Departamento de Química Física, Facultad de Ciencias Ambientales y Bioquímica, and INAMOL, Universidad de Castilla-La Mancha, Toledo, Spain.
J Phys Chem A. 2011 May 26;115(20):5094-104. doi: 10.1021/jp201749u. Epub 2011 May 2.
Steady-state and time-resolved picosecond emission studies were carried out to study the role of the proton concentration in the acid-base properties of the anticancer drug camptothecin (CPT) in its ground and electronically first excited states. The results show that, under acidic conditions, the excited-state proton-transfer (ESPT) reaction is irreversible, in contrast to previous literature data. We found that the prototropic species are equilibrated at the excited state (pK(a)* = 1.85) only in a restricted range of pH (1.5 < pH < 3), whereas only one species, either the neutral form (τ(N) = 3.76 ns) or the protonated form (τ(C) = 2.83 ns), can be detected at pH > 3 and pH < 1.5, respectively. The proton motion from the acidic solution to the neutral form in the pH 1-2 domain is diffusion-controlled. Within the range of pH 1-2, the reaction rate constant for the formation (k(d)) of the encounter complex between the proton and the neutral form ranges from 1.17 × 10(10) to 7.33 × 10(10) M(-1) s(-1), respectively. Under more acidic conditions (pH 0.9-0.95), the protonation of CPT does not depend on the diffusive step, because of the large amount of protons. The direct proton-transfer rate constant (k(DPT)*) increases with the proton concentration (time constants change from 24 ps to ∼1 ns at pH 0.9 and 2, respectively). The number of protons involved in the proton transfer changes from approximately one, for the diffusive regime, to approximately four, for the static regime. We found good agreement between the Birks model for equilibrated flourophores and the Debye-Smoluchowski equation (DSE) to accurately explain the ESPT reaction of CPT with acidic water in the reversible range. The proton motion at pH 2 (equilibrium range) exhibits diffusion-controlled behavior and can be explained using the Smoluchowski model. Our results show that the interaction of CPT with acidic water depends on the concentration of the acid, which changes the nature of both the structure and dynamics.
进行了稳态和时间分辨皮秒发射研究，以研究质子浓度在抗癌药物喜树碱（CPT）的基态和电子第一激发态的酸碱性质中的作用。结果表明，在酸性条件下，与先前的文献数据相比，激发态质子转移（ESPT）反应是不可逆的。我们发现，质子转移物种仅在有限的 pH 范围内（1.5<pH<3）在激发态达到平衡（pK(a)=1.85），而在 pH>3 和 pH<1.5 时，只能分别检测到中性形式（τ(N)=3.76 ns）或质子化形式（τ(C)=2.83 ns）中的一种物质。质子从酸性溶液向中性形式的运动在 pH 1-2 域是扩散控制的。在 pH 1-2 范围内，质子与中性形式形成（k(d)）的反应速率常数范围分别为 1.17×10(10)至 7.33×10(10) M(-1) s(-1)。在更酸性的条件下（pH 0.9-0.95），由于质子大量存在，CPT 的质子化过程不依赖于扩散步骤。直接质子转移速率常数（k(DPT)）随质子浓度的增加而增加（在 pH 0.9 和 2 时，时间常数分别从 24 ps 变化到约 1 ns）。质子转移涉及的质子数从扩散区域的大约一个，变为静态区域的大约四个。我们发现，Birks 模型用于平衡荧光团和 Debye-Smoluchowski 方程（DSE）可以很好地解释 CPT 与酸性水中的可逆范围的 ESPT 反应。在 pH 2（平衡范围）时，质子运动表现出扩散控制行为，可以用 Smoluchowski 模型来解释。我们的结果表明，CPT 与酸性水的相互作用取决于酸的浓度，这会改变结构和动力学的性质。
