A post-sulfonated one-pot synthesized magnetic cellulose nanocomposite for Knoevenagel and Thorpe-Ziegler reactions.

The development of biodegradable and active cellulosic-based heterogeneous catalysts for the synthesis of different organic compounds would be attractive in pharmaceutical and petrochemical-related industries. Herein, a post-sulfonated composite of one-pot synthesized magnetite (Fe3O4) and cellulose nanocrystals (CNCs) was used as an effective and easily separable heterogeneous catalyst for activating the Knoevenagel and Thorpe-Ziegler reactions. The composite was developed hydrothermally from microcrystalline cellulose (MCC), iron chlorides, urea, and hydrochloric acid at 180 °C for 20 h in a one-pot reaction. After collecting the magnetic CNCs (MCNCs), post-sulfonation was performed using chlorosulfonic acid (ClSO3H) in DMF at room temperature producing sulfonated MCNCs (SMCNCs). The results confirmed the presence of sulfonated Fe3O4 and CNCs with a hydrodynamic size of 391 nm (±25). The presence of cellulose was beneficial for preventing Fe3O4 oxidation or the formation of agglomerations without requiring the presence of capping agents, organic solvents, or an inert environment. The SMCNC catalyst was applied to activate the Knoevenagel condensation and the Thorpe-Ziegler reaction with determining the optimal reaction conditions. The presence of the SMCNC catalyst facilitated these transformations under green procedures, which enabled us to synthesize a new series of olefins and thienopyridines, and the yields of some isolated olefins and thienopyridines were up to 99% and 95%, respectively. Besides, the catalyst was stable for five cycles without a significant decrease in its reactivity, and the mechanistic routes of both reactions on the SMCNCs were postulated.

Supramolecular polymer/peptide hybrid hydrogels with tunable stiffness mediated by interchain acid-amide hydrogen bonds.

Hydrogels are a class of biomaterials used in the field of tissue engineering and drug delivery. Many tissue engineering applications depend on the material properties of hydrogel scaffolds, such as mechanical stiffness, pore size, and interconnectivity. In this work, we describe the synthesis of peptide/polymer hybrid double-network (DN) hydrogels composed of supramolecular and covalent polymers. The DN hydrogels were prepared by combining the self-assembled pentafluorobenzyl diphenylalanyl aspartic acid (PFB-FFD) tripeptide for the first network and the polymeric PNIPAM-PEGDA copolymer for the second network. During this process, self-assembled peptide nanostructures are cross-linked to the polyacrylamide group in the polymer network through non-covalent interactions. The PNIPAM-PEGDA:PFB-FFD hydrogel exhibited higher mechanical stiffness (G' ∼2 kPa) than the PNIPAM-PEGDA copolymer. Moreover, PNIPAM-PEGDA:PFB-FFD hydrogel shows a decrease in pore size (∼1.2 µm) compared to the original copolymer (∼5.2 µm), with the structural framework of highly interconnected fibrous peptide network. The mechanical stiffness of hydrogels was systematically investigated by rheological analysis in response to various variables, including UV exposure time, concentration of peptides, and amino acid functionalization. Modulating the time of UV irradiation resulted in PNIPAM-PEGDA:PFB-FFD hydrogels with a four-fold increase in stiffness. The influence of amino acid side chains and terminal charge of peptides on the strength of DN hydrogels was also investigated using pentafluorobenzyl diphenylalanyl lysine (PFB-FFK). Interestingly, PFB-FFK, which has an amine group on the side chain, does not exhibit the DN structures. The mechanical properties and pore sizes of PNIPAM-PEGDA:PFB-FFK hydrogel were very similar to those of the PNIPAM-PEGDA copolymer due to poor cross-linking. The biocompatibility of the hydrogel materials was tested with the hMSC cell line using the MTT method, and the results indicate that the materials are non-toxic and potentially useful for biological applications.

Effects of fluoro substitutions and electrostatic interactions on the self-assembled structures and hydrogelation of tripeptides: tuning the mechanical properties of co-assembled hydrogels.

A series of FFK tripeptides capped with phenylacetic acid of various fluoro-substitutions at the N-terminus has been synthesized and examined for self-assembly under aqueous conditions. The material properties of the FFK tripeptides dramatically changed from precipitate to hydrogel phase upon increasing the number of fluorine atoms. Peptides linked with benzyl (B-FFK) or monofluoro-benzyl (MFB-FFK) groups rapidly form solid precipitates under physiological pH conditions. The trifluoro-decorated compound (TFB-FFK) self-assembled into a metastable hydrogel which slowly transformed into a solid precipitate upon standing. A stable hydrogel formation was noticed in the case of the pentafluorobenzyl-diphenylalanyllysine (PFB-FFK) compound. TEM analysis indicates that the PFB-FFK peptide assembled into twisted nanofibril structures, which are predominantly stabilized by strong quadrupole π-stacking interactions and electrostatic interactions of amino acid side chains. Furthermore, the combination of PFB-FFK and PFB-FFD peptides was also investigated for hydrogelation and the self-assembly of such systems resulted in the formation of untwisted 1D nanofibril structures. Supramolecular coassembled hydrogels of variable stiffness have also been achieved by modulating the concentration of the peptide components, which was evident from the rheological analysis. Such low molecular weight (LMW) peptide materials with tuneable mechanical properties might be a potential material for a wide range of applications in nanotechnology and biotechnology.

The crown ether size and stereochemistry affect the self-assembly, hydrogelation, and cellular interactions of crown ether/peptide conjugates.

The discovery of crown ethers and their unique interactions with ions make them play a key role in supramolecular chemistry. In this study, we have developed a new type of amphiphilic crown ether (DB18C6, DB24C8)-conjugated phenylalanine dipeptides for the gelation of water at physiological pH. We report here for the first time that the size of the crown ether controlled the morphology of the self-assembled nanostructures of the hydrogels, as well as their interactions with human mesenchymal stem cells (hMSCs; 3A6-RFP) and mouse fibroblasts (L929). For example, relative to its d-form and other crown sizes, DB18C6LFLF exhibited greater cell adhesion and was nontoxic towards hMSCs after culturing for 72 h. We hypothesize that the steric effect of the crown ether moiety in the assemblies has substantial influences on the morphology of the nanostructures and the cell-material response. Such distinct cell responses should be beneficial for the development of supramolecular biomaterials.