Role Of Noncovalent Interactions Research Articles

Fe-Catalyzed Fluoroalkyl(hetero)arylation of Vinyl Azaarenes: Rapid and Modular Synthesis of Unsymmetrical 1,1-Bis(hetero)arylalkanes.

In contrast to transition-metal-catalyzed difunctionalization of activated alkenes, selective alkylarylation of vinyl azaarenes is underdeveloped. Consequently, the lack of modular and rapid syntheses of 1,1-bis(hetero)arylalkanes limits their exploration in medicinal chemistry. Herein we report a protocol using commercially available iron salts, bisphosphine ligands, fluoroalkyl halides, and Grignard reagents that enables the selective 1,2-fluoroalkyl(hetero)arylation of vinyl azaarenes. We demonstrate the versatility and robustness of the method through the selective synthesis of a range of unsymmetrical 1,1-bis(hetero)arylalkenes, including pyridine N-oxides, triazoles, pyrazines, carbazoles, indazoles, and 1,2-azaborines. Mechanistic insights from experimental and computational investigations support a radical pathway and provide insights into the role of non-covalent interactions in iron catalysis.

Recent Advances in Smart Self-Assembled Bioinspired Hydrogels: A Bridging Weapon for Emerging Health Care Applications from Bench to Bedside.

Stimuli-responsive low molecular weight hydrogel interventions for Biomedical challenges are a rapidly evolving paradigm in the bottom-up approach recently. Peptide-based self-assembled nano biomaterials present safer alternatives to their non-degradable counterparts as demanded for today's most urged clinical needs.Although a plethora of work has already been accomplished, programming hydrogelators with appropriate functionalities requires a better understanding as the impact of the macromolecular structure of the peptides and subsequently, their self-assembled nanostructures remain unidentified. Henceforth this review focuses on two aspects: Firstly, the underlying guidelines for building biomimetic strategies to tailor scaffolds leading to hydrogelation along with the role of non-covalent interactions that are the key components of various self-assembly processes. In the second section, it is aimed to bring together the recent achievements with designer assembly concerning their self-aggregation behaviour and applications mainly in the biomedical arena like drug delivery carrier design, antimicrobial, anti-inflammatory as well as wound healing materials. Furthermore, it is anticipated that this article will provide a conceptual demonstration of the different approaches taken towards the construction of these task-specific designer hydrogels. Finally, a collective effort among the material scientists is required to pave the path for the entrance of these intelligent materials into medicine from bench to bedside.

Theoretically designed M@diaza[2.2.2]cryptand complexes: the role of non-covalent interactions in promoting NLO properties of organic electrides

ABSTRACT Organic excess electron compounds with significant nonlinear optical (NLO) properties are widely employed in optoelectronic applications. Herein, single-alkali metals with diaza[2.2.2] cryptand (M@crypt,M=Li, Na, and K) are investigated for optoelectronic and NLO properties by using the density functional theory. Thermodynamic and kinetic stabilities of present complexes are computed through interaction energy (Eint) and ab-initio molecular dynamic (AIMD) simulations. M@crypt complexes carry excess electrons and mimic molecular electrides. Quantum theory of atoms in molecules (QTAIM) analysis and reduced density gradient (RDG) spectra demonstrate the roles of the weak van der Waals (vdW) interactions between metal and complexant. The remarkable hyperpolarizability (βo) value up to 1.41 × 106 au may be credited to the presence of loosely bound excess electrons. The hyper Rayleigh scattering hyperpolarizability (βHRS) is recorded up to 1.31 × 106 au for the K@crypt. Furthermore, frequency-dependent first-order and second-order hyperpolarizability is more prominent at the applied frequency of ω = 0.042823 au. The electron localizing function (ELF) and localized orbital locator (LOL) analysis further disclose the nature of interaction between alkali metal and complexant. The TD-DFT method is adopted to get excited state parameters and absorbance properties. An electron density difference map (EDDM) is exploited to evaluate the orbital contributions in excited states. Hence, the studied electride may become a promising candidate for NLO materials. We anticipate that the present work will provide insight into further development of molecular electride for optoelectronic applications.

Origin of Unprecedented Formation and Reactivity of FeIV═O Species via Oxygen Activation: Role of Noncovalent Interactions and Magnetic Coupling.

Emulating the capabilities of the soluble methane monooxygenase (sMMO) enzymes, which effortlessly activate oxygen at diiron(II) centers to form a reactive diiron(IV) intermediate Q, which then performs the challenging oxidation of methane to methanol, poses a significant challenge. Very recently, one of us reported the mononuclear complex [(cyclam)FeII(CH3CN)2]2+ (1), which performed a rare bimolecular activation of the molecule of O2 to generate two molecules of FeIV═O without the requirement of external proton or electron sources, similar to sMMO. In the present study, we employed the density functional theory (DFT) calculations to investigate this unique mechanism of O2 activation. We show that secondary hydrogen-bonding interactions between ligand N-H groups and O2 play a vital role in reducing the energy barrier associated with the initial O2 binding at 1 and O-O bond cleavage to form the FeIV═O complex. Further, the unique reactivity of FeIV═O species toward simultaneous C-H and O-H bond activation process has been demonstrated. Our study unveils that the nature of the magnetic coupling between the diiron centers is also crucial. Given that the influence of magnetic coupling and noncovalent interactions in catalysis remains largely unexplored, this unexplored realm presents numerous avenues for experimental chemists to develop novel structural and functional analogues of sMMO.

Neighboring Effects of Sulfur Oxidation State on Dynamic Covalent Bonds and Assemblies.

The impact of a varied sulfur oxidation state (sulfide, sulfoxide, and sulfone) on imine dynamic covalent chemistry is presented. The role of noncovalent interactions, including chalcogen bonds and CH hydrogen bonds, on aldehyde/imine structures and imine exchange reactions was elucidated through experimental and computational evidence. The change in the sulfur oxidation state and diamine linkage further allowed the regulation of imine macrocycles, providing a platform for controlling molecular assemblies.

Predisposition in Dynamic Covalent Chemistry: The Role of Non-Covalent Interactions in the Assembly of Tetrahedral Boronate Cages.

Directional bonding strategies guide the design of complex molecular architectures, yet challenges arise due to emergent behavior. Rigid structures face geometric constraints and sensitivity to mismatches, hindering the efficient assembly of molecular organic cages (MOCs). Harnessing intramolecular non-covalent interactions offers a promising solution, broadening geometrical possibilities and enhancing adaptability to boost assembly yields. However, identifying these interactions remains challenging, with their full potential sometimes latent until final assembly. This study explores these challenges by synthesizing boronic acid tripods with varied oxygen positions at the tripodal feet and investigating their role in assembling tetrahedral boronate MOCs. Our results reveal substantial differences in the assembly efficiency among tripods. While the building blocks with oxygen in the benzylic position relative to the central aromatic ring form the MOCs in high yields, those with the oxygen atom directly bound to the central aromatic ring, only yield traces. Through X-ray crystallography and DFT analyses, we elucidate how intramolecular interactions profoundly influence the geometry of the building blocks and cages in a relay-like fashion, highlighting the importance of considering intramolecular interactions in the rational design of (supra)molecular architectures.

A highly birefringent metal-free crystal assembled by cooperative non-covalent interactions.

Birefringent crystals can manipulate the phase and polarization of light, so they are widely used as essential components in various optical devices. Common strategies to construct birefringent crystals are introducing metal cations that are either able to realize favorable coordination with functional anionic units or are susceptible to polarizability anisotropy. Herein, we report a metal-free crystal, NH4(H2C6N7O3)·2H2O, synthesized using the facile solution method. In the crystal structure of NH4(H2C6N7O3)·2H2O, (H2C6N7O3)- functional units are assembled in an optimal manner by cooperative non-covalent interactions, i.e., hydrogen bonding and π-π interactions. As a result, this metal-free crystal possesses exceptional birefringence up to 0.54@550 nm, which is larger than those of most metal-containing birefringent crystals. In addition, the interference color of this crystal does not change obviously from 243 K to 313 K, indicating that the birefringence is robust at different temperatures. This work will inspire useful insights into the role of non-covalent interactions in designing outstanding birefringent crystals for efficient polarized optical devices.

The effect of second coordination sphere interactions on the magnetic anisotropy of transition metals.

In the study of mononuclear transition metal single molecule magnets (SMMs), extensive research has concentrated on identifying optimal coordination geometries around the central metal ion to enhance SMM properties. However, the role of non-covalent interactions in the second coordination sphere has been relatively underexplored. Here, we study the impact of non-covalent Cl⋯H interactions on the magnetic anisotropy of the central Co(II) ion in the distorted axially compressed octahedral complex CoCl2(tu)4 (1) (tu = SC(NH2)2). By performing cantilever torque magnetometry on 1, the orientation of the magnetic easy axis is found to deviate by almost 40° from the axial Co-Cl bond. Theoretical modelling on structural modifications of the structure of 1, quantifies how the distance between the Cl ligand and the nearest H-atom significantly influences the orientation of the magnetic easy axis and the D-value. Experimental chemical bonding analysis based on multipole modelling of synchrotron X-ray diffraction data on 1 reveal that the nearby H-atoms polarize the electron density of the Cl-ligands. This polarization results in reduced electron density at the axial positions on the Co octahedra, explaining the calculated increase in the magnitude of the D-value, when the H-atoms are moved away from Cl in silico. Topological analysis of theoretical electron densities on modified structures of 1 corroborates an increase in the electron density at the Co-Cl bond critical point, as the nearby H-atoms are moved further from Cl. These findings demonstrate the significant influence that non-covalent interactions have on the magnetic anisotropy of mononuclear transition metals and opens the possibility of utilizing these interactions in the design of transition metal based SMMs.

The role of non-covalent interactions in 4-hydroxybenzylamine macrocyclisation: computational and synthetic evidence.

4-hydroxybenzylamine's intermolecular interactions and their possible influence on the course of 4-hydroxybenzylamine's reaction with formaldehyde are analysed in this article. Computational calculations established that 4-hydroxybenzylamine forms dimers in solution by O-H⋯N hydrogen bonds; such dimers are stabilised by π-stacking interactions. These cyclic dimers' formation led to obtaining a 12-atom azacyclophane through 4-hydroxybenzylamine's reaction with formaldehyde.

The Role of Nitrogen-Rich Moieties in the Selection of Arginine's Tautomeric Form at Different Temperatures.

It is well known that the guanidinium group in Arginine plays an important role in noncovalent interactions. However, its role is not well documented since the selection of its global minimum structure is still controversial. The main difficulties on obtaining accurate results lie on: neutral Arginine can occur in 3 forms, two of which are canonical and one is zwitterion; each form has degenerate enantiomers D- and L-; its numerous degrees of freedom make it challenging to perform a thorough study; the short-range interactions require higher levels of theory to correctly describe them. Thus, we have performed a meticulous global minimum search. We performed optimizations of the systems at the PBE0 /Def2TZVP level of theory and single point calculations at the DLPNO-CCSD(T)/Def2TZVP level with zero-point corrections at PBE0 /Def2TZVP. We also analyzed Thermal Populations and IR Spectra of the systems to fully understand Arginine's behavior. The results show the energy minima structures strongly rely on its internal nitrogen-rich groups.

Pd(II)-Mediated Activation of Halonitriles in Different Solvents: Role of Noncovalent Interactions and Isolation of a Pd(0)/Pd(II) Complex

Pd(II)-Mediated Activation of Halonitriles in Different Solvents: Role of Noncovalent Interactions and Isolation of a Pd(0)/Pd(II) Complex

Solvent–solute and non-covalent interactions on bis(4-Piperidinonium ethyl ketal) oxalate compound: DFT calculations and in silico drug-target profiling

In the present paper, we deliver the synthesis, experimental results, and theoretical examination of a newly developed organic supramolecular compound, entitled bis(4-Piperidinonium ethyl ketal) oxalate, with the subsequent chemical formula: (C7H14NO2)2(C2O4), denoted by 4PEKOX. The stoichiometric 2:1 ratio of 4-Piperidinone ethyl ketal with oxalic acid, and the slow evaporation that follows, produce this new material. X-ray diffraction was carried out to identify the 4PEKOX asymmetric unit and its two-dimensional lattice. The attachment between 4-Piperidinonium ethyl ketal cations and oxalate anions is provided by N(C)-H…O H-bonds forming supramolecular units of type R22(8),R12(5) and R21(6). The inter-molecular interactions that contribute to crystal packing have been assessed through the use of the HS; the percentage participation of each interaction was presented as two-dimensional fingerprints. The infrared (IR) and UV–Visible spectroscopy allowed us to identify the functional groups and study the optical properties of 4PEKOX. Experimental investigations have been combined with quantum chemical calculations to confirm and evaluate the properties of 4PEKOX from a theoretical perspective, allowing us to explain and examine in detail the electronic transfer, polarity, atomic charges and the role of non-covalent interactions in this new compound. Secondly, the expected therapeutic effect of 4PEKOX as an organic supramolecular compound was studied using the molecular docking technique. We examined the effect of 4PEKOX on the SARS-CoV-2 (7JTL) protein and measured their interaction energy with it, comparing it with the energies of oxalic acid and heterocyclic amine separately with the same protein to show the evolution imposed by synthesis through the combination of organic molecules to produce supramolecules more reactive than the starting reagents. In this study, Favipiravir was used as a reference due to its potent therapeutic activity against multiple coronaviruses.

Role of non-covalent interactions in 2,5-di-Me-pyrazine-di-N-oxide - tertiary butyl alcohol - single-walled and multi-walled carbon nanotubes electrocatalytic systems

Oxidation of tert-butyl alcohol (tert-BuOH, Me3COH), a compound with a high C-H bond breaking energy in the absence of precious metals or their oxides as catalysts and using metal-free electrodes, is an inexpensive process and is of interest for practical applications in electrocatalysis and sensors. In this work, electrocatalytic systems 2,5-di-Me-pyrazine-di-N-oxide (Pyr1) - tert-BuOH – single - walled (SWCNT) and multi-walled (MWCNT) carbon nanotube paper electrodes in 0.1 M Bu4NClO4 solution in acetonitrile (MeCN) were studied by the methods of cyclic voltammetry, quantum chemical modeling and electron paramagnetic resonance (EPR) electrolysis. Calculaition of energies of non-covalent interactions between the components of the electrocatalytic system in complexes Me3COH*Me3COH, Me3COH*MeCN, Pyr1*Me3COH and the adsorption energy of Me3COH and complexes of Pyr1*Bu4NClO4, Pyr1*Me3COH, Pyr1*MeCN and Me3COH *Bu4NClO4 on CNTs surface using a cluster model describing the surface of conducting carbon nanotubes (10, 10) was performed. The study made it possible to reveal the regularities characteristic of aromatic-di-N-oxide – CNT electrocatalytic systems and to propose a mechanism of tert-BuOH oxidation in the presence of electrochemically generated radical cation Pyr1. The data will be useful at using CNT electrodes in electrocatalytic processes, as well as aromatic di-N-oxide-CNT catalytic systems in electrocatalysis and sensors.

Synthesis, crystal growth and supramolecular chemistry of 4-dimethylaminopyridinium salts of benzoates and a phenolate ion

Abstract Seven novel molecular salts were synthesized from the commonly available 4-dimethylaminopyridine organic base and benzoic acid derivatives contain additional functional groups. Benzoic acids with additional hydroxyl, nitro, amino, and bromo functional groups, were successfully employed and investigated their role in non-covalent interactions within the supramolecular chemistry of heterosynthons solid-state architecture. The collection of all 4-dimethylamopyrinium salts of benzoates and phenolate was accomplished through the utilization of conventional solvent evaporation technique. The resulting molecular salts were afforded by deprotonation of the acidic moiety such as COOH, or OH to the ring N of 4-dimethylaminopyridine, establishing a strong charged-assisted hydrogen bond between the deprotonated group (benzoate or phenolate) and protonated ring N. The structure of compounds was fully elucidated by single X-ray diffraction, powder X-ray diffraction, 1H NMR, FT-IR, and thermogravimetric analysis. The crystal packing is interpreted by the strong charge-assisted N–H⋯O hydrogen bond between the NH+ and the corresponding deprotonated group and O–H⋯O, N–H⋯N hydrogen bonding. The analysis concluded that C–H⋯O, CH3⋯O, C–H⋯π, CH3⋯π, π–π, C–H⋯Br, and CH3⋯Br contacts contribute significantly to stabilizing and expanding the high-dimensionality (2D–3D framework) of the structures. The structures were thoroughly explored for their various bonding and nonbonding interactions, as well as their supramolecular chemistry in detail. The antimicrobial activities of all compounds were evaluated using the Oxford cup method.

Role of Non-Covalent Interactions in Novel Supramolecular Compound, Bis(4-phenylpiperazin-1-ium) Oxalate Dihydrate: Synthesis, Molecular Structure, Thermal Characterization, Spectroscopic Properties and Quantum Chemical Study

The stoichiometric ratio 2:1 mix of 1-phenylpiperazine and oxalic acid dihydrate followed by slow evaporation results in a new material, bis(4-phenylpiperazin-1-ium) oxalate dihydrate, with the general chemical formula (C10H15N2)2(C2O4).2H2O, indicated by PPOXH. The title compound’s asymmetric unit and three-dimensional network have been determined by single crystal X-ray diffraction. Intermolecular O-H…O, N-H…O and C-H…O hydrogen bonding assist in maintaining and stabilization of the crystal structure of this new compound. Hirshfeld surface analysis and two-dimensional fingerprints have been performed to quantify the non-covalent interactions in the PPOXH structure. The vibrational modes of the different characteristic groups of the title chemical were identified using infrared spectrum analysis. The thermal characterization of this product was studied by a coupled TG/DTA analysis. The ultraviolet-visible absorption spectrum has been used to study the optical properties and the energy gap of this compound. DFT calculations were employed to evaluate the composition and properties of PPOXH. The analysis of HOMO-LUMO frontier orbitals analysis allows us to understand the chemical reactivity of this supramolecular compound and to determine the electrophilic and nucleophilic sites responsible for electron transfer. Topological analysis (AIM), reduced density gradient (RDG), molecular electrostatic potential surface (MEPS) and Mulliken population were analyzed to evaluate the types of non-covalent interactions, localization of electrons in space, atomic charges and molecular polarity in depth.

The Role of Non-Covalent Interactions in the Reactions between Palladium Hydrido Complex with Amidoarylphosphine Pincer Ligand and Brønsted Acids

The interaction between (PNP)PdH (1); PNP = bis(2-diisopropylphosphino-4-methylphenyl)amide and different acids (CF3SO3H, HBF4∙Et2O, fluorinated alcohols and formic acid) was studied in benzene or toluene as well as in neat alcohols by IR and NMR spectroscopies. The structures of hydrogen-bonded complexes were also optimized at the DFT/ωB97-XD/def2-TZVP level. The nitrogen atom of the amidophosphine pincer ligand readily accepts proton not only from strong Brønsted acids but from relatively weak fluorinated alcohols. That suggests that binding to palladium(II) increases the diarylamine basicity, making it a strong base. Nevertheless, H+ can be taken from [(PN(H)P)PdH]+ (2) by pyridine or hexamethylphosphoramide (HMPA). These observations confirm the need for a shuttle base to form [(PN(H)P)PdH]+ (2) as the result of the heterolytic splitting of H2 by [(PNP)Pd]+. At that, a stoichiometric amount of formic acid protonates a hydride ligand yielding an unstable η2-H2 complex that rapidly converts into formate (PNP)Pd(OCHO), which loses CO2 to restore (PNP)PdH, whereas the relatively high acid excess hampers this reaction through competitive protonation at nitrogen atom.

Role of Non-covalent Interaction toward Conductivity in a One-Dimensional Tube-like Silver-Thiolate Structure

We report a new one-dimensional tube-like atomically precise silver-thiolate polymer–chain. The structure consists of Ag14(SR)18 as the building units. Silver atoms are linked with the thiol ligand to form the one-dimensional structure. The non-covalent interactions like argentophilic and C–H···H–C interactions appear as crucial for the long-range structural arrangement. Electronic structure calculations show its semiconductor-type band structure with a band gap of about 2 eV. Conductivity measurements on the single crystal implies its facile charge transfer pathway along the one-dimensional chain. The variation of conductivity between the single crystal and the drop-cast film implies the role of argentophilic and C–H···H–C interactions in the preferred charge transfer pathway.

Role of Non-Covalent Interactions in Carbonic Anhydrase I-Topiramate Complex Based on QM/MM Approach.

Carbonic anhydrase (CA) I with a Topiramate (TPM) complex was investigated on the basis of a Quantum Mechanics/Molecular Mechanics (QM/MM) approach. The QM part was treated using Density Functional Theory (DFT) while the MM was simulated using Amberff14SB and GAFF force fields. In addition, the TIP3P model was applied to reproduce the polar environment influence on the studied complex. Next, three snapshots (after 5 ps, 10 ps, and 15 ps of the simulation time) were taken from the obtained trajectory to provide an insight into the non-covalent interactions present between the ligand and binding pocket of the protein. Our special attention was devoted to the binding site rearrangement, which is known in the literature concerning the complex. This part of the computations was performed using ωB97X functional with Grimme D3 dispersion corrections as well as a Becke-Johnson damping function (D3-BJ). Two basis sets were applied: def2-SVP (for larger models) and def2-TZVPD (for smaller models), respectively. In order to detect and describe non-covalent interactions between amino acids of the binding pocket and the ligand, Independent Gradient Model based on Hirshfeld partitioning (IGMH), Interaction Region Indicator (IRI), Quantum Theory of Atoms in Molecules (QTAIM) and Natural Bond Orbitals (NBO) methods were employed. Finally, Symmetry-Adapted Perturbation Theory (SAPT) was applied for energy decomposition between the ligand and protein. It was found that during the simulation time, the ligand position in the binding site was preserved. Nonetheless, amino acids interacting with TPM were exchanging during the simulation, thus showing the binding site reorganization. The energy partitioning revealed that dispersion and electrostatics are decisive factors that are responsible for the complex stability.

Role of Noncovalent Interactions in N,P-Functionalized Luminescent Carbon Dots for Ultrasensitive Detection of Moisture in D2O: Boosting Visible-NIR Light Sensitivity.

It is highly desirable to design cost-efficient and eco-friendly fluorometric sensors that can efficiently detect water contamination in D2O and other expensive organic solvents. Herein, we have synthesized N,P-codoped carbon dots (N,P-CDs) from o-phenylene diamine (o-PDA) and H3PO4 through the bottom-up carbonization method. Heteroatom co-doping increases the absorption cross section in the visible-NIR range, followed by the formation of stable emissive states in longer-wavelength regions. We have critically investigated the noncovalent interactions (especially H-bonding interactions) of various surface functional groups with surrounding solvent media through a detailed structure-property correlation. Based on the sensitivity of noncovalent H-bonding interactions to the stability of longer-wavelength emissive domains, we have utilized these N,P-CDs as cost-effective fluorometric sensors of water/moisture contamination in D2O especially under visible-NIR light; the optical sensitivity reaches up to 0.1 volume (%) level. The detailed sensing mechanism has been further supported by a computational study through a simple visualization approach by mapping and analyzing all possible noncovalent interactions between the CDs and the solvent medium.

Extending density functional theory with near chemical accuracy beyond pure water

Density functional simulations of condensed phase water are typically inaccurate, due to the inaccuracies of approximate functionals. A recent breakthrough showed that the SCAN approximation can yield chemical accuracy for pure water in all its phases, but only when its density is corrected. This is a crucial step toward first-principles biosimulations. However, weak dispersion forces are ubiquitous and play a key role in noncovalent interactions among biomolecules, but are not included in the new approach. Moreover, naïve inclusion of dispersion in HF-SCAN ruins its high accuracy for pure water. Here we show that systematic application of the principles of density-corrected DFT yields a functional (HF-r2SCAN-DC4) which recovers and not only improves over HF-SCAN for pure water, but also captures vital noncovalent interactions in biomolecules, making it suitable for simulations of solutions.