Structural flexibility versus rigidity of the aromatic unit of DNA ligands: binding of aza- and azoniastilbene derivatives to duplex and quadruplex DNA.
Structural flexibility versus rigidity of the aromatic unit of DNA ligands: binding of aza- and azoniastilbene derivatives to duplex and quadruplex DNA.
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DOI：
10.1039/c9ob00809h
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发表时间：
2019-07
影响因子：
3.2
通讯作者：
Heiko Ihmels;Mohebodin Karbasiyoun;Katharina Löhl;Christopher Stremmel
中科院分区：
文献类型：
--
作者：
Heiko Ihmels;Mohebodin Karbasiyoun;Katharina Löhl;Christopher Stremmel
合成了已知的叠氮斯蒂苯(E)-1,2-二（喹啉-3-基）乙烷（2a）和新型叠氮斯蒂苯衍生物(E)-2-（2-（萘-2-基）乙烯基）喹啉鎓（2b）和(E)-3,3'-（乙烷-1,2-二基）双（1-甲基喹啉-1-ium） （2c）。通过光度法、荧光法、极化法和流动ld分析、热DNA变性研究以及1H-NMR光谱研究了它们与双链和四链DNA （G4-DNA）的相互作用。本研究的主要目的是将这些构象灵活的化合物与已知的g4 - dna结合重氮二苯并[b，k]蒽进行比较，后者具有相当的π系统范围，但结构刚性。我们观察到，偶氮和偶氮茋衍生物2a-c，即具有几乎相同的空间尺寸和空间需求的化合物，与DNA的结合具有亲和力和选择性，这在很大程度上取决于正电荷的数量。而电荷中性衍生物2a非特异性地与双链DNA的DNA主链结合，离子化合物2b和2c是典型的DNA插层剂。值得注意的是，双喹啉衍生物2c以中等亲和力与G4-DNA结合（Kb = 4.8 × 105 M-1），并稳定G4-DNA的热变性（ΔTm = 11°C，配体- dna比= 5.0）。引人注目的是，相应的刚性对应物4a，12a-重氮-8,16-二甲基二苯并[b，k]chrysene在相同的条件下（ΔTm = 27°C）更大程度上稳定了G4-DNA。这些结果表明，与具有基本相同尺寸和π体系范围的刚性配体相比，G4-DNA配体的灵活性增加并不一定导致与G4-DNA更强的相互作用。
The known azastilbene (E)-1,2-di(quinolin-3-yl)ethane (2a) and the novel azoniastilbene derivatives (E)-2-(2-(naphthalen-2-yl)vinyl)quinolizinium (2b) and (E)-3,3'-(ethane-1,2-diyl)bis(1-methylquinolinin-1-ium) (2c) were synthesized. Their interactions with duplex and quadruplex DNA (G4-DNA) were studied by photometric, fluorimetric, polarimetric and flow-LD analysis, and by thermal DNA denaturation studies, as well as by 1H-NMR spectroscopy. The main goal of this study was a comparison of these conformationally flexible compounds with the known G4-DNA-binding diazoniadibenzo[b,k]chrysenes, that have a comparable π-system extent, but a rigid structure. We have observed that the aza- and azoniastilbene derivatives 2a-c, i.e. compounds with almost the same spatial dimensions and steric demand, bind to DNA with an affinity and selectivity that depends significantly on the number of positive charges. Whereas the charge neutral derivative 2a binds unspecifically to the DNA backbone of duplex DNA, the ionic compounds 2b and 2c are typical DNA intercalators. Notably, the bis-quinolinium derivative 2c binds to G4-DNA with moderate affinity (Kb = 4.8 × 105 M-1) and also stabilizes the G4-DNA towards thermal denaturation (ΔTm = 11 °C at ligand-DNA ratio = 5.0). Strikingly, the corresponding rigid counterpart, 4a,12a-diazonia-8,16-dimethyldibenzo[b,k]chrysene, stabilizes the G4-DNA to an even greater extent under identical conditions (ΔTm = 27 °C). These results indicate that the increased flexibility of a G4-DNA ligand does not necessarily lead to stronger interactions with the G4-DNA as compared with rigid ligands that have essentially the same size and π system extent.