Quantum Mechanical Analysis Research Articles

A digital platform for automated analysis of 1H NMR data: prototype framework of digital reference standard

This study introduces an innovative approach to automatically analyzing 1H nuclear magnetic resonance (NMR) data, integrating a quantum mechanical spectral analysis (QMSA) to enhance efficiency over manual data analysis in NMR. This proposed digital platform features a standardized quantitative NMR (qNMR) procedure, digital Reference Spectra within a spectral library, and a visualized interactive interface for streamlined, automated NMR data analysis. This digital platform significantly reduces the need for manual intervention and shows promise in using spectral fitting to compare the calculated spectrum derived from a digital Reference Spectrum with an experimental spectrum. The digital platform excels in processing data of both single chemical and mixture, delivering accurate results, and positioning it as an essential tool for automatic 1H qNMR analyses. Case studies highlight the digital platform’s effectiveness, demonstrating its wide-ranging applicability. This shows that the proposed digital platform, based on a qNMR-based QMSA approach, offers reliable qualitative and quantitative analyses and paves the way for integrating digital reference standards into future compendial tests.Graphical

Examining Prenylated Xanthones as Potential Inhibitors Against Ketohexokinase C Isoform for the Treatment of Fructose-Driven Metabolic Disorders: An Integrated Computational Approach.

Background/Objectives: Fructose-driven metabolic disorders, such as obesity, non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and type 2 diabetes, are significant global health challenges. Ketohexokinase C (KHK-C), a key enzyme in fructose metabolism, is a promising therapeutic target. α-Mangostin, a naturally occurring prenylated xanthone, has been identified as an effective KHK-C inhibitor, prompting exploration of its analogs for enhanced efficacy. This study aimed to identify α-Mangostin analogs with improved inhibitory properties against KHK-C to address these disorders. Methods: A library of 1383 analogs was compiled from chemical databases and the literature. Molecular docking, binding free energy calculations, pharmacokinetic assessments, molecular dynamics simulations, and quantum mechani-cal analyses were used to screen and evaluate the compounds. α-Mangostin's binding affinity (37.34 kcal/mol) served as the benchmark. Results: Sixteen analogs demonstrated binding affinities superior to α-Mangostin (from -45.51 to -61.3 kcal/mol), LY-3522348 (-45.36 kcal/mol), and reported marine-derived inhibitors (from -22.74 to -51.83 kcal/mol). Hits 7, 8, 9, 13, and 15 not only surpassed these benchmarks in binding affinity, but also exhibited superior pharmacokinetic properties compared to α-Mangostin, LY-3522348, and marine-derived inhibitors, indicating strong in vivo potential. Among these, hit 8 emerged as the best performer, achieving a binding free energy of -61.30 kcal/mol, 100% predicted oral absorption, enhanced metabolic stability, and stable molecular dynamics. Conclusions: Hit 8 emerged as the most promising candidate due to its superior binding affinity, favorable pharmacokinetics, and stable interactions with KHK-C. These findings highlight its potential for treating fructose-driven metabolic disorders, warranting further experimental validation.

Hyperthermophilic xylanase and thermophilicity analysis by molecular dynamic simulation with quantum mechanics

Thermophilic xylanases catalyzing the cleavage of β-1,4-glycosidic bonds in xylan have applications in food, feed, biorefinery, and pulp industries. In this study, a hyperthermophilic endo-xylanase was obtained by further enhancement of thermal tolerance of a thermophilic GH11 xylanase originated from metagenome of bagasse pile based on rational design. Introducing N13F and Q34L to the previously reported X11P enzyme shifted the optimal working temperature to 85 °C and led to 20.7-fold improvement in thermostability at 90 °C along with a marked increase in Tm to 93.3 °C. X11PNQ enzyme converted xylan to prebiotic xylooligosaccharides with high specificity on xylobiose to xylohexaose and high operational stability at 85 °C, resulting in 10.3-folds yield improvement compared to the parental enzyme. Molecular dynamic simulation and quantum mechanical analysis revealed improved H-bonding networks within GH11 xylanase principal domains and greater dynamic cross-correlations. A novel thermostabilization mechanism by π-amide interaction with slightly lower interaction energy than the native H-bond, but compensated by increased occurrence frequency was firstly demonstrated for thermophilic enzymes. The enzyme represents one of the most thermostable xylanases ever reported with biotechnological potential.Key points• Hyperthemophilic xylanase X11PNQ was obtained by rational design engineering.• X11PNQ showed specificity to prebiotic xylooligosaccharides (XOS) at 85 °C with improved t1/2 at 90 °C.• Novel thermostabilization by π-amide interaction was demonstrated by MD/QM.

Comparative Study on the Antioxidative Effects and α-Glucosidase Inhibitory Potential In Vitro among Ellagic Acid and Its Metabolites Urolithins.

The current study compared the radical scavenging and α-glucosidase inhibition potentials of ellagic acid (EA) and its metabolites, urolithins (Uros), and further explored the structure-activity relationship. The outcomes indicated that urolithin M5 (Uro-M5), EA, and urolithin M6 (Uro-M6) exhibited superior 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity; EA and urolithin D (Uro-D) expressed better ABTS scavenging ability, and EA and Uro-M5 showed preferable α-glucosidase inhibition activity. The results of CD spectra and fluorescence spectral analysis explained the interaction between Uros and α-glucosidase. Correlation analysis indicated that hydroxyl groups were crucial for the antioxidative effect, while C-8 OH contributed greatly to the α-glucosidase inhibition activity. Quantum mechanical analysis showed that both EA and Uros exhibited strong electrophilic properties. These comparative results showed a biological discrepancy between Uros and provided essential information for exploring the bioactive application of EA as a functional ingredient or dietary supplement.

Nature of the EWS-FLI1 Oncoprotein.

The research presented in this paper focuses on the EWS-FLI1 oncoprotein, a critical factor in Ewing sarcoma, a rare and lethal cancer primarily affecting children and young adults. Through molecular dynamics and quantum mechanics analyses, the study explores the reactivity properties of six snapshots of the EWS-FLI1 oncoprotein, aiming to contribute to the development of targeted therapies. The investigation emphasizes the significance of understanding the molecular behavior of EWS-FLI1 for effective treatment development, utilizing computational methods such as density functional theory. The findings suggest that EWS-FLI1 is a compact, electrophilic protein with localized reactive sites, providing valuable insights for potential drug development and enhancing our knowledge of Ewing sarcoma for targeted treatments.

High-Order B-Spline Finite Difference Approach for Schrodinger Equation in Quantum Mechanics

This paper presents a new numerical method for solving the quantum mechanical complex-valued Schrodinger equation (CSE). The technique combines a second-order Crank-Nicolson scheme based on the finite element method (FEM) for temporal discretisation with nonic B-spline functions for spatial discretisation. This method is unconditionally stable with the help of Von-Neumann stability analysis. To verify our methodology, we examined an experiment utilising a range of error norms to compare experimental outcomes with analytical solutions. Our investigation verifies that the suggested approach works better than current methods, providing better accuracy and efficiency in quantum mechanical error analysis.

Exploring Novel GSK-3β Inhibitors for Anti-Neuroinflammatory and Neuroprotective Effects: Synthesis, Crystallography, Computational Analysis, and Biological Evaluation.

In the pathogenesis of Alzheimer's disease, the overexpression of glycogen synthase kinase-3β (GSK-3β) stands out due to its multifaced nature, as it contributes to the promotion of amyloid β and tau protein accumulation, as well as neuroinflammatory processes. Therefore, in the present study, we have designed, synthesized, and evaluated a new series of GSK-3β inhibitors based on the N-(pyridin-2-yl)cyclopropanecarboxamide scaffold. We identified compound 36, demonstrating an IC50 of 70 nM against GSK-3β. Subsequently, through crystallography studies and quantum mechanical analysis, we elucidated its binding mode and identified the structural features crucial for interactions with the active site of GSK-3β, thereby understanding its inhibitory potency. Compound 36 was effective in the cellular model of hyperphosphorylated tau-induced neurodegeneration, where it restored cell viability after okadaic acid treatment and showed anti-inflammatory activity in the LPS model, significantly reducing NO, IL-6, and TNF-α release. In ADME-tox in vitro studies, we confirmed the beneficial profile of 36, including high permeability in PAMPA (Pe equals 9.4) and high metabolic stability in HLMs as well as lack of significant interactions with isoforms of the CYP enzymes and lack of considerable cytotoxicity on selected cell lines (IC50 > 100 μM on HT-22 cells and 89.3 μM on BV-2 cells). Based on promising pharmacological activities and favorable ADME-tox properties, compound 36 may be considered a promising candidate for in vivo research as well as constitute a reliable starting point for further studies.

Conformational and Substitution Effects on the Donor and Reducing Strength of Tin(II) Porphyrinogens.

Meso-octaalkylcalix[4]pyrrolates are a class of redox-active porphyrinogen ligands. They have been well established in d- and f-block chemistry for over three decades but have only recently been introduced as ligands for p-block elements. Here, we present a study on the influence of meso-substituents on the redox chemistry of calix[4]pyrrolato stannate(II) dianions [2R]2- (R=Me, Et). Expansion of the normal-mode structural decomposition (NSD) method, well known for porphyrin chemistry, provides insights into the ligand conformation of a calix[4]pyrrolato p-block complex. Combined with the results of spectroscopic donor scaling, electrochemical studies, and quantum mechanical bond analysis tools, subtle but significant substitution and conformational effects on the electronic structure are revealed. Exploiting this knowledge rationalizes the role of this class of tin(II) dianions to act as potent reducing agents, but can also be expanded for other central elements. Photoexcitation boosts this reactivity further, allowing for the reduction of even challenging chlorobenzene.

Quantum mechanical analysis of yttrium-stabilized zirconia and alumina: implications for mechanical performance of esthetic crowns

BackgroundYttrium-stabilized zirconia (YSZ) and alumina are the most commonly used dental esthetic crown materials. This study aimed to provide detailed information on the comparison between yttrium-stabilized zirconia (YSZ) and alumina, the two materials most often used for esthetic crowns in dentistry.MethodologyThe ground-state energy of the materials was calculated using the Cambridge Serial Total Energy Package (CASTEP) code, which employs a first-principles method based on density functional theory (DFT). The electronic exchange–correlation energy was evaluated using the generalized gradient approximation (GGA) within the Perdew (Burke) Ernzerhof scheme.ResultsOptimization of the geometries and investigation of the optical properties, dynamic stability, band structures, refractive indices, and mechanical properties of these materials contribute to a holistic understanding of these materials. Geometric optimization of YSZ provides important insights into its dynamic stability based on observations of its crystal structure and polyhedral geometry, which show stable configurations. Alumina exhibits a distinctive charge, kinetic, and potential (CKP) geometry, which contributes to its interesting structural framework and molecular-level stability. The optical properties of alumina were evaluated using pseudo-atomic computations, demonstrating its responsiveness to external stimuli. The refractive indices, reflectance, and dielectric functions indicate that the transmission of light by alumina depends on numerous factors that are essential for the optical performance of alumina as a material for esthetic crowns. The band structures of both the materials were explored, and the band gap of alumina was determined to be 5.853 eV. In addition, the band structure describes electronic transitions that influence the conductivity and optical properties of a material. The stability of alumina can be deduced from its bandgap, an essential property that determines its use as a dental material. Refractive indices are vital optical properties of esthetic crown materials. Therefore, the ability to understand their refractive-index graphs explains their transparency and color distortion through how the material responds to light..The regulated absorption characteristics exhibited by YSZ render it a highly attractive option for the development of esthetic crowns, as it guarantees minimal color distortion.ConclusionThe acceptability of materials for esthetic crowns is strongly determined by mechanical properties such as elastic stiffness constants, Young's modulus, and shear modulus. YSZ is a highly durable material for dental applications, owing to its superior mechanical strength.

Quantum mechanical approaches and molecular docking analysis of platinum metal-based anticancer drugs Lobaplatin and Heptaplatin targeting cancer DNA - a comparative analysis

The structural analysis and chemical reactivity of Lobaplatin and Heptaplatin were done using Spectral analysis, NBO analysis, and Global Chemical Reactivity and HOMO-LUMO values obtained using Density functional theory(DFT). Molecular Docking studies were performed for the drug compounds with DNA structure, Lung cancer, Gastric cancer, and Ovarian cancer cell structures. The obtained binding affinity results were compared and can be concluded that Hepataplatin shows the Lowest binding energy values with DNA structure followed by Lobaplatin than cisplatin and Lobaplatin shows good docking affinity towards Cancer cell structure comparatively. Lobaplatin and Heptaplatin were found to be highly interactive anticancer drug compounds.

Quantum mechanical analysis of halogen-based ionic liquid crystal [C12MIM.X(where X = Cl, Br)] molecules

ABSTRACT The electrical and non-linear optical characteristics of 1-dodecyl 3-methyl-imidazolium chloride (C12MIM.Cl or DDMIM.Cl) and 1-dodecyl 3-methyl-imidazolium bromide (C12MIM.Br or DDMIM.Br) ionic liquid crystals for optoelectronic devices were investigated in this study utilising B3LYP method and 6-311++G(d,p) basis set with Gaussian09 software. The majority of ionic liquid crystal research to date has been experiment-driven, with very few theoretical studies on the material's optical characteristics. Additional understanding of the behaviour of ionic liquid crystals is revealed through molecular spectroscopic research. The electronic properties (molecular energy band gap, electrostatic potential map and HOMO–LUMO orbitals) and spectroscopic (IR, UV) characteristics were assessed with the aid of a theoretical/computational model at B3LYP/6-311++G(d,p), whereas a nonlinear optical (NLO) study was carried out using the B3LYP and M06-2X methods with 6-31G(d) and 6-311++G(d,p) basis sets. Results demonstrate reasonable nonlinear optical characteristics in these molecules.

Exploring nonlinear and linear optical properties of N, N’-bis(salicylidene)-o-phenylenediamine (salophen) through Z-scan technique and TD-DFT computational analysis

This investigation delves into the comprehensive analysis of the linear and nonlinear optical characteristics exhibited by N, N’-bis(salicylidene)-o-phenylenediamine (salophen) using a combination of Z-scan methodology and quantum chemistry calculations. The Z-scan technique facilitated meticulous computations of the third-order susceptibility, nonlinear absorption coefficient, and nonlinear refractive index of the specimen. Specifically, in the solvent DMSO, the assessed values for the nonlinear refractive index, nonlinear absorption coefficient, and third-order susceptibility were determined to be 0.035 × 10–10 cm2 W −1 , −0.024 × 10–5 cm W −1 , and 0.596 × 10–5 esu, respectively. Furthermore, quantum mechanical analyses were employed to meticulously calculate the molecular hyperpolarizabilities (β and γ), dipole moment (μ), and dipole polarizability (α) of salophen. This thorough exploration highlighted a notable congruence between the outcomes derived from experimental observations and those obtained through quantum mechanical simulations. The collective findings from both theoretical computations and experimental assessments distinctly showcase the robust nonlinear potential inherent in salophen. These insights suggest its promising suitability and potential as a viable candidate for applications in optical devices. The alignment between theoretical predictions and experimental results underlines the reliability and potential practicality of salophen in the realm of optical technology, emphasizing its significance as a potential material for advancing optical device functionalities.

Empirical analysis of quantum mechanics and harmonic applications

A brief review of the main ideas (interpretations) of quantum mechanics is given. Each of the considered interpretations contains a number of disputable provisions, the discussion of which allows us to develop our own understanding of the mechanism of paradoxical quantum phenomena. The article is addressed to all students who study the concepts of modern natural science, and to all readers interested in the questions what is the reality beyond the quantum mechanical experiment or if our perception really shapes the physical world in some way. The author believes that the development of quantum information technologies is impossible without answering these fundamental questions.

Quantum mechanical analysis of newly synthesized HIV-1 protease inhibitors: evaluation of wild-type and resistant strain binding interactions.

Inhibition of HIV-1 protease is a cornerstone of antiretroviral therapy. However, the notorious ability of HIV-1 to develop resistance to protease inhibitors (PIs), particularly darunavir (DRV), poses a major challenge. Using quantum chemistry and computer simulations, this study aims to investigate the interactions between two novel PIs, GRL-004 and GRL-063, as well as a wild-type (WT) HIV strain and a DRV-resistant mutant strain. To do this, we used molecular docking, molecular dynamics simulations, and quantum mechanical calculations to check how well GRL-004 and GRL-063 bound to both WT and DRV-resistant proteases. The results show that GRL-004 and GRL-063 bind very well to ASP29 in the WT strain. ASP29 is an important amino acid in the HIV protease dimer. Remarkably, amino acids such as ILE50 in the WT strains showed substantial binding energies to both drugs. Quantum energy calculations showed a slight reduction in the energy affinity of the interaction between the MUT strain and the ligand GRL-063, compared to the WT strain. GRL-004 showed similar interaction energy for both strains, suggesting that it has greater plasticity than GRL-063 despite its lower interaction affinity. Furthermore, GLY49B demonstrated strong binding energies regardless of mutations. Other relevant residues with strong binding energies include GLY49B, PHE82A, PRO81A, ASP29A, ASP25A and ALA28B. This study improves our understanding of receptor-ligand dynamics and the adaptability of new protease inhibitors (PIs), which has profound implications for the innovation of future antiretroviral drugs.

Uncovering Patterns Beneath the Surface: A Glimpse into the Applications of Algebraic Topology

This paper explores the significant impact of algebraic topology on diverse real-world applications. Starting with an introduction to the historical development and essence of algebraic topology, it delves into its applications in neuroscience, physics, biology, engineering, data analysis, and Geographic Information Systems (GIS). Remarkable applications incorporate the analysis of neural networks, quantum mechanics, materials science, and disaster management, showcasing its boundless significance. Despite computational challenges, this study outlines prospects, emphasizing the requirement for proficient algorithms, noise robustness, multi-scale analysis, machine learning integration, user-friendly tools, and interdisciplinary collaborations. In essence, algebraic topology provides a transformative lens for uncovering stowed-away topological structures in complex data, offering solutions to perplexing problems in science, engineering, and society, with vast potential for future exploration and innovation.

Adsorption behavior of Rh-doped graphdiyne monolayer towards various gases: A quantum mechanical analysis

In this study, the conformational properties of pure Graphdiyne (GDY) and Rh-doped (Rh-GDY) for the CO, NO, and NH3 gases are investigated using DFT computations. The doping site is optimized, and the structure parameters and electronic properties of Rh-GDY were evaluated. It is found that Rh-dosing at the optimal site (CII) increases the electrical conductivity due to decreasing of gap energy. The tendency of pure GDY toward CO, NO, and NH3 gases is low and not suitable for sensing due to physical adsorption of gases. However, Rh-GDY demonstrates exceptional performance as a gas sensor due to its strong chemisorption of CO, NO, and NH3 gases through hybridization and chemical reactions with the gas molecular orbital. As a result, Rh-GDY represents a potential gas detection sensor material with notable monitoring capabilities for gases such as CO, NO, and NH3. This research provides valuable information for advancing the creation of innovative and effective gas detection sensor technologies.

The Energetic Origins of Pi-Pi Contacts in Proteins.

Accurate potential energy models of proteins must describe the many different types of noncovalent interactions that contribute to a protein's stability and structure. Pi-pi contacts are ubiquitous structural motifs in all proteins, occurring between aromatic and nonaromatic residues and play a nontrivial role in protein folding and in the formation of biomolecular condensates. Guided by a geometric criterion for isolating pi-pi contacts from classical molecular dynamics simulations of proteins, we use quantum mechanical energy decomposition analysis to determine the molecular interactions that stabilize different pi-pi contact motifs. We find that neutral pi-pi interactions in proteins are dominated by Pauli repulsion and London dispersion rather than repulsive quadrupole electrostatics, which is central to the textbook Hunter-Sanders model. This results in a notable lack of variability in the interaction profiles of neutral pi-pi contacts even with extreme changes in the dielectric medium, explaining the prevalence of pi-stacked arrangements in and between proteins. We also find interactions involving pi-containing anions and cations to be extremely malleable, interacting like neutral pi-pi contacts in polar media and like typical ion-pi interactions in nonpolar environments. Like-charged pairs such as arginine-arginine contacts are particularly sensitive to the polarity of their immediate surroundings and exhibit canonical pi-pi stacking behavior only if the interaction is mediated by environmental effects, such as aqueous solvation.

Observation of resonant tunneling of proton from octahedral to tetrahedral sites in Pd

Hydrogen (H), the lightest element, exhibits quantum nature. Because the quantum tunneling is almost independent of temperature, H diffusion shows a transition from thermal hopping to quantum tunneling at low temperature. The role of the nuclear quantum effects on H diffusion, however, has not been clarified around the crossover region. Hence, we elucidate the hopping mechanism at intermediate temperature by a combination of accurate experimental data on H hopping rates and theoretical calculations for quantum states of H. We derived H hopping rates in Pd from the resistance evolution due to the H ordering associated with the 50 K anomaly. A gradual transition from thermal hopping to quantum tunneling was observed around 65 K. Three-dimensional quantum-mechanical analysis for the H quantum states revealed that the gradual transition is attributed to the resonant tunneling between the discrete vibrational states in the octahedral site and the tetrahedral site via the thermal vibrational excitation. Based on the results at different H concentrations and deuterium, we demonstrated that the tunneling rate is tuned by energy level matching and the resonance nature is manifested as the abruptness of the transition from thermal to quantum hopping.

Kokumi-Enhancing Mechanism of N-l-lactoyl-l-Met Elucidated by Sensory Experiments and Molecular Simulations.

Recent research indicates that N-lactoyl amino acid derivatives have the potential as kokumi substances, with their kokumi profile closely linked to that of amino acids. This study aimed to explore the unexplored effects resulting from the introduction of lactate groups into l-Methional (l-Met), a prevalent flavor compound found in foods, such as tomatoes, known for its ability to activate the monosodium glutamate response. N-l-Lac-l-Met was enzymatically synthesized using food grade, and its taste profile and underlying mechanisms were investigated. The structure of N-l-Lac-l-Met was determined by high-performance liquid chromatography (HPLC)-mass spectrometry (MS)/MS. Sensory evaluation revealed the presence of astringency, kokumi, and bitterness of N-l-Lac-l-Met. In a stimulated broth, N-l-Lac-l-Met exhibited enhanced umami and kokumi taste perception compared to l-Met while demonstrating good stability within pH 5 to 9. A molecular simulation and quantum mechanics analysis indicated that the formation of an amide bond played a crucial role in the kokumi-enhancing effect of N-l-Lac-l-Met, specifically by increasing its affinity with umami receptors T1R1-T1R3 and a kokumi receptor CaSR. These findings established the relationship between amide bond formation and the kokumi-enhancing effect of N-l-Lac-l-Met, presenting its potential application as the kokumi substance in the food industry.

Exploring Quercetin Hydrate’s Potential as an Antiviral Treatment for Oropouche Virus

The Oropouche virus is an orthobunyavirus responsible for causing Oropouche fever, a disease that primarily affects thousands of people in South and Central America. Currently, no specific antiviral treatments or vaccines are available against this virus, highlighting the urgent need for safe, affordable, and effective therapies. Natural products serve as an important source of bioactive compounds, and there is growing interest in identifying natural bioactive molecules that could be used for treating viral diseases. Quercetin hydrate is a compound classified as a flavonoid, which has garnered scientific attention due to its potential health benefits and its presence in various plant-based foods. In this study, we aim to evaluate the in vitro antiviral activity of quercetin hydrate against the Oropouche virus (OROV). Furthermore, we intend to explore its mode of action through in silico approaches. The cytotoxicity and antiviral activity of the compound were assessed using Vero cells. In addition, in silico studies were also performed through molecular docking, molecular dynamics simulations, Molecular Mechanics Poisson–Boltzmann surface area (MM/PBSA), and quantum-mechanical analysis in order to evaluate the interaction with the Gc protein of OROV. The assay revealed that the compound was highly active against the virus, inhibiting OROV with an EC50 value of 53.5 ± 26.5 µM under post-infection treatment conditions. The present study demonstrates that the compound is a promising antiviral agent; however, the mechanisms of action proposed in this study need to be experimentally verified by future assays.