Weak Hydrogen Bond Donor Research Articles

Compliant Iontronic Triboelectric Gels with Phase-Locked Structure Enabled by Competitive Hydrogen Bonding

HighlightsA bionic phase-locked structure-inspired iontronic triboelectric gel is proposed with good mechanical compliance for wearable haptic sensing applications.Competitive hydrogen bonding systems are constructed through polymer-solvent-nonsolvent interactions, and regeneration of polymers with weak hydrogen bond donors triggers controlled phase separation.Self-powered haptic skin constructed with iontronic triboelectric gel has a modulus (150.6 kPa) and stretchability (> 400%) similar to that of the human body, enabling fidelity transmission of haptic signals and precise recognition of sensing objects.

Quantification of Hydrogen-Bond-Donating Ability of Biologically Relevant Compounds.

Hydrogen bonding is a key factor in the design of ligands for biological binding, including drug targets. Our group previously developed a method for experimentally assessing the hydrogen-bond-donating ability of an analyte using UV-vis titrations with a colorimetric sensor. Using this method, 79 new titrations were performed on weak hydrogen-bond donors, with a focus on heterocycles and pharmaceutically relevant motifs. The hydrogen-bond donating abilities of drug compounds and the substructures of drug compounds were also measured. These titrations will be used to build a database of hydrogen-bond donors.

The C[sbnd]F⋅⋅⋅H[sbnd]CF2 interaction: A combination of hydrogen bonding and n → σ* stabilization

In this communication, we explore a unique molecule that exhibits a substantial interaction between a CF2H group and a CF group. In medicinal chemistry, CF2H groups are known as weak hydrogen bond donors, and CF groups as weak H-bond acceptors. Seldom are they paired up together in an array such that their unique properties can be examined. In this case, we establish that along with an attractive hydrogen bonding interaction, an n → σ* component anchors the interactions. A unique combination of steric and hyperconjugative effects ‘switches’ the interaction away from previously reported dominant tetrel-type bonding in the case of a CH2F and CF interation towards an unusualy complex hybrid interaction. Crystallographic, computational, and spectroscopic studies illuminate the problem.

Supramolecular structural influences from remote functionality in coordination complexes of 4-picolylamine ligands

A series of nine cobalt(II), copper(II) and silver(I) coordination complexes of structurally similar picolylamine ligands, N-(4-picolyl)piperidine (L1) and N-(4-picolyl)morpholine (L2), have been prepared and analyzed. These consist of a dinuclear copper(II) complex [Cu2(OAc)4(L1)2] (1), tetranuclear copper(II) complexes [Cu4OCl6(L1)4]·MeCN·H2O (2) and [Cu4OCl7(L2)2 (L2H)]·2MeCN·9H2O (3), trichlorocobaltate complexes [CoCl3 (L1H)]·MeCN (4) and [CoCl3(L2H)] (5), silver coordination polymers poly-[AgL1]SbF6·0.5THF) (6), poly-[Ag(L2)]SbF6·0.5THF (7) and poly-[Ag(L1)(CO2CF3)] (9) and discrete dinuclear silver complex [Ag2(L2)2(THF)4](SbF6)2 (8). While the coordination and classical N–H···X hydrogen bonding in these species is related and largely independent of backbone functionality, differences in ligand composition dictate the d weak interactions and the supramolecular structure. In 1, 2, 4, 6 and 9 piperidine acts as a weak hydrogen bond donor, with C–H···Cl/O/F contacts mostly observed from the methylene groups adjacent to the amine. In the morpholine species 3, 5, 7 and 8 the tendency for morpholine to associate via reciprocated C–H···O interactions overrides the other crystal packing tendencies, changing both the local and extended structures. By studying both strong and weak packing interactions, this study presents a test case for the design of discrete and polymeric coordination compounds with finely tuned modes of intermolecular interaction.

Molecules of the year

Longest, most twisted perphenylacene synthesized Researchers at Tulane University synthesized dodecaphenyltetracene—four fused benzene rings surrounded by 12 pendant phenyl rings—in three steps (Angew. Chem., Int. Ed. 2019, DOI: 10.1002/anie.201812418). The molecule is of interest for organic electronics and photovoltaics. Methane was caged inside C60 This year, researchers trapped methane inside C60 (Angew. Chem., Int. Ed. 2019, DOI: 10.1002/anie.201900983). Methane is the first organic molecule and the largest of any kind to be trapped this way. The University of Southampton researchers made a fullerene cage with a sulfur-containing 17-membered ring, forced methane inside at high pressure, and closed the cage by oxidizing the sulfur and ejecting sulfur monoxide. Cryptand cage had record-breaking affinity for chloride This molecule captured and bound chloride ions using only C–H bonds, which are typically considered weak hydrogen-bond donors (Science 2019, DOI: 10.1126/science.aaw5145). The cage’s affinity for chloride is so high that the Indiana University Bloomington team

Tuning the reduction potential of quinones by controlling the effects of hydrogen bonding, protonation and proton-coupled electron transfer reactions.

An all-organic cell comprising 2,3-dimethyl-1,4-napthoquinone and pyrano[3,2-f]chromene as electroactive elements exhibited a good combination of large cell voltage and stability of the reduced quinone upon the addition of diethyl malonate (a weak organic acid), as compared to the addition of trifluoroethanol (which led to a high cell potential but low stability via strong hydrogen bonding interactions) and the addition of trifluoroacetic acid (which led to a lower cell potential but high stability through proton transfer).

Intermolecular interactions upon carbon dioxide capture in deep-eutectic solvents.

Herein we report the CO2 uptake in potential deep-eutectic solvents (DESs) formed between hydrogen bond acceptors (HBAs) such as monoethanolammonium chloride ([MEA·Cl]), 1-methylimidazolium chloride ([HMIM·Cl]) and tetra-n-butylammonium bromide ([TBAB]) and hydrogen bond donors (HBDs) like ethylenediamine ([EDA]), diethylenetriamine ([DETA]), tetraethylenepentamine ([TEPA]), pentaethylenehexamine ([PEHA]), 3-amino-1-propanol ([AP]) and aminomethoxypropanol ([AMP]) and analyzed the outcome in terms of the specific polarity parameters. Among various combinations of HBAs and HBDs, [MEA·Cl][EDA]-, [MEA·Cl][AP]-, [HMIM·Cl][EDA]- and [HMIM·Cl][AP] showed excellent CO2 uptake which was further improved upon increasing the mole ratio of HBA : HBD from 1 : 1 to 1 : 4. The lowest CO2 uptake in [MEA·Cl][PEHA] (12.7 wt%) and [HMIM·Cl][PEHA] (8.4 wt%) despite the highest basicity of [PEHA] infers that the basicity is not the sole criteria for guiding the CO2 uptake but, in reality, CO2 capture in a DES relies on the interplay of H-bonding interactions between each HBA and HBD. The role of HBAs in guiding CO2 uptake was more prominent with weak HBDs such as [TEPA] and [PEHA]. The speciation of absorbed CO2 into carbamate, carbonate, and bicarbonate was favorable in DES characterized by comparable hydrogen bond donor acidity (α) and hydrogen bond acceptor basicity (β) values, whereas the conversion of carbamate to carbonate/bicarbonate was observed to depend on α. The addition of water in DES resulted in lower CO2 uptake due to the decreased basicity (β).

Cyclic Hydrogen Bonding in Indole Carboxylic Acid Clusters

Monolayers of indole-2-carboxylic acid and indole-3-carboxylic acid on gold are studied using ultrahigh-vacuum scanning tunneling microscopy. Both molecules form symmetric, cyclic, hydrogen-bonded pentamers, a structure that is stabilized by the presence of a weak hydrogen-bond donor (NH or CH) adjacent to the carboxylic acid on the five-membered ring. In addition to pentamers, indole-2-carboxylic acid forms hexamers and catemer chains, while indole-3-carboxylic acid monolayers are generally disordered. Density functional theory calculations show that pentamers and hexamers have stability comparable to dimers or short catemers. The coexistence of all of these structures likely arises from the nonequilibrium conditions present in solution during pulse deposition of the monolayer.

An analysis of hydrated proton diffusion in ab initio molecular dynamics

A detailed understanding of the inherently multiscale proton transport process raises a number of scientifically challenging questions. For example, there remain many (partially addressed) questions on the molecular mechanism for long-range proton migration and the potential for the formation of long-lived traps giving rise to burst-and-rest proton dynamics. Using results from a sizeable collection of ab initio molecular dynamics (AIMD) simulations (totaling ∼2.7 ns) with various density functional approximations (Becke-Lee-Yang-Parr (BLYP), BLYP-D3, Hamprecht-Cohen-Tozer-Handy, B3LYP) and temperatures (300-330 K), equilibrium and dynamical properties of one excess proton and 128 water molecules are studied. Two features in particular (concerted hops and weak hydrogen-bond donors) are investigated to identify modes in the system that are strongly correlated with the onset of periods of burst-and-rest dynamics. The question of concerted hops seeks to identify those time scales over which long-range proton transport can be classified as a series of sequential water hopping events or as a near-simultaneous concerted process along compressed water wires. The coupling of the observed burst-and-rest dynamics with motions of a fourth neighboring water molecule (a weak hydrogen-bond donor) solvating the protonated water molecule is also investigated. The presence (absence) of hydrogen bonds involving this fourth water molecule before and after successful proton hopping events is found to be strongly correlated with periods of burst (rest) dynamics (and consistent with pre-solvation concepts). By analyzing several realizations of the AIMD trajectories on the 100-ps time scale, convergence of statistics can be assessed. For instance, it was observed that the probability for a fourth water molecule to approach the hydronium, if not already proximal at the beginning of the lifetime of the hydronium, is very low, indicative of the formation of stable void regions. Furthermore, the correlations of the neighboring water atoms are identified as the fourth water approaches the hydronium. Finally, the temperature effects on structural and dynamical properties are studied.

Mapping the internal recognition surface of an octanuclear coordination cage using guest libraries.

Size and shape criteria for guest binding inside the cavity of an octanuclear cubic coordination cage in water have been established using a new fluorescence displacement assay to quantify guest binding. For aliphatic cyclic ketones of increasing size (from C5 to C11), there is a linear relationship between ΔG for guest binding and the guest's surface area: the change in ΔG for binding is 0.3 kJ mol(-1) Å(-2), corresponding to 5 kJ mol(-1) for each additional CH2 group in the guest, in good agreement with expectations based on hydrophobic desolvation. The highest association constant is K = 1.2 × 10(6) M(-1) for cycloundecanone, whose volume is approximately 50% of the cavity volume; for larger C12 and C13 cyclic ketones, the association constant progressively decreases as the guests become too large. For a series of C10 aliphatic ketones differing in shape but not size, ΔG for guest binding showed no correlation with surface area. These guests are close to the volume limit of the cavity (cf. Rebek's 55% rule), so the association constant is sensitive to shape complementarity, with small changes in guest structure resulting in large changes in binding affinity. The most flexible members of this series (linear aliphatic ketones) did not bind, whereas the more preorganized cyclic ketones all have association constants of 10(4)-10(5) M(-1). A crystal structure of the cage·cycloundecanone complex shows that the guest carbonyl oxygen is directed into a binding pocket defined by a convergent set of CH groups, which act as weak hydrogen-bond donors, and also shows close contacts between the exterior surface of the disc-shaped guest and the interior surface of the pseudospherical cage cavity despite the slight mismatch in shape.

Nature of the attractive interaction between proton acceptors and organic ring systems

Systematic ab initio calculations are combined with a deconvolution of electrostatic contributions to analyze the interplay between potential hydrogen bond acceptors and organic rings with C(sp(2))-H groups (benzene, pyridine and cyclopentadiene). A distinct anisotropic interaction between the ring systems and the electron lone pairs of cyanide, water and other acceptor species is revealed that favors the in-plane orientation of the proton acceptor group. In the attractive regime this interaction carries a pronounced electrostatic signature. By decomposing the electrostatic contribution into parts attributed to different subunits of the ring systems we demonstrate that a major proportion of the interaction energy gain is originating from the non-adjacent moieties, that are not in close contact with. This behavior holds equally for homocyclic, heterocyclic and non-aromatic rings but contrasts that of the ethyne molecule, taken as reference for a weak hydrogen bond donor clearly exhibiting the expected localized character. The ring interaction requires the presence of π-electron clouds and typically results in an interaction energy gain of 40 to 80 meV. Our findings suggest the proton acceptor-ring interaction as a new category of intermolecular non-covalent interactions.

Synthesis and Biological Evaluation of Isosteric Analogs of Mandipropamid for the Control of Oomycete pathogens

A series of isosteric analogs of mandipropamid were designed and synthesized via 'click chemistry'. The amide bond of mandipropamid was substituted by a 1,2,3-triazole functional group. The bioassay results have indicated that some of the title compounds exhibited moderate fungicidal activity against Pseudoperonospora cubensis, and the activity has been systematically studied as a function of molecular structure. The low activity of the mandipropamid analog that contains a lipid chain is likely due to the presence of a weak hydrogen bond donor in the 1,2,3-triazole. Furthermore, we have performed the molecular modeling and found that N-methylamide could be more effective than amide as the surrogates to 1,2,3-triazole, which ultimately leads to a longer distance (1.1 Å longer) between the two substitutes in the 1,4-disubstituted 1,2,3-triazole compound.

Ferrocene compounds: methyl 1′-aminoferrocene-1-carboxylate

The title compund, [Fe(C(5)H(6)N)(C(7)H(7)O(2))], features one strong intermolecular hydrogen bond of the type N-H...O=C [N...O = 3.028 (2) A] between the amine group and the carbonyl group of a neighbouring molecule, and vice versa, to form a centrosymmetric dimer. Furthermore, the carbonyl group acts as a double H-atom acceptor in the formation of a second, weaker, hydrogen bond of the type C-H...O=C [C...O = 3.283 (2) A] with the methyl group of the ester group of a second neighbouring molecule at (x, -y - 1/2, z - 1/2). The methyl group also acts as a weak hydrogen-bond donor, symmetry-related to the latter described C-H...O=C interaction, to a third molecule at (x, -y - 1/2, z + 1/2) to form a two-dimensional network. The cyclopentadienyl rings of the ferrocene unit are parallel to each other within 0.33 (3) degrees and show an almost eclipsed 1,1'-conformation, with a relative twist angle of 9.32 (12) degrees . The ester group is twisted slightly [11.33 (8) degrees ] relative to the cylopentadienyl plane due to the above-mentioned intermolecular hydrogen bonds of the carbonyl group. The N atom shows pyramidal coordination geometry, with the sum of the X-N-Y angles being 340 (3) degrees .

A theoretical study of the hydrogen bond donor capability and co-operative effects in the hydrogen bond complexes of the diaza-aromatic betacarbolines

In this work, we present a quantum mechanical investigation on the hydrogen bond interactions of N(9)-methyl-9H-pyrido[3,4-b]indole, MBC, and N(2)-methyl-9H-pyrido[3,4-b]indole, BCA, with different hydrogen bond donors. Thus, it has been analysed the influence that the hydrogen bond donor strength and the co-operative effect of the increasing number of donor molecules have on the shape of the potential energy surfaces versus the N···H distances, r(N–H). To rationalize the nature of the interactions, the Bader theory has been applied and the characteristics of the bond critical points analysed. The results show that two different hydrogen bond complexes can be formed depending on the donor capabilities or the number of donor molecules included in the calculations. The topological parameters from the Bader theory are used to justify the statement that the analysed interactions can be classified as weak or partially covalent hydrogen bond interactions, respectively. As experimentally observed, weak hydrogen bond donors form weak hydrogen bond complexes, called HBC. Upon the increase of the donor strength the N···H proton is shifted nearest to the nitrogen atom giving rise to the observation of a stronger hydrogen bond complex, the proton transfer complex, PTC. The most outstanding result of these studies is the fact that the formation of the PTC can also be managed just by changing the number of donor molecules, that is, by a co-operative effect of the hydrogen bonds.

Towards Allosteric Receptors: Adjustment of the Rotation Barrier of 2,2′‐Bipyridine Derivatives

What a difference! The energy differences between anti and syn conformers as well as the energy barrier for the rotation around the aryl-aryl bond of a number of 2,2'-bipyridine molecules were examined by quantum-chemical methods. The energy differences were found to be governed by the substituents directly attached to the bipyridine and their ability to form intramolecular hydrogen bonds.Quantum-chemical calculations at the BP86/TZVP level of theory were performed to determine the energy differences between the syn and the anti conformers, as well as the energy barrier for the rotation of the aryl-aryl bond of 2,2'-bipyridine molecules and a number of disubstituted derivatives. Substitutents with hydrogen-bond donor (or electron acceptor) functions or hydrogen-bond acceptors (or electron donors) are generally found to have large effects on the difference and the barrier. Substitution with a hydrogen-bond donor (or an electron acceptor) at position 6 and 6' leads to a decrease owing to a charge transfer from the pyridine nitrogen lone pair to the donor, which is caused by the formation of weak intramolecular hydrogen bonds and/or dipolar interactions, respectively. Conversely, substitution at position 4 and 4' causes an increase in the energy barrier. Substitution with a hydrogen-bond acceptor (or an electron donor) shows the opposite behavior, which can be explained by the weak intramolecular interactions. Interestingly, even very weak CH hydrogen-bond donors (electron acceptors) such as methyl groups have a significant influence. This indicates the importance of such weak interactions for the structure and energetics of supramolecular systems. The energy differences are mainly governed by the substituents directly attached to the bipyridine core as the introduction of sterically demanding groups in the periphery hardly influences the barriers or energy differences of the conformers. These findings are important for the design of heterotropic positive cooperative allosteric receptors with 2,2'-bipyridines as the allosteric centre.

Volatile Anesthetic Binding to Proteins Is Influenced by Solvent and Aliphatic Residues

The main objective of this work was to characterize VA binding sites in multiple anesthetic target proteins. A computational algorithm was used to quantify the solvent exclusion and aliphatic character of amphiphilic pockets in the structures of VA binding proteins. VA binding sites in the protein structures were defined as the pockets with solvent exclusion and aliphatic character that exceeded minimum values observed in the VA binding sites of serum albumin, firefly luciferase, and apoferritin. We found that the structures of VA binding proteins are enriched in these pockets and that the predicted binding sites were consistent with experimental determined binding locations in several proteins. Autodock3 was used to dock the simulated molecules of 1,1,1,2,2-pentafluoroethane, difluoromethyl 1,1,1,2-tetrafluoroethyl ether, and sevoflurane and the isomers of halothane and isoflurane into these potential binding sites. We found that the binding of the various VA molecules to the amphiphilic pockets is driven primarily by VDW interactions and to a lesser extent by weak hydrogen bonding and electrostatic interactions. In addition, the trend in Delta G binding values follows the Meyer-Overton rule. These results suggest that VA potencies are related to the VDW interactions between the VA ligand and protein target. It is likely that VA bind to sites with a high degree of solvent exclusion and aliphatic character because aliphatic residues provide favorable VDW contacts and weak hydrogen bond donors. Water molecules occupying these sites maintain pocket integrity, associate with the VA ligand, and diminish the unfavorable solvation enthalpy of the VA. Water molecules displaced into the bulk by the VA ligand may provide an additional favorable enthalpic contribution to VA binding. Anesthesia is a component of many health related procedures, the outcomes of which could be improved with a better understanding of the molecular targets and mechanisms of anesthetic action.

De novo Refolding and Aggregation of Insulin in a Nonaqueous Environment: An Inside out Protein Remake

While thermodynamic penalties associated with protein-water interactions are the key driving force of folding, perturbed hydration of destabilized protein molecules may trigger aggregation, which in vivo often causes cellular and histological damage. Here we show, that the denatured state of an alpha-helical protein, insulin, converts to a non-native beta-sheet-rich structure upon de novo "refolding" in an anhydrous environment. The beta-pleated conformer precipitates from solutions of DMSO-denatured insulin upon dilution with chloroform. DMSO destroys hydrogen bond network of the native protein acting as a strong acceptor of main chain hydrogen bonds. Upon the addition of chloroform, which is a weak hydrogen bond donor per se, competitive hydrogen bonds between DMSO and chloroform are formed. This leads to the release of unfolded insulin molecules. In the absence of water, the imminent saturation of polypeptide's dandling hydrogen bonds does not produce the native and predominantly alpha-helical state but a beta-sheet-rich structure, which is morphologically and spectrally distinct from insulin amyloid fibrils. Unlike insulin fibrils, the beta-sheet conformer is metastable and refolds spontaneously to the native form in an aqueous environment. This implies that "folding" in the absence of water results in inefficient burial of hydrophobic side-chains, and thermodynamic frustration at the water-protein interface.

Enhancement of a Lewis Acid−Base Interaction via Solvation: Ammonia Molecules and the Benzene Radical Cation

The interaction between ammonia and the benzene radical cation has been investigated by gas-phase studies of mass selected ion clusters {C(6)H(6)-(NH(3))(n=0-8)}(+) via tandem quadrupole mass spectrometry and through calculations. Experiments show a special stability for the cluster ion that contains four ammonias: {C(6)H(6)(NH(3))(4)}(+). Calculations provide evidence that the first ammonia forms a weak dative bond to the cyclohexadienyl radical cation, {C(6)H(6)-NH(3)}(+), where there is a transfer of electrons from ammonia to benzene. Additional solvating ammonia molecules form stabilizing hydrogen bonds to the ring-bound ammonia {C(6)H(6)-NH(3)}(+).(NH(3))(n), which cause cooperative changes in the structure of the cluster complex. Free ammonia is a weak hydrogen bond donor, but electron transfer from NH(3) to the benzene ring that strengthens the dative bond will increase the hydrogen acidity and the strength of the cluster hydrogen bonds to the added ammonia. A progressive "tightening" of this dative bond is observed upon addition of the first, second, and third ammonia to give a cluster stabilized by three N-(+)H x N hydrogen bonds. This shows that the energetic cost of tightening the dative bond is recovered with dividends in the formation of stable cluster hydrogen bonds.

Search for a Predicted Hydrogen Bonding Motif − A Multidisciplinary Investigation into the Polymorphism of 3-Azabicyclo[3.3.1]nonane-2,4-dione

The predictions of the crystal structure of 3-azabicyclo[3.3.1]nonane-2,4-dione submitted in the 2001 international blind test of crystal structure prediction (CSP2001) led to the conclusion that crystal structures containing an alternative hydrogen bonded dimer motif were energetically competitive with the known catemer-based structure. Here we report an extensive search for a dimer-based crystal structure. Using an automated polymorph screen a new catemer-based metastable polymorph (form 2) and two new catemer-based solvates were found, and concurrent thermal studies reproduced form 2 and identified a plastic phase (form 3), whose powder X-ray diffraction pattern was consistent with the cubic space group I23 (a = 7.5856(1) A). Computational studies on the monomer showed that the imide N-H was a weak hydrogen bond donor, rationalizing the occurrence of the plastic phase which involved the breaking of all hydrogen bonds, and modeling of small clusters showed that dimers could easily reorganize to give the catemer. FTIR spectra confirmed the weakness of the hydrogen bond, with the solute showing no self-assembly in solution. It is concluded that the weakness of the N-H donor, coupled with the globular shape of the molecule, allows unusually facile transformation between alternative hydrogen bonding motifs during aggregation and nucleation.

Theoretical Study of Dihydrogen Bonds between (XH)2, X = Li, Na, BeH, and MgH, and Weak Hydrogen Bond Donors (HCN, HNC, and HCCH)

The dihydrogen-bonded (DHB) complexes formed by (XH)2, with X = Li, Na, BeH, and MgH, with one, two, and four protonic molecules (HCN, HNC, and HCCH) have been studied. These complexes have been compared to those of the XH monomers with the same hydrogen bond donor molecules. The energetic results have been rationalized based on the electrostatic potential of the isolated hydridic systems. The electron density properties have been analyzed within the AIM methodology, both at the bond critical points and the integrated values at the atomic basins. Exponential relationships between several properties calculated at the bond critical points (rho,nabla2rho, lambdai, G, and V) and variation of integrated properties (energy, charge, and volume) vs the DHB distance have been obtained.