Noncovalent Interaction Index Research Articles

σ-Hole Site-Based Interactions within Hypervalent Pnicogen, Halogen, and Aerogen-Bearing Molecules with Lewis Bases: A Comparative Study.

σ-Hole site-based interactions in the trigonal bipyramidal geometrical structure of hypervalent pnicogen, halogen, and aerogen-bearing molecules with pyridine and NCH Lewis bases (LBs) were comparatively examined. In this respect, the ZF5···, XF3O2···, and AeF2O3···LB complexes (where Z = As, Sb; X = Br, I; Ae = Kr, Xe; and LB = pyridine and NCH) were investigated. The electrostatic potential (EP) analysis affirmations outlined the occurrence of σ-holes on the systems under consideration with disparate magnitudes that increased according to the following order: AeF2O3 < XF3O2 < ZF5. In line with EP outcomes, the proficiency of σ-hole site-based interactions increased as the atomic size of the central atom increased with a higher favorability for the pyridine-based complexes over NCH-based ones. The interaction energy showed the most favorable negative values of -35.97, -44.53, and -56.06 kcal/mol for the XeF2O3···, IF3O2···, and SbF5···pyridine complexes, respectively. The preferentiality pattern of the studied interactions could be explained as a consequence of (i) the dramatic rearrangement of ZF5 molecules from the trigonal bipyramid geometry to the square pyramidal one, (ii) the significant and tiny deformation energy in the case of the interaction of XF3O2 molecules with pyridine and NCH, respectively, and (iii) the absence of geometrical deformation within the AeF2O3···pyridine and ···NCH complexes other than the XeF2O3···pyridine one. Quantum theory of atoms in molecules and noncovalent interaction index findings reveal the partially covalent nature of most of the investigated interactions. Symmetry-adapted perturbation theory affirmations declared that the electrostatic component was the driving force beyond the occurrence of the considered interactions. The obtained findings will help in improving our understanding of the effect of geometrical deformation on intermolecular interactions.

Computational study on the characteristics of the complexes resulting from the interaction of carbonyl selenide and hypohalous acids

This study computationally investigates the properties and competition of complexes formed by the interaction between hypohalous acids (HOX, where X = F, Cl, Br, and I) and carbonyl selenide (COSe) at the MP2/aug-cc-pVTZ computational level. Three distinct groups of complexes were obtained. The first group, consisting of complexes with a cyclic structure (HB-TB), exhibited the highest stability. remaining two groups formed less stable linear structures with different characteristics (ChB and XB). In the first group, the electronegativity of the halogen atom significantly influenced the stability of the complexes. Conversely, the stability of complexes in groups II and III was primarily determined by the acid and base strengths of the interacting monomers. To comprehensively evaluate the obtained results, various analyses were employed, including Molecular electrostatic potential (MEP), geometry Optimization, Spectroscopic, Interaction energy (SE), Natural bond orbital (NBO) analysis, Atoms in molecules (AIM) analysis, Non-covalent interaction (NCI) index, Energy decomposition analysis (EDA), and Electron density difference(EDD) analysis.

Exploring the effect of substituents on the supramolecular assemblies built by non-covalent interactions in three closely related 1,3,4-oxadiazole-2(3H)-thione derivatives: An evaluation of antimicrobial and anti-proliferative activities

Three closely related 1,3,4-oxadiazole-2(3H)-thione N-Mannich bases were synthesized and characterized by spectroscopic and single crystal X-ray diffraction methods. X-ray analysis reveals that the title molecules adopt l-shaped conformation, and a slight structural deviation around substituent groups is noted. The Hirshfeld surface and 2D fingerprint plots demonstrate the effect of substituents (piperidine, morpholine, and thiomorpholine) on the intermolecular interactions. The CLP-PIXEL energy analysis identified the most significant interactions in the molecular dimers (that characterize the crystal packing) with respect to the total intermolecular interaction energies. These dimers are held together by various non-covalent interactions including C–H⋅⋅⋅S/N/O/Cl/π interactions in addition to unconventional lone pair⋅⋅⋅π interactions. A molecule with thiomorpholine substituent is favoured by two σ-hole interactions (Cl⋅⋅⋅Cl halogen bond and S⋅⋅⋅N chalcogen bond) in the solid state. Furthermore, the molecular electrostatic potential (MEP) surfaces and deformation electron density help to describe the existence of σ-hole on the Cl and thione S atoms. Noncovalent interaction index (NCI) and quantum theory of atoms in molecules (QTAIM) methods are used to delineate the nature of observed noncovalent interactions in the molecular dimers. In vitro data of antibacterial and anti-proliferative activities indicate that compound with morpholine substituent showed a moderate antibacterial activity against all tested Gram-positive bacterial strains. However, molecules with piperidine and thiomorpholine showed notable effectiveness against the HepG-2 cell line. Molecular docking analysis was performed with two liver cancer targets, VEGFR2 and RET, in order to understand the interactions between the ligand and the active site residues of these targets.

Sensing applications of graphitic carbon nitride (g-C3N4) for sensing SO2 and SO3 – A DFT study

Gas sensors are instruments that detects and monitors the presence of harmful and toxic gases in the atmosphere. They are an essential tool for maintaining environmental health, air quality, and safety, and their invention has prompted an extensive research and advancement in the field of gas detection. The sensing and adsorption behaviour of graphitic carbon nitride are analyzed to detect noxious gases SO2 and SO3 using density functional theory. Upon absorption of SO2 and SO3 analytes on the surface of the carbon nitride (C6N8), moderate physiorption for the SO2 analyte (−37.11 kJ mol−1), and high chemisorption for SO3 analyte (−67.90 kJ mol−1) are observed. The interaction energies depict weak van der Waals forces that is further demonstrated by the noncovalent interaction index (NCI), symmetry perturbation theory (SAPT0) and quantum theory of atoms in molecules (QTAIM) analysis. Using the natural bond orbital analysis, UV–Vis analysis, electron localization function, molecular electrostatic potential, and density of state (DOS) analysis, the electronic properties of complexes were analyzed to determine the significant impacts of the adsorption of these analytes (SO2 and SO3) on the carbon nitride C6N8. Natural bond orbital analysis revealed that charge migration occurs from the carbon nitride C6N8 surface towards the analytes (SO2 and SO3) during complex formation that are −0.032 and −0.189 e−, for SO2@C6N8 and SO3@C6N8 complexes. The analytes (SO2 and SO3) behave as electrophiles and the carbon nitride C6N8 surface serves as a nucleophilic attack in both complexes. The chemical reactivity of both complexes was shown by the development of new excited states in the PDOS spectrum. At 300 K, the recovery period was calculated by applying the transition state theory to analyze the reusability of the carbon nitride C6N8 surface. Our finding provides a theoretical foundation for the possible use of carbon nitride C6N8 surface for gas sensors targeting significant air pollutants such as SO2 and SO3 in the environment.

Aluminium phosphide (Al12P12) nanocage as a potential sensor for volatile organic compounds: A DFT study.

The efficacy of aluminium phosphide (Al12P12) nanocage toward sensing methanol (MeOH) and ethanol (EtOH) volatile organic compounds (VOCs) was herein thoroughly elucidated utilizing various density functional theory (DFT) computations. In this perspective, MeOH⋯ and EtOH⋯Al12P12 complexes were investigated within all plausible configurations. According to the energetic features, the EtOH⋯Al12P12 complexes exhibited larger negative values of adsorption and interaction energies with values up to -27.23 and -32.84 kcal mol-1, respectively, in comparison to the MeOH⋯Al12P12 complexes. Based on the symmetry-adapted perturbation theory (SAPT) results, the electrostatic forces were pinpointed as the predominant component beyond the adsorption process within the preferable MeOH⋯ and EtOH⋯Al12P12 complexes. The findings of the noncovalent interaction (NCI) index and quantum theory of atoms in molecules (QTAIM) outlined the closed-shell nature of the interactions within the studied complexes. Substantial variations were found in the molecular orbitals distribution patterns of MeOH/EtOH molecules and Al12P12 nanocage, outlining the occurrence of the adsorption process within the complexes under investigation. Thermodynamic parameters were denoted with negative values, demonstrating the spontaneous exothermic nature of the most favorable complexes. New energy states were observed within the extracted density of states plots, confirming the impact of adsorbing MeOH and EtOH molecules on the electronic properties of the Al12P12 nanocage. The appearance of additional peaks in Infrared Radiation (IR) and Raman spectra revealed the apparent effect of the adsorption process on the features of the utilized sensor. The emerging results declared the potential uses of Al12P12 nanocage as a promising candidate for sensing VOCs, particularly MeOH and EtOH.

Energy landscape of perylenediimide chromophoric aggregates.

Understanding the self-assembly of conjugated organic materials at the molecular level is crucial in their potential applications as active components in electronic and optoelectronic devices. The type of aggregation significantly influences the intriguing electronic and optical characteristics differing from their constituent molecules. Perylenediimides (PDIs), electron-deficient molecules exhibiting remarkable n-type semiconducting properties, are among the most explored organic fluorescent materials due to their high fluorescence efficiency, photostability, and optoelectronic properties. PDI derivatives are reported to form well-tailored supramolecular architectures: cofacial with minor slip (H-aggregates), staggered with major slip (J-aggregates), magic angle stacking (M-aggregates), rotated (X-aggregates), rotated orthogonal ((+)-aggregates), etc. H*-aggregates are defined here as an ideal case of H-aggregate with an eclipsed configuration. Although numerous reports regarding the formation and optical properties of various PDI aggregates are known, the key driving force within the PDI units guiding the self-assembly to form distinct aggregate systems remains elusive. To unravel the molecular-level mechanisms behind the self-assembly of PDI units by probing the intermolecular interactions, symmetry-adapted perturbation theory-based energy decomposition, potential energy surface scans, and non-covalent interaction index analyses were employed on PDI dimer models. Quantum theory of atoms in molecules and frontier molecular orbital analyses were implemented on the dimer models to comprehend the effect of heteroatoms and orbital interactions in stabilising the X-aggregates over the other PDI aggregate systems. Competition between the attractive and repulsive non-covalent interactions dictates a stability order of X > H > J > M > (+) > H* for the PDI aggregate system, while in the parent perylene system, the stability order was found to be X > (+) > H > M > J > H*.

Ab initio investigation of the competition of pnicogen, halogen, and hydrogen bonds resulting from the interactions between cyanophosphine and hypohalous acids.

The complexes formed as a result of the interactions between cyanophosphine (CP, H2PCN) and hypohalous acid molecules (HOX, X = F, Cl, Br, and I) were studied by employing ab initio computations conducted at the MP2/aug-cc-pVTZ level. Three types of complexes were acquired (I, II, and III) as a result of the (O∙∙∙P) pnicogen bond, the (N∙∙∙H) hydrogen bond, and the (N∙∙∙X) halogen bond interaction, respectively. The results of harmonic vibrational frequency calculations with no imaginary frequencies confirmed the structures as minima. In addition, given the interaction energy of the complexes, hydrogen bond complexes of structure II have the highest stability compared to other structures. In all studied complexes, the strength of the interactions depended on the electronegativity of the halogen atoms. The characteristics and nature of the whole three types of complexes were examined and evaluated with natural bond orbital (NBO), atom in molecules (AIM), molecular electrostatic potential (MEP) maps, non-covalent interaction (NCI) index, and electron density difference (EDD) analyses. The optimization of all complexes and corresponding monomers was conducted through the ab initio method, employing the MP2 level along with the aug/cc-pVTZ basis set for all atoms, except for the iodine (I) atom, for which the aug-cc-pVTZ (PP) basis set was employed. Subsequent frequency calculations were executed to ascertain the minimum energy state of the complexes at the MP2 level and the aug/cc-pVTZ basis set, utilizing Gaussian09 software. The MEP maps of the monomers were generated using the analysis-surface suite (WFA-SAS) software package. To probe the orbital interactions within the studied complexes, NBO analysis was performed employing NBO software. The assessment of bond nature, topological features, and electron density values at critical points for the studied complexes was undertaken using AIMAll software. The NCI index was derived utilizing Multiwfn software, and its three-dimensional representation was rendered using VMD software.

Revealing the Role of Noncovalent Interactions on the Conformation of the Methyl Group in Tricyclic Orthoamide.

Tricyclic orthoamides are valuable molecules with wide-ranging applications, including organic synthesis and molecular recognition. Their structural properties make them intriguing, particularly the eclipsed all-trans conformer, which is typically less stable than the alternated conformation and is a rare phenomenon in organic chemistry. However, it gains stability in crystalline and hydrated settings, challenging the existing theoretical explanations. This study investigates which factors make eclipsed conformers more stable using experimentally reported anhydrous (ATO) and hydrated (HTO) crystal structures. Employing the quantum theory of atoms in molecules, noncovalent interaction index, and pairwise energy decomposition analysis, we delve into the noncovalent interaction environment surrounding the molecule of interest. In ATO, dispersive interactions dominate, whereas in HTO, both dispersive and electrostatic contributions are observed due to the presence of water molecules. Anchored to the lone pairs of the nitrogen atom in the orthoamide tricycle, water molecules prompt the methyl group's eclipsing through intermolecular and intramolecular interactions. This work resolves the long-standing conflict behind why tricyclic orthoamide has an eclipsed conformation by establishing the stabilization factors. These insights have implications for crystal engineering and design, enhancing our understanding of structural behavior in both crystalline and hydrated environments.

Unveiling the Potential of B3O3 Nanoflake as Effective Transporter for the Antiviral Drug Favipiravir: Density Functional Theory Analysis.

In this study, for the first time, boron oxide nanoflake is analyzed as drug carrier for favipiravir using computational studies. The thermodynamic stability of the boron oxide and favipiravir justifies the strong interaction between both species. Four orientations are investigated for the interaction between the favipiravir and the B3O3 nanoflake. The Eint of the most stable orientation is -26.98 kcal/mol, whereas the counterpoise-corrected energy is -22.59 kcal/mol. Noncovalent interaction index (NCI) and quantum theory of atoms in molecules (QTAIM) analyses are performed to obtain insights about the behavior and the types of interactions that occur between B3O3 nanoflake and favipiravir. The results indicate the presence of hydrogen bonding between the hydrogen in the favipiravir and the oxygen in the B3O3 nanoflake in the most stable complex (FAV@B3O3-C1). The electronic properties are investigated through frontier molecular orbital analysis, dipole moments and chemical reactivity descriptors. These parameters showed the significant activity of B3O3 for favipiravir. NBO charge analysis transfer illustrated the charge transfer between the two species, and UV-VIS analysis confirmed the electronic excitation. Our work suggested a suitable drug carrier system for the antiviral drug favipiravir, which can be considered by the experimentalist for better drug delivery systems.

Supramolecular Assemblies of 3/4-Chlorobenzoic Acid and Amino-Chloropyridine Derivatives: Synthesis, X-ray Diffraction, DFT Calculations, and Biological Screening

Organic acids (3-chlorobenzoic acid and 4-chlorobenzoic acid) were treated with 4-amino-2-chloropyridine and 2-amino-4-chloropyridine as coformers for cocrystallization. Acid/base pairs afforded a cocrystal (3-chlorobenzoic acid and 4-amino-2-chloropyridine, compound 1) and molecular salts (2-amino-4-chloropyridinium 3-chlorobenzoate, 2; 2-amino-4-chloropyridinium 4-chlorobenzoate, 3). The products were characterized with the help of FT-IR, UV/visible spectroscopy, PXRD, and SC-XRD. The position of the Cl-substituent on the phenyl ring was explored with respect to proton transfer between acid/base pairs, and its role in supramolecular chemistry is discussed in detail. The existence of supramolecular assemblies was further reproduced using DFT calculations. Further, frontier molecular orbital (FMO), molecular electrostatic potential (MEP), and noncovalent interaction index (NCI) analyses were performed to gain insight into the electronic properties and nature of noncovalent interactions. The prepared compounds were examined for their biological activities against selected Gram-positive and Gram-negative bacterial strains and were also tested as antioxidant agents (DPPH free radical scavenging). Structural parameters determined experimentally and theoretically are within the expected range, and the biological activities of the resultant compounds are moderate.

Partial Methane Oxidation to Methanol on Ru-Porphyrins - on the Role of Non-Innocent Ligands and Spin Crossover.

The partial oxidation reaction of CH4 led to the formation of CH3 OH in the presence of Ru-porphyrin oxo complexes (denoted as POR, POR-O and POR-OH where in the case of the last two, oxygen atom and the OH group were attached to the active site, respectively), in which Ru was present on different oxidation states. The simulations were performed based on Density Functional Theory (DFT) with extended geometric and electronic structure analyses of each reaction step. Moreover, the reaction pathways were investigated in different spin states. The Spin Crossover (SCO) phenomenon was found to play an important role in the kinetics of the reaction in the presence of POR and POR-O. Harmonic Oscillator Model of Aromaticity (HOMA) index was applied for different spin states to estimate the aromaticity changes of the pyrrole rings in the Ru-porphyrin complexes. In order to characterize the nature of bonding, the Natural Bond Orbitals (NBO) analysis including the Wiberg Bond Index (WBI) and Natural Population Analysis (NPA) was carried out. Finally, the Non-Covalent Interactions (NCI) index was employed to gain insight into interactions between the components of the reaction. It was found that the non-covalent interactions cannot be neglected in the studied reaction paths.

Molecular insight into endosulfan degradation by Ese protein from Arthrobacter: Evidence-based structural bioinformatics and quantum mechanical calculations.

Endosulfan is an organochlorine insecticide widely used for agricultural pest control. Many nations worldwide have restricted or completely banned it due to its extreme toxicity to fish and aquatic invertebrates. Arthrobacter sp. strain KW has the ability to degrade α, β endosulfan and its intermediate metabolite endosulfate; this degradation is associated with Ese protein, a two-component flavin-dependent monooxygenase (TC-FDM). Employing in silico tools, we obtained the 3D model of Ese protein, and our results suggest that it belongs to the Luciferase Like Monooxygenase family (LLM). Docking studies showed that the residues V59, V315, D316, and T335 interact with α-endosulfan. The residues: V59, T60, V315, D316, and T335 are implicated in the interacting site with β-endosulfan, and the residues: H17, V315, D316, T335, N364, and Q363 participate in the interaction with endosulfate. Topological analysis of the electron density by means of the Quantum Theory of Atoms in Molecules (QTAIM) and the Non-Covalent Interaction (NCI) index reveals that the Ese-ligands complexes are formed mainly by dispersive forces, where Cl atoms have a predominant role. As Ese is a monooxygenase member, we predict the homodimer formation. However, enzymatic studies must be developed to investigate the Ese protein's enzymatic and catalytic activity.

Exploring benzene Ru(II) complexes of 2-subsitituted quinoline/napthyridine ligands: Synthesis, biomacromolecular binding and DFT investigations

This work reports the synthesis of 2-substituted quinoline/napthyridine ligands by a Friedländer condensation which are employed for the synthesis of half-sandwich benzene ruthenium(II) complexes having formula [(benzene)RuIIL(N∩N)Cl]+. These complexes have been characterized spectroscopically by IR, UV, 1H, and 13C NMR, HR-MS and SC-XRD techniques. The interaction of the [2]PF6 with ct-DNA and HSA have been evaluated using UV–Vis absorption spectroscopy. The binding constants for ct-DNA - [2]PF6 and HSA - [2]PF6 complex were found to be in the order of 104 M–1, which suggests that HSA can transport the complex toward the potential target sites. Furthermore, competitive displacement assay and viscosity measurement reflect that the [2]PF6 binds to the groove region of DNA. Moreover, molecular docking studies with HSA and DNA corroborated the outcome of experimental binding studies, underscoring the potential of these Ru(II) complexes as potential candidates for various biological activities. DFT studies reveal the existence of strong hydrogen bonds (about -35 kJ/mol) between the hydrogens of the -NH2 group (of the cationic part of the complex) and the counter anions (Cl− and PF6−). The existence of NH···Cl− and NH···F (of PF6−) hydrogen bonds in [2]Cl and in [2]PF6 were confirmed with the help of atom-in-molecule (AIM) and non-covalent interaction index (NCI) analysis. The negative H(rc) values obtained from AIM analysis indicates the partial covalent character of the NH···Cl− and N-H···F (of PF6−) hydrogen bonded interaction in [2]Cl and [2]PF6 complexes.

Spectral, quantum chemical, X-ray crystallographic, Hirshfeld surface, energy framework, and molecular docking investigations of 4-acetylphenyl 4-methylbenzenesulfonate (APMBS)

4-acetylphenyl 4-methylbenzenesulfonate (C15H14O4S), a tosyl ester derivative, has been synthesized and characterized by spectroscopic and single crystal X-ray diffraction (SCXRD) techniques. The Hartree-Fock (HF) and the Density functional theory (DFT) methods [B3LYP/6-311 ++ G (d, p) basis set] have been employed to obtain the optimized structural geometry. The structure exhibits C—H···O type of intra- and intermolecular interactions, besides C—O···π and C—H···π interactions. The DFT calculation facilitated the exploration of frontier molecular orbitals (FMOs), Mulliken charges, density of states (DOS), and molecular electrostatic potential (MEP). A detailed Hirshfeld surface analysis has been made. Bader's atoms-in-molecules quantum theory (QTAIM) and non-covalent interaction index analysis as based on reduced density gradient (NCI-RDG) led to a quantitative description of the nature of interactions present in the crystal structure. The molecular docking has been performed against Nucleotide pyrophosphatase/phosphodiesterase (NPP) enzyme.

A mechanistic insight for the biosynthesis of N,N-dimethyltryptamine: An ONIOM theoretical approach

Psychoactive natural products are potent serotonergic agonists capable of modulating brain functions such as memory and cognition. These substances have shown therapeutic potential for treating various mental disorders. The fact that N,N-dimethyltryptamine (DMT) is produced endogenously in several plants and animals, including humans, makes it particularly attractive. As an amino acid-derived alkaloid, the DMT biosynthetic pathway is part of the L-tryptophan biochemical cascade and can be divided into the decarboxylation by an aromatic L-amino acid decarboxylase (AADC) for tryptamine formation and the subsequent double-methylation by the indolethylamine-N-methyltransferase (INMT) through the cofactor S-adenosyl-L-methionine (SAM), a methyl donor. Unlike the decarboxylation mechanism of L-tryptophan, the molecular details of the double methylation of tryptamine have not been elucidated. Therefore, we propose an in silico model using molecular dynamics (MD), non-covalent interaction index (NCI) and density functional theory (DFT) calculations with the ONIOM QM:MM B3LYP/6-31+G(d,p):MM/UFF level of theory. Based on the obtained energetic data, the potential energy surface (PES) indicates an SN2 mechanism profile, with the second methylation energy barrier being the rate-limiting step with δG‡=60kJ∙mol−1 larger than the previous methylation, following the NCI analysis showing more repulsive interactions for the second transition state. In addition, the hybridization information of each reaction step provides geometric details about the double-methylation.

Effect of solvents on intra- and inter-molecular interactions of oligothiophenes.

Oligothiophenes have long been used as model compounds to understand the chemistry of polythiophenes. Herein, we have some quantum chemical calculations and intra- and inter-molecular interaction calculations of a series of oligothiophenes such as terthiophene, quintetthiophene, sevensthiophene, terthiophene-terthiophene, terthiophene-water, terthiophene-methanol, and terthiophene-chloroform performed by time-dependent density functional theory (TD-DFT), density functional theory (DFT), and Multiwfn: a multifunctional wavefunction analyzer. The UV-vis spectra, HOMO-LUMO energies, NBO analysis, MEP, molecular structures, and electronic properties were computed using DFT/TD-DFT at the level of B3LYP/6-31+ G (d,p) and described. The nature of molecular interactions between terthiophene and solvents like water, methanol, and chloroform were also investigated using non-covalent interaction index (NCI), reduced density gradient (RDG), localized orbital locator (LOL), and electron localization function (ELF) topological analyses. Besides, Fukui functions and energy of population density-of-states were computed using the same method. The calculation results show that there are some changes in the terthiophene with the addition of solvent to the medium. DFT calculations were performed using the Gaussian 09 software and GaussView 5.0 visulation program. Multiwfn software is used to calculate the reduced density gradient (RDG) scatterplots, non-covalent interactions (NCI), ELF, LOL, Fukui analysis, and energy of population density-of-states of oligothiophenes.

Non-covalent interactions in biocompatible platforms for drug delivery: Mg2(olsalazine) Metal-Organic Framework with phenylethylamine, dopamine and sertraline

Drug delivery systems can improve the efficacy of therapeutic substances. In this investigation, the biocompatible Mg2(olsalazine) [Mg2(olz)] framework is investigated as a delivery system of phenylethylamine, dopamine and sertraline, substances related to the functioning of the Central Nervous System. Experiments previously reported show that Mg2(olz) encapsulates phenylethylamine and, under physiological conditions, releases the molecules. The hypothesis of this work is that this is possible due to the presence of non-covalent interactions. The non-covalent interactions between Mg2(olz) and phenylethylamine, dopamine and sertraline are analyzed using Quantum Theory of Atoms in Molecules and Non-covalent Interaction Index. It was found that the coordinatively unsaturated metal site of Mg2(olz) is important for the formation of non-covalent interactions. Due to similarity of systems of dopamine and sertraline with that of phenylethylamine, we conclude that Mg2(olz) is also capable to encapsulate and release these two drugs, being a good proposal as a drug delivery system.

The NCIWEB Server: A Novel Implementation of the Noncovalent Interactions Index for Biomolecular Systems.

It is well-known that the activity and function of proteins is strictly correlated with their secondary, tertiary, and quaternary structures. Their biological role is regulated by their conformational flexibility and global fold, which, in turn, is largely governed by complex noncovalent interaction networks. Because of the large size of proteins, the analysis of their noncovalent interaction networks is challenging, but can provide insights into the energetics of conformational changes or protein-protein and protein-ligand interactions. The noncovalent interaction (NCI) index, based on the reduced density gradient, is a well-established tool for the detection of weak contacts in biological systems. In this work, we present a web-based application to expand the use of this index to proteins, which only requires a molecular structure as input and provides a mapping of the number, type, and strength of noncovalent interactions. Structure preparation is automated and allows direct importing from the PDB database, making this server (https://nciweb.dsi.upmc.fr) accessible to scientists with limited experience in bioinformatics. A quick overview of this tool and concise instructions are presented, together with an illustrative application.

Preferability of Molnupiravir, an Anti-COVID-19 Drug, toward Purine Nucleosides: A Quantum Mechanical Study.

Structural aspects of molnupiravir complexed with the RNA of the SARS-CoV-2 virus have been recently resolved inside the RNA-dependent RNA polymerase (RdRp), demonstrating the interactions of molnupiravir with purine nucleosides. However, the preference of molnupiravir to interact with one purine nucleoside over another has not been clearly investigated. Herein, the complexation of molnupiravir in its active form with guanosine and adenosine was compared, using sundry density functional theory calculations. The plausible tautomeric structures of the molnupiravir drug in complex with guanosine/adenosine were minutely scrutinized. The relative energy findings outlined the favorability of amino-molnupiravir···keto-amino-guanosine and imino-molnupiravir···amino-adenosine optimized complexes. According to the interaction (Eint) and binding (Ebind) energy values, higher preferential base-pairing of molnupiravir with guanosine over the adenosine one was recognized with Eint/Ebind values of -31.16/-21.81 and -13.93/-12.83 kcal/mol, respectively. This could be interpreted by the presence of three and two hydrogen bonds within the former and latter complexes, respectively. Observable changes in the electronic properties and global indices of reactivity of the studied complexes also confirmed the preferential binding within the studied complexes. The findings from the quantum theory of atoms in molecules and the noncovalent interaction index also support the partially covalent nature of the investigated interactions. For both complexes, changes in thermodynamic parameters outlined the spontaneous, exothermic, and nonrandom states of the inspected interactions. Inspecting the solvent effect on the studied interactions outlined more observable amelioration within the water medium compared with the gas one. These results would be a durable ground for the forthcoming studies concerned with the interactions of the molnupiravir drug with purine nucleosides.

Boron-π interactions in two 3-(dihydroxyboryl)anilinium salts analyzed by crystallographic studies and supported by the noncovalent interactions (NCI) index theoretical approach.

In the title compounds, 3-(dihydroxyboryl)anilinium bisulfate monohydrate, C6H9BNO2+·HSO4-·H2O (I), and 3-(dihydroxyboryl)anilinium methyl sulfate, C6H9BNO2+·CH3SO4- (II), the almost planar boronic acid molecules are linked by pairs of O-H...O hydrogen bonds, forming centrosymmetric motifs that can be described by the graph-set R22(8) motif. In both crystals, the B(OH)2 group acquires a syn-anti conformation (with respect to the H atoms). The presence of the hydrogen-bonding functional groups B(OH)2, NH3+, HSO4-, CH3SO4- and H2O generates three-dimensional hydrogen-bonded networks, in which the bisulfate (HSO4-) and methyl sulfate (CH3SO4-) counter-ions act as the central building blocks within the crystal structures. Furthermore, in both structures, the packing is stabilized by weak boron-π interactions, as shown by noncovalent interactions (NCI) index calculations.