Oligomeric hydrogels self-assembled from reduction-controlled condensation

Polymer hydrogels and small-molecule-based (SMB) supramolecular hydrogels have been widely explored. But oligomeric hydrogels have remained a challenge because synthetic difficulties of the oligomers and control of their amphiphilicities. Reported herein is the rational design of two precursors Cys(SEt)-Lys-CBT (1) and (Cys-Lys-CBT)2 (2) (CBT=2-cyano-6-aminobenzothiazole) and the use of a biocompatible condensation to prepare oligomeric hydrogels. Glutathione reduction of 1 or 2 yields the same gelator Cys-Lys-CBT (3) which condenses with each other to yield amphiphilic cyclic oligomers. The oligomers instantly self-assemble into nanofibers and form oligomeric hydrogels with similar mechanic properties. Chemical analyses indicated that the major condensation product in both two hydrogels is a cyclic dimer. Considering its biocompatibility, optimal mechanical strength, and biodegradability, we believe that our oligomeric hydrogel might be useful for long-term drug delivery in the future.