Pople Computational Chemistry Laboratory, Departamento de Química, CCET , UFS , 49100-000 , São Cristóvão , Sergipe , Brazil.
Departamento de Química Fundamental, CCEN , UFPE , 50590-470 , Recife , Pernambuco , Brazil.
J Chem Inf Model. 2020 Feb 24;60(2):513-521. doi: 10.1021/acs.jcim.9b00785. Epub 2020 Jan 9.
The elucidation of the action of doxorubicin (DOX) has been considered a challenge for cancer therapy. Using theoretical approaches, we investigated the structure and electronic properties of DOX as a function of pH, which we thought likely to be related to the influence of its tautomers. Regarding the relative stabilities among the tautomers, the results obtained from PM6 were the most similar to those obtained from DFT. The theoretical absorption spectrum for each tautomeric species simply showed a single absorption peak located around 400 nm, in contrast to the experimental absorption spectra in the literature that showed four absorption bands. The experimental evidence was properly explained by considering four tautomeric conformers of DOX. The spectroscopic study of the deprotonated tautomers also suggested the presence of four deprotonated tautomers at more basic pH values. The spectrum at pH 10.08 can be explained by the presence of protonated and deprotonated doxorubicin species.
阐明阿霉素（DOX）的作用一直被认为是癌症治疗的一个挑战。我们使用理论方法研究了 DOX 的结构和电子性质作为 pH 的函数，我们认为这可能与它的互变异构体的影响有关。关于互变异构体之间的相对稳定性，从 PM6 获得的结果与从 DFT 获得的结果最相似。对于每种互变异构体的理论吸收光谱，只显示了一个位于 400nm 左右的单一吸收峰，而文献中的实验吸收光谱显示了四个吸收带。通过考虑 DOX 的四个互变异构构象适当解释了实验证据。对去质子化互变异构体的光谱研究也表明，在更高的碱性 pH 值下存在四种去质子化互变异构体。在 pH 10.08 时的光谱可以用质子化和去质子化的阿霉素物种的存在来解释。
