Oligomeric Clusters Research Articles

A New Combined Computational and Experimental Approach to Characterize Photoactive Conjugated 3D Polymers.

A tractable new computational protocol is proposed to elucidate oligomeric-scale detail from experimental spectra, providing insight into the local and longer-range electronic and molecular structures of amorphous materials. The protocol uses an in-house code Ambuild to grow kinetically-controlled representative oligomeric clusters of an amorphous polymeric material. Generating many clusters, the statistical prevalence of different structural motifs is identified, and used to develop a 'subset' of structures that capture a broad range of important morphologies. Subsequent electronic structure calculations allow the prediction of IR, NMR, and UV-vis spectra of the bulk materials, providing significant insight into oligomeric scale topologies and helping develop structure-property relationships by identifying the underlying structural origins of different spectral features observed experimentally. Two known, and two novel, pyrene-based conjugated microporous polymers (CMPs) are synthesized and characterized as a test bed for this newly-proposed protocol. Meaningful IR, NMR, and UV-vis absorption spectral data, and experimentally comparable computationally derived spectra are obtained. Whilst IR and NMR reliably probe the local environment, UV-vis absorption spectroscopy is found to be particularly sensitive to the longer-range structural motifs observed on an oligomeric scale, providing significant structural insight into the synthesized materials with reasonable computational cost.

Quantitative single-molecule analysis of assembly and Ca2+-dependent disassembly of synaptotagmin oligomers on lipid bilayers

Synaptotagmin-1 (Syt-1) self-assembles into ring-like oligomers, and genetic and biochemical evidence suggest that oligomerization is needed to clamp synaptic vesicles and stabilize them for Ca2+-evoked release. However, oligomerization has not yet been demonstrated on lipid bilayers or studied in quantitative biophysical terms. Here we utilize single-molecule imaging methods to monitor the assembly and disassembly of oligomeric clusters of Syt-1 on lipid bilayers in real-time. Syt-1 assembled into two distinct classes of oligomers, small (5 ± 2 subunits) and large (15 ± 2 subunits). Each class assembled at a constant kon that was always proportional to its ultimate size, but both classes disassembled at the same unit rate (koff) independent of its size. Both large and small oligomers explosively disassembled when Ca2+ was added. The F349A mutation in the Syt-1 nearly eliminates the large class of oligomers but does not reduce the small class. Altogether, the physical-chemical properties of Syt-1 oligomers meet or exceed the physiologic requirements to function as such a clamp.

Spontaneous Formation of π-Conjugated Polymeric Colloidal Molecules Through Stepwise Coacervation and Symmetric Compartmentalization.

Coacervation, the phase separation of liquid induced by polymeric solutes, sometimes results in the formation of oligomeric clusters of droplets. The morphology of the clusters is non-uniform because the clustering is a consequence of the random collisions of the drifting droplets. Herewereportdistinctively organized coacervation, yielding colloidal molecules with monodisperse size, morphological symmetry, and compositional heterogeneity.Weinvestigate the coacervation of a mixture of two types of synthetic polymers and find that one of the polymers coacervates first and serves as a core droplet, on which the other polymer coacervates subsequently to form satellite droplets. The satellite droplets arrange themselves symmetrically around the core and solidify without losing the morphology. The number of satellites and their symmetry are modulable depending on the chemical affinity and the diameter of the droplets. This finding highlights the capability of coacervation as a non-templated and non-covalent pathway to form aspherical colloidal materials with structural and functional complexity.

Both the transcriptional activator, Bcd, and repressor, Cic, form small mobile oligomeric clusters

Transcription factors play an essential role in pattern formation during early embryo development, generating a strikingly fast and precise transcriptional response that results in sharp gene expression boundaries. To characterize the steps leading up to transcription, we performed a side-by-side comparison of the nuclear dynamics of two morphogens, a transcriptional activator, Bicoid (Bcd), and a transcriptional repressor, Capicua (Cic), both involved in body patterning along the anterior-posterior axis of the early Drosophila embryo. We used a combination of fluorescence recovery after photobleaching, fluorescence correlation spectroscopy, and single-particle tracking to access a wide range of dynamical timescales. Despite their opposite effects on gene transcription, we find that Bcd and Cic have very similar nuclear dynamics, characterized by the coexistence of a freely diffusing monomer population with a number of oligomeric clusters, which range from low stoichiometry and high mobility clusters to larger, DNA-bound hubs. Our observations are consistent with the inclusion of both Bcd and Cic into transcriptional hubs or condensates, while putting constraints on the mechanism by which these form. These results fit in with the recent proposal that many transcription factors might share a common search strategy for target gene regulatory regions that makes use of their large unstructured regions, and may eventually help explain how the transcriptional response they elicit can be at the same time so fast and so precise.

Surface Electroactive Sites of Tungstated Zirconia Catalysts for Vanadium Redox Flow Batteries.

Surface electroactive sites for tungstate zirconia (WZ) were created by utilizing tungstate-immobilized UiO-66 as precursors via a double-solvent impregnation method under a mild calcination temperature. The WZ-22-650 catalyst, containing a moderate W content (22%), demonstrated a high density of surface electroactive sites. Proper heat treatment facilitated the binding of oligomeric tungsten clusters to stabilized tetragonal ZrO2, resulting in improved catalytic performance toward the VO2+/VO2+ redox couples compared to other tested samples. The substantial surface area, mesoporous structure, and establishment of new W-O-Zr bonds affirm the firm anchoring of WOx to ZrO2. This robust attachment enhances surface electroactive sites, elevating the electrochemical performance of vanadium redox flow batteries (VRFBs). Charge-discharge tests further demonstrate that the superior voltage efficiency (VE) and energy efficiency (EE) for VRFBs using the WZ-22-650 catalyst are 87.76 and 83.94% at 80 mA cm-2, which are 13.42% VE and 10.88% EE better than heat-treated graphite felt, respectively. Even at a higher current density of 160 mA cm-2, VRFBs utilizing the WZ-22-650 catalyst maintained considerable efficiency, recording VE and EE values of 76.76 and 74.86%, respectively. This facile synthesis method resulted in WZ catalysts displaying superior catalytic activity and excellent cyclability, offering a promising avenue for the development of metal-oxide-based catalysts.

M13 phage grafted with peptide motifs as a tool to detect amyloid-β oligomers in brain tissue

Oligomeric clusters of amyloid-β (Aβ) are one of the major biomarkers for Alzheimer’s disease (AD). However, proficient methods to detect Aβ-oligomers in brain tissue are lacking. Here we show that synthetic M13 bacteriophages displaying Aβ-derived peptides on their surface preferentially interact with Aβ-oligomers. When exposed to brain tissue isolated from APP/PS1-transgenic mice, these bacteriophages detect small-sized Aβ-aggregates in hippocampus at an early age, prior to the occurrence of Aβ-plaques. Similarly, the bacteriophages reveal the presence of such small Aβ-aggregates in post-mortem hippocampus tissue of AD-patients. These results advocate bacteriophages displaying Aβ-peptides as a convenient and low-cost tool to identify Aβ-oligomers in post-mortem brain tissue of AD-model mice and AD-patients.

Sequence-dependent conformational transitions of disordered proteins during condensation.

Intrinsically disordered proteins (IDPs) can form biomolecular condensates through phase separation. It is recognized that the conformation of IDPs in the dense and dilute phases, as well as at the interfaces of condensates, can critically impact their functionality. However, a residue-level understanding of the conformational transitions of IDPs during condensation remains elusive. In this study, we employ a coarse-grained polyampholyte model, comprising an equal number of oppositely charged residues-glutamic acid and lysine-whereby conformations and phase behavior can be tuned by altering the protein sequence. By manipulating sequence patterns from perfectly alternating to block-like, we obtain chains with ideal-like conformations to semi-compact structures in the dilute phase. In the dense phase, however, the chain conformation approaches that of an ideal chain, regardless of the sequence. Simulations across different concentrations reveal that chains transition from small oligomeric clusters in the dilute phase to the dense phase, with a gradual swelling of individual chains. These findings are further validated with naturally occurring protein sequences involved in biological condensate formation. Additionally, we show that chain conformations at the interface display a strong sequence dependence, remaining more collapsed than those in the bulk-like dense phase. This study provides detailed insights into how the conformations of a specific subclass of IDPs (lacking secondary structures) change within condensates and in solution, as governed by their sequences.

Towards Copper(I) Clusters for Photo-Induced Oxidation of Biological Thiols in Living Cells.

The cell redox balance can be disrupted by the oxidation of biological peptides, eventually leading to cell death, which provides opportunities to develop cytotoxic drugs. With the aim of developing compounds capable of specifically inducing fatal redox reactions upon light irradiation, we have developed a library of copper compounds. This metal is abundant and considered essential for human health, making it particularly attractive for the development of new anticancer drugs. Copper(I) clusters with thiol ligands (including 5 novel ones) have been synthesized and characterized. Structures were elucidated by X-ray diffraction and showed that the compounds are oligomeric clusters. The clusters display high photooxidation capacity towards cysteine - an essential amino acid - upon light irradiation in the visible range (450 nm), while remaining completely inactive in the dark. This photoredox activity against a biological thiol is very encouraging for the development of anticancer photoredox drugs.The in vitro assay on murine colorectal cancer cells (CT26) did not show any toxicity - whether in the dark or when exposed to 450 nm light, likely because of the poor solubility of the complexes in biological medium.

What is the role of Mn/Al/Pt for ZSM-11 being a good catalytic oxidation catalyst?

What is the role of Mn/Al/Pt for ZSM-11 being a good catalytic oxidation catalyst?

Anticancer, antimicrobial and biomedical features of polyoxometalate as advanced materials: A review study

• Polyoxometalates (POMs) demonstrate an enhanced anti-viral , anti-tumor, and antibacterial activity. • POMs provide a highly biocompatibility and low cytotoxicity. • POMs with extraordinary feature could be effectively considered and utilized for targeted biomedical applications. Polyoxometalate(POMs) is an oligomeric cluster of transition metal oxoanions that has a well-defined infrastructure with a wide range of sizes, metal-oxygen frameworks, chemical compositions, and unparalleled properties. In the fields of catalysis, materials chemistry, and biochemistry, they are among the most attractive and fastest growing areas of research. Moreover, some POMs and their derivatives are capable of exhibiting antibacterial, antiviral, antitumor, and anticancer properties, in addition to their many valuable properties. Several studies have demonstrated the efficacy of some of these agents in the treatment of symptoms associated with diabetes. Because of these properties, POMs have always been of interest to researchers. In this review, an overview of the biomedical applications of POMs, including their role in pharmaceuticals, is provided based on various scientific publications.

Highly Bright Gold Nanowires Arrays for Sensitive Detection of Urea and Urease.

In this work, highly fluorescent gold nanowire arrays (Au NWs) are successfully synthesized by assembling Zn2+ ions and non-emissive oligomeric gold-thiolate clusters using mercaptopropionic acid both as a reducing agent and a growth ligand. The synthesized Au NWs exhibited strong bluish green fluorescence with an absolute quantum yield up to 32% and possessed ultrasensitive pH stimuli-responsive performance in the range of 7.0-7.8. Based on the excellent properties of the as-prepared nanowire arrays, we developed a facile, sensitive, and selective fluorescent method for quantitative detection of urea and urease. The fabricated nanoprobe showed superior biosensing response characteristics with good linearities in the range of 0-100 μM for urea concentration and 0-12 U/L for urease activity. In addition, this fluorescent probe afforded relatively high sensitivity with the detection limit as low as 2.1 μM and 0.13 U/L for urea and urease, respectively. Urea in human urine and urease in human serum were detected with satisfied results, exhibiting a promising potential for biomedical application.

Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stress

In yeast, ERMES, which mediates phospholipid transport between the ER and mitochondria, forms a limited number of oligomeric clusters at ER-mitochondria contact sites in a cell. Although the number of the ERMES clusters appears to be regulated to maintain proper inter-organelle phospholipid trafficking, its underlying mechanism and physiological relevance remain poorly understood. Here, we show that mitochondrial dynamics control the number of ERMES clusters. Moreover, we find that ER stress causes dissociation of the ERMES clusters independently of Ire1 and Hac1, canonical ER-stress response pathway components, leading to a delay in the phospholipid transport from the ER to mitochondria. Our biochemical and genetic analyses strongly suggest that the impaired phospholipid transport contributes to phospholipid accumulation in the ER, expanding the ER for ER stress attenuation. We thus propose that the ERMES dissociation constitutes an overlooked pathway of the ER stress response that operates in addition to the canonical Ire1/Hac1-dependent pathway.

Effects of Hydrophobic Residues on the Intracellular Self-Assembly of De Novo Designed Peptide Tags and Their Orthogonality

Protein assemblies forming nano- to micro-sized structures underlie versatile biological events in living systems. For mimicking and engineering these protein assemblies through a bottom-up approach, self-assembling peptides (SAPs) that form nanofibril structures via β-sheets serve as potential practical tags. Nevertheless, the development of SAP tags is still in its infancy, and insight into the relationship between peptide sequences and intracellular self-assembly is limited. In this study, we focused on hydrophobic residues in SAPs and examined the self-assembly of SAP-tagged superfolder GFPs (green fluorescent proteins) in COS-7 cells. Based on XEXK (X; hydrophobic amino acids: F, L, I, V, W, or Y) sequence units, we designed a panel of Xn peptides with different hydrophobic residues (X) and chain lengths (n). We observed that the self-assembly propensity, the size of the assemblies, the influence on protein denaturation, and the subcellular localization differed significantly depending on the hydrophobic amino acid. F9, L9, I7, and V13 peptides formed μm-scaled granules, W13 formed small oligomeric clusters in the cytoplasm, and Y15 formed assemblies in the nucleus. In addition, we investigated the orthogonality of their interaction. Strikingly, W13- and Y15-tagged proteins interacted independently and formed two distinct assemblies in cells. Herein, we have demonstrated the great opportunities for rationalizing artificial protein assemblies and orthogonal structures in an intracellular context using the designed SAPs.

Self-association status-dependent inactivation of the endoplasmic reticulum stress sensor Ire1 by C-terminal tagging with artificial peptides.

Upon endoplasmic reticulum (ER) stress, eukaryotic cells commonly induce unfolded protein response (UPR), which is triggered, at least partly, by the ER stress sensor Ire1. Upon ER stress, Ire1 is dimerized or forms oligomeric clusters, resulting in the activation of Ire1 as an endoribonuclease. In ER-stressed Saccharomyces cerevisiae cells, HAC1 mRNA is spliced by Ire1 and then translated into a transcription factor that promotes the UPR. Herein, we report that Ire1 tagged artificially with irrelevant peptides at the C terminus is almost completely inactive when only dimerized, while it induced the UPR as well as untagged Ire1 when clustered. This finding suggests a fundamental difference between the dimeric and clustered forms of Ire1. By comparing UPR levels in S. cerevisiae cells carrying artificially peptide-tagged Ire1 to that in cells carrying untagged Ire1, we estimated the self-association status of Ire1 under various ER stress conditions.

Oligomeric phosphate clusters in macrocyclic channels

Thirty-six-membered ring macrocycles form sandwich-like channels for oligomeric chains of hexaphosphate clusters.

A new method for the synthesis of polynuclear carboxylate complexes of technetium (II, III)

• A new method for obtaining halogen-free polymer clusters of Tc is proposed. • Low molecular weight fragments of Tc-containing clusters were detected using MALDI. • A mechanism for the formation of polymer Tc-containing clusters is proposed. Acetates of actinides and their fission products were essential for the development of radiochemical industries using acetate precipitation technology. Despite this, the literature describes only the synthesis of species containing technetium in the oxidation state +3 and higher. New synthetic routes for the preparation of technetium +2.5 carboxylate polymer clusters using readily available technetium (IV) oxide as a precursor are developed in the present study. The crystal structure of synthesized complexes is studied by X-ray diffraction analysis (XRD) at different temperatures, and the coefficients of thermal expansion along the axes of the crystal lattice and in the direction of the polymer chain growth are determined. Matrix assisted laser desorption/ionization–time of flight (MALDI–ToF) mass-spectrometry showed stability of technetium carboxylates under conditions of laser ionization, which allows suggesting the possibility of technetium coatings deposition from the gas phase. Based on the obtained experimental results a reaction mechanism for the formation of tetracarboxylate oligomeric and polymer complexes of technetium was proposed. Stable oligomeric tetracarboxylate technetium clusters formed in acetic acid solutions can be used to create radiopharmaceuticals.

Structural Dynamics of the Functional Nonameric Type III Translocase Export Gate

Type III protein secretion is widespread in Gram-negative pathogens. It comprises the injectisome with a surface-exposed needle and an inner membrane translocase. The translocase contains the SctRSTU export channel enveloped by the export gate subunit SctV that binds chaperone/exported clients and forms a putative ante-chamber. We probed the assembly, function, structure and dynamics of SctV from enteropathogenic E. coli (EPEC). In both EPEC and E. coli lab strains, SctV forms peripheral oligomeric clusters that are detergent-extracted as homo-nonamers. Membrane-embedded SctV9 is necessary and sufficient to act as a receptor for different chaperone/exported protein pairs with distinct C-domain binding sites that are essential for secretion. Negative staining electron microscopy revealed that peptidisc-reconstituted His-SctV9 forms a tripartite particle of ∼22nm with a N-terminal domain connected by a short linker to a C-domain ring structure with a ∼5nm-wide inner opening. The isolated C-domain ring was resolved with cryo-EM at 3.1Å and structurally compared to other SctV homologues. Its four sub-domains undergo a three-stage "pinching" motion. Hydrogen-deuterium exchange mass spectrometry revealed this to involve dynamic and rigid hinges and a hyper-flexible sub-domain that flips out of the ring periphery and binds chaperones on and between adjacent protomers. These motions are coincident with local conformational changes at the pore surface and ring entry mouth that may also be modulated by the ATPase inner stalk. We propose that the intrinsic dynamics of the SctV protomer are modulated by chaperones and the ATPase and could affect allosterically the other subunits of the nonameric ring during secretion.

Structuring effect of some salts on glycerol carbonate: A near-infrared spectroscopy, small- and wide-angle X-ray scattering study

• Strong basic anions strengthen the structuredness of glycerol carbonate. • SAXS and WAXS profile are combined to give insights on the structural features. • FTIR and NIR analysis shed light on the associated molecular clusters. Alkylene carbonates such as ethylene, glycerol and propylene carbonates offer a valuable tool for the investigation of intermolecular interactions in polar non-aqueous liquids. Their physico-chemical properties suggest the presence of a strong structure that mainly depends on hydrogen bonds. The addition of salts bearing basic anions such as fluoride, carbonate and phosphate leads to the formation of free ions and ion pairs that are well accommodated in the solvent structure. In this work near infrared and attenuated total reflection Fourier-transform infrared spectroscopy, small- and wide-angle X-ray scattering were carried out on pure glycerol carbonate and on its solutions of saturated KF, K 2 CO 3 and K 3 PO 4 in order to probe the structure of the solvent. Linear and cyclic oligomeric clusters produced by the association of the liquid molecules are proposed. The different effectiveness of the studied anions in enhancing the internal arrangement of the liquid can be explained in terms of polarizability (i.e. of the delocalization of their charge), different basicity and hydrogen bonding (HB) accepting capacity and geometry of the anions.

Bridging Polyoxometalate-Based Mn4 Cubane Clusters with Inorganic Phosphates: Structural Transformation and Magnetic Properties.

The mixed-valent tetramanganese MnIII3MnIV (Mn4) cubane clusters have been at the forefront of molecular magnetism and biomimetic catalysis research for decades. Incorporating robust polyoxometalates to Mn4 cubanes significantly improves their stability and aqueous solubility, while providing a great platform for studying their deposition onto selected surfaces during device fabrication. In this work, we discovered that the terminal carboxylate ligands in these polyoxometalate-based [MnIII3MnIVO4] magnetic clusters can be partially or completely replaced by inorganic phosphate/polyphosphate groups. This replacement leads to oligomeric aggregates of the Mn4 clusters. The magnetic data of the monomeric and oligomeric Mn4 clusters suggested that the introduction of inorganic phosphate bridges may not alter the S = 9/2 ground state of individual Mn4 clusters, although different magnetic behaviors, especially at low temperatures, were observed primarily because of intercluster interactions.

Influence of calcination temperature on the evolution of Fe species over Fe-SSZ-13 catalyst for the NH3-SCR of NO

• The low/high calcination temperature results in more isolated Fe 3+ /oligomeric Fe x O y clusters in Fe-SSZ-13. • The low-temperature activity of Fe-SSZ-13 is prompted by active isolated Fe 3+ . • The high-temperature activity of Fe-SSZ-13 is facilitated by active oligomeric Fe x O y clusters. To shed light on the relationships among catalyst calcination temperature, physicochemical properties and catalytic properties of Fe-SSZ-13, a series of catalysts prepared by aqueous post-synthetic exchange and calcined at different temperatures are characterized and evaluated in NH 3 -SCR reaction. The characterizations and kinetic analysis indicate that the calcination temperature has a great effect on the acidity, Fe species distribution and catalytic properties of the Fe-SSZ-13 catalyst. The rise of calcination temperature decreases the low-temperature activity (< 425℃) and conversely improves the high-temperature activity of Fe-SSZ-13. It could be attributed to the following reasons: under low calcination temperatures, more isolated Fe 3+ ions are maintained which can behave as Lewis acid sites and active sites in low reaction temperatures. Simultaneously, stronger surface acidity helps to alleviate NH 3 inhibition effect at low temperatures, resulting in good low-temperature activity. On the other hand, the high calcination temperature brings about slight aggregation of isolated Fe 3+ to form dimeric/oligomeric Fe clusters, leading more superior high-temperature activity. On the whole, the major active Fe species as well as the contribution of acid sites for low/high temperature activity are different. It could be concluded that the isolated Fe 3+ ions and oligomeric Fe clusters are the active sites for low/high SCR reaction temperature, respectively. And zeolite acidity plays a more important role in low-temperature SCR reaction catalyzed by Fe-SSZ-13.