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Thiol Michael-Type Reactions of Optically Active Mercapto-Acids in Aqueous Medium

Published online by Cambridge University Press:  15 July 2019

Makafui Y. Folikumah ,
Axel T. Neffe ,
Marc Behl  and
Andreas Lendlein
Makafui Y. Folikumah
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany Institute of Chemistry, University of Potsdam, Potsdam-Golm, Germany
Axel T. Neffe
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany
Marc Behl
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany
Andreas Lendlein*
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany Institute of Chemistry, University of Potsdam, Potsdam-Golm, Germany
*
*Correspondence to: Prof. Andreas Lendlein Institute of Biomaterial Science, Helmholtz-Zentrum Geesthacht, Kantstr. 55, 14513, Teltow, Germany Email: andreas.lendlein@hzg.de Phone: +49 (0)3328 352-235
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Abstract

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. 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.

Keywords

biomaterialbiomedicalbiomimetic (chemical reaction)chemical synthesis
Type
Articles
Information
MRS Advances , Volume 4 , Issue 46-47: Soft Materials and Biomaterials , 2019 , pp. 2515 - 2525
Copyright
Copyright © Materials Research Society 2019 

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Footnotes

#

Present address: Institute for Technical and Macromolecular Chemistry, University of Hamburg, Hamburg, Germany

References

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