Sharma Hemant, Sidhu Jagpreet S, Hassen Walid M, Singh Narinder, Dubowski Jan J
Laboratory for Quantum Semiconductors and Photon-Based BioNanotechnology, Interdisciplinary Institute for Technological Innovation (3IT), CNRS UMI-3463, Department of Electrical and Computer Engineering, Université de Sherbrooke, Sherbrooke, Québec J1K 0A5, Canada.
Department of Chemistry, Indian Institute of Technology Ropar, Rupnagar, Punjab 140001, India.
ACS Omega. 2019 Mar 31;4(3):5829-5838. doi: 10.1021/acsomega.8b03638. Epub 2019 Mar 26.
The development of organic molecules to target nucleic acid is an active area of research at the interface of chemistry and biochemistry, which involves DNA binding, nuclear imaging, and antitumor studies. These molecules bind with DNA through covalent interactions, electrostatic interactions, or intercalation. However, they are less permeable to membrane, and they have a significant cytotoxicity, which limits their application under in vivo conditions. In the present work, various mono- and disubstituted 1,8-naphthalimides-based derivatives (, , , and ) have been synthesized and characterized through various spectroscopic techniques. Among these, 3-amino-4-bromo-1,8-naphthalimide () was found to have an attractive water solubility and act as a nuclear imaging agent. The spectroscopic absorption and emission data showed that has a strong affinity for salmon sperm DNA with a binding constant of 6.61 × 10 M, and the ratiometric fluorescence intensity ( / ) of has a linear relationship in the 0-50 μM range of DNA concentrations. It intercalates with DNA through the hydrophobic planar naphthalimide core as confirmed through cyclic voltammetry, circular dichroism, H NMR titration, and thermal denaturation studies. Positively charged amine groups also participate in H-bonding with the bases and backbone of DNA. The intercalator showed a large Stokes shift and photostability, which made it attractive for direct imaging of , without the need for a prior membrane permeabilization.
开发靶向核酸的有机分子是化学与生物化学交叉领域的一个活跃研究方向，涉及DNA结合、核成像及抗肿瘤研究。这些分子通过共价相互作用、静电相互作用或嵌入作用与DNA结合。然而，它们的膜通透性较差，且具有显著的细胞毒性，这限制了它们在体内条件下的应用。在本研究中，通过各种光谱技术合成并表征了多种基于单取代和双取代1,8 -萘二甲酰亚胺的衍生物（、、、）。其中，3 -氨基 - 4 -溴 - 1,8 -萘二甲酰亚胺（）具有良好的水溶性，可作为核成像剂。光谱吸收和发射数据表明，对鲑鱼精DNA具有很强的亲和力，结合常数为6.61×10 M，在0 - 50 μM的DNA浓度范围内，的比率荧光强度（/）呈线性关系。通过循环伏安法、圆二色性、核磁共振氢谱滴定和热变性研究证实，它通过疏水平面萘二甲酰亚胺核心与DNA嵌入结合。带正电荷的胺基也参与与DNA碱基和主链的氢键形成。该嵌入剂表现出较大的斯托克斯位移和光稳定性，这使得它无需事先进行膜通透化处理即可直接对进行成像，颇具吸引力。
