Theoretical Studies On Damage Of The DCMP Molecule By OH Radical And The Redox Characteristics Of Hydrophobic Amino Acids

DNA damage and protein damage are important reasons those cause various diseases. In recent years, there are plenty of papers reported research results in the field, but it is still a challenge to the experimental studies that reaction intermediates in damage of DNA and amino acides are present with extremely short-life. The short-life of these reaction intermediates usually results in special difficulties to their analysis. However, by using the methods based on theoretical chemistry one can overcome such problems and gain some new insights into molecular mechanisms of DNA damage and amino acides damage. In this paper, B3LYP/DZP++ method was used to research the chemical properties of many small biological molecules and the theoretcial results are in accordance with the available experimental studies.Many studies indicate that the hydroxyl radical is responsible for gene mutation, canceration and aging of cell. Exploring the molecular geometries and electronic structures of adducts between hydroxyl radical and deoxyribonucleic acid with reliable theoretical method enables us to understand the chemistry of hazardous reaction between hydroxyl radical and DNA nucleotides. The theoretical investigations based on B3LYP/DZP++ method reveal that the relative stability sequence of one hydroxyl radical adducts of cytosine of 2'-deoxycytidine-5'-monophosphate acid (dCMP), one of the smallest units of DNA, is C5＞C6＞＞C4≥C2. The C5 atom of dCMP was found to be the most highly reactive one for addition of the first hydroxyl radical whereas the C6 atom is the second site for another addition of hydroxyl radical when one dCMP molecule is attacked by multi-hydroxyl radicals, according to the analyses of their stabilities, spin densities, electrostatic potentials of adducts and electron densities, electrostatic potentials, charge distributions of dCMP. Once the C2-adduct of dCMP are produced, either a fatal gene mutation during DNA replication or DNA-DNA, DNA-protein cross-links, leading to more complicated damage of DNA, might occur. In contrast, the C5- and C6-adducts of dCMP have no direct significant effect on the stability of DNA.The monomeric building blocks of proteins are 20 amino acids, whose redox process occurred in biological systems will directly affect the stability of the protein.Glycine(Gly), alanine(Ala), valine(Val), leucine(Leu), isoleucine(Ieu), cysteine(Cys), proline(Pro), methionine(Met),phenylalanine (Phe), tyrosine(Tyr) and tryptophan (Trp) molecules are hydrophobic as their nonpolar side chains. These amino acids often aggregate to form the waterinsoluble cores of many proteins, which is important for the stability of protein. The characteristics of one electron redox of hydrophobic amino acids in gas phase was calculated with density functional theory at the B3LYP/DZP++ level in chapter 4. For glycine, alanine, proline, valine, leucine, and isoleucine with small side chains, the computational results indicate that the negative charge are removed from the atoms of their amino, a-carbon and carboxy moieties in one electron oxidation reactions, yielding large values of adiabatic ionization potentials (AIP),8.52-9.15 eV. The AIPs of cysteine, methionine, phenylalanine, tyrosine and tryptophan decrease due to more removal of negative charge from the atoms of their side chains. The attachment of one electron to the molecules of hydrophobic amino acids lead to anions in which the extra electron is bound both to the H atoms of carboxyl group or amino group and to their valence orbitals, reflecting their double natures of dipole-bound state and valence state. The values of electron affinities (EA) for the amino acids are small and negative, ranging from 0.08 to -0.63 eV. The molecules of hydrophobic amino acids are difficult to be oxidized or reduced in gas phase because of their higher VIPs and negative EAs.The single electron oxidation of cysteine molecule results in significant alterations in its molecular geometries and electronic structures. This single electron oxidation reaction, molecular ionization, occurs in two steps. The first one is the vertical ionization with the formation of transient cation which are followed by the second step—structural relaxation of the transient cation, resulting in steady-state cation or ion decomposition. From the resaearches of molecular ionization process by using both experimental methods and quantum chemical methods one can only find the initial molecular geometry and electronic structure of the neutral molecule, the transient and steady-state cation but can not understand the specific process of intramolecular electron transfer during the structural relaxation of the transient cation. In chapter 5, B3LYP/DZP++ was employed to carefully study the electron structures and molecular geometries of Cystine, its cation radicals and five possible intermediate species. By this study, we expect to "observe" the real changes of the geometrical structure and electronic structure during the ionization of cysteine molecule. The computational results indicated that, in this process, the electron redistribute not only in the intra-MO32αand the intra-MO31β, respectively, but also between MO32αand MO31β. Intra-molecular electron redistribution leads to the alteration of molecular geometry and the decrease of energy of transient Cystine cation radical after the vertical ionization of Cystine molecule.