Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QZ, United Kingdom.
Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):19891-5. doi: 10.1073/pnas.1113615108. Epub 2011 Nov 22.
After 35 years the hunt for improved anthracycline antibiotics is unabated but has yet to achieve the levels of clinical success desired. Electrochemical techniques provide a large amount of kinetic and thermodynamic information, but the use of such procedures is hindered by issues of sensitivity and selectivity. This work demonstrates how by harnessing the mechanism of catalytic reduction of oxygen by the quinone functionality present within the anthracycline structure it is possible to study the reactive moiety in nanomolar concentration. This methodology allows electrochemical investigation of the intercalation of quinizarin into DNA and, in particular, the quinone oxidation and degradation mechanism. The reversible reduction of the quinizarin, which in the presence of oxygen leads to the formation of reactive oxygen species, is found to occur at -0.535 V (vs. SCE) pH 6.84 and the irreversible oxidation leading to the molecules degradation occurs at +0.386 V (vs. SCE) pH 6.84.
经过 35 年的努力，人们对改良蒽环类抗生素的研究从未停止，但仍未达到预期的临床成功水平。电化学技术提供了大量的动力学和热力学信息，但这些方法的应用受到灵敏度和选择性问题的限制。本工作展示了如何利用醌官能团在蒽环类结构内催化还原氧气的机制，以在纳摩尔浓度下研究反应性部分。这种方法允许对醌吖嗪嵌入 DNA 进行电化学研究，特别是醌氧化和降解机制。在氧气存在下导致活性氧形成的醌吖嗪的可逆还原，在 pH 值为 6.84 时，其发生在-0.535 V（相对于 SCE），而不可逆氧化导致分子降解发生在 pH 值为 6.84 时，+0.386 V（相对于 SCE）。
