The Interaction Of Methylated Adenine With DNA Bases And The Design Of Fluorescent Probe Molecules

N6-methyladenine(m~6A) is a modified bases which is methylated, widely found inbacteria, prokaryotes and lower eukaryotes, it plays an important role in living organisms.However, in the higher animals, especially mammals, m~6A has not been detected. m~6A is ableto mismatch with natural DNA bases, thereby changing the mode of action of hydrogen bonds,reducing the thermodynamic stability of DNA and changing secondary structure of the DNA.Therefore, the interaction between m~6A and DNA bases is performed and the fluorescentprobe molecules are designed for detecting m~6A. In this thesis, the quantum chemical isapplied to investigate the interaction and measurement mechanism. The main contents are asfollows:In this work, M ller-Plesset second-order (MP2) has been used to investigate the bindingmechanism between m~6A and natural DNA bases in the gas phase and in aqueous solution.The results show that N-CH3has changed the way of m~6A binding to natural DNA bases. m~6Ais different from the base adenine due to its N-CH3. Therefore, the base not only pairs withthymine, but also with other DNA bases (cytosine, adenine and guanine). The properties ofthese hydrogen bonds are analyzed by atom in molecules (AIM) theory, natural bond orbital(NBO) analysis and Wiberg bond indexes (WBI). The binding style significantly influencesthe stability of base pairs. Besides, the trans-m~6A:G and trans-m~6A:G conformers are the moststable among all the base pairs, the solvent effect can remarkably reduce the stability of thebase pairs. And the DNA bases prefer pairing with trans-m~6A to cis-m~6A. In addition, pairingwith m~6A decreases the binding energies compared with the normal Watson-Crick base pairs,it may be explained the instability of the N6site methylated DNA in theory.The fluorescent probe molecules (BF, xBF, yyBF, J-AT, xJ-AT,, and yyJ-AT) are designedfor detecting m~6A. The interaction of adenine, m~6A and fluorescent probe molecules areperformed at the B3LYP level. AIM theory and NBO analysis are used to analyse the featuresof hydrogen bonds. The results show that the new designed fluorescent probe molecules retainthe type of hydrogen bonds and the stability of WC base pairs.The absorption and emission spectra of these fluorescent probe molecules areinvestigated by CIS and TD-DFT method. The results show that the naphtho-ring-expandedbase analogues (yyBF and yyJ-AT) and benzo-homologation (xBF and xJ-AT) have greaterconjugated system, red-shifted is found both in the absorption and emission spectra. Theelectronic spectrum properties of the base pairs are also studied to judge whether thesefluorescent probe molecules suit for detecting m~6A in theory. Although yyBF and yyJ-AThave stronger fluorescence, the maximum wavelengths are not changed compared to themonomers, respectively, so it is not suitable for detecting m~6A. While benzo-homologationand original bases have strong fluorescence, before and after the methylation, the maximum wavelengths of the base pairs change a lot, thus benzo-homologation and original bases aremore suitable for detecting m6A in theory. The benzo-homologation bases are better thanoriginal bases.