Methylation is involved in the regulation of varied biological processes, from cancer to embryonic development. In B-DNA, methylation can alter the frequency with which a dinucleotide step samples one of two substates: BI and BII. Changing the BI-BII equilibrium can in turn affect the ability of proteins to bind to DNA, which may ultimately alter the transcription of genes. Using MD simulations, we evaluate the effects of cytosine methylation on the BI-BII equilibrium and the RMS atomic fluctuations of the backbone of two sequences: (GC)5 and the Dickerson dodecamer (DD). Methylation in (GC)5 stabilizes the BII state in CpG steps and stabilizes the BI state in GpC steps, but the BII state is always less favored than the BI state. The activation energy between the BI/BII states in (GC)5 increases in GpC steps and decreases in CpG steps upon methylation, indicating that backbone dynamics are affected by methylation in a step-dependent manner. The DD simulations suggest that methylation stabilizes the BII state in both CpG and GpC steps, although more sampling is needed to determine the significance of these results. Methylation has little effect on the atomic fluctuations of the backbone in (GC)5 or DD simulations. Thus, in these sequences, methylation does not uniformly stabilize one state, nor does methylation stabilize the state that is favored in the native sequence.

Molecular dynamics simulation was used to study ion permeation through different membrane proteins embedded in a lipid bilayer (DMPC) with different saline solutions. The potential of mean force (PMF) for ion transport was obtained by umbrella sampling simulations. A revised MacKerell force field for tryptophan residues was studied using gramicidin A (gA) channel as a test model. The revised force field contribution to the Na+ PMF was consonant with the prediction from the experimental results, but in stark contrast to the prediction of the CHARMM force field, version 22, for the tryptophan side-chain. A new grid-based correction map algorithm by MacKerell group, called CMAP, was introduced into the CHARMM force field, version 31. The CMAP algorithm focused on optimizing phi, psi dihedral parameters for the peptide backbone. The CMAP corrections reduced the excessive translocation barrier. Decomposition demonstrated the reduction in the translocation barrier was due to effects on the K+ PMFH2O rather than on K+ PMFgA. The presence of negatively charged sulfonate group at the entrance and exit of the gA channel affected the depth and the location of the highly occupied sites. The negatively charged sulfonate group produced a strong attraction for the cations in the bulk towards the channel mouth. In the M2 transmembrane domain channel (M2-TMD), three M2-TMD structures were studied, differing only in whether the selectivity-filter (four His37 side-chains) was uncharged, +2 charged, or +3 charged. M2-TMD structural properties were compared with the structural properties of other models extracted from NMR and X-ray studies. The spontaneous cation and anion entry into the charged selectivity-filter was different from that into a neutral selectivity-filter. Cl- ions had a lower free-energy barrier in the selectivity-filter than either Na+ or NH4+ ions through the M2-TMD channel. NH4+ ions had a lower free-energy barrier in the selectivity-filter than Na+ ions. Based on accessible rotamer conformations, a revised conductance mechanism was proposed. In this conductance mechanism, the His37 side-chain functioned as an acceptor and donor group, whereas the Trp41 side-chain functioned as a carrying group.

The synthesis and properties of metal phosphonates prepared using piperazine-based bisphosphonic acids have been investigated. The ligands N,N’-piperazinebis(methylenephosphonic acid) (H₄L), and the 2-methyl (H₄L-Me) and 2,5-dimethyl (H₄L 2,5-diMe) derivatives have been prepared using a modified Mannich reaction. Hydrothermal reaction of gels prepared from metal (II) acetates and the bisphosphonic acids results in the synthesis of four structures: STA-12, Ni VSB-5, Co H₂L.H₂O and Mg H₂L. STA-12, synthesised by reaction of Mn, Fe, Co or Ni acetate with H₄L or H₄L-Me, has been investigated further. STA-12 crystallises in the space group R⁻₃, and Ni STA-12 is the most crystalline version. Its structure was solved from synchrotron data (a = b = 27.8342(1) Å, c = 6.2421(3) Å, α = β = 90°, γ = 120°), and it has large 10 Å hexagonal shaped pores. Helical chains of Ni octahedra are coordinated by the ligands, resulting in phosphonate tetrahedra pointing towards the pore space. Water is present, both coordinated to the Ni²⁺ cations and physically adsorbed in the pores. Mixed metal structures based on Ni STA-12, where some Ni is replaced in the gel by another divalent metal (Mg, Mn, Fe or Co) can also be synthesised. Dehydration of STA-12 results in two types of behaviour, depending on the metal present. Rhombohedral symmetry is retained on dehydration of Mn and Fe STA-12, the a cell parameter decreasing compared to the as-prepared structures by 2.42 Å and 1.64 Å respectively. Structure solution of dehydrated Mn STA-12 indicates changes in the torsion angles of the piperazine ring bring the inorganic chains closer together. Fe and Mn STA-12 do not adsorb N₂, which is thought to be due to the formation of an amorphous surface layer. Dehydration of Ni and Co STA-12 causes crystallographic distortion. Three phases were isolated for Ni STA-12: removal of physically adsorbed water results in retention of rhombohedral symmetry, while dehydration at 323 K removes some coordinated water forming a triclinic structure. A fully dehydrated structure (dehydrated at 423 K) was solved from synchrotron data (a = 6.03475(5) Å, b = 14.9156(2) Å, c = 16.1572(7) Å, α = 112.5721(7)°, β = 95.7025(11)°, γ = 96.4950(11)°). The dehydration mechanism, followed by UV-vis and Infra-red spectroscopy, involves removal of water from the Ni²⁺ cations and full coordination of two out of three of the phosphonate tetrahedra forming three crystallographically distinct Ni and P atoms. No structural distortion takes place on dehydration of Ni and Co STA-12 prepared using the methylated bisphosphonate, and the solids give a higher N₂ uptake as a result. Dehydrated Ni and Co STA-12 were tested for adsorption performance for fuel related gases and probe molecules. Investigations were undertaken at low temperature with H₂, CO and CO₂, and ambient temperature with CO₂, CH₄, CH₃CN, CH₃OH and large hydrocarbons. Due to the presence of lower crystallinity, Co STA-12 has an inferior adsorption performance to Ni STA-12, although it has similar adsorption enthalpies for CO₂ at ambient temperature (-30 to -35 kJ mol⁻¹). Ni STA-12 adsorbs similar amounts of CO₂ and N₂ at low temperature, indicating the adsorption mechanisms are similar. Also, it adsorbs 10 × more CO₂ than CH₄ at low pressure, meaning it could be used for separation applications. Ni STA-12 adsorbs 2 mmol g⁻¹ H₂ with an enthalpy of -7.5 kJ mol⁻¹, the uptake being due to adsorption on only one-third of the Ni²⁺ cations. The uptake for CO is 6 mmol g⁻¹, with adsorption enthalpies ranging from -24 to -14 kJ mol⁻¹. This uptake is due to adsorption on all the Ni²⁺, meaning the adsorption enthalpies are high enough to allow the structure to relax. This is also observed for adsorption of CH₃CN and CH₃OH, where there is a return to rhombohedral symmetry after uptake. The adsorption sites in dehydrated Ni and Co STA-12 were investigated via Infra-red spectroscopic analysis of adsorbed probe molecules (H₂, CO, CO₂, CH₃CN and CH₃OH). The results indicate the adsorption sites at both low and ambient temperature are the metal cations and the P=O groups. The metal cation sites are also characterised as Lewis acids with reasonable strength. STA-12 was shown to have acidic activity for the liquid phase selective oxidations of 1-hexene and cyclohexene, although there is evidence active sites are coordinated by products and/or solvents during the reaction. STA-12 also demonstrates basic activity for the Knoevenagel condensation of ethyl cyanoacetate and benzaldehyde. Modification of STA-12 by adsorption of diamine molecules causes a slight increase in the basicity, and the highest conversions are where water and diamine molecules are both present.