Departamento de Química Física, Facultad de Ciencias Ambientales y Bioquímica, and INAMOL, Universidad de Castilla-La Mancha, Avenida Carlos III, S/N, 45071 Toledo, Spain.
Phys Chem Chem Phys. 2018 May 23;20(20):14182-14191. doi: 10.1039/c8cp01134f.
This work reports on photophysical studies of the irinotecan (IRT) anti-cancer drug in water solutions of different acidities (pH = 1.11-9.46). We found that IRT co-exists as mono-cationic (C1), di-cationic (C2), or neutral (N) forms. The population of each prototropic species depends on the pH of the solution. At pH = 1.11-3.01, the C1 and C2 structures are stabilized. At pH = 7.00, the most populated species is C1, while at pH values larger than 9.46 the N form is the most stable species. In the 1.11-2.61 pH range, the C1* emission is efficiently quenched by protons to give rise to the emission from C2*. The dynamic quenching constant, KD, is ∼32 M-1. While the diffusion governs the rate of excited-state proton-transfer (ESPT) under these conditions, the reaction rate increases with the proton concentration. A two-step diffusive Debye-Smoluchowski model was applied at pH = 1.11-2.61 to describe the protonation of C1*. The ESPT time constants derived for C1* are 382 and 1720 ps at pH = 1.11 and 1.95, respectively. We found that one proton species is involved in the protonation of C1* to give C2*, in the analyzed acidic pH range. Under alkaline conditions (pH = 9.46), the N form is the most stable structure of IRT. These results indicate the influence of the pH of the medium on the structural and dynamical properties of IRT in water solution. They may help to provide a better understanding on the relationship between the structure and biological activity of IRT.
这项工作报道了喜树碱（IRT）抗癌药物在不同酸度（pH = 1.11-9.46）的水溶液中的光物理研究。我们发现，IRT 以单阳离子（C1）、双阳离子（C2）或中性（N）形式共存。每种质子化物种的种群取决于溶液的 pH 值。在 pH = 1.11-3.01 时，C1 和 C2 结构稳定。在 pH = 7.00 时，最常见的物种是 C1，而在 pH 值大于 9.46 时，N 形式是最稳定的物种。在 1.11-2.61 pH 范围内，C1发射被质子有效地猝灭，产生 C2发射。动态猝灭常数 KD 约为 32 M-1。虽然在这些条件下，扩散控制激发态质子转移（ESPT）的速率，但反应速率随质子浓度的增加而增加。在 pH = 1.11-2.61 时，应用两步扩散德拜-斯莫鲁霍夫斯基模型来描述 C1的质子化。在 pH = 1.11 和 1.95 时，C1的 ESPT 时间常数分别为 382 和 1720 ps。我们发现，在分析的酸性 pH 范围内，一种质子物种参与 C1的质子化生成 C2。在碱性条件下（pH = 9.46），N 形式是 IRT 最稳定的结构。这些结果表明，介质 pH 值对 IRT 在水溶液中的结构和动力学性质有影响。它们可能有助于更好地理解 IRT 的结构与生物活性之间的关系。
