H-bonding Ability Research Articles

The effect of dye structure on the dyeing and optical properties of dichroic dyes for PVA polarizing film

The dyeing behaviour and optical properties of four novel dyes in PVA polarizing films were determined in terms of the linearity, hydrogen bonding ability, intermolecular interaction and transition moment. The linearity and H-bonding ability of the dyes were the dominant factors in terms of both the substantivity and orientation in PVA films, which, in turn, determined the dichroic ratios of the polarizing films. Dye adsorption and optical anisotropy of the dyes were further affected by the substituents within the dyes. The difference in the electrostatic interactions of the substituent within the dyes also had an influence on dye-uptake. Moreover, charge transfer within the dye molecules was reflected in higher dichroic ratios of the dyed polarizing film.

Modified thiourea used as the ligand for the synthesis of novel coordination polymers: Based on its significant conformational behavior and H-bonding preference

Modified thiourea was used as the ligand for the synthesis of three novel coordination complexes, basing on its increased H-bond donor ability of the NH group and decreased H-bond acceptor ability of the C = S bond. Complex 1 is the first 3D network with 1D rod SBU and 2D surface SBU based on the long biscarboxylate ligand; Complex 2 has a 2D layer constructed by 1D chains via H-bonds, which shows a “plywood-like array” with a new AABB type; Complex 3 is a 3-fold interpenetrating 5-connected net with the rare 4664 topology.

Synthesis, Characterization, and H-Bonding Abilities of Ruthenium(II) Complexes Bearing Bidentate NR,NH-Carbene/Phosphine Ligands

Two new diphenylphosphine-substituted benzimidazoles featuring an ethylene (2) or a methylene linker (5) between the benzimidazole and the phosphine have been prepared. These precursors for bidentate carbene/phosphine ligands react with [RuCp*(μ3-Cl)]4 under tautomerization with formation of complexes of type [RuCp*Cl(L)] ([6] and [7], L = NR,NH-carbene/phosphine ligand). The crystal structures of [6] and [7] have been determined by X-ray diffraction. These studies revealed that the length of the bridge between the benzimidazol-2-ylidene and the phosphine determines the geometric parameters of the carbene/phosphine chelate ring and the donor properties of the phosphine. A 1H NMR titration of complex [6] with DMPU revealed the formation of a (carbene)N−H···O(DMPU) hydrogen bond in solution.

Protruding interfacial OH groups and ‘on-water’ heterogeneous catalysis

The key aspect of the remarkable organic catalysis that is observed to occur at theorganic/water phase boundary, the so-called ‘on-water’ catalysis (Narayan et al 2005Angew. Chem. 44 3275), was recently proposed to be the protruding OH groups of watermolecules at the interface that interact with the transition state (TS) via hydrogenbonding and lower activation barriers (Jung and Marcus 2007 J. Am. Chem. Soc. 1295492). In particular, the cycloaddition reaction of quadricyclane (Q) with dimethylazodicarboxylate (DMAD) on-water was calculated to be more than 100 000 timesmore efficient in terms of rate constant than the neat reaction. In this paper, wereview and consider a related reaction of Q with dimethyl acetylenedicarboxylate,where nitrogen, a good H-bond acceptor, in DMAD is replaced by carbon, a poorH-bond acceptor. A very low rate acceleration of acetylenedicarboxylate on-waterrelative to the neat reaction is obtained theoretically, as compared to DMADon-water, due to the relatively low H-bonding ability of acetylenedicarboxylate withwater at the TS relative to the reactants. We suggest that there may also bean ‘intrinsic steric effect’ or orientational advantage in the on-water catalysisin general, and both electronic and steric effects may be in operation for thesmaller on-water catalysis for the cycloaddition reaction of quadricyclane andacetylenedicarboxylate. A preliminary quantum mechanical/molecular mechanical(QM/MM) simulation including 1264 water molecules for the on-water reaction ofDMAD + Q also suggests that there are indeed approximately two–four more H-bonds between theTS and the dangling OH groups than between the reactants and the surface.

Effect of room temperature ionic liquid structure on the enzymatic acylation of flavonoids

Enzymatic acylation reactions of flavonoids (rutin, esculin) with long chain fatty acids (palmitic, oleic acids) were carried out in 14 different ionic liquid media containing a range of cation and anion structures. Classification of RTILs according to flavonoid solubility (using COSMO-RS) was the basis for structural selection. Overall, anion selection had a far greater influence on lipase activity than choice of cationic moiety. RTILs containing TF 2N −, PF 6 − and BF 4 − anions were most successful as reaction media while RTILs containing anions with stronger solvating properties (i.e. H-bonding ability) resulted in decreased yields, likely due to increased interactions with the protein structure of the lipase. Biosynthesis of rutin proceeded much slower than of esculin. All-in-all, judicious selection of RTILs was central to achieving high yields (>98% after 6 days for TOMA·TF 2N) since a balance must be struck that maximized flavonoid solubility with minimum negative impact on lipase activity. The process also benefitted from an increased reaction temperature which may have helped to reduced mass transfer limitations.

Super alcohol-absorbent gels of sulfonic acid-contained poly(acrylic acid)

Alcohol-specific superabsorbing gels (super-alcogels) based on non-neutralized acrylic acid (AA, 60–94 mol%) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) were prepared via solution polymerization in water. Polyethylene glycol dimethacrylate and potassium persulfate were used as crosslinker and initiator, respectively. Characterization of samples was performed using FTIR, 1H-NMR and thermomechanical analyses. Glass transition temperature and modulus of dried samples were found to be directly changed with their AA content. The gels exhibited enormous ability for absorbing and retaining a variety of mono- and poly-hydric alcohols. For example, in lieu of one gram of a typical sample composing 25 mol% AMPS, its absorption capacity was measured to be 53.0 g methanol, 42.1 g ethanol, 12.1 g n-propanol, 3.4 g iso-propanol, 41.2 g ethylene glycol, 20.7 g propylene glycol, 37.8 g 1,3-propanediol and 32.9 g glycerol. The absorbencies were superior to those of a known commercial poly(AA) sample, Carbopol. The alcohol absorbency was improved with increase of AMPS incorporated. It was recognized to be dependant on the alcohol characteristics such as H-bonding ability, OH/C ratio, electronic features (e.g. dielectric constant), steric hindrance of the neighboring groups of the solvent OH group, as well as the solvent viscosity. Normal phase transitions were observed in the gel swelling behavior in the alcohol-water binary mixtures. Rheological measurements of the water-swollen gel showed that more AMPS content resulted in gels with inferior storage modulus. All the empirical observations were discussed based on the related physicochemical principles.

Probing the role of weak outer sphere interactions (H-bonds) in VO(3,5- tBu 2-salophen) – Epoxide adducts by EPR, ENDOR and HYSCORE

The role of H-bonds in controlling the binding mode of epoxides, namely propylene oxide ( 3) and cis-2,3-epoxybutane ( 4), to the vanadyl salen-type complexes, N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-diamino-vanadium (IV) oxide, [VO( 1)], and VO(3,5- t Bu 2-salophen), [VO( 2)], have been examined using cw-EPR, cw-ENDOR and HYSCORE spectroscopy. One of the methine protons from the cyclohexyl backbone in [VO( 1)] has previously been shown to form a weak H-bond with the epoxide oxygen atom. The absence of this methine proton in the salophen derivative [VO( 2)] removes this H-bonding ability of the complex and in turn weakens the epoxide interaction.

In silico Prediction of Human Oral Absorption Based on QSAR Analyses of PAMPA Permeability

The parallel artificial membrane permeation assay (PAMPA) was developed as a model for the prediction of transcellular permeation in the process of drug absorption. Our research group has measured the PAMPA permeability of peptide-related compounds, diverse drugs, and agrochemicals. This work led to a classical quantitative structure-activity relationship (QSAR) equation for PAMPA permeability coefficients of structurally diverse compounds based on simple physicochemical parameters such as lipophilicity at a particular pH (log P(oct) and |pKa-pH|), H-bond acceptor ability (SA(HA)), and H-bond donor ability (SA(HD)). Since the PAMPA permeability of lipophilic compounds decreased with their apparent lipophilicity due to the unstirred water layer (UWL) barrier on membrane surfaces and to membrane retention, a bilinear QSAR model was introduced to explain the permeability of a broader set of compounds using the same physicochemical parameters as those used for the linear model. We also compared PAMPA and Caco-2 cell permeability coefficients of compounds transported by various absorption mechanisms. The compounds were classified according to their absorption pathway (passively transported compounds, actively transported compounds, and compounds excreted by efflux systems) in the plot of Caco-2 vs. PAMPA permeability. Finally, based on the QSAR analyses of PAMPA permeability, an in silico prediction model of human oral absorption for possibly transported compounds was proposed, and the usefulness of the model was examined.

Light chain somatic mutations change thermodynamics of binding and water coordination in the HyHEL-10 family of antibodies

Thermodynamic and structural studies addressed the increased affinity due to L-chain somatic mutations in the HyHEL-10 family of affinity matured IgG antibodies, using ITC, SPR with van’t Hoff analysis, and X-ray crystallography. When compared to the parental antibody H26L26, the H26L10 and H26L8 chimeras binding to lysozyme showed an increase in favorable ΔG° of −1.2±0.1kcalmol−1 and −1.3±0.1kcalmol−1, respectively. Increase in affinity of the H26L10 chimera was due to a net increase in favorable enthalpy change with little difference in change in entropy compared to H26L26. The H26L8 chimera exhibited the greatest increase in favorable enthalpy but also showed an increase in unfavorable entropy change, with the result being that the affinities of both chimeras were essentially equivalent. Site-directed L-chain mutants identified the shared somatic mutation S30G as the dominant contributor to increasing affinity to lysozyme. This mutation was not influenced by H-chain somatic mutations. Residue 30L is at the periphery of the binding interface and S30G effects an increase in hydrophobicity and decrease in H-bonding ability and size, but does not make any new energetically important antigen contacts. A new 1.2-Å structure of the H10L10–HEL complex showed changes in the pattern of both inter- and intra-molecular water bridging with no other significant structural alterations near the binding interface compared to the H26L26–HEL complex. These results highlight the necessity for investigating both the structure and the thermodynamics associated with introduced mutations, in order to better assess and understand their impact on binding. Furthermore, it provides an important example of how backbone flexibility and water-bridging may favorably influence the thermodynamics of an antibody–antigen interaction.

Thermodynamics of organic chemical hydration: QSPR models using physicochemical HYBOT descriptors

Stable and predictive quantitative structure–property relationship (QSPR) models of thermodynamics of chemical hydration (changes in Gibbs energy, ΔG air/water, enthalpy, ΔH air/water and entropy ΔS air/water) were obtained on the basis of physicochemical descriptors calculated by the HYBOT program. The structurally diverse training set (n = 151) and test set (n = 37) included 13 mono-functional chemical classes. The applied HYBOT descriptors comprise molecular polarizability α (as a volume-related term), the sum of partial negative charges on all atoms in a molecule ∑Q – (as an electrostatic term) and the sum of H-bond acceptor and donor factors ∑C a and ∑C d (as H-bond terms). Final equations for changes in Gibbs energy and enthalpy provided good statistical criteria and standard deviations on the level of errors of experimental determinations. All four above-mentioned terms essentially contribute to hydration enthalpy and each of them increases negative values of enthalpy. Hydration Gibbs energy predominantly depends on hydrogen bonding between solute and water molecules. Steric and electrostatic terms act in opposite directions and partly compensate each other. Changes in entropy correlate with increasing H-bond acceptor ability, whereas the other three descriptors exhibit inverse correlations.

Octanol/Water Partition Coefficients of Sulfonamides: Experimental Determination and Calculation Using Physicochemical Descriptors

1-Octanol/water partition coefficients log Kow of 38 sulfonamides were determined by the isothermal saturation method. These values were used both for direct correlation and as test data for the verification of a regression equation for calculation of log Kow on the basis of two physicochemical descriptors (molecular polarizability, a surrogate for molecular size, and H-bond acceptor ability). Comparison of experimental and calculated Kow values demonstrated the wide applicability of those equations.

Role of conserved F α-helix residues in the native fold and stability of the kinase-inhibited oxy state of the oxygen-sensing FixL protein from Sinorhizobium meliloti

The oxygen-sensing FixL protein from Sinorhizobium meliloti is part of the heme-PAS family of gas sensors that regulate many important signal transduction pathways in a wide variety of organisms. We examined the role of the conserved F α-9 arginine 200 and several other conserved residues on the proximal F α-helix in the heme domain of SmFixL* using site-directed mutagenesis in conjunction with UV–visible, EPR, and resonance Raman spectroscopy. The F α-helix variants R200A, E, Q, H, Y197A, and D195A were expressed at reasonable levels and purified to homogeneity. The R200I and Y201A variants did not express in observable quantities. Tyrosine 201 is crucial for forming the native protein fold of SmFixL* while Y197 and R200 are important for stabilizing the kinase-inhibited oxy state. Our results show a clear correlation between H-bond donor ability of the F α-9 side chain and the rate of heme autoxidation. This trend in conjunction with crystal structures of liganded BjFixL heme domains, show that H-bonding between the conserved F α-9 arginine and the heme-6-propionate group contributes to the kinetic stability of the kinase-inactivated, oxy state of SmFixL*.

Study on Mechanism for Amorphous Drug Stabilization Using Gelucire 50/13

Methods of preparation and application of amorphous form are well established but it is equally important to note that devitrification of amorphous drugs has limited their applications. Present study was performed to investigate mechanism for amorphous drug stabilization using Gelucire in comparison with polyvinylpyrrolidone (PVP). Etoricoxib and celecoxib were taken as model drugs for this study, as etoricoxib has only proton accepting site for hydrogen bonding in comparison with celecoxib, which has both proton accepting and donating site. Solid dispersion of celecoxib with polyvinylpyrrolidone and Gelucire was prepared by spray drying and melt-granulation technique respectively. X-ray powder diffractometry and differential scanning calorimetry were used to study the physical state of the drug. Dissolution studies were performed to differentiate dissolution performance. Stability study samples were evaluated for physical state of the drug and dissolution performance. An IR study in correlation with molecular modeling was carried out to study the mechanism for stabilization. Dissolution of melt-granulation of amorphous celecoxib was improved significantly as compared to amorphous celecoxib and Celecoxib-PVP solid dispersion. Melt-granulation with lipid seemed to be more dominant than amorphization of drug for improving dissolution. Stability data revealed that PVP was significantly advantageous for amorphous form stabilization whereas Gelucire failed in case of Celecoxib. In contrast to this, our previous study revealed the stabilization ability of Gelucire for amorphous etoricoxib. Molecular modeling and IR studies revealed that H-bonding was predominant mechanism for stabilization. Out of two proposed mechanism for amorphous drug stabilization by lipids, H-bonding ability is more dominant than immobilization of molecule in lipid matrix.

Dual-Fluorescence Probe of Environment Basicity (Hydrogen Bond Accepting Ability) Displaying no Sensitivity to Polarity

3-Hydroxyquinolones (3HQs) are a new class of water soluble dual fluorescence probes that can monitor both polarity and basicity (H-bond accepting ability) parameters. Both parameters play an important role in proteins and lipid membranes. Nevertheless, no method exists actually to measure the basicity parameter separately from the polarity. To achieve this aim, we synthesized 2-benzofuryl-3-hydroxy-4(1H)-quinolone (3HQ-Bf) and characterized its photophysical properties by UV, steady-state and time-resolved fluorescence spectroscopy. Due to its extended conjugation and totally planar conformation, 3HQ-Bf is characterized by a high fluorescence quantum yield. In solution, this dye shows an excited state intramolecular proton transfer (ESIPT) reaction resulting in two tautomer bands in the emission spectra. The ESIPT reaction can be considered as irreversible and is governed by rate constants from 0.6 to 8 x 10(9) s(-1), depending on the solvent. The analysis of the spectral properties of 3HQ-Bf in a series of organic solvents revealed a marginal sensitivity to the solvent polarity, but an exquisite sensitivity to solvent basicity, as shown by the linear dependence of the logarithm of the emission bands intensity ratio, log(I(N*)/I(T*)), as well as the absorption or emission maxima wavenumbers as a function of the solvent basicity parameter. This probe may find useful applications through coupling to a protein ligand, for characterizing the H-bond acceptor ability at the ligand binding site as well as for studying the basicity changes of lipid membranes during their chemo- and thermotropic conversions.

Asymmetric Aldol Addition by Oligopeptide Immobilized on Magnetic Particles through an Ionic Liquids Spacer

In this work, oligopeptide was covalently bonded on the surface of magnetic particles through an ionic liquids spacer. When ionic liquids containing bulky cations with strong H-bonding ability or having hydrophobic anions were used, the yield and enantioselectivity of aldol reaction were enhanced greatly. Introducing an ionic liquids spacer between the oligopeptide and magnetic resin decreased the minimum number of amino acids for optimizing the efficiency of aldol addition. Varying the amino acid sequence of the oligopeptide showed limited effect on the yield and enantioselectivity; however, introducing a series of lysine groups on the terminal of the oligopeptide, close to the imidazolium ring, would significantly increase the output. The magnetite-loaded oligopeptide had a broader substrate range for ketone donor but restricted the enantioselectivity of aldehyde acceptor than the free oligopeptide. The combinative unit served as a recyclable catalyst for aldol addition of ketone and aldehyde, and its catalytic efficiency and selectivity can be finely designed by the characteristics of each part of the catalyst.

Selective A 3 adenosine receptor antagonists derived from nucleosides containing a bicyclo[3.1.0]hexane ring system

We have prepared 5′-modified derivatives of adenosine and a corresponding (N)-methanocarba nucleoside series containing a bicyclo[3.1.0]hexane ring system in place of the ribose moiety. The compounds were examined in binding assays at three subtypes of adenosine receptors (ARs) and in functional assays at the A 3 AR. The H-bonding ability of a group of 9-riboside derivatives containing a 5′-uronamide moiety was reduced by modification of the NH; however these derivatives did not display the desired activity as selective A 3 AR antagonists, as occurs with 5′- N, N-dimethyluronamides. However, truncated (N)-methanocarba analogues lacking a 4′-hydroxymethyl group were highly potent and selective antagonists of the human A 3 AR. The compounds were synthesized from d-ribose using a reductive free radical decarboxylation of a 5′-carboxy intermediate. A less efficient synthetic approach began with L-ribose, which was similar to the published synthesis of (N)-methanocarba A 3AR agonists. Compounds 33b– 39b ( N 6-3-halobenzyl and related arylalkyl derivatives) were potent A 3AR antagonists with binding K i values of 0.7–1.4 nM. In a functional assay of [ 35S]GTPγS binding, 33b (3-iodobenzyl) completely inhibited stimulation by NECA with a K B of 8.9 nM. Thus, a highly potent and selective series of A 3AR antagonists has been described.

Effects of ring substituents on enantioselective recognition of amino alcohols and acids in uryl-based binol receptors

The uryl-based binol aldehyde, ( S)-2-hydroxy-2′-(3-phenyluryl-benzyl)-1,1′-binaphthyl-3-carboxaldehyde ( 1), binds 1,2-amino alcohols and amino acids stereoselectively by reversible formation of imine bond. Hydrogen bond (between uryl group and alcohol –OH moiety) plays an important role in the stereoselectivity of amino alcohols. Hence, any substituents on phenyl group in 1 are expected to affect H-bond ability of uryl group. To study the effects of ring substituents on the stereoselective recognition of amino alcohols, (substituted phenyl)uryl-based chiral binol receptors have been prepared. The receptors with electron-donating X substituents have been synthesized from ( S)-2-methoxymethoxy-2′-hydroxy-1,1′-binaphthyl-3-carboxaldehyde and X-phenyluryl-benzyl bromide. The receptors with electron-withdrawing Y substituents, however, required a different synthetic strategy including transformation of an aldehyde to alcohol. The incorporation of the electron withdrawing groups slightly accelerated the stereoselective recognition property of the receptor. Though the acceleration is not so remarkable, this work demonstrates the versatile derivatization of 1 in achieving higher stereoselective recognition of 1,2-amino alcohols and stereoconversion of l-amino acids to d-amino acids.

Thermodynamic Interrogation of a Folding Disease. Mutant Mapping of Position 107 in Human Carbonic Anhydrase II Linked to Marble Brain Disease

Marble brain disease (MBD) also known as Guibaud-Vainsel syndrome is caused by autosomal recessive mutations in the human carbonic anhydrase II (HCA II) gene. HCA II is a 259 amino acid single domain enzyme and is dominated by a 10-stranded beta-sheet. One mutation associated with MBD entails the H107Y substitution where H107 is a highly conserved residue in the carbonic anhydrase protein family. We have previously demonstrated that the H107Y mutation is a remarkably destabilizing folding mutation [Almstedt et al. (2004) J. Mol. Biol. 342, 619-633]. Here, the exceptional destabilization by the H107Y mutation has been further investigated. A mutational survey of position H107 and a neighboring conserved position E117 has been performed entailing the mutants H107A, H107F, H107N, E117A and the double mutants H107A/E117A and H107N/E117A. All mutants were severely destabilized versus GuHCl and heat denaturation. Thermal denaturation and GuHCl phase diagram and ANS analyses showed that the mutants shifted HCA II toward populating ensembles of intermediates of molten globule type under physiological conditions. The native state stability of the mutants was in the following order: wt > H107N > E117A > H107A > H107F > H107Y > H107N/E117A > H107A/E117A. (i) H107N is least destabilizing likely due to compensatory H-bonding ability of the introduced Asn residue. (ii) Double mutant cycles surprisingly reveal additive destabilization of H107N and E117A showing that H107 and E117 are independently stabilizing the folded protein. (iii) H107Y and H107F are exceptionally destabilizing due to bulkiness of the side chains whereas H107A is more accommodating, indicating long-range destabilizing effects of the natural pathogenic H107Y mutation.

Endocrine disruptors that disrupt the transcription mediated by androgen receptor

The Ministry of Environment in Japan (formerly the Japan Environment Agency) has made a priority list of compounds, SPEED 98, to preferentially examine whether they act as endocrine active chemicals and conducted a project to scientifically address endocrine disruptor issues. Out of around 100 compounds listed in SPEED 98 and related compounds, thirty-six acted as pure androgen receptor (AR) antagonists, whereas 13 showed both AR agonist and antagonist activities based on an in vitro reporter gene assay. The structural difference between AR agonists and antagonists was explained by Comparative Molecular Field Analysis (CoMFA). The precise structural requirements for AR agonists and/or antagonists are described as follows: in the case of AR agonist, the distance between two functional groups with H-bonding ability corresponding to 3-keto and 17β-OH groups should be near 10 A to maintain a favorable H-bond position while the length axis of antagonists should be less than or more than 10 A so as not to make an H-bond by interaction with Asn705 and Thr877 in the steroid D ring anchoring pocket, preventing the correct positioning of helix 3 (H3) and helix 12 (H12). This hypothetical general rule is named Near 10 A polar Interaction Rule.

Physicochemical Characterization of the PEG8000-Na2SO4 Aqueous Two-Phase System

The polyethylene glycol−sodium sulfate aqueous two-phase system has been characterized at 23 °C. Tie-lines for the phase diagram were obtained experimentally. Phases in equilibrium were characterized by means of the solvatochromic parameters π*, α, and β, which provide a measurement of the polarity/polarizability and the H-bond donor and acceptor abilities, respectively. The ability of the phases to participate in hydrophobic interactions was characterized by means of the free energy of transfer of a methylene group between the conjugated phases, using the partition of a homologous series of dinitrophenylated amino acids. The results show the effect of the presence of polymer and salt in the aqueous phase, and a comparison of both phases with pure water is made.