Rotational Diffusion Kinetics of Copper (I) Catalyzed Alkyne-Azide Cycloaddition Reactions★

doi:10.6023/A25050156

Acta Chimica Sinica ›› 2025, Vol. 83 ›› Issue (11): 1293-1299.DOI: 10.6023/A25050156 Previous Articles Next Articles

Communication

铜(I)催化炔-叠氮环加成反应的转动扩散动力学^★

成泽恺^a, 温子扬^a, 李红卫^b, 李娜^a^,^*(), 王欢^a^,^*()

^a 北京大学化学与分子工程学院北京分子科学国家研究中心北京 100871
^b 北京大学北京核磁共振中心北京 100871

投稿日期:2025-05-11 发布日期:2025-08-12
通讯作者: 李娜, 王欢
作者简介:
^★ “中国青年化学家”专辑.
基金资助:
项目受北京市自然科学基金(QY23027); 国家自然科学基金(22134005); 第33期北京大学大型仪器开放测试基金资助

Rotational Diffusion Kinetics of Copper (I) Catalyzed Alkyne-Azide Cycloaddition Reactions^★

Cheng Zekai^a, Wen Ziyang^a, Li Hongwei^b, Li Na^a^,^*(), Wang Huan^a^,^*()

^a Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871
^b Beijing NMR Center, Peking University, Beijing 100871

Received:2025-05-11 Published:2025-08-12
Contact: Li Na, Wang Huan
About author:
^★For the VSI “Rising Stars in Chemistry”.
Supported by:
Beijing Natural Science Fund(QY23027); National Natural Science Foundation of China(22134005); 33rd Session of the Peking University Open/Shared Experimental Technology Fund.

1. .pdf(825KB)

Abstract

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

Cite this article

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.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 5

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

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

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)

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

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]

References 18

[1]	(a) Bustamante C.; Keller D.; Oster G. Acc. Chem. Res. 2001, 34, 412.
	(b) Purcell E. M. Am. J. Phys. 1977, 45, 3.
	(c) Iino R.; Kinbara K.; Bryant Z. Chem. Rev. 2020, 120, 1.
[2]	(a) Mermall V.; Post P. L.; Mooseker M. S. Scienc. 1998, 279, 527.
	(b) Sellers J. R. Biochim. Biophys. Act., Mol. Cell Res. 2000, 1496, 3.
	(c) Dutcher S. K. Curr. Opin. Cell Biol. 2001, 13, 49.
	(d) Akhmanova A.; Steinmetz M. Nat. Rev. Mol. Cell. Biol. 2015, 16, 711.
	(e) Fang X.-Z.; Zhou T.; Xu J.-Q.; Wang Y.-X.; Sun M.-M.; He Y.-J.; Pan S.-W.; Xiong W.; Peng Z.-K.; Gao X.-H.; Shang Y. Cell Biosci. 2021, 11, 13.
	(f) Kuehlbrandt W. In Annual Review of Biochemistry, Vol. 88, Eds.Eds.: Kornberg, R. D., Annual Reviews, California, 2019, p. 515.
	(g) Du S.; Zhao L.; Zhang Z.; Chen G. Acta Chim. Sinic. 2023, 81, 741 (in Chinese).
	(杜思南, 赵丽曼, 张泽新, 陈国颂, 化学学报, 2023, 81, 741.)
[3]	(a) Silvi S.; Venturi M.; Credi A. J. Mater. Chem. 2009, 19, 2279.
	(b) Kudernac T.; Ruangsupapichat N.; Parschau M.; Maciá B.; Katsonis N.; Harutyunyan S. R.; Ernst K.-H.; Feringa B. L. Natur. 2011, 479, 208.
	(c) Badjić J. D.; Balzani V.; Credi A.; Silvi S.; Stoddart J. F. Scienc. 2004, 303, 1845.
	(d) Zheng J.; Liu J.; Luo C.; Zeng G.; Wu G.; Hou X. Acta Chim. Sinic. 2023, 81, 1394 (in Chinese).
	(郑靖, 刘金坤, 曾国超, 罗淳译, 吴广磊, 侯旭, 化学学报, 2023, 81, 1394.)
	(e) Liu P.; Liu C.; Liu Q.; Ma J. Acta Phys.-Chim. Sin. 2018, 34, 1171 (in Chinese).
	(柳平英, 刘春艳, 刘倩, 马晶, 物理化学学报, 2018, 34, 1171.)
[4]	(a) Dattler D.; Fuks G.; Heiser J.; Moulin E.; Perrot A.; Yao X.; Giuseppone N. Chem. Rev. 2020, 120, 310.
	(b) Feng Y.; Ovalle M.; Seale J. S. W.; Lee C. K.; Kim D. J.; Astumian R. D.; Stoddart J. F. J. Am. Chem. Soc. 2021, 143, 5569.
	(c) Astumian R. D. Phys. Chem. Chem. Phys. 2007, 9, 5067.
[5]	(a) Pavlick R. A.; Dey K. K.; Sirjoosingh A.; Benesi A.; Sen A. Nanoscal. 2013, 5, 1301.
	(b) Butler P. J.; Dey K. K.; Sen A. Cell. Mol. Bioeng. 2015, 8, 106.
	(c) Das S.; Shklyaev O. E.; Altemose A.; Shum H.; Ortiz-Rivera I.; Valdez L.; Mallouk T. E.; Balazs A. C.; Sen A. Nat. Commun. 2017, 8, 14384.
[6]	Wang H.; Park M.; Dong R.; Kim J.; Cho Y.-K.; Tlusty T.; Granick S. Scienc. 2020, 369, 537.
[7]	Zhang Z.; Chen H.; Hu M.; Wang D. J. Am. Chem. Soc. 2023, 145, 10512.
[8]	(a) Günther J.-P.; Fillbrook L. L.; MacDonald T. S. C.; Majer G.; Price W. S.; Fischer P.; Beves J. E. Scienc. 2021, 371, eabe8322.
	(b) Fillbrook L. L.; Günther J.-P.; Majer G.; O’Leary D. J.; Price W. S.; Van Ryswyk H.; Fischer P.; Beves J. E. J. Am. Chem. Soc. 2021, 143, 20884.
	(c) Rezaei-Ghaleh N.; Agudo-Canalejo J.; Griesinger C.; Golestanian R. J. Am. Chem. Soc. 2022, 144, 1380.
	(d) MacDonald T. S. C.; Price W. S.; Astumian R. D.; Beves J. E. Angew. Chem., Int. Ed. 2019, 58, 18864.
[9]	(a) Wang H.; Huang T.; Granick S. J. Phys. Chem. Lett. 2021, 12, 2370.
	(b) Wang H.; Park M.; Dong R.; Kim J.; Cho Y.-K.; Tlusty T.; Granick S. Scienc. 2021, 371, eabe8678.
[10]	Haridasan N.; Kannam S. K.; Mogurampelly S.; Sathian S. P. J. Phys. Chem. B 2019, 123, 4825.
[11]	Wang Y.; Li C.; Pielak G. J. J. Am. Chem. Soc. 2010, 132, 9392.
[12]	(a) Huang H.; Wei H.; Zou M.; Xu X.; Xia B.; Liu F.; Li N. Anal. Chem. 2015, 87, 2748.
	(b) Xiao X.; Zhen S. RSC Adv. 2022, 12, 6364.
[13]	Urban S.; Geppi M. Magn. Reson. Chem. 2014, 52, 656.
[14]	Kruk D.; Florek-Wojciechowska M. In Annual Reports on NMR Spectroscopy, Vol. 99, Eds.Eds.: Webb, G. A., Academic Press, Massachusetts, 2020, pp. 119-184.
[15]	(a) Trinh E. H.; Wolff A. M.; Naumiec G. R. J. Chem. Educ. 2021, 98, 587.
	(b) Eaton S, S.; Eaton G,R. In Methods in Enzymology, Vol. 563, Eds.Eds.: Warncke, K., Academic Press, Massachusetts, 2015, pp. 37-58.
[16]	(a) Zhang Y.; Hess H. Nat. Rev. Chem. 2021, 5, 500.
	(b) Ma A.-J.; Chen S.-J.; Li Y.-X.; Chen Y. Acta Phys. Sin. 2021, 70, 148201 (in Chinese).
	(马奥杰, 陈颂佳, 李玉秀, 陈颖, 物理学报, 2021, 70, 148201.)
[17]	(a) Liang L.; Astruc D. Coord. Chem. Rev. 2011, 255, 2933.
	(b) Nolte C.; Mayer P.; Straub B. F. Angew. Chem., Int. Ed. 2007, 46, 2101.
	(c) Iacobucci C.; Reale S.; Gal J.-F.; De Angelis F. Angew. Chem., Int. Ed. 2015, 54, 3065.
	(d) Jin L.; Tolentino D. R.; Melaimi M.; Bertrand G. Sci. Adv. 2015, 1, e1500304.
	(e) Zhu L.; Brassard C. J.; Zhang X.; Guha P. M.; Clark R. J. Chem. Rec. 2016, 16, 1501.
[18]	(a) Zhao Q.; Tao J.; Feng W.; Uppal J. S.; Peng H.; Le X. C. Anal. Chim. Act. 2020, 1125, 267.
	(b) Jameson D. M.; Ross J. A. Chem. Rev. 2010, 110, 2685.
	(c) Bock V. D.; Hiemstra H.; van Maarseveen J. H. Eur. J. Org. Chem. 2006, 2006, 51.
	(d) Pineda- Castañeda H. M.; Rivera-Monroy Z. J.; Maldonado M. ACS Omeg. 2023, 8, 3650.

铜(I)催化炔-叠氮环加成反应的转动扩散动力学^★

Rotational Diffusion Kinetics of Copper (I) Catalyzed Alkyne-Azide Cycloaddition Reactions^★

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 5

References 18

Related Articles 1

Recommended Articles

Metrics

Comments

铜(I)催化炔-叠氮环加成反应的转动扩散动力学★

Rotational Diffusion Kinetics of Copper (I) Catalyzed Alkyne-Azide Cycloaddition Reactions★

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 5

References 18

Related Articles 1

Recommended Articles

Metrics

Comments

铜(I)催化炔-叠氮环加成反应的转动扩散动力学^★

Rotational Diffusion Kinetics of Copper (I) Catalyzed Alkyne-Azide Cycloaddition Reactions^★