Fluorine Substitution Tunes the Nanofiber Chirality of Supramolecular Hydrogels to Promote Cell Adhesion and Proliferation

Fluorine atoms confer desirable biophysical,chemical,and biological properties to peptides/proteins by participating in various intermolecular interactions with their environment,but they are rarely used to control supramolecular chirality and functional.Herein,to identify the effects of fluorine substitution on the chirality and function of supramolecular assem-blies,C2-symmetric benzene-paradicarboxamide-based phenylalanine(phe)derivatives and three monofluorinated variants that had a single fluorine atom on their benzyl side chain in either the ortho,meta,or para position were synthesized.The experimental and theoretical results clearly show that the resulting assembled fibrils were supported by multiple interactions,including hydrogen bonding,π–πstacking and C/O–H…F–CAr interactions.Compared to nonfluorinated analogs,fluorine and its ring position on the aromatic side chain dictated the type and strength of the F···H interaction and then induced changes in supramolecular chirality and fiber morphology.Further studies on cell behavior showed that the order of positive interac-tion between high-order supramolecular chirality(M,P)and molecular chirality(L,D)on cell proliferation and viability is LM>DM>LP>DP.These findings provide a protocol for leveraging fluorine atoms and their positional dependence on directing chiral nanostructures with desirable handedness and creating fluorinated supramolecular hydrogels as extracellular matrix-mimetic scaffolds for cell culture and regenerative medicine.

[2+2]Photocycloaddition Reaction Regulated the Stability and Morphology of Hydrogels

Photoresponsive supramolecular gels as intelligent non-invasive responsive materials can undergo changes in color,state,morphology and electronic properties upon photo irradiation,making them attractive for a variety of applications.Herein,a novel supramolecular hydrogelator DBE with 1,4-divinylbenzene as the central core,connected via amide linkage to l-phenylalanine and peripheral hydrophilic groups,was designed to evaluate the effect of[2+2]photocycloaddition reaction on supramolecular hydrogels.UV irradiation decreases the solubility of the hydrogelator DBE and hence,causes the destruction of the gel.SEM images clearly show that irradiation with UV light could induce disintegration of the right-handed helical nanofibers entangled network,which turns into nanoparticles and eventually massive crystals.Circular dichroism and vibrational circular dichroism data also indicate the formation of right-handed helical nanofibers in DBE gel.FTIR and MALDI-TOF-MS spectrum confirm that the variation of stability and aggregated morphology of DBE gel after UV irradiation is attributed to[2+2]cycloaddition reaction of vinyl units.This study presents a wonderful model for regulating the stability and aggregated morphology of supramolecular hydrogels via photo irradiation,as well as offers new ideas for designing novel photo responsive materials.

Endogenous peroxynitrite activated fluorescent probe for revealing anti-tuberculosis drug induced hepatotoxicity

Py^(+)razinamide (PZA), isoniazid (INH) and rifampicin (RFP) are all commonly used anti-tuberculosis drugs in clinical practice, and long-term medication may cause severe liver damage and toxicity. The level of peroxynitrite (ONOO^(-)) generated in liver has long been regarded as a biomarker for the prediction and measurement of drug-induced liver injury (DILI). In this article, we constructed a BODIPY-based fluorescent probe (BDP-Py^(+)) that enabled quickly and sensitively detect and image ONOO^(-) in vivo. Utilizing this probe, we demonstrated the change of ONOO^(-) content in cells and mice model of DILI induced by acetaminophen (APAP), and for the first time revealed the mechanism of liver injury induced by antituberculosis drug PZA. Moreover, BDP-Py^(+) could be applied to screen out and evaluate the hepatotoxicity of different anti-tuberculosis drugs. Comparing with the existing serum enzymes detection and H&E staining, the probe could achieve early diagnosis of DILI before solid lesions in liver via monitoring the up-regulation of ONOO^(-) levels. Collectively, this work will promote the understanding of the pathogenesis of anti-tuberculosis drug induced liver injury (ATB-DILI), and provide a powerful tool for the early diagnosis and treatment of DILI.

An Ultrastable π-π Stacked Porous Organic Molecular Framework as a Crystalline Sponge for Rapid Molecular Structure Determination

The crystalline sponge method is a pragmatic and promising strategy for molecular structure determination.However,the dominant metal-organic framework crystal sponge platforms always face poor chemical stability,especially solvent instability,hampering their application in a vaster domain.Herein,we report an ultrastable π-π stacked porous organic molecular framework which exhibits permanent porosity,high thermal stability,and good chemical resistance.It can efficiently implement an approach to molecular structure determination via a single-crystal-to-single-crystal transformation.This is the first example utilizing π-π stacked porous organic molecular framework as“crystalline sponge”to determine a wide variety of guests,ranging from hydrophilic to hydrophobic,and from aliphatic to aromatic,which complements the crystalline sponges based on the famous metal-organic frameworks.More importantly,it can achieve rapid structure determination of small molecules within 3 h.

Hydrogen-bonding regulated supramolecular chirality with controllable biostability

The regulation of natural helical nanostructures is principally supported and actuated by hydrogen bonds(H-bonds)formed from hydrogen-bonding groups(peptide bonds and base pairs)to realize biological activities and specific biofunctional transformations.However,studying the role of H-bonding patterns on the handedness of supramolecular assemblies is still challenging,since supramolecular assemblies will be disassembled or destabilized with slightly varying H-bonding groups for most supramolecules.To circumvent this issue,herein,two types of self-assembled C2-symmetric phenylalanine derivatives differed by a single H-bonding group(ester or amide)are systematically designed for deciphering the role of H-bonding pattern on the chirality of supramolecular assemblies and their related biostability.Opposite handedness nanofibrous structures with tailorable diameter and helical pitch are achieved with the transition from ester to amide groups in the gelators.Experimental and theoretical evidence suggests that helical orientation of ester-containing gelators ascribes to intermolecular H-bonds.In contrast,the helical direction for the amide-counterparts is mainly due to intra-and intermolecular H-bonds.Moreover,these H-bonding groups greatly influence their stability,as revealed by in vitro and in vivo degradation experiments and the left-handed assemblies are more stable than the right-handed ones.Thus,the study offers a feasible model to have valuable insight into understanding the role of H-bonding patterns in biological folding.