Stable Complex Research Articles

Palladium-Catalyzed Acetoxylation of γ-Dehydro-aryl-himachalene: The Synthesis of a Novel Allylic Acetoxylated Sesquiterpene and a π-Allyl Palladium(II) Complex.

Allylic oxygenated derivatives of himachalenes are highly valued molecules due to their potential applications in perfumery, cosmetics, and pharmaceuticals. Previous attempts at catalyzed allylic oxidation of himachalenes led to the formation of a very stable η3-allyl palladium complex, preventing any further reaction development. Herein, we present the first successful palladium-catalyzed synthesis of a novel allylic acetoxylated derivative of himachalenes. This reaction was achieved by incorporating an aromatic ring into the substrate structure. The resulting intermediate complex was isolated and characterized using nuclear magnetic resonance spectroscopy and X-ray crystallography. Density functional theory (DFT) calculations were performed to compare the reactivity of the newly synthesized complex with previously reported ones. The theoretical results confirm that the introduction of an aromatic ring enhances the reactivity of the η³-allyl palladium complex, thereby facilitating the desired transformation.

In-silico and in-vitro studies to identify potential inhibitors of SARS-CoV-2 spike protein from Omani medicinal plants

In the quest for novel therapeutic agents against SARS-CoV-2, the proposed study explores the potential of traditional Omani medicinal plants, focusing on the efficacy of natural ligands against the virus's Spike protein. Among 437 identified medicinal plants across Oman, 47 species that are documented for their traditional use in treating respiratory infections, with 30 species' ligands available were chosen for analysis. Molecular docking was performed using Autodock Vina on these ligands, yielding 406 unique ligands post-duplication removal. The binding affinities of target-ligand complexes were precisely determined, ranking them by interaction strength. This process identified Corilagin, a phytochemical from the Acalypha indica plant (locally known as Aeyan Al Aqrada), as the most promising inhibitor. Subsequent analyses using GROMACS for molecular dynamics simulation confirmed its binding stability and interaction dynamics of the Corilagin-protein complex. The in-vitro studies further validated Corilagin's inhibitory effect on SARS-CoV-2, demonstrating a remarkable 92 % inhibition at 0.5 mM concentration. Dilution studies to ascertain the IC50 value revealed Corilagin's high potency at a micromolar level (IC50 = 2.15 ± 0.13 μM), underscoring its potential as a drug candidate for SARS-CoV-2 treatment. These findings highlight the significance of ethnomedicine and in-silico methodologies in drug discovery, offering promising directions for future antiviral research.

Artemisia campestris L. as a promising source of potential antiviral drugs for SARS-CoV-2: Docking and dynamic simulation studies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been considered as global public health security threats. Due to its rapid spread, high mortality rate and unavailability of treatment, we need to find a potent drug against SARS-CoV-2. Natural products are useful agents for the discovery of new potential drugs to combat coronavirus. Artemisia campestris, an aromatic plant widely used in traditional medicine, particularly in southern region of Algeria, is recognized for its essential oils and phenolics compounds possessing a wide range of biological activities. This study selected sixty-nine compounds from this plant to determine their binding interactions with the SARS-CoV-2 main protease (Mpro) and receptor-binding domain of the spike (S-RBD) protein, by using computational methods. Rutin, isoquercetin, and quercetin-3-O-glucuronide were shown to be the most potent inhibitors for Mpro and S-RBD with docking scores and Ki values ranging from -16.06 to -10.67 Kcal/mol and 0.005 to 30.01 nM, respectively. Evaluation of ADMET pharmacokinetic properties and the drug likeness in silico revealed that only 3,5-dicaffeoylquinic acid, 3–4–5-tricaffeoylquinic acid, isorhamnetin-3-O-glucoside, and rubescensin A could be more effective drugs against COVID-19. Molecular dynamics (MD) simulations (100 ns) and MM-GBSA calculations confirmed the stability of ligand-protein complexes via hydrogen bonding interactions with crucial residues. The analysis of structural parameters (RMSD, RMSF, H-bonds, Rg, and SASA) indicates that 3,4,5-tricaffeoylquinic acid and rubescensin A compounds have good stability and significant binding affinity with the Mpro and S-RBD protein. Taken together, our findings confirm that Artemisia campestris as a plausible source of anti-SARS-COV-2 phytochemicals and suggest that may play important role in this activity.

A Pd(II) Complex Exhibiting Tetradentate NHC‐Phosphine Ligand: On Route to Unconventional Phosphonium Ylide Derivatives

AbstractUnusual open‐chain tetradentate NHC‐phosphine pre‐ligand [Ph2PCH(Ph)ImCH2ImC(H)PhPPh2](BF4)2 was prepared in a good yield by metal‐mediated approach starting from Mn(I) complex [Cp(CO)2Mn(η2‐Ph2P=C(H)Ph)](BF4) and bis(imidazole) derivative ImCH2Im. Its reaction with Pd(OAc)2 afforded dicationic Pd(II) complex of bis(NHC)bis(phosphine) ligand adopting κ4PĈĈP coordination mode as a mixture of two diastereomers. The deprotonation of the C(H)Ph ligand bridge in the latter using KN(SiMe3)2 as base provided stable complex exhibiting unconventional phosphonium ylide moiety, whereas all attempts to detect the corresponding bis(ylide) derivative failed.

Cheminformatics-aided discovery of potential allosteric site modulators of ubiquitin-specific protease 7

Ubiquitin-specific peptidase 7 (USP7) is a deubiquitinating enzyme that mediates the stability and activity of numerous proteins. At basal expression levels, USP7 stabilizes p53 protein, even in the presence of excess MDM2. However, its overexpression leads to the deubiquitination of MDM2 at a rate faster than p53, leading to p53 degradation and pro-tumorigenic roles. Consequently, it is an attractive target for anticancer drug discovery via the modulation of its allosteric site from which the protein is activated. In this study, molecular modeling techniques and cheminformatics approaches were employed to unravel the potential of eighty compounds to serve as its allosteric site modulators. The compounds were initially subjected to virtual screening. Subsequently, the binding free energies of the top four compounds with the highest binding affinities were calculated, and their drug-likeness, and pharmacokinetic and toxicity profiles were evaluated. Ultimately, the complexes of the protein and hit compounds were subjected to a 100 nanoseconds (ns) molecular dynamics simulation. The results of the study revealed eight compounds from the compound library with docking scores ranging from − 7.491 to -11.43 kcal/mol, compared to P217564, which exhibited a docking score of -5.671 kcal/mol. The top four compounds with the highest affinities possessed drug-like properties, and good pharmacokinetic and toxicity profiles, and their predicted inhibitory potentials showed they will be effective at minimal concentration. Also, molecular dynamics simulation confirmed the stability of the protein-ligand complexes. Conclusively, the compounds identified in this study are worthy of further evaluation for the development of allosteric site modulators of USP7.

Stenotrophomonas pavanii MY01 induces phosphate precipitation of Cu(II) and Zn(II) by degrading glyphosate: performance, pathway and possible genes involved.

Microbial bioremediation is an advanced technique for removing herbicides and heavy metals from agricultural soil. In this study, the strain Stenotrophomonas pavanii MY01 was used for its ability to degrade glyphosate, a phosphorus-containing organic compound, producing PO4 3- as a byproduct. PO4 3- is known to form stable precipitates with heavy metals, indicating that strain MY01 could potentially remove heavy metals by degrading glyphosate. Therefore, the present experiment induced phosphate precipitation from Cu(II) (Hereinafter referred to as Cu2+) and Zn(II) (Hereinafter referred to as Zn2+) by degrading glyphosate with strain MY01. Meanwhile, the whole genome of strain MY01 was mined for its glyphosate degradation mechanism and its heavy metal removal mechanism. The results of the study showed that the strain degraded glyphosate best at 34°C, pH = 7.7, and an inoculum of 0.7%, reaching 72.98% within 3d. The highest removal of Cu2+ and Zn2+ in the test was 75.95 and 68.54%, respectively. A comparison of strain MY01's genome with glyphosate degradation genes showed that protein sequences GE000474 and GE002603 had strong similarity to glyphosate oxidoreductase and C-P lyase. This suggests that these sequences may be key to the strain's ability to degrade glyphosate. The GE001435 sequence appears to be related to the phosphate pathway, which could enable phosphate excretion into the environment, where it forms stable coordination complexes with heavy metals.

Designing novel multiepitope mRNA vaccine targeting Hendra virus (HeV): An integrative approach utilizing immunoinformatics, reverse vaccinology, and molecular dynamics simulation.

Human and animal health is threatened by Hendra virus (HeV), which has few treatments. This in-silico vaccine design study focuses on HeV G (glycoprotein), F (fusion protein), and M (matrix protein). These proteins were computationally assessed for B and T-cell epitopes after considering HeV strain conservation, immunogenicity, and antigenicity. To improve vaccination immunogenicity, these epitopes were selectively ligated into a multiepitope construct. To improve vaccination longevity and immunological response, adjuvants and linkers were ligated. G, F, and M epitopes were used to create an mRNA HeV vaccine. Cytotoxic, helper, and linear B-lymphocytes' epitopes are targeted by this vaccine. The population coverage analysis demonstrates that multi-epitope vaccination covers 91.81 percent of CTL and 98.55 percent of HTL epitopes worldwide. GRAVY evaluated the vaccine's well-characterized physicochemical properties -0.503, indicating solubility and functional stability. Structure analysis showed well-stabilized 2° and 3° structures in the vaccine, with alpha helix, beta sheet, and coil structures (Ramachandran score of 88.5% and Z score of -3.44). There was a strong affinity as shown by docking tests with TLR-4 (central score of -1139.4 KJ/mol) and TLR-2 (center score of -1277.9 KJ/mol). The coupled V-apo, V-TLR2, and V-TLR4 complexes were tested for binding using molecular dynamics simulation where extremely stable complexes were found. The predicted mRNA structures provided significant stability. Codon optimization for Escherichia. coli synthesis allowed the vaccine to attain a GC content of 46.83% and a CAI score of 1.0, which supports its significant expression. Immunological simulations indicated vaccine-induced innate and adaptive immune reactions. Finally, this potential HeV vaccine needs more studies to prove its efficacy and safety.

Research on the Synergistic Inhibition of Angiotensin-Converting Enzyme (ACE) by the Gastrointestinal Digestion Products of the ACE Inhibitory Peptide FPPDVA.

To gain a deeper understanding of the ACE inhibition effect, the inhibitory effect of ACE-inhibiting peptide (ACEIP) FPPDVA's digestive products on ACE was further investigated. Two novel peptides, PD (IC50 = 161.1 ± 1.10 μM) and DV (IC50 = 66.51 ± 0.99 μM) were identified in the digestive products of FPPDVA using LC-MS/MS. The Peptide Mix (FPPDVA, PD, and DV) exhibited a remarkable synergistic effect on ACE inhibition by significantly enhancing it by up to 508% compared to the individual peptides alone. Furthermore, theoretical simulations suggest that the Peptide Mix synergistically inhibits ACE activity by forming more stable complexes with the active site of ACE, facilitated by an increased number of hydrogen bonds. Additionally, Lineweaver-Burk plot analysis and spectroscopic studies further verified the presence of these stable complexes. ITC results show that the combination of Peptides Mix and ACE is a spontaneous exothermic process driven by entropy. The study showed that FPPDVA has a stronger inhibitory effect on ACE after digestion, making it suitable as an antihypertensive peptide in functional foods.

Computational Study of Coumarin Compounds as Potential Inhibitors of Casein Kinase 2: DFT, 2D-QSAR, ADMET and Molecular Docking Investigations

Casein kinase 2 (CK2) is an ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Recently, there has been a notable increase in interest in the use of casein kinase 2 (CK2) inhibitors to improve the treatment of a specific form of cancer while minimizing the risk of undesirable side effects. Recently, using different virtual screening approaches, we have identified several novel CK2 inhibitors. In particular, we have discovered that the coumarin moiety can be considered an attractive CK2 inhibitor scaffold. In the present work, quantitative structure-activity relationship (QSAR) analysis has been employed to envisage the inhibitory effects of 32 coumarin derivatives on the CK2 protein. The most efficient model is found by using multiple linear regression (MLR). Its capability is considered by the external and internal validation values found (R2 = 0.884, Q2cv = 0.822, R2pred = 0.821, and R2p = 0.811), which aligned well with Tropsha and Golbraikh’s approach. The highest docking score founded for the newly designed coumarins is −7.50 kcal mol-1, which indicates that candidates can bind to the CK2 receptor with greater affinity. Based on the results of the ADMET properties and drug similarity analyses, a DFT investigation was conducted to confirm the stability of the newly explored compounds. It appears that the most stable complexes are those of compound with the highest binding affinity with a lower risk of toxicité.

Structural Basis of Activity of HER2-Targeting Construct Composed of DARPin G3 and Albumin-Binding Domains.

Non-immunoglobulin-based scaffold proteins (SPs) represent one of the key therapeutic target-specific and high-affinity binders in modern medicine. Among their cellular targets are signaling receptors, in particular, receptor tyrosine kinases, whose dysfunction leads to the development of cancer and other serious diseases. Successful applications of SPs have been reported for HER receptor type 2 (HER2), a member of the human epidermal growth factor receptor family that regulates cell growth and differentiation. To extend the blood residence of SPs and prevent their high accumulation in the kidneys, these proteins are often fused with serum albumin. Promising results for HER2-binding activity were obtained for SP G3 from the DARPins (Designed Ankyrin Repeat Proteins) family fused with an albumin-binding domain (ABD). Interestingly, the detected HER2-G3 binding strongly depended on the position of the G3 module in the sequence of the constructs. Further improvement of these constructs for biomedical applications requires deciphering the molecular mechanism responsible for this effect. Here, we investigate the structural and dynamic aspects of ABD-G3 and G3-ABD chimeras using NMR spectroscopy and molecular modeling. Based on biophysical data, we come to the conclusion that extensive inter-domain contacts form in both constructs, although their binding interfaces and complex stability are somewhat different. Also, it is shown that the domain linker plays an important role-it limits the accessibility of the detected protein-protein binding sites, depending on the order of the domains in the chimeric molecules. These results create a solid structural basis for the rational design of new effective SP constructs targeting the signaling receptors in cells.

Selective recovery of Au from waste printed circuit board by water-soluble organic leaching: The key role of in situ bromine mediation and identificationof pathway

A large amount of gold in electronic waste (E-waste) is not properly recovered owing to the absence of efficient and safe leaching methods. Herein, we proposed the concept of ‘water-soluble organic Au leaching’ and created a new water-soluble organic leaching agent, WS NBS–DMF, by dissolving millimolar amounts of N-bromosuccinimide (NBS) and dimethylformamide (DMF) in water. Under mild conditions (25 ℃, pH 7.0), WS NBS–DMF achieved a 94.9 % leaching efficiency of Au for waste printed circuit board (WPCB) with limited leaching of base metals. The potent bromine radical (Br•) and ligands significantly contributed to Au complexation and oxidization via in situ bromine generation and radical initiation from WS NBS–DMF. The bidirectional hydrogen-bond effect of DMF facilitated the in situ bromine generation. Two Au(I) complexes ([AuBr2]- and [(NHS)AuBr]-) and an Au(III) complex ([(NHS)AuBr3]-) were confirmed as the Au leaching products by spectroscopy and mass spectrometry. Furthermore, reciprocal σ-donations between the Au center and ligands in the bonding orbitals enhanced the stability of the Au complexes, thereby promoting efficient Au leaching. Comparing with other leaching methods, this study of WS NBS–DMF provides a safe, economic and eco-friendly technique for efficient and selective gold recovery from e-waste.

A Quantum Mechanical Approach to The Mechanism of Asymmetric Synthesis of Chiral Amine by Imine Reductase from Stackebrandtia Nassauensis.

The asymmetric synthesis of tetrahydroisoquinolines (THIQs) has gained importance in recent years due to their significant potential in drug development studies. In this study, the conversion of 1-methyl-3,4-dihydroisoquinoline substrate to a chiral amine, 1-methyl-1,2,3,4-tetrahydroisoquinoline, under the catalysis of the stereoselective imine reductase enzyme from Stackebrandtia nassauensis (SnIR) was investigated in detail to elucidate the mechanism and explain the experimental enantioselectivity. The results were found to be in agreement with the experimental data. To elucidate the reaction mechanism, quantum mechanical calculations were performed by considering a large cluster of the active site of the enzyme. In this regard, possible reaction pathways leading to both R- and S-products with the corresponding intermediates and the transition states for the hydride transfer from the cofactor to the substrate were considered by density functional theory (DFT) calculations, and the factors contributing to the observed stereoselectivity were sought. The calculations supported a stepwise mechanism rather than the concerted protonation and the hydride transfer steps. The stereoselectivity in the hydride transfer was found to be due not only to the stability of the enzyme-subtrate complex but also to the corresponding reaction barriers. The calculations were performed at the wB97XD/6-311+G(2df,2p)//B3LYP/6-31G(d,p) level of theory using the PCM approach.

Construction and characteristics of EGCG-porcine serum albumin pickering emulsion: Based on noncovalent interactions mechanism

Pickering emulsion prepared by the interaction between polyphenols and protein can improve the stability of protein-based emulsion. The purpose of this study was to explore the complex formation mechanism of epigallocatechin gallate (EGCG)-porcine serum albumin (PSA) complex and the preparation of food-grade Pickering emulsion. By the UV and fluorescence spectral analysis, it was found that EGCG has an obvious fluorescence quenching effect on PSA, mainly static quenching. The results of synchronous, three-dimensional fluorescence and FT-IR spectroscopy showed that the hydrophobic microenvironment of aromatic amino acids and the secondary structure of PSA changed after EGCG was added. The results of molecular docking examined that EGCG and PSA form more stable complexes due to hydrogen bonds, and the binding energy was −4.43 kcal /mol. Compared with the PSA emulsion, the successfully prepared EGCG-PSA Pickering emulsion had smaller droplets and no obvious color in CLMS. The Pickering emulsion of EGCG-PSA had strong emulsification and high viscosity, which belonged to pseudoplastic non-Newtonian fluid. In addition, the free fatty acids release rate of EGCG-PSA Pickering emulsion was decreased by 9.9 %. The antioxidant performance of the EGCG-PSA Pickering emulsion was improved, and the DPPH radical scavenging rate and the ABTS+ radical scavenging rate reached the highest, which were 93.72 % and 57.16 % respectively. This study provides important insights into the interaction between EGCG and PSA, and a reference for the development of polyphenol-protein complex Pickering emulsion in food, medicine, cosmetics, and other fields.

Evaluation of Alpha-Synuclein and Tau Antiaggregation Activity of Urea and Thiourea-Based Small Molecules for Neurodegenerative Disease Therapeutics.

Alzheimer's disease (AD) and Parkinson's disease (PD) are multifactorial, chronic diseases involving neurodegeneration. According to recent studies, it is hypothesized that the intraneuronal and postsynaptic accumulation of misfolded proteins such as α-synuclein (α-syn) and tau, responsible for Lewy bodies (LB) and tangles, respectively, disrupts neuron functions. Considering the co-occurrence of α-syn and tau inclusions in the brains of patients afflicted with subtypes of dementia and LB disorders, the discovery and development of small molecules for the inhibition of α-syn and tau aggregation can be a potentially effective strategy to delay neurodegeneration. Urea is a chaotropic agent that alters protein solubilization and hydrophobic interactions and inhibits protein aggregation and precipitation. The presence of three hetero atoms (O/S and N) in proximity can coordinate with neutral, mono, or dianionic groups to form stable complexes in the biological system. Therefore, in this study, we evaluated urea and thiourea linkers with various substitutions on either side of the carbamide or thiocarbamide functionality to compare the aggregation inhibition of α-syn and tau. A thioflavin-T (ThT) fluorescence assay was used to evaluate the level of fibril formation and monitor the anti-aggregation effect of the different compounds. We opted for transmission electron microscopy (TEM) as a direct means to confirm the anti-fibrillar effect. The oligomer formation was monitored via the photoinduced cross-linking of unmodified proteins (PICUP). The anti-inclusion and anti-seeding activities of the best compounds were evaluated using M17D intracellular inclusion and biosensor cell-based assays, respectively. Disaggregation experiments were performed with amyloid plaques extracted from AD brains. The analogues with indole, benzothiazole, or N,N-dimethylphenyl on one side with halo-substituted aromatic moieties had shown less than 15% cutoff fluorescence obtained with the ThT assay. Our lead molecules 6T and 14T reduced α-syn oligomerization dose-dependently based on the PICUP assays but failed at inhibiting tau oligomer formation. The anti-inclusion effect of our lead compounds was confirmed using the M17D neuroblastoma cell model. Compounds 6T and 14T exhibited an anti-seeding effect on tau using biosensor cells. In contrast to the control, disaggregation experiments showed fewer Aβ plaques with our lead molecules (compounds 6T and 14T). Pharmacokinetics (PK) mice studies demonstrated that these two thiourea-based small molecules have the potential to cross the blood-brain barrier in rodents. Urea and thiourea linkers could be further improved for their PK parameters and studied for the anti-inclusion, anti-seeding, and disaggregation effects using transgenic mice models of neurodegenerative diseases.

PRC2-EZH1 contributes to circadian gene expression by orchestrating chromatin states and RNA polymerase II complex stability.

Circadian rhythmicity of gene expression is a conserved feature of cell physiology. This involves fine-tuning between transcriptional and post-transcriptional mechanisms and strongly depends on the metabolic state of the cell. Together these processes guarantee an adaptive plasticity of tissue-specific genetic programs. However, it is unclear how the epigenome and RNA Pol II rhythmicity are integrated. Here we show that the PcG protein EZH1 has a gateway bridging function in postmitotic skeletal muscle cells. On the one hand, the circadian clock master regulator BMAL1 directly controls oscillatory behavior and periodic assembly of core components of the PRC2-EZH1 complex. On the other hand, EZH1 is essential for circadian gene expression at alternate Zeitgeber times, through stabilization of RNA Polymerase II preinitiation complexes, thereby controlling nascent transcription. Collectively, our data show that PRC2-EZH1 regulates circadian transcription both negatively and positively by modulating chromatin states and basal transcription complex stability.

Selective Sorption of Noble Metals on Polymer Gel Modified with Ionic Liquid.

The solid phase extraction of Au, Ir, Pd, Pt, and Rh on a polymer gel modified with ionic liquid containing methylimidazolium groups (MIA-PG) has been investigated. The positively charged surface of the sorbent is highly suitable for the sorption of stable chlorido complexes of the studied analytes, while the retention of base metals Cu, Fe, Ni, Zn, and Mn is negligible. Optimization experiments performed showed that, at 0.05 M HCl, the degree of sorption of Au, Ir, Pd, and Pt is above 95%, and only for Rh, the maximum degree is 65%; complete elution is achieved in the mixture of thiourea in HCl. The results obtained from the equilibrium adsorption studies are fitted in various adsorption models, such as Langmuir and Freundlich, and the model parameters have been evaluated. The kinetics analysis indicated that the adsorption of Au, Ir, Pd, Pt, and Rh onto the sorbent follows the pseudo-second-order model. Intraparticle diffusion and ion exchange reactions were the rate-limiting steps. Analytical procedures were developed for Pd, Pt, and Rh determination in road dust and soil and for Au determination in copper ore and copper concentrate. The procedures are validated by the analysis of certified reference materials. Analytical figures of merit confirmed their applicability in routine laboratory practice.

Structure and Energetics of PET-Hydrolyzing Enzyme Complexes: A Systematic Comparison from Molecular Dynamics Simulations.

Discovered in 2016, the enzyme PETase, secreted by bacterial Ideonella Sakaiensis 201-F6, has an excellent hydrolytic activity toward poly(ethylene terephthalate) (PET) at room temperature, while it decreases at higher temperatures due to the low thermostability. Many variants have been engineered to overcome this limitation, which hinders industrial application. In this work, we systematically compare PETase wild-type (WT) and four mutants (DuraPETase, ThermoPETase, FastPETase, and HotPETase) using standard molecular dynamics (MD) simulations and unbinding free energy calculations. In particular, we analyze the enzymes' structural characteristics and binding to a tetrameric PET chain (PET4) under two temperature conditions: T1─300 K and T2─350 K. Our results indicate that (i) PET4 forms stable complexes with the five enzymes at room temperature (∼300 K) and (ii) most of the interactions are localized close to the active site of the protein, where the W185 and Y87 residues interact with the aromatic rings of the substrate. Specifically, (iii) the W185 side-chain explores different conformations in each variant (a phenomenon known in the literature as "W185 wobbling"). This suggests that the binding pocket retains structural plasticity and flexibility among the variants, facilitating substrate recognition and localization events at moderate temperatures. Moreover, (iv) PET4 establishes aromatic interactions with the catalytic H237 residue, stabilizing the catalytic triad composed of residues S160-H237-D206, and helping the system achieve an effective configuration for the hydrolysis reaction. Conversely, (v) the binding affinity decreases at a higher temperature (∼350 K), retaining moderate interactions only for HotPETase. Finally, (vi) MD simulations of complexes formed with poly(ethylene-2,5-furan dicarboxylate) (PEF) show no persistent interactions, suggesting that these enzymes are not yet optimized for binding this alternative semiaromatic plastic polymer. Our study offers valuable insights into the structural stability of these enzymes and the molecular determinants driving PET binding onto their surfaces, sheds light on the mechanistic steps that precede the onset of hydrolysis, and provides a foundation for future enzyme optimization.

Density functional theory investigation for noble gases adsorption on B3C2H5 structure

Quantum chemical calculations were performed to study the binding affinity of the B3C2H5 cluster with noble gases. The results indicate that noble gas atoms especially the heavier ones such as Xe and Kr can form stable complexes with this cluster. Detailed analysis of the interaction mechanism reveals that the noble gas atoms serve as donor fragments in the formation of Ng@B3C2H5, 2Ng@B3C2H5, and 3Ng@B3C2H5 donor–acceptor complexes.

Enhancing antibacterial efficacy through macrocyclic host complexation of fluoroquinolone antibiotics for overcoming resistance

The use of supramolecular assemblies in pharmaceuticals has garnered significant interest. Recent studies have shown that the activities of antibacterial agents can be enhanced through complexation with cyclic oligomers and metal ions. Notably, these complexes sometimes possess greater therapeutic properties than the parent drugs. To develop microbiologically potent supramolecular drugs, the complexation of macrocyclic hosts with fluoroquinolone (FQ) antibiotics was investigated. FQs are a successful family of antibiotics that target the bacterial enzymes DNA gyrase and DNA topoisomerase IV, leading to bacterial cell death through the inhibition of DNA synthesis. However, antibiotic resistance resulting from the repeated use of FQs over time has limited their effectiveness against resistant pathogens. To overcome this issue, the encapsulation of FQs in polyphenolic macrocycles was investigated. This study highlights resorcinarene, a polyphenolic host with antibacterial properties, and its ability to chemically interact with FQs. The inclusion complexation process was analyzed using NMR and FTIR techniques. The binding constants determined by 1H-NMR titration revealed that levofloxacin forms more stable complexes with resorcinarene than with β-cyclodextrin, which aligned with MD simulations. Assessment of the geometric characteristics of the inclusion complexes using 2D NMR analysis confirmed that different moieties of various FQs can fit into a single host cavity and improve activity against gram-negative bacteria. Overall, these findings suggest that encapsulation in polyphenolic macrocycles is a promising strategy for utilizing FQs against antibiotic-resistant bacteria.

Thermodynamics of Polymer Drug Interactions: An Influential Factor for the Development of a Stable Drug Delivery System

Polymer-drug interactions play a pivotal role in the design and optimization of drug delivery systems. Thermodynamic principles, such as enthalpy, entropy and free energy, govern these interactions and significantly influence the stability, efficacy and release profiles of the drug-polymer complexes. In this review we explore the role of thermodynamics in drug-polymer binding, focusing on non-covalent interactions, including van der Waals forces, hydrogen bonding, ionic interactions and hydrophobic effects. These interactions affect the drug encapsulation efficiency, release kinetics and the overall stability of the delivery system. Understanding the balance between the various thermodynamic forces helps in the rational design of advanced drug delivery platforms, such as nanoparticles, micelles and hydrogels, which rely on optimized drug-polymer affinity. Our review further delves into the experimental techniques and modeling approaches used to characterize these interactions, such as isothermal titration calorimetry (ITC), molecular dynamics (MD) simulations and surface plasmon resonance (SPR). By examining these thermodynamic foundations, we believe this article provides insights into developing more efficient and stable drug delivery systems that ensure targeted release, enhanced bioavailability and reduced side effects.