Remarkable Stability of Glutathione-Based Supramolecular Gel in the Presence of Oxidative Stress from Hydrogen Peroxide

Low molecular weight 7-methoxy-3-(<i>p</i>-nitrophenyl)iminocoumarin (<b>MNI</b>) with donor and acceptor groups has been synthesized. The molecule shows typical π-stacking geometry in the crystal structure. In this study, <b>MNI</b>, an achiral small organic molecule, forms a nanostructured supramolecular gel along with a short peptide sequence glutathione (GSH). The self-assembly of the achiral organic coumarin component and chiral biomolecule produces a chiral gel with helical fiber structures. Interestingly, the helicities of chiral gels are controlled by the solvent ratio, where <b>MNI</b> in DMSO and GSH in water has been used. Variation of the solvent ratio from 6:4 to 1:9 for DMSO:H₂O results in six gels (<b>4</b>, <b>5</b>, <b>6</b>, <b>7</b>, <b>8</b> and <b>9</b>), where the gel numbers signify the water content ratio. FE-SEM analysis shows gel fibers with right-handed helical structures, which have been further confirmed by circular dichroism (CD) with notable helicity in <b>4</b> to <b>6</b>. This is the first report of controlled chiral helical nanostructured supramolecular gel formation by a solvent mixture with an organic small molecule and biomolecule. Interestingly, storage modulus (<i>G</i>') initially decreases from <b>4</b> to <b>6</b> and further increases up to <b>9</b>. An opposite strain (%) trend was observed among these six gels. These unusual solvent-dependent gel properties have been further applied to monitor the stability of the gels in the presence of hydrogen peroxide (H₂O₂), which converts GSH to oxidized glutathione (GSSG) in general. The oxidative stress from H₂O₂ disrupts <b>4</b> to <b>6</b> gels, and precipitation occurs. It is noteworthy to mention that GSSG alone cannot form a gel with the <b>MNI</b> molecule and forms a precipitate. Remarkably, on the other hand, <b>7</b> to <b>9</b> remain as strong gels even after H₂O₂ treatment. Among all six gels, <b>9</b> shows extraordinary stability of gels even after H₂O₂ treatment.