Computational Design Of DNA-based Motifs And Theoretical Studies Of Their Structural And Electronic Properties

In vivo, DNA, which possesses the self-assembled and replicated structure, is the fundamental substance for gene storage and expression. The stability of DNA ensures the possibility for DNA to act as carrier of genetic information. Further more, it provides the basis of DNA-based functional molecular wire. The DNA helix is flexible and is extremely successful in it ability to arrange the bases into stacked structures. The nucleobases, which is the "functional group"'of DNA, undertake many functions of information storage and feature recognition. Despite that, they have limitations:there are only four kinds of DNA nucleobases so that there are only four series of ionization energetics; there are only two types of structural units in DNA because of the fixed pairing mode; electric conductivity of DNA is still under discussion; natural nucleobases and base pairs are nearly non-fluorescent. Thus, many efforts have been devoted to the nucleobase-modification. Thus, we devote to modify and expand these properties. Some significant achievements have been made, as discussed below.(1). The design of new DNA motifs is at present a very interesting topic. Recent progress indicates that the hetero-ring-expanded guanine (G) analogues possess enhanced properties compared with natural guanine. In this work, a series of hetero-ring-expanded adenine (A) analogues are designed, and their structures and electronic properties are investigated by means of density functional calculations and molecular dynamics simulations. The results indicate that the designed A-analogues can form stable base pairs with natural counterpart, and the pairing energetics for the Watson-Crick hydrogen-bonded dimers between the expanded A-analogues and natural T exhibit similarity to natural AT. Their tautomeric preferences are close to natural A, too. Furthermore, compared with natural ones, most size-expanded adenines and corresponding base pairs have smaller ionization potentials. In particular, several designed A analogues have ionization potentials even lower than natural G. The electron affinities of these modified A are comparable with that of natural A. The HOMO-LUMO gaps also behave with sensible trends. Most of A-analogues and their interrelated base pairs possess smaller gaps than the corresponding natural base and base pairs. Further, molecular dynamics simulations show the sufficient stabilities of the DNA analogues (dnA-dT)12(where nA represents the size expanded A-analogues designed here) when forming duplexes as the natural one does. Clearly, these observations imply their promising applications as molecular wires and new DNA motifs.(2). Motivated by a promising expansion of the genetic alphabet and a successful design of conductive DNA bases justified from the hetero-ring-expanded purine base (G and A) analogs, we extend our hetero-ring expansion scheme to the pyrimidine bases (C and T) to examine the ring-expansion effects on various properties of these single-ring bases with a comparison with those in the double-ring purine case. Four kinds of the hetero-rings are considered to expand C and T, forming the C and T analogs (nC and nT), respectively. The relevant structures and properties were investigated by means of quantum calculations and molecular dynamics simulations. The results reveal that all the modified bases can form base pairs specifically with their natural counterparts and assemble duplex helices which have comparable stability to native ones. The HOMO-LUMO gaps of G-nC and A-nT are smaller than those of the natural pairs, and the assembled duplex helices ((G-nC)12and (A—nT)12) are diameter-enlarged but with smaller rise and twist, both of which favor DNA-conduction, as confirmed by ionization potentials and spin density distributions. In addition, the hetero-ring expansion can lower the activation barriers and reduce the reaction heats of the inter-base double proton transfers. In particular, as evidenced by NMR parameters and the excited states, the hetero-ring expansion leads to an enhancement of the transverse electronic communication between two pairing bases, clearly facilitating the conduction along the helices. Furthermore, the hetero-ring expansion effect on the pyrimidine bases is larger than that on the purine bases. In summary, this work presents clear theoretical evidence for the possibility of hetero-ring expanded pyrimidine bases as promising candidates for the motifs of the genetic alphabet and DNA nanowires. (3). DNA oxidative damage can be caused by many sources. Long-range charge transport in DNA is strictly dependent on the electronic properties of guanine and surrounding polarized environment. Protein-DNA interaction is considered to be an important factor of charge transfer in DNA. In vivo, ArgH+-G interaction is one of the most typical representatives for protein-DNA interaction. So we investigate charge transfer process which is regulated by ArgH+-G interaction in DNA. Ten isomers which involve two hydrogen bonds between arginine residues and guanine bases are optimized, and among them, three most stable structures are chosen to be the basis of further investigation. Since electronic properties are important indexes of conductivity, both ionization potential and electron affinity of ArgH+-GC compounds are determined. The result shows that ionization potential of GC base pair is obviously increased due to the combination of protonated arginine, while electron affinity is decreased. Energetics of HT and ET processes has been studied to clarify the mechanism of charge transfer in DNA. The result shows that though energy differences of hole transfer (HT) and electron transfer (ET) process become smaller attributed to the ArgH+-G interaction, HT is still dominant mechanism of charge transfer. Further study of HT reveals that the essence of regulating effect of ArgH+-G interaction on charge transfer in DNA is that rate-determining step of HT can be changed. Investigation of HT in nucleosome core particle (NCP) indicates that effects of ArgH+-G interactions on charge transfer depend deeply on interaction distance and it can be ignored when the distance is about over7A.(4). In the present work, cyclopentadienyl radicals have been introduced to nucleobases to gain the building blocks of DNA-based molecular wire with novel electromagnetic characters. The broken symmetry unrestricted formalism has been employed to reveal the magnetic interactions of diradical molecules. The intra-and inter-base-pair interactions are examined by corresponding calculations on diradical base pairs and helices, respectively. The complete active space self-consistent field (CASSCF) calculations have been preformed to these systems to clarify the spin states of them. The magnetic characters of these diradical structures are represented with the magnetic exchange coupling constant (J). According to our investigation, the radical-introduced bases (r-bases) exist to be stable with the spin densities distribute mainly on the extra cyclopentadiene rings. For diradical base pairs, the broken symmetry unrestricted states appear to be the ground states and the intra-base-pair magnetic interactions are relatively weak according to the J values. In contrast, it has been proved by the calculations of diradical helices that the inter-base-pair magnetic interaction is stronger, especially in overlap-stacking diradical helices.Though this area is in the initial stage, it gains increasing attention of researchers. There is no doubt it will develop rapidly. Quickly, we'll see its applications in biological, supramolecular and materials Chemistry.