铜(I)催化炔-叠氮环加成反应的转动扩散动力学★

doi:10.6023/A25050156

摘要/Abstract

在酶化学反应与小分子化学反应过程中的扩散动力学的研究表明, 一部分反应物或催化剂会出现高于本征扩散系数的平动扩散行为, 其扩散系数增幅可以达到20%以上, 而体系温度基本不变. 分子的实际运动是平动与转动的耦合, 但目前针对小分子化学反应过程中的扩散动力学研究都集中在平动扩散上, 鲜有人关注其转动扩散的情况, 本工作研究了3-丁炔酸与叠氮乙酸在Cu(I)催化下发生1,3-偶极环加成反应过程中各物种转动扩散系数的变化, 核磁共振T₁反转恢复实验和荧光各向异性/偏振实验的结果表明在反应过程中底物和产物均存在不同程度的转动扩散系数减小, 结合平动扩散实验结果, 我们认为在反应过程中分子发生了定向对齐, 同时分子的转动能部分转变为了分子的平动能, 使得化学反应中小分子呈现区别于Stokes-Einstein定律的扩散现象.

关键词: 转动扩散, 梯度场核磁共振, T₁弛豫检测, 荧光各向异性, 铜催化炔-叠氮环加成反应

Molecular diffusion in chemical reactions has been observed to deviate from the Stokes-Einstein relationship, however underlying mechanism remains elusive. The diffusion kinetics of enzymatic and small-molecule chemical reactions have shown that some reactants or catalysts exhibit enhanced translational diffusion coefficients exceeding their intrinsic values by over 20%, with minimal temperature fluctuations. While molecular motion inherently couples translational and rotational components, previous studies have primarily focused on translational diffusion, leaving rotational diffusion largely unexplored. In this study, the rotational diffusion coefficients of species involved in the Cu(I)-catalyzed 1,3-dipolar cycloaddition between 3-butynoic acid and azidoacetic acid were investigated through two independent measurements. Specifically, the changes in the translational diffusion coefficients of the substrate and product during the reaction of 3-butynoic acid and azidoacetic acid were determined by nuclear magnetic resonance (NMR) diffusion-ordered spectroscopy, and a significant increase in the substrate's diffusion coefficient was observed at the early stage of the reaction, which confirms a nonclassical diffusion phenomenon in this system. Subsequently, rotational diffusion coefficients of each species during the reaction were measured using a T₁ inversion recovery experiment, the values for both the substrate and the product showed a significant increase as the reaction progressed while the values for sodium ascorbate remained unchanged. Rotational diffusion was further measured by an independent fluorescence anisotropy/polarization experiment. The changes in fluorescence anisotropy were consistent with the NMR experiments, confirming the presence of nonclassical rotational diffusion in the reaction. The changes in rotational and translational diffusion coefficients of 3-butynoic acid and azidoacetic acid were found both strongly correlated with reaction progress and in synchronization. In summary, interpretating from two independent measurements based on NMR and fluorescence anisotropy, we propose that molecular alignment and the conversion of rotational to translational energy contribute to deviations from the Stokes-Einstein relation during reaction.

Key words: rotational diffusion, pulsed-gradient nuclear magnetic resonance, T₁ relaxation determination, fluorescence anisotropy, copper catalyzed alkyne-azide cycloaddition

引用此文

成泽恺, 温子扬, 李红卫, 李娜, 王欢. 铜(I)催化炔-叠氮环加成反应的转动扩散动力学^★[J]. 化学学报, 2025, 83(11): 1293-1299.

Cheng Zekai, Wen Ziyang, Li Hongwei, Li Na, Wang Huan. Rotational Diffusion Kinetics of Copper (I) Catalyzed Alkyne-Azide Cycloaddition Reactions^★[J]. Acta Chimica Sinica, 2025, 83(11): 1293-1299.

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图/表 5

图1. 3-丁炔酸与叠氮乙酸的环加成反应(数字对应NMR中能够检测到的1H信号)

Figure 1. Cycloaddition of 3-butynoic acid with azidoacetic acid (numbers correspond to the 1H signals that can be detected in the NMR)

图2. CuAAC反应过程中平动扩散系数随时间的变化. 数字对应于拟合扩散系数所用的核磁1H信号, 3-丁炔酸与叠氮乙酸的起始浓度为230 mmol/L, CuSO4浓度为10 mol%, 抗坏血酸钠浓度为40 mol%

Figure 2. Translational diffusion coefficients plotted as a function of time during the CuAAC reaction. Numbers correspond to the 1H signal used to fit the translational diffusion coefficient, the starting concentration of 3-butynoic acid and azidoacetic acid were both 230 mmol/L, the concentration of CuSO4 was 10 mol% of the reactant, and the concentration of sodium ascorbate was 40 mol% of the reactant

图3. 不同浓度下CuAAC反应过程中转动扩散系数随时间的变化. 图中浓度为反应物起始浓度. (a)基于抗坏血酸钠的(7)信号拟合的转动扩散系数随时间的变化; (b)基于3-丁炔酸的(4)信号拟合的转动扩散系数随时间的变化; (c)基于叠氮乙酸的(3)信号拟合的转动扩散系数随时间的变化; (d)基于三氮唑的(5)信号拟合的转动扩散系数随时间的变化.

Figure 3. Rotational diffusion coefficient over time during CuAAC reaction at different concentrations. The concentrations in the figure are the starting concentrations of the reactants. (a) Rotational diffusion coefficients of sodium ascorbate over time, fitted with the NMR signals of (7); (b) rotational diffusion coefficients of 3-butynoic acid over time, fitted with the NMR signals of (4); (c) rotational diffusion coefficients of azidoacetic acid plotted as a function of time, fitted with the NMR signals of (3); (d) rotational diffusion coefficients plotted as a function of time of 1,2,3-triazole, fitted with the NMR signals of (5)

图4. 荧光各向异性r随时间的变化

Figure 4. Fluorescence anisotropy r plotted as a function of time

图5. 平动能量和转动能量变化的可能机制. (a)反应过程中3-丁炔酸和叠氮乙酸平动和转动能量改变幅度随时间的变化; (b)可能的反应机理和中间体[17b]

Figure 5. Possible mechanisms for the translational and rotational energy interconversion. (a) Change of translational and rotational energy ploted as a function of time during the reaction for 3-butynoic acid and azidoacetic acid; (b) proposed reaction mechanisms and reaction intermediates.[17b]

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