The formation of base pair radical anions and cations is closely related to many fascinating research fields in biology and chemistry such as genetic mutation, radiation-induced DNA damage and dynamics of charge transfer in DNA. However, the relevant knowledge so far mainly comes from studies on isolated base pair radical anions and cations, and their behavior in the DNA environment is less understood. In this study, we focus on how the nucleobase sequence affects the properties of the guanine¡Vcytosine (G:C) base pair radical anion and cation. The energetic barrier and reaction energy for the proton transfer along the N1(G)¡VH¡E¡E¡EN3(C) hydrogen bond and the stability of (G:C)¡E (i.e., electron affinity and ionization potential of G:C) embedded in different sequences of base-pair trimer were evaluated using density functional theory and two-layer ONIOM method. The computational results demonstrated that the presence of neighboring base pairs has an important influence on the behavior of (G:C)¡E in the gas phase. The excess electron and positive hole were found to be localized on the embedded G:C and the charge leakage to neighboring base pairs was very minor in all of the investigated sequences. Accordingly, the sequence behavior of the proton transfer reaction and the stability of (G:C)¡E is chiefly governed by electrostatic interactions with adjacent base pairs. However, the effect of base stacking, due to its electrostatic nature, is severely screened upon hydration, and thus, the sequence dependence of the properties of (G:C)¡E in aqueous environment becomes relatively weak and less than that observed in the gas phase. The effect of geometry relaxation associated with neighboring base pairs as well as the possibility of proton transfer along the N2(G)¡VH¡E¡E¡EO2(C) channel have also been investigated. The implications of the present findings to the electron transport and radiation damage of DNA are discussed.

Free energy simulations have been widely employed to compute the thermodynamic properties of many important biochemical processes. In the first part of this dissertation, two important biochemical processes, protonation/deprotonation of acid in solution and solvation of small organic molecules, are investigated using free energy simulations. Accurate computation of the pKa value of a compound in solution is important and challenging. To efficiently simulate the free energy change associated with the protonation/deprotonation processes in solution, a new method of mixing Hamiltonian, implemented as an approach using a fractional protonin the hybrid quantum mechanics/molecular mechanics (QM/MM) scheme, is developed. This method is a combination of a large class of λ-coupled free-energy simulation methods and the linear combination of atomic potential approach. Theoretical and technical details of this method, along with the calculation results of the pKa value of methanol and methanethiol molecules in aqueous solution, are discussed. The simulation results show satisfactory agreement with experimental data. Though the QM/MM method is one of the most useful methods in the modeling of biochemical processes, little attention has been paid to the accuracy of QM/MM methods as an integrated unit. Therefore, the solvation free energies of a set of small organic molecules are simulated as an assessment of ab initio QM/MM methods. It shows that the solvation free energy from QM/MM simulations can vary over a broad range depending on the level of QM theory / basis sets employed. Diffuse functions tend to over-stabilize the solute molecules in aqueous solution. The deviations pose a pressing challenge to the future development of new generation of MM force fields and QM/MM methods if consistency with QM methods becomes a natural requirement. In the second part of the dissertation, the dynamic and energetic properties of two molten globule (MG) protein molecules, α-lactalbumin(α-LA) and monomeric chorismate mutase (mCM) are investigated using molecular dynamics simulations. The exploring of the molecular mechanism of protein folding is a never-settled battle while the properties of MG states and their roles in protein folding become an important question. The MGs show increased side chain flexibility while maintain comparable side-chain coupling compared to the native state, which partially explains the preserving of native-like overall conformation. The enhanced sampling method, temperature-accelerated molecular dynamics (TAMD), is used for the study of the hydrophobic interactions inside both biomolecules. The results suggest that these hydrophobic cores could overcome energy barriers and repack into new conformation states with even lower energies. The repacking of the hydrophobic cores in MGs might be served as a criterion for recognizing the MGs in large class of biomolecules. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

The axilla is a major source of human body odour from which the characteristic musky, urinous or acidic odours emanate, and are predominantly due to bacterial metabolism of the protein-rich fluid secreted by the apocrine and sebaceous glands located in this area (Senol and Fireman, 1999). Clothing has been implicated in contributing to body odour intensity, possibly even increasing the intensity (Dravnieks, et al., 1968; Shelley, et al., 1953) by the transfer of secretions, skin debris and bacteria from the body to the fabric substrate. Despite much anecdotal evidence indicating that some fibres and fabrics are better at limiting odour intensity than others, there appears to be no published research confirming this. The purpose of this study therefore, was to determine whether fabrics varying in fibre content (cotton, wool, polyester) and fabric knit structure (interlock, single jersey, 1x1 rib) differed in the extent to which they retained and emanated axillary odour following wear, and whether the intensity of odour was linked to the number of bacteria transferred to the fabrics. A procedure for collecting odour on fabrics was developed as was a method for evaluating odour through use of a sensory panel. Total aerobic bacteria and aerobic coryneform bacteria extracted from the fabrics were counted to determine if an association between bacterial counts and fabrics existed. Sensory analysis recognises the unique capability of humans as odour-detecting instruments whereas, instrumental analysis has the potential to offer information on the concentration and identification of axillary compounds, which a human assessor cannot. To investigate a new method for detecting axillary odour on apparel fabrics, proton transfer reaction mass spectrometry (PTR-MS) was used to analyse volatiles emitted from fabrics differing in fibre type. After removal of garments from the human body, axillary odour can be detected on fabrics, with the intensity of odour being strongly influenced by the fibre type from which the fabrics had been made. Polyester fabrics emanated odour of high intensity, cotton that of mid-low odour intensity, and wool fabrics were low odour. Fabric structural properties such as thickness, mass per unit area and openness of knit structure also had an effect on odour intensity. However, as the principal factor influencing odour intensity was fibre, only fabrics characterised by a high intensity (i.e. polyester) were influenced by structural properties. Differences in odour intensity among fabrics were not necessarily related to bacterial numbers, and no �inherent antimicrobial� properties were evident for any of the fabrics. Bacterial populations persisted in all fabrics up to 28 days. A decline in numbers was apparent for high-odour polyester fabrics, while numbers in low-odour wool fabrics remained relatively stable. PTR-MS detected compounds likely to be short-chain carboxylic acids which increased in the headspace above the polyester fabrics after 7 days. However, this increase was not evident for either the wool or cotton fabrics. Therefore, bacterial numbers per se cannot be a predictor of the odour intensity emanating from fabrics at least on the basis of these fabrics and fibres. The intensity of axillary odour emanating from fabrics was found inversely related to fibre hygroscopicity. Keywords:fibre content, fabric structure, axillary odour, sensory analysis, bacteria, corynebacteria, instrumental analysis, PTR-MS

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Thesis (Ph.D.)--Ohio University, March, 2009. / Title from PDF t.p. Includes bibliographical references.

Thesis (Ph. D.)--Michigan State University. Dept. of Chemistry, 2006. / Title from PDF t.p. (viewed on June 19, 2009) Includes bibliographical references (p. 148-154). Also issued in print.

Thesis (M. S.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009. / Committee Chair: Tolbert, Laren; Committee Member: Bunz, Uwe; Committee Member: Payne, Christine

Thesis (doctoral)--Göteborg University, 1998. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Göteborg University, 1998. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (Ph. D.)--Worcester Polytechnic Institute. / Keywords: kinetic modeling; electrocatalysis; CO tolerance; PEM fuel cells. Includes bibliographical references.