多芳基咪唑CPD的合成及与G-四链体相互作用研究

Synthesis and G-quadruplex Interaction of Polyarylimidazole CPD

以4-氟苯甲醛为起始原料,通过安息香缩合反应、氧化反应、亲核取代反应以及Debus-Radziszewski咪唑合成反应等步骤,合成得到了多芳基咪唑CPD.^(1)H NMR、^(13)C NMR和HRMS确证其结构.紫外光谱实验和荧光光谱实验研究表明CPD对部分G-四链体具有一定的荧光识别作用,特别是可以识别c-myc G-四链体.单链DNA、双链DNA均不能使CPD的荧光产生增强,表现出较好的选择性.分子对接结果表明:CPD能堆积在G-四分体上,两条胺基侧链深入到G-四链体的负电性沟槽中,发生静电吸引作用,导致原有的分子构象发生变化,因而发射出荧光.

Polyarylimidazole CPD was synthesized by using 4-fluorobenzaldehyde as the starting material via benzoin condensation reaction,oxidation reaction,nucleophilic reaction,and Debus-Radziszewski imidazole synthesis reaction,which was characterized by ^(1)H NMR,^(13)C NMR and HRMS.The results of UV spectrum and fluorescence spectroscopy studies demonstrate that CPD could show certain fluorescence recognition effects on most G-quadruplexes,especially c-myc G-quadruplex.Neither single-stranded DNA nor double-stranded DNA could enhance the fluorescence of CPD,showing good selectivity.The molecular docking results showed that CPD could accumulate on the G-tetrad,and two amino side chains could interact with negatively charged phosphate diester backbone of G-quadruplex through electrostatic interactions,causing the change of original molecular structure,and thus emit fluorescence.