Three-dimensional Hydrogen-bonded Network Research Articles

Biochanin-A co-crystal formulation improves bioavailability and ameliorates cerulein-induced pancreatitis by attenuating the inflammation

Co-crystallization of a therapeutic ingredient with an appropriate co-former is a powerful technique to augment the physicochemical and pharmacokinetic properties and the effectiveness of Active Pharmaceutical Ingredients (APIs). Biochanin A (BCA), a flavonoid with medicinal potential, is limited by poor solubility and low oral bioavailability. This study aimed to design and develop a novel BCA-nicotinamide cocrystal as BCC to enhance BCA’s oral bioavailability and explore its therapeutic potential for ameliorating cerulein-induced acute pancreatitis (CIAP) by elucidating the target identification utilizing tissue/serum metabolite profiles. The cocrystal was designed by the supramolecular synthon approach and characterized by single-crystal X-ray diffraction that confirms a robust three-dimensional hydrogen-bonded network of BCA and Nicotinamide (NCT) in the crystal. FT-IR and DSC were used to analyze the cocrystal’s intermolecular interactions and thermal behavior. BCC exhibited enhanced solubility and drug release compared to BCA alone, resulting in enhanced oral bioavailability and pancreatic tissue concentration. Comparing BCC to BCA in the CIAP model, BCC therapy remarkably reduced cerulein-induced pancreatitis, evidenced by significant reductions in inflammation, acinar cell atrophy, and amylase levels in pancreatic tissues. Further, the cocrystal formulation also down-regulated the oxidative stress markers, inflammatory cytokines and macrophage-related proteins. The study has identified distinct metabolomic signatures linked with AP with the help of Orbitrap Exploris mass spectrometry, which could pave the way for creating focused diagnostic tools for a better prognosis. In conclusion, these results offer new insights into exploring mechanistic pathways associated with specific biomarkers and underscore BCC cocrystal as a promising approach to enhance BCA’s therapeutic potential.

Dynamic 3D hydrogen-bond network in siloxene-water system enables efficient moisture-enabled electricity generation

Utilizing ubiquitous moisture as an energy source for moisture-enabled electric generator (MEG) has emerged as a significant technological frontier. The migration process of protons at the water/solid interface is crucial for understanding the mechanism of moisture-to-electricity conversion and efficient energy harvesting. However, the lack of clarity on this scientific question has hindered the substantive development of MEG. Here, a novel dynamic three-dimensional (3D) hydrogen-bond network between the interface of siloxene layers was designed through water molecule intercalation. The spatial bridging effect of this dynamic 3D hydrogen-bond network, formed on the siloxene layers, enhances the load transfer capability of the siloxene-water system, thereby randomizing the direction of proton hopping. Experimental and theoretical calculations demonstrate that the dynamic 3D hydrogen-bond network constructed within and between the siloxene layers facilitates rapid proton conduction. Kinetic simulations further confirm that the strength of the hydrogen-bond network accelerates proton transport rate. The current density of siloxene under high humidity increases significantly, reaching 22.37 µA cm−2, which is 122 times that under low humidity, as well as the open-circuit voltage reaches 0.73 V. This work contributes to understanding the microscopic mechanisms behind efficient moisture-enabled electricity and provides a fresh perspective for enhancing MEG performance.

Пространственная сетка водородных связей в жидкостях и растворах

A review of the author's studies of the problem of a three-dimensional network of hydrogen bonds in liquids and solutions is presented. The main properties of the spatial network are revealed: stability, lability, elasticity and correlation of different types of motion of particles forming the network. Methods and results of description and study of three-dimensional networks are presented. The determining role of spatial networks of hydrogen bonds in a wide range of liquid problems of biology, physics and chemistry in applied and fundamental science is shown. It is proposed to distinguish liquids with a spatial network of hydrogen bonds into a separate class of solvents, headed by water.

Constructing three-dimensional hydrogen-bonding network and porous film from chitosan enables high-performance silicon@carbon anode

Constructing three-dimensional hydrogen-bonding network and porous film from chitosan enables high-performance silicon@carbon anode

Crystal structures of the isomeric dipeptides l-glycyl-l-me-thio-nine and l-me-thionyl-l-glycine.

The oxidation of me-thionyl peptides can contribute to increased biological (oxidative) stress and development of various inflammatory diseases. The conformation of peptides has an important role in the mechanism of oxidation and the inter-mediates formed in the reaction. Herein, the crystal structures of the isomeric dipeptides Gly-Met (Gly = glycine and Met = me-thio-nine) and Met-Gly, both C7H14N2O3S, are reported. Both mol-ecules exist in the solid state as zwitterions with nominal proton transfer from the carb-oxy-lic acid to the primary amine group. The Gly-Met mol-ecule has an extended backbone structure, while Met-Gly has two nearly planar regions kinked at the C atom bearing the NH3 group. In the crystals, both structures form extensive three-dimensional hydrogen-bonding networks via N-H⋯O and bifurcated N-H⋯(O,O) hydrogen bonds having N⋯O distances in the range 2.6619 (13)-2.8513 (13) Å for Gly-Met and 2.6273 (8)-3.1465 (8) Å for Met-Gly.

Crystal structures of 1,1'-bis-(carb-oxy-meth-yl)-4,4'-bipyridinium derivatives.

The crystal structures of 2-[1'-(carb-oxy-meth-yl)-4,4'-bi-pyridine-1,1'-diium-1-yl]acetate tetra-fluoro-borate, C14H13N2O4 +·BF4 - or (Hbcbpy)(BF4), and neutral 1,1'-bis-(carboxyl-atometh-yl)-4,4'-bi-pyridine-1,1'-diium (bcbpy), C14H20N2O8, are reported. The asymmetric unit of the (Hbcbpy)(BF4) consists of a Hbcbpy+ monocation, a BF4 - anion, and one-half of a water mol-ecule. The BF4 - anion is disordered. Two pyridinium rings of the Hbcbpy+ monocation are twisted at a torsion angle of 30.3 (2)° with respect to each other. The Hbcbpy monocation contains a carb-oxy-lic acid group and a deprotonated carboxyl-ate group. Both groups exhibit both a long and a short C-O bond. The cations are linked by inter-molecular hydrogen-bonding inter-actions between the carb-oxy-lic acid and the deprotonated carboxyl-ate group to give one-dimensional zigzag chains. The asymmetric unit of the neutral bcbpy consists of one-half of the bcbpy and two water mol-ecules. In contrast to the Hbcbpy+ monocation, the neutral bcbpy mol-ecule contains two pyridinium rings that are coplanar with each other and a carboxyl-ate group with similar C-O bond lengths. The mol-ecules are connected by inter-molecular hydrogen-bonding inter-actions between water mol-ecules and carboxyl-ate groups, forming a three-dimensional hydrogen-bonding network.

Mixed Network of Hydrogen Bonds in Aqueous Solutions of 3-Amino-1-propanol: Results of Molecular Dynamic Modeling

The H2O–3-amino-1-propanol (3AP) system at 300 K was studied by molecular dynamics, graph theory, and Delaunay simplex methods. All the molecules were shown to be bound into a three-dimensional network of hydrogen bonds over the entire range of concentrations in the system. The characteristics of the networks and their concentration dependences were determined. The frequency at which the environment of molecules changes is discussed. The results were compared with those for mixed networks in aqueous solutions of 1,3-propanediol and monoethanolamine.

Nanoscale Structural Phase Transitions in Aqueous Solutions of Organic Molecules

Adiabatic compressibility βS of the 4-methylpyridine + water solution is investigated in a wide concentration and temperature variation interval using Mandelstam–Brillouin scattering spectroscopy. The adiabatic compressibility minimum caused by the microinhomogeneous structure of the solution is experimentally established at the concentration of 0.06 molar fractions of 4-methylpyridine in the solution. The results of the investigations allow the construction of a diagram of possible states caused by a continuous three-dimensional hydrogen bond network of water. The results of experimental study of the excessive hypersound absorption in acetone + water and 3-methylpyridine + water solutions are discussed based on the conclusions of the theory of high-frequency sound scattering near the critical point (developed by Chaban) and the Landau theory. These results are described within the framework of the Landau and Chaban theories and explained by the existence of two different states with minimum thermodynamic stability in the solution.

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

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

Proton Conduction through Water Chain in a Hydrogen-Bonded Molecular Crystal of Hexaimidazole Ruthenium(II) Complex and Dicarboxylate

Abstract The development of molecular proton conductors has garnered considerable attention owing to their potential for use as solid-state electrolytes for fuel cells. Creating hydrogen-bonding networks between HIm (imidazole) and carboxylate is an attractive approach for constructing efficient proton conducting pathways. Herein, high proton conduction in a new hydrogen-bonded molecular crystal of [RuII(HIm)6](Glu)·4H2O (1·4H2O, H2Glu = glutaric acid) is demonstrated. 1·4H2O exhibited a proton conductivity of 1.33 × 10−4 S cm−1 at 318 K and 100% relative humidity. This is attributed to a three-dimensional (3D) hydrogen-bonding network via hydrogen-bonding between HIm and carboxylate group and water molecules, leading to produce a one-dimensional (1D) hydrogen-bonding water chain, which provides a proton conducting pathway. The calculated activation energy (Ea) value was 0.38 eV at 283–318 K, suggesting that proton transport in 1·4H2O is associated with the Grotthuss mechanism. The hydrogen-bonding networks between HIm and carboxylate may play a role to promote the proton hopping mechanism. This study will provide new molecular proton conductors using imidazole metal complexes.

Molecular Mobility in Aqueous Systems of Primary Aliphatic Amino Alcohols

Self-diffusion coefficients (SDCs) of 3-amino-1-propanol (3AP), monoethanolamine (MEA), and water molecules are measured via 1H NMR using a pulsed magnetic field gradient and a stimulated echo sequence throughout a range of concentrations at temperatures of 293–333 K. It is found that the studied amino alcohols and water form a nearly tetrahedral three-dimensional network of hydrogen bonds between the molecules of the system. It is shown that this network is stable in the liquid phase, despite the mobility of the molecules that constitute the network. The mechanism of molecular mobility is studied. It is shown that the SDC of the molecules of the above amino alcohols and their aqueous solutions depends linearly on temperature. It is concluded that the molecular mobility mechanism has a pattern of activation. To verify this hypothesis and interpret the mechanism, the energies of activation are calculated for the self-diffusion of all the studied molecules in water–amino alcohol systems. The determined energies of activation for the mobility of amino alcohol molecules in aqueous systems have similar values, suggesting they undergo interactions that produce either mixed water–amino alcohol spatial networks or amino alcohol–water molecule associations in the liquid phase.

Formation of Hemihydrate Crystal form Overcomes Milling Issue Induced by Exposed Functional Groups on Cleavage Plane for a Y5 Receptor Antagonist of Neuropeptide Y

This study aimed to investigate the crystal forms of an originally designed Y5 receptor antagonist of neuropeptide Y. Polymorphic screening was performed via solvent evaporation and slurry conversion using various solvents. The obtained crystal forms α, β, and γ were characterized by X-ray powder diffraction analysis. Thermal analysis determined that forms α, β, and γ were hemihydrate, metastable and stable forms, respectively; the hemihydrate and the stable forms were candidates. To arrange the particle size, forms α and γ were subjected to jet milling. However, form γ could not be milled because of powder stiction to the apparatus, whereas form α could be. To investigate this mechanism, single-crystal X-ray diffraction analysis was performed. The crystal structure of form γ was characterized by two-dimensional hydrogen bonding between neighboring molecules. This revealed that the functional groups forming hydrogen bonds were exposed on the cleavage plane of form γ. The three-dimensional hydrogen-bonding network with water stabilized the hemihydrate form, α. These results indicate that the hydrogen bondable groups exposed on the cleavage plane of form γ should result in stiction of the powder and adherence to the apparatus. It was concluded that crystal conversion is a method to overcome the milling issue.

Proton-conducting cobalt(II) hydrogen-bonded organic framework driven by coordinated water molecules with slow magnetic relaxation

Metal hydrogen-bonded organic framework (MHOF) has received ongoing attention because they provide new chances for the design and construction of functional molecular materials. Herein, we reported a rare dual-functional MHOF based on a mononuclear complex, [Co(QLC)2·(H2O)2] (1, HQLC = Quinoline-2-carboxylic acid) with interesting magnetic and electrical properties. Variable-temperature single-crystal diffraction experiments revealed a highly thermal stable three-dimensional (3D) hydrogen-bonded network supported by multiple intermolecular hydrogen bonding and π–π stacking interactions. Importantly, the metal-bound water molecules were found to be critical for the formation of H-bonded 2D layers with the contribution of terminal carboxylic oxygen of QLC. By taking advantage of the enhanced acidity of the coordinated water molecules, variable-temperature and -humility alternating current impedance spectroscopy revealed the compound is a good supramolecular proton conductor with 1.2 × 10−4 S·cm−1 at 70 °C under 97% RH. D.C. susceptibility measurement indicated easy-axis magnetic anisotropy of the Co2+ ions with the experimental D value of -72.1 cm−1 in the complex. Dynamic A.C. susceptibility measurements revealed the compound can display slow magnetic relaxation under an applied dc field. The foregoing results provide not only a rare hydrogen-bonded organic−cobalt framework displaying interesting magnetic and electrical properties but also a promising way to build multifunctional MHOFs via coordinated water molecules.

Chain-Length-Dependent Hydrogen-Bonded Self-Assembly of Terminally Functionalized Discrete Polyketones

Here, we report the synthesis and the chain-length-dependent self-assembling behaviors of discrete di-, tetra-, and hexaketones terminally functionalized with hydrogen-bonding carboxyl (C1, C2, and C3) and 3-acylaminopyridine groups (P1, P2, and P3). These polyketones were prepared by the coupling reactions of silylated analogues of 3,3-dimethylpentane-2,4-dione and t-butyl 2,2-dimethyl-3-oxobutanoate and the subsequent hydrolysis or amidation with 3-aminopyridine. Single-crystal X-ray diffraction analysis revealed that C1 and C2 form helical assemblies in which the components are connected by the dimerization of terminal carboxyl groups, whereas the longer C3 showed infinite hydrogen-bonded chains mediated by 1,4-dioxane used as a crystallization solvent. Pyridine-terminated P1 exhibited a three-dimensional hydrogen-bonded network owing to multiple NH···N(pyridine) hydrogen bonds in the solid state. P2 generated a double-helix-like fiber structure in the crystalline state. Among the pyridine-terminated polyketones P1–P3, only P2 showed gelation behavior in chloroform (100 mM concentration) at 25 °C. The scanning electron microscopy measurement of xerogel P2 revealed the formation of rod-like structures with a thickness of approximately 0.5–3.5 μm. These results demonstrate that the precise control of the polyketone chain length can significantly alter hydrogen-bonded self-assembly in the solid state and in solution even with the same terminal structures.

Tin(IV) Halides Zero-dimensional based Inorganic-Organic Hybrid Materials: Crystal Structures and Hirshfeld Surface Analysis

Two tetramethylguanidinium halostannate inorganic-organic hybrid compounds was isolated and structurally investigated by single crystal X-ray crystallography and Hirshfeld surface analysis. The compound [(C6H14N3)2SnCl6] (1), crystallizes in the orthorhombic space group Fddd with Z = 8 / Z’ = 0.25, a = 7.3474(3) Å, b = 22.3678(8) Å, c = 28.4908(10) Å and V = 4682.3(3) Å3. The compound [(C6H14N3)2SnBr6] (2), crystallizes in the orthorhombic space group Fddd with Z = 8 / Z’ = 0.25, a = 7.5767(5) Å, b = 23.0591(17) Å, c = 29.008(2) Å and V = 5068.0(6) Å3. The isolation of 1 undergoes a redox process from Sn(II) to Sn(IV) in solution and in a non-controlled atmosphere. Both compounds 1 and 2 describe TMG+ ions with a central carbon atom in a trigonal–planar fashion. With respect to this CN3 plane, the pairs of di­methyl­ammonium groups are twisted by 13.70 (8) and 32.21 (8)° for 1, 14.88 (13) and 31.95(13)° for 2. The SnX6 dianions evidence a slightly distorted octahedron (Oh) about Sn centre for hybrids 1 and 2. Within the structures of the hybrid materials 1 and 2, N-H···Cl inter-species hydrogen bonding patterns between the inorganic stannate and the organic entities give rise a one-dimensional chain, wherein inorganic and organic species alternate. The propagation of the chain generates rings. The weak C-H···X hydrogen bonds formed from the methyl groups to adjacent tetramethylguanidinium-stannate chains result in a supramolecular three-dimensional hydrogen-bonded network. The Hirshfeld surface analysis shows existence of both strong and weak hydrogen bonding interactions. Inspection of 1 and 2 by the Hirshfeld surface analysis, show isostructural behavior. Hybrids 1 and 2 are the first crystal reports of a tetramethylguanidinium tetra- or hexa-halostannate.

Structural and thermal analyses of metaxalone cocrystals with succinic, adipic and salicylic acids

Metaxalone (MTX) is a skeletal muscle relaxant drug, crystallized with carboxylic acid coformers like succinic acid (SUC), adipic acid (ADP) and salicylic acid (SAL). Their molecular structure, crystal packing and thermal analysis were studied. In the crystallization screening, two polymorphic forms of MTX-SAL were discovered. Form I of MTX-SAL was obtained from ethanol while form II was obtained concomitantly along with form I in ethyl acetate. All four structures form MTX homodimer of R22(8) motif. In MTX-SUC, the N-H⋅⋅⋅O, O-H⋅⋅⋅N and C-H⋅⋅⋅O hydrogen bonds are involved in the crystal packing and generate a three-dimensional hydrogen-bonded network. In MTX-ADP, the coformer bridges the adjacent MTX homodimers and forms an extended chain. In both the polymorphs of MTX-SAL, the MTX molecule forms a homodimer, which is further connected by SAL coformer. Solvent assisted grinding and slurry techniques were employed to obtain phase pure bulk material. The results obtained in different trials were compared using powder X-ray diffraction (PXRD) and the process was optimized for bulk solid form preparation of MTX-SUC, MTX-ADP and MTX-SAL form I. MTX-SUC exhibits a higher melting point than the other two cocrystals. The close packing indices, crystal densities and melting temperatures between both the MTX-SAL cocrystal polymorphs resulted in the concomitant existence of form II with form I.

Molecular magneto-ionic proton sensor in solid-state proton battery

High proton conductivity originated from its small size and the diffusion-free Grotthuss mechanism offers immense promise for proton-based magneto-ionic control of magnetic materials. Despite such promise, the realization of proton magneto-ionics is hampered by the lack of proton-responsive magnets as well as the solid-state sensing method. Here, we report the proton-based magneto-ionics in molecule-based magnet which serves as both solid-state proton battery electrode and radiofrequency sensing medium. The three-dimensional hydrogen-bonding network in such a molecule-based magnet yields a high proton conductivity of 1.6 × 10−3 S cm−1. The three-dimensional printed vascular hydrogel provides the on-demand proton stimulus to enable magneto-ionics, where the Raman spectroscopy shows the redox behavior responsible for the magnetism control. The radiofrequency proton sensor shows high sensitivity in a wide proton concentration range from 10−6 to 1 molar under a low working radiofrequency and magnetic field of 1 GHz and 405 Oe, respectively. The findings shown here demonstrate the promising sensing application of proton-based magneto-ionics.

The first marine dual-drug cocrystal of cytarabine with 5-fluorouracil having synergistic antitumor effects shows superior biopharmaceutical peculiarities by oral administration

In order to highlight the advantages of cocrystallization technique in perfecting in vitro/vivo natures of marine drug cytarabine (ARC), and fill the gap of the research of marine pharmaceutical cocrystals with synergistic antitumor effects, the first dual-drug cocrystal simultaneously containing ARC and antitumor drug 5-fluorouracil (FU), viz. ARC-FU, is successfully designed and assembled. The accurate structure is perfectly resolved by single-crystal X-ray diffraction and other approaches. The analytical outcomes demonstrate that the codrug cocrystal consists of ARC and FU with a molar ratio of 1:1, in which FU molecule plays an important role by participating in the formation of both “pyrimidine-pyrimidine” and “pyrimidine-sugar” cyclic hydrogen-bonding systems with ARC molecules. In the cocrystal, there are twofold hydrogen-bonding helixes of ARC molecules and a whole three-dimensional hydrogen-bonding network which also contains the aromatic stacking interaction between pyrimidine rings of both components. Such structural feature and aggregation model have crucial influences on the improvements of in vitro/vivo properties, which is methodically verified by the combination of theoretical analyses and experimental measurements. The in vitro studies exhibit the suitably reduced solubility and obviously increased permeability for the cocrystal that is in accord with the theoretical prediction. Importantly, the ameliorated in vitro peculiarities realize in vivo pharmacokinetic optimization including the extended residence time and enhanced relative bioavailability. Of greater significance, ARC exerts synergistic antitumor effects in association with FU that brings about potentiation of cell growth inhibition with lower IC50. Thus, this research not only provides a novel crystalline form for ARC with forward-looking development value, but also breaks new ground for the development of synergistic antitumor pharmaceutical cocrystals with marine characteristics.

Isotropic Anhydrous Superprotonic Conductivity Cooperated with Installed Imidazolium Molecular Motions in a 3D Hydrogen-Bonded Phosphate Network.

Utilizing molecular motion is essential for the use of anhydrous superprotonic molecular proton conductors (σ beyond 10-4 S cm-1 ) as electrolytes in hydrogen fuel cells. However, molecular motion contributing to the improvement of intrinsic proton conduction has been limited and little clarified in relation to the proton conduction mechanism, limiting the development of material design guidelines. Here, a salt with a three-dimensional (3D) hydrogen-bonded (H-bonded) phosphate network with imidazolium cations installed inside was studied, whose components are known to exhibit molecular motions that contribute to proton conduction. Despite its anisotropic H-bonded network, the salt exhibits isotropic anhydrous superprotonic conductivity exceeding 10-3 S cm-1 at ≈351 K, which is the first example for organic molecular crystal. Variable-temperature X-ray structural analysis and solid-state 2 H NMR measurements revealed significant 3D molecular motion of imidazolium cations, which accelerate proton conduction via the 3D H-bonded phosphate network.

Insight into Isomeric Effect on the Photoluminescence and Mechanoluminescence of Cyanostilbene Derivatives.

Molecular structures, packings, and intermolecular interactions significantly affect the photophysical properties of organic luminogens. In this work, the photoluminescence (PL) and mechanoluminescence (ML) of two pairs of isomers, 1/2 and 3/4, were systematically explored. The fluorescence of crystals 1c and 4c is much brighter than that of their isomers 2c and 3c, respectively. Only 1c is ML-active among all four molecules. Single-crystal structural analysis revealed that isomerization of a substituent group affected their molecular packing and intermolecular interactions. Stronger intermolecular interaction and intact three-dimensional hydrogen-bonded networks were formed only in crystal 1c, which were essential for preventing slippage of molecular layers and generating ML; the other molecules were either lacking π-π interactions or C-H···π interactions. Theoretical calculation suggested that the energy barrier between the Franck-Condon (FC) structure and minimum energy crossing point (MECP) structure of 2/3 was much lower than that of 1/4. Nonradiative decay channels of molecules 2 and 3 were thus more easily activated, which led to their lower quantum yield.