Studies on the Related Properties of Negative Dissociation Energy State Associated with the DNA Hole Migration
|Course||Theoretical and Computational Chemistry|
|Keywords||Negative dissociation energy Hole transfer Proton transfer Solvent effect Density functional|
Recently, extensive attention has been paid to long-distance radical cation migration in DNA. The radical cation (hole) formed by one-electron oxidation of DNA can migrate to remote guanines through DNAπ-stack, causing damage selectively at a guanine cluster. Damaged guanines have been believed to be sources of mutagenesis and carcinogenesis which can result in disease and aging. Although base sequences, base stacking, and accessibility of water and/or oxygen to the hole are the principle factors which can significantly affect the site and efficiency of hole trapping, some other factors in the biological environment around DNA can also modulate hole migration due to the presence of major/minor groove of DNA. In the present paper an unusual phenomenon of negative dissociation energy was first discovered in the process of duplex DNA hole transfer affected by some external factors, such as protonated cytosine in the triplex DNA CP·G(?)C, metal ion penetration into the major/minor grooves of DNA and the positively charged amino acid residues. The related properties of negative dissociation energy state and some factors which can affect this phenomenon such as proton transfer, hydrate effect and solvent effect were explored. The exploration of this novel phenomenon can offer some qualitative or quantitative understanding about the energy conversion/transfer mechanisms in the related fields. Some significant progresses have been made, which can be described as follows.1. Negative dissociation energy phenomenon discovered in triplex DNA hole transfer:Ab initio calculations reveal an unknown energetic phenomenon for H-bonds in the hole-trapping triplex CP·G(?)C motif observed experimentally in hole migration which can explain the lower but really available oxidization possibility in CP·G(?)C site. Hole-trapping can considerably destabilize the CP·G(?)C unit and lead to an unexpected barrier-hindered channel with a negative dissociation energy. This channel is governed by a balance between electrostatic repulsion and H-bonding attraction in the two associated moieties and different attenuations of two opposite interactions with respect to the H-bond distance. This CP·G(?)C unit can be viewed as a high-energy node in a DNA wire which modulates migration of a hole into or through it via its unusual energetics. It provides useful information for understanding of an unknown type of the complicated intermolecular interactions, a novel type of "high-energy" bond, and can be applied further to interpret the hidden transport properties and the energy conversion/transfer mechanisms in the related fields.2. Negative dissociation energy phenomenon discovered in duplex DNA hole transfer gated by metal counterion:In the present paper, we investigated the electronic and energetic properties of Na+GC, where sodium ion (Na+) binds to guanine (G) base at the N7 and 06 sites in the major groove, and its hole-trapped derivative [Na+GC]+ by using density functional theory calculations. Different from the normal dissociation of Na+GC which has positive dissociation energies, potential energy surface exploration on the hole-trapped Na+GC reveals an unusual energetics phenomenon that hole-trapping can reduce significantly the dissociation energy of the Na+...N7/O6 bond from positive to negative values (63.09 vs-14.80 kcal/mol), implying that hole-trapping destabilizes the Na+...N7/O6 bond in Na+GC. But frequency analysis verifies that this hole-trapped complex [Na+GC]+is still stable and does not spontaneously dissociate along its Na+...N7/O6 bond vector. This unexpected negative dissociation energy phenomenon indicates that a Na+GC complex could become metastable upon hole-trapping, and thus can reserve some energy (～16kcal/mol) in its Na+...N7/O6 bond zone. The topological properties of the electron densities and its Laplacian values at the bond critical points indicate that this energetics phenomenon mainly origins from additional electrostatic repulsion between two moieties linked via the energy-reserved bond (Na+...N7/O6 bond) due to the hole-trapping. Proton transfer from guanine to cytosine induced by hole-trapping can develop the negative dissociation energy phenomenon over both the Na+...N7/O6 and WC H-bond zones. Similar phenomenon can be observed for the case of the Na+ binding at the minor groove when hole-trapping. Hydration of the hole-trapped complexes may yield different effects on the negative dissociation energies, depending on the binding sites for water molecules. The negative dissociation energy in gas phase decreases with the increase of dielectric constants in the different solvents.3. Negative dissociation energy phenomenon discovered in duplex DNA hole transfer regulated by positive charged amino acid residues:The optimized geometries of complexes formed by the positively charged amino acid residues Y+ (Y+= ArgH+, LysH+ and HisH+) with one-electron oxidized guanine-cytosine (G+C) base pair in the major/minor groove were obtained at the level of B3LYP/6-311++G** and six of them were selected to explore the interaction between two monomers Y+and G+C. The groups of NH and NH2 in the amino acid residues can interact with N7 and O6 atoms of guanine base via one or two hydrogen bonds. From the exploration of potential energy surfaces (PESs) of these complexes, a novel phenomenon of negative dissociation energy was first discovered. That is, the dissociation energy is negative when the hydrogen bonds between the amino acid residues and one-electron oxidized GC base pair were broken, implicating that the energy of complex is larger than sum of energies of two monomers. But frequency calculation indicated that all these complexes are global minimum in their corresponding PESs. Obviously, this is a special phenomenon which is different from general combination. To explore these complexes at the state of high energy, the molecular orbital, electrostatic potential, spin density and the character of critical points of hydrogen bonds were considered. Base on the analysis of atom in molecular (AIM), the nature of negative dissociation energy is attributed to the electrostatic repulsion between two monomers Y+and G+C. The proton transfer reaction from guanine to cytosine can occur easily upon hole-trapping. The dissociation energy of Watson-Crick hydrogen bonds becomes negative in the product of proton transfer. In addition, the relation of dissociation energy and ionization potential (IP) in the complex Y+GC was also explored. The ionization potential of complex Y+GC has great increase when the dissociation energy is negative in the separation of Y+ from the complex Y+GC. 4. Construct energy-reserved bond:The phenomenon of negative dissociation energy is an unusual energetic phenomenon which was first discovered by our group. The chemical bond which has negative dissociation energy is taken as energy-reserved bond. This unusual energetic phenomenon appears not only in the complex in which the amino acid is binding with two positive ions but also the complexes in which one-electron oxidized guanine-cytosine (GC) base pair interacts with protonated cytosine (Cp), metal cations and positively charged amino acid residues. We attribute the nature of this phenomenon of negative dissociation energy to electrostatic repulsion between two monomers which were linked by energy-reserved bond. A series of model moleculars similar to base or base pair were designed to explore how to construct this energy-reserved bond and the external factors which can affect the value of negative dissociation energy were considered. The prerequisite to construct energy-reserved bond is that two monomers linked by energy-reserved bond are with same charge. The value of negative dissociation energy increases as the increase of number of water molecular. The effect of substituent group with different character on the value of negative dissociation energy is different. The value of negative dissociation energy increases in the substitute of electron withdrawing group and decreases in the electron-donating groups. In addition, we also found that the value of negative dissociation energy increases as the increase of bond length of energy-reserved bond.