I to their respective carbodiimides IV via the expulsion of sulfur and dinitrogen. Photoirradiation in the presence of trapping agent (e.g. 1,4-cyclohexadiene) resulted into the formation of their corresponding thioureas. Thus, providing strong evidence for the intermediacy of a 1,3-biradical III, which is believed to be in its triplet spin multiplicity. Further investigations (triplet sensitization and quenching experiments) to determine the precursor of the biradical argued against the involvement of a triplet excited state (T[subscript]1). We believe that the mechanistic pathway that leads to the formation of a 1,3-triplet biradical III is a diradicaloid species II-II" generated directly from the singlet excited state of tetrazolethiones (S[subscript]1) after the expulsion of dinitrogen. Once formed, this diradicaloid species could be envisioned to undergo intersystem crossing to generate the 1,3 triplet biradical III which then undergoes desulfurization to form carbodiimides IV (Chapter 2). Bridgehead-nitrogen containing fused heterocycles are regarded as “privileged structure” in biology and have found widespread applications in pharmaceutical industry. These heterocycles have also been evaluated in electroluminescent devices and organic dyes. Part II of the dissertation present new, concise and low cost strategies to a unique class of bridgehead nitrogen-containing fused heterocyclic scaffolds which involves two sequential intramolecular cyclizations from heteroenyne-allenes in the presence of Lewis acids such as SnCl[subscript]4 and BF[subscript]3.OEt[subscript]2, and trace water. The starting heteroenyne-allenes VI can be prepared from commercially available substrates V in 4 – 5 steps following standard protocols (Chapter 3). Furthermore, we employed density functional theory to gain insights into the optoelectronic properties of select derivatives of phenanthridine-fused quinazoliniminiums (PNQs) VII and their free base in order to evaluate their scope in OLED technology. Our results show that the energies of the Highest Occupied Molecular Orbital (HOMO), Lowest Unoccupied Molecular Orbital (LUMO), the HOMO-LUMO energy gaps, the ionization potentials, electron affinities and the reorganization energies can be finely tuned by varying the substituents on these chromophores. In addition, we found that the introduction of an electron donating group (NMe[subscript]2) on the PNQs and their free base increases the energies of the HOMOs and decreases the ionization potentials, relative to its unsubstituted derivative, whereas substitution by an electron withdrawing group (NO[subscript]2) decreases the energies of the LUMOs and increases the electron affinities which in turn suggests an improvement in their hole and electron creating abilities, respectively (Chapter 4).