Department of Chemistry & Biochemistry , Utah State University , 0300 Old Main Hill , Logan , Utah 84322-0300 , United States.
Department of Chemistry & Biochemistry , Florida State University , Tallahassee , Florida 32306-4390 , United States.
J Am Chem Soc. 2018 Aug 1;140(30):9721-9729. doi: 10.1021/jacs.8b06011. Epub 2018 Jul 23.
The delivery of controlled amounts of carbon monoxide (CO) to biological targets is of significant current interest. Very few CO-releasing compounds are currently known that can be rigorously controlled in terms of the location and amount of CO released. To address this deficiency, we report herein a new metal-free, visible-light-induced CO-releasing molecule (photoCORM) and its prodrug oxidized form, which offer new approaches to controlled, localized CO delivery. The new photoCORM, based on a 3-hydroxybenzo[ g]quinolone framework, releases 1 equiv of CO upon visible-light illumination under a variety of biologically relevant conditions. This nontoxic compound can be tracked prior to CO release using fluorescence microscopy and produces a nontoxic byproduct following CO release. An oxidized prodrug form of the photoCORM is reduced by cellular thiols, providing an approach toward activation in the reducing environment of cancer cells. Strong noncovalent affinity of the nonmetal photoCORM to albumin enables use of an albumin:photoCORM complex for targeted CO delivery to cancer cells. This approach produced cytotoxicity IC values among the lowest reported to date for CO delivery to cancer cells by a photoCORM. This albumin:photoCORM complex is also the first CO delivery system to produce significant anti-inflammatory effects when introduced at nanomolar photoCORM concentration.
向生物靶标递送受控量的一氧化碳（CO）是当前的重要研究兴趣。目前已知的能够严格控制 CO 释放位置和数量的 CO 释放化合物非常少。为了解决这一不足，我们在此报告了一种新的无金属、可见光诱导的 CO 释放分子（photoCORM）及其前药氧化形式，为控制、局部 CO 输送提供了新的方法。基于 3-羟基苯并[g]喹啉骨架的新型 photoCORM 在多种生物相关条件下，通过可见光照射可释放 1 当量的 CO。在 CO 释放之前，可以使用荧光显微镜追踪这种无毒化合物，并在 CO 释放后产生无毒的副产物。photoCORM 的氧化前药形式被细胞硫醇还原，为在癌细胞的还原环境中激活提供了一种方法。非金属 photoCORM 与白蛋白的强非共价亲和力使白蛋白：photoCORM 复合物能够用于向癌细胞进行靶向 CO 输送。与迄今为止报道的通过 photoCORM 向癌细胞输送 CO 的最低毒性 IC 值相比，这种方法产生了细胞毒性。当以毫摩尔级 photoCORM 浓度引入时，这种白蛋白：photoCORM 复合物也是第一个产生显著抗炎作用的 CO 输送系统。
