A Lead-μ2-Tetrylide Complex with Osmium(IV) Terminal Components.

Dinuclear complexes consisting of an α-diimine complex unit with different ortho substituents at the aryl rings and a half sandwich complex unit were prepared, activated with methylaluminoxane (MAO) and tested for the polymerization of ethylene. The dinuclear catalysts bearing zirconium centers showed higher ethylene polymerization activities than the analogous titanium catalysts. Among the dinuclear catalysts with the same metal centers, the bulkier ortho substituents at the aryl moiety gave lower polymerization activities. The GPC spectra of the polyethylenes produced with the dinuclear catalysts displayed bimodal molecular weight distributions due to different active sites.

The primary objective of the research was to develop a new methodology for disruption of antibody bonds. Specifically, the goal was to experimentally demonstrate that specifically-bound proteins can be released from a vibrating surface at physiological conditions. The second objective was to examine how vibration induced release using computational methods. There is a need to develop effective methods for disrupting antibody bonds that do not damage the antibody or binding target. Controlled antibody binding and release is frequently used in industrial bioseparation methods, but the traditional chromatography unit operations have their drawbacks. For instance, consider one of the most prevalent separation unit operations used in the purification of therapeutic antibodies, namely, Protein A chromatography. The Protein A chromatography column contains a resin with surface-immobilized Protein A, which binds tightly to the Fc region of immunoglobulins. In this type of chromatography, the column is operated in a bind-and-elute mode with the following steps: (1) the impure suspension of valuable antibodies is introduced to the column; (2) the antibodies bind and saturate the resin; (3) the suspension is flushed from the column; (3) and, finally, an elution buffer is used to release the antibodies from the resin. Low-pH citrate and glycine-HCl buffers are commonly used to elute the antibodies from the column. While these low-pH buffers are effective at disrupting the electrostatic and hydrophobic interactions in the antibody-Protein A bond, they result in degradation of the antibody product. Thus, an alternative elution method that releases specifically-bound proteins at physiological pH is preferable. Vibration-induced disruption of antibody bonds occurs when the resulting physical forces overwhelm the electrostatic and hydrophobic interactions between the antibodies and their binding partners. Previously, the internally-driven millimeter scale cantilever was observed to inhibit weak, nonspecific interactions between proteins and the vibrating surface. In this work, specifically-bound species were released from a resonating self-driven millimeter-sized cantilever. As a proof of concept, experiments were designed to demonstrate release of the model cellular target, E. coli O157:H7, at physiological pH. Electrochemical measurements and micrographs confirmed that the resonating cantilever released more than 80% (n=11) of antibody-bound E. coli cells from the vibrating cantilever surface. The research then moved to the more challenging task of demonstrating release of specifically-bound antibodies from surface-immobilized binding partners. For the first time, multiple methods demonstrated that vibration could induce release of specifically-bound antibodies: electrochemical impedance and enzyme assays confirmed that the vibrating cantilever released 76±25% (n=6) of anti-Bovine Serum Albumin from its surface-immobilized antigen. Hence, when the cantilever vibrated with sufficient intensity, most of the high-avidity antibody bonds were disrupted. This is a fascinating discovery that could be useful in industry, especially when considering that the Protein A-antibody interaction is weaker than most antibody-antigen bonds. Three-dimensional finite element models indicated that the surface acceleration of a resonating cantilever reached approximately 2.68x105 m/s2 during the E. coli release experiments. Given that the exerted force is the product of the bacterium's mass (~1 pg) and acceleration, the force would reach a maximum of 268 pN. This magnitude of force is well beyond the 50-200 pN range of force required to effect antibody-antigen bond rupture. Hence, inertial force can conceivably result in the release of cellular targets. The release of specifically-bound proteins, however is another matter. The mass of the average antibody is many orders of magnitude lower than that of any cell. Hence, the cantilever fails to generate sufficient inertial force to affect the bond. However, a computational fluid dynamic model, indicated that the resonating cantilever induced a steady fluid flow called acoustic streaming. The resulting steady, high shear rates were thus the likely agent behind protein release.

Gene knockdown by siRNA offers an unrestricted choice of targets and specificity based on the principle of complementary Watson-Crick base pairing with mRNA. However, the negative charge, large molecular size, and susceptibility to enzymatic degradation of siRNA impede its successful transfection, hence limiting its potential for therapeutic use. The development of efficient and safe siRNA transfection agents is, therefore, critical for siRNA-based therapy. Herein, we developed a protein-based biodynamic polymer (biodynamer) that showed potential as a siRNA transfection vector, owing to its excellent biocompatibility, easy tunability, and dynamic polymerization under acidic environments. The positively charged biodynamers formed stable dynamic nanocomplexes (XL-DPs, hydrodynamic diameter of approximately 104 nm) with siRNA via electrostatic interactions and chemical cross-linking. As a proof of concept, the optimized XL-DPs were stable in physiological conditions with serum proteins and demonstrated significant pH-dependent size change and degradability, as well as siRNA release capability. The minimal cytotoxicity and excellent cellular uptake of XL-DPs effectively supported the intracellular delivery of siRNA. Our study demonstrated that the XL-DPs in survivin siRNA delivery enabled potent knockdown of survivin mRNA and induced notable apoptosis of carcinoma cells (2.2 times higher than a lipid-based transfection agent, Lipofectamine 2000). These findings suggested that our XL-DPs hold immense potential as a promising platform for siRNA delivery and can be considered strong candidates in the advancement of next-generation transfection agents.

Three-dimensional (3D) cell assemblies, such as multicellular spheroids, can be powerful biological tools to closely mimic the complexity of cell-cell and cell-matrix interactions in a native-like microenvironment. However, potential applications of large spheroids are limited by the insufficient diffusion of oxygen and nutrients through the spheroids and, thus, result in the formation of a necrotic core. To overcome this drawback, we present a new strategy based on nanoparticle-coated microparticles. In this study, microparticles function as synthetic centers to regulate the diffusion of small molecules, such as oxygen and nutrients, within human mesenchymal stem cell (hMSC) spheroids. The nanoparticle coating on the microparticle surface acts as a nutrient reservoir to release glucose locally within the spheroids. We first coated the surface of the poly(lactic-co-glycolic acid) (PLGA) microparticles with mesoporous silica nanoparticles (MSNs) based on electrostatic interactions and then formed cell-nanofunctionalized microparticle spheroids. Next, we investigated the stability of the MSN coating on the microparticles' surface during 14 days of incubation in cell culture medium at 37 °C. Then, we evaluated the influence of MSN-coated PLGA microparticles on spheroid aggregation and cell viability. Our results showed the formation of homogeneous spheroids with good cell viability. As a proof of concept, fluorescently labeled glucose (2-NBD glucose) was loaded into the MSNs at different concentrations, and the release behavior was monitored. For cell culture studies, glucose was loaded into the MSNs coated onto the PLGA microparticles to sustain local nutrient release within the hMSC spheroids. In vitro results demonstrated that the local delivery of glucose from MSNs enhanced the cell viability in spheroids during a short-term hypoxic culture. Taken together, the newly developed nanofunctionalized microparticle-based delivery system may offer a versatile platform for local delivery of small molecules within 3D cellular assemblies and, thus, improve cell viability in spheroids.

Benefiting from the wide-range absorption and adjustable energy gap, carbon dots (C-dots) have attracted a great deal of attention and they have been used to sensitize semiconductor nanocomposites to boost the efficiency of energy conversion devices, while there is still a lack of fundamental understanding of the interaction between such materials and their influence on the catalytic activity on the reaction process. In this study, C-dots were used to modify TiO2 to form a direct Z-scheme (DZS) junction for enhancement of the photocatalytic activity. The C-dot/TiO2 composite was prepared by ultrasonication at room temperature through coupling between the Ti-O-C bond and electrostatic interaction. The C-dots can dramatically enhance the absorption of the composite by forming the DZS, and the composite is enabled to generate more free radicals, which facilitate ∼10 times higher photocatalytic activity compared to that of TiO2. As a proof of concept, the as-prepared C-dot/TiO2 was used for textile wastewater dye degradation. This study provides an efficient approach for room-temperature preparation of C-dot/TiO2 composites with high photocatalytic activity.

Self-assembly of three bis(pyridyl) ligands with a long flexible spacer, 1,3-bis(2-pyridylaminomethyl)benzene (L1), 1,4-bis(2-pyridylaminomethyl)benzene (L2) and 1,4-bis(3-pyridylaminomethyl)benzene (L3), and group IIB metal salts (MXn, M = Zn(II) and Cd(II), X = NO3−, SO42− and ClO4−, n = 1 or 2) leads to the formation of seven metal–organic complexes, including zero-dimensional (0D) binuclear, one-dimensional (1D) chains , two-dimensional (2D) layer structures, and three-dimensional (3D) frameworks: [CdL1(SO4)(H2O)3]2 (1), [ZnL1(SO4)]n (2), [Cd(L2)1.5(NO3)2]n (3), [ZnL3(NO3)2]n (4), [Cd(L3)2(NO3)2]n (5), [Zn(L3)2]n·2nClO4 (6), and [Cd(L3)3]n·2nClO4·2nH2O (7), which have been characterized by elemental analysis, IR, PL, powder and single-crystal X-ray diffraction. Three flexible bis(pyridyl) ligands exhibit various trans-trans or cis-trans coordination modes, which results in diverse topological structures together with different anions and metal centers. Adjacent binuclear units in complex 1 linked by the sulfate-water tapes into a 2D supramolecular network. Complex 3 exhibits a 1D ladder chain structure, while complex 4 is a zig-zag chain structure. Complexes 2, 5 and 6 display (4,4) layer networks. Complex 7 is a 3D framework with pcu topology. The emission intensities of these complexes exhibit a regular change with different anions: SO42− > ClO4− > NO3−.

Biological systems inspire the design of high-performance biomimetic materials, yet replicating their synergistic interactions and hierarchical structures remains challenging. Here, we present an orthogonal photochemistry-mediated strategy for one-step fabrication of muscle-inspired protein materials. This approach integrates covalent, electrostatic, and hydrogen-bonding interactions to form robust multinetwork architectures within hierarchically organized protein matrices. Prestretching enhances molecular alignment, yielding anisotropic materials with a factor of 3.0, tensile strengths up to 300 MPa, toughness over 22 MJ m-3, and a fatigue threshold of 760 J m-2─surpassing natural proteins such as wool, cotton, and silk. The rapid (∼20 s), precisely controllable process supports scalable 3D manufacturing of continuous fibers exceeding 10 m. Beyond mechanical robustness, the materials dynamically respond to force, humidity, and pH, mimicking biological tissues. As a proof of concept, the fibers function as artificial muscles and flexible capacitive sensors, highlighting their potential for advanced applications in biomaterials, bioengineering, and soft electronics.

Single-Crystalline Mesoporous Palladium and Palladium-Copper Nanocubes for Highly Efficient Electrochemical CO ₂ Reduction

2-Azetidinones substituted with pyridine (2a), quinoline (2b), isoquinoline (2c), imidazole (2d), and benzimidazole (2e) at the 4-position of the four-membered ring have been prepared in order to synthesize tribactams containing a transition metal and its associated ligands, LnM, at the 2-position of the tricyclic skeleton. The developed procedure is compatible with a wide range of transition-metal starting complexes. Thus, the iridium and rhodium dimers [M(η5-C5Me5)Cl2]2 react with 2a–e, in the presence of sodium acetate, to afford irida- and rhodatrinems (1a–j) containing the half-sandwich d6 metal fragments M(η5-C5Me5)Cl (M = Ir, Rh). The reactions of [M(μ-OMe)(η4-COD)]2 (M = Ir, Rh) with 2a lead to irida- and rhodatrinems (1k,l) with the d8 moieties M(η4-COD). The coordination sphere and oxidation state of the metal center in these compounds can be modified, without affecting the 2-azetidinone backbone, by means of substitution and oxidative addition reactions. As a proof of concept, metallatrinems with the M(CO)2 (M = Ir (1m), Rh (1n)) and Ir(Me)I(CO)2 (1o) units are also reported. Osmatrinems 1p,q containing the d4 metal fragment OsH3(PiPr3)2 have been obtained starting from the d2 hexahydride OsH6(PiPr3)2, by reaction with 2a,b, whereas the treatment of the tetrahydroborate complexes MH(η2-H2BH2)(CO)(PiPr3)2 (M = Os, Ru) with 2a yields osma- and ruthenatrinems (1r,s) containing six-coordinate bis(phosphine) d6 metal fragments. The IR stretching frequency of the lactamic carbonyl, the bent angle between the five- and four-membered rings of the tricycle, and the N–CO bond length in the lactamic ring are clearly infuenced by the LnM fragment.

We demonstrate as a proof of principle the capabilities of a novel hybrid MM'/MM polarizable force field to integrate short-range quantum effects in molecular mechanics (MM) through the use of Gaussian electrostatics. This lead to a further gain in accuracy in the representation of the first coordination shell of metal ions. It uses advanced electrostatics and couples two point dipole polarizable force fields, namely, the Gaussian electrostatic model (GEM), a model based on density fitting, which uses fitted electronic densities to evaluate nonbonded interactions, and SIBFA (sum of interactions between fragments ab initio computed), which resorts to distributed multipoles. To understand the benefits of the use of Gaussian electrostatics, we evaluate first the accuracy of GEM, which is a pure density-based Gaussian electrostatics model on a test Ca(II)-H2O complex. GEM is shown to further improve the agreement of MM polarization with ab initio reference results. Indeed, GEM introduces nonclassical effects by modeling the short-range quantum behavior of electric fields and therefore enables a straightforward (and selective) inclusion of the sole overlap-dependent exchange-polarization repulsive contribution by means of a Gaussian damping function acting on the GEM fields. The S/G-1 scheme is then introduced. Upon limiting the use of Gaussian electrostatics to metal centers only, it is shown to be able to capture the dominant quantum effects at play on the metal coordination sphere. S/G-1 is able to accurately reproduce ab initio total interaction energies within closed-shell metal complexes regarding each individual contribution including the separate contributions of induction, polarization, and charge-transfer. Applications of the method are provided for various systems including the HIV-1 NCp7-Zn(II) metalloprotein. S/G-1 is then extended to heavy metal complexes. Tested on Hg(II) water complexes, S/G-1 is shown to accurately model polarization up to quadrupolar response level. This opens up the possibility of embodying explicit scalar relativistic effects in molecular mechanics thanks to the direct transferability of ab initio pseudopotentials. Therefore, incorporating GEM-like electron density for a metal cation enable the introduction of nonambiguous short-range quantum effects within any point-dipole based polarizable force field without the need of an extensive parametrization.

Complex speciation and exchange kinetics of labile ligands are critical parameters for understanding the reactivity of metal complexes in solution. We present a novel approach to determine ligand exchange parameters based on electrospray ionization mass spectrometry (ESI-MS). The introduction of isotopically labelled ligands to a solution of metal host and unlabelled ligands allows the quantitative investigation of the solution-phase equilibria. Furthermore, ion mobility separation can target individual isomers, such as ligands bound at specific sites. As a proof of concept, we investigate the solution equilibria of labile pyridine ligands coordinated in the cavity of macrocyclic porphyrin cage complexes bearing diamagnetic or paramagnetic metal centres. The effects of solvent, porphyrin coordination sphere, transition metal, and counterion on ligand dissociation are discussed. Rate constants and activation parameters for ligand dissociation in the solution can be derived from our ESI-MS approach, thereby providing mechanistic insights that are not easily obtained from traditional solution-phase techniques.

Nuclear magnetic resonance and molecular modeling analysis of the interaction of the antimalarial drugs artelinic acid and artesunic acid with β‐cyclodextrin

Multiple dysregulated pathways in tumors necessitate targeting multiple oncogenic elements by combining orthogonal therapeutic moieties like short-interfering RNAs (siRNA) and drug molecules in order to achieve a synergistic therapeutic effect. In this manuscript, we describe the synthesis of cyclodextrin-modified dendritic polyamines (DexAMs) and their application as a multicomponent delivery vehicle for translocating siRNA and anticancer drugs. The presence of β-cyclodextrins in our DexAMs facilitated complexation and intracellular uptake of hydrophobic anticancer drugs, suberoylanilide hydroxamic acid (SAHA) and erlotinib, whereas the cationic polyamine backbone allowed for electrostatic interaction with the negatively charged siRNA. The DexAM complexes were found to have minimal cytotoxicity over a wide range of concentrations and were found to efficiently deliver siRNA, thereby silencing the expression of targeted genes. As a proof of concept, we demonstrated that upon appropriate modification with targeting ligands, we were able to simultaneously deliver multiple payloads--siRNA against oncogenic receptor, EGFRvIII and anticancer drugs (SAHA or erlotinib)--efficiently and selectively to glioblastoma cells. Codelivery of siRNA-EGFRvIII and SAHA/erlotinib in glioblastoma cells was found to significantly inhibit cell proliferation and induce apoptosis, as compared to the individual treatments.

Polyanions effectively prevent protein conjugation and activity loss during hydrogel cross-linking

Polyoxometalates (POMs), anionic metal-oxide clusters, are actively studied for their versatile structural designs and element selectivity. A series of Keplerate-type POMs with core-shell structures, known as POM capsules, that feature a Keggin-type POM core, has been reported. These POM capsules, with their neutral to negative charge and large molecular surface area, can serve as platforms for proton (H+) conduction. In this study, we aimed to introduce proton carriers into the POM capsule through a proton-coupled electron transfer (PCET) reaction. It is crucial to avoid excessive reduction, as it increases electrostatic interaction between the proton and the POM capsule, hindering proton conduction. The number of incorporated electrons was varied from 0 to 11, and the POM capsule containing 3 electrons exhibited proton conductivity an order of magnitude higher than that of pristine or highly reduced POM capsules. This study serves as a proof of concept, demonstrating that PCET, combined with the core-shell structure, can effectively enhance the proton conductivity without being limited by the choice of constituent elements.