Cluster Ligands Research Articles

In Situ Oxidative Ring-Opening of Calix[8]arene to Construct Stable Bismuth-Oxo Clusters with Exposed Catalytic Sites for Specific Electroreduction of CO2 to HCOOH.

Nanocluster catalysts typically face challenges in balancing stability with catalytic efficiency. This study introduces a unique bismuth-oxo cluster, solely protected by two ring-opened calixarenes, which demonstrates not only enhanced structural stability but also superior catalytic performance in the sustained conversion of CO2 to HCOOH via electrocatalysis. For the first time, we reveal that under specific solvothermal conditions, tert-butylcalix[8]arene (TBC[8]) can undergo in situ oxidative cleavage of its C-C bond, leading to ring-opened polyphenolic molecules. These molecules serve as protective ligands for the bismuth-oxo cluster, bestowing exceptional structural stability and offering a more flexible and diverse configuration compared to intact TBC[8]. This adaptability promotes the exposure of active bismuth sites on the cluster surface, enhancing catalytic efficiency. Notably, the Bi10 cluster, featuring a monobismuth active site, achieves an exceptional formate production efficiency of 98.79% at -1.25 V vs RHE while maintaining superb durability over 8 h. The stability and catalytic processes of Bi10 surpass those of the Bi13 cluster, which is structurally reinforced by two intact TBC[8] molecules and stabilized by four benzoic ligands. Through in situ infrared spectroscopy and density functional theory calculations, we demonstrate that the monobismuth active site in Bi10 more effectively stabilizes the *OCHO intermediate, thereby promoting the electrocatalytic reduction of CO2 to HCOOH compared to Bi13. This comparative performance underscores the potential of ring-opened calixarene ligands in enhancing the functionality of nanocluster catalysts.

Sub-10 μm Soft Interlayers Integrating Patterned Multivalent Biomolecular Binding Environments.

Designing surfaces that enable controlled presentation of multivalent ligand clusters (e.g., for rapid screening of biomolecular binding constants or design of artificial extracellular matrices) is a cross-cutting challenge in materials and interfacial chemistry. Existing approaches frequently rely on complex building blocks or scaffolds and are often specific to individual substrate chemistries. Thus, an interlayer chemistry that enabled efficient nanometer-scale patterning on a transferrable layer and subsequent integration with other classes of materials could substantially broaden the scope of surfaces available for sensors and wearable electronics. Recently, we have shown that it is possible to assemble nanometer-resolution chemical patterns on substrates including graphite, use diacetylene polymerization to lock the molecular pattern together, and then covalently transfer the pattern to amorphous materials (e.g., polydimethylsiloxane, PDMS), which would not natively enable high degrees of control over ligand presentation. Here, we develop a low-viscosity PDMS formulation that generates very thin films (<10 μm) with dense cross-linking, enabling high-efficiency surface functionalization with polydiacetylene arrays displaying carbohydrates and other functional groups (up to 10-fold greater than other soft materials we have used previously) on very thin films that can be integrated with other materials (e.g., glass and soft materials) to enable a highly controlled multivalent ligand display. We use swelling and other characterization methods to relate surface functionalization efficiency to the average distance between cross-links in the PDMS, developing design principles that can be used to create even thinner transfer layers. In the context of this work, we apply this approach using precision glycopolymers presenting structured arrays of N-acetyl glucosamine ligands for lectin binding assays. More broadly, this interlayer approach lays groundwork for designing surface layers for the presentation of ligand clusters on soft materials for applications including wearable electronics and artificial extracellular matrix.

An Atom-Precise Understanding of DNA-Stabilized Silver Nanoclusters.

ConspectusDNA-stabilized silver nanoclusters (AgN-DNAs) are sequence-encoded fluorophores. Like other noble metal nanoclusters, the optical properties of AgN-DNAs are dictated by their atomically precise sizes and shapes. What makes AgN-DNAs unique is that nanocluster size and shape are controlled by nucleobase sequence of the templating DNA oligomer. By choice of DNA sequence, it is possible to synthesize a wide range of AgN-DNAs with diverse emission colors and other intriguing photophysical properties. AgN-DNAs hold significant potential as "programmable" emitters for biological imaging due to their combination of small molecular-like sizes, bright and sequence-tuned fluorescence, low toxicities, and cost-effective synthesis. In particular, the potential to extend AgN-DNAs into the second near-infrared region (NIR-II) is promising for deep tissue imaging, which is a major area of interest for advancing biomedical imaging. Achieving this goal requires a deep understanding of the structure-property relationships that govern AgN-DNAs in order to design AgN-DNA emitters with sizes and geometries that support NIR-II emission.In recent years, major advances have been made in understanding the structure and composition of AgN-DNAs, enabling new insights into the correlation of nanocluster structure and photophysical properties. These advances have hinged on combined innovations in mass characterization and crystallography of compositionally pure AgN-DNAs, together with combinatorial experiments and machine learning-guided design. A combined approach is essential due to the major challenge of growing suitable AgN-DNA crystals for diffraction and to the labor-intensive nature of preparing and solving the molecular formulas of atomically precise AgN-DNAs by mass spectrometry. These approaches alone are not feasibly scaled to explore the large sequence space of DNA oligomer templates for AgN-DNAs.This account describes recent fundamental advances in AgN-DNA science that have been enabled by high throughput synthesis and fluorimetry together with detailed analytical studies of purified AgN-DNAs. First, short introductions to nanocluster chemistry and AgN-DNA basics are presented. Then, we review recent large-scale studies that have screened thousands of DNA templates for AgN-DNAs, leading to discovery of distinct classes of these emitters with unique cluster core compositions and ligand chemistries. In particular, the discovery of a new class of chloride-stabilized AgN-DNAs enabled the first ab initio calculations of AgN-DNA electronic structure and present new approaches to stabilize these emitters in biologically relevant conditions. Near-infrared (NIR) emissive AgN-DNAs are also found to exhibit diverse structures and properties. Finally, we conclude by highlighting recent proof-of-principle demonstrations of NIR AgN-DNAs for targeted fluorescence imaging. Continued efforts may future push AgN-DNAs into the tissue transparency window for fluorescence imaging in the NIR-II tissue transparency window.

Navigating the 18-n+m Isomers of PdSn2: Chemical Pressure Relief through Isolobal Bonds and Main Group Clustering.

The 18-n electron-counting rule provides structural guidelines for electronically feasible transition metal (T)-main group (E) phases, contributing toward the goal of material design. However, the availability of numerous potential structure types at any electron count creates a challenge for the prediction of the preferred structures of specific compounds, as is illustrated by the concept of 18-n+m isomerism. In this Article, we explore the driving forces stabilizing one 18-n+m isomer over another with an analysis of the structure of PdSn2, a layered intergrowth of the fluorite and CuAl2 structure types. The DFT-reversed approximation Molecular Orbital (DFT-raMO) method reveals that PdSn2 and its hypothetical parent structures all adhere to bonding schemes approximating the electronic configurations expected from the 18-n rule, with various degrees of isolobal Pd-Pd bonding and Sn clustering. However, partial electron transfer between the Pd 5p orbitals to the Sn 5s orbitals contributes to the absence of convincing electronic pseudogaps near their Fermi energies. As such, there is no clear electronically driven preference among the structure types. This situation allows for atomic packing effects to prevail: DFT-Chemical Pressure (DFT-CP) analysis illustrates that in the fluorite-type parent structure, positive Pd-Sn CPs lead to overcompression of the Pd atoms and a stretching of the relatively open Sn sublattice. In contrast, in the CuAl2-type parent structure, Sn atoms cluster into tetrahedra, opening space for an expanded Pd environment and the formation of Pd-Pd interactions. However, the tetrahedral packing of the Sn atoms here leads to frustration between negative and positive Sn-Sn CPs. Through the development of the angular CP correlation function (CPcor+) as a tool to quantify frustration among interatomic interactions, we demonstrate how the observed PdSn2 structure balances these effects by tuning the degree of Sn-Sn clustering and expansion of the Pd environment. These observations point to generalizations for most 18-n+m isomers, where increased main group ligand clustering (+m) and isolobal bonds (+n) can accommodate compositions with different T and E atomic sizes.

Membrane Fluctuation Model for Understanding the Effect of Receptor Nanoclustering on the Activation of Natural Killer Cells through Biomechanical Feedback.

We investigated the role of ligand clustering and density in the activation of natural killer (NK) cells. To that end, we designed reductionist arrays of nanopatterned ligands arranged with different cluster geometries and densities and probed their effects on NK cell activation. We used these arrays as an artificial microenvironment for the stimulation of NK cells and studied the effect of the array geometry on the NK cell immune response. We found that ligand density significantly regulated NK cell activation while ligand clustering had an impact only at a specific density threshold. We also rationalized these findings by introducing a theoretical membrane fluctuation model that considers biomechanical feedback between ligand-receptor bonds and the cell membrane. These findings provide important insight into NK cell mechanobiology, which is fundamentally important and essential for designing immunotherapeutic strategies targeting cancer.

Bimetal-Organic Frameworks Incorporating Both Hard and Soft Base Active Sites for Heavy Metal Ion Capture.

The design and synthesis of stable porous materials capable of removing both hard and soft metal ions pose a significant challenge. In this study, a novel metal-organic framework (MOF) adsorbent named CdK-m-COTTTB was developed. This MOF material was constructed using sulfur-rich m-cyclooctatetrathiophene-tetrabenzoate (m-H4COTTTB) as the organic ligand and oxygen-rich bimetallic clusters as the inorganic nodes. The incorporation of both soft and hard base units within the MOF structure enables effective removal of various heavy metal ions, including both soft and hard acid species. In single-component experiments, the adsorption capacity of CdK-m-COTTTB for Pb2+, Tb3+, and Zr4+ ions reached levels of 636.94, 432.90, and 357.14 mg·g-1, respectively, which is comparable to specific MOF absorbents. The rapid adsorption process was found to be chemisorption. Furthermore, CdK-m-COTTTB exhibited the capability to remove at least 12 different metal ions in both separate and multicomponent solutions. The material demonstrated excellent acid-base stability and renewability, which are advantageous for practical applications. CdK-m-COTTTB represents the first reported pristine MOF material for the removal of both hard and soft acid metal ions. This work serves as inspiration for the design and synthesis of porous crystalline materials that can efficiently remove diverse heavy metal pollutants.

Functional Integrity of Radical SAM Enzyme Dph1•Dph2 Requires Non-Canonical Cofactor Motifs with Tandem Cysteines.

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif is found next to another ill-defined cysteine that we show is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCMs) suggests a candidate Fe-S cluster ligand role. Hence, we generated, by site-directed DPH1 and DPH2 mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo.

Effect of Monovalent Cations on the Structure and Dynamics of Multimodal Chromatographic Surfaces.

While multimodal (MM) chromatography is a promising approach for purifying proteins, the lack of a fundamental understanding of how ion-ligand interactions govern selectivity limits its use in the biopharmaceutical industry. This study uses molecular dynamics simulations to study the interactions between simple monovalent cations and two commonly used structurally similar multimodal chromatography ligands, the Capto ligand and Nuvia cPrime, immobilized on the surface. On the Capto ligand surface, ion presence and type play a key role in modulating the formation of phenyl rings and carboxylate clusters. The flexible linkage attaching the Capto ligand to the self-assembled monolayer (SAM) surface allowed multiple ligands to form interactions with the small cations, while large cations interacted less strongly, following the order Li+ > Na+ > K+ > Cs+. Thus, smaller cations resulted in greater ordering on the surface and lower ion diffusivities, while larger cations resulted in less ordering and higher ion diffusivities, following the order Li+ < Na+ < K+ < Cs+. In contrast, due to the rigid attachment of Nuvia cPrime to the SAM surfaces, the cations bound less strongly and had a much smaller effect on ligand clustering or ordering. Additionally, ions in the presence of the Nuvia cPrime surface had generally greater diffusivities than those in the presence of the Capto ligand. Overall, the interaction of cations with the multimodal ligands can lead to unique configurations on the SAM that likely contribute to differential behavior in biological separations.

Relativistic effect influencing the diverse bonding character of the interfacial Ag staple motifs in thiolate-protected nanoclusters.

Thiolate-protected noble-metal nanoclusters have recently attracted extensive attention due to their appealing properties in optics, catalysis, etc. Within the same group element, experiments indicate that Ag staples exhibit di-, tri-, or even tetra-coordination, in contrast to the di-coordination observed in Au staples, rendering the structures of Ag nanoclusters more intricate. However, the underlying chemical insight of the bonding feature of multiple-coordinated Ag staples remains unclear. In this study, we employed density functional theory coupled with all-electron scalar relativistic calculations to elucidate the critical role of relativistic effect in determining the conformational complexity of Ag staples. Unlike Au, the relatively weaker relativistic effect induces fewer contributions of d orbitals in bonding for the Ag atom, showing an extreme sensitivity to the structural architecture in liganded clusters. A relatively higher d orbital percentage favors di-coordination with a shortened Ag-S bond, while a relatively lower d orbital percentage favors tri- and tetra-coordinations with an elongated Ag-S bond. The Lewis structures of the multi-coordinated Ag motifs were also unveiled. In addition, two AgNCs, including the [Ag29(SCH3)18]3- cluster with tri-coordinated Ag motifs and [Ag29(SCH3)18(PCH3)6]3- with tetra-coordinated Ag motifs, were predicted after clarifying the bonding characters of the multiple-coordinated Ag motifs. This work not only deepens the understanding of the bonding characteristics of the Ag staple motif in AgNCs and AuAg alloy clusters but also provides a new perspective to understand the relativistic effect in the thiolate-protected noble-metal nanocluster.

Unraveling the ligand specificity and promiscuity of the Staphylococcus aureus NorA efflux pump: a computational study

Staphylococcus aureus, a gram-positive bacterial pathogen, develops antibiotic resistance partly through enhanced activity of transmembrane multi-drug efflux pump proteins like NorA. Being a prominent member of the Major Facilitator Superfamily (MFS), NorA transports various small molecules including hydrophilic fluoroquinolone antibiotics across the cell membrane. Intriguingly, NorA is inhibited by a structurally diverse set of small molecule inhibitors as well, indicating a highly promiscuous ligand/inhibitor recognition. Our study aims to elucidate the structural facets of this promiscuity. Known NorA inhibitors were grouped into five clusters based on chemical class and docked into ligand binding pockets on NorA conformations generated via molecular dynamics simulations. We discovered that several key residues, such as I23, E222, and F303, are involved in inhibitor binding. Additionally, residues I244, T223, F303, and F140 were identified as prominent in interactions with specific ligand clusters. Our findings suggest that NorA's substrate binding site, encompassing residues aiding ligand recognition based on chemical nature, facilitates the recognition of chemically diverse ligands. This insight into NorA's structural promiscuity in ligand recognition not only enhances understanding of antibiotic resistance mechanisms in S. aureus but also sets the stage for the development of more effective efflux pump inhibitors, vital for combating multidrug resistance. Communicated by Ramaswamy H. Sarma

TiO2 Nano-Biopatterning Reveals Optimal Ligand Presentation for Cell-Matrix Adhesion Formation.

Nanoscale organization of transmembrane receptors is critical for cellular functions, enabled by the nanoscale engineering of bioligand presentation. Previously, a spatial threshold of ≤60nm for integrin binding ligands in cell-matrix adhesion is demonstrated using monoliganded gold nanoparticles. However, the ligand geometric arrangement is limited to hexagonal arrays of monoligands, while plasmonic quenching limits further investigation by fluorescence-based high-resolution imaging. Here, these limitations are overcome with dielectric TiO2 nanopatterns, eliminating fluorescence quenching, thus enabling super-resolution fluorescence microscopy on nanopatterns. By dual-color super-resolution imaging, high precision and consistency among nanopatterns, bioligands, and integrin nanoclusters are observed, validating the high quality and integrity of both nanopattern functionalization and passivation. By screening TiO2 nanodiscs with various diameters, an increase in fibroblast cell adhesion, spreading area, and Yes-associated protein (YAP) nuclear localization on 100 nm diameter compared with smaller diameters was observed. Focal adhesion kinase is identified as the regulatory signal. These findings explore the optimal ligand presentation when the minimal requirements are sufficiently fulfilled in the heterogenous extracellular matrix network of isolated binding regions with abundant ligands. Integration of high-fidelity nano-biopatterning with super-resolution imaging allows precise quantitative studies to address early signaling events in response to receptor clustering and their nanoscale organization.

FRET-Sensing of Multivalent Protein Binding at the Interface of Biomimetic Microparticles Functionalized with Fluorescent Glycolipids.

Cell adhesion is a central process in cellular communication and regulation. Adhesion sites are triggered by specific ligand-receptor interactions inducing the clustering of both partners at the contact point. Investigating cell adhesion using microscopy techniques requires targeted fluorescent particles with a signal sensitive to the clustering of receptors and ligands at the interface. Herein, we report on simple cell or bacterial mimics, based on liquid microparticles made of lipiodol functionalized with custom-designed fluorescent lipids. These lipids are targeted toward lectins or biotin membrane receptors, and the resulting particles can be specifically identified and internalized by cells, as demonstrated by their phagocytosis in primary murine bone marrow-derived macrophages. We also evidence the possibility to sense the binding of a multivalent lectin, concanavalin A, in solution by monitoring the energy transfer between two matching fluorescent lipids on the surface of the particles. We anticipate that these liquid particle-based sensors, which are able to report via Förster resonance energy transfer (FRET) on the movement of ligands on their interface upon protein binding, will provide a useful tool to study receptor binding and cooperation during adhesion processes such as phagocytosis.

Cuboctahedral Pd13 as a spherical aromatic noble metal core: insights from a ligand-protected [Pd13(Tr)6]2+ cluster.

Low-valent palladium nanoparticles are efficient species promoting catalytic activity and selectivity in a number of chemical reactions. Recently, an atom-centered cuboctahedral Pd13 motif has been characterized as a ligand-protected [Pd13(Tr)6]2+ cluster featuring a 1s2 superatomic shell structure. In this report, we describe the ligand-cluster of and endohedral-cage interaction in [Pd13(Tr)6]2+, which accounts for a favorable situation in the overall cluster. In addition, the spherical aromatic properties of the cluster were evaluated to understand the behavior of the ligand-protected Pd13 cluster core. Our results indicate a sizable interaction towards carbon-based ligands in an overall spherical aromatic cluster featuring a long-range shielding cone. Thus, [Pd13(Tr)6]2+ is rationalized as the first ligand-protected palladium cluster to date exhibiting spherical aromatic properties, serving as a stable building block for molecule-based materials or as a dopant in porous carbon materials.

Two structurally new Lindqvist hexaniobate-templated silver thiolate clusters.

Two structurally new Lindqvist hexaniobate-templated silver thiolate clusters, [Nb6O19@Ag45(iPrS)23(CH3COO)14] (Ag45) and (H3O)4[Nb6O19@Ag41KS2.5O2(H2O)7.5(iPrS)24(CH3COO)5] (Ag41), were synthesized using a facile one-pot solvothermal approach. Single crystal X-ray diffraction analyses revealed the presence of a classical Lindqvist-type [Nb6O19]8- anion template, with iPrS- and CH3COO- surface-protecting ligands in both silver clusters, which can further form two-dimensional Ag45 assembly and one-dimensional Ag41 chain packing structures. Both Ag45 and Ag41 clusters exhibited intriguing photothermal conversion properties and temperature-dependent emission behavior.

A bis-aromatic MOF system constructed with a copper iodine cluster and porphyrinic ligand for enhancing near-infrared photothermal conversion

An organic–inorganic bis-aromatic system achieves an NIR-II photothermal efficiency of up to 63.77%.

Au9 nanocluster adsorption and agglomeration control through sulfur modification of mesoporous TiO2.

In the present work phenyl phosphine-protected Au9 nanoclusters were deposited onto (3-mercaptopropyl) trimethoxysilane (MPTMS) modified and unmodified mesoporous screen printed TiO2. The removal of the cluster ligands by annealing was applied to enhance the interaction between Au cluster cores and semiconductor surfaces in the creation of efficient photocatalytic systems. The heat treatment could lead to undesired agglomeration of Au clusters, affecting their unique properties as size specific clusters. To address this challenge, the semiconductor surfaces were modified by MPTMS. Characterization techniques confirm the effectiveness of the modification processes, and XPS demonstrates that S functionalized MTiO2 is more efficient than MTiO2 in increasing Au9 NCs adsorption by a factor of 10 and preventing Au cluster agglomeration even after annealing. Overall, this work contributes valuable insights into photocatalytic systems through controlled modification of semiconductor surfaces and Au nanocluster deposition.

Effect of ligand and shell densities on the surface structure of core-shell nanoparticles self-assembled from function-spacer-lipid constructs.

Biomolecular corona is the major obstacle to the clinical translation of nanomedicines. Since corona formation is governed by molecular interactions at the nano-bio interface, nanoparticle surface properties such as topography, charge and surface chemistry can be tuned to manipulate biomolecular corona formation. To this end, as the first step towards a deep understanding of the processes of corona formation, it is necessary to develop nanoparticles employing various biocompatible materials and characterize their surface structure and dynamics at the molecular level. In this work, we applied molecular dynamics simulation to study the surface structure of organic core-shell nanoparticles formed by the self-assembly of synthetic molecules composed of a DOPE lipid, a carboxymethylglycine spacer and biotin. Lipid moieties form the hydrophobic core, spacer motifs serve as a hydrophilic shell and biotin residues function as a targeting ligand. By mixing such function-spacer-lipid, spacer-lipid and lipid-only constructs at various molar ratios, densities of the ligand and spacer on the nanoparticle surface were modified. For convenient analysis of the structure and dynamics of all regions of the nanoparticle surface, we compiled topography maps based on atomic coordinates. It was shown that an increase in the density of the shell does not reduce exposure of the core, but increases shell average thickness. Biotin, due to its alkyl valeric acid chain and spacer flexibility, is localized primarily near the hydrophobic core and its partial presentation on the surface occurs only in nanoparticles with higher ligand densities. However, an increase in biotin density leads to its clustering. In turn, ligand clustering diminishes the stealth properties of the shell and targeting efficiency. Based on nanoparticle surface structures, we determined the optimal density of biotin. Experimental studies reported in the literature confirm these conclusions. We also suggest design tips to achieve the preferred biotin presentation. Simulation results are consistent with the synchrotron SAXS profile. We believe that such studies will contribute to a better understanding of nano-bio interactions towards the rational design of efficient drug delivery systems.

Probing the mechanism of the dedicated NO sensor [4Fe-4S] NsrR: the effect of cluster ligand environment

NsrR from Streptomyces coelicolor is a bacterial nitric oxide (NO) sensor/nitrosative stress regulator as its primary function, and has been shown to have differential response at low, mid, and high levels of NO. These must correspond to discrete structural changes at the protein-bound [4Fe-4S] cluster in response to stepwise nitrosylation of the cluster. We have investigated the effect of the monohapto carboxylate ligand in the site differentiated [4Fe-4S] cluster cofactor of the protein NsrR on modulating its reactivity to NO with a focus on indentifying mechanistic intermediates. We have prepared a synthetic model [4Fe-4S] cluster complex with tripodal ligand and one single site differentiated site occupied by either thiolate or carboxylate ligand. We report here the mechanistic details of sequential steps of nitrosylation as observed by ESI MS and IR spectroscopy. Parallel non-denaturing mass spectrometry analyses were performed using site-differentiated variants of NsrR with the native aspartic acid, cysteine, or alanine in the position of the forth ligand to the cluster. A mono-nitrosylated synthetic [4Fe-4S] cluster was observed for the first time in a biologically-relevant thiolate-based coordination environment. Combined synthetic and protein data give unprecedented clarity in the modulation of nitrosylation of a [4Fe-4S] cluster.

Synthesis of iron-boride/carbon-nitride composites and their applications in chemodynamic therapy

Chemodynamic therapy (CDT) is an emerging treatment strategy that inhibits tumor growth by catalyzing the generation of reactive oxygen species (ROS), such as hydroxyl radicals (•OH), using specific nanomaterials. Herein, we have developed a new class of iron-based nanomaterials, i.e., iron-based borides (FeB), using the superchaotropic effect of a boron cluster (closo-[B12H12]2–) and organic ligands, followed by high-temperature calcination. Experimental data and theoretical calculations revealed that FeB nanoparticles exhibit a Fenton-like effect, efficiently decomposing hydrogen peroxide into •OH and thus increasing the concentration of ROS. FeB nanomaterials demonstrate excellent catalytic performance, efficiently generate ROS, and exert significant antitumor effects in cell experiments and animal models. Therefore, FeB nanomaterials have considerable potential for application in tumor treatment and offer new insights for the development of novel and efficient cancer therapy strategies.

Iron homeostasis proteins Grx4 and Fra2 control activity of the Schizosaccharomyces pombe iron repressor Fep1 by facilitating [2Fe-2S] cluster removal

The Bol2 homolog Fra2 and monothiol glutaredoxin Grx4 together play essential roles in regulating iron homeostasis in Schizosaccharomyces pombe. In vivo studies indicate that Grx4 and Fra2 act as co-inhibitory partners that inactivate the transcriptional repressor Fep1 in response to iron deficiency. In Saccharomyces cerevisiae, Bol2 is known to form a [2Fe-2S]-bridged heterodimer with the monothiol glutaredoxins Grx3 and Grx4, with the cluster ligands provided by conserved residues in Grx3/4 and Bol2 as well as glutathione (GSH). In this study, we characterized this analogous [2Fe-2S]-bridged Grx4-Fra2 complex in S. pombe by identifying the specific residues in Fra2 that act as ligands for the Fe-S cluster and are required to regulate Fep1 activity. We present spectroscopic and biochemical evidence confirming the formation of a [2Fe-2S]-bridged Grx4-Fra2 heterodimer with His66 and Cys29 from Fra2 serving as Fe-S cluster ligands in S. pombe. In vivo transcription and growth assays confirm that both His66 and Cys29 are required to fully mediate the response of Fep1 to low iron conditions. Furthermore, we analyzed the interaction between Fep1 and Grx4-Fra2 using circular dichroism spectroscopy to monitor changes in Fe-S cluster coordination chemistry. These experiments demonstrate unidirectional [2Fe-2S] cluster transfer from Fep1 to Grx4-Fra2 in the presence of GSH, revealing the Fe-S cluster dependent mechanism of Fep1 inactivation mediated by Grx4 and Fra2 in response to iron deficiency.