A 11B-NMR Method for the In Situ Monitoring of the Formation of Dynamic Covalent Boronate Esters in Dendrimers

Yi-Wen Yao; Ching-Hua Tsai; Chih-Yi Liu; Fang-Yu Wang; Sodio C N Hsu; Chun-Cheng Lin; Hui-Ting Chen; Chai-Lin Kao

doi:10.3390/polym16233258

A 11B-NMR Method for the In Situ Monitoring of the Formation of Dynamic Covalent Boronate Esters in Dendrimers

Polymers (Basel). 2024 Nov 23;16(23):3258. doi: 10.3390/polym16233258.

Authors

Yi-Wen Yao¹, Ching-Hua Tsai¹, Chih-Yi Liu¹, Fang-Yu Wang¹, Sodio C N Hsu¹, Chun-Cheng Lin^{1

2}, Hui-Ting Chen³, Chai-Lin Kao^{1

4

5

6

7

8}

Affiliations

¹ Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
² Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan.
³ Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
⁴ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
⁵ Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁶ Center for Tropical Medicine and Infectious Disease Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁷ Department of Chemistry, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
⁸ College of Professional Studies, National Pingtung University of Science and Technology, Pingtung 912, Taiwan.

Abstract

The in situ monitoring of dynamic covalent macromolecular boronate esters represents a difficult task. In this report, we present an in situ method using fluoride coordination and ¹¹B NMR spectroscopy to determine the amount of boronate esters in a mixture of boronic acids and cis-diols. With fluoride coordination, the boronic acid and boronate esters afforded trifluoroborate and fluoroboronate esters, giving identical resonances at 3 and 9 ppm in the ¹¹B NMR spectra. The same titration did not alter the resonance of amine-coordinated boronate esters, which gave resonances of 14 ppm in the ¹¹B NMR spectra. Therefore, boronic acids, boronate esters, and amine-coordinated boronate esters gave three identical resonances, and the ratio of each component was obtained by deconvolution for a further equilibrium analysis. This method monitored the conversion among three species in various conditions, including separation. Accordingly, boronate esters were more stable after precipitation than chromatography, in which 29% and 20% of boronate esters were lost after purification. This method was applied to study the reaction between the boronic acid-decorated defect lysine dendron (16) and dopamine. No boronic acid signal was observed after adding 1 equivalent of dopamine; no boronic acid signal was observed in the NMR spectrum. According to the spectrum, the product contains 65% boronate ester and 35% N-B-coordinated derivatives. This method helps identify the presence of the three intermediates and provides more insights into this reaction.

Keywords: 11B NMR; amine-coordinated boronate ester; boronate ester; dynamic covalent chemistry.

Grants and funding

This research was funded by the government of Taiwan through the Ministry of Science and Technology (grant number 113-2113-M-037 -004, 113-2823-8-037 -001 and 112-2113-M-037 -009), the University of Kaohsiung Medical University and National Tsing Hua University (grant number KT113P002).