This thesis involves two parts. The first is a new-proposed theoretical approach
called generalized atoms in molecules (GAIM). The second is a computational study
on the deamination reaction of adenine with OH⁻/nH₂O (n=0, 1, 2, 3) and 3H₂O.
The GAIM approach aims to solve the energy of each atom variationally in the first
step and then to build the energy of a molecule from each atom. Thus the energy of
a diatomic molecule (A-B) is formulated as a sum of its atomic energies, EA and EB.
Each of these atomic energies is expressed as,
EA = Hᴬ + Vₑₑᴬᴬ + 1/2Vₑₑᴬᴮ
EB = Hᴮ + Vₑₑᴮᴮ + 1/2Vₑₑᴬᴮ
where; Hᴬ and Hᴮ are the kinetic and nuclear attraction energy of electrons of atoms
A and B, respectively; Vₑₑᴬᴬ
and Vₑₑᴮᴮ
are the interaction energy between the electrons
on atoms A and B, respectively; and Vₑₑᴬᴮ is the interaction energy between the
electrons of atom A with the electrons of atom B. The energy of the molecule is then
minimized subject to the following constraint,
|ρA(r)dr + |ρB(r)dr = N
where ρA(r) and ρB(r) are the electron densities of atoms A and B, respectively, and
N is the number of electrons. The initial testing of the performance of GAIM was done through calculating dissociation curves for H₂, LiH, Li₂, BH, HF, HCl, N₂, F₂, and Cl₂.
The numerical results show that GAIM performs very well with H₂, LiH, Li₂, BH, HF,
and HCl. GAIM shows convergence problems with N₂, F₂, and Cl₂ due to difficulties
in reordering the degenerate atomic orbitals Pₓ, Py, and Pz in N, F, and Cl atoms.
Further work for the development of GAIM is required.
Deamination of adenine results in one of several forms of premutagenic lesions
occurring in DNA. In this thesis, mechanisms for the deamination reaction of adenine
with OH⁻/nH₂O, (n = 0, 1, 2, 3) and 3H₂O were investigated. HF/6-31G(d),
B3LYP/6-31G(d), MP2/6-31G(d), and B3LYP/6-31+G(d) levels of theory were employed
to optimize all the geometries. Energies were calculated at the G3MP2B3 and
CBS-QB3 levels of theory. The effect of solvent (water) was computed using the polarizable
continuum model (PCM). Intrinsic reaction coordinate (IRC) calculations were
performed for all transition states. Five pathways were investigated for the deamination
reaction of adenine with OH⁻/nH₂O and 3H₂O. The first four pathways (A-D)
begin with by deprotonation at the amino group of adenine by OH⁻, while pathway
E is initiated by tautomerization of adenine. For all pathways, the next two steps
involve the formation of a tetrahedral intermediate followed by dissociation to yield
products via a 1,3-hydrogen shift. Deamination with a single OH⁻ has a high activation
barrier (190 kJ mol⁻¹ using G3MP2B3 level) for the rate-determining step. Addition
of one water molecule reduces this barrier by 68 kJ mol⁻¹ calculated at G3MP2B3
level. Adding more water molecules decreases the overall activation energy of the reaction,
but the effect becomes smaller with each additional water molecule. The most
plausible mechanism is pathway E, the deamination reaction of adenine with 3H₂O,
which has an overall G3MP2B3 activation energy of 139 and 137 kJ mol⁻¹ in the gas
phase and PCM, respectively. This barrier is lower than that for the deamination with
OH⁻/3H₂O by 6 and 2 kJ mol⁻¹ in the gas phase and PCM, respectively