Diverse Non-covalent Interactions Research Articles

Exploring a Solvent Dependent Strategy to Control Self-Assembling Behavior and Cellular Interaction in Laminin-Mimetic Short Peptide based Supramolecular Hydrogels.

Self-assembled hydrogels, fabricated through diverse non-covalent interactions, have been extensively studied in regenerative medicines. Inspired from bioactive functional motifs of ECM protein, short peptide sequences have shown remarkable abilities to replicate the intrinsic features of the natural extracellular milieu. In this direction, we have fabricated two short hydrophobic bioactive sequences derived from the laminin protein i. e., IKVAV and YIGSR. Based on the substantial hydrophobicity of these peptides, we selected a co-solvent approach as a suitable gelation technique that included different concentrations of DMSO as an organic phase along with an aqueous solution containing 0.1 % TFA. These hydrophobic laminin-based bioactive peptides with limited solubility in aqueous physiological environment showed significantly enhanced solubility with higher DMSO content in water. The enhanced solubility resulted in extensive intermolecular interactions that led to the formation of hydrogels with a higher-order entangled network along with improved mechanical properties. Interestingly, by simply modulating DMSO content, highly tunable gels were accessed in the same gelator domain that displayed differential physicochemical properties. Further, the cellular studies substantiated the potential of these laminin-derived hydrogels in enhancing cell-matrix interactions, thereby reinforcing their applications in tissue engineering.

Ultraviolet Organic Laser from Rhombus Microcrystal: Benefits of Single-Molecule Emission from Twisted Structure.

Light-emitting molecular crystals with efficient emission behavior are crucial for fabricating low-threshold ultraviolet organic lasers. Herein, we demonstrated a rhombus microcrystal from a fluorene-based conjugated molecule (CL-1) with robust emission behavior for an ultraviolet organic laser. Due to the synergistic effect of twisted intramolecular conformation and weak π-interaction, the CL-1 single crystal showed an extremely high photoluminescence quantum yield (PLQY) of ∼82%, due to their single-molecule excitonic behavior. Considering the diverse noncovalent interactions, CL-1 molecules easily self-assembled into the rhombus microcrystals. Finally, a low-threshold ultraviolet organic laser was fabricated with a sharp emission at 379 nm, attributed to the 0-1 vibration band of a single CL-1 molecule, also further confirming the single twisted-molecule emission in crystal states. Precisely controlling the intramolecular twisted structure and intermolecular interaction of organic conjugated molecules is a precondition to obtain robust ultraviolet emission for optoelectronic applications.

A new mixed-ligand mononuclear Co(II) complex derived from 4,4,4-trifluoro-1-phenylbutane-1,3-dione and 1,10-phenanthroline: Synthesis, structural elucidation and quantum-computational studies

In this study, a novel mixed-ligand mononuclear Co(II) complex, denoted as {[Co(TFPBD)2(PHE)]DMF}, was synthesized and characterized using single crystal X-ray diffraction analysis. The central cobalt atom coordinated with two 4,4,4-trifluoro-1-phenylbutane-1,3-dione ligands (TFPBD1 and TFPBD2) and a 1,10-phenanthrene (PHE) ligand, adopting a slightly distorted octahedral geometry. Notably, the non-planar characteristics of the ligands led to the manifestation of non-covalent interactions within the molecular structure, further enhanced by the involvement of the lattice DMF solvent. The crystal lattice arrangement in the {[Co(TFPBD)2(PHE)]DMF} complex was a result of diverse non-covalent interactions, including hydrogen bonds, C-F…π, and Π…π stacking interactions, influenced the crystal's stability. Additionally, the study delved into the unique lattice arrangement consisted of pairwise R12(5) ring motifs along with one-dimensional molecular arrays formed along the crystallographic axes. Furthermore, intermolecular C-F…π Cg…Cg interactions resulting in two-dimensional linear molecular arrays along the a- and b-axes. Quantum computational studies using density functional theory (DFT) were employed to examine the complex's electronic structure and stability and reactivity, highlighting electron-rich and electron-deficient regions. Hirshfeld surface analysis (HSA) and Non-covalent interaction analysis confirmed the significance of intermolecular interactions where 2D fingerprint plots emphasized the prominence of CH…F interactions within the crystal structure. These findings contribute significantly to our understanding of mixed-ligand metal complexes and their potential applications in various scientific domains.

Facilitating the drug repurposing with iC/E strategy: A practice on novel nNOS inhibitor discovery.

Over the past decades, many existing drugs and clinical/preclinical compounds have been repositioned as new therapeutic indication from which they were originally intended and to treat off-target diseases by targeting their noncognate protein receptors, such as Sildenafil and Paxlovid, termed drug repurposing (DRP). Despite its significant attraction in the current medicinal community, the DRP is usually considered as a matter of accidents that cannot be fulfilled reliably by traditional drug discovery protocol. In this study, we proposed an integrated computational/experimental (iC/E) strategy to facilitate the DRP within a framework of rational drug design, which was practiced on the identification of new neuronal nitric oxide synthase (nNOS) inhibitors from a structurally diverse, functionally distinct drug pool. We demonstrated that the iC/E strategy is very efficient and readily feasible, which confirmed that the phosphodiesterase inhibitor DB06237 showed a high inhibitory potency against nNOS synthase domain, while other two general drugs, i.e. DB02302 and DB08258, can also inhibit the synthase at nanomolar level. Structural bioinformatics analysis revealed diverse noncovalent interactions such as hydrogen bonds, hydrophobic forces and van der Waals contacts across the complex interface of nNOS active site with these identified drugs, conferring both stability and specificity for the complex recognition and association.

AIE-doped Poly(Ionic Liquid) Photonic Spheres for the Discrimination of Psychoactive Substances.

Drugs of abuse has drawn intense attention due to increasing concerns to public health and safety. The construction of a sensing platform with the capability to identify them remains a big challenge because of the limitations of synthetic complexity, sensing scope and receptor extendibility. Here a kind of poly(ionic liquid) (PIL) photonic crystal spheres doped with aggregation-induced emission (AIE) luminogens was developed. As diverse noncovalent interactions involve in PIL moieties, the single sphere shows different binding affinity to a broad range of psychoactive substances. Furthermore, the dual-channel signals arising from photonic crystal structures and sensitive AIE-luminogens provide high-dimensional information for discriminative detection of targets, even for molecules with slight structural differences. More importantly, such single sphere sensing platform could be flexibly customized through ion-exchange, showing great extendibility to fabricate high-efficiency/high-throughput sensing arrays without tedious synthesis.

Real-Time Reaction Monitoring of Azide-Alkyne Cycloadditions Using Benchtop NMR-Based Signal Amplification by Reversible Exchange (SABRE).

Rufinamide, possessing a triazole ring, is a new antiepileptic drug (AED) relatively well-absorbed in the lower dose range (10 mg/kg per day) and is currently being used in antiepileptic medications. Triazole derivatives can interact with various enzymes and receptors in biological systems via diverse non-covalent interactions, thus inducing versatile biological effects. Strain-promoted azide-alkyne cycloaddition (SPAAC) is a significant method for obtaining triazoles, even under physiological conditions, in the absence of a copper catalyst. To confirm the progress of chemical reactions under biological conditions, research on reaction monitoring at low concentrations is essential. This promising strategy is gaining acceptance for applications in fields such as drug development and nanoscience. We investigated the optimum Ir catalyst and magnetic field for achieving maximum proton hyperpolarization transfer in triazole derivatives. These reactions were analyzed using signal amplification by reversible exchange (SABRE) to overcome the limitations of low sensitivity in nuclear magnetic resonance spectroscopy, when monitoring copper-free click reactions in real time. Finally, a more versatile copper-catalyzed click reaction was monitored in real time, using a 60 MHz benchtop NMR system, in order to analyze the reaction mechanism.

Cyclic dipeptide-based small molecules modulate zinc-mediated liquid-liquid phase separation of tau.

Liquid-liquid phase separation (LLPS) is a complex physicochemical phenomenon mediated by multivalent transient weak interactions among macromolecules like polymers, proteins, and nucleic acids. It has implications in cellular physiology and disease conditions like cancer and neurodegenerative disorders. Many proteins associated with neurodegenerative disorders like RNA binding protein FUS (FUsed in Sarcoma), alpha-synuclein (α-Syn), TAR DNA binding protein 43 (TDP-43), and tau are shown to undergo LLPS. Recently, the tau protein responsible for Alzheimer's disease (AD) and other tauopathies is shown to phase separate into condensates in vitro and in vivo. The diverse noncovalent interactions among the biomolecules dictate the complex LLPS phenomenon. There are limited chemical tools to modulate protein LLPS which has therapeutic potential for neurodegenerative disorders. We have rationally designed cyclic dipeptide (CDP)-based small-molecule modulators (SMMs) by integrating multiple chemical groups that offer diverse chemical interactions to modulate tau LLPS. Among them, compound 1c effectively inhibits and dissolves Zn-mediated tau LLPS condensates. The SMM also inhibits tau condensate-to-fibril transition (tau aggregation through LLPS). This approach of designing SMMs of LLPS establishes a novel platform that has potential implication for the development of therapeutics for neurodegenerative disorders.

Synthesis, spectroscopic studies, and single‐crystal structures of two 3‐D supramolecular zinc(II) and nickel(II) complexes containing thiazole ring: Antimicrobial assays, time‐dependent density functional theory calculations, and Hirshfeld surface analysis

Two novel complexes [Zn(L)2·(NO3)2] (1) and [Ni(L)2·2H2O]·2CH3OH·(NO3)2 (2) (L = 2‐(2‐thiazolyl)‐4‐methyl‐1,2‐dihydroquinazoline‐N3‐oxide) were synthesized successfully and characterized by elemental analysis, as well as various spectroscopic techniques. Specifically, the photoluminescence behavior of complex 1 was explored in different solvents. The structural characterization of both complexes has been determined single‐crystal X‐ray diffraction. It revealed that the metals in 1 and 2 are chelated by two L ligands in centro‐symmetrically fashion and the complexes are counterbalanced by nitrate ions which act as coordinating species in 1, while two water molecules complete the Ni coordination sphere in 2. In the crystal structures, the adjacent molecules of complex 1 disclosed a ladder‐like 2‐D network and 3‐D supramolecular self‐assembly. Simultaneously, an infinite 1‐D chain, 2‐D layered skeleton, and even meter‐shaped 3‐D network of 2 was governed by molecular interactions (H–bonds, C–H⋯π). Most strikingly, the research of antibacterial activity proved that two complexes had good activity against two standard bacteria strains. To ascertain deeply the optimum geometric configurations and detect the frontier molecular orbital energy gaps, density functional theory (DFT) calculations were also investigated. Additionally, analyses of Hirshfeld surfaces (HS) and electrostatic potential (ESP) were also performed to quantify the presence of diverse noncovalent interactions.

Reliable prediction of association (free) energies of supramolecular complexes with heavy main group elements - the HS13L benchmark set.

We introduce a set of 13 supramolecular complexes featuring diverse non-covalent interactions with heavy main group elements (Zn, As, Se, Te, Br, I), high charges (-2 up to +4), and large systems with up to 266 atoms (HS13L). The experimental Gibbs free energies of association cover the typical range (-1.9 to -9.2 kcal mol-1). An efficient automated multilevel theoretical workflow is applied for the determination of the respective minimum structures in solution by conformer ensemble generation with the CREST program at the semiempirical GFN2-xTB level. Subsequent refinement is performed with the r2SCAN-3c composite DFT method including thermostatistical corrections at the GFN2-xTB level and solvation contributions by COSMO-RS using the CENSO free energy ranking algorithm. Various density functional approximations in combination with three London dispersion correction schemes are assessed against "back-corrected" experimental association energies as well as accurate local coupled cluster reference values. Our protocol predicts association free energies with a mean absolute deviation of only 2 kcal mol-1 from the measured values. Thus, it is well suited to generate reference association free energies for assessing theoretical methods on realistically sized supramolecular complexes or to support experimental chemists. For specifically evaluating methods for calculating gas-phase association energies, we recommend using the provided accurate coupled cluster reference values. We propose to use this set as an extension of the S30L benchmark set [Sure et al., J. Chem. Theory Comput., 2015, 11, 3785-3801] with a special focus on the challenging computation of non-covalent interactions of heavy main group elements.

Spontaneous Resolution of Chiral Multi-Thiolate-Protected Ag30 Nanoclusters.

Despite significant progress achieved in the preparation of chiral nanoparticles, the enantioseparation of racemates still presents a big challenge in nanomaterial research. Herein, we report the synthesis and structural characterization of racemic anisotropic nanocluster Ag30(C2B10H9S3)8Dppm6 (Ag30-rac), which is protected by mixed carboranetrithiolate and phosphine ligands. Spontaneous self-resolution of the racemates was realized through conglomerate crystallization in dimethylacetamide (DMAc). The homochiral nanoclusters in the racemic conglomerates adopt enantiomeric helical self-assemblies (R/L-Ag30). Diverse noncovalent interactions as the driving force in directing superstructure packing were elucidated in detail. Furthermore, the nanoclusters show red luminescence in both solid and solution states, and the racemic conglomerates display a mirror-image CPL response. This work provides atom-precise helical nanoparticle superstructures that facilitate an in-depth understanding of the helical-assembly mechanism.

Crystal structures and biological activity of homologated (N)-n-alkylammonium salts of 2-bromo-3-oxido-1,4-naphthoquinone

Homologated (N)-n-alkylammonium salts of 2-bromo-3-oxido-1,4-naphthoquinone (BS-1 to BS-8) have been synthesized and characterized from the single crystal X-ray diffraction experiments combined with density functional theory. The crystal structures revealed diverse noncovalent interactions such as hydrogen bonding, π∙∙∙π, Br∙∙∙π, and others. The measured antifungal activities of the BS-1 to BS-6 against fungal strains Saccharomyces cerevisiae and Candida albicans suggest them to be effective compared to standard drug amphotericin B. Antibacterial activity of BS-1 to BS-6 has been evaluated against Gram-positive and Gram-negative bacteria.

Crystal Multi-Conformational Control Through Deformable Carbon-Sulfur Bond for Singlet-Triplet Emissive Tuning.

Crystal-state luminophores have been of great interest in optoelectronics for years, whereas the excited state regulation at the crystal level is still restricted by the lack of control ways. We report that the singlet-triplet emissive property can be profoundly regulated by crystal conformational distortions. Employing fluoro-substituted tetrakis(arylthio)benzene luminophores as prototype, we found that couples of molecular conformations formed during different crystallizations. The deformable carbon-sulphur bond essentially drove the distortion of the molecular conformation and varied the stacking mode, together with diverse non-covalent interactions, leading to the proportional adjustment of the fluorescence and phosphorescence bands. This intrinsic strategy was further applied for solid-state multicolor emissive conversion and mechanoluminescence, probably offering new insights for design of smart crystal luminescent materials.

Optimizing the Accuracy and Computational Cost in Theoretical Squaramide Catalysis: The Henry Reaction

This study represents the first example where the accuracy of different combinations of density functional theory (DFT) methods and basis sets have been compared in squaramide catalysis. After an optimization process of the precision obtained and the computational time required in the computational calculations, highly precise results were achieved compared to the experimental outcomes while requiring the least amount of time possible. Here, we have explored computationally and experimentally the mechanism of the squaramide-catalyzed Henry reaction. This is a complex reaction of about 100 atoms and a great number of diverse non-covalent interactions. Moreover, this research is one of the scarce examples where the organocatalyst acts in a trifunctional manner and is the first investigation in which a trifunctional squaramide catalyst has been employed. Functional ωB97X-D showed the best results when used with different versions of the 6-311 basis sets, leading to highly accurate calculations of the outcomes of the Henry reaction when using nine aldehydes with different structural characteristics. Furthermore, in these relatively large systems, the use of a split-valence triple-zeta basis set saves a large amount of time compared with using larger basis sets that are sometimes employed in organocatalytic studies, such as the TZV and Def2TZV basis set families.

Molecular structures and biological activities of (N)-n-alkylammonium 2-chloro-3-oxido-1,4-naphthoquinone salts

Single crystal X-ray structures and vibrational spectra of (N)-n-alkylammonium 2-chloro-3-oxido-1,4-naphthoquinone salts (alkyl = methyl to octyl, CS-1 to CS-8) possessing X-H⋯Y (X = N, C and YO, Cl) hydrogen bonding and diverse noncovalent interactions have been characterized. Except for the CS-2 and CS-7 rest of the compounds facilitate π⋯π and Cl⋯π interactions. The compound CS-3 showed the presence of Cl⋯O interactions. Electronic structure and spectral characteristics of obtained are in consonance with the density functional theory. These complexes showed remarkable antiproliferative and antifungal activities.

Synthesis and supramolecular self-assembly of thioxothiazolidinone derivatives driven by H-bonding and diverse π–hole interactions: A combined experimental and theoretical analysis

Two new 3-aryl-5-(4-nitrobenzylidene)-2-thioxothiazolidin-4-one derivatives (1 &2) were synthesized by the Knoevenagel condensation reaction of 3-(4-aryl)-2-thioxo-1,3-thiazolidin-4-ones with 4-nitrobenzaldehyde. Both products were isolated as orange crystalline solids in good yields and were fully characterized by analytical, spectroscopic and structural methods. The interesting supramolecular assemblies of the title compounds observed in the solid state were analyzed by Density Functional Theory (DFT) calculations (M06-2X/def2-TZVP), Molecular Electrostatic Potential (MEP) surfaces and characterized by means of the Bader's theory of “atoms-in-molecules” (AIM) and NCIplot. The computation of the energy features of the diverse noncovalent interactions including CH⋯π, π⋯π and lp⋯π-hole interactions revealed their conspicuous role in the stabilization of the three-dimensional supramolecular frameworks for both compounds in addition to the CH⋯O/S H-bonding interactions.

Understanding the molecular gelation processes of heteroatomic conjugated polymers for stable blue polymer light-emitting diodes

Designing optoelectronic properties using heteroatomic conjugated polymers (HCPs).

Noncovalent interactions underlying binary mixtures of amino acid based ionic liquids: insights from theory

Mixtures of ionic liquids formed by blending a common 1-methyl-3-butylimidazolium [Bmim] cation with the dicarboxylic amino acid anions viz., aspartic acid [Asp], asparagine [Asn], glutamic acid [Glu], and glutamine [Gln], have been investigated by employing dispersion corrected density functional theory. Binary mixtures of [Bmim]2[Asp][Asn] and [Bmim]2[Glu][Gln] ionic liquids emerge with distinct structural patterns. Competition between the constituting anions towards cationic binding sites in acidic and basic (polar) amino acid binary mixtures engenders diverse noncovalent interactions, viz., C-HO hydrogen bonding, π-π stacking, and lpπ and CHπ interactions, which impart local liquid structure to these systems governing the structural and physicochemical properties of such double salt ionic liquids (DSILs). The DSIL conformers reveal distinct structural features arising from the middle, normal and front arrangements of anions combined with parallel, antiparallel, rotated or displaced orientations of the cations. The inclusion of dispersion corrections through the D3 method affects their binding energies significantly bringing forth alteration in their energy rank order. Molecular insights accompanying the ion aggregates provide directives for the use of DSILs with improved performance in tribological applications.

Dihydrogen phosphate-water tape and layers vs dihydrogen phosphate layers tuned by hydrophobic isomeric pyridine-diamine functionalized molecules

Assembly of six isomeric pyridine-diamine-based molecules, N,N′-bis(pyridin-4-ylmethyl)ethane-1,2-diamine (M1), N,N′-bis(pyridin-3-ylmethyl)ethane-1,2-diamine (M2), N,N′-bis(pyridin-2-ylmethyl)ethane-1,2-diamine (M3), N,N′-bis(pyridin-4-ylmethyl)propane-1,3-diamine (M4), N,N′-bis(pyridin-3-ylmethyl)propane-1,2-diamine (M5), and N,N′-bis(pyridin-2-ylmethyl)propane-1,3-diamine (M6), with phosphoric acid (H3PO4) in different ratio (1:2 and 1:4), leads to the formation of nine salts, H2M12+·2H2PO4−·4H2O (1), H2M22+·2H2PO4−·2H2O (2), H2M32+·2H2PO4−·2H2O (3), H4M14+·4H2PO4− (4), H4M24+·4H2PO4− (5), H4M34+·4H2PO4− (6), H2M42+·2H2PO4−·3H2O (7), 2H2M52+·4H2PO4−·2H3PO4 (8), and H2M62+·2H2PO4− (9), which have been characterized by elemental analysis, IR, TG, PL, powder and single-crystal X-ray diffraction. Structural analyses indicate that hydrogen-bonding patterns of H2PO4− anions, conformation of protonated cations can effectively influence the supramolecular architectures through diverse non-covalent interactions. Hydrous salts 1–3 and 7 present 2D and 3D host-guest supramolecular networks, in which the connection of H2PO4− anions and water molecules generates diverse tape and layer motifs. H2PO4− anions in anhydrous salts 4–6 interconnect with each other through hydrogen bonds to form two types of layers, which are joined by discrete H4M4+ cations into 3D inorganic-organic hybrid supramolecular networks. Salts 8–9 also present 2D and 3D host-guest supramolecular networks where the interconnection of H2PO4− anions and its combination with H3PO4 molecules leads to diverse layers. Luminescent analyses indicate that salts 1–9 exhibit violet and blue emission maximum in the range of 390–467 nm at room temperature.

Two novel uranyl complexes of a semi-rigid aromatic tetracarboxylic acid supported by an organic base as an auxiliary ligand or a templating agent: an experimental and theoretical exploration

Two novel uranyl coordination polymers, namely, UO2(bptc)(H2bpy)·(bpy) (1) and (UO2)3(bptc)1.5(phen)2(H2O)2·H2O (2) (H4bptc = 3,3′,4,4′-benzophenonetetracarboxylic acid; bpy = 4,4′-bipyridine; phen = 1,10-phenanthroline), have been obtained via a hydrothermal method based on a semi-rigid aromatic tetracarboxylic ligand and two different auxiliary or templating N-containing ligands. Complex 1 shows a one-dimensional (1D) structure derived from double chains with two types of rings arranged alternately, which further exhibits an intriguing 3D supramolecular network induced by diverse non-covalent interactions. Complex 2 displays a dislocated “double floor” of a 2D structure (2D zigzag layers), in which the carboxylate groups of the bptc4− ligand adopt a variety of fascinating bridging modes. In addition, quantum chemical calculations were used to investigate the coordination properties and bonding nature of the as-synthesized complexes, and the results indicate that in these two complexes the 5f, 6d, and 7p orbitals of uranium and 2p orbitals of O and N atoms mainly contribute to the covalency of the U–O and U–N bonds.

ChemInform Abstract: Noncovalent Interaction‐Assisted Polymeric Micelles for Controlled Drug Delivery

AbstractReview: 176 refs.