Hydrogen-bonding Capability Research Articles

C2'-pyrene-functionalized triazole-linked DNA: universal DNA/RNA hybridization probes.

Development of universal hybridization probes, that is, oligonucleotides displaying identical affinity toward matched and mismatched DNA/RNA targets, has been a longstanding goal due to potential applications as degenerate PCR primers and microarray probes. The classic approach toward this end has been the use of "universal bases" that either are based on hydrogen-bonding purine derivatives or aromatic base analogues without hydrogen-bonding capabilities. However, development of probes that result in truly universal hybridization without compromising duplex thermostability has proven challenging. Here we have used the "click reaction" to synthesize four C2'-pyrene-functionalized triazole-linked 2'-deoxyuridine phosphoramidites. We demonstrate that oligodeoxyribonucleotides modified with the corresponding monomers display (a) minimally decreased thermal affinity toward DNA/RNA complements relative to reference strands, (b) highly robust universal hybridization characteristics (average differences in thermal denaturation temperatures of matched vs mismatched duplexes involving monomer W are <1.7 °C), and (c) exceptional affinity toward DNA targets containing abasic sites opposite of the modification site (ΔT(m) up to +25 °C). The latter observation, along with results from absorption and fluorescence spectroscopy, suggests that the pyrene moiety is intercalating into the duplex whereby the opposing nucleotide is pushed into an extrahelical position. These properties render C2'-pyrene-functionalized triazole-linked DNA as promising universal hybridization probes for applications in nucleic acid chemistry and biotechnology.

Hydrogen-Bonded Inclusion Compounds with Reversed Polarity: Anionic Metal-Complexes and Cationic Organic Linkers

Synthesized and structurally characterized is a new series of soft-host frameworks assembled by charge-assisted hydrogen bonds between an anionic metal complex (MC) and cationic organic linkers (OL), specifically [Co(en)(ox)(2)](-) and diprotonated 4,4'-bipyridinium (H(2)bpy) or 1,2-bis(4-pyridinium)ethylene (H(2)bpye). While frameworks built of cationic complexes and anionic organic linkers are already well-known, the seven new compounds described here represent the first series of frameworks with reversed polarity, that is, made of anionic complexes and cationic organic linkers. The compounds have a general formula [OL][MC](2)·n(guest), where the guest molecules 4,4'-biphenol (bp), 4-methoxyphenol (mp), 1,4-dimethoxybenzene (dmb), 1,6-dimethoxynaphtalene (dmn), and 4-nitroanisole (na). Structurally the compounds can be described as pillared-layer frameworks with layers constructed of MC anions and linked together by hydrogen-bonded cationic OL pillars. The guest molecules occupy the galleries between the pillars while their steric, electronic, and π-π and hydrogen-bonding capabilities influence the overall structure of the soft frameworks.

Comment on “Revisiting the Ramachandran plot from a new angle”

Comment on “Revisiting the Ramachandran plot from a new angle”

Cocrystals of 6-propyl-2-thiouracil: N—H...OversusN—H...S hydrogen bonds

In order to investigate the relative stability of N-H···O and N-H···S hydrogen bonds, we cocrystallized the antithyroid drug 6-propyl-2-thiouracil with two complementary heterocycles. In the cocrystal pyrimidin-2-amine-6-propyl-2-thiouracil (1/2), C(4)H(5)N(3)·2C(7)H(10)N(2)OS, (I), the `base pair' is connected by one N-H···S and one N-H···N hydrogen bond. Homodimers of 6-propyl-2-thiouracil linked by two N-H···S hydrogen bonds are observed in the cocrystal N-(6-acetamidopyridin-2-yl)acetamide-6-propyl-2-thiouracil (1/2), C(9)H(11)N(3)O(2)·2C(7)H(10)N(2)OS, (II). The crystal structure of 6-propyl-2-thiouracil itself, C(7)H(10)N(2)OS, (III), is stabilized by pairwise N-H···O and N-H···S hydrogen bonds. In all three structures, N-H···S hydrogen bonds occur only within R(2)(2)(8) patterns, whereas N-H···O hydrogen bonds tend to connect the homo- and heterodimers into extended networks. In agreement with related structures, the hydrogen-bonding capability of C=O and C=S groups seems to be comparable.

Cationic Polybenzoxazines. A Novel Polyelectrolyte Class with Adjustable Solubility and Unique Hydrogen-Bonding Capabilities

This article fuses the world of benzoxazine chemistry with the field of polyelectrolyte chemistry and introduces a new approach toward water-soluble polybenzoxazines. The synthesis of a novel class of polybenzoxazine-based polyelectrolytes carrying cationic charges in the side chain and/or the backbone is described. Tertiary nitrogen atoms of the backbone or side chain have been methylated in a polymer analogous reaction leading to cationic polybenzoxazines with structure dependent, adjustable solubility in various solvents including water providing unique hydrogen-bonding capabilities. The polymers have been investigated by 13C NMR, SEC, TGA, and DSC.

Click to Join Peptides/Proteins Together

Copper(I) is able to catalyze Huisgen 1,3-dipolar cycloaddition in a "click" fashion. This copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction presents excellent chemoselectivity and occurs over a wide-range of reaction conditions. It shows tolerance to variation in both pH and solvent polarity, thereby facilitating the ligation of peptides and proteins to produce peptidomimetics and synthetic proteins. In addition, the only product formed is a 1,4-disubstituted-1,2,3-triazole moiety, in many aspects resembling the natural peptide bond, including hydrogen-bonding capability, planarity, distance between the 1 and 4 substituents, and conformational restriction of the peptide backbone; thus the triazole-backbone-modified peptide, in which a triazole replaces the amide bond, may be anticipated to present a secondary structure similar to that of its natural counterpart. This Focus Review describes the scope and applications of copper(I)-catalyzed alkyne–azide cycloaddition in synthetic peptide/protein chemistry.

Kinetics of Hydrogen Bonding between Anthracene Urea Derivatives and Anions in the Excited State

Urea compounds are useful anion sensors due to their hydrogen-bonding capabilities. We investigated the emissive properties of complexes consisting of urea-anthracene (nPUA, n = 1, 2) host compounds and acetate anions held as guests through intermolecular hydrogen bonding. The kinetics of a new emission band formed by conformational changes in the excited singlet state were revealed. The new band is thought to arise from a charge-transfer interaction between the anthracene and urea moieties after intermolecular hydrogen-bond reconfiguration in the excited state, with rate constants of 2.4 × 10(9) and 4.0 × 10(7) s(-1) for 1PUA and 2PUA, respectively.

Hydrogen-Bonding Capability of a Templating Difluorotoluene Nucleotide Residue in an RB69 DNA Polymerase Ternary Complex

Results obtained using 2,4-difluorotoluene nucleobase (dF) as a nonpolar thymine isostere by Kool and colleagues challenged the Watson-Crick dogma that hydrogen bonds between complementary bases are an absolute requirement for accurate DNA replication. Here, we report crystal structure of an RB69 DNA polymerase L561A/S565G/Y567A triple mutant ternary complex with a templating dF opposite dTTP at 1.8 Å-resolution. In this structure, direct hydrogen bonds were observed between: (i) dF and the incoming dTTP, (ii) dF and residue G568 of the polymerase, and (iii) dF and ordered water molecules surrounding the nascent base pair. Therefore, this structure provides evidence that a templating dF can form novel hydrogen bonds with the incoming dTTP and with the enzyme that differ from those formed with a templating dT.

Conformation and Dynamics of Poly(N-isopropyl acrylamide) Trimers in Water: A Molecular Dynamics and Metadynamics Simulation Study

Conformational features, structure, and dynamic properties of the trimer of poly(N-isopropyl acrylamide), (NIPAAm)(3), in aqueous solution at 293 and 323 K were investigated by a double simulation approach. The free energy behavior as a function of backbone conformation was obtained by metadynamics-umbrella sampling simulations. The structural characteristics, the intramolecular and water hydrogen bonding, and the torsional dynamics were analyzed by molecular dynamics simulations. The four stereoisomers of (NIPAAm)(3), representing syndiotactic, isotactic, and atactic sequences, were studied to highlight the tacticity effect on the system properties. The simulation results indicate that the experimentally observed lower hydrophilicity of isotactic poly(N-isopropyl acrylamide), in comparison with the syndiotactic one, is related to a lower conformational entropy. The atactic stereoisomers display the highest intramolecular hydrogen bond capability, at both studied temperatures, due to formation of hydrogen bonds between external amide groups. The mobility of the backbone in the syndiotactic trimer is more homogeneous than in other stereoisomers. The temperature increase was found mainly to affect the conformation of N-isopropyl amide side chains, and a structural rearrangement was observed for the atactic stereoisomers, in agreement with their experimental solution behavior. Simulation results are discussed in relation with available experimental data on solution properties and reactivity of poly(N-isopropyl acrylamide).

Substituent dependent topologies in cobalt isophthalate coordination polymers with bis(pyridylmethyl)piperazine coligands

Divalent cobalt coordination polymers containing bis(4-pyridylmethyl)piperazine (4-bpmp) or bis(3-pyridylmethyl)piperazine (3-bpmp) ligands and 5-substituted isophthalate ligands have been hydrothermally prepared and structurally characterized by single-crystal X-ray diffraction. [Co(OHip)(4-bpmp)] n ( 1, OHip = 5-hydroxyisophthalate) manifests a (4,4) grid 2D coordination polymer structure, with anti-syn bridged {Co 2(OCO) 2} dimers serving as connecting nodes. Similar dinuclear {Co 2(OCO) 2} clusters are evident in [Co(OMeip)(4-bpmp)] n ( 2, OMeip = 5-methoxyisophthalate). However, the lack of hydrogen-bonding capability of the methoxy substituent promotes formation of a rarer 6-connected (3,6) triangular net. {[Co(H 2O) 4(H 23-bpmp)](NO 2ip) 2·6H 2O} n ( 3, NO 2ip = 5-nitroisophthalate) possesses cationic [ Co ( H 2 O ) 4 ( H 2 3 -bpmp ) ] n 4 n + chains connected into a supramolecular lattice by unligated NO 2ip dianions and water molecules of crystallization. The variable temperature magnetic susceptibility behavior of 1 and 2 is ascribed to cooperation between single-ion effects and weak ferromagnetic superexchange.

Lessons on O2 and NO bonding to heme from ab initio multireference/multiconfiguration and DFT calculations

This commentary focuses on the conceptual interpretation of the bonding of O(2) and NO to heme in oxyheme and nitrosylheme complexes, using high-level ab initio complete active space self-consistent field (CASSCF)/molecular mechanical (MM), gas-phase CASSCF, and CASSCF followed by second-order perturbation theory (CASPT2) calculations as well as density functional theory (DFT) calculations. The commentary shows that expanding the complex multiconfigurational (MC) wave functions into valence bond (VB)-type configurations based on localized orbitals provides significant insight into bonding and precise definitions of oxidation states. Furthermore, the VB "reading" of the wave function unifies the descriptions of DFT and MC theories, reconciling controversies and surprises. In so doing, we demonstrate the impact of the protein bulk polarity and its hydrogen-bonding capability on the bonding. The insight provided by "reading" the VB content of the MC wave functions highlights the potential of this approach as a general paradigm in future computational bioinorganic chemistry. A great deal of insight lies in this road.

Solvatochromic and Fluorescence Behavior of Sulfisoxazole

The Fluorescence spectroscopic and solvatochromic behavior of Sulfisoxazole, a sulfa drug with antimicrobial activities, in various pure solvents of different polarity and hydrogen bonding capability is reported. The fluorescence emission spectrum of sulfisoxazole was found to be solvent polarity dependent, where a notable red shift in emission maximum was observed with increasing solvent polarity as well as hydrogen bonding capability. The effects of the latter two solvent parameters were quantitatively investigated using the methods of Lippert-Mataga and solvatochromic comparison method (SCM) that is based on the Kamlet-Taft equation. Particularly, the Lippert-Mataga method was applied to estimate the dipole moment of the excited state (μ(e)) upon plotting Stokes shift versus solvent polarizability (Δf), where a value of 11.54 Debye was obtained. On the other hand, applying the multiple regression analysis to the SCM method revealed that solvent polarizability (π*) and hydrogen-bond donor capability (α) approximately equally stabilize sulfisoxazole in the excited state with minor destabilization contribution by the hydrogen-bond acceptor capability (β). These findings revealed that the excited state of sulfisoxazole is stabilized by polar solvents, indicating that this drug molecules exhibit larger dipole moment in the excited state than in the ground state, which in turn implies that a potential intramolecular charge transfer (ICT) occurs after excitation.

Quantifying the energetic contributions of desolvation and π-electron density during translesion DNA synthesis

This report examines the molecular mechanism by which high-fidelity DNA polymerases select nucleotides during the replication of an abasic site, a non-instructional DNA lesion. This was accomplished by synthesizing several unique 5-substituted indolyl 2′-deoxyribose triphosphates and defining their kinetic parameters for incorporation opposite an abasic site to interrogate the contributions of π-electron density and solvation energies. In general, the Kd, app values for hydrophobic non-natural nucleotides are ∼10-fold lower than those measured for isosteric hydrophilic analogs. In addition, kpol values for nucleotides that contain less π-electron densities are slower than isosteric analogs possessing higher degrees of π-electron density. The differences in kinetic parameters were used to quantify the energetic contributions of desolvation and π-electron density on nucleotide binding and polymerization rate constant. We demonstrate that analogs lacking hydrogen-bonding capabilities act as chain terminators of translesion DNA replication while analogs with hydrogen bonding functional groups are extended when paired opposite an abasic site. Collectively, the data indicate that the efficiency of nucleotide incorporation opposite an abasic site is controlled by energies associated with nucleobase desolvation and π-electron stacking interactions whereas elongation beyond the lesion is achieved through a combination of base-stacking and hydrogen-bonding interactions.

Models for liquid–liquid partition in the system formamide–organic solvent and their use for estimating descriptors for organic compounds

Partition coefficients for varied compounds were determined for the organic solvent–formamide biphasic partition system where the organic solvent is 1,2-dichloroethane, 1-octanol or isopentyl ether. These partition coefficient databases are analyzed using the solvation parameter model facilitating a quantitative comparison of the formamide-based partition systems with other totally organic and water-based partition systems. Formamide is shown to be a less cohesive and hydrogen-bond acidic solvent than water with similar hydrogen-bond basicity and dipolarity/polarizability. Compared with other organic solvents its higher cohesion, dipolarity/polarizability and hydrogen-bonding capability make it a useful base solvent for forming biphasic partition systems with a range of system properties obtained through variation of the counter solvent. Formamide–organic solvent systems offer a complementary approach to water-based partition systems for sample preparation and the determination of descriptors for compounds virtually insoluble in water or unstable in water.

Introducing extended substrate selectivity into trypsin through redesign

The objective of this research was to evaluate how a residue with hydrogen bond capability may affect substrate selection by a previously engineered threonine protease. C42S/C58V/S195T trypsin (SVT‐Tn) was characterized and compared to trypsin variants C42A/C58V/S195T‐Tn (AVT‐Tn) and C42A/C58A/S195T (AAT‐Tn). p‐Nitroanilide (pNA) and 7‐amino 4‐methyl coumarin (AMC) derivatives of benzyloxycarbonyl‐Gly‐Pro‐Arg (Z‐GPR) were use to kinetically evaluate the activity and specificity of SVT‐Tn. Their respective kcat/KM values show that SVT‐Tn is 8‐ and 40‐fold more efficient in Z‐GPR‐pNA and Z‐GPR‐AMC hydrolysis, respectively, than AVT‐Tn. Additionally, SVT‐Tn was 5‐fold less efficient in Z‐GPR‐pNA hydrolysis and 2‐fold more efficient in Z‐GPR‐AMC hydrolysis than AAT‐Tn. However, the (kcat/KM)pNA/(kcat/KM)AMC ratios show that SVT trypsin is 3.5‐fold more selective for the pNA substrate, less discriminatory than the AVT and AAT variants. The results suggest that a serine at position 42 in the S195T/C58V context significantly affects catalytic efficiency in a substrate dependent manner for the two substrates tested, but selectivity between the two substrates was only moderate. However, longer peptide substrates are needed to thoroughly evaluate the degree of the selectivity of SVT‐Tn.(This work was supported by NSF Award MCB‐0643988‐02)

Synthesis of 2,4,5-triaminocyclohexanecarboxylic acid as a novel 2-deoxystreptamine mimic

Abstract Since aminoglycosides have been known to exert their antibacterial activities by binding to various RNA targets, 2-deoxystreptamine served as a particularly important model in understanding RNA-small molecule interaction. Herein, 2,4,5-triaminocyclohexanecarboxylic acid was prepared as a novel 2-deoxystreptamine (2-DOS) mimic, which replaces highly flexible glycosidic bonds of aminoglycosides with amide bonds and may improve binding selectivity toward RNA targets through increased rigidity and additional hydrogen-bonding capability. This unnatural g-amino acid can also be used as a potential component for synthetic foldamers.

L-Tyrosine on Ag(111): Universality of the Amino Acid 2D Zwitterionic Bonding Scheme?

We present a combined study of the adsorption and ordering of the l-tyrosine amino acid on the close-packed Ag(111) noble-metal surface in ultrahigh vacuum by means of low-temperature scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. On this substrate the biomolecules self-assemble at temperatures exceeding 320 K into linear structures primarily following specific crystallographic directions and evolve with larger molecular coverage into two-dimensional nanoribbons which are commensurate with the underlying atomic lattice. Our high resolution topographical STM data reveal noncovalent molecular dimerization within the highly ordered one-dimensional nanostructures, which recalls the geometrical pattern already seen in the l-methionine/Ag(111) system and supports a universal bonding scheme for amino acids on smooth and unreactive metal surfaces. The molecules desorb for temperatures above 350 K, indicating a relatively weak interaction between the molecules and the substrate. XPS measurements reveal a zwitterionic adsorption, whereas NEXAFS experiments show a tilted adsorption configuration of the phenol moiety. This enables the interdigitation between aromatic side chains of adjacent molecules via parallel-displaced pi-pi interactions which, together with the hydrogen-bonding capability of the hydroxyl functionality, presumably mediates the emergence of the self-assembled supramolecular nanoribbons.

Influence of hydrogen bonding upon the TiO 2 photooxidation of isopropanol and acetone in aqueous solution

This study investigates the aqueous photocatalytic degradation of small polar organic compounds (SPOCs) that bear hydrogen-bonding capabilities but do not readily adsorb to the TiO 2 catalyst. The effect of pH on the TiO 2 surface hydroxyl speciation and surface acid/base equilibria was used to elucidate the possible role of hydrogen-bonding interactions in the degradation of acetone and isopropanol in aqueous TiO 2 photocatalytic systems. The kinetic parameters describing the decomposition of these two model compounds were obtained by gas chromatographic analysis of their photoreaction systems and interpreted on the grounds of the Brönsted acid/base properties of the TiO 2 surface speciation and solute hydrogen-bonding numerical scales. The results showed that the fastest initial degradation rates of acetone and isopropanol occurred in a pH range where the optimal conditions for adsorption through hydrogen bonding to the TiO 2 surface and optimum concentration of hydroxyl radicals (OH ) coincide. The fastest degradation constants were observed at pH 6.04 and 8.61 for acetone and isopropanol, respectively. The hypothesis of hydrogen bonding to surface hydroxyl groups presented in this study challenges the common assumption that these model compounds do not adsorb to surface sites, and that their oxidative pathways of degradation only occur via homogeneous-phase reaction with free OH radicals.

Steady-State and Time-Resolved Spectroscopy of 2,2′-Bipyridine-3,3′-diol in Solvents and Cyclodextrins: Polarity and Nanoconfinement Effects on Tautomerization

The ground- and excited-state tautomerization of the 2,2'-bipyridine-3,3'-diol molecule (BP(OH)(2)) was studied in different solvents and in confined nanocavities of cyclodextrins (CDs) using steady-state and lifetime spectroscopic measurements. In all solvents, a dizwitterion (DZ) tautomer is produced in the excited state after intramolecular double-proton transfer. This tautomer is stabilized in the ground state in water only and produces two unique absorption peaks in the region of 400-450 nm. The DZ tautomer fluoresces in the green and as the solvent polarity increases, the fluorescence peak is blue-shifted (498 nm in cyclohexane versus 462 nm in water), and the fluorescence lifetime gets shorter (3.10 ns in cyclohexane versus 0.65 ns in water). The results indicate the sensitivity of this tautomer to solvent polarity, particularly the solvent's hydrogen-bonding capability. In water, another photoinduced tautomerization mechanism takes place via a water network solvating each of the two hydrogen-bonding centers of the molecule. The second tautomer is detected as a small shoulder in the blue side of the fluorescence peak and has a lifetime of 5.40 ns. Using BP(OH)(2) to probe the nanocavities of aqueous CDs reveals the degree of hydrophobicity of the cavities and the different mechanisms of probe encapsulation. As the cavity size decreases in the order gamma-CD to beta-CD to alpha-CD, the cavity is more hydrophobic, which is reflected in an intensity decrease of the absorbance of the DZ tautomer and a red shift in its fluorescence peak. The measured lifetimes show the same trend and reveal how the probe interacts with the CD moiety. In gamma-CD, the probe is located near the secondary rim of the CD annulus, whereas in alpha-CD, the probe is completely sequestered between two CDs, and the hydrophobicity is close to that observed in cyclohexane. In beta-CD and its derivatives, the spectral changes and the measured lifetimes indicate that the CD cavity gets more hydrophobic as a result of methyl substitution of the primary and secondary hydroxyls of the beta-CD rims. In the fully methylated 2,3,6-tri-O-methyl-beta-CD, the probe is exposed to water near the secondary rim due to the steric effect at the entrance rim that prevents the probe from full encapsulation.

Local Dynamics and Hydrogen Bonding in Hyperbranched Aliphatic Polyesters

We report results from fully atomistic molecular dynamics simulations of commercially available aliphatic hydroxyl-terminated hyperbranched polyesters of two different architectures/sizes in the bulk, exploring dynamic mechanisms associated with their physical behavior as it has been described by pertinent experimental techniques. Particular emphasis is given on the role of the hydrogen-bonding capabilities of the examined systems and the impact on their local dynamic response. Analysis of the simulation results reveals that certain key aspects of their unique behavior, such as the molecular weight dependence of local group reorientation as well as the more restricted motion of these moieties in low-generation polyesters, can be explained by considering the distinct hydrogen-bonding pattern, which is realized at the intra- and intermolecular levels. This interconnection is shown to be realized through a coupling mechanism of local bond relaxation with the time scale pertinent to the formed hydrogen bond network. Quantitative accounts are provided for the relative percentage of the different kinds of hydrogen bonds as well as for their corresponding lifetimes. The detail afforded by the present work provides new insight into the structure/properties relation of such molecules and offers new ground for the interpretation of relevant experimental findings.