Crystal Structure Research Articles

Covalent Inhibitors of S100A4 Block the Formation of a Pro-Metastasis Non-Muscle Myosin 2A Complex.

The S100 protein family functions as protein-protein interaction adaptors regulated by Ca2+ binding. Formation of various S100 complexes plays a central role in cell functions, from calcium homeostasis to cell signaling, and is implicated in cell growth, migration, and tumorigenesis. We established a suite of biochemical and cellular assays for small molecule screening based on known S100 protein-protein interactions. From 25 human S100 proteins, we focused our attention on S100A4 because of its well-established role in cancer progression and metastasizes by interacting with nonmuscle myosin II (NMII). We identified several potent and selective inhibitors of this interaction and established the covalent nature of binding, confirmed by mass spectrometry and crystal structures. 5b showed on-target activity in cells and inhibition of cancer cell migration. The identified S100A4 inhibitors can serve as a basis for the discovery of new cancer drugs operating via a novel mode of action.

Expediting the bioactivity of zinc sulfide nanoparticles with copper oxide as a nanocomposite

The regulatory role of zinc in bone formation extends to the activation of proteins associated with bone homeostasis. Furthermore, copper is well known for its antibacterial properties. This dual function underscores the significance of zinc and copper in maintaining a balance of bone structure and function. In light of the aforementioned, zinc sulphide/copper oxide nanocomposites were created in this instance using a straightforward coprecipitation technique. Copper oxide was used as a nanocomposite to improve the structural, morphological, and biological performance of zinc sulphide nanoparticles. The X-ray diffraction pattern confirmed a transformation in the crystal structure from cubic to rhombohedral, along with increase in intensity. Fourier transforms infrared analysis indicated the presence of functional groups. Scanning electron microscopy images demonstrated a morphological shift from non-uniform to distinct spherical nanoparticles, impacting the enhancement of material properties. The pathogenic activity of the zinc sulphide/copper oxide nanocomposites was tested against nine bacterial strains. In antimicrobial testing, zinc sulphide/copper oxide nanocomposites showed promising results, particularly against Klebsiella pneumoniae (zone of inhibition: 14 mm at 100 µg/mL compared to 7 mm by standard) and Escherichia coli (zone of inhibition: 11 mm at 100 µg/mL compared to 10 mm by standard) after 24 h with zone of inhibition matching or exceeding that of the standard (chloramphenicol). Zinc sulphide nanoparticles and zinc sulphide/copper oxide nanocomposites were evaluated for their antifungal activity against fungal stains from Trichophyton rubrum, Aspergillus niger, and Aspergillus flavus. After a 24-h period, it was discovered that zinc sulphide/copper oxide nanocomposites were effective against Aspergillus flavus (zone of inhibition: 19.4 mm at 100 µg/mL compared to 6.3 mm by standard) at all concentrations (25–100 mg/mL), with zones of inhibition identical to or greater than those of the standard (fluconazole). Certainly, based on these results, zinc sulphide/copper oxide nanocomposites could be promising materials for drug delivery.Clinical trial registration: Not applicable.

High-throughput screening of halide solid-state electrolytes for all-solid-state Li-ion batteries through structural descriptor

All-solid-state Li-ion batteries (ASSLIBs) have attracted great attention due to their intrinsic safety and high potential energy density. To realize ASSLIBs, the development of solid-state electrolytes (SSEs) with favorable electrochemical stability and high Li-ion conductivity is of utmost significance. Compared to trial-and-error searches, theoretical computation-based methods are recognized as a powerful tool for accelerating the exploration of SSEs. However, the development of appropriate descriptors is often the first hurdle toward implementing accurate and meaningful screening process. Here we quantified the structural properties pertaining to low Li-ion migration barriers and performed a high-throughput screening of 3119 Li-containing halides obtained from the Materials Project (MP) database to search for promising SSEs. After excluding previously reported SSEs, three candidate materials, Li4ZrF8, Li3ErBr6, and Li2ZnI4 with crystal structure exhibiting 3D diffusion pathway were obtained. Subsequent theoretical calculations of these materials were performed to evaluate their thermodynamic stability, chemical/electrochemical stability, and ionic conductivity. The three halide materials appeared to be promising SSE candidates due to their robust thermodynamical stability against cathodes, and high ionic conductivity. This research provides a new insight and a systematic quantitative understanding of the relationship between the structural properties and Li-ion migration barriers, which can motivate future computational studies on new fast-ion conductors and accelerate the discovery of high ionic conductivity SSEs for the use in ASSLIBs.

Widening the frequency bandgap and reducing thermal conductivity in phononic crystals by tuning structural parameters using a novel computational simulation method

AbstractThis paper introduces and models a phononic structure based on single-crystal silicon, aiming to investigate the width of its frequency bandgap and the impact of key parameters on thermal conductivity. The modeled phononic crystal structure features a periodic arrangement of cylindrical holes in a silicon matrix. This research holds the potential to enhance thermal management performance of thermal metamaterials. Utilizing a 3D finite element method (FEM) model in COMSOL, we have computed phonon dispersion to estimate thermal conductivity. The study systematically has explored the influence of phononic crystal parameters—specifically, porosity, lattice constant, and thickness—along with their interactions on both thermal conductivity and frequency bandgap width.A comprehensive investigation of these parameters has been conducted for their optimization to achieve the maximum frequency bandgap width and minimum thermal conductivity using the response surface method model. Eigenfrequencies and wave vector parameters are extracted from the finite element model using a MATLAB script. Subsequently, thermal conductivity is calculated through the Callaway–Holland model, a simplification of the Boltzmann transport equation (BTE).Our results indicate that the frequency bandgap begins to form at approximately 43% porosity for a lattice constant and thickness of 100 nm each. Furthermore, adjusting the parameters led to a significant reduction in thermal conductivity, decreasing from 43.89 W m−1 K−1 to 0.39 W m−1 K−1. The novelty of our research lies in thermal conductivity control of phononic crystal metamaterials through their parameter variations, or a predictive method of thermal conductivity and its parameter sensitivity. This study advances the state of the art in phononic crystal metamaterial research, contributing to improved thermal management performance by enlarging frequency bandgaps.Overall, our findings deepen the understanding of how porosity, lattice constant, and thickness influence thermal conductivity and frequency bandgap width. They offer valuable insights into optimizing phononic crystal parameters, enhancing thermal management performance, and designing more efficient and effective phononic crystal structures.

Effects of polyunsaturated fatty acid and diacylglycerol on the crystallization behaviors of palm-based oil

Diacylglycerol (DAG) is a novel functional structural lipid, but its application in base oils remains underexplored. This research investigated the effect of three liquid oils (groundnut oil, corn oil, and flaxseed oil), with varying polyunsaturated fatty acid (PUFA) (39.60, 69.50, and 77.65 %) and DAG content (0.00, 40.00, 80.00 %), on the crystallization behaviors of palm-based oil. DAG (40.00 %), obtained through enzymatic glycerolysis and molecular distillation, was found to stabilize the binary system with good compatibility and fine crystal structure. “Liquid” DAG played a dual role: diluting solid lipids, and promoting crystallization. Increasing DAG content led to larger crystalline domain size, while higher PUFA content accelerated crystallization and increased crystal orderliness, though decreasing crystal density. These results demonstrated the clear influence of PUFA and DAG content on palm-based oil crystallization. This knowledge can guide the utilization of different unsaturated DAGs for tailored fat crystallization in food application.

Effects of Eu3+ doping on the structural, magnetocaloric effect and critical behavior of Ruddlesden-Popper compounds La1.4-xEuxSr1.6Mn2O7 (0 ≤ x ≤ 0.1)

The effects of Eu3+ doping on the structural and magnetocaloric effect of Ruddlesden-Popper compounds La1.4-xEuxSr1.6Mn2O7 (0 ≤ x ≤ 0.1) were investigated. The X-ray diffraction and infrared spectroscopy confirmed that La1.4-xEuxSr1.6Mn2O7 compounds exhibited the tetragonal lattice symmetry (I4/mmm) of the Ruddlesden-Popper phase. The crystal structure of La1.4-xEuxSr1.6Mn2O7 compounds distorted and phase separated as the amount of Eu3+ doping varied. The magnetization-temperature curves demonstrated that La1.4-xEuxSr1.6Mn2O7 compounds display a notable transition temperature attributed to its anisotropic exchange coupling. The maximum magnetic entropy changes (−ΔSMmax) of La1.4-xEuxSr1.6Mn2O7(x = 0, 0.075, and 0.1) compounds are 2.82, 3.12 and 3.40 J/(kg·K) at the 5 T applied magnetic field. Meanwhile, its relative cooling power (RCP) was 186.37, 207.42 and 242.54 J/kg, respectively. The critical behavior of La1.4-xEuxSr1.6Mn2O7 (0≤x≤0.1) compounds was analyzed around Tc, and it was found that the critical index (β = 0.413, γ = 1.020, δ = 3.038) is essentially in line with the mean field theory.

Load-based divergence in the dynamic allostery of two TCRs recognizing the same pMHC.

Increasing evidence suggests that mechanical load on the αβ T cell receptor (TCR) is crucial for recognizing the antigenic peptide-loaded major histocompatibility complex (pMHC) molecule. Our recent all-atom molecular dynamics (MD) simulations revealed that the inter-domain motion of the TCR is responsible for the load-induced catch bond behavior of the TCR-pMHC complex and peptide discrimination. To further examine the generality of the mechanism, we perform all-atom MD simulations of the B7 TCR under different conditions for comparison with our previous simulations of the A6 TCR. The two TCRs recognize the same pMHC and have similar interfaces with pMHC in crystal structures. We find that the B7 TCR-pMHC interface stabilizes under ∼15-pN load using a conserved dynamic allostery mechanism that involves the asymmetric motion of the TCR chassis. However, despite forming comparable contacts with pMHC as A6 in the crystal structure, B7 has fewer high-occupancy contacts with pMHC during the simulation. These results suggest that the dynamic allostery common to the TCR αβ chassis can amplify slight differences in interfacial contacts into distinctive mechanical responses and potentially nuanced biological outcomes.

Phonon-Induced Geometric Chirality.

Chiral properties have seen increasing use in recent years, leading to the emerging fields of chiral quantum optics, plasmonics, and phononics. While these fields have achieved manipulation of the chirality of light and lattice vibrations, controlling the chirality of materials on demand has yet remained elusive. Here, we demonstrate that linearly polarized phonons can be used to induce geometric chirality in achiral crystals when excited with an ultrashort laser pulse. We show that nonlinear phonon coupling quasistatically displaces the crystal structure along phonon modes that reduce the symmetry of the lattice to that of a chiral point group corresponding to a chiral crystal. By reorienting the polarization of the laser pulse, the two enantiomers can be induced selectively. Therefore, geometric chiral phonons enable the light-induced creation of chiral crystal structures and therefore the engineering of chiral electronic states and optical properties.

Study on the deep deoxidation mechanism of titanium powder using Y/YOCl/YCl3 and Y/Y2O3 systems

Low-oxygen high-purity titanium (oxygen concentration ≤ 500 ppm) is a critical material for advanced semiconductor and biomedical applications. Current deoxidation methods limit oxygen concentration in titanium to approximately 1000–2000 ppm, failing to meet the demand for ultra-low oxygen levels in high-performance materials. This study investigated the preparation mechanism and conditions for low-oxygen high-purity titanium utilizing a molten salt thermochemical method, employing Y as the deoxidant with a theoretical deoxidation limit below 10 ppm. We experimentally explored the deoxidation mechanisms of titanium using Y/YOCl/YCl3 and Y/Y2O3 systems, successfully reducing the oxygen concentration in titanium to 200 ppm, and proving that the Y/YOCl/YCl3 system is more efficient than the Y/Y2O3 system. Additionally, the titanium samples were analyzed using SEM-EDS, XRD, XPS, and 3D surface profilometry before and after deoxidation. These analyses examined the impact of the deoxidation process using Y on the crystal structure, oxide film, and surface roughness of titanium specimens, which are useful for understanding the deoxidation mechanism. During the sintering process of titanium powder attached to Y, the deoxidation process will produce YOCl or Y2O3. The formation of these deoxidation products leads to local oxygen diffusion, and the crystals of YOCl or Y2O3 are gathered at grain boundaries, which will resolve during the subsequent acid etching process, thus reducing the oxidation concentration of the titanium. The above results provide further theoretical guidance and technical support for the production of ultra-high-purity titanium powder.

‘Rhythmite’, Ca29(SiO4)8Cl26, an Anthropogenic Phase from the Chelyabinsk Coal Basin (Ural, Russia) with a Complex Modular Structure Related to α-Ca3SiO4Cl2 (‘Albovite’): Crystal Structure, Raman Spectra, and Thermal Expansion

‘Rhythmite’, Ca29(SiO4)8Cl26, an anthropogenic calcium chloride silicate from the Chelyabinsk coal basin (South Ural, Russia), was investigated using chemical microprobe analysis, in situ single-crystal X-ray diffraction analysis (27–727 °C), and Raman spectroscopy. ‘Rhythmite’ is orthorhombic, Pnma: a = 17.0749(6), b = 15.1029(5), c = 13.2907(4) Å, and V = 3427.42(18) Å3 (R1 = 0.045). The crystal structure of ‘rhythmite’ consists of a porous framework formed by Ca-O bonds and SiO4 tetrahedra with additional Ca2+ cations and Cl− anions in the structure interstices. The framework is built up from multinuclear [Ca15(SiO4)4]14+ fundamental building blocks (FBBs) cut from the crystal structure of α-Ca3SiO4Cl2 (‘albovite’). The FBBs are linked by sharing common Ca atoms to form a network with an overall pcu topology. The empirical chemical formula was calculated as Ca29.02(Si7.89Al0.05P0.05)Ʃ7.99O32Cl26 (on the basis of Cl + O = 58). ‘Rhythmite’ is stable up to 627 °C and expands slightly anisotropically (αmax/αmin = 1.40) in the ab and bc planes and almost isotropically in the ac plane (α33/α11 = 1.02) with the following thermal expansion coefficients (×106 °C−1): α11 = 14.6(1), α22 = 20.5(4), α33 = 15.0(3), and αV = 50.1(6) (room temperature). During expansion, the silicate tetrahedra remain relatively rigid with average bond length changes of less than 0.5%. A structural complexity analysis indicates that ‘rhythmite’ is complex, with IG,total = 920.313 (bits/u.c.), which significantly exceeds the average value of structural complexity for silicates and is caused by the modular framework construction and the presence of a large number of independent positions in the crystal structure.

Dual metal centers within a water-stable Co/Ni bimetallic metal-triazolate framework contribute to durable photocatalysis for water treatment.

Bimetallic metal-organic frameworks (MOFs) have been studied extensively in various fields, including photocatalytic and electrocatalytic applications. The enhanced catalytic activity is typically attributed to the synergistic effect of the two metals, often without further explanation. Here, we demonstrate a CoNi-bimetallic triazolate MOF with fixed metal occupancy within the MOF's secondary building unit. Due to the difference in electronegativity and so on, the charge redistribution between the two metal centers could be responsible for the enhanced photocatalytic activity. In addition, the metal(II)-triazolate MOFs we synthesized exhibit unique metal-N coordination and a strong bond between the metal center and triazole ring. Therefore, their crystal structure and high porosity are highly retained even after exposure to humid environments for several months or stirring in water for several days. Overall, the CoNi-bimetallic triazolate MOF combines the excellent water stability and high surface area of its two monometallic counterparts. It can be further tailored to yield the highest colloidal stability during photocatalytic water treatment. As a result, the dual metal centers within the bimetallic MOF, combined with boosted colloidal stability, demonstrate the highest reactive oxygen species generation and promising antibacterial performance compared to their Ni- or Co-based counterparts. These findings shed light on the future design of robust MOF-based photocatalysts, particularly bimetallic ones.

Synergistic effect of lone-pair electron and atomic distortion in introducing anomalous phonon transport in layered PbXSeF (X= Cu, Ag) compounds with low lattice thermal conductivity

Using first-principles calculations, self-consistent phonon theory and Boltzmann transport theory, the crystal structure, phonon and electronic transport, and thermoelectric (TE) properties of PbXSeF (X = Cu, Ag) compounds are comprehensive explored in the current work. The heterogeneous bonding characteristics along the in-plane and out-of-plane directions lead to low lattice thermal conductivities in PbXSeF (X = Cu, Ag) compounds. The low lattice thermal conductivity is primarily attributed to strong anharmonicity caused by the lone-pair electrons of Pb. Notably, the PbCuSeF compound, despite the lighter mass in comparison with PbAgSeF, exhibits relatively lower lattice thermal conductivity. Such finding can be attributed to the distortion introduced by Cu atom, which leads to strong quartic anharmonicity, and thereby suppressing the heat-carrying phonons through the rattling-like behavior of Cu atom. The lone-pair electrons of Pb2+ and the heterogeneous bonding characteristics in PbXSeF (X = Cu, Ag) compounds contribute the multi-valley band degeneracy, resulting the decoupling of Seebeck coefficient and electrical conductivity with carrier concentration while generating in a high power factor. Our current work not only illustrates the fundamental insights into the low lattice thermal conductivity and related anomaly of layered PbXSeF (X = Cu, Ag) compounds based on the four-phonon scattering and multiple carrier scattering rates, but also highlights the anisotropic feature of electronic and thermal transport properties.

Generation and Clearance of Superoxide Radicals at Buried Interfaces of Perovskites with Different Crystal Structures.

One of the most notorious issues with classic perovskite (MAPbI3) is its rapid degradation caused by generating superoxide radicals (O2 •-) on its surface under light and oxygen environments (light/O2). The differences in O2 •- generation rate and tolerance to O2 •- among perovskite with different structures are pending. For the first time it is validated through solid-electron paramagnetic resonance (EPR) that MAPbI3 and Cs0.175FA0.75MA0.075PbI3 (PVSK) crystals can generate O2 •- in an air atmosphere. The rapid degradation of perovskite buried interfaces caused by O2 •- dominates the nonexposed air aging process of SnO2-based perovskite film, and the degradation rate of MAPbI3 film is faster than that of PVSK film. The fullerene pyridine derivatives (C60OPD), which function as a buffer layer between SnO2 and PVSK to scavenge O2 •- and prevent degradation at the buried interface of the PVSK film, reduce the density of defect states, and accelerate the transmission of photogenerated electrons. The photoelectric conversion efficiency (PCE) of perovskite solar cells (PSCs) optimizes with C60OPD increased from 21.15% to 23.11% while significantly improving the stability in light/O2. This work reveals the hidden degradation of perovskite-buried interfaces caused by O2 •- and explores efficient ways for perovskite to resist O2 •-.

Slowed Singlet Exciton Fission Enhances Triplet Exciton Transport in Select Perylenediimide Crystals.

Singlet fission (SF) materials used in light-harvesting devices must not only efficiently produce spin-triplet excitons but also transport them to an energy acceptor. N,N'-Bis(2-phenylethyl)-3,4,9,10-perylenedicarboximide (EP-PDI) is a promising SF chromophore due to its photostability, large extinction coefficient, and high triplet yield, but the energy transport mechanisms in EP-PDI solids are minimally understood. Herein, we use transient absorption microscopy to directly characterize exciton transport in EP-PDI crystals. We find evidence for singlet-mediated transport in which pairs of triplet excitons undergo triplet fusion (TF), producing spin-singlet excitons that rapidly diffuse. This interchange of singlet and triplet excitons shuttles triplets as far as 205 nm within the first 500 ps after photoexcitation. This enhanced transport comes at a cost, however, as it necessitates favoring triplet recombination and thus requires fine-tuning of SF dynamics to balance triplet yields with triplet transport lengths. Through numerical modeling, we predict tuning the ratio of SF and TF rate constants, kSF/kTF, to between 1.9 and 3.8 allows for an optimized triplet transport length (425-563 nm) with minimal loss (7-10%) in triplet yield. Interestingly, by adjusting the size of EP-PDI crystals, we find that we can subtly tune their crystal structure and thereby alter their SF and TF rates. By slowing SF within small EP-PDI crystals, we are able to boost their triplet transport length by ∼20%. Although counterintuitive, our work suggests slowing SF by introducing moderate structural distortions can be preferential when optimizing triplet exciton transport, provided singlet exciton transport is not significantly hindered.

An environmentally friendly depressant for magnesite and calcite flotation separation: Selective depression and adsorption mechanism

The similar crystal structures and chemical properties of magnesite and calcite make their effective separation through flotation challenging. This study explores the use of Glutamic acid diacetic acid tetrasodium salt (GLDA), a novel environmentally friendly chelating reagent, to enhance the flotation separation of magnesite and calcite. Flotation test results indicate that in a sodium oleate (NaOL) system, GLDA selectively inhibits the flotation of calcite. Under optimal conditions (slurry pH=9.20, GLDA 15 mg/L, and NaOL 140 mg/L), a flotation concentrate with an MgO grade of 46.21 %, CaO grade of 1.39 %, and an MgO recovery rate of 73.17 % was achieved. GLDA minimally affects the hydrophobicity of magnesite but significantly reduces the hydrophobicity of calcite. The selective inhibition mechanism of GLDA was investigated using zeta potential measurements, FTIR, and XPS analyses. Results show that GLDA selectively reacts with Ca sites on the calcite surface, adsorbing and covering it, thereby preventing NaOL from adsorbing on the calcite. Conversely, GLDA has a minor impact on the Mg sites on the magnesite surface, resulting in a negligible effect on NaOL adsorption by magnesite. Consequently, GLDA enhances the flotation separation efficiency of magnesite and calcite. The research results have potential for application in the purification of low-grade magnesite ore.

Synthetic Approaches to and Structures of Diplatinum Polyynediyl Complexes trans,trans‐[(C6F5)(R3P)2Pt(C≡C)nPt(PR3)2(C6F5)] With Odd Numbers of Triple Bonds; Avoiding Complicating Ethynediyl Extrusions

AbstractReactions of trans‐(C6F5)(p‐tol3P)2Pt(C≡C)nSiEt3 (PtC2nSi; n=5, 7, 9) and excess PtCl in the presence of wet n‐Bu4N+ F− (to effect protodesilylation) under Sonogashira‐type conditions (CuCl, base, other additives) afford the title compounds PtC10Pt, PtC14Pt, and PtC18Pt in 42–32 % yields. A four‐fold substitution of the phosphine ligands in PtC10Pt by PEt3 affords Pt'C10Pt’ (78 %), and a Sonogashira reaction of Pt'C2H and Pt'Cl affords Pt'C2Pt’ (68 %). The analogous reaction with PtC2Si and PtCl is unsuccessful, presumably for steric reasons. The crystal structures of PtC10Pt, PtC14Pt, Pt'C10Pt′, and Pt'C2Pt’ exhibit a number of interesting trends and features. Certain sp chain extension reactions that lead to or employ the precursors PtC10Si, PtC12Si, PtC14Si, and PtC18Si sometimes give byproducts derived from C2 loss, and possible origins are discussed. Related phenomena have been reported by others in the course of synthesizing extended conjugated polyynes.

A sustainable strategy to improve photocatalytic degradation properties of CuO and CuO-rGO nanocomposite using Eucalyptus leaf extract

In this study, Copper oxide (CuO) nanoparticles were synthesized using a sustainable approach. The process comprised Eucalyptus leaf extract as both a biological capping agent and a reducing agent. The synthesis process used a one-pot hydrothermal technique to efficiently combine CuO nanoparticles with reduced graphene oxide (rGO). Analytical methods were utilized to investigate the prepared nanocomposite's structural, crystalline, morphological, functional, optical, and thermal characteristics. The prepared sample was analyzed using X-ray diffraction, which revealed that CuO nanoparticles have a monoclinic crystal structure, and no impurity peaks were observed. Field emission scanning microscopes displayed the uniform dispersion of spherical CuO nanoparticles with layered and non-agglomerated, resembling a sponge-like structure of rGO. The microstructural analysis also confirmed the dispersion of copper inside reduced graphene oxide (rGO) sheets. The optical properties, including light absorption and bandgap width, were investigated using UV–visible spectroscopy using bandgap energies of 2.5 and 2.8 eV. In addition, the nanocomposite's ability to degrade cationic Rhodamine 6G and anionic Rose Bengal dyes by photocatalysis was evaluated. The degradation of RB and Rh6G dyes was characterized by nanocatalysis using UV–visible spectroscopy and a pseudo-first-order kinetics model. The pseudo-first-order degradation kinetic rate of Rhodamine 6G was determined to be 2.55 x 10−2 min−1, indicating that the nanocomposite effectively initiates this dye's degradation. The results showed that dye degradation was effective even at reduced catalyst concentrations.

Potentiostatic electrodeposition of copper, indium, and cadmium sulfides for CO2 electroreduction: A path toward sustainable hydrogen generation

This study focuses on the potentiostatic electrodeposition of copper indium and cadmium sulfide (CuS, In2S3, and CdS) thin films on copper substrates, aiming to develop efficient electrocatalysts for the electrochemical reduction of CO2 and sustainable hydrogen generation. Utilizing Cu Kα radiation for X-ray diffraction (XRD) analysis, the crystal structures of the electrodeposited films were confirmed, revealing well-defined crystalline phases. The films exhibited average particle sizes of 55.99 nm for CuS, 50.37 nm for In2S3, and 63.51 nm for CdS. Cyclic voltammetry and chronoamperometry were employed to optimize the deposition parameters, ensuring efficient nucleation and growth of the metal sulfide films. The electrochemical performance of the synthesized electrocatalysts was rigorously tested, demonstrating their potential for CO2 reduction under optimized conditions with the highest efficiency for CdS electrodes. Additionally, the electrodeposited CuS and CdS are of the p-type, and In2S3 is of the n-type semiconductor were studied and verified by the Mott–Schottky test. CuS, In2S3, and CdS were found to have donor and acceptor concentrations (ND) of 1.68 × 106, 1.44 × 105, and 8.9 × 105 cm3, respectively. The photoelectrochemical measurements of the electrodeposited metal sulfides were studied at ambient temperature and under illumination, providing higher photocurrent responses for CdS and demonstrating its strong potential as a photoelectrode material for CO2 reduction. This work underscores the significance of facile electrochemical synthesis methods in developing cost-effective and scalable electrocatalysts, paving the way for their integration into photoelectrochemical systems for green energy applications.

Molecular Dynamics (MD) Simulations Provide Insights into the Activation Mechanisms of 5-HT2A Receptors

Recent breakthroughs in the determination of atomic resolution 3-D cryo-electron microscopy structures of membrane proteins present an unprecedented opportunity for drug discovery. Structure-based drug discovery utilizing in silico methods enables the study of dynamic connectivity of stable conformations induced by the drug in achieving its effect. With the ever-expanding computational power, simulations of this type reveal protein dynamics in the nano-, micro-, and even millisecond time scales. In the present study, aiming to characterize the protein dynamics of the 5HT2A receptor stimulated by ligands (agonist/antagonist), we performed 1 µs MD simulations on 5HT2A/DOI (agonist), 5HT2A/GSK215083 (antagonist), and 5HT2A (APO, no ligand) systems. The crystal structure of 5HT2A/zotepine (antagonist) (PDB: 6A94) was used to set up the simulation systems in a lipid bilayer environment. We found the monitoring of the ionic lock residue pair (R3.50-E6.30) of 5HT2A in MD simulations to be a good approximation of the effects of agonists (ionic lock breakage) or antagonists (ionic lock formation) on receptor activation. We further performed analyses of the MD trajectories, including Principal Component Analysis (PCA), hydrogen bond, salt bridge, and hydrophobic interaction network analyses, and correlation between residues to identify key elements of receptor activation. Our results suggest that in order to trigger receptor activation, DOI must interact with 5HT2A through residues V5.39, G5.42, S5.43, and S5.46 on TM5, inducing significant conformational changes in the backbone angles of G5.42 and S5.43. DOI also interacted with residues W6.48 (toggle switch) and F6.51 on TM6, causing major conformational shifts in the backbone angles of F6.44 and V6.45. These structural changes were transmitted to the intracellular ends of TM5, TM6, and ICL3, resulting in the breaking of the ionic lock and subsequent G protein activation. The studies could be helpful in future design of selective agonists/antagonists for various serotonin receptors (5HT1A, 5HT2A, 5HT2B, 5HT2C, and 5HT7) involved in detrimental disorders, such as addiction and schizophrenia.

On the humanization of VHHs: Prospective case studies, experimental and computational characterization of structural determinants for functionality.

The humanization of camelid-derived variable domain heavy chain antibodies (VHHs) poses challenges including immunogenicity, stability, and potential reduction of affinity. Critical to this process are complementarity-determining regions (CDRs), Vernier and Hallmark residues, shaping the three-dimensional fold and influencing VHH structure and function. Additionally, the presence of non-canonical disulfide bonds further contributes to conformational stability and antigen binding. In this study, we systematically humanized two camelid-derived VHHs targeting the natural cytotoxicity receptor NKp30. Key structural positions in Vernier and Hallmark regions were exchanged with residues from the most similar human germline sequences. The resulting variants were characterized for binding affinities, yield, and purity. Structural binding modes were elucidated through crystal structure determination and AlphaFold2 predictions, providing insights into differences in binding affinity. Comparative structural and molecular dynamics characterizations of selected variants were performed to rationalize their functional properties and elucidate the role of specific sequence motifs in antigen binding. Furthermore, systematic analyses of next-generation sequencing (NGS) and Protein Data Bank (PDB) data was conducted, shedding light on the functional significance of Hallmark motifs and non-canonical disulfide bonds in VHHs in general. Overall, this study provides valuable insights into the structural determinants governing the functional properties of VHHs, offering a roadmap for their rational design, humanization, and optimization for therapeutic applications.