Intelligent stimulus-response (S/R) systems are the basis of natural process and machine control, which are intensively explored in biomimetic design and analytical/biological applications. However, nonmonotonic multi-S/R systems are still rarely studied so far. In this work, a rational design strategy is proposed to achieve such a unique S/R system by integrating opposite luminescence behaviors in one molecule. When solvent polarity increases, many heterocyclic or carbonyl-containing compounds often become more emissive due to the suppression of the proximity effect, whereas molecules with donor-acceptor (D-A) structures tend to be less emissive because of the twisted intramolecular charge transfer. Meanwhile, protonation on D/A moieties will weaken/strengthen the D-A interaction to result in blue/redshifted emissions. By combining a protonatable heterocyclic acceptor and a protonatable donor together in one molecule, nonmonotonic brightness responses to polarity stimuli and nonmonotonic color responses to pH stimuli can be achieved. The design strategy is successfully verified by a simple molecule named 4-(dimethylamino)styryl)quinoxalin-2(1H)-one (ASQ). ASQ exhibits nonmonotonic responses to polarity and pH stimuli, and aggregation-induced emission (AIE) with a nonmonotonic AIE curve. Meanwhile, ASQ can be adjusted to emit white light in an acidic environment, and it shows multivalent functionalities including albumin protein sensing, ratiometric pH sensing, and amine gas sensing.
Molecular dynamics (MD) simulation has become a powerful tool to investigate the structurefunction relationship of proteins and other biological macromolecules at atomic resolution and biologically relevant timescales. MD simulations often produce massive datasets containing millions of snapshots describing proteins in motion. Therefore, clustering algorithms have been in high demand to be developed and applied to classify these MD snapshots and gain biological insights. There mainly exist two categories of clustering algorithms that aim to group protein conformations into clusters based on the similarity of their shape (geometric clustering) and kinetics (kinetic clustering). In this paper, we review a series of frequently used clustering algorithms applied in MD simulations, including divisive algorithms, agglomerative algorithms (single-linkage, complete-linkage, average-linkage, centroid-linkage and ward-linkage), center-based algorithms (K-Means, K-Medoids, K-Centers, and APM), density-based algorithms (neighbor-based, DBSCAN, density-peaks, and Robust-DB), and spectral-based algorithms (PCCA and PCCA+). In particular, differences between geometric and kinetic clustering metrics will be discussed along with the performances of different clustering algorithms. We note that there does not exist a one-size-fits-all algorithm in the classification of MD datasets. For a specific application, the right choice of clustering algorithm should be based on the purpose of clustering, and the intrinsic properties of the MD conformational ensembles. Therefore, a main focus of our review is to describe the merits and limitations of each clustering algorithm. We expect that this review would be helpful to guide researchers to choose appropriate clustering algorithms for their own MD datasets.
The
analysis of albumin has clinical significance in diagnostic
tests and obvious value to research studies on the albumin-mediated
drug delivery and therapeutics. The present immunoassay, instrumental
techniques, and colorimetric methods for albumin detection are either
expensive, troublesome, or insensitive. Herein, a class of water-soluble
tetrazolate-functionalized derivatives with aggregation-induced emission
(AIE) characteristics is introduced as novel fluorescent probes for
albumin detection. They can be selectively lighted up by site-specific
binding with albumin. The resulting albumin fluorescent assay exhibits
a low detection limit (0.21 nM), high robustness in aqueous buffer
(pH = 6–9), and a broad tunable linear dynamic range (0.02–3000
mg/L) for quantification. The tetrazolate functionality endows the
probes with a superior water solubility (>0.01 M) and a high binding
affinity to albumin (K
D = 0.25 μM).
To explore the detection mechanism, three unique polar binding sites
on albumin are computationally identified, where the multivalent tetrazolate–lysine
interactions contribute to the tight binding and restriction of the
molecular motion of the AIE probes. The key role of lysine residues
is verified by the detection of poly-l-lysine. Moreover,
we applied the fluorogenic method to quantify urinary albumin in clinical
samples and found it a feasible and practical strategy for albumin
analysis in complex biological fluids.
<div><div><div><p>Electrolyte interaction is of pivotal importance for chemical, biochemical, and environmental processes, including cellular signal transduction, DNA attraction, and protein dynamics. Although its investigation has been at the focus of extensive research, direct visualization of electrolyte interaction at the molecular level is exceptionally challenging. Here, we report a highly sensitive and readily-accessible technique to visualize the electrolyte interactions in water through molecular design and fluorescence spectroscopy. Two water-soluble luminogens with either cationic or anionic groups are designed as electrolyte models. The hydration shell of isolated luminogens is able to restrict their intramolecular motion, which enhances the emission. Consequently, the occurred electrolyte interactions can be optically detected since they affect the reorientation dynamics of water molecules in the hydration shell and vary the restriction strength on the intramolecular motion of the luminogens. Moreover, this technology allows us to reveal how electrolyte interaction affects the internal motion of an electrolyte within its hydration shell, which has rarely been achieved through experimental approaches.</p></div></div></div>
<p>Intelligent stimulus-response (S/R) systems are the basis of natural process and machine control, and have been intensively explored in biomimetic design, analytical chemistry and biological applications. However, nonmonotonic multi-S/R systems are still rarely studied so far. Now, we propose a rational design strategy to achieve such a unique S/R system by integrating opposite luminescence behaviors in one molecule. When solvent polarity increases, many heterocycles often become more emissive due to the suppression of the proximity effect. However, molecules with donor-acceptor (D-A) structures tend to be less emissive because of the twisted intramolecular charge transfer. Meanwhile, protonation on D/A moieties will weaken/strengthen the D-A interaction to result in blue/red-shifted emissions. By combining a protonatable heterocyclic acceptor and a protonatable donor together in one molecule, we can easily achieve nonmonotonic brightness responses to polarity stimuli and nonmonotonic color responses to pH stimuli. In this work, a simple molecule, namely ASQ is chosen as the model compound to verify the design strategy feasibility. It successfully shows two opposite trends of responses to polarity and pH stimuli, and aggregation-induced emission (AIE) with a nonmonotonic AIE curve. Moreover, the acidified ASQ solution is also a pure organic up-conversion and white-light-emitting system. A new mechanistic viewpoint is established to explain its unique anti-Stokes emission. Besides, ASQ shows multivalent functionalities including albumin protein sensing, ratiometric pH sensing, and amine gas sensing, etc. Therefore, ASQ is proved to be a fundamentally important and versatile functional “intelligent” AIE luminogen with nonmonotonic multi-responses to multi-stimuli. <br></p>
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