Non-covalent Interaction Analysis Research Articles

Exploring the antiviral potency of γ-FP and PA compounds: Electronic characterization, non-covalent interaction analysis and docking profiling with emphasis on QTAIM aspects

As focuses on a set of pertinent compounds that incorporate a γ-substituted halophenol linkage with pentanamide (PA). The properties of these compounds were comprehensively assessed through various analytical techniques, including density functional theory (DFT) calculations, offering insights into their geometry and electronic energy gap characteristics. Charge delocalization and stability were explored via natural bond orbital (NBO) analysis. The chemical reactivity was further scrutinized by evaluating NBO, Molecular Electrostatic Potential (MEP), Hirshfeld surface analysis and Fukui functions. The compounds were found to exhibit stability attributed to a robust hydrogen bonding network, which was corroborated by Interaction Region Indicator (IRI) and Electron Density (ED) assessments. Additionally, pharmacological properties were predicted using the PASS (Prediction of Activity Spectra for Substances) server. Molecular docking studies suggested potential antiviral and antioxidant properties, particularly concerning carbonic anhydrase. The overall results imply that these compounds possess favorable drug-like characteristics and show promise for biological efficacy. The study also includes a 2D interaction profile image of the four most interacted proteins and a Ramachandran plot to elucidate the stereochemistry of a selected protein. Furthermore, the activities of 6FDM were investigated following a comprehensive literature survey, with detailed findings presented.

An ab-initio investigation of transition metal-doped graphene quantum dots for the adsorption of hazardous CO2, H2S, HCN, and CNCl molecules

The quantum confinement and size effects make graphene quantum dots (GQDs) remarkable candidates for sensing applications. Gas molecules can easily be adsorbed on GQDs because of their large specific areas and exposed edges. This computational work concerns the adsorption performance of pristine and transition metal [chromium (Cr) or nickel (Ni)]-doped coronene GQD to hazardous gases carbon dioxide (CO2), hydrogen sulfide (H2S), hydrogen cyanide (HCN), and cyanogen chloride (CNCl), along with structural properties such as bond length and angle, electronic properties including molecular orbital analysis, natural bond orbital and Mulliken charge analysis, spectroscopic properties of infrared and ultraviolet spectra, quantum theory of atoms in molecules with non-covalent interaction analysis, and sensing properties of recovery time, work function, and sensing response. As pristine GQDs show poor gas adsorption, doping with Cr and Ni enhance performance. The results of Cr-doped coronene GQD indicate that the gas molecules have strong interaction with GQDs as the computed adsorption energies are highly negative (−3.56, −3.81, −4.02, and −4.81 eV). Since the computed recovery times are extremely long, the Cr-doped GQDs can be used as removers of CO2, H2S, HCN, and CNCl gas molecules from specific environments. In the case of Ni-doped GQDs, only the interaction with CNCl yields chemisorption, with adsorption energy of −0.83 eV. However, the short recovery time (9.36 ms–93.6 s) indicates its potential candidature as a CNCl sensor.

NMR-Based Studies on Odorant Polymer Interactions and the Influence on the Aroma Perception of Red Wine.

The aroma of red wine is suggested to be influenced by interactions with nonvolatile polymers. To investigate this aroma binding effect in red wine, the key aroma compounds of a Primitivo red wine were quantified using GC-MS and an aroma recombinant with 27 odorants was prepared. In sensory experiments, an overall strong effect on the odor perception of the aroma recombinant was observed when high-molecular-weight (HMW) polymers of Primitivo red wine were added. An 1H NMR-based approach was developed to get an insight into the molecular mechanisms of this aroma binding effect in red wine. Evaluation of qualitative changes in the NMR spectra and quantitative time-dependent measurements revealed a clear distinction between different molecular interaction types: (i) no interactions for esters, alcohols, furanones, ketones, and C13-norisoprenoids, (ii, iii) noncovalent interactions for acids, aldehydes, and lactones, and (iv) π-π interactions for pyrazines and phenols. Additionally, the influence of the molecular weight of polymers was evaluated, where the HMW fraction 30-50 kDa showed the highest interaction activity, for example for π-π interactions. Based on these results, the new approach allowed the direct analysis of noncovalent interactions between odorants and HMW polymers and therefore allowed for the first time the description of the aroma binding effect on a molecular basis.

Unraveling the structural and dynamic heterogeneities of hydroxyl-functionalized di-cationic ionic liquids (HFDILs): An integrated ab initio and molecular dynamics approach

This study comprehensively investigates the effects of hydroxyl groups in side chains and cation symmetry on intra- and inter-molecular structures, dynamics, and thermodynamic properties of two hydroxyl-functionalized di-cationic ionic liquids (HFDILs). Using a combination of molecular dynamics (MD) simulations and quantum chemistry (QC) calculations, we compare the influence of these effects on various properties with corresponding non-hydroxyl DILs reported in previous works. The structure of HFDILs is explored using angle distribution, radial distribution, spatial distribution, and combined distribution functions. Also, the averaged noncovalent interaction (aNCI) analysis is used to characterize the weak noncovalent interactions in fluctuating environment of HFDILs. Results showed that the oxygen atoms of anion have the strongest interaction with the hydrogen atom of hydroxyl group, followed by the hydrogen atom at the top of the imidazolium ring. Domain analysis and Voronoi calculations are performed to investigate the number of polar and non-polar subunits, revealing that symmetric HFDILs with two hydroxyl groups in their side chains have greater structural heterogeneity than asymmetric ones with only one hydroxyl group due to the larger accumulation of non-polar subunits. To investigate dynamical heterogeneity, we calculate the non-Gaussian parameter, van Hove correlation, hydrogen bond, ion pair, ion cage, and reorientation dynamics. Results indicated that symmetric HFDILs have slower dynamics, greater dynamic heterogeneity, and more stability than asymmetric ones. Finally, the structure and strength of ion triplet interactions are examined using quantum mechanical methods, revealing that symmetric HFDILs are more stable than asymmetric ones. This study provides valuable information for understanding DILs and their potential applications in various fields.

Chemo selective C-H alkylation of isoquinolones with maleimides: A combined experimental and computational case study

A comparative study of C8-alkylation of isoquinolone with maleimides is reported under different catalytical systems. Among different catalytical systems, Ru and Rh catalysts were found to be excellent in providing C8-alkylated products in good yields, and complete selectivity was achieved using Ru-catalyst. Density functional theory (DFT) investigations suggest a reaction mechanism involving three major steps: C-H activation at C8 position of the isoquinolone, maleimide migratory insertion into the metal-aryl bond, and protonation by the acetic acid. Non-covalent interaction (NCI) analysis was also executed to understand the reaction feasibility and selectivity pattern. Experimental mechanistic studies combined with DFT calculations and NCI analysis provide in-depth information to unravel the mystery behind the selective formation of alkylated products. The current catalytic methodology is further elaborated with a broad substrate scope and late-stage modification.

An extensive experimental and DFT studies on highly selective detection of nitrobenzene through deferasirox based new fluorescent sensor

A deferasirox based substituted triazole amine sensor TAD has been synthesized for the highly selective detection of nitrobenzene in real samples. Sensor TAD exhibited selective quenching response against nitrobenzene among the other nitroaromatic compounds (NACs). Photoinduced electron transfer (PET) process was devised as plausible sensing mechanisms which was supported via UV–visible and fluorescence spectroscopy, 1H NMR titration experiment, density functional theory (DFT) analysis and Job’s plot. Non-covalent interaction (NCI) analysis and Bader’s quantum theory of atoms in molecules (QTAIM) analysis were performed to investigate the presence of non-covalent interactions and symmetry perturbation theory (SAPT0) was performed for energy decomposition and quantitative analysis of interaction energies between sensor TAD and NB. Furthermore, sensor TAD was practically applied for the identification of NB in real samples.

Strategies Toward End-group Engineering of Chrysene Core-based Non-fullerene Acceptors for High Performance Organic Solar Cells: A DFT Study

In this study, seven new molecules (OA1–OA7) were introduced with the goal of enhancing the photovoltaic efficiency of solar cells. All these molecules were evaluated by using density functional theory (DFT). All the designed molecules have shorter band gap and higher values of [Formula: see text] than the reference. For confirming the charge mobility, the optoelectronic characterization has been carried out by densities of states (DOS), transition density matrix (TDM), molecular electrostatic potential (MEP) and reorganization energy. The [Formula: see text] values in designed molecules were also improved. The stability of designed molecules was also confirmed by the analysis of non-covalent interactions (NCIs). These results elaborate on the superiority of these novel-designed molecules over pre-existing (R) molecule as potential blocks for better organic solar cell applications.

Cu(II) and Ni(II) metallacycles derived from barbituric acids: Synthesis with solvent/agent effects in crystallization and structural characterization with non-covalent interaction analysis

It is well known that solvent molecules and additional agents significantly impact crystal structures. In relation to this, the barbituric acid-based 1,3-dimethyl-2,4,6-trioxo-hexahydro-pyrimidine-5-(2,6-dimethylphenylamino)methylene (HL1) as ligand and three novel copper(II) complexes, 2[Cu(L1)2] (1), 2[Cu(L1)2(4,4′bpy)] (2), Cu(L1)2(CH3)2SO (3), (where H is the deprotonatable hydrogen) were synthesized and characterized by elemental analysis, FT-IR spectroscopy. As a comparison, a potentially tridentate barbituric acid-based ligand, 1,3-dimethyl-2,4,6-trioxo-hexahydro-pyrimidine-5-(8-quinolylamino)methylene (HL2), and its three new copper(II) and nickel(II) complexes, Cu(L2)2 (4), Cu(L2)2 (5) and Ni(L2)2 (6), were also synthesized and characterized by elemental analysis, FT-IR spectroscopy. The crystal structures of the ligands and their complexes were determined based on an X-ray diffraction study. X-ray diffraction studies have shown that the ligands HL1 and HL2 exist in keto-enamine form. The crystal structure of complexes of HL1 revealed that Cu center is distorted square-planar in 2[Cu(L1)2] (1), while it is found in distorted square-pyramidal in relation to additional agent (4,4′ bpyridine) and solvent (DMSO) conditions in 2[Cu(L1)2(4,4′bpy)] (2) and Cu(L1)2(CH3)2SO (3), respectively. In the crystal structure, [M(L2)2] (M = Cu (4 and 5), Ni (6)), metal ions possess a distorted octahedral environment, and the HL2 ligands coordinate with a meridional geometry. Structures of all complexes reveal a tendency to form C–H···O, C–H···π and π···π interactions, except for molecule Cu(L1)2(CH3)2SO (3) in terms of C–H···O bonds which was not observed. Exploring noncovalent interactions indicates similar molecular structures in [M(L2)2] (M = Cu (4 and 5), Ni (6)) suggesting the difference in packing due to the solvent of crystallization (CH2Cl2) in the lattice of Cu(L2)2 (5) and the different metal ion in the molecular structure of Ni(L2)2 (6). The packing in the structures of HL1 complexes is found to be strongly dependent on the additional agent (4,4′ bpyridine) and solvent (DMSO) fused in molecular structure with different supramolecular assemblies such as 1D chains, π···π dimers, 2D sheets, etc. In addition, Hirshfeld surface analysis and 2D fingerprint plots were employed to verify intermolecular interactions in both ligands and their complexes.

Structural elucidation and in-silico evaluation of 1,2,4-triazole derivative as potent Omicron variant of SARS-CoV-2 spike protein inhibitor with pharmacokinetics ADMET and drug-likeness predictions

One of the most significant issues in contemporary medicine and pharmacy is the search for powerful bioactive, efficient, low-toxic anti-COVID agents. In this contrast, present work involves the synthesis of triazole derivative 6-(4-Flurophenyl)-3-(pyridine-4yl)-7H-(1,2,4)triazolo(3,4-b) (1,3,4)thiadiazine (FPTT) and its characterizations using various spectroscopic techniques (LCMS, NMR, UV-vis, FTIR). The vibrational wavenumbers were evaluated and found to be in good agreement with theoretical values. The crystal structure is determined using single crystal X-ray diffraction study and the structure is reinforced by several intra-, intermolecular and π···π interactions. These interactions result in the formation of R12(7), R33(17), S(5) and S(6) synthons which significantly contribute towards the stability of the crystal structure. Further, these interactions are validated through Hirshfeld surface and 2D fingerprint plot analysis. The C-H···N and H···H contacts are the major contributors and are in consistency with the topology and natural bond orbital results. The optimized geometrical parameters through density functional theory (DFT) are in good agreement with the experimental data. Further, various electronic properties of the compound were evaluated using the optimized structure. The molecular electrostatic potential map (MEP) and Fukui function analysis revealed the most active sites. Analysis of non-covalent interactions based on a gradient of reduced density revealed the presence of van der Waals interactions. Intrigued, by the presence of large amounts of non-covalent interactions the pharmacokinetic profiles of the compound were evaluated through ADMET provides an insight into potential inhibitors and novel drug candidates. Further in-silico studies such as molecular docking was carried out against the Omicron variant of SARS-CoV-2 spike protein with an intention to assist towards the production of improved vaccines and therapeutics.

Adsorption of Choline Phenylalanilate on Polyaromatic Hydrocarbon-Shaped Graphene and Reaction Mechanism with CO2: A Computational Study.

The interaction of ionic liquids (ILs) with carbon materials is of fundamental importance in several areas of materials science, physics, and chemistry. Their adsorption on pristine and N-doped graphene surfaces is discussed here on the basis of results of density functional theory calculations. The nature of adsorption was investigated for an amino acid (AA)-based IL consisting of the choline cation [Ch] and the l-phenylalanilate anion [Phe] that interacts with a sheet of N-doped graphene. The interaction mechanism, binding energy, electron density, and non-covalent interaction analysis were evaluated by considering the cation, anion, and ion pair adsorbed on graphene separately. The distribution of cations and anions in the liquid bulk and on the graphene surface was then analyzed by molecular dynamics simulations. Since AA-based ILs are efficient absorbents for capture of CO2 due to the pronounced affinity of carbon dioxide to react with amino groups, we investigated the capacity of [Ch][Phe] to react with CO2 under various conditions. We considered the multistep mechanism of the reaction of [Phe] with CO2 first for the anion in the liquid bulk and then for the [Phe] anion adsorbed on the graphene surface. The initial step, the formation of the zwitterionic addition product, is followed by its structural rearrangement through intramolecular proton transfer and conformational isomerization processes to form carboxylic acid derivatives. The entire mechanism was evaluated for the [Phe] anion before and after adsorption on graphene to investigate how interactions with surfaces of carbon materials can affect the CO2 capture capacity of an AA-based IL such as [Ch][Phe].

Computational study of Be, Mg and Ca decorated Si12B12 nanocages with proficient nonlinear optical properties

Scientists have paid much attention to nanoscale nonlinear optical (NLO) materials in recent decades due to their promising applications in telecommunications, electronics, and optics. Here, we endeavored to design alkaline earth metals (Be, Mg, and Ca) doped Si12B12 nanocage to meet the rapidly widening requirement for NLO materials. Density functional theory (DFT) and time-dependent DFT (TDDFT) assisted computational tools are utilized to explore the impact of alkaline earth metals doping on the NLO response of Si12B12 nanocage to reveal a unique method for developing NLO materials. Theoretically, ten new isomers of alkaline earth metals doped Si12B12 nanocages are designed. The computational findings demonstrated that the doped isomers of Si12B12 nanocage have significant thermodynamic stabilities, with the highest binding energy of −74.15 kcal mol −1. The E H-L gap is excellently declined upon Be, Mg, and Ca doping and the lowermost E H-L gap is found at 0.92 eV. Calculations using TD-DFT revealed that isomers of the Si12B12 nanocage are transparent in the ultraviolet (UV) region. Confirmation of charge transfer and participation of different segments is explored by natural bond orbital (NBO) and total density of state (TDOS) as well as partial density of state (PDOS) analysis respectively. The types of interactions are investigated using non-covalent interaction (NCI) analysis. The isomer SiB-XV of Ca doped Si12B12 nanocage exhibits the eye-catching static first hyperpolarizability value of 4.71×104 au. Overall findings conclusively confirm that alkaline earth metals doped isomers of Si12B12 nanocage are potential contenders for nanoscale NLO materials because they have excellent stability and boosted NLO response. This research will cover the approach for the fabricating of large NLO response materials for innovative NLO applications.

Interplay between energy and geometry of parallel-displaced interactions in S8 dimer structures

Elemental sulfur exists in various allotropes, with the most stable form being the cyclic S8 allotrope. Although the orthorhombic α-S8 modification has been extensively studied, there has been no systematic analysis of noncovalent interactions between sulfur rings and their nature, geometries, and energies until now. To achieve this, we conducted a comprehensive study analyzing all crystal structures from the Cambridge Structural Database involving contacts between S8 molecules. Then, we combined those data with high-level quantum chemical calculations. The results revealed that the preferred orientation in the crystal structures is parallel-displaced. Quantum chemical calculations supported this finding, demonstrating that the most stable interaction in the S8 dimer occurs when two molecules adopt a parallel-displaced geometry resembling the one observed in the crystal structures. The interaction in the S8 dimer is very strong, with an energy of −8.70 kcal/mol, calculated at a highly accurate CCSD(T)/CBS level. In this stacking-like geometry, multiple S…S interactions can form, and the NCI analysis indicated an overlap of large surfaces of interacting molecules, significantly contributing to the system's stability. The SAPT2+(3) energy decomposition analysis showed that the predominant attractive force between two S8 molecules is dispersion, although the electrostatic component is also significant. This research holds importance in understanding the molecular assembly in solid sulfur and in systems that exhibit interactions between S8 molecules.

Interaction behavior study of HCl on (ZnS)n (n = 1–12) clusters and HCl effect on Hg0 adsorption

AbstractThe interaction behavior of HCl and (ZnS)n (n = 1–12) clusters and HCl effect on Hg0 adsorbed by (ZnS)n have been studied theoretically. The combined genetic algorithm and density functional theory (GA‐DFT) method has been used to obtain the structures of (ZnS)nHCl and (ZnS)nHgHCl (n = 1–12) clusters. The structural properties of (ZnS)nHCl and (ZnS)nHgHCl have been analyzed. The adsorption energies and interaction energies have been calculated. Bond length and bond order analysis has revealed that SH and ZnCl bonds form after HCl adsorbed on (ZnS)n clusters, while Hg0 can only weakly bind with (ZnS)nHCl clusters. According to thermodynamic adsorption analysis, the formation of (ZnS)nHCl clusters from (ZnS)n and HCl are spontaneous because of their negative Gibbs free energy changes. The formation of (ZnS)nHgHCl from (ZnS)nHCl and Hg are nonspontaneous for n = 1–4 and 9, and the Gibbs free energy changes have small negative values for other sizes. Electron localization function and noncovalent interaction (NCI) analysis of (ZnS)10HgHCl manifest that Hg and its nearest Zn form zinc amalgam. Projected density of state study has been performed to obtain the interaction nature of HCl and (ZnS)n clusters and Hg0 adsorption on (ZnS)nHCl clusters. Based on our study, HCl is chemical adsorbed by (ZnS)n clusters except (ZnS)4 cluster. After (ZnS)n adsorbs HCl, Hg0 can physically adsorb on (ZnS)nHCl clusters. The strength of Hg0 on (ZnS)nHCl is comparable to that of Hg0 on (ZnS)n, indicating that HCl can hardly affect the adsorption of Hg0 on ZnS clusters.

Theoretical study of an N-heterocyclic carbene-catalyzed annulation reaction between an enal and a β-silyl enone: Mechanism and origin of stereoselectivity

In this study, the mechanism and origin of the stereoselectivity of an N-heterocyclic carbene (NHC)-catalyzed transformation reaction between an enal and a β-silyl enone are systematically investigated using density functional theory (DFT) at the M06-2X level. Multiple pathways are proposed and studied to identify the most energetically favorable mechanism for the reaction. The calculation results show that the most energetically favorable pathway comprises the following processes: nucleophilic addition of NHC to the Si-face of the enal to form a zwitterionic intermediate, two sequential CsHCO3-assisted intramolecular proton shifts to produce an enolate intermediate, Michael-type addition of the enolate intermediate to the β-silyl enone, ring closure to construct a six-membered ring intermediate, and the dissociation of NHC to release the final product. The reaction between the enolate intermediate and the β-silyl enone is identified as the stereoselectivity-determining step, preferentially generating an RS-configured product. Subsequent atoms-in-molecules (AIM) and noncovalent interaction (NCI) analyses verify that the main factor for inducing stereoselectivity is the higher number of noncovalent intermolecular interactions in the low-energy transition state.

In-Silico Aided Screening and Characterization Results in Stability Enhanced Novel Roxadustat Co-Crystal

Roxadustat (RXD) is an approved drug substances for the treatment of renal anemia. It has poor aqueous solubility and photochemical stability. This study employs a comprehensive approach to enhance the stability and physicochemical properties RXD through coformer selection and characterization. The investigation integrates delta pKa analysis, molecular complementary assessment, molecular electrostatic potential surface analysis, and machine learning techniques to predict potential co-crystal formation and binding interactions between drug molecules and coformers. The co-crystal screening which lead to in a novel RXD-nicotinamide co-crystal (RXD-NA). Experimental characterization underscores the physical and chemical stability of the co-crystals. To elucidate the supramolecular synthons and understand the intermolecular interactions in the RXD-NA co-crystal, Hirshfeld surfaces analysis, quantum theory of atoms in molecules (QTAIM) analysis and non-covalent interaction (NCI) analysis were performed. Computational analysis of photo-isomer formation aligns with experimental observations, further enhancing our understanding of RXD-coformer interactions. RXD-NA co-crystal was found photo-chemically stable as compared to free base API drug substance. This integrated methodology provides a systematic framework for informed co-crystal design, holding promise for optimizing RXD formulations based on molecular interactions and stability considerations. Consequently, this study contributes valuable insights to the field of rational drug design and formulation optimization.

Controlling the Energetic Properties of N-Methylene-C-Linked 4-Hydroxy-3,5-dinitropyrazole- and Tetrazole-Based Compounds via a Selective Mono- and Dicationic Salt Formation Strategy.

In the quest to synthesize high-performing insensitive high-energy density materials (HEDMs), the main challenge is establishing an equilibrium between energy and stability. For this purpose, we explored 4-hydroxy-3,5-dinitropyrazole- and tetrazole-based energetic scaffolds connected via a N-methylene-C bridge. The hydroxy functionality between nitro groups on the pyrazole ring promotes physical stability via inter- and intramolecular hydrogen bonding and contributes to oxygen balance, supporting better energetic performance. Due to two acidic sites (OH and NH) with different reactivities, a series of monocationic and dicationic salts were synthesized, and their overall performance was compared. All compounds synthesized in this study have high physical stability with impact sensitivity >40 J and friction sensitivity >360 N. Monocationic salts were generally found to have better thermal stability with respect to their corresponding dicationic energetic salts, which showed better energetic performance. The salt formation strategy effectively improved the thermal stability of 2 (Td = 168 °C), where most energetic salts have decomposition temperatures higher than 220 °C. All of the compounds were characterized through IR, multinuclear NMR spectroscopy, high-resolution mass spectrometry (HRMS), and elemental analysis. The structure-property relationship was studied using Hirshfeld surface analysis, noncovalent interaction (NCI) analysis, and electrostatic potential studies.

Structural and computational insights into two trimethylenedipyridine co-crystals: Inputs from X-ray diffraction, Hirshfeld surface, PIXEL, QTAIM and NCI plots

Two trimethylenedipyridine co-crystals, [(TMDP)·(H2OBA)] (1) and [(TMDP)·(SUC)] (2) [TMDP = 4, 4′-trimethylenedipyridine, H2OBA = 4,4′-oxybis(benzoic acid), and SUC = succinic acid) were designed, synthesized and their single crystals were grown by slow evaporation technique. The grown crystals were characterized by elemental analysis and UV–Vis spectroscopic technique, and the structures of the grown crystals were elucidated using single-crystal X-ray diffraction analysis. Supramolecular assemblies of co-crystal (1) are stabilized through several intermolecular hydrogen bonds such as O‒H···N, C‒H···O, C‒H···π, as well as π···π interactions whereas for co-crystal (2) only intramolecular hydrogen bonding interaction, O‒H···N is responsible for stabilization of supramolecular network. Hirshfeld surfaces were used to gain additional insight into non-covalent interactions in molecular crystals, and 2D fingerprint plots provided a quantitative analysis of different non-covalent interactions in the crystal structures. The interaction energies of the molecular pairs, as well as the lattice energies of the crystal structures, have been studied using the PIXEL method. The nature and strength of the non-covalent interactions at their (3, –1) bond critical points (BCPs) have been explored using Bader's quantum theory of “Atoms in Molecules” (QTAIM). The non-covalent interactions were further characterized through the NCI plots.

Effect of binding pockets on the kinetics and thermodynamics of Diels-alder reaction in cucurbit-Uril family

Cucurbit-uril (CB-uril) family has witnessed a considerable increase in popularity over the last two decades due to its amazing binding ability which impart broad range of applications. Cucurbit-uril family members exhibit diversity in their binding pocket to accommodate guest molecules of different sizes which in turn impact the remarkable properties of these molecules. Herein, we have studied the influence of encapsulation on the kinetics and thermodynamics of the Diels-Alder reaction. Effects of binding pockets on the Diels-Alder reaction are explored by selecting CBn(n = 5–8)-uril. Bond evolution theory (BET) and non-covalent interaction (NCI) analyses have also been performed to gain insight into electronic distribution along the reaction route as well as bond formation/breakage to understand the mechanism of action and the role of weak/strong interactions between CBn-uril and reaction during the process. Activation energies for Diels-Alder reaction in CBn=6–8-uril (22.63 kcal mol−1, 21.37 kcal mol−1, and 19.45 kcal mol−1, respectively) are significantly lower than that of the bare reaction (25.45 kcal mol−1). While for P-DA reactions, activation energies within CBn=7,8-uril are observed as 19.29 kcalmol−1 and 14.45 kcalmol−1 (cis-1,2-dicyanoethylene), 18.46 kcalmol−1 and 14.65 kcalmol−1 (trans-1,2-dicyanoethylene), and 16.01 kcalmol−1 and 20.86 kcalmol−1 (tetracyanoethylene). CB7-uril has predicted the lowest activation energies for DA reaction with cis-1,2-dicyanoethylene and trans-1,2-dicyanoethylene compared to bare Ea ≈ 20.15 kcalmol−1 and 19.57 kcalmol−1, respectively. By making the reaction more exothermic with ER ≈ -40 kcal mol−1, CB6-uril has the lowest activation energy of ≈ 19.45 kcal mol−1, predicting CBn-uril as an effective cavity for researching the Diels-Alder process.

Intra- and Intermolecular Cation-π Interactions between Onium Salts and Alkynes/Acetylene: Experimental and Theoretical Insights.

Cation-π interactions between various onium salts, alkynes, and acetylene were studied, taking into account the substituents of the triple bond, the nature of the anions, and the polarity of the solvent, through a combination of MP2 calculations and experiments. In an intramolecular setting, these data (including single-crystal X-ray crystallography) concurred with the stability of folded conformers of alkynyl onium salts, even substituted with electron-withdrawing groups. To examine the contribution of these interactions on the alkyne electronic population, a thorough in silico study was carried out using natural bonding orbital analysis of the conformers. Intramolecular interactions from sulfonium salt tethered to phenylalkyne were highlighted, as illustrated above by the computed folded conformation (MP2) along with noncovalent interaction (NCI) analysis. Furthermore, investigations of intermolecular interactions, involving acetylene or phenylacetylene with various onium ions, revealed the high energy interactions of their complexes with phenyldimethylsulfonium chloride, as illustrated above with the complex PhC≡CH/PhMe2SCl (MP2 calculations and NCI analysis).

A stereoselective nontraditional Heck reaction mechanism: Origins of enantioselectivity and diastereoselectivity

Nontraditional Heck-type reactions of C = heteroatomic variants have been a great challenge. Herein, we computationally investigate a nontraditional stereoselective Heck mechanism regarding hydrazone C = N-NH2 by using density functional theory (DFT) methods. Calculations indicate that the total potential barrier of the conversion is 25.6 kcal/mol, which is reasonable to be crossed under the current reaction conditions. Unlike C = C π-bonds, the coordination of C = N with transition metal palladium into a η1-complex is confirmed. A larger π-bond insertion barrier for C = N is required, which is rationalized by frontier molecular orbital (FMO) analysis with a wider LUMO-HOMO energy gap. π-bond insertion is the enantioselectivity determining step of the strategy and that the pathway toward the R-isomer exhibits a much lower energy barrier (24.2 vs 40.1 kcal/mol). π-bond insertion is also the diastereoselective control step with using DBBP ligands. Non-covalent interaction (NCI) analysis confirms that greater spatial hindrance is responsible for the stereoselectivity of the protocol. Meanwhile, calculations show that using an acid-promoted tactic can effectively improve the in situ production of hydrazone and significantly reduce the energy barrier.