Bifurcated Hydrogen Bonds Research Articles

Optimization and Synthesis of Nano-Niosomes for Encapsulation of Triacontanol by Box-Behnken Design.

Triacontanol is a long-chain primary alcohol derived from policosanol, known for its diverse biological activities, including functioning as a plant growth regulator and exhibiting anti-inflammatory and antitumoral effects. However, its application is limited due to its high hydrophobicity, resulting in poor absorption and reduced therapeutic effectiveness. A potential solution to this problem is the use of niosomes. Niosomes are carriers composed of non-ionic surfactants, cholesterol, charge-inducing agents, and a hydration medium. They are effective in encapsulating drugs, improving their solubility and bioavailability. The objective of this study was to optimize and synthesize nano-niosomes for the encapsulation of triacontanol. Niosomes were synthesized using a thin-film hydration method combined with ultrasonication, following a Box-Behnken design. Niosomes were characterized using various techniques including dynamic light scattering, Fourier-transform infrared spectroscopy (FTIR), confocal microscopy, high-resolution scanning electron microscopy, and transmission electron microscopy (TEM). Formulation 14 of niosomes achieved the desired size, polydispersity index (0.198 ± 0.008), and zeta potential (-31.28 ± 1.21). FTIR analysis revealed a characteristic signal in the 3400-300 cm-1 range, indicating intermolecular interactions due to a bifurcated hydrogen bond between cholesterol and S60. Confocal microscopy confirmed the presence of triacontanol through Nile Red fluorescence. TEM revealed the spherical structure of niosomes.

The pattern of bifurcated hydrogen bonds in thiourea cocrystals with diazine derivatives: experimental and quantum theoretical studies.

Cocrystals of thiourea with pyrazine N-oxide as thiourea-pyrazine N-oxide (2/1), C4H4N2O·2CH4N2S, (I), and with phenazine as thiourea-phenazine (6/7), 7C12H8N2·6CH4N2S, (II), both crystallize in the monoclinic space group P21/c. In the crystalline state, molecules of both components are linked by N-H...N hydrogen bonds. In addition, there are R22(8) hydrogen-bond synthons between thiourea molecules in both crystal structures. Furthermore, bifurcated hydrogen bonds between the -NH groups in the thiourea molecule and the N and O atoms in the N-oxide ring [in (I)], as well as the N atom in the central phenazine ring [in (II)], play a significant role in both structures. This emerging motif was thoroughly examined using quantum chemistry methods.

Fluoride-Based Deep Eutectic Solvents with Amide Dual-Hydrogen-Bond Donors.

Developing F--containing electrolytes is crucial for electrochemical and chemical fluorination. However, balancing the F- concentration and electrochemical stability of the electrolytes remains a challenge. In this study, fluoride-based deep eutectic solvents (F-DESs) were obtained by using amide hydrogen-bond donors (HBDs) containing dual N-H bonds. The obtained F-DES, [TMA]F·3.5[1,3-DMU], was prepared by facilely mixing solid compounds of tetramethylammonium fluoride ([TMA]F) and 1,3-dimethylurea (1,3-DMU), resulting in a high F- concentration (2.6 mol dm-3) and a wide electrochemical window (3.1 V) at room temperature. The electrochemical window was much wider than that of [TMA]F·3.5[EG] (EG, ethylene glycol) as another F-DES with an alcohol HBD (1.9 V). Moreover, [TMA]F·3.5[1,3-DMU] exhibited an ionic conductivity that was 2 orders of magnitude higher than that of [TMA]F·3.5[1,3-DMTU] (1,3-DMTU, 1,3-dimethylthiourea) around room temperature because of the bifurcated hydrogen bonds between the dual N-H bonds of 1,3-DMU and one F-. Thus, [TMA]F·3.5[1,3-DMU] was demonstrated to be applicable to electrochemical fluorination.

Stabilizing Bifurcated Hydrogen Bond in 8-Aminoquinoline Appended Peptides.

The hydrogen bonding interaction between an amide N-H and the amide N of the preceding residue is prevalent in proline-containing proteins and peptides. However, the N-H⋅⋅⋅N hydrogen bonding interaction is rare in non-prolyl natural peptides due to restricted dihedral angles. Herein, we stabilize this type of interaction in 8-aminoquinoline appended non-prolyl peptides through bifurcated N⋅⋅⋅H⋅⋅⋅N hydrogen bond. The 8-aminoquinoline-incorporated model peptides 2 a-i were designed, synthesized, and the crystal structures of 2 a-c and 2 i were solved. Analysis of crystal data reveals that the amide N-H of aminoquinoline is involved in bifurcated hydrogen bonding interaction with the nitrogen of the preceding amino acid residue and the nitrogen in quinoline. Analysis of crystal packing, Hirshfeld surface and fingerprint plots confirms that the intermolecular O⋅⋅⋅H contacts significantly contribute to stabilizing bifurcated N⋅⋅⋅H⋅⋅⋅N hydrogen bonding interaction. Furthermore, NMR experiments and CD spectroscopy were conducted to examine the preferred conformation in solution, and the data corroborate with the crystal structure conformation.

Cooperative Bifurcated Chalcogen Bonding and Hydrogen Bonding as Stereocontrolling Elements for Selective Strain-Release Septanosylation.

The exploitation of noncovalent interactions (NCIs) is emerging as a vital handle in tackling broad stereoselectivity challenges in synthesis. In particular, there has been significant recent interest in the harnessing of unconventional NCIs to surmount difficult selectivity challenges in glycosylations. Herein, we disclose the exploitation of an unconventional bifurcated chalcogen bonding and hydrogen bonding (HB) network, which paves the way for a robust catalytic strategy into biologically useful seven-membered ring sugars. Through 13C nuclear magnetic resonance (NMR) in situ monitoring, NMR titration experiments, and density functional theory (DFT) modeling, we propose a remarkable contemporaneous activation of multiple functional groups consisting of a bifurcated chalcogen bonding mechanism working hand-in-hand with HB activation. Significantly, the ester moiety installed on the glycosyl donor is critical in the establishment of the postulated ternary complex for stereocontrol. Through the 13C kinetic isotopic effect and kinetic studies, our data corroborated that a dissociative SNi-type mechanism forms the stereocontrolling basis for the excellent α-selectivity.

Structure, thermal and optical properties of hydrogen bond stabilized hybrid rare-earth selenates: [(CH3)3NH][Ln(H2O)4(SeO4)2], (Ln = Pr, Nd)

Herein the structures, thermal stabilities and optical properties of hydrated hybrid double selenate of trimethylammonium and Ln(III), as [(CH3)3NH][Ln(H2O)4(SeO4)2]; for Ln = Pr, Nd, (named as PrTMAS and NdTMAS) are reported. Both the hydrated double selenates were crystalized from aqueous solution under controlled atmosphere and temperature, and their crystal structures were determined by single crystal X-ray diffraction. Both the Pr3+ and Nd3+ compounds are isostructural and have triclinic (space group P-1) lattices with distorted cubical [LnO4(OH2)4], and tetrahedral (CH3)3NH+ and SeO42─ entities as structure building units. The [LnO4(OH2)4] and SeO42─ units are linked together through oxygen atoms forming chains of [Ln(H2O)4(SeO4)2]─ and these chains are linked together by cyclic, acyclic and bifurcated hydrogen bonds. The charge neutralization in the unit cell is attained by trimethylammonium ions occupied in between the chains. The FTIR and Raman spectroscopic investigations indicated the characteristic vibrations of selenate, water, hydrated praseodymium and trimethylammonium groups. The photoluminescence spectra of PrTMAS revealed intense emission near red side of visible spectrum centred at 661 nm upon excitation with 350 nm whereas that of NdTMAS shows blue-green emission on excitation with 400 nm. The diffused reflectance spectra of PrTMAS and NdTMAS compounds indicated band edges absorption at 4.4 and 5.0 eV, respectively. The compounds were found to be stable at room temperature, but with increasing temperature, the water molecules are lost where the lattices collapse, and subsequently the SeO42─ ions are lost as gaseous SeO2.

Strong structuring arising from weak cooperative O-H···π and C-H···O hydrogen bonding in benzene-methanol solution

Weak hydrogen bonds, such as O-H···π and C-H···O, are thought to direct biochemical assembly, molecular recognition, and chemical selectivity but are seldom observed in solution. We have used neutron diffraction combined with H/D isotopic substitution to obtain a detailed spatial and orientational picture of the structure of benzene-methanol mixtures. Our analysis reveals that methanol fully solvates and surrounds each benzene molecule. The expected O-H···π interaction is highly localised and directional, with the methanol hydroxyl bond aligned normal to the aromatic plane and the hydrogen at a distance of 2.30 Å from the ring centroid. Simultaneously, the tendency of methanol to form chain and cyclic motifs in the bulk liquid is manifest in a highly templated solvation structure in the plane of the ring. The methanol molecules surround the benzene so that the O-H bonds are coplanar with the aromatic ring while the oxygens interact with C-H groups through simultaneous bifurcated hydrogen bonds. This demonstrates that weak hydrogen bonding can modulate existing stronger interactions to give rise to highly ordered cooperative structural motifs that persist in the liquid phase.

The hydrogen-bond network in sodium chloride tridecahydrate: analogy with ice VI.

The structure of a recently found hyperhydrated form of sodium chloride (NaCl·13H2O and NaCl·13D2O) has been determined by in situ single-crystal neutron diffraction at 1.7 GPa and 298 K. It has large hydrogen-bond networks and some water molecules have distorted bonding features such as bifurcated hydrogen bonds and five-coordinated water molecules. The hydrogen-bond network has similarities to ice VI in terms of network topology and disordered hydrogen bonds. Assuming the equivalence of network components connected by pseudo-symmetries, the overall network structure of this hydrate can be expressed by breaking it down into smaller structural units which correspond to the ice VI network structure. This hydrogen-bond network contains orientational disorder of water molecules in contrast to the known salt hydrates. An example is presented here for further insights into a hydrogen-bond network containing ionic species.

Synergistic Spectroscopic and Computational Characterization Evidencing the Preservation or Flipping of the Hydroxyl Group of 2-Phenylethyl Alcohol upon Single and Double Hydration.

Even apparently simple, obtaining and analyzing observations on molecules and clusters and unambiguously assigning their structures is challenging. We report here the first ionization-loss Raman spectra compared to quantum chemical predictions for establishing the structural preferences of hydrates of the neurotransmitters hydroxy analogue, 2-phenylethyl alcohol (PEAL). The spectra encode two monohydrates and two previously unnoticed dihydrates, consequences of water insertion and sidewise attachment to the O-H group of gauche PEALs, in PEAL-H2O and PEAL-(H2O)2, or the higher-energy gauche-trans PEAL in the latter. The electronic structures retain the stable PEAL or flip its O-H to convert the gauche-trans PEAL conformer to the global minimum-energy dihydrate. We disclose conventional and bifurcated hydrogen bonds and electron steric repulsions by noncovalent interaction analysis and correlations between the experimental O-H stretching vibrational frequencies and the O-H and H···X bond lengths and electron densities, pointing to implications on hydrate forms and our approach virtue.

Bifurcated Hydrogen Bonds in a Peptide Crystal Unveiled by X-ray Diffraction and Polarized Raman Spectroscopy

The strength of hydrogen bonds in molecular crystals has been investigated through X-ray structural analysis and vibrational spectroscopy, and the interatomic distances and the stretching vibrational frequency involving hydrogen bonds have been known to exhibit a linear relationship. However, these studies are limited to relatively small molecular compounds, such as amino acids. In this study, we employed tetrapeptide as a model system to investigate the hydrogen bond network in the peptide crystal. Single crystal X-ray diffraction revealed that the peptide crystal structure had bifurcated hydrogen bonds. Raman spectroscopy exhibited that the vibrational frequency of amide bonds correlated linearly to their interatomic distance, but the rate of the change was significantly low compared with previous works. Fragment molecular orbital calculations also revealed that bifurcated hydrogen bonds affect the strength of the hydrogen bonds. This study provides a valuable model system for discussing the effects of bifurcated hydrogen bonds in various crystals of peptides.

Transition State Stabilization by SCF2 -H⋅⋅⋅O Bifurcated Hydrogen Bond.

The difluoromethylthio group (SCF2 H), which is generally considered a highly lipophilic weak hydrogen bonding donor, has attracted special interest from the pharmaceutical and agrochemical industry. Remarkably, there have been relatively few literature investigations of SCF2 H hydrogen bonding interactions. Here, we report the determination of the hydrogen bond acidity parameter A of the SCF2 H in the most popularly used electrophilic difluoromethylthiolating reagent. We present kinetic and computational evidence of the RSCF2 -H⋅⋅⋅O2 bifurcated hydrogen bond for stabilizing the SCF2 H-transferring transition state, which could cause a reversal of apparent electrophilic reactivity of difluoromethylthiolating and trifluoromethylthiolating reagents. Solvent effects on the RSCF2 -H⋅⋅⋅O2 bifurcated hydrogen bonds will also be discussed.

Molecular characteristics of 1-benzhydrylazetidin-3-ol by time-dependent density functional theory analysis

1-benzhydrylazetidin-3-ol (BA3) molecule was characterized by its experimental UV–Visible (200–400 nm) spectrum in a solution of chloroform and simulated spectrum using time-dependent density functional theory (TD-DFT). The computations were made using density functional theory employing B3LYP exchange–correlation functional in conjunction with the 6–311++G(d,p) basis set. Good agreement was observed between measured and computed quantities corresponding to structure parameters and UV–Visible spectrum. The chemical reactivity of the molecule was identified with the help of frontier molecular orbital (FMO) parameters. The non-linear optical (NLO) behavior of the molecule was studied by computing the values of hyperpolarizability (βt), polarizability (αt), and dipole moment (μt). NBO analysis has been used to examine the molecule's stability as a result of hyper-conjugative interactions and charge delocalization. According to NBO analysis, the title molecule has O-H• • • N and C-H• • •N bifurcated hydrogen bonds, which is compatible with the result of the molecular structure study. It is evident from the computed HOMO and LUMO energies that charge transfer takes place within the molecule. The NLO parameters also confirm these findings. Thermodynamic parameters were also computed for this molecule.

Molecular Tetris by sequence-specific stacking of hydrogen bonding molecular clips

A face-to-face stacking of aromatic rings is an effective non-covalent strategy to build functional architectures, as elegantly exemplified with protein folding and polynucleotide assembly. However, weak, non-directional, and context-sensitive van der Waals forces pose a significant challenge if one wishes to construct well-organized π-stacks outside the confines of the biological matrix. To meet this design challenge, we have devised a rigid polycyclic template to create a non-collapsible void between two parallel oriented π-faces. In solution, these shape-persistent aromatic clips self-dimerize to form quadruple π-stacks, the thermodynamic stability of which is enhanced by self-complementary N–H···N hydrogen bonds, and finely regulated by the regioisomerism of the π-canopy unit. With assistance from sufficient electrostatic polarization of the π-surface and bifurcated hydrogen bonds, a small polyheterocyclic guest can effectively compete against the self-dimerization of the host to afford a triple π-stack inclusion complex. A combination of solution spectroscopic, X-ray crystallographic, and computational studies aided a detailed understanding of this cooperative vs competitive process to afford layered aromatics with extraordinary structural regularity and fidelity.

Use of BOPYOs as a protection strategy for Pyrrole-based Chalcones: Removal of BF2, optical properties and AIE effect

Chelating ligands play a central role for clinical medicine, transition metal catalyst reaction. Herein, we report the first facile method for the deprotection of seven membered BOPYO involving a solvent-assisted procedure for the removal of BF2 unit, and liberation of the corresponding free-base pyrrole-based chalcones. Interestingly, these compounds have high sensitivity to acid, and stable in the condition of repeated addition of acid and base with more than five times titration. Meanwhile, 3a shows AIE phenomenon with 13.1-fold increase for the fluorescent intensity. That's probably attributed to centrosymmetric dimer with the monomeric units (3a) linking by C = O, NH bifurcated hydrogen bonds in this crystal.

Molecular mechanisms from reaction coordinate graph enabled multidimensional free energies illustrated on water dimer hydrogen bonding.

Computing the free energies of molecular mechanisms in multidimensional space relies on combinations of geometrically complex reaction coordinates. We show how a graph theory implementation reduces complexity, and illustrate this on the arrangements of hydrogen bonding of a water dimer. The reaction coordinates and forces are computed using graphs that define the dependencies on the atoms in the Free Energy from Adaptive Reaction Coordinate Forces (FEARCF) library. The library can be interfaced with classical molecular dynamics as well as quantum molecular dynamics packages. Multidimensional interdependent reaction coordinates are constructed to produce complex free energy hypersurfaces. The reaction coordinates are graphed from atomic and molecular components to define points, distances, vectors, angles, planes and combinations thereof. The resultant free energy surfaces that are a function of the distance, angles, planes, and so on, can represent molecular mechanisms in reduced dimensions from the component atomic Cartesian coordinate degrees of freedom. The FEARCF library can be interfaced with any molecular package. Here, we demonstrate the link to NWChem to compute a hyperdimensional DFT (aug‐cc‐pVDZ basis set and X3LYP exchange correlation functionals) free energy space of a water dimer. Analysis of the water dimer free energy hypervolume reveals that while the chain and cyclic hydrogen bonding configurations are located in stable minimum energy wells, the bifurcated hydrogen bond configuration is a gateway to instability and dimer dissociation.

Simple Rules for Complex Near-Glass-Transition Phenomena in Medium-Sized Schiff Bases.

Glass-forming ability is one of the most desired properties of organic compounds dedicated to optoelectronic applications. Therefore, finding general structure–property relationships and other rules governing vitrification and related near-glass-transition phenomena is a burning issue for numerous compound families, such as Schiff bases. Hence, we employ differential scanning calorimetry, broadband dielectric spectroscopy, X-ray diffraction and quantum density functional theory calculations to investigate near-glass-transition phenomena, as well as ambient- and high-pressure molecular dynamics for two structurally related Schiff bases belonging to the family of glycine imino esters. Firstly, the surprising great stability of the supercooled liquid phase is shown for these compounds, also under high-pressure conditions. Secondly, atypical self-organization via bifurcated hydrogen bonds into lasting centrosymmetric dimers is proven. Finally, by comparing the obtained results with the previous report, some general rules that govern ambient- and high-pressure molecular dynamics and near-glass transition phenomena are derived for the family of glycine imino esters. Particularly, we derive a mathematical formula to predict and tune their glass transition temperature (Tg) and its pressure coefficient (dTg/dp). We also show that, surprisingly, despite the presence of intra- and intermolecular hydrogen bonds, van der Waals and dipole–dipole interactions are the main forces governing molecular dynamics and dielectric properties of glycine imino esters.

Complex hydrogen bonding and thermal behaviour over a wide temperature range of kainite KMg(SO4)Cl⋅2.75H2O

AbstractKainite, KMg(SO4)Cl⋅2.75H2O, is one of the most common hydrated sulfate minerals, and it plays an important role as a source of potassium. However, its properties and structure have, to date, been insufficiently studied. In our present work, kainite was investigated using multiple techniques, including single-crystal and powder X-ray diffraction, thermogravimetry, differential scanning calorimetry (DSC), and infrared spectroscopy (IR). The mineral is monoclinic, C2/m, a = 19.6742(2), b = 16.18240(10), c = 9.49140(10) Å, β = 94.8840(10)°, V = 3010.86(5) Å3 and Z = 16. The structure was refined to R1 = 0.0230 for 3080 unique observed reflections with |Fo| ≥ 4σF. The complex hydrogen bonding system for kainite is described for the first time. The structure of kainite contains seven symmetrically independent sites occupied by water molecules, six of which are strongly bonded to Mg2+ cations while the seventh resides in the framework cavities. The acceptors of the hydrogen bonds are either chloride anions, neighbouring water molecules or oxygens atoms of sulfate groups. A bifurcated hydrogen bond was described for one of the water molecules. Based on the analysis of the crystal structure, we have confirmed and propose the correct formula for kainite as KMg(SO4)Cl⋅2.75H2O. The thermal studies of kainite in the temperature range of –150°C to +600°C indicate its stability to 190°C. The decomposition products are K2Mg2(SO4)3, KCl and K2SO4. The thermal expansion was calculated, which for kainite has a character typical for monoclinic crystals and similar to the compressibility tensor described earlier.

Cynarine monohydrate from synchrotron powder X-ray diffraction data.

The crystal structure of cynarine monohydrate (systematic name: 1,3-bis{[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}-4,5-dihydroxycyclohexane-1-carboxylic acid monohydrate), C25H24O12·H2O, has been solved and refined using synchrotron powder X-ray diffraction data, and optimized using density functional techniques. Despite being purchased as anhydrous, cynarine crystallizes as a monohydrate and the crystal structure is characterized by alternating layers of hydrocarbon and hydrogen-bonding interactions parallel to the bc plane. Hydrogen bonds are significant in the crystal structure. The carboxylic acid group forms a strong intermolecular hydrogen bond to a hydroxy group of the quinic acid ring. Most of the hydroxy groups act as donors in O-H...O hydrogen bonding to carbonyl O atoms. One hydroxy group participates in bifurcated hydrogen bonds, one to a hydroxy group on the quinic acid ring and the other, an intramolecular interaction, to another hydroxy group. The powder pattern has been submitted to the International Centre for Diffraction Data (ICDD) for inclusion in the Powder Diffraction File (PDF-4).

Stabilization of the DMSO Solvate of 2-Chloro-5-nitrobenzoic acid (Mesalazine Impurity M) by Bifurcated Hydrogen Bonds: Crystallographic, Spectroscopic, Thermal and Computational Studies

Stabilization of the DMSO Solvate of 2-Chloro-5-nitrobenzoic acid (Mesalazine Impurity M) by Bifurcated Hydrogen Bonds: Crystallographic, Spectroscopic, Thermal and Computational Studies

A novel hydrogen-bonding N-oxide-sulfonamide-nitro N-H...O synthon determining the architecture of benzenesulfonamide cocrystals.

The structures of novel cocrystals of 4-nitropyridine N-oxide with benzenesulfonamide derivatives, namely, 4-nitrobenzenesulfonamide-4-nitropyridine N-oxide (1/1), C5H4N2O3·C6H6N2O4S, and 4-chlorobenzenesulfonamide-4-nitropyridine N-oxide (1/1), C6H6ClNO2S·C5H4N2O3, are stabilized by N-H...O hydrogen bonds, with the sulfonamide group acting as a proton donor. The O atoms of the N-oxide and nitro groups are acceptors in these interactions. The latter is a double acceptor of bifurcated hydrogen bonds. Previous studies on similar crystal structures indicated competition between these functional groups in the formation of hydrogen bonds, with the priority being for the N-oxide group. In contrast, the present X-ray studies indicate the existence of a hydrogen-bonding synthon including N-H...O(N-oxide) and N-H...O(nitro) bridges. We present here a more detailed analysis of the N-oxide-sulfonamide-nitro N-H...O ternary complex with quantum theory computations and the Quantum Theory of Atoms in Molecules (QTAIM) approach. Both interactions are present in the crystals, but the O atom of the N-oxide group is found to be a more effective proton acceptor in hydrogen bonds, with an interaction energy about twice that of the nitro-group O atoms.