Non-covalent Interaction Analysis Research Articles

Solvent influence on the optical absorption, frontier molecular orbitals, and electronic structure of 1-bromo adamantane.

The study of the influence of solvent on 1-bromo adamantane (BAD) exposes prominent solvatochromatic shifts in the optical absorbance and substantial solvent effects on the electronic structure. This facilitates the molecular probe abilities for the BAD with respect to the surrounding environments such as dielectric constant and polarity. BAD exhibits positive solvatochromism for nonpolar solvents and negative solvatochromatic shifts for polar and aromatic solvents. In accordance with this, significant energy changes are obtained on the orbital occupancies of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), resulting in a large difference in energy among the various solvation environments. According to this, the HOMO-LUMO gap decreases in nonpolar solvents, and it increases with respect to polarity in the case of polar and aromatic solvents. Computed thermodynamic parameters and noncovalent interaction analysis also demonstrate the noticeable changes for different solvent dielectric continuums with more changes for solvent continuums with large dielectric constants. Experimentally recorded UV-Vis absorption spectra of the solvents exhibit positive and negative solvatochromism for the n to σ* electronic transition. Computational investigations carried out with equation-of-motion coupled-cluster with single and double excitations and configuration interaction singles calculations by means of the solvent model density implicit solvation model clearly demonstrate the strong influence of solvents on the electronic structure of the BAD molecule.

Computational insight into the formation of cation-π/cation-lone pair complexes between 3d-metal (II) ions and furan.

Cation-π and cation-lone pair interactions between 3d-metal (II) ions [Fe(II), Co(II), Ni(II) and Cu(II)] and furan are explored in the formation of 1:1 and 1:2 type complexes. Both cation-π (IEgas = -192.27 to -312.65 kcal mol-1) and cation-lone pair (IEgas = -163.13 to -271.76 kcal mol-1) interactions are reasonably strong and lead to the formation of stable 1:1 and 1:2 type complexes in gas phase. The complexes are also stable in solvent phase, but their stability is reduced significantly in presence of solvent dielectrics, especially in ethanol, DMSO and water. Formation of the complexes is thermodynamically favourable (exothermic and spontaneous). Charge transfer (Δq = 0.62 to 1.92 e-), Laplacian of electron density (∇2ρ = 0.1435 to 0.6628 au) and total electron energy density (H(r) = -0.0019 to -0.0436 au) analysis have argued in favour of partial ionic and partial covalent character of the interactions. Density functional theory (DFT) is exclusively used for the study. Polarizable continuum model (PCM) is used to perform solvent phase study. Natural bond orbital (NBO), quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) analyses are performed for understanding other aspects of complex formation.

Steric and Electronic Effects of Zirconocenealkyl-Borate Ion Pairs on Catalyst Activation: A Theoretical Study.

The effectiveness of metallocene catalysts in the cationic ring-opening polymerization (cationic ROP) of ε-caprolactone (CL) is influenced by the choice of metallocene/borate systems, particularly their bulkiness. Recent research examines this effect on the initiation and propagation stages of cationic ROP. We conducted a density functional theory study on the precatalyst activation of cationic CL ROP by zirconocene/borate catalysts, where four models of zirconocene precatalysts (Cp2ZrMe2 (a), (Me5Cp)CpZrMe2 (b), (Me5Cp)2ZrMe2 (c), and Ind2ZrMe2 (d)) were combined with boron cocatalysts B(C6F5)3 and [X+][B(C6F5)4 -] (X+ = Ph3C+ or PhMe2NH+). We modeled and predicted their thermodynamic, steric, and electronic properties during ion-pair formation and separation. The calculated Gibbs energies of ion-pair formation correlated with the positive charge at the metal center and steric congestion of the catalyst. All catalyst precursors showed exothermic and exergonic insertion of CL, toluene solvent, and contact ion pairs; solvent-separated ion pairs were the preferred activation pathway. Catalyst c showed the most stable ion pair in precatalyst activation, with the lowest separation energy, aided by methyl group bulkiness and toluene solvent. We evaluated Cp'-based ligands using percent buried volume (%V Bur) trends. Noncovalent interaction analysis indicated weak interactions at ion-pair contacts. This study enhances our understanding of cationic ROP and could aid in developing new polymerization catalysts for polyester synthesis.

In Silico Structural Insights and Potential Inhibitor Identification Based on the Benzothiazole Core for Targeting Leishmania major Pteridine Reductase 1.

Leishmaniasis is reported as the second most common protozoonosis, with the highest prevalence and mortality rate. Among the Leishmania drug targets, Pteridine Reductase 1 of Leishmania major (LmPTR1) proved to be promising because Leishmania is auxotrophic for folates. Thus, this study employed a combination of ligand- and structure-based approaches to screen new benzothiazole compounds as LmPTR1 inhibitor candidates. Initially, a highly predictive quantitative structure-activity relationship (QSAR) model was able to identify the relevant hybrid descriptors, with an accuracy of over 93%. Insights into the mechanism of action indicated Phe113, His241, Leu188, Met183, and Leu226 as key residues. New commercially available compounds were screened using QSAR, docking, and pharmacokinetic properties as filters. Molecular dynamics, non-covalent interactions analysis, and quantum chemical calculation of binding enthalpy demonstrated that the lead compound (ZINC 72229720) forms a stable complex with LmPTR1, indicating it as a new promising LmPTR1 inhibitor.

Docking heparan sulfate-based ligands as a promising inhibitor for SARS-CoV-2.

Heparan sulfate (HS) linear polysaccharide glycosaminoglycan compound is linked to components from the cell surface and the extracellular matrix. HS mediates SARS-CoV-2 infection through spike protein binding to cell surface receptors and is required to bind ACE2, prompting the need for electronic structure and molecular docking evaluation of this core system to exploit this attachment in developing new derivatives. Therefore, we have studied five molecules based on HS using molecular docking and electronic structure analysis. Non-covalent interaction analysis shows hydrogen bonding and van der Waals interactions in the binding to RBD-ACE2 interface and 3CLpro. SDM3 and SDM1 molecules present the lowest gap, including solvent effect under 154.6kcal/mol, and exhibit the most reactivity behavior in this group, potentially leading to enhanced interaction in docking studies. Heparan sulfate and four derivatives were optimized using B3LYP functional with two basis sets 6-31 + G(d,p) and def2SVP. Electronic structure was used to explore the main interactions and the reactivity of these molecules, and these optimized structures were used in the molecular docking study against 3CLpro, RBD, and ACE2.

Intermolecular Interactions in Mixed Choline Acetate and Maleic Acid Systems

Mixed systems based on ionic liquids are promising innovative solvents due to their properties, which are strictly connected to the interactions that arise among the components. The present work investigates the intermolecular interactions of a mixed choline acetate and maleic acid system and their modifications with increasing acid content. MM/DFT calculations provided indications about the possible geometric configurations of the systems while Non-Covalent Interaction analysis was useful to describe and distinguish secondary interactions. The number of available configurations decreases at high acid concentration. Moreover, intramolecular hydrogen bonding was observed in all configurations except that in the most stable one of the lowest acid content mixture. Concomitantly, far-infrared spectroscopy was used to investigate intermolecular interactions and provided support to the computational results.

Effect of a single water molecule on the conformational preferences of a capped Pro–Gly dipeptide in the gas phase

Herein, we have investigated the effect of microhydration on the secondary structure of a capped dipeptide Boc-DPro-Gly-NHBn-OMe (Boc = tert-butyloxycarbonyl, Bn = Benzyl), i.e., Pro–Gly (PG) with a single H2O molecule using gas-phase laser spectroscopy combined with quantum chemistry calculations. Observation of a single conformer of the monohydrated peptide has been confirmed from IR-UV hole-burning spectroscopy. Both gas-phase experimental and theoretical IR spectroscopy results confirm that the H2O molecule is inserted selectively into the relatively weak C7 hydrogen bond (γ-turn) between the Pro C=O and NHBn N–H groups of the peptide, while the other C7 hydrogen bond (γ-turn) between the Gly N–H and Boc C=O groups remains unaffected. Hence, the single H2O molecule in the PG⋯(H2O)1 complex significantly distorts the peptide backbone without appreciable modification of the overall secondary structural motif (γ–γ) of the isolated PG monomer. The nature and strength of the intra- and inter-molecular hydrogen bonds present in the assigned conformer of the PG⋯(H2O)1 complex has also been examined by natural bond orbital and non-covalent interaction analyses. The present investigation on the monohydrated peptide demonstrates that several H2O molecules may be required for switching the secondary structure of PG from the double γ-turn to a β-turn that is favorable in the condensed phase.

Quenching Rate Constants of Lewis Base-Boryl Radical by Substrates: a Laser Flash Photolysis Study.

The advanced strategy using Lewis base-boryl radicals (LBRs) has recently been proposed for the addition of alkyl substituents to the full-carbon quaternary center of an organic molecule. However, as the rate-determining step in the whole route, reaction rate constants of LBRs with substrates are extremely lacking. In this paper, 4-dimethylaminopyridine (DMAP)-BH2⋅ was selected as a representative of LBRs, and its reactions with six monochloro-substituted substrates, including three methyl chlorobenzoates and three chlorinated acetanilides were studied in experiments and theoretical calculations. The bimolecular reaction rate constants, kq, were determined using laser flash photolysis approach. By comparing activation energies along the two addition pathways, we have clarified the rate-determining step as the attacking to carbonyl oxygen instead of chlorine atom. Furthermore, noncovalent interaction (NCI) analyses on these substrates indicate that weak interactions, such as hydrogen-bonding and van der Waals interactions, have significant influence on the reactivity of these substrates. Our study provides concrete clues to extend this synthetic strategy.

An AIE-based fluorescent dye for selective staining of polyamide microplastics without pretreatment: Applications to environmental samples and zebrafish

A novel staining dye, BEM ((1E,1'E)-1,1'-([2,2'-bithiophene]-5,5'-diyl)bis(N-(9-ethyl-9H-carbazol-3-yl)methanimine)) was synthesized for selective identification of polyamide (PA) micrplastics. BEM showed unique photophysical properties such as solvatochromism, intramolecular charge transfer (ICT), and aggregation induced emission (AIE) which were demonstrated through spectroscopic analysis and density functional theory (DFT) calculations. The optimal staining conditions for selective staining of PA by BEM were established by evaluating the staining efficiency according to the variation of the solvent compositions, concentrations of BEM, and staining durations. BEM demonstrated outstanding selective staining of PA among 11 types of microplastics (MPs) and 5 types of non-plastics through the emission of green fluorescence. BEM successfully identified PA without any noticeable influence on the size change of PA, aging of PA, and pH alteration of the solvent. In addition, BEM was practically applied to environmental samples like river water, seawater, and soil for selective identification of PA without pretreatment. In particular, the cost-effective technique of BEM-labeled PA allowed to monitor the location and accumulation of PA in living zebrafish. The interaction between PA and BEM was investigated through scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS), which suggested that BEM might be adsorbed onto the surface of PA. Moreover, non-covalent interaction (NCI) analysis demonstrated that the intermolecular hydrogen bonds and van der Waals interactions would play a significant role in the adsorption process between PA and BEM.

Drug molecules beyond chemical biology: fluorescence- and DFT-based investigations for fluoride ion sensing and the trace detection of chloroform.

Excessive unmonitored use of fluoride has remained a threatening issue for a long time now as its long-term use is linked to several health issues. Similarly, chloroform is a highly carcinogenic solvent that requires proper monitoring. The increasing demand for a convenient, selective and sensitive fluoride and chloroform sensor intrigued us to utilize etoricoxib (ECX) as a sensor as it is highly safe and easily available. The photophysical properties of ECX, which were previously unexplored, were now studied with increasing water fractions and a significant aggregation-induced emission enhancement (AIEE) was seen through fluorescence spectroscopy. ECX was also successfully used for the trace level detection of chloroform through a significant emission enhancement. Similarly, the ECX-based sensor successfully detected fluoride ions by showing enhancement in emission intensity with maximum emission wavelength at 373 nm. Through fluorescence titration experiments, the effects of different conditions and interfering species on the sensing efficiency of ECX were studied, and the results showed that the sensor was highly selective and sensitive towards fluoride, with a limit of detection of 20 nM. Other than fluorescence spectroscopy, the type of interaction between the sensor and analyte was also studied through UV-Vis spectroscopy, revealing a non-covalent type of interaction, which was further validated through DFT studies. Frontier molecular orbital (FMO) analysis was performed along with density of state (DOS) studies to investigate the energy levels of the orbitals. Non-covalent interaction (NCI) and natural bond orbital (NBO) analysis provided information about the types of interaction and charge transfer. ECX has the potential to be used for real-time sensing applications and could be used for sensing moisture and fluoride in real samples.

Computational Library Enables Pattern Recognition of Noncovalent Interactions and Application as a Modern Linear Free Energy Relationship.

A quantitative and predictive understanding of how attractive noncovalent interactions (NCIs) influence functional outcomes is a long-standing goal in mechanistic chemistry. In that context, better comprehension of how substituent effects influence NCI strengths, and the origin of those effects, is still needed. We sought to build a resource capable of elucidating fundamental origins of substituent effects in NCIs and diagnosing NCIs in chemical systems. To accomplish this, a library of 893 NCI energies was calculated encompassing cation-π, anion-π, CH-π, and π-π interactions across 60 different arenes and heteroarenes. The interaction energies (IEs) were calculated using symmetry-adapted perturbation theory (SAPT), which identifies electrostatic, inductive, exchange-repulsive, and dispersive contributions to total IE. This descriptor library provides a comprehensive platform for evaluating substituent effect trends beyond traditional molecular descriptors such as Hammett values, frontier molecular orbital energies, and electrostatic potential, thereby expanding the tools available to analyze modern chemical processes that involve NCIs. To demonstrate the application of this library, three case studies in asymmetric catalysis and supramolecular chemistry are presented. These case studies informed the development of an automated NCI analysis tool, which employs statistical analyses to diagnose a particular NCI in a chemical system of interest.

POCOP-Ni(II) pincer compounds derived from phloroglucinol. Cytotoxic and antioxidant evaluation.

POCOP-Ni(II) pincer compounds have primarily been explored as catalysts, but their potential biological activity has been scarcely studied. To address this gap, we evaluated the anticancer and antioxidant potential of four POCOP-Ni(II) complexes derived from phloroglucinol. A comprehensive supramolecular analysis, based on single-crystal X-ray diffraction (DRX) structures, was conducted using Hirshfeld surfaces and non-covalent interaction analysis. The cytotoxicity of all complexes was systematically assessed against various cancerous cell lines, as well as a non-cancerous cell line (COS-7). The results revealed that complexes 1b and 1c exhibited remarkable antiproliferative activity, with IC50 values ranging from 2.43 to 7.85μM against cancerous cell lines U251, K562, HCT-15, MCF-7, and SK-LU-1. To further elucidate their mechanism of action, a competitive fluorescence displacement assay with ethidium bromide (EB) suggested that these complexes possess the ability to intercalate with DNA. This multifaceted investigation not only enhances our understanding of the biological potential of POCOP-Ni complexes but also provides valuable insights into their structural features and interactions, paving the way for future exploration in both catalytic and therapeutic domains.

Probing the hybridized triazole-chalcones: an in-depth investigations of molecular structure journey towards antibacterial potential against DNA gyrase

The present study delves into the comprehensive structural investigations of the six Chalcone derivatives (4A–F), each featuring the 1, 2, 3 triazole linkages. The work commences with the synthesis by employing a multifaceted approach to unravel its molecular properties and potential biological significance. Single crystal X-ray diffraction technique was used to determine the precise 3D structure of the grown single crystals of 4D and 4F. The crystal structure exhibited significant investigations on intermolecular interactions, particularly hydrogen bonding, π–π stacking, Van der Waals forces and other intra-intermolecular interactions contributing to the molecular assembly. Density Functional Theory (DFT) was employed using the B3LYP functional and 6-311++ G (d, p) basis set to explore compound’s electronic structure and physicochemical properties. Quantum theory of atoms in molecule (QTAIM) and non-covalent interactions (NCI) analysis provided insights into the topology of the compounds. Further the biological assessments were performed to know the antimicrobial properties of the compounds against both gram-negative and gram-positive bacteria. The research also culminated the evaluation of the drug-likeness of the compounds, drawing upon ADME-T predictions. Further, in silico molecular docking and dynamics simulation analysis were conducted to anticipate the most favorable binding configuration of the derivatives within the active site cavity of the Type II topoisomerase DNA gyrase receptors. In vitro antimicrobial study was also performed and it demonstrated notable results. Overall, this extensive study offers a deep study into the structural intricacies of these compounds, providing insights for chemical and biological evaluations, particularly in the context of bacterial enzyme inhibition.

End Group Effects on Anion Binding in Tetraglycine Peptide: A Computational Study.

The importance of anions in various processes has led to a search for molecules that can effectively recognize and interact with these anions. This study explores how the tetraglycine [(Gly)4] peptide in its zwitterionic, neutral, and terminally capped forms acts as a receptor for H2PO4 - and HSO4 - anions within the framework of supramolecular host-guest chemistry. Using molecular dynamics (MD) simulations, we obtained the conformations of the receptor-anion complexes. Density functional theory (DFT), quantifies the complexes' interaction energies in both gas and solvent phases. Proton transfer within the zwitterionic complex with H2PO4 - anion alters peptide charge distribution, affecting its conformation and binding site arrangement, as analysed by quantum mechanics/molecular mechanics (QM/MM) methods. Symmetry-adapted perturbation theory (SAPT) and noncovalent interactions analysis highlight the role of electrostatic interactions in these receptor-anion complexes. It emphasizes the key interactions such as N-H⋅⋅⋅⋅O and O-H⋅⋅⋅O=C between the peptide backbone and anions and elucidates the molecular recognition mechanism driven by crucial noncovalent interactions. The termination of the peptide's end groups modulates anion binding sites from the backbone to the charged N-terminal, resulting in distinct binding sites. Our findings provide insights for designing peptides tailored to function as anion receptors in diverse supramolecular chemistry applications.

Unraveling the noncovalent interactions in a organic crystal using Quantum theory of atoms in molecules

X-ray diffraction analysis, combined with the Quantum Theory of Atoms in Molecules (QTAIM), serves as a powerful tool for describing chemical bonding in real space for solids. By integrating theoretical and experimental data, a more accurate representation of atomic interactions including Van der Waals forces, hydrogen bonds, covalent, ionic, and metallic bonds is achieved. The analysis of noncovalent interactions through electronic density enables the identification of Lewis acid and base sites, while also revealing the directional ‘key-lock’ interactions that correspond to molecular recognition. The examination of critical points in the electron density and its derivatives allows for the characterization of the types of interactions present in crystal packing. This study focuses on the experimental and theoretical investigation of noncovalent interactions within a molecular crystal of a newly synthesized carbohydrazide derivative. The crystal structure was determined using X-ray single-crystal diffraction, and the crystallographic asymmetric unit was optimized via DFT, with the results compared to experimental data. Noncovalent interactions in real space such as Van der Waals forces, hydrogen bonds, and inter- and intramolecular steric repulsions were analyzed in terms of electron density and its derivatives. The QTAIM framework was applied to quantify the strength of these interactions, employing Voronoi deformation density and electron localization and delocalization indices for solids. The results presented in this work, using crystal engineering, reveal that derivatives of diurea compounds crystallize following a characteristic pattern that forms a synthon configuration. The strength of this interaction, quantified through QTAIM analysis of the electronic density, provides a deeper understanding of the chemistry of these compounds, both in terms of biological activity and coordination chemistry.

Engaging Two Anions with Single Cation in Energetic Salts: Approach for Optimization of Oxygen Balance in Energetic Materials.

The field of high energy density materials faces a long-standing challenge to achieve an optimum balance between energy and stability. While energetic salt formation via a combination of oxygen- and nitrogen-rich anions (providing energy) with nitrogen-containing cations (providing stability) has been a proven approach for improving physical stability, constraints such as lowering density and energetic performance remain unresolved. This can be addressed by utilizing oxygen-containing cations for salt formation. However, this approach is rarely explored because its synthesis is challenging. In this work, we have designed an oxygen-rich cationic precursor 2 by incorporating 4-amino-3,5-dinitropyrazole with 3,4-diaminotriazole via an N-methylene-C bridge. Further combination with energetic acids resulted in the formation of high-performing, physically stable energetic salts 3-10. The salts were found to be generally more energetic than the salts of respective energetic acids with previously reported cations and showed prominent improvement in physical stability with respect to their anionic precursors. All the compounds were thoroughly characterized through IR, NMR spectroscopy, HRMS, and elemental analysis. Salt 9 was confirmed through 15N NMR analysis, and salts 2 and 8 were confirmed through single-crystal X-ray diffraction. Additional analyses such as Hirshfeld surface analysis, noncovalent interaction (NCI) analysis, and electrostatic potential studies were also carried out to correlate the structure-property relationship.

Impact of UV-B Photoaging on Chlorpyrifos Adsorption by PET Microplastics: Insights from Experimental and DFT Analysis.

Microplastics (MPs) in the environment pose a persistent concern, as these plastic particles can adversely impact both aquatic ecosystems and human health. MPs are subject to natural weathering and aging processes, such as photodegradation, which significantly alter their surface morphology and physicochemical properties, thereby influencing their fate, transport, and sorption behavior. To better understand how aging affects these properties and to elucidate the mechanisms behind the interactions with the chlorpyrifos pesticide, poly(ethylene terephthalate) (PET) microplastics (<100 μm) were subjected to accelerated photoaging in a UV-B chamber for varying exposure times. Several characterization techniques were employed, including scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), X-ray diffraction (XRD), infrared spectroscopy (IR), point of zero charge (pHPZC), and thermogravimetric analysis (TGA). Additionally, the percentage of crystallinity and carbonyl index (CI) were calculated. The results demonstrated a decrease in pHPZC following photodegradation, likely due to an increase in δ- (-C=O) groups, consistent with the CI findings. SEM revealed surface deterioration caused by aging, while TGA indicated an early thermal degradation stage associated with water volatilization, suggesting enhanced hydrophilicity. Density functional theory (DFT) calculations showed that the PET monomer absorbs slightly in the UV-B region, leading to excitation and subsequent radical reactions that form Norrish type I products. The adsorption capacity of aged PET increased compared to the pristine material, likely due to the molecular geometry becoming more planar, facilitating interactions between the aged MPs and chlorpyrifos, as confirmed by noncovalent interaction (NCI) analysis. These findings highlight the significant potential of aged microplastics to adsorb micropollutants and act as vectors in aquatic environments.

Solvents and their influence on electronic properties in IEFPCM solvation model, anticancer activity, and docking studies on (E)-2-((4-chlorobenzylidene) amino)phenol

The Schiff base (E)-2-((4-chlorobenzylidene)amino)phenol (4CL2AM) has been synthesized from 4-chlorobenzaldehyde and 2-aminophenol. Spectroscopic techniques like FTIR, Raman, UV, fluorescence, and NMR were used to characterize the synthesized compound. The experimental data well matched with the DFT method (B3LYP/cc-pVDZ basis set). The frontier molecular orbital (FMO), molecular electrostatic potential (MEP), and electronic spectra (UV–visible) analysis were conducted on three different solvents such as gas, DMSO, and water. The frontier molecular orbital (FMO) analysis calculated the HOMO-LUMO energy gap as 4.0109 eV, 4.0406 eV, and 4.0411 eV for the gas phase, DMSO, and water respectively. Molecular electrostatic potential (MEP), localized orbital locator (LOL), and electron localize function (ELF) analysis revealed positions of localized and delocalized orbitals as well as electrophilic and nucleophilic attack sites. The natural bond orbital analysis (NBO) predicted highest stabilization energy was 33.37 kcal/mol. The locations of the covalent and non-covalent interactions were investigated by density overlaps region indicator (DORI), interaction region indicator (IRI), and noncovalent interaction (NCI) analysis. Drug likeness and ADME analysis were investigated. In vitro, anticancer activity studies revealed against MCF-7 breast cancer cell lines. In the molecular docking study, the predicted lowest binding energy is −5.77 kcal/mol for the 6NLV-4CL2AM system.

Behaviour of 1-butyl-3-methylimidazolium chloride, 1-butyl-3-methylimdazolium thiocyanate and 1-butyl-1-methypyrrolidium chloride in dimethyl sulfoxide: Experimental, NCI and QTAIM analysis

The aim of this study is to examine the cation and anion influence on intermolecular interactions of mixtures comprising ionic liquids (ILs): 1-butyl-3-methylimidazolium chloride [Bmim][Cl], 1-butyl-3-methylimdazolium thiocyanate [Bmim][SCN] and 1-butyl-1-methylpyrrolidium chloride [Bmpym][Cl] with dimethyl sulfoxide (DMSO) at various temperatures. To understand the influence of cation and anion as well as temperature on interactions between the mixtures, thermodynamics parameters: apparent molar properties were calculated from the measured density (ρ) and sound velocity (u) data and fitted to the Redlich-Mayer type equation in order to obtained limiting apparent molar properties of the studied mixtures. A detailed non-covalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analysis was done using density functional theory calculations. These calculations provided information on the electrostatic interactions between the anion, cation, and solvent. The experimental and computational results show that there is hydrogen bonding and strong ionic interactions in the studied systems.

Exploring the Impact of Protein Chain Selection in Binding Energy Calculations with DFT.

Calculation of binding free energies between a protein and a ligand are highly desired for computer-aided drug design. Here we approximate the binding energies of ABL1, an enzyme which is the target for drugs used in the treatment of chronic myeloid leukaemia, with minimal models and density functional theory (DFT). Starting from the crystal structures of protein-drug complexes, we estimated the binding free energies having used all available individual molecules (protein chains) within each structure, not only a single one as commonly used, in order to see if the choice of the protein chain is important in such calculations. Differences were observed between chains in the same file. Energy decomposition analysis (EDA) revealed that the most important factors for binding were exchange, repulsion and electrostatics. The desolvation term varied dramatically between the inhibitors (between 4.2 and 92.3 kcal/mol). All functionals showed similar patterns in the EDA and in discriminating between the ligands. Non-covalent interactions (NCI) analysis was used to further explain the differences between protein chains and functionals. Overall, it is shown that small minimal models of a drug binding site can be useful to infer on the suitability of an initial crystal structure for further analysis such as EDA.