Electronic Chemical Potential Research Articles

Kinetic and Theoretical Studies of 3,5-Dicyanothiophene Reactivity with Cyclic Secondary Amines in Water and Acetonitrile: Quantification, Correlation, and Prediction.

The kinetics of the σ-complexation reactions of 3,5-dicyanothiophene 1 with a series of cyclic secondary amines 2a-c has been studied in water and acetonitrile at 20 °C. Through the linear free energy relationship (LFER) log k = sN (N + E), the electrophilicity parameter E of 3,5-dicyanothiophene 1 has been determined and then integrated into the electrophilicity scale established by Mayr. Molecular dynamics (MD) simulations have been employed to elucidate the reversal in reactivity order between piperidine and pyrrolidine observed in water. Reactivity descriptors like the electronic chemical potential (μ) and the chemical hardness (η) for a series of thiophenes were calculated using the density functional theory (DFT) method. Satisfactory linear correlation (r2 > 0.98) between the experimental electrophilicity parameter (E) of thiophenes 1 and 5a-c and their theoretical global electrophilicity index (ω) has been observed and discussed. In addition, we explore how the E vs. ω relationship can be used to evaluate the electrophilicity parameter E values for other thiophenes that cannot directly measure.

Study anti-viral drugs for their efficiency against multiple SARS CoV-2 drug targets within molecular docking, molecular quantum similarity, and chemical reactivity indices frameworks

The study focused on drug discovery for COVID-19, emphasizing the challenges posed by the pandemic and the importance of understanding the virus’s biology. The research utilized molecular docking and quantum similarity analyses to explore potential ligands for SARS-CoV-2 RNA-dependent RNA polymerase. Docking Results Docking outcomes for various ligands, including Oseltamivir, Prochloraz, Valacyclovir, Baricitinib, Molnupiravir, Penciclovir, Famciclovir, Lamivudine, and Nitazoxanide, were presented. Interactions between ligands and specific residues in the RNA-dependent RNA polymerase were analyzed. Reactivity Descriptors Global parameters, such as electronic chemical potential, chemical hardness, global softness, and global electrophilicity, were computed for the ligands. For the local reactivity descriptors, the Fukui Functions were used. Fukui functions, representing electrophilic and nucleophilic sites, were calculated for selected ligands (Valacyclovir and Penciclovir). Nucleophilic character assignments for specific molecular regions were discussed, providing insights into potential charge-donating interactions. Results and Discussion Challenges in COVID-19 drug discovery, such as virus mutability, rapid evolution, and resource limitations, were summarized. Progress in vaccine development and the need for ongoing research to address variants and breakthrough cases were emphasized. Overlap Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.5742) indicates structural and electronic similarity. Lowest MQSM between Oseltamivir and Prochloraz (0.2233) implies structural dissimilarity. Coulomb Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.9178) suggests both structural and electronic similarity. Lowest MQSM between Baricitinib and Famciclovir (0.6001) indicates greater structural diversity. Measurements above 0.5 in Table 3 suggest electronic similarity, emphasizing the electronic aspects in molecular analysis. In this sense, it study employed a multi-faceted approach combining molecular docking, quantum similarity analyses, and chemical reactivity assessments to explore potential drug candidates for COVID-19. The findings provide valuable insights into ligand interactions, reactivity patterns, and the challenges associated with drug discovery in the context of the global pandemic.

Tunable anisotropic plasmons in monolayer Ca4N2 induced by orbital-selective transitions

Plasmons in two-dimensional (2D) materials have attracted considerable interest due to their ability to confine light at subwavelength scales. Anisotropic 2D materials, in particular, offer unique opportunities for directional control over plasmon propagation and light-matter interactions. In this study, employing first-principles calculations, we demonstrate that monolayer Ca4N2 can host tunable anisotropic plasmon modes. The electronic band structure of Ca4N2 exhibits pronounced anisotropy, characterized by a pair of saddle-like points. The spatial symmetries of the Bloch wave functions enable orbital-selective interband transitions between these points, which are allowed along the y-direction but forbidden along the x-direction. The anisotropy of plasmons can be enhanced (or diminished) by improving (or reducing) the electron chemical potential, leading to the topological transition of surface plasmon polaritons among elliptical, hyperbolic and isotropic wavefronts. These findings deepen our understanding of anisotropic plasmon behaviors in 2D materials and provide a potential pathway for designing highly tunable plasmonic devices.

Theoretical investigations of some isolated compounds from Calophyllum flavoramulum as potential antioxidant agents and inhibitors of AGEs

In this paper, we have attempted a theoretical calculation of some plant-isolated compounds as potential inhibitors of oxidative stress and Advanced Glycation Endproducts (AGEs). Herein, theoretical reactivity indices based on the CDFT theory were computed to explore the reactivity of five isolated products from Calophyllum flavoramulum. Global reactivity indices based on HOMO and LUMO energy such as electronic chemical potential, hardness, electrophilicity and the local reactivity descriptors Parr function, molecular electrostatic potentials(MEP), electrostatic potential (ESP) and thermodynamic parameters for the studied compounds are computed and discussed using DFT method and two functionals B3LYP and CAM-B3LYP with 6-31 G(d,p) basis set. The free radical scavenging activity mechanisms (HAT, SET-PT, and SPLET) of some of the isolated products with DPPH are also presented in this work. SET-PT mechanism of the antiradical activity is found to be thermodynamically favorable. Furthermore, a molecular docking study with RAGE receptor and AtGSTF2 enzyme was conducted, in which flavonoids 4 and 5 show a low binding affinity with −8.42 and −10.49 kcal/mol for RAGE, −8.67 and −9.00 kcal/mol for AtGSTF2. After the encouraging outcomes from the molecular docking study, the 4-AtGSTF2 and 5-RAGE complex were subjected to 200 ns molecular dynamics simulation using Desmond, where both studied systems exhibited remarkable stability throughout the 200 ns simulations. Also, the MM-GBSA method was measured by calculating the binding free energy using the individual energy components. Finally, the ADMET predictions were assessed to anticipate the behavior of a drug candidate within the human body.

The shift in chemical potential of electrons upon intercalation of ZrSe2 by copper

The effective valence of copper in the region of its concentration up to x = 0.25 in CuxZrSe2 has been determined based on an analysis of binding energies of the Zr3d and Se3d core levels and the electromotive forces from an electrochemical experiment for CuxZrSe2, as a function of Cu concentration x. It has been shown that the domination of covalent bonding between copper and the ZrSe2 host lattice within this concentration range results in a notable reduction in the effective valence of copper in comparison to its nominal value.

Editors’ Choice—The Butler-Volmer Equation Revisited: Effect of Metal Work Function on Electron Transfer Kinetics

We revisit the classical derivation of the Butler-Volmer equation to include the effect of the electrode metal. If the metal is replaced by one with a different work function, keeping other conditions in the electrode constant, the chemical potential of electrons μ e and the Galvani potential φ change in a complementary manner. Changes in μ e and φ each impact the free energies of activation of the forward and backward electron transfer reactions, so we modify the classical expressions which relate them to applied voltage E by including also the effect of μ e . Inserting these expressions in an Eyring-Polyani or Arrhenius type equation in the traditional way, we obtain a modified Butler-Volmer equation which expresses current density as a function of both E and Δ μ e . The exchange current density j 0 appears as an exponential function of Δ μ e . For the work function Φ of the metal, the approximation Δ μ e ≈ − F Δ Φ yields a linear relationship between ln j 0 and Φ . The linear increase in ln j 0 with Φ has long been reported. We show two experimental examples: the aqueous Fe2+/Fe3+ couple with positive slope and the hydrogen evolution reaction (HER) with parallel lines for the d and sp metals, both with positive slopes.

Adsorption grand potential of OH on metal oxide surfaces.

Describing chemical processes at solid-liquid interfaces as a function of a fixed electron chemical potential presents a challenge for electronic structure calculations and is essential for understanding electrochemical phenomena. Grand Canonical Density Functional Theory (GCDFT) allows treating solid-liquid interfaces in such a way that studying the influence of a fixed electron potential arises naturally. In this work, GCDFT is used to compute the adsorption grand potential (AGP), a key parameter for understanding and predicting the behavior of adsorbates on surfaces. We focused on the adsorption of an OH molecule on three metallic surfaces commonly used in electrochemical processes, such as the oxygen evolution reaction (OER). Our study aims to offer insights into how AGP can be used to compare adsorption strengths under different fixed electron chemical potentials, which is crucial for designing efficient electrode materials. By determining the average number of electrons self-consistently under varying chemical potentials, we showed how one can distinguish between electron acquisition and depletion during the adsorption process, offering a deeper understanding of the adsorbate-surface interactions. The approach used in this work employs the Kohn-Sham-Mermin formulation of the Grand Canonical Density Functional Theory. The computations were performed using the periodic open-source density functional theory software, JDFTx, with the Garrity-Bennett-Rabe-Vanderbilt library of ultrasoft pseudopotentials. Calculations were made using truncated Coulomb potentials and the auxiliary Hamiltonian method with the PBE exchange-correlation functional, along with DFT-D2 long-range dispersion corrections. The implicit solvation model CANDLE was used to describe the electrolyte with a 1M concentration.

Effect of non-covalent interactions on the stability and structural properties of 2,4-dioxo-4-phenylbutanoic complex: a computational analysis.

The 2,4-dioxo-4-phenylbutanoic acid (DPBA) is a subject of interest in pharmaceutical research, particularly in developing new drugs targeting viral and bacterial infections. Complexation with metal ions can improve the stability and solubility of organic compounds. The present study uses quantum chemical calculations to explore the structural and electronic results arising from the interaction between the metal cation (Fe2+) and the π-system of DPBA in different solvents. For this purpose, the analyses of atoms in molecules (AIM) and natural bond orbital (NBO) are employed to comprehend the interaction features and the charge delocalization during the process of complexation. The results demonstrate that the strongest/weakest interactions are evident when the complex is situated in non-polar/polar solvents, respectively. In addition, the investigated complex exhibits two intramolecular hydrogen bonds (IMHBs) characterized by the O-H···O motif. The results indicate that the HBs present in the complex fall within the category of weak to medium HBs. Moreover, the O-H···O HBs are influenced by cation-π interactions, which can increase/decrease their strength in polar/non-polar solvents. To enhance understanding of the interactions above, an examination is conducted on various physical properties including the energy gap, electronic chemical potential, chemical hardness, softness, and electrophilicity power. All calculations are conducted within the density functional theory (DFT) using the ωB97XD functional and 6-311 + + G(d,p) basis set. The computations are performed using the quantum chemistry package GAMESS, and the obtained results are visualized by employing the GaussView program.

Equation of state of the relativistic electron–positron–photon plasma at arbitrary temperature and degeneracy

We consider the plasma made of relativistic electrons and positrons in thermodynamic equilibrium with photons at arbitrary temperature and degeneracy. We establish various thermodynamic identities as a function of the electron and positron chemical potentials and temperature. The high-temperature regime in which the electrons and positrons are ultrarelativistic is recovered. The excess of electrons with respect to positrons or the excess of positrons with respect to electrons depends on the thermodynamic conditions. Doing so, we go beyond what is usually found in the literature where only the high temperature regime is usually tackled.

Calculating the Theoretical Octane Number for a Number of Petroleum Derivatives Using Quantum Mechanical Methods AM1 and PM3

This research included calculating a number of physical variables that affect the octane number using semi-empirical methods of quantum mechanics, including AM1, PM3, hardness (η), electron-chemical potential (µ), spherical electrophilic index (W, ∆G, ∆H, ∆S, ∆E and dipole moment). Multiple statistical analyses were used to find the relationship between the calculated variables and the practical value of the octane number and then calculate the octane number theoretically. Through the four-way statistical analysis, we obtained the best correlation coefficient (R2) for the variables (HOMO + η + ∆S + ∆E) calculated by the PM3 method (R2 = 0.998) and the correlation coefficient values for the variables (HOMO + η + W+ µ) calculated by the AM1 method (R2 = 0.980). Through the single and multiple statistical analysis, the most influential variables on the octane number values are (HOMO, LOMO).

Nanostructured electrochemical platform for sensitive detection of melatonin in human serum and tablets

Melatonin (MT) is a crucial hormone for biological rhythms that influences sleep-wake cycles. The therapeutic value of MT in neurological disorders highlights the need for precise detection. However, challenges like low concentrations in biological samples and complex matrix interferences persist, necessitating rapid and precise analytical techniques. This study presents the novelty of designing a novel sensor that combines a molecularly imprinted polymer with polytoluidine blue O (PTBO) and multi-walled carbon nanotubes on a glassy carbon electrode for MT detection and the study of the interaction between MT and the proposed sensor using density functional theory (DFT). DFT showed that MT has a high nucleophilic character and low electrophilicity compared to TBO, which is a strong electrophile. This supports electron transfer from MT to TBO/PTBO, as indicated by the electronic chemical potentials and molecular electrostatic potentials. Scanning electron microscopy was used to see the morphology. Electrochemical measurements using differential pulse voltammetry demonstrated enhanced sensitivity and selectivity. Under optimized conditions, the sensor exhibited a linear response ranging from 1 to 1000 µM with a limit of detection and limit of quantification of 0.027 µM and 0.092 µM respectively. The performance of the sensor was evaluated in pharmaceutical tablets and human serum. Validation experiments confirmed the reliability of the sensor, with recovery rates of 97.5 % for serum and 98.0 % for pharmaceutical tablets, alongside low relative standard deviations indicating good precision. Interference studies showed minimal effects from coexisting substances, highlighting the selectivity of the proposed sensor. Comparative analysis with existing sensors showed superior performance.

Exploring ethylene insertion reaction mechanism in nickel complexes: a comparative study by the reaction force and reaction electronic flux in molecular and SiO2-supported catalysts.

This study investigates the ethylene insertion reaction mechanism for polymerization catalysis, aiming to discern differences between Ni-α-imine ketone-type catalyst and their SiO2-supported counterpart. The reaction force analysis unveils a more intricate mechanism with SiO2 support, shedding light on unexplored factors and elucidating the observed lower catalytic activity. Furthermore, reactivity indexes suggest earlier ethylene activation in the supported catalyst, potentially enhancing overall selectivity. Finally, the reaction electronic flux analysis provides detailed insights into the electronic activity at each step of the reaction mechanism. In sum, this study offers a comprehensive understanding of the ethylene insertion reaction mechanism in both molecular and supported catalysts, underscoring the pivotal role of structural and electronic factors in catalytic processes. Density functional theory (DFT) calculations were conducted using the ωB97XD functional and the 6-31 + G(d,p) basis sets with Gaussian16 software. Computational techniques utilized in this study encompassed the IRC method, reaction force analysis, and evaluation of electronic descriptors such as electronic chemical potential, molecular hardness, and electrophilicity reactivity indexes. Additionally, reaction electronic flux analysis was employed to investigate electronic activity along the reaction coordinate.

DFT studies on N-(1-(2-bromobenzoyl)-4-cyano-1H-pyrazol-5-yl)

In this work, molecular descriptors of N-(1-(2-bromobenzoyl)-4-cyano-1H-pyrazol-5-yl) halogenated benzamides (1a-h) have been computed using a quantum chemical technique through DFT. Prior work involved the synthesis of compounds (1a-h) and the assessment of their anticancer activity on breast, colon, and liver tumors: MCF-7, HCT-116, and HepG-2 cell lines respectively. Since 1a, 1b, and 1d showed the most potential anticancer impact, their ability to inhibit EGFRWT was investigated. Based on the biological data, 1b inhibited EGFRWT the most. According to the docking evaluation, an H-bond with the threonine residue was one of the main non-covalent contacts between 1b and the EGFRWT active site residues. PES, MESP, HOMOs, LUMOs, energy band gap, global reactivity indices [electron affinity (A), ionization energies (I), electrophilicity index (ω), nucleophilicity index (ε), chemical potential (μ), electronegativity (χ), hardness (η), and softness (S)], condensed Fukui functions, NBO, and NCIs are the molecular descriptors of 1a-h that were computed using DFT technique. According to the theoretical investigation results, compounds (1a-h) might have anticancer effects; these findings are consistent with the biological findings from our previous research. Compound 1b had the lowest binding energy, according to an assessment of the binding energies between the threonine and the three most active compounds (1a, 1b, and 1d). This is consistent with the outcomes of the docking study and the biological examination of the influence of 1a, 1b, and 1d on EGFRWT.

Insights into the variations of kinetic and potential energies in a multi-bond reaction: the reaction electronic flux perspective.

The debate over whether kinetic energy (KE) or potential energy (PE) are the fundamental energy components that contribute to forming covalent bonds has been enduring and stimulating over time. However, the supremacy of these energy components in reactions where multiple bonds are simultaneously formed or broken has yet to be explored. In this study, we use the reaction electronic flux (REF), an effective tool for investigating changes in driving electronic activity when bond formation or dissociation occurs in a chemical reaction, to examine the fluctuations in the KE and PE in a multi-bond reaction. To that end, the activation of CO by low-valent group 14 catalysts through a concerted -bond metathesis mechanism is analyzed. The findings of this preliminary study suggest that the REF can be utilized as a tool to rationalize alterations in the KE and PE in a multi-bond reaction. Specifically, analyses across the reaction coordinate reveal that changes in the KE and PE precede activation in the REF, stimulating the electronic activity where bond formation or dissociation processes dominate. The activation of CO by the low-valent LEH catalysts (L = N,N'-bis(2,6-diisopropyl phenyl)- -diketiminate; E = Si, Ge, Sn, and Pb) was studied along the reaction coordinate at the M06-2X/6-31G(d,p)-LANL2DZ(E) level of theory. The respective minimum energy path calculations were obtained using the intrinsic reaction coordinate (IRC) procedure. The reaction electronic flux (REF) was calculated through the computation of the electronic chemical potential using the frontier molecular orbital approximation. Mayer bond orders along the reaction coordinate have been determined using the NBO 3.1 program in Gaussian16. Most of the reaction coordinate quantities reported in this study (REF, KE, PE, among others) have been determined using the Kudi program and custom Python scripts.

Non-gaussian Saha’s ionization in Rindler spacetime and the equivalence principle

We investigate the non-Gaussian effects of the Saha equation in Rindler space via Tsallis statistics. By considering a system with cylindrical geometry, we deduce the non-Gaussian Saha ionization equation for a partially ionized hydrogen plasma that expands with uniform acceleration. We demonstrate conditions for the validity of the equivalence principle within the realms of both Boltzmann–Gibbs and Tsallis statistics. In the non-Gaussian framework, our findings reveal that the effective binding energy exhibits a quadratic dependence on the frame acceleration, in contrast to the linear dependence predicted by Boltzmann–Gibbs statistics. We show that an accelerated observer shall notice a more pronounced effect on the effective binding energy for a>0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$a>0$$\\end{document} and a more attenuated one when a<0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$a<0$$\\end{document}. We also ascertain that an accelerated observer will measure values of q smaller than those measured in the rest frame. Besides, assuming the equivalence principle, we examine the effects of the gravitational field on the photoionization of hydrogen atoms and pair production. We show that both photoionization and pair production are more intensely suppressed in regions with a strong gravitational field in a non-Gaussian context than in the Boltzmann–Gibbs framework. Lastly, constraints on the gravitational field and the electron and positron chemical potentials are derived.

Hydrogen storage on MgO supported TiMgn (n = 2–6) clusters: A first principle investigation

The current study explores the potential of MgO-supported finite-sized TiMgn (n = 2–6) nanoclusters as hydrogen storage materials, employing density functional theory with a spin-polarized generalized gradient approximation (GGA). These systems' structural stability and electronic characteristics reveal that supported clusters offer superior hydrogen storage capabilities compared to their unassisted counterparts. Various parameters, including cluster-adsorption energy (Eads), hydrogen-adsorption energy in supported clusters (Eads-H), HOMO-LUMO gap, vertical ionization potential (VIP), vertical electron affinity (VEA), chemical potential (μ), and chemical hardness (ɳ) are computed. Substrate support notably enhances the thermodynamic stability and chemical reactivity of the TiMg5 cluster when contrasted with the bare TiMg5 cluster. Furthermore, a remarkable increase in the gravimetric hydrogen storage density, from 1.63 wt% for bare Mg5 clusters to 3.45 wt% for bare TiMg5 clusters, reaching 5.62 wt% in the supported TiMg5 cluster system is observed. These findings indicate the substrate-supported TiMg5 cluster as a promising candidate for hydrogen storage applications.

Understanding the coupling of non-metallic heteroatoms to CO2 from a Conceptual DFT perspective

ContextA Conceptual DFT (CDFT) study has been carry out to analyse the coupling reactions of the simplest amine (CH3NH2), alcohol (CH3OH), and thiol (CH3SH) compounds with CO2 to form the corresponding adducts CH3NHCO2H, CH3OCO2H, and CH3SCO2H. The reaction mechanism takes place in a single step comprising two chemical events: nucleophilic attack of the non-metallic heteroatoms to CO2 followed by hydrogen atom transfer (HAT). According to our calculations, the participation of an additional nucleophilic molecule as HAT assistant entails important decreases in activation electronic energies. In such cases, the formation of a six-membered ring in the transition state (TS) reduces the angular stress with respect to the non-assisted paths, characterised by four-membered ring TSs. Through the analysis of the energy and reaction force profiles along the intrinsic reaction coordinate (IRC), the ratio of structural reorganisation and electronic rearrangement for both activation and relaxation energies has been computed. In addition, the analysis of the electronic chemical potential and reaction electronic flux profiles confirms that the highest electronic activity as well as their changes take place in the TS region. Finally, the distortion/interaction model using an energy decomposition scheme based on the electron density along the reaction coordinate has been carried out and the relative energy gradient (REG) method has been applied to identify the most important components associated to the barriers.MethodsThe theoretical calculation were performed with Gaussian-16 scientific program. The B3LYP-D3(BJ)/aug-cc-pVDZ level was used for optimization of the minima and TSs. IRC calculations has also been carried out connecting the TS with the associated minima. Conceptual-DFT (CDFT) calculations have been carried out with the Eyringpy program and in-house code. The distortion/interaction model along the reaction coordinate have used the decomposition scheme of Mandado et al. and the analysis of the importance of each components have been done with the relative energy gradient (REG) method.

Structural, band profiles and optical reflectivity studies of ALi2B (A = Cu, Ag; B = Ge, Sn, Pb) compounds

Abstract The subject of given project is to highlight the basic elastic, electronic and optical reflectivity of ALi2B (A = Cu, Ag; B = Ge, Sn, Pb). For the calculation of these properties, we used the full potential linearized augmented plane wave (FP-LAPW) procedures carry through Wien2k package. Specifically, the Perdew, Burke and Ernzerhof’s generalized gradient approximation (PBE-GGA) and Wu and Cohen generalized gradient approximation (WC-GGA) have been used. The obtained results fit well with existing experimental data. Different elastic parameters, such as constant of elasticity, elastic moduli, Poisson’s ratio, anisotropy factor and Cauchy pressure, are calculated for the first time for the compounds. The elastic properties clearly summarized the compound’s elastically stability and brittleness in both zinc blend phase. The band structure results for ALi2B shows that the compounds are metallic having overlapping bands across the electron chemical potential. The valance band highest energy state is composed from combination of Cu-d and Sn-p state, disclosed through these compound’s total (DOS) plots, whereas the conduction band primarily constitution is from Li-p, Sn-s Cu-s and Sn-p states. The intraband transitions play vital rule in the description of the optical reflectivity of the ALi2B compounds.

Study anti-viral drugs for their efficiency against multiple SARS CoV-2 drug targets within molecular docking, molecular quantum similarity, and chemical reactivity indices frameworks

The study focused on drug discovery for COVID-19, emphasizing the challenges posed by the pandemic and the importance of understanding the virus’s biology. The research utilized molecular docking and quantum similarity analyses to explore potential ligands for SARS-CoV-2 RNA-dependent RNA polymerase. Docking Results Docking outcomes for various ligands, including Oseltamivir, Prochloraz, Valacyclovir, Baricitinib, Molnupiravir, Penciclovir, Famciclovir, Lamivudine, and Nitazoxanide, were presented. Interactions between ligands and specific residues in the RNA-dependent RNA polymerase were analyzed. Reactivity Descriptors Global parameters, such as electronic chemical potential, chemical hardness, global softness, and global electrophilicity, were computed for the ligands. For the local reactivity descriptors, the Fukui Functions were used. Fukui functions, representing electrophilic and nucleophilic sites, were calculated for selected ligands (Valacyclovir and Penciclovir). Nucleophilic character assignments for specific molecular regions were discussed, providing insights into potential charge-donating interactions. Results and Discussion Challenges in COVID-19 drug discovery, such as virus mutability, rapid evolution, and resource limitations, were summarized. Progress in vaccine development and the need for ongoing research to address variants and breakthrough cases were emphasized. Overlap Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.5742) indicates structural and electronic similarity. Lowest MQSM between Oseltamivir and Prochloraz (0.2233) implies structural dissimilarity. Coulomb Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.9178) suggests both structural and electronic similarity. Lowest MQSM between Baricitinib and Famciclovir (0.6001) indicates greater structural diversity. Measurements above 0.5 in Table 3 suggest electronic similarity, emphasizing the electronic aspects in molecular analysis. In this sense, it study employed a multi-faceted approach combining molecular docking, quantum similarity analyses, and chemical reactivity assessments to explore potential drug candidates for COVID-19. The findings provide valuable insights into ligand interactions, reactivity patterns, and the challenges associated with drug discovery in the context of the global pandemic.

Understanding the Effects of Ligand Configuration on Protoporphyrinogen IX Oxidase with Rationally Designed 3-(N-Phenyluracil)but-2-enoates.

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is a promising target for green herbicide discovery. However, the ligand configuration effects on PPO activity were still poorly understood. Herein, we designed 3-(N-phenyluracil)but-2-enoates using our previously developed active fragments exchange and link (AFEL) approach and synthesized a series of novel compounds with nanomolar ranges of Nicotiana tabacum PPO (NtPPO) inhibitory potency and promising herbicidal potency. Our systematic structure-activity relationship investigations showed that the E isomers of 3-(N-phenyluracil)but-2-enoates displayed improved bioactivity than their corresponding Z isomers. Using molecular simulation studies, we found that the E isomers showed a relatively lower entropy change and could sample more stable binding conformation to the receptor than the Z isomers. Our density functional theory (DFT) calculations showed that the E isomers showed higher chemical reactivity and lower electronic chemical potential than their corresponding Z isomers. Compound E-Ic emerged as the optimal compound with a Ki value of 3.0 nM against NtPPO, exhibiting a broader spectrum of weed control than saflufenacil at 37.5-75 g ai/ha and also safe to maize at 75 g ai/ha, which could be considered as a promising lead herbicide for further development.