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Thiol Michael-Type reactions of optically active mercapto-acids in aqueous medium
- Defined chemical reactions in a physiological environment are a prerequisite for the in situ synthesis of implant materials potentially serving as matrix for drug delivery systems, tissue fillers or surgical glues. ‘Click’ reactions like thiol Michael-type reactions have been successfully employed as bioorthogonal reaction. However, due to the individual stereo-electronic and physical properties of specific substrates, an exact understanding their chemical reactivity is required if they are to be used for in-situ biomaterial synthesis. The chiral (S)-2-mercapto-carboxylic acid analogues of L-phenylalanine (SH-Phe) and L-leucine (SH-Leu) which are subunits of certain collagenase sensitive synthetic peptides, were explored for their potential for in-situ biomaterial formation via the thiol Michael-type reaction. In model reactions were investigated the kinetics, the specificity and influence of stereochemistry of this reaction. We could show that only reactions involving SH-Leu yielded the expected thiol-Michael product. TheDefined chemical reactions in a physiological environment are a prerequisite for the in situ synthesis of implant materials potentially serving as matrix for drug delivery systems, tissue fillers or surgical glues. ‘Click’ reactions like thiol Michael-type reactions have been successfully employed as bioorthogonal reaction. However, due to the individual stereo-electronic and physical properties of specific substrates, an exact understanding their chemical reactivity is required if they are to be used for in-situ biomaterial synthesis. The chiral (S)-2-mercapto-carboxylic acid analogues of L-phenylalanine (SH-Phe) and L-leucine (SH-Leu) which are subunits of certain collagenase sensitive synthetic peptides, were explored for their potential for in-situ biomaterial formation via the thiol Michael-type reaction. In model reactions were investigated the kinetics, the specificity and influence of stereochemistry of this reaction. We could show that only reactions involving SH-Leu yielded the expected thiol-Michael product. The inability of SH-Phe to react was attributed to the steric hindrance of the bulky phenyl group. In aqueous media, successful reaction using SH-Leu is thought to proceed via the sodium salt formed in-situ by the addition of NaOH solution, which was intented to aid the solubility of the mercapto-acid in water. Fast reaction rates and complete acrylate/maleimide conversion were only realized at pH 7.2 or higher suggesting the possible use of SH-Leu under physiological conditions for thiol Michael-type reactions. This method of in-situ formed alkali salts could be used as a fast approach to screen mercapto-acids for thio Michael-type reactions without the synthesis of their corresponding esters.…
Author details: | Makafui Yao FolikumahORCiD, Axel T. NeffeORCiDGND, Marc BehlORCiDGND, Andreas LendleinORCiDGND |
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DOI: | https://doi.org/10.1557/adv.2019.308 |
ISSN: | 2059-8521 |
Title of parent work (English): | MRS advances : a journal of the Materials Research Society |
Publisher: | Springer Nature Switzerland AG |
Place of publishing: | Cham |
Publication type: | Article |
Language: | English |
Date of first publication: | 2019/09/16 |
Publication year: | 2019 |
Release date: | 2021/04/29 |
Tag: | biomaterial; biomedical; biomimetic (chemical reaction); chemical synthesis |
Volume: | 4 |
Issue: | 46-47 |
Number of pages: | 11 |
First page: | 2515 |
Last Page: | 2525 |
Funding institution: | Helmholtz Association through Helmholtz Graduate School for Macromolecular Bioscience [VH-GS-503] |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
DDC classification: | 6 Technik, Medizin, angewandte Wissenschaften / 60 Technik / 600 Technik, Technologie |
Peer review: | Referiert |