Hydrogen-bonding complexes of functionalized BEDT-TTF derivatives with chloranilic acid

The two crystalline donor-acceptor complexes showing hydrogen-bondings between bis(ethylenedithio) tetrathiofulvalene (BEDT-TTF) derivatives containing pyridine and pyrazine groups and 2,5-dichloro-3,6-dihydroxyl-1,4-benzoquinone (chloranilic acid) were prepared. X-ray structure analyses revealed that functional groups play an important role in constructing the unique crystal structures.

Recognition by viral and cellular DNA polymerases of nucleosides bearing bases with nonstandard hydrogen bonding patterns.

The ability of DNA polymerases (pols) to catalyze the template-directed synthesis of duplex oligonucleotides containing a nonstandard Watson-Crick base pair between a nucleotide bearing a 5-(2,4-diaminopyrimidine) heterocycle (d kappa) and a nucleotide bearing either deoxyxanthosine (dX) or N1-methyloxoformycin B (pi) has been investigated. The kappa-X and kappa-pi base pairs are jointed by a hydrogen bonding pattern different from and exclusive of those joining the AT and GC base pairs. Reverse transcriptase from human immunodeficiency virus type 1 (HIV-1) incorporates dXTP into an oligonucleotide opposite d kappa in a template with good fidelity. With lower efficiency and fidelity, HIV-1 reverse transcriptase also incorporates d kappa TP opposite dX in the template. With d pi in the template, no incorporation of d kappa TP was observed with HIV reverse transcriptase. The Klenow fragment of DNA pol I from Escherichia coli does not incorporate d kappa TP opposite dX in a template but does incorporate dXTP opposite d kappa. Bovine DNA pols alpha, beta, and epsilon accept neither dXTP opposite d kappa nor d kappa TP opposite d pi. DNA pols alpha and epsilon (but not beta) incorporate d kappa TP opposite dX in a template but discontinue elongation after incorporating a single additional base. These results are discussed in light of the crystal structure for pol beta and general considerations of how polymerases must interact with an incoming base pair to faithfully copy genetic information.

Direct measurement of hydrogen bonding in DNA nucleotide bases by atomic force microscopy.

We have used self-assembled purines and pyrimidines on planar gold surfaces and on gold-coated atomic force microscope (AFM) tips to directly probe intermolecular hydrogen bonds. Electron spectroscopy for chemical analysis (ESCA) and thermal programmed desorption (TPD) measurements of the molecular layers suggested monolayer coverage and a desorption energy of about 25 kcal/mol. Experiments were performed under water, with all four DNA bases immobilized on AFM tips and flat surfaces. Directional hydrogen-bonding interaction between the tip molecules and the surface molecules could be measured only when opposite base-pair coatings were used. The directional interactions were inhibited by excess nucleotide base in solution. Nondirectional van der Waals forces were present in all other cases. Forces as low as two interacting base pairs have been measured. With coated AFM tips, surface chemistry-sensitive recognition atomic force microscopy can be performed.

Toxin-induced pore formation is hindered by intermolecular hydrogen bonding in sphingomyelin bilayers

Sticholysin I and II (StnI and StnII) are pore-forming toxins that use sphingomyelin (SM) for membrane binding. We examined how hydrogen bonding among membrane SMs affected the StnI- and StnII-induced pore formation process, resulting in bilayer permeabilization. We compared toxin-induced permeabilization in bilayers containing either SM or dihydro-SM (lacking the trans 4 double bond of the long-chain base), since their hydrogen-bonding properties are known to differ greatly. We observed that whereas both StnI and StnII formed pores in unilamellar vesicles containing palmitoyl-SM or oleoyl-SM, the toxins failed to similarly form pores in vesicles prepared from dihydro-PSM or dihydro-OSM. In supported bilayers containing OSM, StnII bound efficiently, as determined by surface plasmon resonance. However, StnII binding to supported bilayers prepared from dihydro-OSM was very low under similar experimental conditions. The association of the positively charged StnII (at pH 7.0) with unilamellar vesicles prepared from OSM led to a concentration-dependent increase in vesicle charge, as determined from zeta-potential measurements. With dihydro-OSM vesicles, a similar response was not observed. Benzyl alcohol, which is a small hydrogen-bonding compound with affinity to lipid bilayer interfaces, strongly facilitated StnII-induced pore formation in dihydro-OSM bilayers, suggesting that hydrogen bonding in the interfacial region originally prevented StnII from membrane binding and pore formation. We conclude that interfacial hydrogen bonding was able to affect the membrane association of StnI- and StnII, and hence their pore forming capacity. Our results suggest that other types of protein interactions in bilayers may also be affected by hydrogen-bonding origination from SMs.

Chapter 1 : nucleobases with designed patterns of hydrogen bonding

The chemistry used in key bond-forming steps to prepare nucleobases with designed patterns of hydrogen bonding is surveyed. Incorporation of the nucleobases into DNA and RNA oligomers is achieved either chemically using building blocks such as nucleoside phosphoramidites or enzymatically using nucleotide triphosphates. By varying the hydrogen bonding pattern within nucleobases, and by incorporating additional substituents, new structures have been designed that "reach over" so that contacts with both strands in targeted duplex DNA can be made in antigene strategies to control gene expression. Various new base-pairing systems have been evaluated that expand the genetic alphabet beyond Watson-Crick base pairs A.T and G.C. For example, benzo-homologated analogs of the natural DNA bases represent a new genetic set of orthogonal, size-expanded derivatives that have been shown to encode amino acids of a protein in a living organism.

Studies on the hydrogen bonding of organic chemicals

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June Sutor and the C-H…O hydrogen bonding controversy

In 1962, D. June Sutor published the first crystallographic analysis of C–H…O hydrogen bonding based on a selection of structures then known. Her follow-up paper the next year cited more structures and provided more details, but her ideas met with formidable opposition. This review begins by describing knowledge of C-H…O hydrogen bonding available at the time from physico-chemical and spectroscopic studies. By comparison of structures cited by Sutor with modern redeterminations, the soundness of her basic data set is assessed. The plausibility of the counter-arguments against her is evaluated. Finally, her biographical details are presented along with consideration of factors that might have impeded the acceptance of her work. © 2012 Taylor & Francis.

Histidine hydrogen bonding in MHC at pH 5 and pH 7 modeled by molecular docking and molecular dynamics simulations

Hydrogen bonds play important roles in maintaining the structure of proteins and in the formation of most biomolecular protein-ligand complexes. All amino acids can act as hydrogen bond donors and acceptors. Among amino acids, Histidine is unique, as it can exist in neutral or positively charged forms within the physiological pH range of 5.0 to 7.0. Histidine can thus interact with other aromatic residues as well as forming hydrogen bonds with polar and charged residues. The ability of His to exchange a proton lies at the heart of many important functional biomolecular interactions, including immunological ones. By using molecular docking and molecular dynamics simulation, we examine the influence of His protonation/deprotonation on peptide binding affinity to MHC class II proteins from locus HLA-DP. Peptide-MHC interaction underlies the adaptive cellular immune response, upon which the next generation of commercially-important vaccines will depend. Consistent with experiment, we find that peptides containing protonated His residues bind better to HLA-DP proteins than those with unprotonated His. Enhanced binding at pH 5.0 is due, in part, to additional hydrogen bonds formed between peptide His+ and DP proteins. In acidic endosomes, protein His79β is predominantly protonated. As a result, the peptide binding cleft narrows in the vicinity of His79β, which stabilizes the peptide - HLA-DP protein complex. © 2014 Bentham Science Publishers.

Cross-strand disulfides in the non-hydrogen bonding site of antiparallel β-sheet (aCSDns): poised for biological switching

Forbidden disulfides are stressed disulfides found in recognisable protein contexts previously defined as structurally forbidden. The torsional strain of forbidden disulfides is typically higher than for structural disulfides, but not so high as to render them immediately susceptible to reduction under physionormal conditions. The meta-stability of forbidden disulfides makes them likely candidates as redox switches. Here we mined the Protein Data Bank for examples of the most common forbidden disulfide, the aCSDn. This is a canonical motif in which disulfide-bonded cysteine residues are positioned directly opposite each other on adjacent anti-parallel β-strands such that the backbone hydrogen bonded moieties are directed away from each other. We grouped these aCSDns into homologous clusters and performed an extensive physicochemical and informatic analysis of the examples found. We estimated their torsional energies using quantum chemical calculations and studied differences between the preferred conformations of the computational model and disulfides found in solved protein structures to understand the interaction between the forces imposed by the disulfide linkage and typical constraints of the surrounding β-sheet. In particular, we assessed the twisting, shearing and buckling of aCSDn-containing β-sheets, as well as the structural and energetic relaxation when hydrogen bonds in the motif are broken. We show the strong preference of aCSDns for the right-handed staple conformation likely arises from its compatibility with the twist, shear and Cα separation of canonical β-sheet. The disulfide can be accommodated with minimal distortion of the sheet, with almost all the strain present as torsional strain within the disulfide itself. For each aCSDn cluster, we summarise the structural and strain data, taxonomic conservation and any evidence of redox activity. aCSDns are known substrates of thioredoxin-like enzymes. This, together with their meta-stability, means they are ideally suited to biological switching roles and are likely to play important roles in the molecular pathways of oxidative stress.

Hydrogen bonding interactions in poly(ε-caprolactone-dimethyl siloxane-ε-caprolactone)/poly(hydroxyether of bisphenol A) triblock copolymer/homopolymer blends and the effect on crystallization, microphase separation and self-assembly

This study investigated the self-assembled microphase separated morphologies that are obtained in bulk, by the complexation of a semicrystalline poly(ε-caprolactone-dimethyl siloxane-ε-caprolactone) (PCL-PDMS-PCL) triblock copolymer and a homopolymer, poly(hydroxyether of bisphenol A) (PH) in tetrahydrofuran (THF). In these blends, microphase separation takes place due to the disparity in intermolecular interactions; specifically, the homopolymer interacts with PCL blocks through hydrogen bonding interactions. The crystallization, microphase separation and crystalline structures of a triblock copolymer/homopolymer blends were investigated. The phase behavior of the complexes was investigated using small-angle X-ray scattering and transmission electron microscopy. At low PH concentrations, PCL interacts relatively weakly with PH, whereas in complexes containing more than 50 wt% PH, the PCL block interacts significantly with PH, leading to the formation of composition-dependent nanostructures. SAXS and TEM results indicate that the lamellar morphology of neat PCL-PDMS-PCL triblock copolymer changes into disordered structures at 40-60 wt% PH. Spherical microdomains were obtained in the order of 40-50 nm in complexes with 80 wt% PH. At this concentration, the complexes show a completely homogenous phase of PH/PCL, with phase-separated spherical PDMS domains. The formation of these nanostructures and changes in morphology depends on the strength of hydrogen bonding between PH/PCL blocks and also the phase separated PDMS blocks.

Novel approach to trigger nanostructures in thermosets using competitive Hydrogen-Bonding-Induced Phase Separation (CHIPS)

A new route to prepare nanostructured thermosets by the utilization of intermolecular hydrogen-bonding interactions is demonstrated here. In this study, competitive hydrogen-bonding-induced microphase separation (CHIPS) in epoxy resin (ER) containing an amphiphilic block copolymer poly(ε-caprolactone)-block-poly(2-vinylpyridine) (PCL-b-P2VP) is investigated for the first time. The phase separation takes place due to the disparity in the hydrogen-bonding interactions in ER/P2VP and ER/PCL pairs leading to the formation of ordered nanostructures in the ER/block copolymer blends. SAXS and TEM results indicate that the hexagonally packed cylindrical morphology of neat PCL-b-P2VP block copolymer remains but becomes a core-shell structure at 10 wt % addition of ER, and changes to regular lamellae structures at 20-50 wt % then to disordered lamellae with 60 wt % ER. Wormlike structures are obtained in the blends with 70 wt % ER, followed by a completely homogeneous phase of ER/P2VP and ER/PCL. The formation of nanostructures and changes in morphologies depend on the relative strength of hydrogen-bonding interactions between each component block copolymer and the homopolymer. This versatile method to develop nanostructured thermosets, involving competitive hydrogen-bonding interactions, could be used for the fabrication of hierarchical and functional materials.

The 310 Helical Conformation of the Amino Terminal Decapeptide of Suzukacillin. 270 MHz 'H NMR Evidence for Eight Intramolecular Hydrogen Bonds

The amino terminal suzukacillin decapeptide fragment, Boc-Aib-Pro-Val-Aib-Val-Ala-Aib-Ala-Aib-Aitbh-eO Me, two pentapeptides Boc-AibPrc-Val-AibVal-OMe and Boc-Ala-AibAla-AibAibOMe, and the tripeptide Boc-Ala-AibAibOMe have been studied by 270-MHz 'H NMR spectroscopy. By use of solvent dependence of chemical shifts in a CDC13-(CD3),S0 system and temperature dependence of amide NH chemical shifts in (CD3),S0, the intramolecularly hydrogen bonded NH groups in these peptides have been identified. The tripeptide possesses one hydrogen bond, both pentapeptides show evidence for three intramolecular hydrogen bonds, and the decapeptide has eight NH groups participating in hydrogen bonding. An Ala( 1)-Aib(2) @ turn is proposed for the tripeptide. Both pentapeptides favor 310 helical conformations composed of three consecutive B turns. The decapeptide adopts a 310 helical conformation with some flexibility at the Va1(5)-Ala(6) segment. The proposed conformations are consistent with the known stereochemical preferences of Aib residues.