Non-covalent Interaction Analysis Research Articles

4D-QSAR and MIA-QSAR Studies of Aminobenzimidazole Derivatives as Fourth-generation EGFR Inhibitors.

The epidermal growth factor receptor (EGFR) protein has been intensively studied as a therapeutic target for non-small cell lung cancer (NSCLC). The aminobenzimidazole derivatives as the fourth-generation EGFR inhibitors have achieved promising results and overcame EGFR mutations at C797S, del19 and T790M in NSCLC. In order to understand the quantitative structure-activity relationship (QSAR) of aminobenzimidazole derivatives as EGFRdel19 T790M C797S inhibitors, the four-dimensional QSAR (4D-QSAR) and multivariate image analysis (MIA-QSAR) have been performed on the data of 45 known aminobenzimidazole derivatives. The 4D-QSAR descriptors were acquired by calculating the association energies between probes and aligned conformational ensemble profiles (CEP), and the regression models were established by partial least squares (PLS). In order to further understand and verify the 4D-QSAR model, MIA-QSAR was constructed by using chemical structure pictures to generate descriptors and PLS regression. Furthermore, the molecular docking and averaged noncovalent interactions (aNCI) analysis were also performed to further understand the interactions between ligands and the EGFR targets, which was in good agreement with the 4D-QSAR model. The established 4D-QSAR and MIA-QSAR models have strong stability and good external prediction ability. These results will provide theoretical guidance for the research and development of aminobenzimidazole derivatives as new EGFRdel19 T790M C797S inhibitors.

Hierarchical Self‐Assembly of Curved Aromatics: From Donor–Acceptor Porphyrins to Triply Periodic Minimal Surfaces

AbstractA saddle‐shaped π‐extended zinc porphyrin containing a peripheral pyridyl ligand undergoes quantitative self‐assembly into a cyclic trimer. The trimer has a prismatic structure with negatively curved side walls, which promote the formation of supramolecular organic frameworks stabilized by dispersion interactions. The first framework type, UWr‐1, has the npo topology, with a hexagonal structure analogous to the Schwartz H triply periodic minimal surface. Co‐crystallization of the trimer with either C60 and C70 produces the isomorphous cubic UWr‐2 and UWr‐3 phases, characterized by the ctn network topology and a structural relationship to the Fischer‐Koch minimal surface S. All three phases contain complex labyrinths of solvent‐filled channels, corresponding to very large probe‐accessible volumes (68 % to 76 %). The UWr‐2 network could be partly desolvated while retaining its long range dimensional order, indicating remarkable strength of the dispersion interactions in the crystal. A theoretical analysis of noncovalent interactions shows the role of geometrical matching between the negatively curved porphyrin units and positively curved fullerenes.

Hierarchical Self-Assembly of Curved Aromatics: From Donor-Acceptor Porphyrins to Triply Periodic Minimal Surfaces.

A saddle-shaped π-extended zinc porphyrin containing a peripheral pyridyl ligand undergoes quantitative self-assembly into a cyclic trimer. The trimer has a prismatic structure with negatively curved side walls, which promote the formation of supramolecular organic frameworks stabilized by dispersion interactions. The first framework type, UWr-1, has the npo topology, with a hexagonal structure analogous to the Schwartz H triply periodic minimal surface. Co-crystallization of the trimer with either C60 and C70 produces the isomorphous cubic UWr-2 and UWr-3 phases, characterized by the ctn network topology and a structural relationship to the Fischer-Koch minimal surface S. All three phases contain complex labyrinths of solvent-filled channels, corresponding to very large probe-accessible volumes (68 % to 76 %). The UWr-2 network could be partly desolvated while retaining its long range dimensional order, indicating remarkable strength of the dispersion interactions in the crystal. A theoretical analysis of noncovalent interactions shows the role of geometrical matching between the negatively curved porphyrin units and positively curved fullerenes.

Investigating the adsorption potential and sensitivity of pristine along with carbon, boron, and nitrogen substituted hetero-nanocages towards azacitidine drug

The use of nanomaterials as carriers for the delivery of a diverse array of anticancer drugs and their application as effective sensors in clinical environments has been steadily growing as a result of advancements in nanoscience. Using density functional theory at the B3LYP-D3/6-31G(d,p) level, this study made a comparative adsorption efficiency assessment of pure C24 and B12N12 nanocages along with some of their hetero-counterpart nanocages toward the anticancer drug azacitidine. Out of the nanostructures that were examined in this study, B6C6N12 nanocage appeared as the most prominent adsorbent by developing drug delivery conjugated structure that demonstrates the highest degree of stability in adsorbing the azacitidine, making it most suitable for transportation or detection purposes in both gaseous and aqueous environments. The confirmation of the interaction between the azacitidine and the adsorbents is further supported by examining frontier molecular orbitals, natural bond orbital, quantum theory of atoms in molecules, and non-covalent interaction analysis. The simulation of ultraviolet–visible spectra was performed for all systems to assess the feasibility of using ultraviolet–visible spectroscopy to track and monitor the binding of azacitidine to the suggested adsorbents. The findings presented here open up endless possibilities for these nanocages as drug delivery and detection systems of nanomedicine.

Hydantoin-D,L-valine: Synthesis, characterization, and non-covalent interaction analysis from crystallographic studies, DFTB calculations, and Hirshfeld surface analysis

The title compound, hydantoin-D,L-daline or (RS)-5-isopropyl-imidazolidine-2,4‑dione, a new amino acid hydantoin derivative with formula C6H10N2O2 has been synthesized and structurally characterized by FT-IR, NMR, and X-ray diffraction techniques. Spectroscopy results are consistent with the skeleton structure. The powder X-ray diffraction data confirms the phase purity of the crystalline sample. Single-crystal X-ray diffraction analysis indicated that the title compound crystallizes in the monoclinic space group P21/c (N°14), Z = 4, and unit cell parameters a = 5.493(3) Å, b = 23.53(2) Å, c = 6.254(3) Å, β= 115.09(4)°, V = 732.1(9) Å3. The molecular structure and crystal packing are stabilized by intermolecular N–H···O, C–H···O, and C–H···π hydrogen bonds forming an infinite two-dimensional network with chains described by the graph-set notation C(5), and centrosymmetric rings with graphs R22(8) and R44(16). The non-covalent interactions were analyzed employing DFTB calculations, which reproduce the main features of the stereochemistry and geometries exhibited by X-ray diffraction. Additionally, these intermolecular interactions were analyzed using Hirshfeld surfaces analysis and 2D fingerprint plots.

Insights into the Mechanism, Regio-/Diastereoselectivities and Ligand Role of Nickel-Initiated [3+2] Cycloadditions between Vinylcyclopropane and N-Tosylbenzaldimine

Density functional theory (DFT) was employed to explore the reaction mechanism, regio- and diastereoselectivities of nickel-initiated [3+2] cycloaddition between vinylcyclopropane (VCP) and N-tosylbenzaldimine assisted by phosphine ligands. Four different binding modes of the nickel center to VCP substrate were explored during the ring-opening of VCP, among which the C,C_anti and C,C_syn modes were verified to be the most accessible ones. Further explorations about four different phosphine ligand-assisted reactions based on the two most probable binding modes show that the difference in binding mode of bi- and monodentate phosphine ligands can vary the optimal reaction pathway, especially in the [3+2] cycloaddition process between the ring-opened intermediate and N-tosylbenzaldimine. The formation of C–C and C–N bonds between N-tosylbenzaldimine and the ring-opened intermediate through [3+2] cycloaddition is found to be stepwise, with the former acting as the rate-determining step (RDS) in most cases. Computed free energy barriers of RDS transition states on the optimal path I or II not only give out good predictions for reaction rates and half-lives, but also provide reasonable explanations for the major generation of cis-pyrrolidine. Noncovalent interaction analyses of key stationary points suggest the rate is influenced by both electronic effects and steric hindrance, while the diastereoselectivity is mainly controlled by electronic effects.

High-Density Energetic Materials with Low Mechanical Sensitivity and Twinning Derived from Nitroimidazole Fused Ring.

The innovative synthesis of 3,8-dibromo-2,9-dinitro-5,6-dihydrodiimidazo [1,2-a:2',1'-c]pyrazine and 3,9-dibromo-2,10-dinitro-6,7-dihydro-5H-diimidazo [1,2-a:2',1'-c][1,4]diazepine is described in this study. The tricyclic fused molecular structures are formed by the respective amalgamation of piperazine and homopiperazine with the imidazole ring containing nitro. Compound 1 and 2 possess excellent high-density physical properties (ρ1 = 2.49 g/cm3, ρ2 = 2.35 g/cm3) due to the presence of a fused ring structure and Br atom. In addition to their high density, they have high decomposition temperatures (Td > 290 °C) which means that they have excellent thermal stability and can be used as potential heat-resistant explosives. Low mechanical sensitivities (IS > 40 J, FS > 360 N) are observed. The twinning structure of 2 was resolved by X-ray diffraction. Non-covalent interaction analysis, Hirshfeld surfaces, 2D fingerprint plot, and Electrostatic potential analysis were used to understand the intramolecular interactions in relation to physicochemical properties. The unique structures of this type of compound provide new potential for the evolution of energetic materials.

Computational analysis of anti-cancer drug hydroxyurea adsorption on nanocages of gold, silver and copper: SERS and DFT assessment

The use of nanostructures in targeted drug delivery is effective in decreasing anticancer drug toxicity. Here, we discuss the theoretically predicted adsorption and interaction behavior of hydroxyurea [HU] with nano metal cages (nmC). HU interact the nmC through the N4 in primary amine with energies of −29.776, −30.684 and −22.105 kcal/mol for Au, Ag and Cu cage, respectively. As a result of reactivity studies, HU complexes with nmC (Au/Ag/Cu) are becoming more electrophilic and this gives the nmC system their bioactivity. It is suggested that nanocage is going to change the FMO's energy levels by means of absorption, so that it is used in drug administration. DOS and MEP were accomplished to gain additional understandings into the reactivity of proposed complexes. Method for improving the Raman signal of biomolecules is surface enhanced Raman scattering (SERS), which uses nanosized metal substrates. Chemical enhancement is evidenced by Mulliken charge distributions of all systems for detection and chemical compositions and exerts a significant role in determining them. In HU complexes containing nmC (Au/Ag/Cu), electron density was detected via ELF and LOL calculations. Based on the results of a non-covalent interaction (NCI) analysis, Van der Waals/hydrogen bonds/repulsive steric – interactions have been found. The title compound will also be analyzed in order to determine its bioactivity and drug likeness parameters, as a result, we will able to create a molecule with a highly favorable pharmacological profile and use the docking method to determine the values of the interaction energies for drug delivery. This study suggests that adsorption of drugs on nanocage surface occurs physically and functionalizing the nanocage has increased adsorption energy.

Promising sensors for pharmaceutical pollutant adsorption using Clar’s goblet-based 2D membranes

This study focuses on the design of new 2D membranes from connected Clar’s Goblet as a potential sensor for pharmaceutical pollutants, specifically the painkiller drugs aspirin, paracetamol, ibuprofen, and diclofenac. The electronic, optical, and interaction properties are investigated using density functional theory calculations. The Clar’s Goblet membranes (CGMs) that were chosen are semiconductors with an energy gap of around 1.5 eV, according to energy gap calculations and density of states. Molecular electrostatic potential (ESP) analysis shows that CGMs have electrophilic and nucleophilic sites, suggesting their suitability for interacting with pharmaceutical pollutants. The adsorption energies confirm the chemical adsorption of pharmaceutical pollutants with diclofenac showing the strongest adsorption. The UV–Vis absorption spectra of CGMs-drug complexes are analyzed, revealing a redshift compared to the absorption spectrum of CGMs alone, confirming the adsorption of these drugs. Further analysis using hole/electron examinations indicates that the type of excitation is local excitation rather than charge transfer excitation. This study quantitatively characterized hole and electron distribution in excited states using various indices. The analysis revealed local excitation transitions and significant charge transfer between the CGMs molecule and pharmaceutical pollutants. Additionally, non-covalent interaction analysis indicates the presence of van der Waals interactions, highlighting the adsorption behavior of the drugs. These results demonstrate the potential of CGMs as a highly sensitive sensor for pharmaceutical pollutants.

Investigations of the reaction mechanism of sodium with hydrogen fluoride to form sodium fluoride and the adsorption of hydrogen fluoride on sodium fluoride monomer and tetramer.

The reaction between Na and HF is a typical harpooning reaction which is of great interest due to its significance in understanding the elementary chemical reaction kinetics. This work aims to investigate the detailed reaction mechanisms of sodium with hydrogen fluoride and the adsorption of HF on the resultant NaF as well as the (NaF)4 tetramer. The results suggest that the reaction between Na and HF leads to the formation of sodium fluoride salt NaF and hydrogen gas. Na interacts with HF to form a complex HF···Na, and then the approaching of F atom of HF to Na results in a transition state H···F···Na. Accompanied by the broken of H-F bond, the bond forms between F and Na atoms as NaF, then the product NaF is yielded due to the removal of H atom. The resultant NaF can further form (NaF)4 tetramer. The interaction of NaF with HF leads to the complex NaF···HF; the form I as well as II of (NaF)4 can interact with HF to produce two complexes (i.e., (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF), but the form III of (NaF)4 can interact with HF to produce only one complex (NaF)4(III)···HF. These complexes were explored in terms of noncovalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analyses. NCI analyses confirm the existences of attractive interactions in the complexes HF···Na, NaF···HF, (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF, and (NaF)4(III)···HF. QTAIM analyses suggest that the F···Na interaction forms in the HF···Na complex while the F···H hydrogen bonds form in NaF···HF, (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF, and (NaF)4(III)···HF complexes. Natural bond orbital (NBO) analyses were also applied to analyze the intermolecular donor-acceptor orbital interactions in these complexes. These results would provide valuable insight into the chemical reaction of Na and HF and the adsorption interaction between sodium fluoride salt and HF. The calculations were carried out at the M06-L/6-311++G(2d,2p) level of theory which were performed using the Gaussian16 program. Intrinsic reaction coordinate (IRC) calculations were carried out at the same level of theory to confirm that the obtained transition state was true. The molecular surface electrostatic potential (MSEP) was employed to understand how the complex forms. Quantum theory of atoms in molecules (QTAIM) and noncovalent interaction (NCI) analysis was used to know the topology parameters at bond critical points (BCPs) and intermolecular interactions in the complex and intermediate. The topology parameters and the BCP plots were obtained by the Multiwfn software.

Investigating the sensing efficiency of C6O6Li6 for detecting lung cancer-related volatile organic compounds: A computational density functional theory approach

Volatile organic compounds (VOCs), such as acetone (AC), isoprene (IS), 1-hexene (HX), and benzene (BN), are important biomarkers in the exhaled breath of lung cancer patients. This research evaluates the potential of C6O6Li6 as a sensor for detecting these VOCs in the early stages of lung cancer. The adsorption of VOCs on C6O6Li6 was explored using Density Functional Theory (DFT) calculations at ωB97X-D3/def2-TZVP level of theory. Interaction energies for the most stable complexes were observed as −18.08 kcal/mol for AC@C6O6Li6, −14.06 kcal/mol for HX@C6O6Li6, −9.12 kcal/mol for IS@C6O6Li6, and −8.31 kcal/mol for BN@C6O6Li6. These values indicate the physiosorption of VOCs on C6O6Li6. Noncovalent interactions between the VOCs and C6O6Li6 were studied through Quantum Theory of Atom in Molecule (QTAIM) and Non-Covalent Interaction (NCI) analyses. The electronic properties were evaluated through Frontier Molecular Orbital (FMO), Natural Bond Orbital (NBO), Electron Density Difference (EDD), and Density of States (DOS) analyses. FMO analysis shows an increase in the HOMO-LUMO energy gap upon interaction of these VOCs with the C6O6Li6 surface, while NBO analysis indicates charge transfer from the surface to the VOCs. This study significantly enhances our understanding of C6O6Li6′s potential as a sensor material for early lung cancer detection using breath biomarkers.

Solvent effects on the structural, spectroscopic, electronic properties, NCI-RDG analysis, molecular docking and molecular dynamics studies of 1-benzyl-indole-3-carbinol

This investigation focuses on the 1-benzyl-indole-3-carbinol (1-benzyl-I3C) molecule and its capacity as a drug to combat breast cancer. The research employs different computational approaches including DFT simulations, molecular docking, and molecular dynamics calculations. The molecular configuration of 1-benzyl-I3C was optimized in the COSMO solvation model, using B3LYP/cc-pVTZ basis set. The modes of vibration of the compound were identified through Potential Energy Distribution (PED) simulations, and the results were found to be consistent with the available FT-IR and Raman data. The analysis of Natural Bond Orbitals (NBO) supports the idea that 1-benzyl-I3C has bioactive properties. The impact of solvents on the electronic characteristics of studied molecule is discussed. The reactive sites of 1-benzyl-I3C were confirmed by the local reactivity descriptors and the molecular electrostatic potential (MEP) surface analyses. Additionally, Non-covalent interaction (NCI) analysis confirms the existence of the Van der Waals interactions in the compound under investigation. Anti-breast cancer activities of the 1-benzyl-I3C molecule were examined based on molecular docking analysis, which reveals a good inhibitor nature of the studied molecule against the progesterone receptor (PR). The molecular dynamics analysis through the RMSD, RMSF, and Rg plots confirms the overall stability of the obtained 1-benzyl-I3C-PR complex.

Use quantum mechanical computational methods to investigate interactions between imidacloprid and boron nitride nanotubes

The study investigates the interaction between a boron nitride nanotube (BNNT) and an imidacloprid (IM) molecule. The structure of the BNNT is detailed, measuring 9.964 Å in diameter and 18.186 Å in length. Six interaction geometries (BNNT_IM_1 to BNNT_IM_6) between BNNT and IM are investigated, with BNNT_IM_6 showing the most thermodynamically stable interaction. The electronic interaction energies are calculated, and BNNT_IM_6 presents the lowest value (−1.89 eV), indicating a favorable interaction. Quantum theory of atoms in molecules (QTAIM) and analysis of noncovalent interactions (NCI) support the findings. BNNT_IM_6, with IM inside the nanotube, shows the highest electron sharing, explaining its superior stability. The chlorine-BNNT interaction was revealed to be a determining attractive component. The attraction/repulsion indices highlight BNNT_IM_1 as having the most attractive interaction, driven mainly by oxygen-BNNT and chlorine-BNNT interactions. The investigation emphasizes the importance of considering multiple factors, including electron density and interaction volume, in evaluating the strength of BNNT-IM interactions. This study model opens a proposal to assess the impact of functional groups, from a physicochemical perspective, of a molecule interacting with a nanotube surface.

O USO DAS FERRAMENTAS DA ANÁLISE DA SUPERFÍCIE DE HIRSHFELD NO ESTUDO DAS LIGAÇÕES NÃO-COVALENTES EM COMPLEXOS CORRELATOS

THE USE OF HIRSHFELD SURFACE ANALYSIS TOOLS IN THE STUDY OF NON-COVALENT BONDS IN RELATED COMPLEXES. The analysis of non-covalent interactions in crystalline structures through the Hirshfeld surface method using the CrystalExplorer® software has been widely used by the global scientific community over the past few decades. Although widely recognized, as far as we know, there has been no publication on this subject in the Química Nova journal. Therefore, in this work, we intended to demonstrate how these tools could be employed to study and compare the non-covalent bonds in 21 mononuclear complexes of the type [MY2(o-XPy)2], [MY2(m-XPy)2], and [MY2(p-XPy)2], where M = Zn2+ or Co2+, Y = Cl-, Br-, or I-; Py = pyridinic ligand ortho-, meta-, or para-monosubstituted by X, where X = Cl-, Br-, or I-. With a main emphasis on halogen bonds and π···π stacking interactions, the study demonstrates how Hirshfeld analysis can be used for a qualitative and quantitative comparison of non-covalent bonds, proving to be an important tool for a comprehensive understanding of the forces that stabilize these complexes in the solid-state. The study demonstrates the potential of Hirshfeld surface analysis as a valuable resource for synthetic chemists to select chemical species for rational synthesis and achieve desired properties or supramolecular arrays.

Trans vs. cis: a computational study of enasidenib resistance due to IDH2 mutations.

Isocitrate dehydrogenase 2 (IDH2) is a homodimeric enzyme that plays an important role in energy production. A mutation R140Q in one monomer makes the enzyme tumourigenic. Enasidenib is an effective inhibitor of IDH2/R140Q. A secondary mutation Q316E leads to enasidenib resistance. This mutation was hitherto only found in trans, i.e. where one monomer has the R140Q mutation and the other carries the Q316E mutation. It is not clear if the mutation only leads to resistance when in trans or if it has been discovered in trans only by chance, since it was only reported in two patients. Using molecular dynamics (MD) simulations we show that the binding of enasidenib to IDH2 is indeed much weaker when the Q316E mutation takes place in trans not in cis, which provides a molecular explanation for the clinical finding. This is corroborated by non-covalent interaction (NCI) analysis and DFT calculations. Whereas the MD simulations show a loss of one hydrogen bond upon the resistance mutation, NCI and energy decomposition analysis (EDA) reveal that a multitude of interactions are weakened.

Chemical bonding within AIIIBVI materials under uniaxial compression.

The work provides a comprehensive explanation of the nature of chemical bonding through quantum chemical topology for multilayers of AIIIBVI compounds, such as GaSe, InSe, and GaTe, spanning pressures from 0 GPa to 30 GPa. These compounds are subjected to pressure orthogonal to the multilayers. Quantum chemical topological indices indicate that uniaxial pressure induces changes in hybridisation, leading to the disappearance of interlayer van der Waals forces. The distinct nature of the elements within the compounds results in different pressures at which van der Waals interactions disappear, as revealed by non-covalent interaction analysis. The presence or absence of chemical bonding is assessed by quantum topological indices as Espinosa indices, charge density distribution difference, and crystal orbital Hamilton populations. The varying changes in hybridisation, as indicated by topological indices, are corroborated by variations in the population of the electronic projected density of states. Ultimately, the type of chemical bonding is identified through the Espinosa indices in the field of Bader theory. This analysis confirms the existence of shared shell bonds between AIII and BVI atoms in vacuum that goes to an intermediate bond between shared and closed shells called the transition zone with increasing pressure. The implications and importance of this work extend beyond the presented results. It suggests that many other classes of two-dimensional materials may undergo phase transitions under uniaxial stress, leading to the formation of new phases with potentially interesting electronic properties.

Systematic surface bowing in 2D III-nitride monolayers.

In this article we report novel composite materials of bucky ball (C60 fullerene) and III-nitrides (BN, AlN, GaN, InN). The experimental feasibility of the novel composite materials is confirmed through negative binding energies and molecular dynamics simulations performed at 500 K. The structural properties of the novel composites are explored through density functional theory. An unusual phenomenon of surface bowing is observed in the 2D structure of the III-nitride monolayers due to the C60 sticking. This surface bowing systematically increases as one proceeds from BN → AlN → GaN → InN. The electron density difference and Hirshfeld charge density analysis show smaller charge transfer during the complexation, which is probably due to weak van der Waal's forces. The presence of van der Waal's forces is also confirmed by the Atom in Molecule analysis, Reduced Density Gradient Technique and Non-covalent Interaction analysis. This work provides a foundation for further theoretical and experimental studies of the novel phenomenon of systematic bowing in the 2D structure of III-nitride monolayers.

Assessing the catalytic potential of novel halogen substituted carbene NHC (F, Cl, Br, I) catalysts in [3 + 2] cycloaddition reactions: A computational investigation.

This study investigated the catalytic behavior of NHC-X ligands (X = F, Cl, Br, I) in cycloaddition reactions, focusing on both mononuclear and binuclear pathways. Using NCI (noncovalent interaction), RDG (reduced density gradient), ELF (electron localization function), and LOL (localized orbital locus) computational analyses, the electronic interactions and stability of the ligands were examined. The results showed that NHC-Cl exhibited the least steric hindrance and strongest transition state stabilization, making it the most efficient catalyst. NHC-F also demonstrated strong stabilization, particularly in the binuclear pathway. In contrast, NHC-Br showed moderate efficiency, whereas NHC-I was the least effective owing to higher Gibbs free energy values and greater steric hindrance, especially in polar solvents such as water and acetonitrile. This study emphasizes the crucial role of solvent effects and thermodynamic factors in influencing the catalytic efficiency. These findings provide a framework for optimizing NHC-based catalysts for chemical transformations.

Binary conformers of a flexible, long-chain fluoroalcohol: dispersion controlled selectivity and relative abundances in a jet.

The complex conformational panorama of binary 4,4,4-trifluoro-1-butanol (TFB) aggregates was investigated using chirped-pulse Fourier transform microwave spectroscopy, aided by conformational searches using CREST (Conformer-Rotamer Ensemble Sampling Tool) and quantum chemistry calculations. From nearly 1500 initial dimer geometries, 16 most stable binary candidates were obtained within a relative energy window of ∼4 kJ mol-1. Rotational spectra of five binary conformers were experimentally observed in supersonic expansion and assigned. Interestingly, three out of the five observed binary conformers are composed solely of monomer conformers, which were not observed in their isolated gas phase forms in jet expansion. In addition, an observed dimer that is made exclusively of the most stable TFB monomer subunits does not correspond to the global minimum. The intricate kinetically and thermodynamically controlled dimer formation mechanisms are discussed, and a modified kinetic-thermodynamic model was developed, providing conformational abundances that are in good agreement with the experiment. Subsequent non-covalent interaction analyses reveal that the observed conformers are held together by one primary O-H⋯O hydrogen bond and secondary intermolecular C-H⋯O, C-H⋯F, and/or O-H⋯F interactions, as well as C-H⋯H-C London dispersion interactions between the methylene groups. Further symmetry-adapted perturbation theory analyses of the TFB dimer conformers and related alcohol dimers reveal a considerable rise in dispersion contributions with increasing n-alkyl carbon chain length and highlight the role of dispersion interactions in preferentially stabilizing the global minimum of the TFB dimer.

Mechanism of cationic ring-opening polymerisation of ε-caprolactone using metallocene/borate catalytic systems: a DFT and NCI study on chain initiation, propagation and termination.

We present a comprehensive DFT investigation on the cationic ring-opening polymerisation (CROP) of ε-caprolactone (CL) using zirconocene/borate catalyst systems. All possible pathways of the interaction between cationic species [Cp2ZrMe+] and counteranions, [A-] = [MeB(C6F5)3]- and [B(C6F5)4]-, were examined during chain initiation, propagation, and termination steps. The calculations reveal an active chain-end mechanism with O-alkyl bond cleavage of the polymerisation. The catalytic performance of the two counteranions is found to be identical, and they influence the initial process through stabilisation of the cationic species via non-covalent interactions (NCI), with the [MeB(C6F5)3]- anion stabilising the catalyst-monomer complex more effectively than the [B(C6F5)4]- anion by 24.3 kJ mol-1. The first two propagations are likely the rate-determining step, with calculated free-energy barriers of 61.4-71.2 and 73.9-80.6 kJ mol-1 with and without the anions (A-), respectively. The presence of the counteranion significantly affects the third propagation rate, lowering the barriers up to 20 kJ mol-1. Comparison of the first termination and the third propagation shows that they are not competitive, with the termination being less facile. We also studied the initiation and propagation steps for the hafnocene catalyst and found that the Hf catalyst slightly favours the CL CROP in comparison to the Zr catalyst. Analysis of solvent and dispersion interaction demonstrates that both factors play an important role in the process. NCI analysis reveals weak (van der Waals) interactions at the contacts between the cationic species and the counteranions during the reaction course. Overall, our results offer insights into the structures and interactions involved in the polymerisation.