H-bonding Ability Research Articles

Tweezer Dyads for H-Bond Assisted Cooperativity in Tandem Uncaging Systems.

"Tandem" uncaging systems, in which a photolabile protecting group (PPG) is sensitized by an energy-harvesting antenna, may increase the photosensitivity of PPGs by several orders of magnitude for two-photon (2P) photorelease. Yet, they remain poorly accessible because of arduous multi-step synthesis. In this work, we design efficient tandem uncaging systems by (i) using a convenient assembly of the building blocks relying on click chemistry, (ii) introducing H-bonding induced proximity thus facilitating (iii) photoinduced electron transfer (PeT) as a cooperative mechanism. A strong two-photon absorber electron-donating quadrupolar antenna and various electron-accepting PPGs (mDEAC, MNI or MDNI) were clicked stepwise onto a "tweezer-shaped" pyrido-2,6-dicarboxylate platform whose H-bonding and π-stacking abilities were exploited to keep the antenna and the PPGs in close proximity. The different electron-accepting ability of the PPGs led to dyads with wildly different behaviors. Whilst the MDNI and MNI dyads showed poor dark stability or no photo-uncaging ability due to their too high electron-accepting character, the mDEAC dyad benefited from optimum redox potentials to promote PeT and slow down charge recombination, resulting in enhanced uncaging quantum yield (Φu=0.38) compared to mDEAC (Φu=0.014). This unique combination resulted in large 2P photo-sensitivity in the near-infrared window (240 GM at 710 nm).

Aroma Compounds in Essential Oils: Analyzing Chemical Composition Using Two-Dimensional Gas Chromatography-High Resolution Time-of-Flight Mass Spectrometry Combined with Chemometrics.

Analyzing essential oils is a challenging task for chemists because their composition can vary depending on various factors. The separation potential of volatile compounds using enantioselective two-dimensional gas chromatography coupled with high-resolution time-of-flight mass spectrometry (GC×GC-HRTOF-MS) with three different stationary phases in the first dimension was evaluated to classify different types of rose essential oils. The results showed that selecting only ten specific compounds was enough for efficient sample classification instead of the initial 100 compounds. The study also investigated the separation efficiencies of three stationary phases in the first dimension: Chirasil-Dex, MEGA-DEX DET-β, and Rt-βDEXsp. Chirasil-Dex had the largest separation factor and separation space, ranging from 47.35% to 56.38%, while Rt-βDEXsp had the smallest, ranging from 23.36% to 26.21%. MEGA-DEX DET-β and Chirasil-Dex allowed group-type separation based on factors such as polarity, H-bonding ability, and polarizability, whereas group-type separation with Rt-βDEXsp was almost imperceptible. The modulation period was 6 s with Chirasil-Dex and 8 s with the other two set-ups. Overall, the study showed that analyzing essential oils using GC×GC-HRTOF-MS with a specific selection of compounds and stationary phase can be effective in classifying different oil types.

HERBAL INFUSIONS AS INHIBITORS OF TRYPSIN ACTIVITY IN WATER AND POLAR ORGANIC SOLVENT–WATER SYSTEMS

The inhibition of digestive enzyme trypsin by polyphenolic compounds derived from mountainous herbal infusions, as well as the effect of polarity and acidity of the media on this process were studied by virtue of UV-Vis absorption spectroscopy at 293.15 K. Mountainous herbal infusions (thyme, peppermint) are well known due to their biomedical significance and wide use as a beverage. The binding constant (Kb) and standard Gibbs energy change (ΔG0) were calculated. The obtained results show that polyphenols extracted from herbal infusions significantly inhibit trypsin. Moreover, the effect of thyme infusion is stronger compared with that of peppermint. The results show that the change of both polarity and H-bonding ability of polar organic cosolvent significantly alters the value of Kb, indicating that H-bonds and electrostatic interactions are the main driving forces in these interactions.

Reaction characteristics of metal-salt coordinated deep eutectic solvents during lignocellulosic pretreatment

A binary deep eutectic solvent consisting of choline chloride and glycerol (ChCl/Gly) is proven to be ineffective in lignocellulosic pretreatment, and arbitrarily screening coordination agents makes it difficult to directionally construct a valid solvent. This study investigated the designable diversity of ternary ChCl/Gly coordinated with various metal-salts by elucidating solvent properties and reaction characteristics. Alkaline/acidic strengths and hydrogen-bonding forces were key factors for component fractionation. Pretreatment performance was typically poor for solvents with few acidic sites and active protons (i.e., ChCl/Gly-KCl and MgCl2), as well as those with close proximity of H-bond donor and acceptor abilities (ChCl/Gly-ZnCl2). By contrast, strong alkaline ChCl/Gly-K2CO3 could achieved 72 % of delignification with a remarkable holo-cellulose preservation (70.8–80.9 %). Delignification underwent an independent rate-control of solvent diffusion and surface reaction with an endothermic nature (17.1 kJ/mol of ΔH and 20.3 kJ/mol of apparent activation energy). High temperature was beneficial for mitigating diffusion constraint at the initial pretreatment stage, maximally increasing the reaction rate by 7.7-fold. Moreover, Lewis acidic ChCl/Gly-FeCl3 (or AlCl3) removed 76–84.4 % of hemicellulose and 47.6–61.9 % of lignin while significantly deconstructing the aryl-ether bonds and β-O-4 linkages. But for acidic ChCl/Gly solvents, biomass dissolution was inconformity with the independent diffusion/reaction-controlling process, owing to the excessive hemicellulose degradation and hydrolytic by-product formation (maximally 91 g/kg xylose and 4 g/kg furans). Based on the lignin structural characterization, the potential reaction mechanism related to solvent properties was proposed to develop efficient ternary coordinated deep eutectic solvents.

Theoretical insight on the importance of CH···O and NH···O interactions in the crystal packing of a decavanadate synthesized from a simple V(IV) precursor

In this manuscript, the synthesis and X-ray characterization of a new decavanadate complex, [H2L1]2[HL2]2[V10O28], is reported, where [H2L1] and [HL2] are the protonated forms of ligands L1 and L2 [L1 = 4-(2-aminoethyl)morpholine and L2 = N-ethylidene-2-morpholinoethanamine]. H-bonding interactions between the bridging oxygen atoms of the anion and the ammonium groups (N+–H···O) of the ligands are selectively formed. Moreover, a multitude of CH···O interactions are also established between the counter ions. DFT calculations have been used to rationalize the interactions observed in the solid state and to compare the relative importance of the charge assisted NH···O H-bonds with the CH···O ones, evidencing that almost 40 % of the interaction energies are due to CH···O contacts. Moreover, using MEP surface calculations, the H-bond acceptor ability of the different O-atoms of [V10O28]6- anion has been studied. To our knowledge, such analysis is unprecedented in the literature.

Chemical Tools for the Study of DNA Repair.

ConspectusDNA repair enzymes continuously provide surveillance throughout our cells, protecting the enclosed DNA from the damage that is constantly arising from oxidation, alkylating species, and radiation. Members of this enzyme class are intimately linked to pathways controlling cancer and inflammation and are promising targets for diagnostics and future therapies. Their study is benefiting widely from the development of new tools and methods aimed at measuring their activities. Here, we provide an Account of our laboratory's work on developing chemical tools to study DNA repair processes in vitro, as well as in cells and tissues, and what we have learned by applying them.We first outline early work probing how DNA repair enzymes recognize specific forms of damage by use of chemical analogs of the damage with altered shapes and H-bonding abilities. One outcome of this was the development of an unnatural DNA base that is incorporated selectively by polymerase enzymes opposite sites of missing bases (abasic sites) in DNA, a very common form of damage.We then describe strategies for design of fluorescent probes targeted to base excision repair (BER) enzymes; these were built from small synthetic DNAs incorporating fluorescent moieties to engender light-up signals as the enzymatic reaction proceeds. Examples of targets for these DNA probes include UDG, SMUG1, Fpg, OGG1, MutYH, ALKBH2, ALKBH3, MTH1, and NTH1. Several such strategies were successful and were applied both in vitro and in cellular settings; moreover, some were used to discover small-molecule modulators of specific repair enzymes. One of these is the compound SU0268, a potent OGG1 inhibitor that is under investigation in animal models for inhibiting hyperinflammatory responses.To investigate cellular nucleotide sanitation pathways, we designed a series of "two-headed" nucleotides containing a damaged DNA nucleotide at one end and ATP at the other; these were applied to studying the three human sanitation enzymes MTH1, dUTPase, and dITPase, some of which are therapeutic targets. The MTH1 probe (ARGO) was used in collaboration with oncologists to measure the enzyme in tumors as a disease marker and also to develop the first small-molecule activators of the enzyme.We proceed to discuss the development of a "universal" probe of base excision repair processes (UBER), which reacts covalently with abasic site intermediates of base excision repair. UBER probes light up in real time as the reaction occurs, enabling the observation of base excision repair as it occurs in live cells and tissues. UBER probes can also be used in efficient and simple methods for fluorescent labeling of DNA. Finally, we suggest interesting directions for the future of this field in biomedicine and human health.

Ionic liquid assisted nanocellulose production from microcrystalline cellulose: Correlation between cellulose solubility and nanocellulose yield via COSMO-RS prediction

The use of ionic liquids (ILs) in nanocellulose (NC) production from cellulosic materials has gained significant interest due to the intrinsic physical solubility of cellulosic materials in many ILs. However, given the numerous possible cation–anion combinations, selecting potential candidates from thousands of ILs for NC production is rather difficult. In addition, NC yield depends on the types of ILs and their capability in dissolution of cellulosic materials. In this study, we investigate NC production from microcrystalline cellulose (MCC) using various ILs as a reaction medium. Firstly, the prediction of MCC solubility in 300 ILs (15 cations and 20 anions) was obtained by deploying the conductor-like screening model for real solvents (COSMO-RS) which has emerged as a reliable and promising tool for solvents screening based on the dominant interactions of H-bonds, misfits, and Van der Waals energies of the fluid mixture. Experimental measurement of NC production from MCC in six ILs, namely [Emim][OAc], [Bmim][OAc], [Bmim][Cl], [Emim][HSO4], [Bmim][HSO4], and [Hmim][HSO4], was conducted. Based on the logarithmic activity coefficient prediction at infinite dilution, there was a negative correlation between cellulose solubility and experimental NC yield obtained. [Hmim][HSO4] IL showed the highest nanocellulose yield (65%) due to a relatively weaker H-bonding ability with cellulose. Moreover, the multiparameter scale of the Kamlet-Taft of six ILs revealed that the increase in alkyl side chain length of the IL cation resulted in a decrease of hydrogen bonding acidity, which contributed to higher NC yield. The quantitative prediction of COSMO-RS, coupled with the experimental study, can therefore be utilized to screen, and classify the potential ILs to prepare nanocellulose.

Facile synthesis of hypercrosslinked polymer as high-efficiency adsorbent for the enrichment of nitroimidazoles from water, honey and chicken meat

Design and fabrication of functionalized hypercrosslinked polymers (HCPs) for enhancing their performance by using green renewable monomers has attracted considerable research interest. In this study, hydroxyl‑functional HCP (labeled as OHHCP) was prepared via the knitting method by applying natural naringenin as a monomer for the first time. Due to the good hydrophilicity and strong H-bonding ability, the OHHCP showed high extraction capacity for nitroimidazoles. Thus, it was successfully applied as a potent adsorbent for solid phase extraction of five nitroimidazoles in water, honey and chicken meat, followed by high-performance liquid chromatography-diode array detector analysis. At the optimized conditions, the limit of detections (S/N = 3) of the proposed method for water, honey and chicken samples were 0.02 - 0.06 ng mL−1, 0.5 - 1.0 ng g−1 and 0.8 - 1.0 ng g−1, respectively. The recoveries were 80.0 - 110%, and the relative standard deviations were below 10.0%. The OHHCP also displayed good application prospects for other organic compounds with H-bonding capability. This study highlights the facile preparation of OH-functionalized HCPs from renewable and natural resources as potent adsorbents for polar compounds.

Synergistic effect of nanoparticles and super absorbent polymer on self-healing ability of cement pastes

This paper analyzed the co-effects of super absorbent polymer (SAP) and nanomaterials such as silver nanoparticles (AgNPs), graphene oxide (GO) and multiwall carbon nanotubes (MWCNT) in cement pastes. While the SAP cement pastes provided a 25.23% higher 90/28-day compressive strength rate compared to the control sample, the MWCNT- and GO-added-SAP pastes provided a 37.84% and 74.77% higher rate, respectively. GO and MWCNTs increased the 90/28-day ultrasonic pulse velocity rates of SAP cement pastes by 1.25 and 1.38 times, respectively. The cracks initially formed by plastic shrinkage were completely closed with the H-bond ability of MWCNT and GO.

Gutmann's Donor and Acceptor Numbers for Ionic Liquids and Deep Eutectic Solvents.

An experimental and computational methodology for the analysis of the Lewis acid/base responses of ionic liquids (ILs) and deep eutectic solvents (DES) is proposed. It is based on the donor and acceptor of the electronic charge ability of Lewis acid and bases concepts (donicity and acceptor numbers, DN and AN, respectively) proposed by Viktor Gutmann. The binding enthalpy between the IL/DES with the probe antimony pentachloride (SbCl5) in dichloroethane displays good correlations with experimental data. This approach could serve as a first approximation to predict the responses to H-bonding abilities of new IL or DES. Although useful, the problems encountered to model the electron AN of these solvents limit the usefulness of the approach to completely describe their polarity properties. The experimental data were recorded using UV–Vis spectroscopy for a wide range of ILs and a couple of DES. Two reactions were used as benchmarks to test the reliability of the DN model to discuss the reactivity of real systems in these neoteric solvents.

(+)-Catharanthine potentiates the GABAA receptor by binding to a transmembrane site at the β(+)/α(-) interface near the TM2-TM3 loop

(+)-Catharanthine, a coronaridine congener, potentiates the γ-aminobutyric acid type A receptor (GABAAR) and induces sedation through a non-benzodiazepine mechanism, but the specific site of action and intrinsic mechanism have not beendefined. Here, we describe GABAAR subtype selectivity and location of the putative binding site for (+)-catharanthine using electrophysiological, site-directed mutagenesis, functional competition, and molecular docking experiments. Electrophysiological and in silico experiments showed that (+)-catharanthine potentiates the responses to low, subsaturating GABA at β2/3-containing GABAARs 2.4–3.5 times more efficaciously than at β1-containing GABAARs. The activity of (+)-catharanthine is reduced by the β2(N265S) mutation that decreases GABAAR potentiation by loreclezole, but not by the β3(M286C) or α1(Q241L) mutations that reduce receptor potentiation by R(+)-etomidate or neurosteroids, respectively. Competitive functional experiments indicated that the binding site for (+)-catharanthine overlaps that for loreclezole, but not those for R(+)-etomidate or potentiating neurosteroids. Molecular docking experiments suggested that (+)-catharanthine binds at the β(+)/α(-) intersubunit interface near the TM2-TM3 loop, where it forms H-bonds with β2-D282 (TM3), β2-K279 (TM2-TM3 loop), and β2-N265 and β2-R269 (TM2). Site-directed mutagenesis experiments supported the in silico results, demonstrating that the K279A and D282A substitutions, that lead to a loss of H-bonding ability of the mutated residue, and the N265S mutation, impair the gating efficacy of (+)-catharanthine. We infer that (+)-catharanthine potentiates the GABAAR through several H-bond interactions with a binding site located in the β(+)/α(-) interface in the transmembrane domain, near the TM2-TM3 loop, where it overlaps with loreclezole binding site.

Solvent-driven thiol protected luminescent cobalt nanoclusters

The choice of solvent in the wet chemical synthesis of metal nanoclusters plays a critical role in engineering the cluster size, stoichiometry composition, geometric configurations and activity via regulating the adsorption of thiol staple motifs over the core of these nanoclusters. Herein, we report a facile synthesis of thiophenol(TP) stabilized cobalt nanoclusters (CoNCs) in a DMSO medium by chemical reduction method. The significant impact of solvents over CoNCs was explored by altering the chemical environment of NCs with definite volume fractions of polar protic (Chloroform, Acetic acid) and aprotic (DMSO, Acetone) solvents. The tunable H-bonding ability of polar protic solvents with varying dipole moments induces changes in the physicochemical properties of CoNCs. On the other hand, the use of polar aprotic solvents influences the Co(II)-SR staple motifs to aggregate over CoNCs. The stability of CoNCs with aprotic solvent i.e., acetone was accompanied with etching, gives rise to the changes in the molecular composition leading to structure-property changes. The insights on solvent-dependent properties might be from the synergetic factors of hydrogen bonding and hydrophobic interactions between thiol and solvent molecules. The solvent-derived structure-property changes were confirmed using TEM, UV–visible absorption studies, XRD, FT-IR, Raman, MALDI-MS analysis, photoluminescence and lifetime decay studies. The PL emission peak of CoNCs in DMSO observed at 440 nm (blue emission) is red-shifted to 555 nm with greenish-yellow emission, while changing the environment with less polar aprotic acetone as a solvent. In the polar protic solvent environment, the crucial role of H-bonding interactions promotes the emission peak at 562 nm by activating a new emissive state along with 440 nm emission. The cytotoxicity examination of these CoNCs compounds on MCF-7 cells has indicated their biocompatibility and non-toxic property as an alternative agent for bioimaging and biolabeling for research aspects in in-vitro studies. This work addresses the impact of different polar solvent environments and their substantial dependency on the structure-property correlation of aromatic thiol stabilized cobalt nanoclusters and their applicability for cell imaging in biomedical research.

Newly identified C-H⋯O hydrogen bond in histidine.

New Cδ-H⋯O histidine hydrogen bonding interactions in various proteins are identified by neutron diffraction and computationally characterized. Neutron diffraction data shows several H-bond motifs with the Cδ-H moiety in histidine side chains, including interactions in β-sheets and with coordinated waters, mostly with histidinium and τ-tautomers. In yellow protein, an active site histidine H-bonds via Cδ-H to a main chain carbonyl while the Cε-H bond coordinates a water molecule. Although the H-bonding ability of Cε-H bonds in histidine have been previously identified, analysis of neutron diffraction structures reveals Cε-H H-bonds in notable active site interactions: for the proximal histidine in myoglobin; a zinc-bound histidine in human carbonic anhydrase II; within the Ser-Asp-His catalytic triad of the trypsin active site; and a histidine in the proton shuttle mechanism of RNase A, in addition to more general roles of coordinating water and forming H-bonds with carbonyl groups in β-sheets within a number of proteins. Properties of these H-bonds were computationally investigated using 5-methylimidazole and 5-methylimidazolium as models for histidine and histidinium. The π- and τ-tautomeric states of 5-methylimidazole were investigated, as both histidine tautomers are observed in the crystal structures. The newly characterized Cε-H⋯O and Cδ-H⋯O model complexes with water and acetone meet the overwhelming majority of IUPAC H-bonding criteria. 5-Methylimidazolium forms complexes that are nearly twice as strong as the respective neutral τ-5-methylimidazole and π-5-methylimidazole complexes. While the τ- and π-tautomers form Cε-H⋯O complexes of similar strength, the τ-Cδ-H⋯O interaction is approximately twice as strong as the π-Cδ-H⋯O interaction. Calculated charges on C-H (and N-H) hydrogens not participating in the H-bond are only slightly perturbed upon complex formation, implying that formation of one H-bond does not diminish the molecule's capacity for further H-bond formation at other sites in the imidazole ring. Overall, findings indicate that the Cδ-H⋯O interaction may be important for β-sheet stability, conformation, interactions with solvent, and mechanisms in the active site. Recognition of C-H bond polarity and hydrogen bonding ability in histidine may improve molecular modeling and provide further insight into the diverse roles of histidine in protein structure-function-dynamics.

Guanidinium solvents with exceptional hydrogen bond donating abilities.

Guanidinium chloride-based solvents have been prepared using deep eutectic solvent principles. Strong hydrogen-bond (H-bond) donating abilities are established based on a range of measures of solvent polarity, including a novel 31P NMR chemical shift method. The physical properties and origin of the strong H-bonding ability of these solvents have been explored.

Structural Characterization of 6-Thioguanosine and Its Monohydrate in the Gas Phase.

Detailed structural analysis of 6-thioguanosine (6TGs) in relation to its tautomerization and sugar conformation is performed in the gas phase using UV and IR spectroscopy combined with ab initio calculations. We have observed a thiol tautomer of 6TGs with its sugar moiety in the syn conformation that is stabilized by a strong intramolecular H-bonding between O5'H of the sugar and N3 atom of the guanine moiety. This observation is consistent with previous results for guanosine (Gs) in which the corresponding enol form is solely detected. We have also identified a monohydrate of 6TGs consisting of a thiol tautomer with the water linking guanine moiety and sugar OH group. It is demonstrated that hydration behavior of 6TGs is significantly different from that of Gs as a result of a weaker H-bonding ability of the thiol group.

Structural Diversity of Hydrogen-Bonded 4-Aryl-3,5-Dimethylpyrazoles for Supramolecular Materials.

The 1H-pyrazoles have high versatility and ability to form hydrogen-bonded supramolecular materials. In this study, the thermal stability, fluorescence, and H-bonding ability of the studied 3,5-dimethyl-4-(4-X-phenyl)-1H-pyrazoles showed large differences depending on the terminal substituent. Supramolecular structures were analyzed using X-ray diffraction and Hirshfeld surface calculations. Compounds were found to arrange in different hydrogen-bonded structures, depending on the substitution at the para position of the phenyl ring (X = OCH3, NO2, NH2). The methoxy-substituted compounds arranged in dimers through methanol bridges, the nitro-substituted compound formed supramolecular polymers or catemers, and the amino-substituted compound gave rise to a new structure based on a 2D hydrogen-bonded network.

Enhanced Hydrodynamic Radius of AOT/n-heptane/Water Reverse Micellar System Through Altered Electrostatic Interactions and Molecular Self-Assemblies.

We have demonstrated a unique approach to alter the aqueous pool size of an AOT/n-heptane/water reverse micellar system. A positively charged dye Rhodamine B (RhB) and negatively charged Rose Bengal (RB) were incorporated in the reverse micellar pool to investigate the effect of electrostatic interactions and stacking effects among the dye molecules on the AOT/n-heptane/water interface. Dynamic light scattering revealed increase in reverse micellar pool size in presence of positively charged dye aggregates at the oil-water interface. However, less expansion was observed in presence of negatively charged dye aggregates (RB). This confirms the role of electrostatic interaction in modulating the hydrodynamic radius. A head-to-tail type of stacking of RhB molecules at the interface favors this expansion. The differences in stacking of the two dyes inside the reverse micelles and their torsional mobility indicated the role of the reverse micellar interface and H-bonding ability of the microenvironment on dye aggregation. Conductivity measurements demonstrated a significant drop in percolation temperature of the reverse micellar system in presence of dye aggregates. This confirms the effect of dye aggregation and electrostatic interaction on such expansion. This strategy can be exploited for solubilizing greater amounts and a wider variety of drug molecules in microemulsions.

Mechanisms controlling wheat starch gelatinization and pasting behaviour in presence of sugars and sugar replacers: Role of hydrogen bonding and plasticizer molar volume

The effect of sugars and sugar replacers (i.e. plasticizers) on the gelatinization and pasting behaviour of wheat starch was studied. The intrinsic properties of the plasticizers, i.e. the molar volume density of effective hydroxyl groups NOH,s/vs, and the volumetric density of hydrogen bonds in the sugar solutions treated as a single solvent, i.e. Φw,eff, were proposed as factors controlling swelling (i.e. pasting) and gelatinization behaviour. Different classes of plasticizers were used including sugars, polyols, amino acids, soluble fibres such as oligofructoses, and mixtures thereof. The onset, peak and end temperature of starch gelatinization obtained by differential scanning calorimetry could be well described by Φw,eff for all solutions, following predictions from an adapted Flory-Huggins model for polymer melting. The multiple transitions involved in starch gelatinization could be well related to different ranges of Φw,eff following a side chain liquid crystalline model for starch. Deviations from the model predictions were observed mainly for Tonset in conditions of intermediate and excess solvent with high sugar concentrations (50% w/w). In such conditions phase separation likely occurs, increasing the effective starch concentration and consequently gelatinization temperatures. Pasting behaviour related to swelling, i.e. peak viscosity, was found to be a sigmoidal Fermi function of NOH,s/vs of the plasticizers. Plasticizers with high NOH,s/vs enhanced swelling compared to water while those with low NOH,s/vs had an inhibition effect. Overall, a comprehensive mechanism of starch plasticization, swelling and melting is proposed. Swelling associated with solvent ingress and helix-helix dissociation is affected by kinetic factors related to size and viscosity of the plasticizers (both described by NOH,s/vs) and by thermodynamic factors related to sugar partitioning and H-bonding ability (both related to Φw,eff). Melting of crystalline domains associated to helix-coil transition is controlled by thermodynamics, based on solvent H-bonding ability Φw,eff.

Tensile properties of structural I clathrate hydrates: Role of guest—host hydrogen bonding ability

Clathrate hydrates (CHs) are one of the most promising molecular structures in applications of gas capture and storage, and gas separations. Fundamental knowledge of mechanical characteristics of CHs is of crucial importance for assessing gas storage and separations at cold conditions, as well as understanding their stability and formation mechanisms. Here, the tensile mechanical properties of structural I CHs encapsulating a variety of guest species (CH4, NH3, H2S, CH2O, CH3OH, and CH3SH) that have different abilities to form hydrogen (H-) bonds with water molecule are explored by classical molecular dynamics (MD) simulations. All investigated CHs are structurally stable clathrate structures. Basic mechanical properties of CHs including tensile limit and Young’s modulus are dominated by the H-bonding ability of host-guest molecules and the guest molecular polarity. CHs containing small CH4, CH2O and H2S guest molecules that possess weak H-bonding ability are mechanically robust clathrate structures and mechanically destabilized via brittle failure on the (101) plane. However, those entrapping CH3SH, CH3OH, and NH3 that have strong H-bonding ability are mechanically weak molecular structures and mechanically destabilized through ductile failure as a result of gradual global dissociation of clathrate cages.

NMR quantification of H-bond donating ability for bioactive functional groups and isosteres.

The H-bond donating ability for 127 compounds including drug fragments and isosteres have been quantified using a simple and rapid method with 31P NMR spectroscopy. Functional groups important to medicinal chemistry were evaluated including carboxylic acids, alcohols, phenols, thioic acids and nitrogen group H-bond donors. 31P NMR shifts for binding to a phosphine oxide probe have a higher correlation with equilibrium constants for H-bonding (log KHA) than acidity (pKa), indicating that these binding experiments are representative of H-bonding ability and not proton transfer. Additionally, 31P NMR binding data for carboxylic acid isosteres correlates with physicochemical properties such as lipophilicity, membrane permeability and plasma protein binding. This method has been used to evaluate the H-bond donating ability of small molecule drug compounds such as NSAIDs and antimicrobials.