A General Protocol for Synthesizing Thiolated Folate Derivatives

Jie Li; Yao Wang; Liangang Shan; Lei Qian; Wenchao Wang; Jixian Liu; Jianguo Tang

doi:10.3390/molecules28135228

Molecules (Jul 2023)

A General Protocol for Synthesizing Thiolated Folate Derivatives

Jie Li,
Yao Wang,
Liangang Shan,
Lei Qian,
Wenchao Wang,
Jixian Liu,
Jianguo Tang

Affiliations

Jie Li: Institute of Hybrid Materials, National Center of International Research for Hybrid Materials Technology, National Base of International Science & Technology Cooperation, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China
Yao Wang: Institute of Hybrid Materials, National Center of International Research for Hybrid Materials Technology, National Base of International Science & Technology Cooperation, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China
Liangang Shan: Institute of Hybrid Materials, National Center of International Research for Hybrid Materials Technology, National Base of International Science & Technology Cooperation, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China
Lei Qian: Institute of Hybrid Materials, National Center of International Research for Hybrid Materials Technology, National Base of International Science & Technology Cooperation, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China
Wenchao Wang: Institute of Hybrid Materials, National Center of International Research for Hybrid Materials Technology, National Base of International Science & Technology Cooperation, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China
Jixian Liu: Institute of Hybrid Materials, National Center of International Research for Hybrid Materials Technology, National Base of International Science & Technology Cooperation, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China
Jianguo Tang: Institute of Hybrid Materials, National Center of International Research for Hybrid Materials Technology, National Base of International Science & Technology Cooperation, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China

DOI: https://doi.org/10.3390/molecules28135228
Journal volume & issue: Vol. 28, no. 13
p. 5228

Abstract

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Folic acid (FA) has shown great potential in the fields of targeted drug delivery and disease diagnosis due to its highly tumor-targeting nature, biocompatibility, and low cost. However, FA is generally introduced in targeted drug delivery systems through macromolecular linkage via complex synthetic processes, resulting in lower yields and high costs. In this work, we report a general protocol for synthesizing thiolated folate derivatives. The small molecule thiolated folate (TFa) was first synthesized with a purity higher than 98.20%. First, S-S-containing diol was synthesized with a purity higher than 99.44 through a newly developed green oxidation protocol, which was carried out in water with no catalyst. Then, folic acid was modified using the diol through esterification, and TFa was finally synthesized by breaking the disulfide bond. Further, the synthesized TFa was utilized to modify silver nanoparticles. The results showed that TFa could be easily bonded to metal particles. The protocol could be extended to the synthesis of a series of thiolated derivatives of folate, such as mercaptohexyl folate, mercaptoundecyl folate, etc., which would greatly benefit the biological applications of FA.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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