In this thesis a method is presented for the modelling the effects of the excluded volume (ion-ion) and ion excess polarisability (ion-solvent) interactions in an electrolyte at a smooth planar electrode. The impact of these interactions is studied in terms of the equilibrium state of single and mixed electrolytes, the dynamic response of single electrolytes to a time-dependent applied potential, and their effect on the reaction rate, for both steady and time-dependent applied potentials. For reacting systems, the reaction rate is modelled using a modified form of the Frumkin-Butler-Volmer equation, in which the interactions are explicitly accounted for. At equilibrium, the model offers improvement over models which only account for the excluded volume interaction, in terms of both the predicted electrolyte structure and the electrical properties of the electrode. For example accounting for the polarisability interaction is shown to limit and then reverse the growth in the differential capacitance at the point of zero charge as the bulk concentration increases, an effect is not seen when only the excluded volume interaction is accounted for. Another example is for mixed electrolytes, in which accounting for the polarisability interaction leads to better agreement with experimental data regarding the composition of the double layer. For the response of an electrolyte to a potential step, the two interactions both lead to peaks in the time taken to reach equilibrium as a function of the potential. The effect of the domain length on the equilibration time is qualitatively discussed, together with the differences between the two interaction models. The response to a time-dependent potential is analysed through simulated electrochemical impedance spectroscopy and consideration of the capacitance dispersion effect. Between this and the potential step response data it is shown that the interactions themselves have little direct effect on the dynamic processes beyond the way in which they limit the ion concentrations in the double layer and alter the differential capacitance of the system. The investigation of the effect of the ion interactions on the reaction rate shows that both terms can either increase or decrease the rate, relative to a system with no interactions, depending on the details of the reaction and the applied potential. This is linked to the changes in the electric field within the double layer, which are caused by the interactions, and how this affects the reactant flux in that region. In terms of simulated EIS, deviations are observed relative to the equivalent circuit for the system, the reasons for which are discussed.

M-DNA is a complex formed between normal double-stranded DNA and the transition metal ions Zn2+, Ni2+, and Co2+ that is favoured by an alkaline pH. Previous studies have suggested that M-DNA formation involves replacement of the imino protons of G and T bases by the transition metal ions involved in forming the complex. Owing to the conductive properties of this unique DNA conformation, it has potential applications in nanotechnology and biosensing. This work was aimed at improving existing methods and developing new methods of characterizing M-DNA. The effects of base substitutions, particularly those of G and T, were evaluated in light of the proposed structure. Differences between M-DNA conformations induced by Zn2+ and Ni2+ were also investigated with a variety of techniques and compared to the effects of Cd2+ and Mg2+ on double-stranded DNA. M-DNA formation and stability were studied with an ethidium bromide (EtBr) based assay, M-DNA induced fluorescence quenching of DNA labelled with fluorescein and a compatible quenching molecule, isothermal titration calorimetry (ITC), and surface plasmon resonance (SPR). Production of monoclonal antibodies against the conformation was also attempted but was unsuccessful. The EtBr-based assay showed Ni(II) M-DNA to be much more stable than Zn(II) M-DNA as a function of pH and in the presence of ethylenediaminetetraacetic acid. Sequence-dependency and the effect of base substitutions were measured as a function of pH. With regards to sequence, d(G)nd(C)n tracts were found to form the conformation most easily. Base substitutions with G and T analogues that lowered the pKa of these bases were found to stabilize M-DNA more strongly than other base substitutions. A combination of temperature-dependant EtBr and ITC assays showed M-DNA formation to be endothermic, and therefore entropy driven. The SPR studies demonstrated many qualitative differences between Zn(II) and Ni(II) M-DNA formation, allowed characterization of Zn2+, Ni2+, Cd2+, and Mg2+ complexes with single-stranded DNA, and provided unambiguous evidence that M-DNA formation results in very little denaturation of double-stranded DNA. Specifically, the SPR study showed Ni(II) M-DNA to be more stable than Zn(II) M-DNA in the absence of transition metal ions, but also showed that Ni(II) M-DNA required higher concentrations of Ni2+ than Zn2+ to fully form the respective M-DNA conformations. Finally, quenching studies demonstrated Zn(II) M-DNA formation over a pH range from 6.5 to 8.5 provided that a Zn2+:H+ ratio of roughly 105 was maintained. The Keq for this interaction was 1.3 x 10-8 with 1.4 H+ being liberated per base bair of M-DNA formed. These results support the proposed structural model of M-DNA, as lowering the pKa of the bases having titratable protons over the pH range studied facilitated M-DNA formation. The fact that Zn(II) M-DNA formation was observed by fluorescence quenching at any pH provided that a constant ratio of Zn2+:H+ was maintained was consistent with a simple mass-action interaction for M-DNA formation. The differences between Zn(II) and Ni(II) M-DNA formation show that although it requires a higher pH or transition metal ion concentration, Ni(II) M-DNA is more stable than Zn(II) M-DNA once formed. This difference could play an important role in applications of M-DNA which required modulation in the stability of the M-DNA conformation.

M-DNA is a complex formed between normal double-stranded DNA and the transition metal ions Zn2+, Ni2+, and Co2+ that is favoured by an alkaline pH. Previous studies have suggested that M-DNA formation involves replacement of the imino protons of G and T bases by the transition metal ions involved in forming the complex. Owing to the conductive properties of this unique DNA conformation, it has potential applications in nanotechnology and biosensing. This work was aimed at improving existing methods and developing new methods of characterizing M-DNA. The effects of base substitutions, particularly those of G and T, were evaluated in light of the proposed structure. Differences between M-DNA conformations induced by Zn2+ and Ni2+ were also investigated with a variety of techniques and compared to the effects of Cd2+ and Mg2+ on double-stranded DNA. M-DNA formation and stability were studied with an ethidium bromide (EtBr) based assay, M-DNA induced fluorescence quenching of DNA labelled with fluorescein and a compatible quenching molecule, isothermal titration calorimetry (ITC), and surface plasmon resonance (SPR). Production of monoclonal antibodies against the conformation was also attempted but was unsuccessful. The EtBr-based assay showed Ni(II) M-DNA to be much more stable than Zn(II) M-DNA as a function of pH and in the presence of ethylenediaminetetraacetic acid. Sequence-dependency and the effect of base substitutions were measured as a function of pH. With regards to sequence, d(G)nd(C)n tracts were found to form the conformation most easily. Base substitutions with G and T analogues that lowered the pKa of these bases were found to stabilize M-DNA more strongly than other base substitutions. A combination of temperature-dependant EtBr and ITC assays showed M-DNA formation to be endothermic, and therefore entropy driven. The SPR studies demonstrated many qualitative differences between Zn(II) and Ni(II) M-DNA formation, allowed characterization of Zn2+, Ni2+, Cd2+, and Mg2+ complexes with single-stranded DNA, and provided unambiguous evidence that M-DNA formation results in very little denaturation of double-stranded DNA. Specifically, the SPR study showed Ni(II) M-DNA to be more stable than Zn(II) M-DNA in the absence of transition metal ions, but also showed that Ni(II) M-DNA required higher concentrations of Ni2+ than Zn2+ to fully form the respective M-DNA conformations. Finally, quenching studies demonstrated Zn(II) M-DNA formation over a pH range from 6.5 to 8.5 provided that a Zn2+:H+ ratio of roughly 105 was maintained. The Keq for this interaction was 1.3 x 10-8 with 1.4 H+ being liberated per base bair of M-DNA formed. These results support the proposed structural model of M-DNA, as lowering the pKa of the bases having titratable protons over the pH range studied facilitated M-DNA formation. The fact that Zn(II) M-DNA formation was observed by fluorescence quenching at any pH provided that a constant ratio of Zn2+:H+ was maintained was consistent with a simple mass-action interaction for M-DNA formation. The differences between Zn(II) and Ni(II) M-DNA formation show that although it requires a higher pH or transition metal ion concentration, Ni(II) M-DNA is more stable than Zn(II) M-DNA once formed. This difference could play an important role in applications of M-DNA which required modulation in the stability of the M-DNA conformation.

G-quadruplexes (GQs) are highly stable noncanonical nucleic acid structures that form in the DNA of human cells and play fundamental roles in maintaining genomic stability and regulating gene expression. These unique structures exert broad influence over biologically important processes and can modulate cell survival and human health. In fact, mutations, hyper-stability, and dissociation of GQs are implicated in neurodegenerative disease, mental retardation, premature-aging conditions, and various cancers. As such, GQs are novel drug targets. GQ-targeting therapeutics are developed to influence the folding and genetic interactions of GQs that are implicated in diseased states. To do so requires a greater understanding of GQ structure and dynamics and molecular dynamics (MD) simulations are well suited to provide these fundamental insights. Previous MD simulations of GQs have provided limited information due to inaccuracies in their models, namely the nonpolarizable nature of their force fields (FFs). The cutting-edge Drude polarizable FF models electronic degrees of freedom, allowing charge distribution to change in response to its environment. This is an important component for modeling ion-ion and ion-DNA interactions and can influence the overall stability of GQ structures. The work herein employs the Drude polarizable FF to 1) describe the role of electronic structure on the dynamics and folded stability of GQs, 2) determine the impact of ion interaction on GQ stability, and 3) characterize the role of G-hairpin motifs in GQ intermediates. Such fundamental investigations will help clarify GQs role in healthy and diseased states and transform our understanding of noncanonical DNA, improving human health, therapeutic design, and fundamental science. / Doctor of Philosophy / Human health and disease are influenced by unique nucleic acid structures called G-quadruplexes (GQs). GQs form when DNA or RNA fold into a square-shaped structure that is stabilized by ion interactions and special hydrogen bonding patterns. These GQ structures exert broad influence over normal biological processes, but also play a role in neurodegeneration, intellectual disabilities, premature-aging conditions, and various cancers, many of which are chemotherapeutic resistant. As such, modulating GQ structures, or their interactions with proteins, is a promising therapeutic approach. However, a greater understanding of GQ folding, folded structure, and interactions with other biomolecules is needed to do so. Computational techniques such as molecular dynamics (MD) simulations use experimental data and fundamental biophysics to gain new insights on these properties and inform novel drug design. In this project, we explored the dynamics of several distinct GQ structures and folding intermediates with state-of-the-art MD simulation methods. In doing so, we provided new insight on their structural features as well as their interactions with extended DNA sequences and different ion types, which serve as fundamental information for future structural or computer-aided drug design studies.

Cations are essential for ribonucleic acids (RNA), as they neutralize the negatively charged phosphate backbone. Divalent metals play important roles in the folding and function of RNA. The relationship between RNA and divalent cations magnesium (Mg(II)) and iron (Fe(II)) has been investigated. Mg(II) is involved in tertiary interactions of many large RNAs, and necessary for ribozyme activity. The influence of Mg(II) on RNA secondary and tertiary structure is investigated experimentally. Mg(II) binding to A-form RNA is accompanied by changes in CD spectra, indicating that Mg-RNA interactions influence the helical structure of RNA duplexes and helical regions of unfolded RNAs. Quantum mechanics calculations are used to probe the energetics of Mg(II)-chelation with phosphate oxygen atoms of nucleic acids. We identify the specific forces that contribute to stability of Mg(II)-chelation complexes in RNA. Fe(II) can serve as a substitute for Mg(II) in RNA folding and function. Fe(II) was abundant on early earth, it is plausible that RNA folding and function was mediated by Fe(II) instead of, or in combination with, Mg(II) in the anoxic environment of early earth. We have investigated oxidoreductase catalytic activity observed in RNA when in combination with Fe(II). This activity, only observed in the presence of Fe(II) and absence of Mg(II)appears to be a resurrection of ancient RNA capabilities that were extinguished upon the depletion of Fe(II) from the environment during the rise of oxygen after the great oxidation event. Finally, metal-ion based cleavage of RNA is used to identify the binding sites of Mg(II) and Fe(II). We observe that both metals cleave RNA in similar positions, providing further support for Fe(II) as a substitute for Mg(II) in RNA.

Due to the successful commercialization of lithium-ion batteries (LIBs), there is a growing interest in developing new battery materials with beneficial electrochemical properties. However, the uneven distribution of lithium resources and the low abundance of lithium in the earth crust are the main obstacles for further development and large-scale production of LIBs. Sodium-ion batteries (SIBs), an alternative that can partly meet the energy storage challenges, are getting attentions of researchers due to the wide availability and lower cost of sodium resources. Nevertheless, the conventional liquid electrolytes of either LIBs or SIBs composed of fluorinated salts dissolved in volatile organic solvents, posing serious safety issues due to the instability of the salts and flammability of the solvents. There is an urge to develop new fluorine-free electrolytes with improved physicochemical and electrochemical properties. In this context, the conventional fluorinated salts should be replaced with fluorine-free salts and the flammable solvents should be substituted with non-flammable solvents. There are a number of strategies to develop high-performant electrolytes including ambient-temperature ionic liquids (ILs), organic ionic plastic crystals (OIPCs) and highly concentrated electrolytes (HCEs) utilizing new salts and solvents. In this thesis, novel phosphorus-based ionic materials and electrolytes are introduced and their properties are thoroughly investigated. In the first part (Paper I), fluorine-free NaDEEP salt and TEOP solvent are employed to make “solvent-in-salt” (SIS) sodium electrolytes, also known as HCEs. Unexpectedly, the addition of TEOP solvent lead to an increase in the oxidation stability of the SIS electrolytes. In addition, an unusual ionic conductivity behavior is found – the ionic conductivities of Na electrolytes increase with increasing salt concentration. The “salt-rich” and “solvent-rich” phases formed within the electrolytes are investigated using multinuclear liquid-state NMR spectroscopy and NMR diffusometry. In the second part (Paper II), a series of orthoborate-based ionic materials, specifically OIPCs, containing phosphonium/ammonium cations are prepared to compare with the popular fluorine-free, bis(oxalato)borate (BOB) salts. The tetrabutyl phosphonium bis(glycolato)borate ([P4444][BGB]) OIPC displays much higher decomposition temperature than the structural analogous [P4444][BOB] IL. The crystal structures of LiBGB and NaBGB salts are resolved using single-crystal X-ray diffraction analysis. Unlike LiBOB, the BGB-based salts revealed excellent moisture stability over an extended time of up to 8-weeks air exposure. Multinuclear solid-state NMR spectroscopy indicates weaker cation-anion interactions in phosphonium-based salts than the ammonium-based ones. Finally, in the third part (Paper III), two-component and three-component eutectic electrolytes, composed of pyrrolidinium saccharin (PySc), lithium saccharin (LiSc) and/or [P4444][BGB] salt. The resulting mixtures showed significantly lower melting temperatures than the neat salts. The physicochemical and thermal properties of these salts are thoroughly investigated and discussed.