Energy Decomposition Analysis Research Articles

Single Crystal, Conformational, Quantum reactivity, Hirshfeld surface, Molecular interactions, ADMET, and Molecular Docking Investigations on HIV-1 site of 3-isopropyldiphenyl-1-(2-(thiophen-2yl)acetyl)piperidin-4-one

The 3-isopropyl-2,6-diphenyl-1-(2-(thiophen-2yl)acetyl)piperidin-4-one (IPTP) single crystals were grown by slow evaporation method and the structure is confirmed through FT-IR, 1H NMR, and 13C NMR spectral analyses. Single crystal X-ray diffraction revealed that the title compound having chair conformation of the piperidine ring, with an axial orientation of phenyl rings at C-2 and C-6 positions and an isopropyl group at C-3. Hirshfeld surface analysis was employed to examine intermolecular contacts and strong and weak attractive, repulsive, and van der Waals interactions in the molecule were determined using the reduced density gradient method (RDG). The geometrical parameters obtained through Density Functional Theory are compared with experimental values and also conducted to optimize structural parameters, frontier molecular orbitals (FMOs), and molecular electrostatic potential surface analysis (MEPS). NBO calculations were employed to investigate intermolecular and intramolecular charge movement, as well as the molecule's stability. Vibrational Energy Distribution Analysis (VEDA) software facilitated potential energy decomposition (PED) analysis using FT-IR wave numbers. The title compound molecular docking data were compared with the markedly available FDA-approved anti-HIV drug of Nelfinavir and their results were discussed, ADME analysis studies were discussed concerning FDA-approved anti-HIV drugs, including Nelfinavir, Betulinic Acid, Haloperidol, and Donepezil.

Theoretical insights into enantioselective [2 + 1] cyclopropanation reactions of diazo compounds with electron-deficient olefins.

The cyclopropane skeleton plays a significant role in bioactive molecules due to its distinctive structural properties. This has sparked keen interest and in-depth exploration in the field of stereoselective synthesis of cyclopropane derivatives. In the present study, the mechanism and the origin of stereoselectivity of diastereodivergent synthesis of cyclopropane derivatives via the catalyst-free [2 + 1]-cyclopropanation reactions of 3-diazo-N-methylindole (R1) with two types of electron-deficient olefins (R2 and R3) in both aqueous and toluene media have been studied using the DFT calculations. The findings indicate that these [2 + 1] cycloaddition reactions proceed in two stages, where the first step is not only the rate-determining step but also critically dictates the stereoselectivity of the product. The calculated diastereomeric ratios are in agreement with the experimental results. Furthermore, by utilizing non-covalent interaction (NCI) analysis and energy decomposition analysis based on molecular force fields (EDA-FF), we elucidated that the electrostatic interactions between reactant fragments in the transition state TS1s for the first step are the predominant factors determining the stereoselectivity, as opposed to the experimentally hypothesized steric hindrance and π-π stacking interactions. The geometrical structures of all minima and transition states on the potential energy surface (PES) in solvents water and toluene were fully optimized using the DFT method at the M06-2X(D3)/SMD/6-31 + G(d,p) level of theory. Single-point energy calculations were carried out based on the optimized geometries in the solution at the M06-2X(D3)/6-311 + G(d,p) level. All the DFT calculations were performed using the Gaussian 09 software. The optimized molecular structures were visualized using CYLview software. NCI analysis was performed using the Multiwfn and VMD softwares. The Multiwfn program was also used for CDFT and EDA-FF analyses.

Spectroscopic investigation of size-dependent CO2 binding on cationic copper clusters: analysis of the CO2 asymmetric stretch.

Photofragmentation spectroscopy, combined with quantum chemical computations, was employed to investigate the position of the asymmetric CO2 stretch in cold, He-tagged Cun[CO2]+ (n = 1-10) and Cun[CO2][H2O]+ (n = 1-7) complexes. A blue shift in the band position was observed compared to the free CO2 molecule for Cun[CO2]+ complexes. Furthermore, this shift was found to exhibit a notable dependence on cluster size, progressively redshifting with increasing cluster size. The computations revealed that the CO2 binding energy is the highest for Cu+ and continuously decreases with increasing cluster size. This dependency could be explained by highlighting the role of polarization in electronic structure, according to energy decomposition analysis. The introduction of water to this complex amplified the redshift of the asymmetric stretch, showing a similar dependency on the cluster size as observed for Cun[CO2]+ complexes.

Modulation of the Intermolecular Interactions of Cucurbit[7]uril with Phenylalanine Derivatives by the Functional Groups

Abstract Intermolecular interactions in 1:1 inclusion complexes of cucurbit[7]uril (CB[7]) with phenylalanine derivatives were investigated by density functional theory (B97-D) calculations. For each complex, two optimized geometries were found: conformer C in which a guest molecule resided in the center of CB[7], and conformer E where a guest molecule was present at the edge of CB[7]. The order of energy differences between these conformers agreed well with previously reported differences in the affinity of guest molecules for CB[7]. Molecular dynamics simulations of the complexes showed that the guest molecules in CB[7] had different stabilities, and the calculated binding free energies between them also qualitatively agreed with the experimental results. Pair-interaction energy decomposition analyses of the complexes at FMO-MP2/6-31G(d) and aug-cc-pVDZ level of theory were performed using snapshot structures at 500 ns of simulations. The dispersion interaction characterized the interaction, and the order of total interaction energies between the guest molecules and CB[7] was also associated with the experimental results. A significant difference in electrostatic interaction energies was observed in conformer E, which was correlated with the stability of the guest molecules at the edge of CB[7]. The balance between the stabilities of these conformers was correlated with the affinity of guest molecules for CB[7].

Anion-Carbonyl Interactions.

Presented herein is the exploration of a novel non-covalent anion-carbonyl (X-···C═O) interaction using aromatic imides as receptors and halides as lone pair donors. Combined theoretical calculations and experimental methods including 13C NMR, IR, and crystallographic analyses were performed to provide the physical origin and experimental evidence of anion-carbonyl interactions. The EDA analysis (energy decomposition analysis) based on DFT calculation indicates that electrostatic terms are the dominant contributions for the binding energy while electron delocalization also significantly contributes alongside the electrostatic attraction. Orbital interaction (n → π*) involving the delocalization of halide lone pairs on the carbonyl antibonding orbitals was visualized with NBO (Natural Bond Orbital) analysis. 13C NMR and IR spectra demonstrated upfield chemical shifts and red-shift frequency of hosts upon the addition of halides, reflecting the effect of orbital overlap between the halide lone pairs and π* of carbonyl (n → π* contribution). The anion-carbonyl interactions were directly revealed by X-ray structural analysis of anion and benzene triimide complexes.

Ab initio investigation of the geometrical behavior in solution and electronic structure of the anion complexes [bis(1,3-dithiole-2-thione-4,5-dithiolate)M], for M = Bi(III), Sb(III), and Zn(II).

1,3-Dithiole-2-thione-4,5-dithiolate (dmit) ligands are known for their conductive and optical properties. Dmit compounds have been assessed for use in sensor devices, information storage, spintronics, and optical material applications. Associations with various metallic centers endow dmit complexes with magnetic, optical, conductive, and antioxidant properties. Optical doping can facilitate the fabrication of magnetic conductor materials from ground-state nonmagnetic cations. While most studied complexes involve transition-metal centers due to their diverse chemistry, compounds with representative elements are less explored in the literature. This study investigated the structural and electronic properties of bisdmit complexes with representative Bi(III), Sb(III), and Zn(II) cations. AIMD calculations revealed two new geometries for Bi(III) and Zn(II) complexes, diverging from the isolated geometry typically used in quantum chemical calculations. The coordination of acetonitrile molecules to the cationic centers of the complexes resulted in unstable structures, while the dimerization of the complexes was stable. SA-CASSCF/NEVPT2 calculations were applied to the structures of the isolated complexes and stable dimers, confirming the multireference character of the electronic structure of the three systems and the multiconfigurational character of the Bi(III) complex. The electronic spectra simulated by the STEOM-DLPNO-CCSD calculations accurately reproduced the experimental UV‒Vis spectra indicating the participation of the isolated Bi(III) dmit complex and its dimeric form in solution. AIMD calculations of the dmit salts were conducted using the GFN2-xTB method with 60 explicit acetonitrile molecules as the solvent at 300K for a total simulation time of 50.0ps, with printing intervals of 0.5fs. The final geometries were optimized employing the PBEh-3c compound method, incorporating implicit conductor-like polarizable continuum model (CPCM) solvation for acetonitrile. Local energy decomposition (LED) analysis at the DLPNO-CCSD(T)/Def2-TZVP level of theory was utilized to investigate the stability of the complex geometries identified by AIMD. The electronic structures of the complexes were assessed using the SA-CASSCF/NEVPT2/Def2-TZVP method to confirm the multiconfigurational and multireference nature of their electronic structures. Electronic spectra were analyzed using the STEOM-DLPNO-CCSD/Def2-TZVP method, with CPCM used to simulate an acetonitrile medium.

Chalcogen Noncovalent Interactions between Diazines and Sulfur Oxides in Supramolecular Circular Chains.

The noncovalent chalcogen interaction between SO2/SO3 and diazines was studied through a dispersion-corrected DFT Kohn-Sham molecular orbital together with quantitative energy decomposition analyses. For this, supramolecular circular chains of up to 12 molecules were built with the aim of checking the capability of diazine molecules to detect SO2/SO3 compounds within the atmosphere. Trends in the interaction energies with the increasing number of molecules are mainly determined by the Pauli steric repulsion involved in these σ-hole/π-hole interactions. But more importantly, despite the assumed electrostatic nature of the involved interactions, the covalent component also plays a determinant role in its strength in the involved chalcogen bonds. Noticeably, π-hole interactions are supported by the charge transfer from diazines to SO2/SO3 molecules. Interaction energies in these supramolecular complexes are not only determined by the S···N bond lengths but attractive electrostatic and orbital interactions also determine the trends. These results should allow us to establish the fundamental characteristics of chalcogen bonding based on its strength and nature, which is of relevance for the capture of sulfur oxides.

Chalcogen Noncovalent Interactions between Diazines and Sulfur Oxides in Supramolecular Circular Chains

The noncovalent chalcogen interaction between SO2/SO3 and diazines was studied through a dispersion-corrected DFT Kohn–Sham molecular orbital together with quantitative energy decomposition analyses. For this, supramolecular circular chains of up to 12 molecules were built with the aim of checking the capability of diazine molecules to detect SO2/SO3 compounds within the atmosphere. Trends in the interaction energies with the increasing number of molecules are mainly determined by the Pauli steric repulsion involved in these σ-hole/π-hole interactions. But more importantly, despite the assumed electrostatic nature of the involved interactions, the covalent component also plays a determinant role in its strength in the involved chalcogen bonds. Noticeably, π-hole interactions are supported by the charge transfer from diazines to SO2/SO3 molecules. Interaction energies in these supramolecular complexes are not only determined by the S···N bond lengths but attractive electrostatic and orbital interactions also determine the trends. These results should allow us to establish the fundamental characteristics of chalcogen bonding based on its strength and nature, which is of relevance for the capture of sulfur oxides.

Initial pyrolysis of perhydroacenaphthene conformers: A multi-scale simulation and experimental analysis

The enduring quest for a fuel that embodies both high density and superior heat sink capacity has been a long-standing goal within the scientific community. Perhydroacenaphthene (PHAN) fuels, characterized by five-membered ring structure that enhances density, also serve as hydrogen donors to inhibit coking, showcasing significant potential in fuel applications. Given their "strain-free" cyclic configuration, PHAN fuels manifest diverse conformations like chair, boat, and twist, among others, each influencing fuel properties and subsequently affecting pyrolysis process and the utilization of heat sink. In this work, leveraging the five preferred PHAN conformers substantiated by experiments, we embarked on a comprehensive investigation into their microstructures, properties, pyrolysis behavior, and initial pyrolysis mechanisms combining with molecular simulation and experimental analysis. Among them, interaction region indicator (IRI) analysis was employed to elucidate the differences in density. Upon this foundation, taking trans-trans-trans and cis-cis-cis PHAN with minimum and maximum density as models, the effects of different conformations on the initial pyrolysis reaction were explored by micro-pyrolysis system attached to an online GC-MS/FID strategy. It was found that compared to the trans-trans-trans conformation, the cis-cis-cis conformation manifested superior initial pyrolysis activity and more substantial heat sink capacity. Moreover, upon delving into the reaction mechanism and microkinetic analysis, it became evident that the favored initial reaction type of PHAN pyrolysis was H-abstraction reaction, and cis-cis-cis PHAN presented a lower barrier and a faster reaction rate than trans-trans-trans. Additionally, in conjunction with the calculation of free energy barrier and reaction heat of numerous reactions, the kinetic and thermodynamic dominances for the initial pyrolysis pathways of trans-trans-trans and cis-cis-cis PHAN were identified. Finally, utilizing intermolecular interaction energy (ΔE), independent gradient model based on Hirshfeld partition (IGMH) and Xiamen energy decomposition analysis (XEDA), the microscale justification for cis-cis-cis PHAN conformation displaying superior initial pyrolysis activity was further unveiled. This endeavors pioneer innovative pathways for the directional development and application of PHAN conformers.

Polydopamine coating for enhanced electrostatic adsorption of methylene blue by multiwalled carbon nanotubes in alkaline environments

The removal of dye molecules in alkaline environments is an issue that should receive increased attention. In this study, the interaction mechanism between polydopamine-modified multiwalled carbon nanotubes (P-MWCNTs) and multiwalled carbon nanotubes (MWCNTs) with the cationic dye methylene blue (MB) in alkaline environments was explained in depth by adsorption, spectroscopy, and density functional theory (DFT). The mechanism of action and dominant forces between the adsorbent and adsorbate were analyzed graphically by introducing energy decomposition analysis (EDA) and an independent gradient model (IGM) into the DFT calculations. In addition, the force distribution was investigated through an isosurface. Moreover, batch adsorption studies were conducted to evaluate the performance of MWCNTs and P-MWCNTs for MB removal in alkaline environments. The maximum MB adsorption capacities of the MWCNTs and P-MWCNTs in solution were 113.3 mg‧g−1 and 230.4 mg‧g−1, respectively, at pH 9. The IGM and EDA showed that the better adsorption capacity of the P-MWCNTs originated from the enhancement of the electrostatic effect by the proton dissociation of polydopamine. Moreover, the adsorption of MB by MWCNTs and P-MWCNTs in alkaline environments was governed by dispersion and electrostatic effects, respectively. Through this study, it is hoped that progress will be made in the use of DFT to explore the mechanism of adsorbent-adsorbate interactions.

Exploring the Nature of Chemical Bonding between Noble Gases and Hypercoordinate Group 13 Compounds: Beyond Boron.

In this article, we systematically study the stability and chemical bond nature of EH4Ng+ compounds (E = Al-Tl; Ng = He-Rn) at the CCSD(T) and ωB97XD levels of theory. Thermochemical calculations obtained by exploring different dissociation pathways show that these compounds could be stable at low temperatures. In addition, studied compounds have a strong E-Ng bond, which has been characterized using different methodologies such as quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO) theory, and natural energy decomposition analysis (NEDA). Results indicate that the nature of the chemical bond is predominantly covalent, especially in the case those including the heavier gases (Ar-Rn), occurring through a charge transfer from the noble gas to the group 13 element. However, the electrostatic contribution is also important in the stabilization of this bond. This study extends the universe of group 13 molecules containing noble gas bonds beyond boron and other elements from the second period.

Prediction of the binding mechanism of a selective DNA methyltransferase 3A inhibitor by molecular simulation

DNA methylation is an epigenetic mechanism that introduces a methyl group at the C5 position of cytosine. This reaction is catalyzed by DNA methyltransferases (DNMTs) and is essential for the regulation of gene transcription. The DNMT1 and DNMT3A or -3B family proteins are known targets for the inhibition of DNA hypermethylation in cancer cells. A selective non-nucleoside DNMT3A inhibitor was developed that mimics S-adenosyl-l-methionine and deoxycytidine; however, the mechanism of selectivity is unclear because the inhibitor–protein complex structure determination is absent. Therefore, we performed docking and molecular dynamics simulations to predict the structure of the complex formed by the association between DNMT3A and the selective inhibitor. Our simulations, binding free energy decomposition analysis, structural isoform comparison, and residue scanning showed that Arg688 of DNMT3A is involved in the interaction with this inhibitor, as evidenced by its significant contribution to the binding free energy. The presence of Asn1192 at the corresponding residues in DNMT1 results in a loss of affinity for the inhibitor, suggesting that the interactions mediated by Arg688 in DNMT3A are essential for selectivity. Our findings can be applied in the design of DNMT-selective inhibitors and methylation-specific drug optimization procedures.

Frustrated Lewis pair-mediated hydro-dehalogenation: crucial role of non-covalent interactions.

Organic halides stand as invaluable reagents with diverse applications in synthetic chemistry and various industrial processes. Despite their utility, concerns arise due to their inherent toxicity. Addressing these apprehensions, hydro-dehalogenation has emerged as a promising strategy involving the replacement of halogen atoms with hydrogen atoms to transform toxic organic halides into hydrocarbons. This study delves into the computational exploration of hydro-dehalogenation reactions of benzyl halide, mediated by frustrated Lewis pairs (FLPs), using density functional theory (DFT). The reactions entail the formation of FLP1 or FLP2 in the presence of TMP or lutidine with B(C6F5)3, respectively. This is followed by heterolytic cleavage of dihydrogen and subsequent reaction with benzyl halides. Non-covalent interaction analysis underscores the significance of π-π stacking and CH-π interactions in stabilizing transition states. Additionally, the activation strain model (ASM) dissects activation energies, revealing the substantial impact of strain energy on reaction barriers. Energy decomposition analysis (EDA) offers insights into the contributions of electrostatic, orbital, and dispersion energies to the overall attractive interaction energy. The investigation extends to hydro-dehalogenation reactions of ethyl halides, uncovering distinct mechanisms and activation barriers. This comprehensive analysis illuminates the intricacies of hydro-dehalogenation reactions, providing valuable insights into their mechanisms and paving the way for future studies in this field. Geometry optimizations were carried out at the M06-2X/def2-SVP level of theory, which was performed using the Gaussian 16 program. Solvent-corrected single-point energies were also calculated using the polarizable continuum model (PCM) at the PCM(chloroform)-M06-2X/def2-TZVP//M06-2X/def2-SVP level of theory. The Gibbs free energy correction was determined from computations performed at the M06-2X/def2-SVP level of theory. Principal interacting orbital (PIO) analysis was conducted using the NBO 6.0 software. The nature of bonding in the respective transition state (TS) structures was analyzed using atoms-in-molecules (AIM) analyses. Additionally, the presence of non-covalent interactions (NCI) was exemplified using Multiwfn software.

Reactivity of zinc fingers in oxidizing environments: insight from molecular models through activation strain analysis.

The reactivity of Zn2+ tetrahedral complexes with H2O2 was investigated in silico, as first step for the process of their disruption. The substrates were chosen to represent the cores of three different zinc finger protein motifs, i.e., a Zn2+ ion coordinated to four cysteines (CCCC), to three cysteines and one histidine (CCCH), and to two cysteines and two histidines (CCHH). The cysteine and histidine ligands were further simplified to methyl thiolate and imidazole, respectively. H2O2 was chosen as oxidizing agent because of its biological role as metabolic product and species involved in signaling processes. The mechanism of oxidation of a coordinated cysteinate to sulfenate-κS and the trends for the different substrates wererationalized through activation strain analysis and energy decomposition analysis in the framework of scalar relativistic DFT calculations at ZORA-M06/TZ2P ae // ZORA-BLYP-D3(BJ)/TZ2P. CCCCis oxidized most easily, an outcome explained considering both electrostatic and orbital interactions. The isomerization to sulfenate-κO was attempted to assess whether this step may affect the ligand dissociation; but it was found to introduce a kinetic barrier without improving the energetics of the dissociation. Lastly, ligand exchange with free thiolates and selenolates was investigated as trigger for ligand dissociation, possibly leading to metal ejection.

Electron Dynamics in Alkane C-H Activation Mediated by Transition Metal Complexes.

Alkanes, ideal raw materials for industrial chemical production, typically exhibit limited reactivity due to their robust and weakly polarized C-H bonds. The challenge lies in selectively activating these C-H bonds under mild conditions. To address this challenge, various C-H activation mechanisms have been developed. Yet, classifying these mechanisms depends on the overall stoichiometry, which can be ambiguous and sometimes problematic. In this study, we utilized density functional theory calculations combined with intrinsic bond orbital (IBO) analysis to examine electron flow in the four primary alkane C-H activation mechanisms: oxidative addition, σ-bond metathesis, 1,2-addition, and electrophilic activation. Methane was selected as the representative alkane molecule to undergo C-H heterolytic cleavage in these reactions. Across all mechanisms studied, we find that the CH3 moiety in methane consistently uses an electron pair from the cleaved C-H bond to form a σ-bond with the metal. Yet, the electron pair that accepts the proton differs with each mechanism: in oxidative addition, it is derived from the d-orbitals; in σ-bond metathesis, it resulted from the metal-ligand σ-bonds; in 1,2-addition, it arose from the π-orbital of the metal-ligand multiple bonds; and in electrophilic activation, it came from the lone pairs on ligands. This detailed analysis not only provides a clear visual understanding of these reactions but also showcases the ability of the IBO method to differentiate between mechanisms. The electron flow discerned from IBO analysis is further corroborated by results from absolutely localized molecular orbital energy decomposition analysis, which also helps to quantify the two predominant interactions in each process. Our findings offer profound insights into the electron dynamics at play in alkane C-H activation, enhancing our understanding of these critical reactions.

Unveiling the Intermolecular Interactions between Drug 5-Fluorouracil and Watson-Crick/Hoogsteen Base Pairs: A Computational Analysis.

The adsorption of 5-fluorouracil (5FU) on Watson-Crick (WC) base pairs and Hoogsteen (HT) base pairs has been studied using the dispersion-corrected density functional theory (DFT). The adsorption, binding energy, and thermochemistry for the drug 5FU on the WC and HT base pairs were determined. The most stable geometries were near planar geometry, and 5FU has a higher preference for WC than HT base pairs. The adsorption energies of 5FU on nucleobase pairs are consistently higher than pristine nucleobase pairs, indicating that nucleobase pair cleavage is less likely during the adsorption of the 5FU drug. The enthalpy change for the formation of 5FU-DNA base pairs is higher than that for the formation of 5FU-nucleobases and is enthalpy-driven. The E gap of AT base pairs is higher, suggesting that their chemical reactivity toward further reaction would be less than that of GC base pairs. The electron density difference (EDD) analysis shows a significant decrease in electron density in aromatic regions on the purine bases (adenine/guanine) compared to the pyrimidine bases. The MESP diagram of the stable 5FU-nucleobase pair complexes shows a directional interaction, with the positive regions in a molecule interacting with the negative region of other molecules. The atoms in molecule analysis show that the ρ(r) values of C=O···H-N are higher than those of N···H/N-H···O. The N···H intermolecular bonds between the base pair/drug and nucleobases are weak, closed shell interactions and are electrostatic in nature. The noncovalent interaction analysis shows that several new spikes are engendered along with an increase in their strength, which indicates that the H-bonding interactions are stronger and play a dominant role in stabilizing the complexes. Energy decomposition analysis shows that the drug-nucleobase pair complex has a marginal increase in the electrostatic contributions compared to nucleobase pair complexes.

Dispersion-Driven Cooperativity in Alkyl Perylene Diimide Oligomers: Insights from Density Functional Theory.

The cooperative mechanism is of paramount importance in the synthesis of supramolecular polymers with desired characteristics, including molecular mass, polydispersity, and morphology. It is primarily driven by the presence of intermolecular interactions, which encompass strong hydrogen bonding, metal-ligand interactions, and dipole-dipole interactions. In this study, we utilize density functional theory and energy decomposition analysis to investigate the cooperative behavior of perylene diimide (PDI) oligomers with alkyl chains at their imide positions, which lack the previously mentioned interactions. Our systematic examination reveals that dispersion interactions originating from the alkyl side-chain substituents play an important role in promoting cooperativity within these PDIs. This influence becomes even more pronounced for alkyl chain lengths beyond hexyl groups. The energy decomposition analysis reveals that the delicate balance between dispersion energy and Pauli repulsion energy is the key driver of cooperative behavior in PDIs. Additionally, we have developed a mathematical model capable of predicting the saturated binding energies for PDI oligomers of varying sizes and alkyl chain lengths. Overall, our findings emphasize the previously undervalued significance of dispersion forces in cooperative supramolecular polymerization, enhancing our overall understanding of the cooperative mechanism.

Identification of the inhibition mechanism of carbonic anhydrase II by fructooligosaccharides.

Polygonatum sibiricum (P. sibiricum), recognized as a precious nourishing Chinese traditional medicine, exhibits the pharmacological effect of anti-aging. In this work, we proposed a novel mechanism underlying this effect related to the less studied bioactive compounds fructooligosaccharides in P. sibiricum (PFOS) to identify the inhibition effect of the small glycosyl molecules on the age-related zinc metalloprotease carbonic anhydrase II (CA II). Molecular docking and molecular dynamics simulation were used to investigate the structural and energetic properties of the complex systems consisting of the CA II enzyme and two possible structures of PFOS molecules (PFOS-A and PFOS-B). The binding affinity of PFOS-A (-7.27 ± 1.02kcal/mol) and PFOS-B (-8.09 ± 1.75kcal/mol) shows the spontaneity of the binding process and the stability of the combination in the solvent. Based on the residue energy decomposition and nonbonded interactions analysis, the C-, D- and G-sheet fragments of the CA II were found to be crucial in binding process. Van der Waals interactions form on the hydrophobic surface of CAII mainly with 131PHE and 135VAL, while hydrogen bonds form on the hydrophilic surface mainly with 67ASN and 92GLN. The binding of PFOS results in the blocking of the zinc ions pocket and then inhibiting its catalytic activity, the stability of which has been further demonstrated by free energy landscape. These findings provide evidence of the effective inhibition of PFOS to CA II enzyme, which leads to a novel direction for exploring the mechanism of traditional Chinese medicine focused on small molecule fructooligosaccharides.

Metal-Induced Enhancement of Tetrel Bonding. The Case of C⋅⋅⋅X-IrIII (X=Cl, Br) Tetrel Bond Involving a Methyl Group.

In X-ray structures of the isomorphic mer-[IrX3(THT)(CNXyl)2] (X=Cl 1, Br 2; THT=tetrahydrothiophene; Xyl=2,6-Me2C6H3-) complexes, we revealed short intermolecular contacts between the C-atom of an isocyanide methyl group and halide ligands of another molecule. Geometrical consideration of the X-ray data and analysis of appropriate DFT studies allowed the attribution of these contacts to CMe⋅⋅⋅X-IrIII (X=Cl, Br) tetrel bond. Specifically, through the application of DFT calculations and various theoretical models, the presence of tetrel bonding interactions was validated, and the contribution of the CMe⋅⋅⋅X-IrIII interaction was assessed. The reinforcement of the tetrel bond upon the isocyanide coordination to iridium(III) is substantiated by molecular electrostatic potential (MEP) surface calculations. To distinguish the tetrel bonding characteristics of CMe⋅⋅⋅X-IrIII (X=Cl, Br) interactions from conventional hydrogen bonding, we employed multiple computational methodologies, including Natural Bond Orbital (NBO) analysis and Electron Localization Function (ELF) analysis. Additionally, Energy Decomposition Analysis (EDA) was applied to selected model systems to explore the underlying physical nature of these interactions.

Non-covalent interaction induces controlled reinforcement of thermoplastic elastomer composites homologously incorporated with hydrophobized cellulose nanocrystals

Surface hydrophobization of cellulose nanocrystal (CNC) is developed through Pickering emulsion method and esterification-grafting, consequentially enhancing its thermal properties and hydrophobicity, and tensile modulus in thermoplastic elastomer composites. n-Tetradecenylsuccinic anhydride (TDSA) provides a high level of compatibility owing to the structural homology by non-covalent interactions between CNC-graft-TDSA and poly(styrene)-block-poly(isoprene)-block-poly(styrene) (SIS). Theoretical calculations supports the molecular-level insight on how the nanofiller and SIS interacts. Density functional theory calculations and the energy decomposition analysis reveal the stabilization free energy of −2.59 kcal mol−1 gained through hydrophobic and OH–π interactions, which is assigned as the key component for the superior mechanical properties. At the filler contents of 0.6–2.5 vol %, the moduli of the TPE nanocomposites gradually strengthen while retaining thermoplasticity, without sacrificing the ultimate tensile characteristics of SIS, although it is below the calculated φc of 5.9 vol % (critical percolation threshold) for filler-filler interactions. Origin of the controlled boost in filler-matrix binding is rationalized by pronounced hydrophobic interactions in isoprene-rich rubbery phase (86 wt % in SIS). Interestingly, at 5.1 vol % near to filler-filler interactions, even though reinforcements in storage/initial modulus, and toughness increase by up to 14/4.0-, and 1.2-fold, the tensile stress at break only decreases by 27 %.