Regular Hydrogen Bonds Research Articles

"Hydridic Hydrogen-Bond Donors" Are Not Hydrogen-Bond Donors.

Herein, we dismiss a recent proposal by Civiš, Hobza, and co-workers to modify the IUPAC definition of hydrogen bonds in order to expand the scope from protonic Y-Hδ+ to hydridic Y-Hδ- hydrogen-bond donor fragments [J. Am. Chem. Soc. 2023, 145, 8550]. Based on accurate Kohn-Sham molecular orbital (KS-MO) analyses, we falsify the conclusion that interactions involving protonic and hydridic hydrogens are both hydrogen bonds; they are not. Instead, our quantitative KS-MO, energy decomposition, and Voronoi deformation density analyses reveal two fundamentally different bonding mechanisms for protonic Y-Hδ+ and hydridic Y-Hδ- fragments which go with charge transfer in opposite directions. On one hand, we confirm the IUPAC definition for regular hydrogen bonds in the case of protonic Y-Hδ+ fragments. On the other hand, complexes involving Y-Hδ- fragments are, in fact, acceptors in other well-known families of Lewis-acid/base interactions, such as halogen bonds, chalcogen bonds, and pnictogen bonds. These mechanisms lead to the same spectroscopic phenomenon in both the Y-Hδ+ and Y-Hδ- fragments, that is, the redshift in the Y-H stretching frequency, which is, thus, not an exclusive indicator for hydrogen bonding.

Unprecedented Strength Polysiloxane-Based Polyurethane for 3D Printing and Shape Memory.

Thermoplastic polysiloxane-based polyurethane (Si-TPU) has been attracting a great deal of attention because of the dual advantages of polysiloxane and polyurethane. However, the strength of Si-TPU with a traditional structure is low, and improvement is urgently needed for diverse applications. Herein, we design a polysiloxane-based soft segment (SS) with two urethane groups at the end of the polysiloxane chain, and then we prepare a series of Si-TPUs through a designed SS, isophorone diisocyanate and 1,4-butanediol. Such structural design improves the polarity of the SS and endows more regular hydrogen bonds to the polymer molecular chain. As a result, the prepared Si-TPUs exhibit a good microphase separation structure, unprecedentedly high strength, repeatable processing, noncytotoxicity, shape memory properties, and three-dimensional printing capabilities. Moreover, a maximum tensile strength of Si-TPUs can reach 20.3 MPa, exceeding that of other existing Si-based polymer materials. Si-TPUs show great potential for biomedical applications.

Structural and binding studies of cyclin-dependent kinase 2 with NU6140 inhibitor.

Cyclin-dependent kinase 2 (CDK2) is an established target protein for therapeutic intervention in various diseases, including cancer. Reported inhibitors of CDK2 target the ATP-binding pocket to inhibit the kinase activity. Many small molecule CDK2 inhibitors have been discovered, and their crystal structure with CDK2 or CDK2-cyclin A complex has been published. NU6140 is a CDK2 inhibitor with moderate potency and selectivity. Herein, we report the cocrystal structure determination of NU6140 in complex with CDK2 and confirmation of the binding using various biophysical methods. Our data show that NU6140 binds to CDK2 with a Kd of 800nM as determined by SPR and stabilizes the protein against thermal denaturation (ΔTm -5°C). The cocrystal structure determined in our study shows that NU6140 binds in the ATP-binding pocket as expected for this class of compounds and interacts with Leu83 and Glu81 with regular hydrogen bonds and with Asp145 via water-mediated H-bond. Based on these data, we propose structural modifications of NU6140 to introduce new interactions with CDK2 that can improve its potency while retaining the selectivity.

Kinetics of Hydrogen Bonding between Ions with Opposite and Like Charges in Hydroxyl-Functionalized Ionic Liquids.

Hydrogen-bonded structures and their lifetimes in ionic liquids (ILs) are governed by the subtle balance between Coulomb interactions, hydrogen bonding, and dispersion forces. Despite the dominant Coulomb interaction, local and directional hydrogen bonds (HBs) can play an important role in the behavior of ILs. Compared to water, the archetype of hydrogen-bonded liquids, ILs have larger constituents and higher viscosities but are typically lacking a three-dimensional HB network. Hydroxyl-functionalized ionic liquids are even more special: regular HBs between cations and anions (ca) are accompanied by HBs between pairs of cations (cc). Recently, infrared (IR) measurements have suggested that the (cc) HBs are even stronger than their (ca) counterparts and their strength can be controlled via the hydroxyalkyl chain length. In this paper, we show by means of molecular dynamics (MD) simulations that the presence of HBs has a profound effect on the molecular mobility of the ions. We investigate the kinetic mechanism of hydrogen bonding in ILs and show that the lifetimes and hence the stability of (cc) HBs increase with the chain length, making them more stable than the respective (ca) HBs. The observed HB equilibrium can explain the peculiar chain length dependence of the relative molecular mobilities of the ions by a direct comparison between hydroxyl-functionalized ILs with their nonfunctionalized counterparts.

Dihydrogen Bonds in Aqueous NaBD4 Solution by Neutron and X-ray Diffraction.

Neutron diffraction, X-ray diffraction, and empirical potential structure refinement modeling were employed to study the structure of alkaline aqueous NaBD4 solutions at different NaBD4 concentrations and temperatures. In 1.0 mol·dm-3 NaBD4 aqueous solutions, about 5.6 ± 1.6 water molecules bond to BD4- via tetrahedral edges or tetrahedral corners without a very specific hydration geometry; that is, each hydrogen atom of BD4- bonds to 2.2 ± 1.0 water molecules through dihydrogen bonds with the D(B)···D(W) distance of 1.95 Å. The number of dihydrogen bonds decreases with increasing concentration and increases with temperature. Dihydrogen bonding is a predominantly electrostatic interaction which shows relatively lower directionality and saturability in comparison with the regular hydrogen bonds between water molecules. The water orientation around BD4- shows that the proportion of tetrahedral-edge dihydrogen bonds increases with temperature and decreases with concentration.

Shear-Induced Structuring for Multiple Parallel Gel Filaments Obtained from Casein-Alginate Hybrids.

The addition of more than 1 wt % sodium alginate to a 7.5 wt % sodium caseinate solution induced aqueous two-phase separation (ATPS). Alginate and caseinate were effectively condensed in the upper and lower phases, respectively, thereby forming an alginate-casein assembly. The rigid structure of the alginate, which was formed by repeated regular hydrogen bonds between guluronic acid units, became supple when casein micelles penetrated and were adsorbed into the coiled alginate chains to weaken the diaxial linkages of the alginate hydrogen bonds. Protein-polysaccharide hybrid gel fibrils with a bundled structure were formed due to the deformation of the alginate-casein assembly in an aqueous solution by shear in a co-flow double tube, followed by cross-linking with Ca2+ supplied as the sheath fluid. The combination of ATPS and shear-induced elongation of the alginate-casein assemblies enabled the fabrication of hundreds of parallel gel filaments (φ = 1-10 μm) along the flow direction. These multiple parallel gel filaments can be applied to biomimetic chemistry for fibrous living tissues, as a biodegradable scaffold for cell engineering, and as a release carrier of physiologically active substances or drugs. Our proposed technique enables the formation of biomimetic protein-polysaccharide hybrid gel filaments with a bundled structure using Ca2+ chelation under laminar flow in a capillary, without the need for enzymatic cross-linking and multihole nozzles.

(Invited) Shear-Induced Fabrication of Multiple Parallel Gel Filaments Using Aqueous Two-Phase Separation

Macroscopic structures of gel fibers have been prepared by control of the polymer solution properties and by design of the nozzle and flow path of the microfluidic device. In this research, we investigated a method to simultaneously fabricate hundreds to thousands of gel filaments simply by flowing the polymer solution inside the capillary without spinneret. An aqueous two-phase separation (ATPS) can be induced by adjusting their concentration in certain combinations of two polymers. The respective polymer concentration in each phase can be determined from the phase diagram, whereas an assembly of heterogeneous polymers generate in each phase. Hydrodynamic properties of pre-gel solution can be controlled by inducing such heterogeneous polymer assemblies. A co-axial flow double capillary was used to fabricate gel filaments, where an inner capillary (inner diameter 0.7 mm) was fixed at the insert position of an outer capillary. To induce ATPS, an ionic strength for the aqueous solution of sodium alginate (Alg) / polyethylene glycol (PEG) mixture was controlled by NaCl addition. The pre-gel Alg/PEG solution was flown as an inner flow of glass double capillaries, where a crosslinker solution (Ca2+ soln.) was flown as a sheath flow. The obtained gel was composed of multiple parallel gel filaments with a diameter of several micrometers, while a single gel without filament structure was obtained from the homogeneous solution without NaCl addition. In aqueous solution, the Alg chain has a structure with few entanglements because of its rigidity. The rigid assembly of alginate is mainly caused by guluronic acid block, that is stabilized by diaxial linkages via intramolecular hydrogen bonds. The shear stress generated by flowing the aqueous Alg solution inside the capillary cannot induce deformation of its rigid assembly, results in the single thick gel filament. By complexation with PEG, destruction of regular hydrogen bond was responsible for breaking the rigid structure of Alg. Thus, deformation of Alg/PEG assembly was enabled to elongate as the fibrous structure by the shear stress, followed by gelation in contact with Ca2+ ions at the outlet of the inner capillary. Such shear-induced deformation of the Alg/PEG assembly was studied by measuring viscoelastic properties with a spindle viscometer. Besides, Alg/PEG assembly generation in each phase was determined by size-exclusion chromatography with a multi angle light scattering detector. This presentation will discuss a simple technique for preparing multiple gel filaments simply by passing a polymer solution through a capillary.

A new structural arrangement in proteins involving lysine NH3+ group and carbonyl

Screening of the Protein Data Bank led to identification of a recurring structural motif where lysine NH3+ group interacts with backbone carbonyl. This interaction is characterized by linear atom arrangement, with carbonyl O atom positioned on the three-fold symmetry axis of the NH3+ group (angle Cε-Nζ-O close to 180°, distance Nζ-O ca. 2.7-3.0 Å). Typically, this linear arrangement coexists with three regular hydrogen bonds formed by lysine NH3+ group (angle Cε-Nζ-acceptor atom close to 109°, distance Nζ-acceptor atom ca. 2.7-3.0 Å). Our DFT calculations using polarizable continuum environment suggest that this newly identified linear interaction makes an appreciable contribution to protein’s energy balance, up to 2 kcal/mol. In the context of protein structure, linear interactions play a role in capping the C-termini of α-helices and 310-helices. Of note, linear interaction involving conserved lysine is consistently found in the P-loop of numerous NTPase domains, where it stabilizes the substrate-binding conformation of the P-loop. Linear interaction NH3+ – carbonyl represents an interesting example of ion-dipole interactions that has so far received little attention compared to ion-ion interactions (salt bridges) and dipole-dipole interactions (hydrogen bonds), but nevertheless represents a distinctive element of protein architecture.

A novel form of RNA double helix based on G·U and C·A+ wobble base pairing.

Wobble base pairs are critical in various physiological functions and have been linked to local structural perturbations in double-helical structures of nucleic acids. We report a 1.38-Å resolution crystal structure of an antiparallel octadecamer RNA double helix in overall A conformation, which includes a unique, central stretch of six consecutive wobble base pairs (W helix) with two G·U and four rare C·A+ wobble pairs. Four adenines within the W helix are N1-protonated and wobble-base-paired with the opposing cytosine through two regular hydrogen bonds. Combined with the two G·U pairs, the C·A+ base pairs facilitate formation of a half turn of W-helical RNA flanked by six regular Watson–Crick base pairs in standard A conformation on either side. RNA melting experiments monitored by differential scanning calorimetry, UV and circular dichroism spectroscopy demonstrate that the RNA octadecamer undergoes a pH-induced structural transition which is consistent with the presence of a duplex with C·A+ base pairs at acidic pH. Our crystal structure provides a first glimpse of an RNA double helix based entirely on wobble base pairs with possible applications in RNA or DNA nanotechnology and pH biosensors.

Improved synthesis of per-O-acetylated C1 hydroxyglycopyranose and structural study as non-covalent organic framework

An improved method for the synthesis of per-O-acetylated C-1-hydroxyglycopyranose was developed by hydrolysis of per-O-acetylated glycopyranosyl α-chlorides derived from sugars with C-2 axial acetates for example l-rhamnose and d-mannose. 2,3,4-Tri-O-acetyl-α-l-rhamnopyranose crystallized in tetragonal space group I4, a rare phenomenon in carbohydrate literature. The three dimensional packing of the molecule with the help of regular hydrogen bond and C–H···O interactions resulted in the formation of porous framework showing channels with pore size 7Å.

On the physical origin of the cation–anion intermediate bond in ionic liquids Part I. Placing a (weak) hydrogen bond between two charges

The intermediate bond forces in ionic liquids are investigated from static quantum chemical calculations at various methods and two basis sets. The experimentally observed red-shift of the donor-proton bond stretching frequency due to a bond elongation is confirmed by all methods. Comparing Hartree-Fock to second-order Møller-Plesset perturbation theory, the Hartree-Fock method gives in many cases an erroneous description of the geometries. Furthermore, the Hartree-Fock interaction energies can deviate up to 60 kJ mol(-1) from Møller-Plesset perturbation theory indicating the importance of dispersion interaction. While the usual trends of decreasing stability or interaction energies with increasing ion sizes are found, the geometries involving hydrogen atoms do not change this order of total interaction energies. Therefore, the hydrogen bond is not the most important interaction for ion pairs with regard to the total interaction energy. On the other hand, the different established analysis methods give rise to hydrogen bonding in several ion pairs. Charge analysis reveals the hydrogen-bonding character of the ion pair and shows, depending on the type of ions combined and further on the type of conformers considered, that a hydrogen bond can be present. The possibility of hydrogen bonding is also shown by an analysis of the frontier orbitals. Calculating potential energy surfaces and observing from this the change in the donor proton bond indicates that regular hydrogen bonds are possible in ion pairs of ionic liquids. Thereby, the maximum of bond elongation exceeds the one of a usual hydrogen bond by far. The more salt-like hydrogen-bonded ion pair [NH(4)][BF(4)] exhibits a steeper maximum than the more ionic liquid like ion pair [EtNH(3)][BF(4)]. The fact that imidazolium-based ionic liquids as [Emim][Cl] can display two faces, hydrogen bonding and purely ionic bonding, points to a disturbing rather than stabilizing role of hydrogen bonding on the interaction of the counterions in imidazolium-based ionic liquids. While geometry and charge analysis provides attributes of weak (blue-shifted) hydrogen bonds, large bond elongations accompanied by red-shifts are obtained for the ion pairs investigated. This can be understood by the simple fact that these imidazolium-based ionic liquid ion pairs constitute weak hydrogen bonds placed between two delocalized charges.

Nucleation mechanism of polyhydroxybutyrate and poly(hydroxybutyrate‐co‐hydroxyhexanoate) crystallized by orotic acid as a nucleating agent

AbstractThe mechanism involved in the crystallization of bacterial polyhydroxybutyrate (PHB) and poly(hydroxybutyrate‐co‐hydroxyhexanoate) P(HB‐co‐HH) induced by orotic acid as a nucleant was investigated by using differential scanning calorimetry (DSC), gel permeation chromatography (GPC) and proton nuclear magnetic resonance spectroscopy (1H‐NMR). GPC measurements both carried on solvent cast and hot pressed samples did not show any significant drop of the molecular weight caused by the addition of the nucleant, indicating that no chemical reaction happened during the nucleation process. This result was confirmed by 1H‐NMR analysis of oligohydroxybutyrate (OHB) treated with an excess amount of orotic acid. The possibility of epitaxial growth of the polymer crystal on the surface of the nucleant crystal was then investigated. It was found that there is an outstanding crystalline lattice matching between the plane (100) of the PHB crystal and the plane (001) of the orotic acid crystal. In comparison, the matching obtained with conventional nucleating agents, such as boron nitride and talc, was worse. Moreover, some regular hydrogen bonds between the polyester and orotic acid could stabilize the physical process. According to these results, the physical mechanism involving the epitaxial matching between orotic acid and PHB appears to be the most probable nucleation mechanism. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

The interactions of glyoxals with proteins and DNA in relation to cancer

The interactions of glyoxal and methyl glyoxal with formamide, as a prototype of the peptide bond, and with DNA bases arc investigated using the cndo/2 method. For electron charge transfer to occur from the form-amide to the glyoxal, a stacked structure is needed. An unexpected planar hydrogen-bonded structure between the two molecules involving the regular hydrogen bond and a “pseudo hydrogen bond”, which involves the aldehydic proton of glyoxal and the oxygen atom of formamide, is found. Such a “hydrogen-bonded” arrangement is perfect geometrically for interaction with all four DNA bases. By exerting a competitive effect on base pairing between adenine and uracil (thymine), such interactions can account for the “brakelike” action of the glyoxals on cell proliferation, and hence cancerous growth, suggested by Szent-Györgyi.

Examination of the effect of structural variation on the N-glycosidic torsion ( ΦN) among N-(β- d-glycopyranosyl)acetamido and propionamido derivatives of monosaccharides based on crystallography and quantum chemical calculations

GlcNAcβAsn linkage is conserved in the N-glycoproteins of all eukaryotes. l-Glutamine (Gln), which is a one carbon higher homolog of Asn, is never glycosylated. X-ray crystallographic study of several β-1- N-acetamido- and propionamido derivatives of monosaccharides has earlier shown that the N-glycosidic torsion, Φ N, is influenced to a larger extent by the structural variation of the sugar part than that of the aglycon moiety. In order to examine the influence of the carbohydrate pendent groups on the conformational preference of the N-glycosidic linkage with respect to Φ N, several models and analogs with gluco and manno configuration have been studied in the present work by computational chemistry. The crystal structure of XylβNHPr is reported here and its molecular packing compared with related analogs. The conjunction of combining Crystallographic and computational studies allows to demonstrate the strong influence that the group at C2, and environmental factors particularly inter- and intramolecular interactions involving regular hydrogen bonds and the weak C–H···O contacts, have on the energy preference of the Φ N torsion angle.

The Catalytic Role of Aspartate in a Short Strong Hydrogen Bond of the Asp274–His32 Catalytic Dyad in Phosphatidylinositol-specific Phospholipase C Can Be Substituted by a Chloride Ion

Phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis catalyzes the cleavage of the phosphorus-oxygen bond in phosphatidylinositol. The focus of this work is to dissect the roles of the carboxylate side chain of Asp(274) in the Asp(274)-His(32) dyad, where a short strong hydrogen bond (SSHB) was shown to exist based on NMR criteria. A regular hydrogen bond (HB) was observed in D274N, and no low field proton resonance was detected for D274E and D274A. Comparison of the activity of wild type, D274N, and D274A suggested that the regular HB contributes significantly (approximately 4 kcal/mol) to catalysis, whereas the SSHB contributes only an additional 2 kcal/mol. The mutant D274E displays high activity similar to wild type, suggesting that the negative charge is sufficient for the catalytic role of Asp(274). To further support this interpretation and rule out possible contribution of regular HB or SSHB in D274E, we showed that the activity of D274G can be rescued by exogenous chloride ions to a level comparable with that of D274E. Comparison between different anions suggested that the ability of an anion to rescue the activity is due to the size and the charge of the anion not the property as a HB acceptor. In conclusion, a major fraction of the functional role of Asp(274) in the Asp(274)-His(32) dyad can be attributed to a negative charge (as in D274E and D274G-Cl(-)), and the SSHB in the wild type enzyme provides minimal contribution to catalysis. These results represent novel insight for an Asp-His catalytic dyad and for the mechanism of phosphatidylinositol-specific phospholipase C.

Controlling diaza-Cope rearrangement reactions with resonance-assisted hydrogen bonds.

NMR studies reveal that the equilibrium between 1 and 2 lies essentially toward 1 to the left without any detectable amount of 2. DFT computation shows that the value of K1 is about 1.4 x 10-5, and X-ray crystal structures show that the resonance-assisted hydrogen bond (RAHB) in 1 (1.66 A) is shorter than the regular hydrogen bond in 2 (1.75 A). The enormous selectivity can be explained in terms of the strength of the RAHBs in 1 compared to that of the regular hydrogen bonds in 2.

Tetraammonium benzene-1,2,4,5-tetracarboxylate tetrahydrate

The anions in the title compound, 4NH4+·C10H2O84−·4H2O, are held together by regular hydrogen bonds from the carboxyl­ate O atoms to the ammonium cations and water mol­ecules, forming a three-dimensional network.

Bifurcated Hydrogen Bonds: Three-Centered Interactions

The nature of bifurcated or three-centered hydrogen bonds (HB) has been investigated. Different families of compounds were chosen: monomers with intramolecular three-centered HB, dimers with a HB donor (HBD) and a molecule with two HB acceptor (HBA) groups, and trimers with one HBD and two HBAs. All the systems were optimized at the B3LYP/6-31G* level, and, in the case of the complexes, the interaction energies were evaluated and corrected with the basis set superposition error (BSSE). The electronic nature of these three-centered HBs was analyzed by means of the atoms in molecules (AIM) approach. The present study indicates the existence of bifurcated bond paths in the AIM analysis with electron densities that can be classified as follows: (i) compounds with symmetric three-centered HBs presenting two symmetric bond critical points with equal values of electron density; (ii) compounds with asymmetric three-centered HBs presenting two bond critical points with different values of electron density; (iii) compounds with a regular HB and a van der Waals interaction showing two bond critical points with different electron density values one of which is very small; (iv) van der Waals complexes with two bond critical points having very small electron densities. Therefore, looking at the geometry, electron density, and energy results, the nature as HB of these three-centered interactions has been confirmed.

Structure and properties of 6/6.9 copolyamide series. I. Amorphous phase

The amorphous phase of a series of random 6/6.9 copolyamides was investigated. It was characterized by the glass transition temperature (Tg) and the hydrogen bond content, as a function of the copolymer composition, compared to the corresponding homopolymers, polyamide 6 and polyamide 6.9. The hydrogen bonds in the amorphous phase have a major influence on the copolymer properties. The glass transition temperature decreases as either comonomer content increases, attaining a minimum value at about 1 : 1 molar composition. This is due to the decreased content of hydrogen bonds, their broader strength distribution, and the decreased degree of crystallinity. In addition to the usual effects, quenching in the present system causes the formation of a less dense and less regular hydrogen bonds network, reducing the Tg. Following room temperature aging, the usual hydrogen bond content is restored. © 1996 John Wiley & Sons, Inc.