光诱导的DNA交联过程具有高空间-时间分辨率和控制优势。我们设计、合成并表征了几种通过350纳米辐射激活可以诱导各种DNA损伤的4,4'-二溴萘类似物(1a-f)，包括DNA链间交联(ICL)形成、链断裂和碱性易损DNA损伤。这些化合物诱导的DNA损伤的程度和类型取决于底物的离去基团、缓冲溶液的pH值和DNA序列。DNA ICL产物是通过氧化1a-f光诱导产生的自由基生成的碳正离子形成的。大多数这些化合物单独对癌细胞表现出最小的细胞毒性，而350纳米辐射大大增强了它们的抗癌效果（最多增强40倍），因为它们能引起细胞DNA的光诱导损伤。这项研究为进一步设计可光诱导的DNA交联剂作为具有毒性和选择性良好控制的光激活型抗癌前药提供了指导。版权所有 © 2023 Elsevier Inc.

Photoinduced DNA cross-linking process showed advantages of high spatio-temporal resolution and control. We have designed, synthesized, and characterized several 4,4'-dibromo binaphthalene analogues (1a-f) that can be activated by 350 nm irradiation to induce various DNA damage, including DNA interstrand cross-links (ICL) formation, strand cleavages, and alkaline labile DNA lesions. The degree and types of DNA damage induced by these compounds depend on the leaving groups of the substrates, pH value of the buffer solution, and DNA sequences. The DNA ICL products were produced from the carbocations formed via the oxidation of free radicals photo-generated from 1a-f. Most of these compounds alone exhibited minimum cytotoxicity towards cancer cells while 350 nm irradiation greatly improved their anticancer effects (up to 40-fold enhancement) because of photo-induced cellular DNA damage. This work provides guidance for further design of photo-inducible DNA cross-linking agents as potent photo-activated anticancer prodrugs with good control over toxicity and selectivity.Copyright © 2023. Published by Elsevier Inc.