The Study On The Interaction Of Mn-oxo Corrole Complexes And DNA

Corrole is a kind of macrocyclic compound with similar structure of porphyrin,it is easy to combine metal to form high valence metal complexes.The Mn-oxo corrole complexes can catalyze oxidative cleavage of DNA and act as artificial nuclease,attracting more and more attention.At present,there is little research on the theoretical study of Mn-oxo corrole complexes and DNA.Therefore,the interaction between Mn-oxo corrole complexes and DNA was explored by density functional theory and molecular docking to discuss the effects of substituents and spin states.The results of simulation can provide theoretical support and important supplement for the experiment,explaining to some extent the mechanism of the interaction between Mn-oxo corrole complexes and DNA,so as to help the molecular structure design and provide guidance for the next experiment and theoretical research.The main contents include the following aspects:1.The effect of substituents on the catalytic oxidation activity of Mn-oxo corrole complexes were studied by density functional theory.The results show that the substituents with electron donating group can significantly improve the electron cloud density of the corrole ring,and then the corrole skeleton becomes smaller,the Mn?O bond grows longer and the raman vibration frequency is moving toward low frequency,and the bonding effect of triple bond is weakened.The Mn?O bond of Mn-oxo corrole complexes is a triple bond property,which is composed of d orbit and p orbit.The donating-electron substituents make the Mn?O group more and more negative,so that the nucleophilic reactivity is improved,which is beneficial to the abstract the hydrogen atoms of DNA,promoting the transfer of oxygen atoms and improve the activity of the oxidative DNA.2.The effect of substituents on the interaction of Mn-oxo corrole and DNA was discussed by molecular docking method.The docking results show that the Mn-oxo corrole complexes are mainly associated with DNA at the ditch position,including the minor groove and the major groove binding mode,and the minor groove is the main binding mode.The binding free energy of Mn-oxo corrole complexes and DNA mainly come from van der Waals forces,hydrogen bonds and desolvation interactions,while the contribution of electrostatic interactions is small.The Mn-oxo corrole complexes with electron donating substituents areattracted to the phosphosomal framework of DNA.The axial oxygen atom of the Mn-oxo corrole complexes and the H4' atom of DNA form hydrogen bonds.3.The effect of the spin state on the interaction of the Mn-oxo corrole complexes and DNA was studied by density functional theory and molecular docking method.The results show that the spin density of the axial oxygen atom of Mn-oxo corrole complexes with high spin state increases,and gradually shows the free radical property,which is beneficial to abstract the hydrogen atoms of DNA.The Mn-oxo corrole complexes with different spin states bind in the minor groove position,Mn-oxo corrole complexes with high spin is strong binding.The the axial oxygen atom of Mn-oxo corrole complexes with different spin states and the H4' atom of DNA form hydrogen bonds,and the high spin state lead to decrease the bond length of the hydrogen bonds.TheMn-oxo corrole complexes with high spin state are more likely to abstract hydrogen atom of DNA.