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Steady-state fluorescence spectroscopy has a central role not only for sensing applications, but also in biophysics and imaging. Light switching probes, such as ruthenium dipyridophenazine complexes, have been used to study complex systems such as DNA, RNA, and amyloid fibrils. Nonetheless, steady-state spectroscopy is limited in the kind of information it can provide. In this paper, we use time-resolved spectroscopy for studying binding interactions between amyloid-β fibrillar structures and photoluminescent ligands. Using time-resolved spectroscopy, we demonstrate that ruthenium complexes with a pyrazino phenanthroline derivative can bind to two distinct binding sites on the surface of fibrillar amyloid-β, in contrast with previous studies using steady-state photoluminescence spectroscopy, which only identified one binding site for similar compounds. The second elusive binding site is revealed when deconvoluting the signals from the time-resolved decay traces, allowing the determination of dissociation constants of 3 and 2.2 μM. Molecular dynamic simulations agree with two binding sites on the surface of amyloid-β fibrils. Time-resolved spectroscopy was also used to monitor the aggregation of amyloid-β in real-time. In addition, we show that common polypyridine complexes can bind to amyloid-β also at two different binding sites. Information on how molecules bind to amyloid proteins is important to understand their toxicity and to design potential drugs that bind and quench their deleterious effects. The additional information contained in time-resolved spectroscopy provides a powerful tool not only for studying excited state dynamics but also for sensing and revealing important information about the system including hidden binding sites. 

Abstract We have rationally designed a peptide that assembles into a redox-responsive, antimicrobial metallohydrogel. The resulting self-healing material can be rapidly reduced by ascorbate under physiological conditions and demonstrates a remarkable 160-fold change in hydrogel stiffness upon reduction. We provide a computational model of the hydrogel, explaining why position of nitrogen in non-natural amino acid pyridyl-alanine results in drastically different gelation properties of peptides with metal ions. Given its antimicrobial and rheological properties, the newly designed hydrogel can be used for removable wound dressing application, addressing a major unmet need in clinical care. 

As COVID‐19 infection caused severe public health concerns recently, the development of novel antivirals has become the need of the hour. Main protease (M^pro) has been an attractive target for antiviral drugs since it plays a vital role in polyprotein processing and virus maturation. Herein we report the discovery of a novel class of inhibitors against the SARS‐CoV‐2, bearing histidineα‐nitrile motif embedded on a simple dipeptide framework.In‐vitroandin‐silicostudies revealed that the histidineα‐nitrile motif envisioned to target the M^procontributes to the inhibitory activity. Among a series of dipeptides synthesized featuring this novel structural motif, some dipeptides displayed strong viral reduction (EC₅₀=0.48 μM) with a high selectivity index, SI>454.54. These compounds also exhibit strong binding energies in the range of −28.7 to −34.2 Kcal/mol. The simple dipeptide structural framework, amenable to quick structural variations, coupled with ease of synthesis from readily available commercial starting materials are the major attractive features of this novel class of SARS‐CoV‐2 inhibitors. The histidineα‐nitrile dipeptides raise the hope of discovering potent drug candidates based on this motif to fight the dreaded SARS‐CoV‐2.