Pairwise Intermolecular Interactions Research Articles

The interaction mechanism of polystyrene microplastics with pharmaceuticals and personal care products

Microplastics (MPs) have been detected in the hydrosphere, with hazardous implications in transporting coexisting water pollutants. Our knowledge about the interaction mechanisms that MPs establish with organic pollutants are still growing, which is essential to understand the adsorption properties of MPs and their relative stability with adsorbates. Here, we used classical (force field methods) and ab-initio (density functional theory) computational chemistry tools to characterize the interaction mechanisms between Polystyrene-MPs (PS-MPs) and pharmaceuticals/personal care products (PPCPs). Adsorption conformations and energies, thermochemistry, binding, and energy decomposition analyses were performed to obtain the quantitative mechanistic information. Our results show that PS-MPs have permanent dipoles, increasing the interaction with neutral PPCPs while repelling the charged pollutants; in all cases, a stable physisorption takes place. Moreover, PS-MPs increase their solubility upon pollutant adsorption due to an increase in the dipole moment, increasing their co-transport ability in aqueous environments. The stability of the PS-MPs/PPCPs complexes is further confirmed by thermochemical and molecular dynamics trajectory analysis as a function of temperature and pressure. The interaction mechanism of high pKa pollutants (pKa > 5) is due to a balanced contribution of electrostatic and dispersion forces, while the adsorption of low pKa pollutants (pKa < 5) maximizes the electrostatic forces, and steric repulsion effects explain their relative lower adsorption stability. In this regard, several pairwise intermolecular interactions are recognized as a source of stabilization in the PS-MPs/PPCPs binding: hydrogen bonding, π-π, OH⋯π, and CH⋯π, CCl⋯CH and CH⋯CH interactions. The ionic strength in solution slightly affects the adsorption stability of neutral PPCPs, while the sorption of charged pollutants is enhanced. This mechanistic information provides quantitative data for a better understanding of the interactions between organic pollutants and MPs, serving as valuable information for sorption/kinetic studies.

Structural examination, theoretical calculations, and pharmaceutical scanning of a new tetralone based chalcone derivative

A tetralone based chalcone compound, (2E)-2-(2,3,4-trimethoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one [TBDN] was synthesized, and crystals were grown by repeated crystallization in a mixture of acetone and ethyl methyl ketone (EMK) [1:2] at room temperature. The crystal structure of the compound was derived by single-crystal X-ray diffraction studies (SXRD). The title compound was crystallized in a monoclinic crystal system with a P21/c space group and the crystal structure is stabilized by C-H…O type intermolecular hydrogen bonds. Hirshfeld surfaces and the associated 2D fingerprint plots were generated and their analysis provides information regarding the weak intermolecular interactions and the intra contacts contribution to the total Hirshfeld surface in the crystal structure. The pair-wise intermolecular interactions and their role in stabilizing the molecule were investigated via energy frameworks. The modes of vibrational frequencies were assigned through FTIR spectral analysis both experimentally and theoretically. In addition, Density functional theory (DFT) based calculations including HOMO-LUMO energies, Molecular Electrostatic potential surface (MEPs), Mulliken charges, and Fukui functions were also performed. The donor-acceptor interactions were studied with the help of natural bond orbital (NBO) analysis. Bioactivity assessment reveals that the compound obeys Lipinski's rule and showed good drug-likeness with the score -0.17 to -0.39. Molecular docking studies on the title compound complexed with Gram-negative (E. Coli) and Gram-positive (Staphylococcus aureus) bacteria reveal an excellent binding affinity between the ligand and the target protein. Thus, the title compound can be a promising antibacterial agent but require further biological and pharmaceutical investigation.

Structure-property relationship in thioxotriaza-spiro derivative: Crystal structure and molecular docking analysis against SARS-CoV-2 main protease

Detailed structural and non-covalent interactions in thioxotriaza-spiroderivative (DZ2) are investigated by single crystal structure anslysis and computational approaches. Its results were compared with the previously reported spiroderivative (DZ1). The crystal structure analysis revealed various C–H…O, N–H…O, C–H…N and N–H…S hydrogen bonds involved in constructing several dimeric motifs to stabilize the crystal packing. The differences and similarities in the relative contribution of non-covalent interactions in DZ1 and DZ2 compounds are compared using the Hirshfeld surface analysis and 2D fingerprint plots. The binding energies of specific molecular pairs and homodimers have been obtained using molecule–molecule interaction energy calculation. The hierarchy and topology of pair-wise intermolecular interactions are visualized through energy frameworks. The nature and strength of intra and intermolecular interactions were characterized using non-covalent interaction index analysis and the quantum theory of atoms in molecule approach. Further, molecular docking of compounds (DZ1 and DZ2) with SARS-CoV-2 main protease for COVID-19 is performed. And the superposition of these ligands and inhibitor N3, which is docked into the binding pocket of 7BQY, is presented. The binding affinity of −6.7 kcal/mol is observed, attributed to hydrogen bonding and hydrophobic interactions between the ligand and the amino acid residues of the receptor.

Structural and biological characterization of a biomolecule: (3E)-3-(2, 4, 5-trimethoxyphenyl) methylidene) - 2, 3-dihydro-4H-1-benzopyran-4-one

The title compound, C19H18O5, has been synthesized using the Claisen-Schmidt condensation reaction from the mixture of 2,3 dihydro-4H-1-benzopyran-4-one and 2,4,5 trimethoxy benzaldehyde using ethanol as solvent. The crystal has been characterized for its 3 D structure and structural parameters were elucidated via the X-ray diffraction (XRD) method. The crystallographic parameters such as bond lengths, bond angles, and torsion angles were estimated and are comparable with the literature values. Hirshfeld surfaces namely dnorm, electrostatic potential, shape index, and curvedness were analyzed to visualize and to evaluate the weak intermolecular interactions, positive and negative potential regions, C-H…π, and π…π stacking interactions, respectively. The 2 D fingerprint plots for the whole and delineated interactions were also generated to estimate their contributions to the total Hirshfeld surface. The pairwise intermolecular interactions were calculated as the sum of four scaled energy components namely electrostatic (Eele), polarization (Epol), dispersion (Edis), and exchange-repulsion (Erep), and graphically represented as energy frameworks. The energy frameworks analysis reveals that the total stabilizing energy is highly influenced by dispersion (Edis) energy than the other components. The material has been screened for its cytotoxic effect on normal cell lines (VERO) and anticancer activity on breast cancer cell lines (MCF-7) and the material is found to be a potential candidate against cancer proliferation.

Crystal Structure, Hirshfeld Surfaces and Energy Framework Studies of a Biologically Active Compound (3E)-3- (2,4- dimethoxybenzyldene) -2,3-dihydro- 4H-chromen-4-one

A new chalcone derivative (3E)-3-(2,4-dimethoxybenzyldene)-2,3-dihydro-4H-chromen-4-one (DBDB) has been synthesized by following the Claisen-Schmidt condensation reaction method at ambient temperature using the slow evaporation technique. The 3D crystal structure was solved using the single-crystal X-ray diffraction method (XRD). XRD intensity data reveal that the title compound crystallizes in an orthorhombic crystal system with non-centrosymmetric space group P21 21 21. The crystallographic parameters such as bond lengths, bond angles, torsion angles were estimated and are found to be in the normal range and comparable with the literature values. The unit cell packing of the molecules shows that the adjacent molecules are linked via C-H…O hydrogen bonds. Hirshfeld surfaces namely dnorm, electrostatic potential, shape index, and curvedness were analyzed to visualize and to evaluate the weak intermolecular interactions, positive and negative potential regions, C-H…π, and π…π stacking interactions, respectively. The 2D fingerprint plots for the whole and delineated interactions were generated and analyzed to estimate their contributions to the total Hirshfeld surfaces. The pairwise intermolecular interactions were calculated as the sum of four scaled energy components namely electrostatic (Eele), polarization (Epol), dispersion (Edis), and exchange-repulsion (Erep) and graphically represented as energy frameworks. The energy frameworks analysis reveals that the total stabilizing energy is highly influenced by dispersion (Edis) energy than the other components. In-vitro and in-silico investigations have also been performed for the title molecule which discloses the efficacious for use as a drug in inhibiting breast cancer cells without affecting the normal cells.

3,6-bis (2,2,2-trinitroethylnitramino)-1,2,4,5-tetrazine. Structure and energy abilities as a component of solid composite propellants

The work addresses to the study of the molecular and crystal structure and properties of a new energy-intensive compound 3,6-bis(2,2,2-trinitroethylnitramino)-1,2,4,5-tetrazine (NBTAT), first obtained by the authors in 2020. NBTAT compound crystallizes in the monoclinic system, space group P2(1)/n, density at room temperature 1.939 g/cm3. The energies of crystal packing and pairwise intermolecular interactions in NBTAT and its unnitrated analogue BTAT were calculated, and their comparative analysis was carried out. The enthalpy of formation of NBTAT molecules was calculated by quantum-chemical methods using Gaussian 09, and the enthalpy of formation of NBTAT in the solid phase (618 kJ/mol) was estimated. The energy capabilities of NBTAT as an oxidizer of solid composite propellants are estimated. It is shown that in metal-free compositions NBTAT is significantly superior to ammonium perchlorate (AP), dinitramide ammonium salt (ADN), HMX, BTAT at all stages of rocket systems, and is comparable to the superdense CL-20 yielding to the latter at the lower stages and slightly winning at the upper stages.

Intra-molecular 1,5-S⋯N σ-hole inter-action in (E)-N'-(pyridin-4-yl-methyl-idene)thio-phene-2-carbohydrazide.

The title compound, C11H9N3OS, (I), crystallizes in the monoclinic space group P21/n. The mol-ecular conformation is nearly planar and features an intra-molecular chalcogen bond between the thio-phene S and the imine N atoms. Within the crystal, the strongest inter-actions between mol-ecules are the N-H⋯O hydrogen bonds, which organize them into inversion dimers. The dimers are linked through short C-H⋯N contacts and are stacked into layers propagating in the (001) plane. The crystal structure features π-π stacking between the pyridine aromatic ring and the azomethine double bond. The calculated energies of pairwise inter-molecular inter-actions within the stacks are considerably larger than those found for the inter-actions between the layers.

Relating the tableting behavior of piroxicam polytypes to their crystal structures using energy-vector models

Piroxicam crystallises into two polytypes, α1 and α2, with crystal structures that contain identical molecular layers but differ in the way that these layers are stacked. In spite of having close structural similarity, the polytypes have significantly different powder tabletting behaviour: α2 forms only weak tablets at low pressures accompanied by extensive capping and lamination, which make it impossible to form intact tablets above 100 MPa, while α1 exhibits superior tabletability over the investigated pressure range (up to 140 MPa). The potential structural origin of the different behaviour is sought using energy-vector models, produced from pairwise intermolecular interaction energies calculated using the PIXEL method. The analysis reveals that the most stabilising intermolecular interactions define columns in both crystal structures. In α2, a strongly stabilising interaction between inversion-related molecules links these columns into a 2-D network, while no comparable interaction exists in α1. The higher dimensionality of the energy-vector model in α2 may be one contributor to its inferior tabletability. A consideration of probable slip planes in the structures identifies regions where the benzothiazine groups of the molecules meet. The energy-vector models in this region are geometrically similar for both structures, but the interactions are more stabilising in α2 compared to α1. This feature may also contribute to the inferior tabletability of α2.

Mimicking Intermolecular Interactions of Tight Protein-Protein Complexes for Small-Molecule Antagonists.

Tight protein-protein interactions (Kd <100 nm) that occur over a large binding interface (>1000 Å2 ) are highly challenging to disrupt with small molecules. Historically, the design of small molecules to inhibit protein-protein interactions has focused on mimicking the position of interface protein ligand side chains. Here, we explore mimicry of the pairwise intermolecular interactions of the native protein ligand with residues of the protein receptor to enrich commercial libraries for small-molecule inhibitors of tight protein-protein interactions. We use the high-affinity interaction (Kd =1 nm) between the urokinase receptor (uPAR) and its ligand urokinase (uPA) to test our methods. We introduce three methods for rank-ordering small molecules docked to uPAR: 1) a new fingerprint approach that represents uPA's pairwise interaction energies with uPAR residues; 2) a pharmacophore approach to identify small molecules that mimic the position of uPA interface residues; and 3) a combined fingerprint and pharmacophore approach. Our work led to small molecules with novel chemotypes that inhibited a tight uPAR⋅uPA protein-protein interaction with single-digit micromolar IC50 values. We also report the extensive work that identified several of the hits as either lacking stability, thiol reactive, or redox active. This work suggests that mimicking the binding profile of the native ligand and the position of interface residues can be an effective strategy to enrich commercial libraries for small-molecule inhibitors of tight protein-protein interactions.

Supramolecular Architecture of Substituted Tetraphenyl-carbo-benzenes from the Energetic Viewpoint.

The use of DFT-calculated energy-vector diagrams (EVDs) featuring the topology of pairwise intermolecular interaction energies is applied to crystals of carbo-benzenes. A homogeneous set of six ideally centrosymmetric tetraphenyl-carbo-benzenes is selected, with various substituents R in para positions: R=4-anisyl, 1-ethyl-2-phenyl-1H-indol-3-yl, 2-chloro-2-(1-ethyl-2-phenyl-1H-indol-3-yl)ethenyl, tetradecyl, and 9,9-dihexyl-9H-fluoren-2-yl, 2-(9,9-dihexyl-9H-fluoren-2-yl)ethynyl. The basic structural motifs (BSMs) of the crystals vary from layers to columns, depending on the size and shape of the substituents R. The BSM cohesion is shown to rely on π-stacking, CH-π and dispersive interactions. Solvate molecules are shown to have a negligible role in the formation of the BSM, whereas they loosen the interaction between neighbouring BSMs.

Intermolecular Interaction Energies in Hydroquinone Clathrates at High Pressure

The energy landscape and its evolution with pressure have been studied for two hydroquinone clathrates in combination with the apohost β-hydroquinone structure. Pressure is used as a means for probing interatomic, or intermolecular, potentials. The forces in organic clathrates are generally dominated by strong intermolecular interactions in a host framework, with smaller contributions from subtle interactions between the guest molecules and the surrounding framework. Pairwise intermolecular interactions energies have been quantified for the hydroquinone–methanol and hydroquinone–acetonitrile clathrate up to pressures of 8.6(2) and 14.1(4) GPa, respectively. In both cases, reversible pressure induced phase transitions are observed, where the host framework tilts to form skewed cavity channels and break the 3-fold rotation symmetry. The compression of the hydroquinone–acetonitrile structure is found to be isotropic, whereas it is anisotropic for the hydroquinone–methanol compound, emphasizing the implicatio...

Energy frameworks: insights into interaction anisotropy and the mechanical properties of molecular crystals.

We present an approach to understanding crystal packing via 'energy frameworks', that combines efficient calculation of accurate intermolecular interaction energies with a novel graphical representation of their magnitude. In this manner intriguing questions, such as why some crystals bend with an applied force while others break, and why one polymorph of a drug exhibits exceptional tabletability compared to others, can be addressed in terms of the anisotropy of the topology of pairwise intermolecular interaction energies. This approach is applied to a sample of organic molecular crystals with known bending, shearing and brittle behaviour, to illustrate its use in rationalising their mechanical behaviour at a molecular level.

Two-dimensional convex-molecule fluid model for surface adsorption of proteins: effect of soft interaction on adsorption equilibria.

Adsorption of proteins on membrane surfaces plays an important role in cell biological processes. In this work, we develop a two-dimensional fluid model for proteins. The protein molecules have been modeled as two-dimensional convex and soft particles. The Lennard-Jones potential for circular particles and Kihara (12,6) potential for elliptical particles with hard core have been used to model pairwise intermolecular interactions. The equation of state of the fluid model has been derived using Weeks-Chandler-Andersen decomposition and it involves three parameters, an attraction, a repulsion, and a size parameter, which depend on the shape and core size of the molecules. For validation of the model, a two-dimensional molecular dynamics simulation has been performed. Finally, the model has been applied to study the adsorption of proteins on a flat membrane. In comparison with the existing model of hard and convex particles for protein adsorption, our model predicts a higher packing fraction for the adsorption equilibria. Although the present work is based on Lennard-Jones-type interaction, it can be extended for other specific soft interactions between convex molecules. Thus the model has general applicability for any other two-dimensional adsorption systems of molecules with soft interaction.

Spatially Homogeneous QM/MM for Systems of Interacting Molecules with on-the-Fly ab Initio Force-Field Parametrization.

Quantum and classical mechanics are combined in a hybrid many-body interaction model to enable the computationally affordable study of systems containing many interacting molecules. This model treats intramolecular and pairwise intermolecular interactions quantum mechanically, while many-body electrostatic induction effects are approximated using a polarizable force field. In this paper, we demonstrate that parametrizing the force field with distributed multipoles and atom-centered polarizabilities obtained on-the-fly from ab initio quantum mechanical monomer calculations makes the model very accurate and eliminates nearly all empiricism. Test calculations on water, formamide, hydrogen fluoride, and glycine-water clusters, all of which exhibit strong many-body interactions, are presented. The performance of the hybrid model is competitive with related point-charge embedding models.

High-Pressure19F NMR Measurements of a Series of Fluorinated Benzenes in Supercritical Carbon Dioxide

The high-pressure and high-resolution NMR cell method has been developed for precise measurements of supercritical carbon dioxide solutions. 19F NMR chemical shifts of a series of fluorinated benzenes, C6H n F m (n = 6 − m and m = 1 ∼ 6) in CO2 at dilute concentrations were measured over a wide pressure range up to 35 MPa at 314.3 K. The density dependence of the corrected chemical shift, where the bulk magnetic susceptibility contribution was subtracted, was well represented by a cubic function of CO2 density for any fluorinated benzene. The linear coefficients, arising from pairwise intermolecular interactions, were found to be dependent on the numbers and positions of fluorine atoms in the fluorinated benzenes. The solute–solvent interaction between fluorine and CO2 was discussed.

Experimental and molecular-statistical investigation of adsorption of aminoadamantanes on graphitized thermal carbon black

Thermodynamic characteristics of adsorption of some isomeric aminoadamantanes on graphitized thermal carbon black were determined by molecular-statistic calculations and gas-chromatographic measurements. The parameters of the potential function for the pairwise intermolecular interactions between nitrogen in saturated amines and carbon in graphite were calculated. The best agreement between the experimental and calculated Henry constants for 1-aminoadamantane is attained by introducting a correction taking into account the influence of the “cage” effect on α-substituents in the adamantane unit in the parameters of the ϕN...C(GTCB) atom-atom potential.

Investigation of CO2/Fluorine Interactions through the Intermolecular Effects on the 1H and 19F Shielding of CH3F and CHF3 at Various Temperatures and Pressures

The nuclear shielding for both the 1H and 19F nuclei of CH3F and CHF3 was investigated as a function of pressure and temperature. The density region investigated extended from low, gaslike conditions to study pairwise intermolecular interactions to high, liquidlike densities to study multibody effects on nuclear shielding. The temperature range was from 30 to 150 °C. Neat samples of CH3F and CHF3, along with CO2 mixtures of these fluorocarbons, were investigated by 1H and 19F high-pressure NMR. Molecular dynamics simulations were undertaken to describe the pair-distribution functions for both the neat samples and mixtures to aid in the interpretation of the 1H and 19F nuclear shielding determined from high-pressure NMR. The NMR spectra of the neat fluoromethanes and their CO2 mixtures suggest that there are no distinct or specific interactions between the fluoromethanes and CO2 and that as the temperature increases the multibody effects play less of a role in nuclear shielding.

Potential curves of two-molecule interactions in some smectic and ferroelectric liquid crystals

The atom-atomic potential method is used to study the potential curve of pairwise intermolecular interactions in smectic crystals C [C5H11O-(OH)C6H3-CH=N-C6H4-C5H11 (A), C10H21O-C6H4-CH=CH-C6H4-OC10H21 (B)], ferroelectric smectic liquid crystals C* [C7H15O-C6H4-C6H4-COOCH2C*H(CH3)C2H5 (C), C8H17O-C6H4-C6H4-C2H4C*H(CH3)C2H5 (D)], and binary systems A+C and A+D. Both inter- and intramolecular parameters as well as their mutual effects are taken into consideration. The intermolecular interactions are shown to significantly affect the conformations of isolated molecules. For the CC, DD, and AD interactions, the antiparallel ⇅ packing of molecules is found to be most favorable. In the case of the AA and AC interactions, the ⇈ and ⇅ packings are equally favorable in terms of energy (energy difference Upair does not exceed 0.8 kcal/mole). Despite the structural similarity between the chiral molecules C and D, the presence of the highly polar groups -O- , OH, CH=N, and COO leads to pronounced changes in the position and orientation of molecules in their packing in the AC and AD pairs. The pair interaction energy Upair near the minimum point was studied as a function of the shift of molecules relative to each other along the long axis X and of the angle 9 between the long molecular axes. The curve of U(pair) vs the shift along X has a few deep local extrema. The possibility of formation of energetically favorable molecular associates (dimers) in the compounds is demonstrated. The associates are stabilized by dipole-dipole intermolecular interactions.

Prediction of the Senses of Helical Amphiphilic Assemblies from Effective Intermolecular Pair Potential: Studies on Chiral Monolayers and Bilayers

It is well-known that the senses (or the handedness) of the helical assemblies formed from compressed monolayers and bilayers of chiral amphiphiles are highly specific about the chirality of the monomers concerned. We present here a molecular approach that can successfully predict the senses of such helical morphologies. The present approach is based on a reduced tractable description in terms of an effective pair potential (EPP) which depends on the distance of separation and the relative orientations of the two amphiphiles. This approach explicitly considers the pairwise intermolecular interactions between the groups attached to the chiral centers of the two neighboring amphiphiles. It is found that for a pair of the same kind of enantiomers the minimum energy configuration favors a twist angle between molecules and that this twist from neighbor to neighbor gives rise to the helicity of the aggregate. From the known twist angles at the minimum energy configuration the successive arrangement of an array of molecules can be predicted. Therefore, the sense of the helicity can be predicted from the molecular interactions. The predicted senses of the helical structures are in complete agreement with all known experimental results.

Determination of long-range intermolecular interaction energies using RPA/moment function methods. Application to H 2O, H 2O 2 and H 2O/H 2O 2 mixtures

The fully expanded expression for the Boltzmann-averaged pairwise intermolecular interaction energy of two molecules of arbitrary symmetry in the long-range (interaction < kT) limit has recently been determined explicitly as a series in r − n ( r is the intermolecular separation) for n < 11. The resultant expression contains only multipolar products (point moment functions: PMFs) and energy terms which are characteristic of the ground state and excitation properties of the isolated molecules. These quantities are determined for H 2O and H 2O 2 using the single particle-hole RPA method, and the interaction energy contributions determined by direct state summation. Static electric dipole polarizabilities are determined as a by-product of the procedure, and are shown to agree closely with finite field results using a comparable basis. For the chiral H 2O 2/H 2O 2 system, the r −6 and r −9 discrimination energies are also calculated, suggesting that the r −9 contributions could well exceed the r −6 discriminatory terms for separations less than 20 au.