Saraswathi Sajena Kanangat, Karunakaran Varsha, Maiti Kaustabh Kumar, Joseph Joshy
Photosciences and Photonics Section, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
Front Chem. 2021 Jul 22;9:716771. doi: 10.3389/fchem.2021.716771. eCollection 2021.
Development of small organic chromophores as DNA condensing agents, which explore supramolecular interactions and absorbance or fluorescence-based tracking of condensation and gene delivery processes, is in the initial stages. Herein, we report the synthesis and electrostatic/groove binding interaction-directed synergistic self-assembly of the aggregates of two viologen-functionalized tetraphenylethylene () molecules with CT-DNA and subsequent concentration-dependent DNA condensation process. molecules differ in their chemical structure according to the number of viologen units. Photophysical and morphological studies have revealed the interaction of the aggregates of in Tris buffer with CT-DNA, which transforms the fibrous network structure of CT-DNA to partially condensed beads-on-a-string-like arrangement with aggregates as beads electrostatic and groove binding interactions. Upon further increasing the concentration of , the "beads-on-a-string"-type assembly of complex changes to completely condensed compact structures with 40-50 nm in diameter through the effective charge neutralization process. Enhancement in the melting temperature of CT-DNA, quenching of the fluorescence emission of ethidium bromide/CT-DNA complex, and the formation of induced CD signal in the presence of molecules support the observed morphological changes and thereby verify the DNA condensation abilities of molecules. Decrease in the hydrodynamic size, increase in the zeta potential value with the addition of molecules to CT-DNA, failure of TPE-V/cucurbit(8)uril complex to condense CT-DNA, and the enhanced DNA condensation ability of with two viologen units compared to with a single viologen unit confirm the importance of positively charged viologen units in the DNA condensation process. Initial cytotoxicity analysis on A549 cancer and WI-38 normal cells revealed that these DNA condensing agents are non-toxic in nature and hence could be utilized in further cellular delivery studies.
作为DNA凝聚剂的小型有机发色团的开发尚处于初始阶段，该类发色团探索超分子相互作用以及基于吸光度或荧光的凝聚和基因传递过程追踪。在此，我们报告了两种紫精功能化的四苯乙烯（）分子与CT-DNA的聚集体的合成及其基于静电/沟槽结合相互作用的协同自组装，以及随后的浓度依赖性DNA凝聚过程。根据紫精单元的数量，分子的化学结构有所不同。光物理和形态学研究揭示了在Tris缓冲液中与CT-DNA相互作用，它将CT-DNA的纤维网络结构转变为部分凝聚的串珠状排列，其中聚集体作为珠子 静电和沟槽结合相互作用。进一步增加的浓度后，复合物的“串珠状”组装通过有效的电荷中和过程转变为直径为40-50nm的完全凝聚的致密结构。CT-DNA解链温度的升高、溴化乙锭/CT-DNA复合物荧光发射的猝灭以及在分子存在下诱导CD信号的形成支持了观察到的形态变化，从而验证了分子的DNA凝聚能力。向CT-DNA中添加分子后流体力学尺寸减小、zeta电位值增加、TPE-V/葫芦脲(8)复合物无法凝聚CT-DNA以及与单个紫精单元的相比具有两个紫精单元的DNA凝聚能力增强，证实了带正电的紫精单元在DNA凝聚过程中的重要性。对A549癌细胞和WI-38正常细胞的初步细胞毒性分析表明，这些DNA凝聚剂本质上无毒，因此可用于进一步的细胞递送研究。
