Noncovalent Research Articles

Computational study on non-covalent interactions in benzene–X complexes (X = He, Ne and Ar)

Computational study on non-covalent interactions in benzene–X complexes (X = He, Ne and Ar)

Synthesis of Chloro‐Substituted β‐Ketiminate Palladium Complexes, Spectral and Thermal Investigation of their Structures

AbstractThe synthesis and characterization of nine palladium(II) complexes featuring β‐ketoiminato ligands of type [Pd(ArNacac)2] (4) with Ar=2‐chlorolphenyl (a); 3‐chlorophenyl (b); 4‐chlorophenyl (c); 2,3‐dichlorophenyl (d); 2,4‐dichlorophenyl (e); 2,6‐dichlorophenyl (f); 3,5‐dichlorophenyl (g); 2,4,5‐trichlorophenyl (h); 2,4,6‐trichlorophenyl (i) is reported. The molecular structure of 4 a–f, 4 h and 4 i in the solid state was confirmed by single‐crystal X‐ray diffraction studies. All eight crystal structures are centrosymmetric, with the metal positioned in a slightly distorted square plane. Intermolecular non‐covalent interactions such as C−H⋅⋅⋅Pd, Cl⋅⋅⋅Cl, Cl⋅⋅ π, C−H⋅⋅⋅Cl, Cl⋅⋅⋅O, C−H⋅⋅ π, and π⋅⋅⋅π play crucial roles in the formation of the supramolecular structures. The crystal structures of 4 b, 4 c, and 4 e revealed unique intermolecular C−H⋅⋅⋅Pd anagostic interactions between the hydrogen atom on the substituted ligand and the palladium centers, which enable the formation of 1‐D polymeric chains. The intermolecular non‐covalent interactions were analyzed using Hirshfeld surface. The proportional contributions of each individual atom to the formation of these non‐covalent interactions are shown in the 2D fingerprint plots. Furthermore, density functional theory (DFT) has been used to compute the energetic estimation of non‐covalent interactions in 4 b, 4 c and 4 e. Furthermore, computational methods such the non‐covalent interaction (NCI) plot index and quantum theory of atoms in molecules (QTAIM) analysis have been used to study the non‐covalent interactions in 4 b, 4 c, and 4 e.

Highly Precise Prediction of Micro- and Supra-pKa Based on 3D Descriptors Integrating Non-Covalent Interactions.

Accurate pKa prediction is crucial for understanding proton dissociation in complex molecular systems. However, existing models often face challenges in addressing subtle stereoelectronic effects and conformational flexibility. This study presents H-SPOC, a localized 3D descriptor that captures covalent and non-covalent interactions and incorporates solvent effects to predict site-specific pKavalues accurately. H-SPOC was validated on multiple benchmark datasets, including SAMPL6, SAMPL7, and SAMPL8, where it outperformed state-of-the-art methods. H-SPOC also proved versatile across various applications, including aspirin's non-equilibrium conformations, glycine's microstate distributions, and the stereoelectronic anomalies of Janus Sponge and Meldrum's Acid. It addressed challenging supra-pKapredictions in crystalline environments and accurately correlated pKa with reaction rates, selectivity, tautomerism, and pharmacokinetic properties. With its chemically intuitive design and computational efficiency, H-SPOC provides an efficient framework for rapid and precise micro- and supra-pKapredictions, offering significant potential in drug discovery, catalysis, and materials science.

Multiple combinatorial interactions among natural structural variants of Brassica SOC1 promoters and SVP: conservation of binding affinity despite diversity in bimolecular interactions.

Analysis of binding patterns of biomolecules underpin new paradigms for trait engineering. One way of designing early flowering crops is to manipulate genes controlling flowering time. SOC1, a central integrator of flowering, is downregulated by SVP. In amphidiploid Brassica juncea, flowering is plausibly mediated by combinatorial interactions involving natural variants of SOC1 promoter and SVP protein homologs. Although fluctuating temperatures influence energetics of molecular interactions and phenotypes, mechanistic insights on these remain unknown. Herein, we report diversity in 50 homologs of SVP proteins from 25 Brassicaceae species. Sequence and phylogenetic analysis of 9 natural variants of B. juncea SVP revealed differences in MIKC domains and sub-genome of origin. Generation and refinement of 15 SVP protein models (natural and hypothetical) using I-TASSER and ALPHAFOLD, and 3 SOC1 promoter fragments using 3D-DART, revealed structural diversity. Notwithstanding, binding affinity of 48 docked complexes analysed using HADDOCK and PreDBA were similar. Analysis of 27 docked complexes for distribution of shared or unique binding patterns and type of molecular contacts (π-π stacking, hydrophobic interactions, Van-der-Waals forces, H-bonds) using PyMOL, CCP4i, DNAproDB, PremPDI and DIMPLOT revealed extensive variation implicating compensatory mutations in preserving binding affinity. Yeast one-hybrid assays validated binding potential predicted in docked complexes. Conserved amino-acid and nucleotide residues involved in non-covalent interactions were identified. Computational alanine substitution established cruciality of amino-acid hotspots conferring stability to docked complexes. Our study is important as identification of crucial amino-acid hotspots is essential for rational protein design. Targeted mutagenesis resulting in modified binding spectrum of regulatory proteins suggests a way forward for trait engineering.

Supramolecular Chiral Amplification Mediated by Tiny Structural Changes in Natural Binary Carrier‐Free Hydrogels with Promotion Methicillin‐Resistant Staphylococcus aureus‐Infected wound Healing by Inhibiting the Complement System

Natural small molecules self‐assembled to carrier‐free hydrogels have attracted widespread attention due to their simple preparation process, high drug loading capacity, good biodegradability, and biocompatibility. A group of structurally similar chiral phytochemical baicalin (BA), scutellarin (SCU), and achiral isoquinoline alkaloids chelerythrine (CHE) can self‐assemble to form binary hydrogels with helical nanofibers or twisted nanofibers. Interestingly, there is only one OH difference between SCU and BA, but the hydrogel formed by self‐assembly with CHE has huge differences in material properties, which is related to the chiral helicity of the formed supramolecules. Compared with BA‐CHE, the binary hydrogel formed by SCU‐CHE shows chiral amplification with greater helicity, is more stable, and exhibits excellent material properties, which is due to the magical noncovalent bond balance controlled by OH. This self‐assembled chiral hydrogel based on the inherent anti‐inflammatory and antibacterial activities of phytochemicals (BA, SCU, and CHE) can promote wound healing in bacterial infections by inhibiting the complement system. The phenomenon of supramolecular chirality amplification caused by tiny structural changes discovered in this study provides a horizon for the self‐assembly of natural small molecule drugs to form two‐component chiral supramolecular hydrogels and expands its application in the field of biomaterials.

A novel cocrystal of the Zn(II) coordination molecule and the benzimidazole for efficient detection of triethylamine and antibacterial property

A new cocrystal of the Zn(II) coordination molecule and the benzimidazole (bim), [Zn(bim)(SCN)3]-[Hbim] (C10H6N5S3Zn-C7H7N2, cocrystal 1) was directly synthesized at room temperature. X-ray single crystal diffraction analysis showed that cocrystal 1 is extended into a 3D supramolecular network via hydrogen bonding and π⋅⋅⋅π stacking interactions. Information on non-covalent interactions were gathered by calculating the Hirshfeld surface and fingerprint of the crystal stacking of cocrystal 1. Photoluminescence experiments demonstrated that cocrystal 1 not only possessed good solid-state fluorescence performance but also favorable fluorescence characteristics and stability in aqueous solutions. Notably, cocrystal 1 exhibited excellent anti-interference properties, high sensitivity, high fluorescence enhancement, and low limit of detection (LOD: 59.8 μM) against triethylamine (TEA) in aqueous medium via the “Turn-On” effect. In addition, the antimicrobial properties of the cocrystal were investigated. The results of antimicrobial experiments revealed that cocrystal 1 inhibited Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA). Molecular docking analysis unraveled the mode of interaction with DNA in bacteria. Cocrystal 1 is a potential multifunctional material for the preparation of TEA sensors and antimicrobial agents. Finally, the possible enhancing mechanism and potential antimicrobial mechanism were researched.

A study on fullerene as a polymer-assisted antiepileptic drug delivery system: A non-covalent interaction

A study on fullerene as a polymer-assisted antiepileptic drug delivery system: A non-covalent interaction

Insights into the separation, enantioseparation and recognition mechanisms of methamphetamine isotopologues on achiral and polysaccharide-based chiral columns in high-performance liquid chromatography.

Isotopologues resulting from the labelling of molecules with deuterium have attracted interest due to the isotope effect observed in chemistry and biosciences. Isotope effect may also play out in noncovalent interactions and mechanisms leading to intermolecular recognition. In chromatography, differences in retention time between isotopologues, as well as between isotopomers have been observed resulting in two different elution sequences (isotope effects): the normal isotope effect when heavier isotopologues retain longer than lighter analogues, and the inverse isotope effect featuring the opposite elution order. Although several cases of deuterium isotope effects have been reported so far, the molecular bases of these phenomena remain unclear. We report the separation of isotopologues of methamphetamine (N-methyl-1-phenylpropan-2-amine) (MET), featuring different number and location of deuterium substituents, on an achiral column by high-performance liquid chromatography (HPLC), as well as the simultaneous separation of isotopologues and their enantiomers on some polysaccharide-based chiral columns. The effects of the number and location of deuterium substituents introduced in MET's structure, of the surface chemistry of the adsorbent, and the mobile phase composition and pH on the retention and separation of isotopologues and their enantiomers were examined. In several cases, the effect of temperature was also evaluated, and the thermodynamic quantities associated with isotopologue adsorption, separation, and enantioseparation were also calculated. To elucidate the molecular bases of the experimental observations, quantum mechanics calculations were performed focusing on the vibrational degree of freedom calculated for models of isotopologue-selector complexes. On this basis, zero-point vibrational energies were computed as useful descriptors to differentiate computationally between deuterated isotopologues. Using HPLC as experimental technique with the following dual function: 1) separation of MET isotopologues and their enantiomers; 2) exploring noncovalent interactions underlying their separation. The degree of deuteration, location of deuterium substituents, and mobile phase pH play key roles in isotopologue separations. By integrating experimental and computational analyses, noncovalent interactions underlying normal and inverse isotope effects were deconvoluted, highlighting the contribution of hydrogen bond, hydrophobic and dispersive forces in isotopologue and enantiomer separation.

Raman non-coincidence effect of C ˭ O stretching modes of ethyl, butyl, and amyl acetate

Raman non-coincidence effect of the C ˭ O stretching mode of ethyl, butyl, and amyl acetate was studied. The Raman non-coincidence effect decreased when these liquids were dissolved in a non-polar carbon tetrachloride solvent. That is, it was determined that the structure-breaking effect is observed in this solution. Density functional theory (DFT) analysis was performed in order to further understand the Raman non-coincidence effect. DFT analysis of the dimers of the studied liquids strongly supported their isotropic and anisotropic Raman spectral properties. Topological analyses, such as non-covalent interaction and reduced density gradient, were performed in order to understand the nature of intermolecular interactions in these selected dimers.

Ternary complex of soluble undenatured type II collagen-hydrophobic phytochemical-chondroitin sulfate facilitates high stability and targeted intestinal release properties to active substance.

Researchers have reported that soluble undenatured type II collagen (SC II) and hydrophobic phytochemicals (HPs) can ameliorate osteoarthritis (OA) through several mechanisms. However, the solubility of HPs, the stability of SC II, and the bio-accessibility of both need to be greatly improved before they can be successfully used for this purpose. In this study, two common HPs, curcumin (CUR, a hydrophobic polyphenol) and astaxanthin (AST, a carotenoid), were first loaded into SC II, which was then complexed with chondroitin sulfate (CS) to form ternary complexes: SC II-HP-CS. The results showed that SC II had the highest loading capacity for CUR (19.00±0.76μg/mg) and AST (21.15±1.67μg/mg) at pH2.0. The CUR and AST bound to the SC II through non-covalent interactions (mainly hydrophobic interaction) and they both existed in an amorphous form within the complexes. In addition, the binding affinity and hydrophobic interaction between SC II and CUR was higher than those of AST. The thermal stability of the SC II-CUR-CS (Td=118.0±2.1°C) and SC II-AST-CS (Td=118.8±3.5°C) complexes were significantly higher than that of the SC II-CUR (Td=104.27±0.28°C) and SC II-AST (Td=103.8±1.6°C) complexes. SC II-HP complexes dissolved in gastric fluids, resulting in serious degradation of the SC II, while SC II-HP-CS complexes existed in an insoluble form to protect the triple helix structure of SC II (24-46% retained). The CUR release (94.2±5.8%) and the free radical scavenging activity (84.6±5.3%) of SC II-CUR-CS was relatively high after 6h of intestinal digestion, while AST in SC II-AST and SC II-AST-CS had low solubility and antioxidant activity. Therefore, the ternary complex of SC II-HP-CS was more advantageous as multifunctional delivery systems for the encapsulation, protection, and controlled release of hydrophobic polyphenols, which may provide guidance for the synergistic use of hydrophobic polyphenols and SC II to improve OA.

Structural and theoretical studies of amantadinium fenamates.

Two new crystals of amantadinium salts were obtained from fenamic and tolfenamic acid. The salt of fenamic acid is a model compound for interaction analysis, while amantadinium tolfenamate is a composition of a drug used in the treatment of symptoms of Parkinsonism and as a nonsteroidal anti-inflammatory drug. The crystal structures were studied and a theoretical analysis of the hydrogen bonds and weak interactions was carried out using quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) methods.

Experimental and computational analysis of C≡N and C–H stretching bands in acetonitrile solutions

Raman and FTIR spectra of pure acetonitrile (ACN) and its solutions with water, dimethyl sulfoxide (DMSO) and formamide were investigated experimentally and by means of computer simulation. The research is focused on the C≡N and C–H stretching vibrations of H-bonded complexes in the solutions. Potential energy distribution analysis was carried out for obtained vibrational frequencies. Experiments reveal a blue shift of the C≡N and C–H stretching bands for ACN dissolved in water. In DMSO solutions, the frequencies of these bands were almost unchanged, only their intensity changed. In formamide solution, the C≡N stretching band is blue-shifted, and the C–H stretching vibration band is slightly red-shifted. It is estimated that the main reason for this is weak hydrogen bonds or van der Waals interaction of C–H⋅⋅⋅O and N⋅⋅⋅H–O types. This viewpoint is supported by the results of atom in molecule, non-covalent interaction, and reduced density gradient analyses.

Selective extraction performance and mechanism of lithium using Lewis base ligands containing phosphoryl/carbonyl groups

With the rapidly increasing demand for lithium resources, lithium extraction from low-grade and secondary resources has received widespread attention. The combination of tributyl phosphate (TBP) and FeCl3 is the most studied and reported separation system. However, the selective extraction mechanism for lithium is not clear. In this study, the extraction systems consisting of different Lewis base ligands (L) with phosphoryl/carbonyl groups and FeCl3 were employed for lithium extraction from the LiCl-MgCl2-H2O system. The extraction efficiency and selectivity of lithium by various Lewis base ligands with different branched structures were investigated. The interactions between Li+ and the ligands were deeply analyzed by spectroscopic characterization and quantum chemistry calculations. Meanwhile, the relationship between the ligand structures and the selective binding ability of Li+ was innovatively established. The results show that the extraction efficiency and selectivity of lithium by various ligands descend in the order: TIBP > TBP > N503 > MIBK > P350 > TBPO > TOA. The extracted complexes [LiLn]+·[FeCl4]− are formed through the non-covalent interaction between Li+ and the O atoms of the ligands as well as the Cl atoms of [FeCl4]−. The ligand with low basicity, strong Mulliken electronegativity, and low average localized ionization energy is preferable for the selective extraction of Li+. On the contrary, the ligand is more likely to be protonated. The study provides a theoretical basis for deeply understanding the relationship between the ligand structures and their selective binding ability towards Li+, which is also conducive to developing more efficient systems for lithium recovery from complex solutions.

Advanced characterization of fish skin gelatin-proanthocyanidins covalent and non-covalent composite emulsions for benzyl isothiocyanate delivery.

This research endeavored to engineer robust delivery matrices for bioactives, specifically benzyl isothiocyanate (BITC), by harnessing the synergistic covalent and non-covalent interactions between fish skin gelatin (FSG) and proanthocyanidins (PC) to synthesize novel composite emulsions. The objective was to delineate the influence of these molecular interactions on the emulsion's structural integrity and stability, which are pivotal for the efficacious encapsulation and controlled release of BITC. Employing a suite of analytical techniques, including Fourier transform infrared spectroscopy (FTIR), fluorescence spectroscopy, and contact angle measurements, the study delineated the predominant molecular forces at play within the FSG-PC complex, identifying electrostatic and hydrophobic interactions as the cornerstones of this interaction. An assessment of the emulsions' physicochemical properties, encompassing chromaticity, antioxidant efficacy, microstructural attributes, particle dimensions, zeta potential, and BITC retention, was undertaken to discern the optimal encapsulation strategy. The data unequivocally indicated that emulsions enriched with 0.06wt% PC, in non-covalent synergy with FSG, afforded the most pronounced stability and retention of BITC. This work paves the way for future studies and the translational application of FSG-PC composite emulsions in the realm of bioactive substance delivery, offering a promising avenue for innovation in pharmaceutical and nutraceutical formulations.

Prolamin-pectin complexes: Structural properties, interaction mechanisms and food applications.

Prolamin, a class of plant protein mainly derived from grains, and pectins, complex-structured polysaccharides, are natural biological macromolecules with versatile functional properties. The interactions between prolamins and pectin have been widely studied and applied, demonstrating that both covalent and non-covalent interactions play pivotal roles in the formation of prolamin-pectin complexes. These interactions impart exceptional physicochemical and functional properties to the complexes. This review also details the main applications of prolamin-pectin complexes, including emulsions, nanoparticles, hydrogels and films. The similarities in their reaction principles are based on the interaction of complexes that improve their physicochemical and functional properties, while the difference lies in the specific modes of action, involving the emulsifying properties, self-assembly properties, gelling properties and film-forming properties of prolamin and pectin. By delving into the intricate mechanisms underlying prolamin-pectin interactions and their diverse applications in the food industry, this review offers valuable insights for advancing the development and utilization of these complexes.

Synthesis, characterization and computational studies of the triangle shape complex of silver nitrate with 2-amino-1,3,4-thiadiazole

A new mononuclear salt-like silver(I) complex [AgL3]NO3 (Complex 1), which was readily fabricated from 2-amino-1,3,4-thiadiazole (L), is reported. Complex 1 was analyzed by elemental analysis, FT-IR and UV–vis spectroscopy, and single crystal X-ray diffraction. Intermolecular contacts for the cation [AgL3]+ in the crystal structure of Complex 1 were examined using the Hirshfeld surface analysis. The DFT-based calculations were additionally applied to reveal electronic features of Complex 1. The molecular structure of Complex 1 exhibits a mononuclear planar cation [AgL3]+ of the triangle shape with three ligands L being monocoordinated through thiadiazole the nitrogen atom, located at the third position. Two cations [AgL3]+, which, in turn, are stabilized by three NH⋯N hydrogen bonds, are stacked through a rich variety of noncovalent interactions formed by the thiadiazole π-system, yielding a supramolecular dimer {[AgL3]2}2+. These dimers are linked through Ag⋯Ag interactions with the formation of a 1D supramolecular cationic pillar {[AgL3]n}n+. A solution of Complex 1 in EtOH absorbs in the UV region due to intraligand transitions within L. Theoretical calculations revealed a strong electrophilic nature of the optimized structure of Complex 1.

Peculiarities of ibuprofen interaction with polyethylene glycol polymer matrix

The peculiarities of the interaction of ibuprofen with polyethylene glycol (PEG 400) have been studied by FTIR spectroscopy and computer simulation. Quantum chemical calculations of the optimal geometry and IR spectra of two conformers of the ibuprofen molecule were performed at the MP2/6-311 + G (2d,p) level of theory. The calculation results were compared with the experimentally recorded spectra of pure ibuprofen. FTIR spectra of pure ibuprofen and PEG 400 and their solutions at different concentrations (4% and 30%) were registered and analyzed. Molecular docking simulation of non-covalent interactions between ibuprofen and PEG molecules was performed using AutoDock4.2.6 software. It was established that PEG 400 can act as an effective inert matrix for the transfer of ibuprofen without changing its functional properties.

A doubly Phenoxyacetate-bridged dinuclear manganese(II) complex with 1,10-Phenanthroline: Synthesis, 1-D supramolecular structure, Hirshfeld surface analysis, magnetic and theoretical studies

We report herein the synthesis and characterization of [Mn2(POA)2(Phen)4](BF4)2·H2O, 1 where POA = phenoxyacetate; Phen = 1,10-phenthroline, respectively. The crystalline complex was obtained via slow evaporation at room temperature and characterized by single crystal X-ray diffraction. FTIR and UV–vis spectroscopy were utilized to elucidate the structure of the new compound. Complex 1 crystallizes in the monoclinic crystal system with space group P21/n. Hirshfeld surface analysis revealed various intermolecular interactions in the crystal lattice. Quantum Theory of Atoms in Molecules (QTAIM), Reduced Density Gradient (RDG), and Natural Bond Orbital (NBO) analyses were employed to investigate the diverse non-covalent interactions stabilizing the crystal structure. In complex 1, the BF4− counterion plays a crucial role in crystal assembly through a network of F···H C interactions with varying strengths governed by the interaction angle and consequent ellipticity. Additionally, B − F···π interactions were observed. Other interactions include weak-to-medium hydrogen bonds and π-interactions (CH···π and π···π) within the asymmetric units and dimers extracted from the unit cell. Notably, unconventional interactions were identified and characterized in complex 1, which is C H···π interactions with the σ(CH) orbital donating to an empty p orbital in the asymmetric unit of 1. Variable-temperature magnetic susceptibility data disclosed the occurrence of weak antiferromagnetic coupling within the doubly bridged manganese(II) core with a J value of – 2.11 cm−1.

Raman and DFT study of non-covalent interactions in liquid benzophenone and its solutions

Analysis of intermolecular interactions in liquid benzophenone and its solutions in acetone and acetic acid by Raman spectroscopy and quantum-chemical simulation is presented. The results of the experiment show that in binary solutions of benzophenone, a red shift was observed for the C ˭ O stretching band, and a blue shift was observed for the C–H stretching and breathing bands. Such shifts were predicted to occur due to weak (non-classical) hydrogen bonds of C–H⋅⋅⋅O ˭ C type between benzophenone and solvent molecules. The nature and strength of solute-solvent interactions are discussed. The electron density distribution in benzophenone and its complexes with acetone and acetic acid molecules was visualized using the molecular electrostatic potential surface. The electronic properties of the molecular complexes were characterized using the frontier molecular orbitals and localization functions.

Antagonistic Effects of Distance and Overlap toward Anomalous Pressure-Induced Blueshift of π-π Excimer Fluorescence in 9-(2,2-Diphenylvinyl)anthracene Crystals.

Piezochromic materials usually exhibit a gradual redshift of emission as pressure increases due to the formation of a low-energy "dark" state, e.g., excimer. However, our study presents an anomalous excimer-based pressure-induced emission blueshift. A crystal was investigated here with a discrete π-π anthracene dimer stacking and excimer emission, and the dimer is characterized by an overshifted off-center stacking pattern. Intriguingly, under isotropic hydrostatic pressure, this crystal exhibits negative linear compressibility almost along the c-axis of the unit cell. Furthermore, an antagonistic effect between overlap ratio (Sπ-π) and interplanar distance (Dπ-π) within the dimer on emission was identified: reduced Dπ-π typically dominates the emission redshift, while decreasing Sπ-π can cause emission blueshift. When the pressure reaches around 5.00 GPa, the π-π excimer fluorescence exhibits an unexpected blueshift, indicating the reign of decreasing Sπ-π. This study not only sheds light on the modulation of fluorescence properties by noncovalent interactions but also introduces an innovative approach to anomalous piezochromism.