Pi-pi Interactions Research Articles

Functionalized iminodiacetic acid pectin/montmorillonite hydrogel for enhanced adsorption of 4-nitrophenol from simulated water: An integrated approach of response surface optimization and non-linear modeling

This research focuses on the modification of pectin through an amination reaction, followed by the development of a novel iminodiacetic acid-functionalized pectin/montmorillonite hydrogel nanocomposite (IMAP/MMT) using gamma radiation. This composite was investigated as an adsorbent for 4-nitrophenol removal from aqueous solutions. Central composite design was utilized for numerical optimization, identifying the maximum adsorption capacity under optimal conditions [0.8 g/L; 52 min;4 pH, 73 mg/L). A decrease in Qm (330.19 to 273.96 mg/g) with increasing temperature indicated an exothermic adsorption process, supported by the calculated ΔH° value of −28.39 kJ/mol. Analysis of pH, FTIR, and XPS results revealed that the primary mechanisms for 4-nitrophenol uptake include hydrogen bonding, π-π interactions, and n-π interactions. Additionally, the Temkin and D-R isotherms, along with ΔH° values, confirmed the physical nature of the adsorption process, as evidenced by bT (0.70–0.86 kJ/mol) and E (0.74–0.82 kJ/mol) values. The IMAP/MMT composite exhibited superior adsorption selectivity, efficient performance in real water, and good reusability, with a rate of 79.4 % maintained for up to five cycles, highlighting its potential for practical applications as an effective adsorbent. Overall, the findings suggest that IMAP/MMT can serve as an environmentally and economically sustainable material for the removal of 4-nitrophenol from wastewater.

Novel Bis(4-aminophenoxy) Benzene-Based Aramid Copolymers with Enhanced Solution Processability.

Aramid copolymers have garnered significant interest due to their potential applications in extreme environments such as the aerospace, defense, and automotive industries. Recent developments in aramid copolymers have moved beyond their traditional use in high-strength, high-temperature resistant fibers. There is now a demand for new polymers that can easily be processed into thin films for applications such as electrical insulation films and membranes, utilizing the inherent properties of aramid copolymers. In this work, we demonstrate two novel aramid copolymers that are capable of polymerizing in polar organic solvents with a high degree of polymerization, achieved by incorporating flexible bis(4-aminophenoxy) benzene moieties into the chain backbone. The synthesized MBAB-aramid and PBAB-aramid have enabled the fabrication of exceptionally thin, clear films, with an average molecular weight exceeding 150 kDa and a thickness ranging from 3 to 10 μm. The dynamic mechanical analysis (DMA) and thermogravimetric analysis (TGA) reveal that the thin films of MBAB-aramid and PBAB-aramid exhibited glass transition temperatures of 270.1 °C and 292.7 °C, respectively, and thermal decomposition temperatures of 449.6 °C and 465.5 °C, respectively. The mechanical tensile analysis of the 5 μm thick films confirmed that the tensile strengths, with elongation at break, are 107.1 MPa (50.7%) for MBAB-aramid and 113.5 MPa (58.4%) for PBAB-aramid, respectively. The thermal and mechanical properties consistently differ between the two polymers, which is attributed to variations in the linearity of the polymer structures and the resulting differences in the density of intermolecular hydrogen bonding and pi-pi interactions. The resulting high-strength, ultra-thin aramid materials offer numerous potential applications in thin films, membranes, and functional coatings across various industries.

Screening the effective components of Lysionotus pauciflorus Maxim. on the treatment of LPS induced acute lung injury mice by integrated UHPLC-Q-TOF-MS/MS and network pharmacology

Ethnopharmacological relevanceAcute lung injury (ALI) is an inflammatory reaction produced through various injury-causing factors acting on the lungs in a direct or indirect way, with a high morbidity and mortality rate. A review of clinical experience has revealed that Lysionotus pauciflorus Maxim (LP) has a significant therapeutic effect on ALI. However, the comprehensive effective components of LP are uncertain, and the mechanisms, especially the potential therapeutic target for anti-ALI, are still unknown. Aims of the studyIn vitro and in vivo validation of the pharmacodynamics of LP in the treatment of ALI and exploration of its potential mechanism of action based on network pharmacology, molecular docking and experimental validation. Materials and methodsUltra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was employed to identify the ingredients of LP extracts. The potential bioactive ingredients, key targets and signalling pathways were identified by network pharmacology, based on the results of the mass spectrometry analysis. Subsequently, molecular docking was performed on the screened core components and key targets to calculate their molecular binding energies and binding potentials, and to explore the mutual binding modes of small-molecule ligands and large-molecule proteins. Finally, lipopolysaccharide (LPS)-induced RAW264.7 cell model and ALI mice model were used to validate the therapeutic effects and potential mechanism of LP extract towards ALI. ResultsFrom the mass spectrometry results of LP extracts, a total of 89 chemical components were identified, including 46 phenylethanol glycosides, 26 flavonoids, 9 organic acids and their derivatives and 8 other compounds. And furthermore 39 core active components were screened by network pharmacology. The top 10 core components (4 phenylethanol glycosides, 6 flavonoids) have been screened in the composition -target-disease network, and 37 core targets related to LP efficacy were obtained by fitting PPI network analysis. 10 signalling pathways and their targets associated with LP treatment of ALI were obtained by GO/KEGG analysis, indicating that LP could regulate TLR4 and NF-κB signalling pathways through 4 key targets, namely NFKB1, RELA, TLR4 and TNF. The results of the molecular docking procedure indicated a strong affinity, with the binding energies between each component and the target site being less than −6 kcal/mol. The binding modes included Hydrogen Bonds, Pi-Pi interaction, Hydrophobic Interactions, Salt Bridges, Pi-cation interactions. These observations were subsequently validated in vitro and in vivo experiments. The outcomes of in vitro and in vivo experiments demonstrated that LP was effective in reducing the infiltration of inflammatory bacteria in lung tissues and attenuated the expression of pro-inflammatory cytokines in LPS-stimulated mice bronchoalveolar lavage fluid (BALF) and RAW264.7 cells. Furthermore, LP inhibited the expression and phosphorylation of TLR4 protein and NF-κB protein, thus playing a role in the prevention of ALI. ConclusionsIn this study, mass spectrometry analysis was combined with biomolecular networks to initially elucidate the potential of LP to treat ALI by modulating the TLR4/NF-κB pathway. This offers a definitive experimental basis for the development of new LP drugs.

Synthesis and application of novel sodium carboxy methyl cellulose-g-poly acrylic acid carbon dots hydrogel nanocomposite (NaCMC-g-PAAc/ CDs) for adsorptive removal of malachite green dye

This study aimed on synthesizing novel sodium carboxy methyl cellulose-g-poly acrylic acid carbon dots hydrogel nanocomposite (NaCMC-g-PAAc/ CDs) to remove malachite green (MG) dye from aqueous media. The characterisation of functionalities, morphology, particle size and crystallography of NaCMC-g-PAAc/ CDs nanocomposite both before and after adsorption. The results of the characterization analysis revealed the presence of numerous ionic functionalities such as carboxyl, amino and hydroxyl groups in nanocomposite. The morphological study revealed the presence of porosity, heterogenous and amorphous nature of adsorbent favoring the adsorption of MG. Furthermore, elemental analysis also confirmed the presence of carbon and oxygen as main elemental composition of nanocomposite. The temperature of 30 °C and the nanocomposite (having pHPZC of 3) dose of 0.06 g at pH 10 results in achieving 96.92 % of MG dye removal. The experimental data fits closely with pseudo-second and Freundlich models. The enhanced MG dye adsorption by NaCMC-g-PAAc/ CDs was attributed to different mechanisms such as electrostatic or H-bonding as well as pi-pi interactions. Thermodynamically, the studied process was spontaneous and is of endothermic kind. Overall, the study reveals adsorptive property of novel NaCMC-g-PAAc/ CDs nanocomposite as a promising adsorbent for MG dye adsorption from water.

Rapid Iodination Kinetic Studies of o-Toluidine in Aqueous Medium: A Pharmacokinetic Insight from QSAR and Molecular Docking of its Iodo Product with Cytochrome P450

The kinetic data of uncatalyzed rapid iodination of o-toluidine using molecular iodine in aqueous medium was investigated by employing hydrodynamic voltammetry (HV) technique. The frequency factor, activation energy and entropy change accompanying the reaction were evaluated. The reaction followed second order kinetics that had a half-life of 90 s and specific reaction rate 888.87 M s–1 at 22.1 ºC. The iodo product was formed via the green route in the aqueous solvent. The physico-chemical characteristics, lipophilicity, water solubility and pharmacokinetic parameters were derived by QSAR analysis. The docking of the iodo product with cytochrome P450 exhibited steric and physiological complementarity of the ligand-protein interface through hydrogen bonding and pi-pi stacking interactions, indicating that the product exhibited metabolic activity was similar to the existing drugs.

Novel triazole-nucleoside hybrids as potential antimicrobial agents: Design, synthesis, and molecular docking

Despite decoding many important genes in the formation of microbes, particularly pathogenic and mutant ones that lead to resistance to a wide range of antibiotics, this opens the door to discovering new antimicrobial compounds, whether synthetic or natural in origin. A new set of nucleoside-triazole hybrids was created to provide a more effective topoisomerase II for microbial therapy. All freshly synthesized compounds' structures were confirmed using spectral data and elemental analysis. The newly synthesized compounds were docked to the area of topoisomerase II's active site; compounds 3, 7, 15, 18, and 19 exhibited distinct hydrogen bonding formation and pi-pi interactions. The results of testing every compound against six different microbial strains were expressed as the width of the inhibitory zone.Except for Aspergillus Niger, most of the synthetic compounds inhibit all bacteria. Compounds 15 and 19 had the lowest MIC values (1.95, 3.9 µg/mL against B. subtills and 1.95, 3.9 µg/mL against S. aureus). Nucleoside 15 had MBC values between 3.9 and B. subtills. The in-vitro topoisomerase II enzyme assay revealed that compounds 3, 15, 18, and 19 had IC50 values of 0.17, 0.05, 0.13, and 0.08 µmol/mL, respectively. A transmission electron microscope (TEM) was utilized to assess morphological changes on the bacterial surface following treatment with nucleoside 15. It was discovered that nucleoside 15 induced substantial cell wall weakening, which exacerbated cell membrane rupture.

Identification of potential inhibitors against Corynebacterium diphtheriae MtrA response regulator protein; an in-silico drug discovery approach

Corynebacterium diphtheriae is a multi-drug resistant bacteria responsible for the life-threatening respiratory illness, diphtheria which can lead to severe Nervous system disorders, mainly infecting the lungs, heart, and kidneys if left untreated. In the current study, Corynebacterium diphtheriae MtrA response regulator protein was targeted, which regulates a two-component system of bacterial pathogenesis, and initiates DNA replication and cell division. In the current study a computational approach have been described for drug development against C. diphtheriae infections by inhibiting MtrA protein by small molecules acting as potential inhibitors against it. Molecular docking analysis of the equilibrated MtrA protein revealed compound-0.2970, compound-0.3029, and compound-0.3016 from Asinex Library as the promising inhibitors based on their lowest binding energies (−9.8 kJ/mol, −9.2 kJ/mol, and −8.9 kJ/mol), highest gold scores (40.53, 47.41, and 48.41), drug-likeness and pharmacokinetic properties. The MD simulation studies of the identified top-ranked inhibitors at 100 ns elucidated the system stability and fluctuations in the binding pocket of MtrA protein. Molecular Dynamics Simulations of the top three docked complexes further revealed that the standard binding pocket was retained ensuring the system stability. The rearrangements of H-bonds, van der Waals, pi-pi, and solid hydrophobic interactions were also observed. The binding free energy calculations (MM/PBSA and MM/GBSA) suggested a fundamental binding capability of the ligand to the target receptor MtrA. Therefore, the current study has provided excellent candidates acting as potent inhibitors for developing therapeutic drugs against C. diphtheriae infections. However, in vivo and in vitro animal experiments and accurate clinical trials are needed to validate the potential inhibitory effect of these compounds.

(Invited) Developing a Graphene Field-Effect Biosensor for Genetic Biomarkers: Simulations Unveil How the Device Sensitivity Is Related to DNA-Graphene Interactions at the Nanoscale

Graphene field-effect transistor biosensors (GFETs) offer a promising platform to detect cancer DNA biomarkers at low concentration [1]. At their core, they have an electronic circuit containing a graphene sheet – a two-dimensional nanomaterial made of a single layer of carbon atoms – whose electronic properties are very sensitive to nearby electric charges. Leveraging that feature, the electrical current generated by a GFET can thus be made very sensitive to the concentration of a specific DNA sequence in a biological sample. To achieve this, the complementary DNA sequence is linked to the graphene to bind specifically the target DNA. In most GFETs, the link is done using 1-pyrenebutanoic acid succinimidyl ester (PBASE) because its pyrene group stacks on the graphene through pi-pi interactions, without disrupting the electronic properties of the graphene. However, recent experiments in the Bouilly group have shown variations in GFET sensitivity depending on the incubation time of graphene with PBASE.Here, we use a computational approach developed in our previous work [2] to investigate at the nanoscale the role of PBASE linker molecules on the sensitivity of the GFET. First, we use molecular dynamics simulations to characterize the conformational ensemble of a 10-nt single-stranded DNA sequence linked to a graphene sheet using PBASE. Second, we estimate the electrical response of the GFET from the electrostatic potential generated by these DNA conformations on the graphene, as determined using electrostatic Poisson-Boltzmann simulations. Our results show that the conformational ensemble of DNA is strongly affected by the presence of other PBASE adsorbed on the graphene, thus changing the electrostatic potential generated on the graphene. The predicted change of the electrostatic potential should impact measurably the detection signal of the GFET.We are now using these simulations to explain the experimental characterizations of a GFET designed to detect a genetic biomarker important in breast cancer profiling. Our simulations have the potential to support the development of GFETs with better sensitivity for DNA detection.[1] Béraud, A., Sauvage, M., Bazán, C. M., Tie, M., Bencherif, A., and Bouilly, D. (2021) Graphene field-effect transistors as bioanalytical sensors: design, operation and performance. Analyst. 146:403-428.[2] Côté, S., Mousseau, N., and Bouilly, D. (2022) The molecular origin of the electrostatic gating of single-molecule field-effect biosensors investigated by molecular dynamics simulations. Phys. Chem. Chem. Phys. 24:4174-4186.

Mechanistic Insights into How the Single Point Mutation Change the Autoantibody Repertoire.

A recent study showed that just one point mutation F33 to Y in the complementarity-determining region 1 of heavy chain (H-CDR1) could lead to the auto-antibody losing its DNA binding ability. However, the potential molecular mechanisms have not been well elucidated. In this study, we investigated how the antibody lost the DNA binding ability caused by mutation F33 to Y in the H-CDR1. We found that the electrostatic force was not the primary driving force for the interaction between anti-DNA antibodies and the antigen single strand DNA (ssDNA), and that the H-CDR2 largely contributed to the binding of antigen ssDNA, even larger than H-CDR1. The H-F33Y mutation could increase the hydrogen-bond interaction but impair the pi-pi stacking interaction between the antibody and ssDNA. We further found that F33H, W98H and Y95L in the wiletype antibody could form the stable pi-pi stacking interaction with the nucleotide bases of ssDNA. However, the Y33 in mutant could not form the parallel sandwich pi-pi stacking interaction with the ssDNA. To further confirm the importance of pi-pi stacking, the wildtype antibody and the mutants (F33YH, F33AH, W98AH and Y95AL) were experimentally expressed in CHO cells and purified, and the results from ELISA clearly showed that all the mutants lost the ssDNA binding ability. Taken together, our findings may not only deepen the understanding of the underlying interaction mechanism between autoantibody and antigen, but also broad implications in the field of antibody engineer.

Integration of High-Resolution LC-Q-TOF Mass Spectrometry and Multidimensional Chemical-Biological Analysis to Detect Nanomolar-Level Acetylcholinesterase Inhibitors from Different Parts of Zanthoxylum nitidum.

Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer's disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 μM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer's disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.

Investigation of Antioxidant Mechanisms of Novel Peptides Derived from Asian Swamp Eel Hydrolysate in Chemical Systems and AAPH-Induced Human Erythrocytes.

Sixteen novel antioxidant peptides from Asian swamp eel (ASE) were identified in previous studies. However, their chemical and cellular antioxidant mechanisms remain unclear. Molecular docking of these peptides with ABTS and DPPH radicals revealed the critical role of hydrogen bonding and Pi-Pi stacking hydrophobic interactions between hydrophobic amino acid residues and free radicals. Residues, such as tryptophan, proline, leucine, and valine, played significant roles in these interactions. All these peptides exhibited notable erythrocyte morphoprotective effects in a model of AAPH-induced oxidative damage of human erythrocytes. Erythrocyte hemolysis was reduced primarily through the modulation of both non-enzymatic (GSH/GSSG) and enzymatic antioxidant systems (SOD, CAT, and GSH-Px) by these peptides. A decrease in levels of MDA, LDH release, and hemoglobin oxidation was observed. Among the peptides, VLYPW demonstrated superior chemical and cellular antioxidant activities, which may be attributed to its higher levels of tyrosine and tryptophan, as well as to its increased hydrophobic amino acid content.

Remarkable enhancement in radio-cesium uptake from acidic feeds into an extraction chromatography resin containing a calix[4]arene-mono-crown-6 ligand

An extraction chromatography resin, prepared by the impregnation of bis-octyloxy-calix[4]arene-mono-crown-6 (BOCMC)onto an acrylic ester based polymeric support material, gave excellent uptake data for the removal of radio-cesium (Cs-137) from nitric acid feed solutions. The weight distribution coefficient (Kd) value of >300 obtained during the present study at 3 M HNO3 was the highest reported so far while using a calix-crown-6 based extraction chromatographic resin material. Analogous resin reported previously has yielded a Kd value <100 at comparable feed conditions. The sorbed metal ions could be efficiently desorbed with de-ionized water. Kinetic modeling of the uptake data indicated that both the film and the intra-particle diffusion mechanism are simultaneously operating in the sorption of Cs+ion onto the BOCMC resin. The metal ion sorption data were fitted to the sorption isotherm models and did not conform to the chemisorptions of physisorption models and indicated a pi-pi interaction between the benzene rings of the calix-crown-6 ligand and the Cs+ ion. The reusability of the resins was quite satisfactory after 5 cycles and the radiation stability of the resin material was very good upto an absorbed dose of 500 kGy. The results of column studies were quite encouraging with 15 mL (9 bed volumes) as the breakthrough volume while the elution was complete in about 12 bed volumes of de-ionized water.

LC-MS/MS profiling and analysis of Bacillus licheniformis extracellular proteins for antifungal potential against Candida albicans

Candida albicans, a significant human pathogenic fungus, employs hydrolytic proteases for host invasion. Conventional antifungal agents are reported with resistance issues from around the world. This study investigates the role of Bacillus licheniformis extracellular proteins (ECP) as effective antifungal peptides (AFPs). The aim was to identify and characterize the ECP of B. licheniformis through LC-MS/MS and bioinformatics analysis. LC-MS/MS analysis identified 326 proteins with 69 putative ECP, further analyzed in silico. Of these, 21 peptides exhibited antifungal properties revealed by classAMP tool and are predominantly anionic. Peptide-protein docking revealed interactions between AFPs like Peptide chain release factor 1 (Q65DV1_Seq1: SASEQLSDAK) and Putative carboxy peptidase (Q65IF0_Seq7: SDSSLEDQDFILESK) with C. albicans virulent SAP5 proteins (PDB ID 2QZX), forming hydrogen bonds and significant Pi-Pi interactions. The identification of B. licheniformis ECP is the novelty of the study that sheds light on their antifungal potential. The identified AFPs, particularly those interacting with bonafide pharmaceutical targets SAP5 of C. albicans represent promising avenues for the development of antifungal treatments with AFPs that could be the pursuit of a novel therapeutic strategy against C. albicans. Significance of studyThe purpose of this work was to carry out proteomic profiling of the secretome of B. licheniformis. Previously, the efficacy of Bacillus licheniformis extracellular proteins against Candida albicans was investigated and documented in a recently communicated manuscript, showcasing the antifungal activity of these proteins. In order to achieve high-throughput identification of ES (Excretory-secretory) proteins, the utilization of liquid chromatography tandem mass spectrometry (LC-MS) was utilized. There was a lack of comprehensive research on AFPs in B. licheniformis, nevertheless. The proteins secreted by B. licheniformis in liquid medium were initially discovered using liquid chromatography-tandem mass spectrometry (LC-MS) analysis and identification in order to immediately characterize the unidentified active metabolites in fermentation broth.

Efficient removal of ciprofloxacin from aqueous solution using Zn–C battery derived graphene oxide enhanced by hydrogen bonding, electrostatic and π-π interaction

In this study, graphene oxide (GO) derived from waste Zinc–Carbon (Zn–C) batteries was proposed for the efficient removal of antibiotics from the aqueous solution. Ciprofloxacin (CIP) antibiotic was selected as a typical contaminants. GO was prepared via an economical and environment-friendly route by using carbon rods from waste Zn–C batteries as the precursor. Characterization techniques were applied to determine the properties of as prepared GO. Effects of pH, contact time, and adsorbent dose on the adsorption were explored, and an optimum condition was established. Adsorption equilibrium was established in just 20 min for maximum removal of CIP (99.0%) at pH 5.7 for the adsorbent dose of 20 mg L−1 and at the initial concentration of CIP 2.0 mg L−1. The rapid and efficient removal of CIP was greatly influenced by the electrostatic attractions, pi-pi interactions and hydrogen bonding on the surface and edge of GO which was also proved by density functional theory (DFT). Langmuir model showed the best fit among the isotherm models and the calculated maximum adsorption capacity (qm) was 419.62 mg g−1 at 30°C. The kinetic studies also revealed that the adsorption process followed the pseudo-second-order model. The endothermic and spontaneous nature of adsorption was evaluated in thermodynamic studies.

Miracle in "White":Hexagonal Boron Nitride.

The exploration of 2D materials has captured significant attention due to their unique performances, notably focusing on graphene and hexagonal boron nitride (h-BN). Characterized by closely resembling atomic structures arranged in a honeycomb lattice, both graphene and h-BN share comparable traits, including exceptional thermal conductivity, impressive carrier mobility, and robust pi-pi interactions with organic molecules. Notably, h-BN has been extensively examined for its exceptional electrical insulating properties, inert passivation capabilities, and provision of an ideal ultraflat surface devoid of dangling bonds. These distinct attributes, contrasting with those of h-BN, such as its conductive versus insulating behavior, active versus inert nature, and absence of dangling surface bonds versus absorbent tendencies, render it a compelling material with broad application potential. Moreover, the unity of such contradictions endows h-BN with intriguing possibilities for unique applications in specific contexts. This review aims to underscore these key attributes and elucidate the intriguing contradictions inherent in current investigations of h-BN, fostering significant insights into the understanding of material properties.

Computational analysis of missense mutations in dystrophin protein: Insights into domain-specific effects and functional implications

BackgroundDystrophin is a structural protein primarily found in skeletal muscles that connects trans-membrane component of dystrophin-glycoprotein complex to the intracellular cytoskeleton network. N-terminal domain of dystrophin binds to F-actin and its C-terminal domain attaches to dystrophin-associated complex (DAG) in the membrane. It serves as the bridge connecting the extracellular matrix to the actin based cytoskeleton of muscle cells across the plasma membrane. This complex works together to strengthen muscle fibers and shield them from damage as they contract and relax. ObjectiveOur Objective is to investigate the different pathogenic mutations in four distinct domains of dystrophin protein and to decipher how these mutations impact protein structure and function. In this study, we investigated the impact of disease causing missense mutations in isoforms of dystrophin – P.11532–1 (K18N.A165V, D3187G, F3228L); P11532–4 (Y223N, D3179G) and P-11532-11 (Y227N,D3183G).Occurrence of pathogenic mutations in dystrophin might compromise structural stability, interfere with protein-protein interactions or alter cellular signaling pathways collectively. All these can contribute to the progressive muscle degeneration observed in Duchene or Becker muscular dystrophy(DMD or BMD) and X-lined dilated cardiomyopathy(CMD3B) affected individuals. MethodsEvolutionary conservation analysis using multiple sequence alignment followed by pathogenicity prediction using web based server was performed. Homology modeling of mutants was performed bySWISS MODEL a fully automated homology-modeling server, accessible through the Expasy web server. These models were then analyzed using various servers such as Dynamut. Pymol was used for visualization and structural analysis. ResultsAnalyzed mutations cause structural instability by either gaining or losing specific interactions involved in the folding of protein. Loss of pi-pi stacking interactions has the potential to significant impact the overall stability of the protein. It is important to note that the majority of the mutations lead to stability defects rather than functional defects, ultimately contributing to different forms of muscular dystrophy. ConclusiónThe mutations in different domains of Dystrophin protein significantly alters the protein structure. This may in turn impact its ability to interact with other proteins. Understanding the specific impacts of these mutations can pave the way for development of targeted therapies that aims at restoring functionality of dystrophin and ameliorating the debilitating effects of muscular dystrophy.

Controlled Molecular Arrangement of Cinnamic Acid in Layered Double Hydroxide through pi-pi Interaction for Controlled Release.

Cinnamic acid (CA) was successfully incorporated into Zn-Al layered double hydroxide (LDH) through coprecipitation. The CA moiety was stabilized in the interlayer space through not only electrostatic interaction but also intermolecular π-π interaction. It was noteworthy that the CA arrangement was fairly independent of the charge density of LDH, showing the important role of the layer-CA and CA-CA interactions in molecular stabilization. Computer simulations using the Monte Carlo method as well as analytical approaches including infrared, UV-vis spectroscopy, and differential scanning calorimetry showed the existence of intermolecular interaction. In order to reinforce molecular stabilization, a neutral derivative of CA, cinnamaldehyde (CAD), was additionally incorporated into LDH. It was clearly shown that CAD played a role as a π-π interaction mediator to enhance the stabilization of CA. The time-dependent release of CA from LDH was first governed by the layer charge density of LDH; however, the existence of CAD provided additional stabilization to the CA arrangement to slow down the release kinetics.

Sustainable Bio-Based Adsorbents for Simultaneous and Efficient Removal of Hazardous Dyes from Aqueous Solutions.

Dyes provide a notable environmental issue as a result of their intrinsic poisonous and carcinogenic characteristics. An estimated 60,000 metric tons of dyes has been discharged into the environment, leading to a substantial increase in water pollution. The mitigation of these dyes is a substantial and intricate challenge. The primary objective of this research is to conduct a comprehensive analysis of the adsorption of cationic dyes containing positively charged groups such as sulphonates, amines, and triphenylmethanes. The adsorption study was carried out using four different low-cost adsorbents derived from biowaste, specifically Groundnut Shell (GS), Mosambi Peel (MP), Mango Bark (MBARK), and Mango Leaves (ML). The adsorbent materials were characterized using FTIR, UV-Vis spectroscopy, scanning electron microscopy (SEM), point-of-zero charge (PZC), and BET techniques. The adsorption capacity was found to be between 1.5 and 2.2 mg/gm for Groundnut Shell, Mosambi Peel, Mango Bark, and Mango Leaves for individual dye removal (Crystal violet, Methylene blue, Rhodamine B, and Malachite green). It was observed that adsorbent derived from mango bark showed excellent adsorption (%) in a mono-component dye system and, thus, was explored for the simultaneous removal of a mixture of the same dyes. MBARK exhibited an excellent overall dye removal efficiency of 94.44% (Qe = 2.7 mg/g) for the dye mixture in 60 min. From a detailed kinetic investigation, it was concluded that the adsorption followed the pseudo-second-order model (R2= 0.99963 to 1 for different dyes and adsorbents) hinting at chemisorption. The effect of the pH of the analyte solution and the dosage of adsorbent was also studied for simultaneous removal. The isothermal studies demonstrated that the Langmuir adsorption model (R2 = 0.99416) was the best-fitted model, suggesting monolayer adsorption. The adsorption process was predicted to be governed by ion exchange, electrostatic interaction, hydrogen bonding, pi-pi interaction, etc., based on charge, functional groups, and pH of dyes and adsorbent. Thus, this study highlights the application of low-cost biowaste as a potential adsorbent for the mitigation of toxic industrial dyes present in wastewater.

Natural compound plumbagin based inhibition of hIAPP revealed by Markov state models based on MD data along with experimental validations.

Human islet amyloid polypeptide (amylin or hIAPP) is a 37 residue hormone co-secreted with insulin from β cells of the pancreas. In patients suffering from type-2 diabetes, amylin self-assembles into amyloid fibrils, ultimately leading to the death of the pancreatic cells. However, a research gap exists in preventing and treating such amyloidosis. Plumbagin, a natural compound, has previously been demonstrated to have inhibitory potential against insulin amyloidosis. Our investigation unveils collapsible regions within hIAPP that, upon collapse, facilitates hydrophobic and pi-pi interactions, ultimately leading to aggregation. Intriguingly plumbagin exhibits the ability to bind these specific collapsible regions, thereby impeding the aforementioned interactions that would otherwise drive hIAPP aggregation. We have used atomistic molecular dynamics approach to determine secondary structural changes. MSM shows metastable states forming native like hIAPP structure in presence of PGN. Our in silico results concur with in vitro results. The ThT assay revealed a striking 50% decrease in fluorescence intensity at a 1:1 ratio of hIAPP to Plumbagin. This finding suggests a significant inhibition of amyloid fibril formation by plumbagin, as ThT fluorescence directly correlates with the presence of these fibrils. Further TEM images revealed disappearance of hIAPP fibrils in plumbagin pre-treated hIAPP samples. Also, we have shown that plumbagin disrupts the intermolecular hydrogen bonding in hIAPP fibrils leading to an increase in the average beta strand spacing, thereby causing disaggregation of pre-formed fibrils demonstrating overall disruption of the aggregation machinery of hIAPP. Our work is the first to report a detailed atomistic simulation of 22 μs for hIAPP. Overall, our studies put plumbagin as a potential candidate for both preventive and therapeutic candidate for hIAPP amyloidosis.

Variable Mechanical Properties in Layered Copper Bromide Hybrid Solids Based on Configuration of Organic Cations.

Organic-inorganic organohalide hybrid solids have garnered significant attention due to their unique structural diversity, desirable electronic structures, and excellent optoelectronic properties. Here, we investigate the mechanical properties of a homologous series of 2D copper bromide hybrids (A2CuBr4, ACuBr4) through nanoindentation to analyze the contribution of organic interlayer interactions to bulk mechanical response. We identify a direct correlation between the identity of the organic spacer and the bulk mechanical response, where stronger bonding interactions in the organic interlayer resulted in increased hardness and elasticity. Additionally, we uncover a unique conformational dependence within the series of arylammonium spacers which was found to periodically modulate pi-pi interactions between neighboring molecules, leading to an alternating even-odd bulk material response.