Theoretical Study On The Interaction Of Mn-oxo Corrole And DNA With The Oxidative Cleavage Mechanism

Corrole as a kind of macrocyclic molecule with 18π electron that is structurally similar to porphyrin has been gradually attracted widespread attention to recent years. The studies have shown that the transition metal corrole complex also has reactivity of catalytic oxidative cleavage of DNA, and this may be due to the generation of reactive metal-oxo structure. Currently, theoretical study of the interaction of the transition metal corrole with DNA is still rare, relevant interaction and cleavage mechanism remains to be further elucidated. In this paper, quantum mechanics and molecular mechanics were applied to theoretical study the interaction of metal-oxo corrole with DNA. The main contents are as follows:1. DFT method was used to optimize the structures of Mn-oxo corrole complexes and its intermediates and products of catalytic oxidation reaction with different spin multiplicities, and the spin density and the frontier orbitals of these complexes were analyzed. The results showed that, when Mn-oxo corrole is singlet or triplet spin state, the Mn≡O structure has reactivity to absorb an electron from guanine which can lead to gaunine oxidation and oxidative cleavage of DNA through charge transfer reaction; when Mn-oxo corrole is quinet spin state, the oxygen atom in the Mn≡O structure has the character of free radical which can lead to H?-atom abstraction of the deoxyribose and oxidative cleavage of DNA by Oxygen transfer reaction.2. Molecular docking method was used to study the interaction and binding conformation of three Mn-oxo corrole complexes that have different substituents and two kinds of DNA that is composed by AT and GC base pair sequence respectively. The results showed that, the only binding mode between all Mn-oxo corrole complexes and DNA composed by AT base pair sequence is minor groove binding mode. Between Mn-oxo corrole complexes which have methylpyridine substituents and DNA composed by GC base pair sequence, there are two kinds of binding mode which are minor groove binding mode and major groove binding mode respectively. At the same time, the corrole rings of Mn-oxo corrole complexes have different charge distribution because of the different substituents which also lead to the different length of O-H structure that related to oxygen transfer oxidative cleavage of DNA Reaction in the binding conformations which were the Mn-oxo corrole complexes binding by minor groove binding mode.3. Molecular dynamics simulation was used to simulate the optimal binding conformation in the molecular binding results. The trajectory of the binding conformations and the changing of interaction energy between Mn-oxo corrole complex and DNA with time were analyzed. The results showed that, when Mn-oxo corrole complexes bind to the DNA by minor groove mode, the conformations between Mn-oxo corrole complexes and DNA composed by AT base pair sequence are more stable than that between Mn-oxo corrole complexes and DNA composed by GC base pair sequence, meanwhile the length of O-H structure of the former bonding conformation was shorter. When Mn-oxo corrole complexes bind to the DNA composed by GC base pair sequence by minor groove mode, the conformations of Mn-oxo corrole complexes change a lot but remain in the major groove binding site.