Network Of Intermolecular Hydrogen Bonds Research Articles

Targeting PCNA with Peptide Mimetics for Therapeutic Purposes.

Proliferating cell nuclear antigen (PCNA) is an excellent inhibition target to shut down highly proliferative cells and thereby develop a broad-spectrum cancer therapeutic. It interacts with a wide variety of proteins through a conserved motif referred to as the PCNA-interacting protein (PIP) box. There is large sequence diversity between high-affinity PCNA binding partners, but with conservation of the binding structure-a well-defined 310 -helix. Herein, all current PIP-box peptides crystallised with human PCNA are collated to reveal common trends between binding structure and affinity. Key intra- and intermolecular hydrogen-bonding networks that stabilise the 310 -helix of PIP-box partners are highlighted and related back to the canonical PIP-box motif. High correlation with the canonical PIP-box sequence does not directly afford high affinity. Instead, we summarise key interactions that stabilise the binding structure that leads to enhanced PCNA binding affinity. These interactions also implicate the "non-conserved" residues within the PIP-box that have previously been overlooked. Such insights will allow a more directed approach to develop therapeutic PCNA inhibitors.

Magnetic field-temperature phase diagram of multiferroic (NH4)2FeCl5\xb7H2O

Owing to their overall low energy scales, flexible molecular architectures, and ease of chemical substitution, molecule-based multiferroics are extraordinarily responsive to external stimuli and exhibit remarkably rich phase diagrams. Even so, the stability and microscopic properties of various magnetic states in close proximity to quantum critical points are highly under-explored in these materials. Inspired by these opportunities, we combined pulsed-field magnetization, first-principles calculations, and numerical simulations to reveal the magnetic field–temperature (B–T) phase diagram of multiferroic (NH4)2FeCl5⋅H2O. In this system, a network of intermolecular hydrogen and halogen bonds creates a competing set of exchange interactions that generates additional structure in the phase diagram—both in the vicinity of the spin flop and near the 30 T transition to the fully saturated state. Consequently, the phase diagrams of (NH4)2FeCl5⋅H2O and its deuterated analog are much more complex than those of other molecule-based multiferroics. The entire series of coupled electric and magnetic transitions can be accessed with a powered magnet, opening the door to exploration and control of properties in this and related materials.

Two nitrates of dapsone: New candidates for non-linear optical materials

Non-linear optical properties (NLO) and hyperpolarizability calculations of two new hybrid organic-inorganic compounds were investigated. Compound (4-amino, 4ʹ-azaniumyldiphenyl) sulfone nitrate (1) and [(4,4ʹ-diazaniumylphenyl) sulfone] dinitrate (2) were prepared from dapsone (DDS) and characterized. Their structures were established by X-ray single-crystal analysis. While [4-amino, 4ʹ-azaniumyldiphenyl) sulfone nitrate] is mono-protonated, [(4,4ʹ-diazaniumylphenyl) sulfone] dinitrate is di-protonated. The crystals were stabilized by a three-dimensional network of intermolecular hydrogen bonds. The Hirshfeld surface analysis with 2D Fingerprint plots have revealed that the O/H, C/H, H/H and N/H contacts in 1 and the O/H, C/H, H/H, N/H and C/C contacts in 2 are the main intermolecular interactions.

Fracture of the Intermolecular Hydrogen Bond Network Structure of Glycerol Modified by Carbon Nanotubes

An intermolecular hydrogen bond network structure is usually formed in the liquid state and affects physicochemical properties, such as melting point, boiling point, and viscosity. The intermolecul...

Inferences on hydrogen bond networks in water from isopermitive frequency investigations

Intermolecular hydrogen bonds play a crucial role in determining the unique characteristics of liquid water. We present low-frequency (1 Hz–40 MHz) dielectric spectroscopic investigations on water in the presence and absence of added solutes at different temperatures from 10 °C to 60 °C. The intersection points of temperature dependent permittivity contours at the vicinity of isopermitive frequency (IPF) in water are recorded and its properties are presumed to be related to the extent of hydrogen bond networks in water. IPF is defined as the frequency at which the relative permittivity of water is almost independent of temperature. The set of intersection points of temperature dependent permittivity contours at the vicinity of IPF are characterized by the mean and root-mean-square deviation/standard deviation associated with IPF. The tunability of MIPF by the addition of NaCl and MgCl2 salt emphasizes the strong correlation between the concentration of ions in water and the MIPF. The is surmised to be related to the orientational correlations of water dipoles as well as to the intermolecular hydrogen bond networks in water. Further, alterations in is observed with the addition of kosmotropic and chaotropic solutes into water and are thought to arise due to the restructuring of hydrogen bond networks in water in presence of added solutes. Notably, the solute induced reconfiguration of hydrogen bond networks in water or often-discussed structure making/breaking effects of the added solutes in water can be inferred, albeit qualitatively, by examining the MIPF and . Further, the Gaussian deconvoluted OH-stretching modes present in the Raman spectra of water and aqueous solutions of IPA and DMF strongly endorses the structural rearrangements occurring in water in presence of kosmotropes and chaotropes and are in line with the results derived from the root-mean-square deviation in IPF.

Crystal structures of two polymorphic forms of DOTAM-mono-acid dihydrate

The structural chemistry of 2-[4,7,10-tris(carbamoylmethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid dihydrate, C16H31N7O5·2H2O, is described. The macrocyclic compound, also known by the abbreviation DOTAM-mono-acid, crystallized at room temperature and was isolated concomitantly as two polymorphic forms. The structures of both polymorphs were determined at 90 K. The first polymorph crystallized as a zwitterionic dihydrate [systematic name: 4,7,10-tris(carbamoylmethyl)-1-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-ium dihydrate] in the space group P21/n, with Z' = 1. The second polymorph crystallized as a zwitterionic dihydrate in the space group P21 at 90 K, with Z' = 2. The two independent molecules are related by a local center. In each polymorph, the zwitterion is formed between the negatively-charged carboxylate group and the ring N atom that bears the acetate pendant arm. Extensive inter- and intramolecular hydrogen bonding exists in both polymorphic structures. In polymorph 1, an intermolecular hydrogen-bonding network propagating parallel to the a direction creates an infinite chain. A second hydrogen-bonding network is observed through a water molecule of hydration in the b direction. Polymorph 2 also has two intermolecular hydrogen-bonding networks. One propagates parallel to the a direction, while the other propagates in the [-110] direction. Increasing the temperature of polymorph 2 yields the same structure at T = 180 K, but the pseudocenter becomes exact at 299 K. The higher-temperature structure has Z' = 1 in the space group P21/c.

A novel Mn(II) oxalato-bridged 2D coordination polymer: synthesis, crystal structure, spectroscopic, thermal and magnetic properties

Besides the fact that direct synthesis of oxalate-based Mn(II) complexes did not succeed a lot due to the high insolubility of manganese oxalate $$(\hbox {Mn}^{\mathrm{II}}(\hbox {C}_{2}\hbox {O}_{4})\cdot \hbox {2H}_{2}\hbox {O})$$ , a new 2D polymeric Mn(II) salt has been synthesized by slow evaporation at room temperature and its structure has been determined by single-crystal X-ray diffraction. The structure was solved by direct methods and refined to conventional agreement indices. The crystal structure is built from anionic, two-dimensional, honeycomb networks formed by the oxalate-bridged Mn(II) ions, interleaved by 2,6-diaminopyridinium cations that are entrapped between the layers. The interactions between adjacent layers result from the extended network of intermolecular hydrogen bonds created by the mentioned cations and water molecules. The complex has been fully characterized by single crystal X-ray diffraction, FT-IR and UV–Vis spectroscopy, Rietveld refinement, TGA–DSC analysis and magnetic susceptibility. The title compound exhibits antiferromagnetic coupling between Mn(II) centres. SYNOPSIS A new 2D polymeric oxalate-based Mn(II) salt has been synthesized by slow evaporation at room temperature and its structure has been determined by single-crystal X-ray diffraction. The crystal structure is built from anionic, two-dimensional, honeycomb networks formed by the oxalate-bridged Mn(II) ions, interleaved by 2,6-diaminopyridinium cations that are entrapped between the layers.

Phenyl-β-D-glucopyranoside and Phenyl-β-D-galactopyranoside Dimers: Small Structural Differences but Very Different Interactions

We report a combination of laser spectroscopy in molecular jets and quantum mechanical calculations to characterize the aggregation preferences of phenyl-β-D-glucopyranoside (β-PhGlc) and phenyl-β-D-galactopyranoside (β-PhGal) homodimers. At least two structures of β-PhGlc dimer were found maintaining the same intramolecular interactions of the monomers, but with additional intermolecular interactions between the hydroxyl groups. Several isomers were also found for the dimer of β-PhGal forming extensive hydrogen bond networks between the interacting molecules, of very different shape. All the species found present several CH•••Pi and OH•••Pi interactions that add stability to the aggregates. The results show how even the smallest change in a substituent, from axial to equatorial position, plays a decisive role in the formation of the dimers. These conclusions reinforce the idea that the small structural changes between sugar units are amplified by formation of intra and intermolecular hydrogen bond networks, helping other molecules (proteins, receptors) to easily read the sugar code of glycans.

Molecular structure, spectroscopic properties, and Hirshfeld surface analysis of chlorobis(N-methyl-1,3-propanediamine)copper(II) tetrafluoroborate and azidobis(2,2-dimethyl-1,3-propanediamine)copper(II) azide

Two new copper (II) complexes, [Cu(N-Metn)2Cl]BF4 (1) and [Cu(Me2tn)2(N3)]N3 (2) (N-Metn = N-methyl-1,3-propanediamine; Me2tn = 2,2-dimethyl-1,3-propanediamine), have been prepared, fully characterized, and their structures established by X-ray single-crystal analysis from synchrotron diffraction data. For these complexes, the Cu(II) ions are five-coordinate in an axially elongated square-pyramidal environment, with the four amine N atoms at the equatorial positions and the Cl atom (1) or N atom of one azide (2) at an apical site. The CuN bond lengths for amine N atoms in the complex 1 (2.0198(13)–2.0735(12) A°) and complex 2 (2.0239(9)–2.0489(9) Å) are typical, but the axial ligands are coordinated with a CuCl bond length of 2.5962 (7) Å for complex 1, and the CuN (azido) bond length is 2.1990 (10) Å for complex 2, adopting square-planar geometry around the Cu(II) with four N atoms from two N-Metn or Me2tn ligands. The crystals are stabilized by a three-dimensional network of intermolecular hydrogen bonds that are formed between the primary and secondary amine groups of the N-Metn ligands, the Cl ligands, and the F atoms of BF4− anion in 1, and by the primary amine groups of the Me2tn ligands and the N atoms of the azido ligand and azide ion in 2. Hirshfeld surface analysis with 2D fingerprint plots revealed that the H⋯H, F⋯H, Cl⋯H contacts in 1 and the H⋯H and N⋯H contacts in 2 are the main intermolecular interactions. The electronic absorption and IR spectral properties are also discussed.

Ferrocenecarboxylic anhydride: identification of a new polymorph.

A new monoclinic polymorph of ferrocenecarboxylic anhydride, [Fe2(C5H5)2(C12H8O3)], was obtained. Three molecules are present in the asymmetric unit, two of them being nearly identical (r.m.s. deviation = 0.11 Å), with the Fe atoms on the same side of the anhydride functional group. In the third molecule, the two Fe atoms are located at opposite sides of the functional group (ferrocene-ferrocene pseudo-torsion angle = 146.2°), a very unsual feature in metallocene anhydrides. A network of weak intermolecular hydrogen bonds was also disclosed.

Bioelastomers Based on Cocoa Shell Waste with Antioxidant Ability

In this study, a new strategy for the utilization of cocoa shell waste, a by‐product of cocoa industry, is presented for the development of new bioelastomers. The cocoa shell waste (CSW) is first micronized and then incorporated into single component acetoxy‐poly(dimethylsiloxane) (acetoxy‐PDMS) macromolecular matrix by a mixing process to produce bioelastomer composites with tunable properties. A detailed study is carried out to investigate the influence of micronized cocoa waste concentration on the curing process and on the properties of final materials. It is found that addition of CSWs has a strong effect on the curing behavior of PDMS due to establishment of an intermolecular hydrogen bond network between the two components. CSW bioelastomers are hydrophobic and exhibit good water barrier properties. In addition, the bioelastomers show effective antioxidant scavenging activity against 2,2‐diphenyl‐1‐picrylhydrazyl free radical (DPPH•) and 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) radical cation (ABTS•+). The incorporation of micronized CSW into PDMS is also found to significantly enhance the Young's modulus of the elastomers. Hence, these antioxidant bioelastomers originating from food industry waste can be highly suitable as materials for active food packaging applications.

Structure of CC Chemokine Receptor 5 with a Potent Chemokine Antagonist Reveals Mechanisms of Chemokine Recognition and Molecular Mimicry by HIV

CCR5 is the primary chemokine receptor utilized by HIV to infect leukocytes, whereas CCR5 ligands inhibit infection by blocking CCR5 engagement withHIV gp120. To guide the design of improved therapeutics, we solved the structure of CCR5 in complex with chemokine antagonist [5P7]CCL5. Several structural features appeared to contribute to the anti-HIV potency of [5P7]CCL5, including the distinct chemokine orientation relative to the receptor, the near-complete occupancy of the receptor binding pocket, the dense network of intermolecular hydrogen bonds, and the similarity of binding determinants with the FDA-approved HIV inhibitor Maraviroc. Molecular modeling indicated that HIV gp120 mimicked the chemokine interaction with CCR5, providing an explanation for the ability of CCR5 to recognize diverse ligands and gp120 variants. Our findings reveal that structural plasticity facilitates receptor-chemokine specificity and enables exploitation by HIV, and provide insight into the design of small molecule and protein inhibitors for HIV and other CCR5-mediated diseases.

Structural analysis of the foldecture derived from racemic peptide foldamers

The molecular packing structure of an elongated parallelogram plate shaped foldecture composed of a 1:1 racemic mixture of 11-helical peptide foldamers was resolved by powder X-ray diffraction (PXRD) analysis. A comprehensive Rietveld refinement procedure compensated for powder texture and identified the principal face of the foldecture. Each foldamer makes head-to-tail intermolecular hydrogen bonds, creating extended chains of single enantiomers that form a network of hydrophobic close contacts with foldamers of both the opposite and the same chiralities. An isosurface for anisotropic microstrain was calculated and found to be smallest along the x-axis, which is parallel to the network of intermolecular hydrogen bonds. Comparison with the single crystal structure found molecular packing motifs to be almost identical—a result infrequently observed in enantiopure foldectures. This is the first powder X-ray diffraction structural analysis of a foldecture composed of multiple components.

Controlled self-assembling structures of ferrocene-dipeptide conjugates composed of Ala-Pro-NHCH2CH2SH chain

Bioorganometallic ferrocene-dipeptide conjugates with the Ala-Pro-cysteamine chain, Fc-L-Ala-L-Pro-NHCH2CH2SH (2) and Fc-L-Ala-D-Pro-NHCH2CH2SH (4) (Fc=ferrocenoyl), were prepared by the reduction of the ferrocene-dipeptide conjugates, Fc-L-Ala-L-Pro-cystamine-L-Pro-L-Ala-Fc (1) or Fc-L-Ala-D-Pro-cystamine-D-Pro-L-Ala-Fc (3), respectively. Control of the self-assembling structures of the ferrocene-dipeptide conjugates was demonstrated by changing the chirality of the amino acid. The molecular structure of 2 composed of the L-Ala-L-Pro-NHCH2CH2SH chain confirmed the formation of intramolecular hydrogen bond of N-H⋯N pattern between the NH of cysteamine moiety and the nitrogen of Pro moiety. Furthermore, intermolecular hydrogen bonds between NH (Ala) and CO (Pro of another molecule) and between NH (cysteamine) and CO (the ferrocenoyl moiety of another molecule) were formed, wherein each molecule is connected to four neighboring molecules by continuous intermolecular hydrogen bonds to form the hydrogen-bonded molecular assembling structure. On the contrary, the left-handed helical assembly through an intermolecular hydrogen-bonding network of 15-membered intermolecularly hydrogen-bonded ring between NH (Ala) and CO (the ferrocenoyl moiety of another molecule) and between NH (the cysteamine moiety of another molecule) and CO (Ala) was observed in the crystal packing of 4 composed of the L-Ala-D-Pro-NHCH2CH2SH chain.

Phosphorylation of KLHL3 at serine 433 impairs its interaction with the acidic motif of WNK4: a molecular dynamics study.

Interaction between the acidic motif (AM) of protein kinase WNK4 and the Kelch domain of KLHL3 are involved in the pathogenesis of pseudohypoaldosteronism type II, a hereditary form of hypertension. This interaction is disrupted by some disease-causing mutations in either WNK4 or KLHL3, or by angiotensin II- and insulin-induced phosphorylation of KLHL3 at serine 433, which is also a site frequently mutated in patients. However, the mechanism by which this phosphorylation disrupts the interaction is unclear. In this study, we approached this problem using molecular dynamics simulation with structural, dynamical and energetic analyses. Results from independent simulations indicate that when S433 was phosphorylated, the electrostatic potential became more negative in the AM binding site of KLHL3 and therefore was unfavorable for binding with the negatively charged AM. In addition, the intermolecular hydrogen bond network that kept the AM stable in the binding site of KLHL3 was disrupted, and the forces for the hydrophobic interactions between the AM of WNK4 and KLHL3 were also reduced. As a result, the weakened interactions were no longer capable of holding the AM of WNK4 at its binding site in KLHL3. In conclusion, phosphorylation of KLHL3 at S433 disrupts the hydrogen bonds, hydrophobic and electrostatic interactions between the Kelch domain of KLHL3 and the AM of WNK4. This study provides a key molecular understanding of the KLHL3-mediated regulation of WNK4, which is an integrative regulator of electrolyte homeostasis and blood pressure regulation in the kidney. Significances Statement: WNK4 is an integrative regulator of electrolyte homeostasis, which is important in the blood pressure regulation by the kidney. Interaction between WNK4 and KLHL3 is a key physiological process that is impaired in a hereditary form of hypertension. This study provides substantial new insights into the role of phosphorylation of KLHL3 in regulating the interaction with WNK4, and therefore advances our understanding of molecular pathogenesis of hypertension and the mechanism of blood pressure regulation.

Preparation and Physicochemical Characterization of an Inclusion Complex Between Dimethylated β-Cyclodextrin and a Drug Lead From a New Class of Orally Active Antimalarial 3,5-Diaryl-2-Aminopyridines

Cyclodextrins (CDs) were used to increase the aqueous solubility of a recently discovered orally active 3,5-diaryl-2-aminopyridine antimalarial drug lead (MMP). Phase-solubility studies using β-CD, hydroxypropyl-β-CD, and heptakis(2,6-di-O-methyl)-β-CD (DIMEB) as potential solubilizers for MMP yielded solubility enhancement factors of 17, 49, and 65, respectively, at 25°C with CD concentrations ∼20 mM. A crystalline complex, DIMEB⋅MMP⋅2H2O, was prepared and characterized by thermal and single-crystal X-ray analyses. The latter technique revealed preferential encapsulation of the hydrophobic methylsulfonylphenyl moiety of MMP within the CD cavity and protrusion of the more polar methoxypyridinyl and aminopyridine residues from the cavity. This inclusion mode results in a DIMEB complex with a new packing arrangement and an intricate network of intermolecular hydrogen bonds linking guest residues that protrude from 21-related host cavities. A summary of the results of the performance of the inclusion complex in preliminary pharmacokinetic and efficacy tests in mouse models is provided.

Furazans with Azo Linkages: Stable CHNO Energetic Materials with High Densities, Highly Energetic Performance, and Low Impact and Friction Sensitivities.

Various highly energetic azofurazan derivatives were synthesized by simple and efficient chemical routes. These nitrogen-rich materials were fully characterized by FTIR spectroscopy, elemental analysis, multinuclear NMR spectroscopy, and high-resolution mass spectrometry. Four of them were further confirmed structurally by single-crystal X-ray diffraction. These compounds exhibit high densities, ranging from 1.62 g cm(-3) up to a remarkably high 2.12 g cm(-3) for nitramine-substituted azofurazan DDAzF (2), which is the highest yet reported for an azofurazan-based CHNO energetic compound and is a consequence of the formation of strong intermolecular hydrogen-bonding networks. From the heats of formation, calculated with Gaussian 09, and the experimentally determined densities, the energetic performances (detonation pressure and velocities) of the materials were ascertained with EXPLO5 v6.02. The results suggest that azofurazan derivatives exhibit excellent detonation properties (detonation pressures of 21.8-46.1 GPa and detonation velocities of 6602-10 114 m s(-1) ) and relatively low impact and friction sensitivities (6.0-80 J and 80-360 N, respectively). In particular, they have low electrostatic spark sensitivities (0.13-1.05 J). These properties, together with their high nitrogen contents, make them potential candidates as mechanically insensitive energetic materials with high-explosive performance.

A Family of Chiral Ferrocenyl Diols: Modular Synthesis, Solid-State Characterization, and Application in Asymmetric Organocatalysis.

Readily available chiral diol scaffolds are useful as sources of chirality for asymmetric synthesis, however, few such scaffolds are readily available in enantiopure form. Reported herein is a cheap and modular synthesis of a novel family of chiral ferrocenyl diols in excellent yields with excellent enantio- and diastereoselectivity (>99 % ee and 99 % de). These diols possess not only planar and central chirality, but also axial chirality around the central iron atom. Characterization of these diols by X-ray crystallography revealed intra- and intermolecular hydrogen-bond networks depending on substitution at the carbinol positions. The potential of these diols as catalysts was subsequently demonstrated in an asymmetric hetero-Diels-Alder reaction which provided cycloadducts in up to 84 % yield with ee values ranging from -92 to +72 %.

Thermodynamic description of the solvophobic effect in ionic liquids

The solvophobic effect is a driving force for self-assembly processes that acts in protic molecular organic solvents as well as in both protic and aprotic ionic liquids. It is known to reduce the solubility of apolar compounds and influence the magnitudes of thermodynamic functions of solvation in molecular solvents. In ionic liquids, thermodynamic aspects of the solvophobic effects have not yet been carefully considered. By comparing the relations between the Gibbs free energy and enthalpy of solvation of different compounds, we show that the solvophobic effect in aprotic ionic liquids can be even stronger than in organic solvents forming a network of intermolecular hydrogen bonds, such as formamide and ethylene glycol. The strength of the solvophobic effect expressed in terms of energy contributions is correlated with the average number of ions per unit volume, which is inversely proportional to the molar volume of the liquid. It is shown that the solvophobic effects become stronger when we change the cation or anion of the ionic liquid with another of a smaller size, and can be extremely weak when the cation contains long alkyl chains, but they are a general phenomenon for all ionic liquids.

Janus all-cis-1,2,3,4,5,6-Hexafluorocyclohexane: A Molecular Motif for Aggregation-Induced Enhanced Polarization.

Recently synthesized all-cis-1,2,3,4,5,6-hexafluorocyclohexane is the least stable among all possible configurational isomers of 1,2,3,4,5,6-hexafluorocyclohexane. This molecule has a remarkably large dipole moment (6.2 D) as well as high facial polarization. Solid-state, dispersion-corrected DFT (DFT-D3) calculations are performed on the crystalline phase of all-cis-1,2,3,4,5,6- hexafluorocyclohexane, which reveal that dispersion interactions play a crucial role in its stabilization. A number of thermodynamically favorable orientations of dimers, trimers and tetramers are demonstrated for this molecule. Parallel-stacked aggregates, from dimers to higher-order aggregates, which are absent in the crystal, are found to be thermodynamically most favorable due to the presence of strong short-range C-H⋅⋅⋅F-C intermolecular hydrogen-bonding networks. Because of their cooperative nature, binding energies, dipole moments, and polarizations per molecule increase from monomer to tetramer, whereas the HOMO-LUMO gaps follow the opposite trend. Based on the DFT-D3 calculations, it is proposed that this parallel-stacked arrangement can be further extended to prepare stable a 1D crystal such that a large dipole moment and macroscopic polarizations can arise, which might be useful in designing electronic and nonlinear optical devices. Because the molecule has conformational flexibility, the potential energy surface is investigated for ring flipping and the effects of fluorine substitution are studied by comparing the barrier with respect to cyclohexane and all-cis-1,2,3-trifluorocyclohexane.