Radical reaction pathway and kinetics of cationic radicals, an important intermediate of cytosine oxidative damage, in i-motif DNA structure

Nucleic acid is a kind of biological information macromolecule with nucleotide as the basic unit, which has complex structure and important biological function The secondary structure of nucleic acid is not only the DNA double helix structure which was first confirmed by Watson and Crick through X-ray crystal diffraction, but also the novel secondary structure of nucleic acid which plays an important role in regulating the life process For example, i-motif is a c-quadruplex structure formed by the C-base of cytosine rich DNA sequence protonated in one chain under the condition of micro acidity, and then hydrogen bonded with another chain (non protonated) for C (H) +: C I-motif exists in the promoter region of proto oncogene, which is the target of gene regulation and anticancer therapy, and it can also be used as a transcription activator to regulate gene expression With the discovery of i-motif in human nucleus, its importance has become more and more prominent Recently, Professor Su Hongmei's research group of School of chemistry, Beijing Normal University has studied the radical reaction pathway and kinetics of C • + which is an important intermediate of cytosine oxidative damage in i-motif DNA structure The key free radical intermediates in the reaction process were detected by time-resolved spectroscopy It was observed that the reaction pathway of C • + in i-motif structure was quite different from that of deproton reaction in single base DC, which was mainly manifested as C • + hydration reaction The products of hydration reaction were C (5OH) • and C (6oh) · The characteristic spectrum of free radicals, the rate constant of hydration reaction (1.3 × 104 s-1) Furthermore, the mechanism of structure related reaction kinetics was revealed by pH dependent experiment, single strand DNA control experiment and silver ion regulated i-motif DNA control experiment The author found that in i-motif DNA, the C (H) +: C hydrogen bond structure inhibited the formation of more stable imine radicals by C (- H) isomerization of C • + deproton radicals, making the proton balance change to C • +, which led to the formation of C (- H) tends to retain the characteristics of C • +, so the hydration of C • + mainly occurred in i-motif DNA This study not only reveals the significant influence of hydrogen bond structure microenvironment on the reaction pathway, but also helps to understand the molecular mechanism of gene mutation related to oxidative damage of C-base in organism at a deeper level Especially for i-motif DNA, the results show that C • + hydration and the C (5OH) • and C (6oh) • radicals produced by hydration can cause a series of secondary reactions and destroy the stability and structure of i-motif DNA, while the biological function of i-motif DNA is highly dependent on its four strand structure Relevant achievements were published in J am Chem SOC (J am Chem SOC 2019, 141, 1970-1979) under the title of "graduation of cytosine radical categories in 2 '- deoxycytidine and in i-motifdna: hydrogen binding guided pathways" The school of chemistry of Beijing Normal University is the first unit The research work has been greatly supported by NSFC Science Fund for Distinguished Young Scholars and Beijing Normal University Talent Introduction Program.