Preferred Binding Sites Research Articles

Electronic structure of biochar modified through self-doping with boron, nitrogen and sulfur atoms for rapid and efficient adsorption of COVID-19 drug residues

Self-doping of biochar with various heteroatoms can significantly modify its electronic structure and surface properties, thereby enhancing its adsorption capacity. Allium mongolicum Regel (AM) was a desert herb known for hyperaccumulating boron and possessing a cavity structure. AMAC-3 derived from the pyrolysis of AM, exhibited a high specific surface area (2754 cm2g−1), a larger pore volume (2.513 cm3g−1), an appropriate degree of graphitization (IG/ID = 0.99), and a certain content of heteroatoms (boron, nitrogen and sulfur). AMAC-3 achieved equilibrium adsorption of 20 mg L−1COVID-19 drugs residues within 5–8 min, with equilibrium adsorption capacity ranging from 158 to 195mg g−1 and the drug removal rate between 79 % and 98 %. Furthermore, AMAC-3 maintained high adsorption efficiency in the presence of coexisting anions and spiked real water samples. The shorter adsorption equilibrium time and higher removal rate of AMAC-3 were attributed to the rapid mass transfer in the 3D pores, as well as the rapid binding of more electrons. Boron was the preferred binding site for heteroatom sites due to its electron deficient nature. This study offered insights into the utilization of self-doped heteroatoms for modulating the electronic structure of adsorbent, thereby reducing adsorption equilibrium time and enhancing removal efficiency.

Binding characteristics of the major kratom alkaloid, mitragynine, towards serum albumin: Spectroscopic, calorimetric, microscopic, and computational investigations

Mitragynine (MTG) is a prominent indole alkaloid that is present abundantly in Mitragyna speciosa, commonly referred to as kratom. MTG has garnered significant attention due to its selective agonistic characteristics towards opioid receptors and related analgesic effects. In the circulatory system, the in vivo efficacy of MTG is dictated by its interaction with plasma proteins, primarily human serum albumin (HSA). In the present study, we utilized a broad methodology that included spectroscopic, calorimetric, microscopic, and in silico approaches to characterize the interaction between MTG and HSA. Alterations in the UV absorption spectrum of HSA by the presence of MTG demonstrated a ground-state complexation between the protein and the ligand. The Ka values obtained for the MTG–HSA interaction were in the range 103–104 M−1 based on analysis of fluorescence and ITC data, respectively, indicating an intermediate binding affinity. The binding reaction was thermodynamically favorable as revealed by ΔH, ΔS, and ΔG values of −16.42 kJ mol−1, 39.97 J mol−1 K−1, and −28.34 kJ mol−1, respectively. Furthermore, CD spectroscopy results suggested MTG binding induced minimal effects on the structural integrity of HSA, supported by computational methods. Changes in the dimensions of HSA particles due to aggregation, as observed using atomic force microscopy in the presence of MTG. Competitive drug displacement results seemingly suggested site III of HSA located at subdomain IB as the preferred binding site of MTG, but were in inconclusive. However, docking results showed the clear preference of MTG to bind to site III, facilitated by hydrophobic (alkyl and pi-alkyl) and van der Waals forces, together with carbon hydrogen bonds. Additionally, the MTG–HSA complexation was demonstrated to be stable based on molecular dynamics analysis. The outcomes of this study shed light on the therapeutic potential of MTG and can help in the design of more effective derivatives of the compound.

Sodium dodecyl sulfate rearranges the conformation of transferrin and attenuates its iron-binding capacity

Sodium dodecyl sulfate (SDS), an anionic surfactant used in many cleaning and hygiene products, is known for its dermal and respiratory toxicity. However, how this surfactant influences the iron dynamics within the body and the mechanism is unknown. We explored the interaction between SDS and human transferrin (HTF), focusing on the effects on iron-binding capacity and structural changes. Results revealed that SDS exposure led to a significant release of iron from HTF in a dose-dependent manner, changing its structure and reducing the iron-binding ability. Spectroscopic analyses showed that the protein secondary structure and skeleton, as well as the micro-environment of aromatic amino acids of HTF, were destroyed after SDS binding. Isothermal titration calorimetry (ITC) results (ΔG, ΔS, and ΔH were −40.1 kcal·mol−1, 0.16 kcal·mol−1·K-1, and 10.1 kcal·mol−1, respectively) indicated a spontaneous and hydrophobic interaction with one strong binding site. Molecular docking identified the preferred binding sites, emphasizing hydrophobic forces (with the hydrophobic tail) and hydrogen bonds (with the hydrophilic head) as the primary driving forces, which aligns with the ITC results. Overall, this comprehensive analysis sheds light on the intricate interplay between SDS and HTF, providing insights into potential health risks associated with SDS exposure.

Therapeutic Porphyrin “Hemin” Binds and Unfolds Hen Egg White Lysozyme: Experimental and In Silico Approaches to Study the Interaction

AbstractHemin is an important iron‐containing porphyrin that has important therapeutic properties to control the symptoms of porphyria attacks that include pain, high blood pressure, rapid heartbeat, mental changes, and so forth. Lysozyme has many applications, which include from therapeutic to preservation of foods. The interaction of hemin with an important model protein, hen egg white lysozyme (HEWL), has been observed in this study through hybrid in silico with biophysical studies. There was a strong 1:1 cooperative binding between hemin and HEWL, which was revealed from the strong quenching of the latter by the former. The binding was favored by the decrease in temperature, which is due to the involvement of static type of quenching mechanism in the interaction. Experimental analyses suggested that the major forces involved in the binding were polar ones, and there was an efficient energy transfer from the fluorophore to the ligand. The combination of far‐UV CD spectroscopy and Rayleigh light scattering experiments established that hemin has the strong tendency to unfold HEWL. An extensive molecular docking investigation involving 2000 docking runs recognized the preferred binding site of hemin within HEWL, and also suggested that apart from the polar forces, hydrophobic interactions have also played an important role in the binding.

Hemoglobin targeting potential of aminocarb pesticide: Investigation into dynamics, conformational stability, and energetics in solvent environment

Aminocarb (AMC), a carbamate pesticide, due to its prevalent usage exhibits increased accumulation in the environment affecting both insects and humans. It enters the human body via food grains and be transported through bloodstream. AMC's chemical structure, containing specific molecular frameworks and functional groups, enables it to bind with proteins like albumin and hemoglobin. Given that molecules with similar architecture are known to bind with hemoglobin, we aimed to explore Aminocarb's binding capability and the potential mechanism or mode of its interaction with hemoglobin. Hb being a tetramer with a profound interface between amino acid chains offers multiple binding sites. It is therefore important to investigate the structural aspects of binding of AMC by employing various spectroscopic and in-silico methods. The surface of the α1 chain near the α1β2 interface emerges as the preferred binding site for AMC, primarily due to its conformational restrictions. In its bound state, AMC tends to maintain a relaxed conformation, closely resembling its globally optimized geometry, and resides in close proximity to the α1 chain via multiple hydrophobic contacts and water bridge as observed in molecular dynamics (MD) simulations. Fluorescence quenching experiments showed moderate binding strength (7.7 × 10⁴ L M⁻1 at 288 K, 7.8 × 10⁴ L M⁻1 at 298 K, 7.9 × 10⁴ L M⁻1 at 308 K) and spontaneous binding, driven by hydrophobic and van der Waals interactions, as indicated by enthalpy (0.80–0.91 kJ mol⁻1), entropy (0.0970–0.0974 kJ mol⁻1), and Gibbs free energy (−27.13 to - 29.08 kJ mol⁻1). Circular dichroism experiments reveal no major structural changes in Hb. Quantum chemical calculations and MD simulations reveal conformation-dependent energy differences, enhancing our understanding of AMC's binding mechanism to Hb.

Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy.

Background/Objectives: YAT2150 is a first-in-class antiplasmodial compound that has been recently proposed as a new interesting drug for malaria therapy. Methods/Results: The fluorescence of YAT2150 rapidly increases upon its entry into Plasmodium, a property that can be of use for the design of highly sensitive diagnostic approaches. YAT2150 blocks the in vitro development of the ookinete stage of Plasmodium and, when added to an infected blood meal, inhibits oocyst formation in the mosquito. Thus, the compound could possibly contribute to future transmission-blocking antimalarial strategies. Cell influx/efflux studies in Caco-2 cells suggest that YAT2150 is internalized by endocytosis and also through the OATP2B1 transporter, whereas its main export route would be via OSTα. YAT2150 has an overall favorable drug metabolism and pharmacokinetics profile, and its moderate cytotoxicity can be significantly reduced upon encapsulation in immunoliposomes, which leads to a dramatic increase in the drug selectivity index to values close to 1000. Although YAT2150 binds amyloid-forming peptides, its in vitro fluorescence emission is stronger upon association with peptides that form amorphous aggregates, suggesting that regions enriched in unstructured proteins are the preferential binding sites of the drug inside Plasmodium cells. The reduction of protein aggregation in the parasite after YAT2150 treatment, which has been suggested to be directly related to the drug's mode of action, is also observed following treatment with quinoline antimalarials like chloroquine and primaquine. Conclusions: Altogether, the data presented here indicate that YAT2150 can represent the spearhead of a new family of compounds for malaria diagnosis and therapy due to its presumed novel mode of action based on the interaction with functional protein aggregates in the pathogen.

In(III) pyridinecarboxylate complexes: Composition, solution equilibria estimation, bioevaluation and interactions with HSA

Two In(III) – pyridinecarboxylates ([In(Pic)2(NO3)(H2O)] (InPic; HPic = picolinic acid), [In(HDpic)(Dpic)(H2O)2]·5H2O (InDpic; H2Dpic = dipicolinic acid), have been synthesized by one-step procedure. The complexes composition was confirmed by physicochemical analyses and X-ray diffraction confirmed molecular structure of both complexes. Moreover, complex species speciation was described in both systems by potentiometry and 1H NMR spectroscopy and mononuclear complex species were determined; [In(Pic)]2+ (logβ011 = 6.94(4)), [In(Pic)2]+ (logβ021 = 11.98(9)), [In(Dpic)]+ (logβ011 = 10.42(6)), [In(Dpic)2]− (logβ021 = 17.58(7)) and [In(Dpic)2(OH)]2− (logβ−121 = 10.18(6)). To confirm the complexes stability in 1 % DMSO, 1H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial and anticancer assays indicate a more significant sensitivity of S. aureus bacteria and MDA-MB-231 cancer cells to the InPic complex (IC50 = 25 and 340.7 μM) than to the InDpic (IC50 = 50 and 975.4 μM). The interaction and binding mechanism of picolinic/dipicolinic acid and their indium(III) complexes with HSA (human serum albumin) were studied using fluorescence and CD spectroscopy. The results confirmed that the studied compounds had bound successfully to HSA, and the binding parameters and constants (KSV, Kq, Kb) were calculated together with the number of binding sites. The binding forces were identified based on calculated thermodynamic parameters (ΔG, ΔH, ΔS). Synchronous spectra were used to study the microenvironment of Tyr and Trp residues and displacement assays revealed that site I was the preferred binding site. After binding, conformational changes were found to have occurred in the HSA molecule and the % α-helical content had decreased.

The utility of MOF-based materials in direct air capture (DAC) application to ppm-level CO2

Metal-organic frameworks (MOFs) are well-suited materials for CO2 removal and have robust capture capacity and selectivity. Although the adsorption of CO2 in MOFs has been studied, the implementation of ppm-level CO2 uptake in MOFs and the effects of the pore size and charge have not been fully explored. We performed grand canonical Monte Carlo (GCMC) simulations combined with the Density Functional Theory plus U (DFT + U) charge method to investigate MOF screening for ppm-level CO2 uptake and its application in a direct air capture (DAC) system. Three types of MOFs containing eight members were studied: i.e., ZIF-68, 69, 70; UiO-66, 67, 68; CAU-10; and MIL-125. The pore landscape characterization, electrostatic field-induced enhancement, and preferential binding sites of these MOFs were examined for CO2 capture. MOFs with pore limited diameters (PLD) 1.5 times the size of CO2 molecules and with large cavity diameters (LCD) smaller than 10 Å exhibit robust confinement capacity. Polar functional groups and metal ions dominate the electrostatic contributions and subsequently enhance the surface adhesion of CO2 molecules. For a given framework, favorable CO2 binding occurs in the following order: small pores/cages > polar functional group/metal ions > larger pores/cages. ZIF-69 which comprises smaller pores (7.5 Å) and robust polar functional groups (–Cl) collectively enhances CO2 capture; thus, ZIF-69 outperforms other MOFs; the performance of ZIF-69 is followed by that of CAU-10 which has an optimal pore size of 6 Å. These findings are of fundamental and practical importance for the application of MOFs in DAC technologies for CO2 removal.

Protection of the Telomeric Junction by the Shelterin Complex.

Shelterin serves critical roles in suppressing superfluous DNA damage repair pathways on telomeres. The junction between double-stranded telomeric tracts (dsTEL) and single-stranded telomeric overhang (ssTEL) is the most accessible region of the telomeric DNA. The shelterin complex contains dsTEL and ssTEL binding proteins and can protect this junction by bridging the ssTEL and dsTEL tracts. To test this possibility, we monitored shelterin binding to telomeric DNA substrates with varying ssTEL and dsTEL lengths and quantified its impact on telomere accessibility using single-molecule fluorescence microscopy methods in vitro. We identified the first dsTEL repeat nearest the junction as the preferred binding site for creating the shelterin bridge. Shelterin requires at least two ssTEL repeats, while the POT1 subunit of shelterin that binds to ssTEL requires longer ssTEL tracts for stable binding to telomeres and effective protection of the junction region. The ability of POT1 to protect the junction is significantly enhanced by the 5'-phosphate at the junction. Collectively, our results show that shelterin enhances the binding stability of POT1 to ssTEL and provides more effective protection compared with POT1 alone by bridging single- and double-stranded telomeric tracts.

Polyvalent Glycomimetic-Gold Nanoparticles Revealing Critical Roles of Glycan Display on Multivalent Lectin-Glycan Interaction Biophysics and Antiviral Properties.

Multivalent lectin-glycan interactions (MLGIs) are widespread and vital for biology, making them attractive therapeutic targets. Unfortunately, the structural and biophysical mechanisms of several key MLGIs remain poorly understood, limiting our ability to design spatially matched glycoconjugates as potential therapeutics against specific MLGIs. We have recently demonstrated that natural oligomannose-coated nanoparticles are powerful probes for MLGIs. They can provide not only quantitative affinity and binding thermodynamic data but also key structural information (e.g, binding site orientation and mode) useful for designing glycoconjugate therapeutics against specific MLGIs. Despite success, how designing parameters (e.g., glycan type, density, and scaffold size) control their MLGI biophysical and antiviral properties remains to be elucidated. A synthetic pseudodimannose (psDiMan) ligand has been shown to selectively bind to a dendritic cell surface tetrameric lectin, DC-SIGN, over some other multimeric lectins sharing monovalent mannose specificity but having distinct cellular functions. Herein, we display psDiMan polyvalently onto gold nanoparticles (GNPs) of varying sizes (e.g., ∼5 and ∼13 nm, denoted as G5- and G13 psDiMan hereafter) to probe how the scaffold size and glycan display control their MLGI properties with DC-SIGN and the closely related lectin DC-SIGNR. We show that G5/13 psDiMan binds strongly to DC-SIGN, with sub-nM K ds, with affinity being enhanced with increasing scaffold size, whereas they show apparently no or only weak binding to DC-SIGNR. Interestingly, there is a minimal, GNP-size-dependent, glycan density threshold for forming strong binding with DC-SIGN. By combining temperature-dependent affinity and Van't Hoff analyses, we have developed a new GNP fluorescence quenching assay for MLGI thermodynamics, revealing that DC-SIGN-Gx-psDiMan binding is enthalpy-driven, with a standard binding ΔH 0 of ∼ -95 kJ mol-1, which is ∼4-fold that of the monovalent binding and is comparable to that measured by isothermal titration calorimetry. We further reveal that the enhanced DC-SIGN affinity with Gx-psDiMan with increasing GNP scaffold size is due to reduced binding entropy penalty and not due to enhanced favorable binding enthalpy. We further show that DC-SIGN binds tetravalently to a single Gx-psDiMan, irrespective of the GNP size, whereas DC-SIGNR binding is dependent on GNP size, with no apparent binding with G5, and weak cross-linking with G13. Finally, we show that Gx-psDiMans potently inhibit DC-SIGN-dependent augmentation of cellular entry of Ebola pseudoviruses with sub-nM EC50 values, whereas they exhibit no significant (for G5) or weak (for G13) inhibition against DC-SIGNR-augmented viral entry, consistent to their MLGI properties with DC-SIGNR in solution. These results have established Gx-psDiMan as a versatile new tool for probing MLGI affinity, selectivity, and thermodynamics, as well as GNP-glycan antiviral properties.

Multispectroscopic and Theoretical Investigation on the Binding Interaction of a Neurodegenerative Drug, Lobeline with Human Serum Albumin: Perturbation in Protein Conformation and Hydrophobic-Hydrophilic Surface.

Lobeline (LOB), a naturally occurring alkaloid, has a broad spectrum of pharmacological activities and therapeutic potential, including applications in central nervous system disorders, drug misuse, multidrug resistance, smoking cessation, depression, and epilepsy. LOB represents a promising compound for developing treatments in various medical fields. However, despite extensive pharmacological profiling, the biophysical interaction between the LOB and proteins remains largely unexplored. In the current article, a range of complementary photophysical and cheminformatics methodologies were applied to study the interaction mechanism between LOB and the carrier protein HSA. Steady-state fluorescence and fluorescence lifetime experiments confirmed the static-quenching mechanisms in the HSA-LOB system. "K" (binding constant) of the HSA-LOB system was determined to be 105 M-1, with a single preferable binding site in HSA. The forces governing the HSA-LOB stable complex were analyzed by thermodynamic parameters and electrostatic contribution. The research also investigated how various metal ions affect complex binding. Site-specific binding studies depict Site I as probable binding in HSA by LOB. We conducted synchronous fluorescence, 3D fluorescence, and circular dichroism studies to explore the structural alteration occurring in the microenvironment of amino acids. To understand the robustness of the HSA-LOB complex, we used theoretical approaches, including molecular docking and MD simulations, and analyzed the principal component analysis and free energy landscape. These comprehensive studies of the structural features of biomolecules in ligand binding are of paramount importance for designing targeted drugs and delivery systems.

Discerning the Role of DNA Sequence, Shape, and Flexibility in Recognition by Drosophila Transcription Factors.

The precise spatial and temporal orchestration of gene expression is crucial for the ontogeny of an organism and is mainly governed by transcription factors (TFs). The mechanism of recognition of cognate sites amid millions of base pairs in the genome by TFs is still incompletely understood. In this study, we focus on DNA sequence composition, shape, and flexibility preferences of 28 quintessential TFs from Drosophila melanogaster that are critical to development and body patterning mechanisms. Our study finds that TFs exhibit distinct predilections for DNA shape, flexibility, and sequence compositions in the proximity of transcription factor binding sites (TFBSs). Notably, certain zinc finger proteins prefer GC-rich areas with less negative propeller twist, while homeodomains mainly seek AT-rich regions with a more negative propeller twist at their sites. Intriguingly, while numerous cofactors share similar binding site preferences and bind closer to each other in the genome, some cofactors that have different preferences bind farther apart. These findings shed light on TF DNA recognition and provide novel insights into possible cofactor binding and transcriptional regulation mechanisms.

Inhibition of soluble epoxide hydrolase by natural isothiocyanates

GoalThe long-term goal of our research is to develop safe and effective soluble epoxide hydrolase (sEH) inhibitors. The objective of this study is to evaluate the potency and selectivity of six natural isothiocyanates (ITCs) as sEH inhibitors. MethodsMolecular docking was used to model likely interactions between the ligands and receptors. The sEH inhibitory activity was tested using a validated fluorescence-based assay and PHOME as a substrate. To evaluate their selectivity as sEH inhibitors, the inhibitory potential of the ITCs was determined on microsomal epoxide hydrolase (mEH) and cytochrome P450 (CYP) enzymes in human liver microsomes. Probe substrates such as styrene oxide (mEH substrate) and established substrates for CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 were used in this study. The metabolites of these substrates were analyzed using validated LC-MS/MS and HPLC-UV assays. ResultsMolecular Docking revealed significant differences in binding site preference among the ITCs in silico and pointed to important interactions between the ligands and the catalytic residues of the sEH enzyme. In vitro, the ITCs showed varying degrees of sEH inhibition, but sulforaphane (SFN) and phenyl isothiocyanate (PITC) were the most potent inhibitors with IC50 values of 3.65 and 7.5 μM, respectively. mEH was not significantly inhibited by any of the ITCs. Erucin and iberin were the only ITCs that did not inhibit the activity of any of the tested CYP enzymes. ConclusionOur results demonstrate that natural ITCs have the potential to offer safe, selective, and potent sEH inhibition.

Hydroxyl-functionalized linker endows an ultra-microporous aluminum based metal–organic framework with electronegative site for enhancing ethane/ethylene separation

Efficient purification of ethylene (C2H4) from the cracking gas containing a small amount of ethane (C2H6) by selective adsorption of C2H6 is meaningful but remains challenging. Aluminum-based metal–organic frameworks (Al-MOFs) with ultra-microporous structure show preferential adsorption of C2H6 over C2H4, relying on the existence of multiple hydrogen bonding acceptors (e.g., AlO6 polyhedra) for C2H6 molecule in the confined pores. However, most Al-MOFs exhibit limited C2H6/C2H4 selectivity (<2), which lack other strong preferential binding sites for C2H6. Here we report that a hydroxyl functionalized Al-MOF (i.e., CAU-1-OH) exhibits notably improved C2H6/C2H4 selectivity (2.13) and C2H6 uptake (3.95 mmol g−1) at 298 K and 1 bar compared to its amino-functionalized counterpart, CAU-1-NH2. Prior to experiment, theoretical calculations were performed, revealing that O atom from hydroxyl group in CAU-1-OH acts as a fairly strong hydrogen bond acceptor due to its more negative charge than N atom in CAU-1-NH2. The in-situ infrared experiment further confirmed the formation of multiple hydrogen bonds (C–H⋅⋅⋅O) between CAU-1-OH and C2H6 molecules, which plays vital role for C2H6-selective capture. The actual potential for C2H4 purification was fully demonstrated by dynamic breakthrough experiments, in which CAU-1-OH displayed excellent separative performance from C2H6/C2H4 (1/15, v/v) mixture. Moreover, the structural stability and excellent recyclability suggested and the promise for cost-effective industrial application in C2H6/C2H4 separation.

Exploring the Relationship between Small Peptides and the T1R1/T1R3 Umami Taste Receptor for Umami Peptide Prediction: A Combined Approach.

Umami peptides are known for enhancing the taste experience by binding to oral umami T1R1 and T1R3 receptors. Among them, small peptides (composed of 2-4 amino acids) constitute nearly 40% of reported umami peptides. Given the diversity in amino acids and peptide sequences, umami small peptides possess tremendous untapped potential. By investigating 168,400 small peptides, we screened candidates binding to T1R1/T1R3 through molecular docking and molecular dynamics simulations, explored bonding types, amino acid characteristics, preferred binding sites, etc. Utilizing three-dimensional molecular descriptors, bonding information, and a back-propagation neural network, we developed a predictive model with 90.3% accuracy, identifying 24,539 potential umami peptides. Clustering revealed three classes with distinct logP (-2.66 ± 1.02, -3.52 ± 0.93, -2.44 ± 1.23) and asphericity (0.28 ± 0.12, 0.26 ± 0.11, 0.25 ± 0.11), indicating significant differences in shape and hydrophobicity (P < 0.05) among potential umami peptides binding to T1R1/T1R3. Following clustering, nine representative peptides (CQ, DP, NN, CSQ, DMC, TGS, DATE, HANR, and STAN) were synthesized and confirmed to possess umami taste through sensory evaluations and electronic tongue analyses. In summary, this study provides insights into exploring small peptide interactions with umami receptors, advancing umami peptide prediction models.

Mechanistical Insights into the Ultrasensitive Detection of Radioactive and Chemotoxic UO22+ Ions by a Porous Anionic Co-Metal-Organic Framework.

Development of a simple, cost-efficient, and portable UO22+ sensory probe with high selectivity and sensitivity is highly desirable in the context of monitoring radioactive contaminants. Herein, we report a luminescent Co-based metal-organic framework (MOF), {[Me2NH2]0.5[Co(DATRz)0.5(NH2BDC)]·xG}n (1), equipped with abundant amino functionalities for the selective detection of uranyl cations. The ionic structure consists of two types of channels decorated with plentiful Lewis basic amino moieties, which trigger a stronger acid-base interaction with the diffused cationic units and thus can selectively quench the fluorescence intensity in the presence of other interfering ions. Furthermore, the limit of detection for selective UO22+ sensing was achieved to be as low as 0.13 μM (30.94 ppb) with rapid responsiveness and multiple recyclabilities, demonstrating its excellent efficacy. Density functional theory (DFT) calculations further unraveled the preferred binding sites of the UO22+ ions in the tubular channel of the MOF structure. Orbital hybridization between NH2BDC/DATRz and UO22+ together with its significantly large electron-accepting ability is identified as responsible for the luminescence quenching. More importantly, the prepared 1@PVDF {poly(vinylidene difluoride)} mixed-matrix membrane (MMM) displayed good fluorescence activity comparable to 1, which is of great significance for their practical employment as MOF-based luminosensors in real-world sensing application.

Multifacets of Fullerene-Metal Clusters: From Fundamental to Application.

ConspectusBuckminsterfullerene, C60, was discovered through a prominent mass peak containing 60 atoms produced from laser vaporization of graphite, driven by Kroto's interest in understanding the formation mechanisms of carbon-containing molecules in space. Inspired by the geodesic dome-shaped architecture designed by Richard Buckminster Fuller, after whom the particle was named, C60 was found to have a football-shaped structure comprising 20 hexagons and 12 pentagons. It sparked worldwide interest in understanding this new carbon allotrope, resulting in the awarding of the Noble Prize in Chemistry to Smalley, Kroto, and Curl in 1996.Intrinsically, C60 is an exceptional species because of its high stability and electron-accepting ability and its structural tunability by decorating or substituting either on its exterior surface or interior hollow cavity. For example, metal-decorated fullerene complexes have found important applications ranging from superconductivity, nanoscale electronic devices, and organic photovoltaic cells to catalysis and biomedicine. Compared to the large body of studies on atoms and molecules encapsulated by C60, studies on the exteriorly modified fullerenes, i.e., exohedral fullerenes, are scarcer. Surprisingly, to date, uncertainty exists about a fundamental question: what is the preferable exterior binding site of different kinds of single atoms on the C60 surface?In recent years, we have developed an experimental protocol to synthesize the desired fullerene-metal clusters and to record their infrared spectra via messenger-tagged infrared multiple photon dissociation spectroscopy. With complementary quantum chemical calculations and molecular dynamics simulations, we determined that the most probable binding site of a metal, specifically a vanadium cation, on C60 is above a pentagonal center in an η5 fashion. We explored the bonding nature between C60 and V+ and revealed that the high thermal stability of this cluster originates from large orbital and electrostatic interactions. Through comparing the measured infrared spectra of [C60-Metal]+ with the observational Spitzer data of several fullerene-rich planetary nebulae, we proposed that the complexes formed by fullerene and cosmically abundant metals, for example, iron, are promising carriers of astronomical unidentified spectroscopic features. This opens the door for a real consideration of Kroto's 30-year-old hypothesis that complexes involving cosmically abundant elements and C60 exhibit strong charge-transfer bands, similar to those of certain unidentified astrophysical spectroscopic features. We compiled a VibFullerene database and extracted a set of vibrational frequencies and intensities for fullerene derivatives to facilitate their potential detection by the James Webb Space Telescope. In addition, we showed that upon infrared irradiation C60V+ can efficiently catalyze water splitting to generate H2. This finding is attributed to the novel geometric-electronic effects of C60, acting as "hydrogen shuttle" and "electron sponge", which illustrates the important role of carbon-based supports in single-atom catalysts. Our work not only unveils the basic structures and bonding nature of fullerene-metal clusters but also elucidates their potential importance in astrophysics, astrochemistry, and catalysis, showing the multifaceted character of this class of clusters. More exciting and interesting aspects of the fullerene-metal clusters, such as ultrafast charge-transfer dynamics between fullerene and metal and their relevance to designing hybrid fullerene-metal junctions for electronic devices, are awaiting exploration.

Exploring the molecular basis of tucatinib interaction with human serum albumin: A spectroscopic and computational analysis

This study delves into the kinetics of interaction among anticancer drug tucatinib (TCT) and human serum albumin (HSA), a pivotal protein that transports substances in the bloodstream of humans. Employing biophysical techniques alongside in-silico approaches, the TCT-HSA complex formation is substantiated. This binding interaction is unequivocally confirmed by the inverse relationship between temperature and Stern-Volmer constant (KSV) and the hyperchromicity in UV–visible spectra. The binding constant (Kb) value (5.34 x 104 M−1) indicates a moderate affinity between TCT and HSA, with thermodynamic analysis pointing towards stabilization through hydrogen bonds and hydrophobic and van der Waals interactions. Moreover, despite causing alterations in the vicinity of Tyr and Trp amino acids, the introduction of TCT to HSA confers a substantial protective effect against the thermal denaturation of the protein. Circular dichroism unveils a decrease in the content of alpha helices upon TCT binding. At the same time, CD thermal analysis hints at a marginal increase in the melting temperature of HSA, indicating heightened stability at elevated temperatures. Molecular docking and competitive displacement assays confirm that the preferred binding site for TCT is subdomain IIA (Sudlow's site I) of HSA. Molecular dynamics simulations emphasize the stability of the TCT-HSA complex. This work sheds light on a detailed characterization of the HSA-TCT interaction, elucidating binding mechanisms and their consequential impact on HSA structure and stability.

Probing the toxic effect of chlorpyrifos as an environmental pollutant on the structure and biological activity of lysozyme under physiological conditions

The pervasive use of pesticides like chlorpyrifos (CPY) has been associated with deleterious effects on biomolecules, posing significant risks to environmental integrity, public health, and overall ecosystem equilibrium. Accordingly, in this study, we investigated the potential binding interaction between the well-conserved enzyme, lysozyme (LSZ), and CPY through various spectroscopic techniques and molecular modeling. The UV–vis absorption and fluorescence experiments confirmed the complex formation and static quenching of the intrinsic fluorescence intensity. LSZ revealed a singular binding site for CPY, with binding constants around 105 M−1 across different temperature ranges. Analysis of thermodynamic parameters showed the spontaneous nature of the complexation process, while also revealing the pivotal role of hydrophobic interactions in stabilizing the LSZ-CPY system. According to circular dichroism and Fourier transform infrared studies, CPY binding changed the secondary structure of LSZ by boosting α-helix presence and reducing the levels of β-sheet and β-turn content. Further, CPY decreased the stability and activity of LSZ. Computational docking delineated the specific and highly preferred binding site of CPY within the structure of LSZ. Molecular dynamic simulation indicated the enduring stability of the LSZ/CPY complex and revealed structural modifications in the LSZ after binding with CPY. This research provides a detailed understanding of the intermolecular dynamics between CPY and LSZ, concurrently elucidating the molecular-level implications for the potential hazards of pesticides in the natural environment.

Molecular insights into the interaction between myoglobin and Imidacloprid: Multi-spectral experiments and computational simulations

Imidacloprid (IMI) belongs to the neonicotinoid insecticides, specifically the imidazole chemical group, which exhibits a high level of contact, digestive, and systemic effects on the central nervous system of insects. In this study, we investigated the impact of IMI on the conformation and structural stability of myoglobin (Mb) protein using spectroscopic techniques combined with molecular docking and simulation approaches. Additionally, we examined the thermal stability of the resulting complex. The UV–Visible results demonstrated the interaction between IMI and Mb protein. The intrinsic fluorescence of Mb was effectively quenched by IMI, indicating successful binding and the formation of a stable complex. Thermodynamic analysis revealed that the spontaneous bonding process was primarily governed by van der Waals forces and hydrogen bonds. FT-IR analysis indicated that IMI induced conformational changes in Mb, providing further evidence of its potential toxicity and structural damage to Mb. Furthermore, the interaction significantly enhanced the thermal stability of Mb compared to Mb alone. Molecular docking revealed the preferred binding site of IMI within the Mb structure. Molecular dynamics (MD) simulation results further supported the findings by demonstrating a decrease in compactness and an increase in the stability of the Mb-IMI complex. These findings offer valuable insights into the potential toxicity risks of IMI to human health and shed light on the binding mechanism between IMI and Mb. The results of this study serve as a useful model for gaining a deeper understanding of the effects of these pesticides on proteins and body health.