Small Guest Research Articles

An Examination of the Prediction of Hydrate Formation Conditions in the Presence of Thermodynamic Inhibitors

Abstract Gas hydrates are crystalline compounds, solid structures where water traps small guest molecules, typically light gases, in cages formed by hydrogen bonds. They are notorious for causing problems in oil and gas production, transportation and processing. Gas hydrates may form at pressures and temperatures commonly found in natural gas and oil production pipelines, thus causing partial or complete pipe blockages. In order to inhibit hydrate formation, chemicals such as alcohols (e.g., ethanol, methanol, mono-ethylene glycol) and salts (sodium, magnesium or potassium chloride) are injected into the produced stream. The purpose of this work is to briefly review the literature on hydrate formation in mixtures containing light gases (hydrocarbons and carbon dioxide) and water in the presence of thermodynamic inhibitors. Four calculation methods to predict hydrate formation in those systems were examined and compared. Three commercial packages (Multiflash®, PVTSim® and CSMGem) and a hydrate prediction routine in Fortran90 using the van der Waals and Platteeuw theory and the Peng-Robinson equation of state were tested. Predictions given by the four methods were compared to independent experimental data from the literature. In general, the four methods were found to be reasonably accurate. CSMGem and Multiflash® showed the best results.

A novel H-bonding self-assembly heteromeric molecular duplex bearing host and guest energy transfer units as high-performance electroluminescent material

Two oligoamide strands with complementary H-bonding sequences bearing 4HB-NIM and 4HB-CzNI were synthesized. 4HB-NIM and 4HB-CzNI could be self-assembled into a heterodimeric dyad (namely 4HB-NIM-CzNI)via quadruple H-bond interactions. Photoluminescence measurements revealed that in both dilute solution and doped film states, more efficient host-guest energy transfer processes could be observed in the duplex 4HB-NIM-CzNI than the physical blends of the small molecular guest reference compound NIM and the host single strand 4HB-CzNI, which should be attributed to the shortened spatial distances in 4HB-NIM-CzNI. In addition, in comparison with NIM and the guest single strand 4HB-NIM, 4HB-NIM-CzNI shows much higher photoluminescence quantum yield [0.53 vs 0.04 (NIM) or 0.35 (4HB-NIM)] in neat-film state, indicative of the more alleviated concentration quenching of the guest fluorophore in 4HB-NIM-CzNI than 4HB-NIM and NIM. As a consequence, an organic light-emitting diode (OLED) with 4HB-NIM-CzNI as the light-emitting dopant shows much more improved electroluminescent performance than its 4HB-NIM-based reference OLED: with lower turn-on voltage (5.0 vs 5.9 V), higher maximum luminance (5260 vs 2980 cd m−2) and current efficiency (3.5 vs 3.0 cd A−1) as well as lower efficiency roll-off. All these results indicated that the integration of both host and guest fluorophores into H-bonding self-assembled material should be an effective strategy to construct high performance supramolecular electroluminescent materials.

Trapping White Phosphorus within a Purely Organic Molecular Container Produced by Imine Condensation.

Three tetrahedral organic cages have been obtained by condensing a triamino linker with a set of three ostensibly analogous triformyl precursors. Despite the large number of imine bonds formed, the corresponding cages were obtained in exceptionally high yields. Both theory and experimental results demonstrate that intramolecular CH⋅⋅⋅π interactions within all of the cage frameworks play an important role in abetting the condensations and contributing to the near-quantitative synthetic yields. The three cages of this study exhibit high thermodynamic and kinetic stability. A variety of small neutral guest molecules with complementary sizes and geometries may be used as templates in the cage forming reactions. Among the guests that may be used in this way is white phosphorus (P4 ), whose inherent reactivity towards oxygen is almost fully attenuated when bound within one of the cages.

Trapping White Phosphorus within a Purely Organic Molecular Container Produced by Imine Condensation

AbstractThree tetrahedral organic cages have been obtained by condensing a triamino linker with a set of three ostensibly analogous triformyl precursors. Despite the large number of imine bonds formed, the corresponding cages were obtained in exceptionally high yields. Both theory and experimental results demonstrate that intramolecular CH⋅⋅⋅π interactions within all of the cage frameworks play an important role in abetting the condensations and contributing to the near‐quantitative synthetic yields. The three cages of this study exhibit high thermodynamic and kinetic stability. A variety of small neutral guest molecules with complementary sizes and geometries may be used as templates in the cage forming reactions. Among the guests that may be used in this way is white phosphorus (P4), whose inherent reactivity towards oxygen is almost fully attenuated when bound within one of the cages.

Systematic Study of the Effect of Lower-Rim Methylation on Small Guest Binding within the Host Cavity of Calix[4]arene.

The efficacy of calixarenes for the storage and/or detection of small guest molecules at the upper-rim is well-known. As part of our continuing efforts to investigate the ability to fine-tune the structure and hence host-guest binding characteristics of calixarenes, we present a systematic investigation of the effect of methylation of the lower-rim tetraphenolic pocket of calix[4]arene (C[4]) on binding at the upper-rim for a test-suite of guest molecules consisting of H2, O2, N2, H2O, CO2, NH3, H2S, N2O, HCN, and SO2. Results of the effects on the host-guest binding for all permutations of single, double, triple and quadruple methylations are presented. It was found that while a tetraphenolic C[4] host does not discriminate between many of the guest molecules in terms of binding energies, progressively methylated lower-rim C[4] hosts introduce differences in guest binding energies within the upper cavity to the extent where it may be possible to competitively bind one guest over another over a wide range of guests. In this regard, this family of methylated C[4] hosts show promise as gas separation devices.

Temperature responsive fluorescent polymer nanoparticles (TRFNPs) for cellular imaging and controlled releasing of drug to living cells

Recent studies have demonstrated that drug delivery by using functional nanomaterials with imaging capability could afford plenty of insightful information for the better control of the delivery process. In this work, we developed temperature responsive fluorescent nanoparticles (TRFNPs) for drug delivery and cellular imaging. The TRFNP was fabricated by one-pot co-precipitation of thermal sensitive amphiphilic block copolymers polystyrene-b-poly(N-isopropyl acrylamide) (PS-b-PNIPAM) and fluorescent conjugated polymer poly [(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(1,4-benzo(2,1′,3)-thiadiazole)] (PFBT) in the presence of desired small guest molecules. The dynamic light scattering (DLS) measurements verified that this functional nanoparticle exhibited temperature dependent size variation, which could therefore regulate the releasing rate of loaded guest molecules (e.g. drugs) inside the polymer core. Besides, the TRFNPs displayed good photostability in terms of optical characterization. The cellular cytotoxicity characterization demonstrated that this nanoparticle exhibited good biocompatibility even under the mass concentration of 10μg/mL. By using Nile Red as a model molecule, the temperature-controlled releasing process from TRFNPs in solution as well as inside living cells was monitored directly according to the spectroscopic and microscopic characterizations. Furthermore, anti-cancer drug was successfully delivered into living cells via TRFNPs and released in a temperature dependent manner. As a consequence, owing the attractive merits as mentioned above, this nanostructure would find broad applications in nanomedicine in the future.

BILP-19-An Ultramicroporous Organic Network with Exceptional Carbon Dioxide Uptake.

Porous benzimidazole-based polymers (BILPs) have proven to be promising for carbon dioxide capture and storage. The polarity of their chemical structure in combination with an inherent porosity allows for adsorbing large amounts of carbon dioxide in combination with high selectivities over unpolar guest molecules such as methane and nitrogen. For this reason, among purely organic polymers, BILPs contain some of the most effective networks to date. Nevertheless, they are still outperformed by competitive materials such as metal-organic frameworks (MOFs) or metal doped porous polymers. Here, we report the synthesis of BILP-19 and its exceptional carbon dioxide uptake of up to 6 mmol·g−1 at 273 K, making the network comparable to state-of-the-art materials. BILP-19 precipitates in a particulate structure with a strongly anisotropic growth into platelets, indicating a sheet-like structure for the network. It exhibits only a small microporous but a remarkable ultra-microporous surface area of 144 m2·g−1 and 1325 m2·g−1, respectively. We attribute the exceptional uptake of small guest molecules such as carbon dioxide and water to the distinct ultra-microporosity. Additionally, a pronounced hysteresis for both guests is observed, which in combination with the platelet character is probably caused by an expansion of the interparticle space, creating additional accessible ultra-microporous pore volume. For nitrogen and methane, this effect does not occur which explains their low affinity. In consequence, Henry selectivities of 123 for CO2/N2 at 298 K and 12 for CO2/CH4 at 273 K were determined. The network was carefully characterized with solid-state nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy, thermal gravimetry (TG) and elemental analyses as well as physisorption experiments with Ar, N2, CO2, CH4 and water.

Analytical techniques for characterizing cyclodextrins and their inclusion complexes with large and small molecular weight guest molecules

Cyclodextrins are oligosaccharides that have truncated cone like structures, making them capable of forming non-covalent bonds with a large variety of molecules (especially hydrophobic molecules). Additionally, as the outer rims of their truncated cones are lined with several hydroxyl groups, secondary interactions with and functionalization of these hydroxyl groups are also possible. Current techniques available to analyze and characterize these interactions, although somewhat limited, can be accomplished by judicious selection of analytical tools. However, for emerging applications, the currently utilized techniques summarized in this review may not be sufficient. The purpose of this review is to provide an overview, including their possible limitations, of current techniques commonly employed to investigate such interactions. In view of CD-based materials for emerging applications, wherever possible, analytical tools used for these studies are also discussed.

Flexible Force Field Parameterization through Fitting on the Ab Initio-Derived Elastic Tensor.

Constructing functional forms and their corresponding force field parameters for the metal–linker interface of metal–organic frameworks is challenging. We propose fitting these parameters on the elastic tensor, computed from ab initio density functional theory calculations. The advantage of this top-down approach is that it becomes evident if functional forms are missing when components of the elastic tensor are off. As a proof-of-concept, a new flexible force field for MIL-47(V) is derived. Negative thermal expansion is observed and framework flexibility has a negligible effect on adsorption and transport properties for small guest molecules. We believe that this force field parametrization approach can serve as a useful tool for developing accurate flexible force field models that capture the correct mechanical behavior of the full periodic structure.

Evaluating Force Field Performance in Thermodynamic Calculations of Cyclodextrin Host–Guest Binding: Water Models, Partial Charges, and Host Force Field Parameters

Computational prediction of noncovalent binding free energies with methods based on molecular mechanical force fields has become increasingly routine in drug discovery projects, where they promise to speed the discovery of small molecule ligands to bind targeted proteins with high affinity. Because the reliability of free energy methods still has significant room for improvement, new force fields, or modifications of existing ones, are regularly introduced with the aim of improving the accuracy of molecular simulations. However, comparatively little work has been done to systematically assess how well force fields perform, particularly in relation to the calculation of binding affinities. Hardware advances have made these calculations feasible, but comprehensive force field assessments for protein–ligand sized systems still remain costly. Here, we turn to cyclodextrin host–guest systems, which feature many hallmarks of protein–ligand binding interactions but are generally much more tractable due to their small size. We present absolute binding free energy and enthalpy calculations, using the attach-pull-release (APR) approach, on a set of 43 cyclodextrin-guest pairs for which experimental ITC data are available. The test set comprises both α- and β-cyclodextrin hosts binding a series of small organic guests, each with one of three functional groups: ammonium, alcohol, or carboxylate. Four water models are considered (TIP3P, TIP4Pew, SPC/E, and OPC), along with two partial charge assignment procedures (RESP and AM1-BCC) and two cyclodextrin host force fields. The results suggest a complex set of considerations when choosing a force field for biomolecular simulations. For example, some force field combinations clearly outperform others at the binding enthalpy calculations but not for the binding free energy. Additionally, a force field combination which we expected to be the worst performer gave the most accurate binding free energies – but the least accurate binding enthalpies. The results have implications for the development of improved force fields, and we propose this test set, and potential future elaborations of it, as a powerful validation suite to evaluate new force fields and help guide future force field development.

Using Predefined M3(μ3-O) Clusters as Building Blocks for an Isostructural Series of Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) have attracted much attention in the past decade owing to their unprecedented internal surface areas, tunable topologies, designable surfaces, and various potential applications. One bottleneck in the field regarding MOF synthesis is controlling the metal-containing secondary building unit (SBU) incorporated into the structure. In this work we report the synthesis and characterization of five trimeric [M3(μ3-O)(CH3CO2)6]x clusters (where M = Fe3+, Cr3+, Fe3+/Cr3+, Fe3+/Co2+, or Fe3+/Ni2+ and x = +1 or 0). The monocarboxylate capping ligand, acetate in this case, readily undergoes exchange with several difunctional counterparts, including 1,4-benzenedicarboxylic acid (H2-BDC) and biphenyl-4,4'-dicarboxylic acid (H2-BPDC), for the formation of an isostructural series of MOFs, several of which are newly reported (for M = Fe3+/Cr3+, Fe3+/Co2+, and Fe3+/Ni2+) and show excellent CO2 adsorption properties. In this report, a host of techniques including NMR, ICP, and ESI-MS are used to probe the ligand exchange process and composition of the SBUs, and XAS is used to monitor the Fe3+ and Cr3+ environment throughout the reactions, giving strong evidence that the clusters stay intact throughout the MOF synthesis. This work reveals that predefined SBUs is an effective means to create metal-substituted analogues of known frameworks. Further, CO adsorption and in situ IR are used to probe accessibility of the metals after solvent removal. We show for the first time that the incorporation of the neutral clusters, containing weaker Lewis acids like Ni2+ and Co2+, can promote the formation of open metal sites in the MOF frameworks, structural features known to enhance the binding energy of small guest molecules like CO2.

Synthesis of polyglycerol-citric acid nanoparticles as biocompatible vectors for biomedical applications

Citric acid and glycerol play an important role in the food and drug industries. In this work, we present for the first time a facile and gram scale method for the preparation of polyglycerol-citric acid nanoparticles (PGCN) in the presence of silica gel blue as both catalyst and water removal agent. PGCN are highly biocompatible without significant toxicity up to 1mg/ml. They are able to load small guest molecules and transfer them through the cell membrane, efficiently. Taking advantage of their straightforward synthesis and high biocompatibility as well as their ability to load and transfer small guest molecules, PGCN could be used for a variety of future biomedical applications.

NH3 as unique non-classical content-former within clathrate hydrates.

High quality FTIR spectra of aerosols of NH3-THF and NH3-TMO binary clathrate hydrates (CHs) have been measured. Our recently developed all-vapor sub-second approach to clathrate-hydrate formation combined with computational studies has been used to identify vibrational spectroscopic signatures of NH3 within the gas hydrates. The present study shows that there are three distinct NH3 types, namely, classical small-cage NH3, nonclassical small-cage NH3, and NH3 within the hydrate network. The network ammonia does not directly trigger the non-classical CH structure. Rather, the ammonia within the network structure perturbs the water bonding, introducing orientational defects that are stabilized by small and/or large cage guest molecules through H-bonding. This unusual behavior of NH3 within CHs opens a possibility for catalytic action of NH3 during CH-formation. Furthermore, impacts over time of the small-cage NH3-replacement molecules CO2 and CH4 on the structure and composition of the ternary CHs have been noted.

Inclusion Crystal Growth and Optical Properties of Organic Charge-transfer Complexes Built from Small Aromatic Guest Molecules and Naphthalenediimide Derivatives

Inclusion crystals were effectively formed from a simple naphthalenediimide derivative with toluene, 4-fluorotoluene, and p-xylene by the aid of cooperative intermolecular interactions, such as charge-transfer interactions and inclusion phenomena. The crystals showed intense guest-dependent solid-state emission based on ground state CT complexes between naphthalenediimide and small aromatic guests.

Thermodynamic Stability of Structure II Methyl Vinyl Ketone Binary Clathrate Hydrates and Effects of Secondary Guest Molecules on Large Guest Conformation.

Clathrate hydrates have received massive attention because of their potential application as energy storage materials. Host water frameworks of clathrate hydrates provide empty cavities that can capture not only small molecular guests but also radical species induced by γ-irradiation. In this work, we investigated structure II methyl vinyl ketone (MVK) binary clathrate hydrates with CH4, O2, and N2 and the effects of secondary guest species on MVK conformation in the cavity of hydrate and on the thermodynamic stability of unirradiated and γ-irradiated hydrate phases. The present findings provide meaningful information to understand the nature of guest–host interactions in γ-irradiated clathrate hydrates and to open up practical applications for hydrate-based nanoreactors.

Poly-cyclodextrin cryogels with aligned porous structure for removal of polycyclic aromatic hydrocarbons (PAHs) from water

Cyclodextrins (CDs) are sugar-based cyclic oligosaccharides, which form inclusion complexes with small guest molecules through their hydrophobic cavity. Here we successfully synthesized highly porous poly-cyclodextrin (poly-CD) cryogels, which were produced under cryogenic conditions by the cross-linking of amine-functional CDs with PEG-based diepoxide cross-linker. The poly-CD cryogels showed aligned porous network structures owing to the directional freezing of the matrix, of which the pore size and architecture exposed variations depending on the composition of the reactants. The cryogels were employed for the removal of genotoxic polycyclic aromatic hydrocarbons (PAHs) from aqueous solutions. They reached PAH sorption capacities as high as 1.25mg PAH per gram cryogel. This high sorption performance is due to interactions between PAHs and the complete swollen network, and thus, is not restricted by interfacial adsorption. Given that the hydrophilic nature of the components, the sorption performance could only be attributed to the inclusion complex formation of CDs with PAH molecules. The poly-CD cryogels could be recycled with an exposure to ethanol and reused without any significant loss in the sorption capacity of PAHs.

Modular Synthetic Approach for Adjusting the Disassembly Rates of Enzyme-Responsive Polymeric Micelles.

Self-assembled nanostructures and their stimuli-responsive degradation have been recently explored to meet the increasing need for advanced biocompatible and biodegradable materials for various biomedical applications. Incorporation of enzymes as triggers that can stimulate the degradation and disassembly of polymeric assemblies may be highly advantageous owing to their high selectivity and natural abundance in all living organisms. One of the key factors to consider when designing enzyme-responsive polymers is the ability to fine-tune the sensitivity of the platform toward its target enzyme in order to control the disassembly rate. In this work, a series of enzyme-responsive amphiphilic PEG-dendron hybrids with increasing number of hydrophobic cleavable end-groups was synthesized, characterized, and compared. These hybrids were shown to self-assemble in aqueous media into nanosized polymeric micelles, which could encapsulate small hydrophobic guests in their cores and release them upon enzymatic stimulus. Utilization of dendritic scaffolds as the responsive blocks granted ultimate control over the number of enzymatically cleavable end-groups. Remarkably, as we increased the number of end-groups, the micellar stability increased significantly and the range of enzymatic sensitivity spanned from highly responsive micelles to practically nondegradable ones. The reported results highlight the remarkable role of hydrophobicity in determining the micellar stability toward enzymatic degradation and its great sensitivity to small structural changes of the hydrophobic block, which govern the accessibility of the cleavable hydrophobic groups to the activating enzyme.

Stimuli‐Responsive Core Multishell Dendritic Nanocarriers

Multidomain polymeric nanoparticles containing different blocks with different properties have gained great interest for a wide range of applications in the past two decades. In this work, core multishell (CMS) structures consisting of hyperbranched polyglycerol as core and polylactide and polycaprolactone as shell structures are presented. Number of arms and thickness of shells have been manipulated by precise control over the molar ratios of monomer to terminal functional groups in the reaction feed. The ability of CMS to load and release small guest molecules and also the loading capacities are studied using Rose Bengal as a model dye. Loading capacity of CMS depends on molecular weight, type, and thickness of shells. Due to the difference in polarity and solubility of different blocks, the CMS nanocarriers show medium‐responsive behavior whereupon the encapsulated guest molecules are released in a controlled manner. image

Trapping of organophosphorus chemical nerve agents by pillar[5]arene: A DFT, AIM, NCI and EDA analysis

The encapsulation of organophosphorus (OP) nerve agents by pillar[5]arene (P5) molecule, shows that adsorption occurs with a larger structural reorganization of the host molecule. The computed binding energies shows that the complexes formed are more stable inside the cavity. Tabun was found to have the highest binding energy among the studied OPs. The computed Gibbs free energy is negative for Dimethyl methylphosphonate, sarin and tabun, and are positive for soman (GD) and ethyl-S-dimethylaminoethyl methylphosphonothiolate (VX). The inclusion complexes were found to have lower band gap. The quantum theory of Atoms-in-molecules analysis shows that ρ values were positive which implies the existence of noncovalent interactions. The Laplacian of the charge density ∇2ρ for bond critical points bonds are small and are negative which indicates the depletion of electronic charge along the bond paths and existence of an electrostatic nature of bonding between the guest and host molecule. The noncovalent interactions analysis clearly shows the existence of hydrogen bonding and van der Waals bonding in these inclusion complexes. The energy decomposition analysis shows that the, interaction between the P5 and the larger guest molecules VX and GD are mainly due to electrostatic interaction and for small guest, the interactions are mostly of van der Waals type.

Efficient removal of crystal violet and methylene blue from wastewater by ultrasound nanoparticles Cu-MOF in comparison with mechanosynthesis method

The present investigation reports the synthesis of CuBTC (BTC=1,3,5-benzenetricarboxylate) metal–organic frameworks (MOFs) under solid-state conditions and ultrasound irradiation. Herein, we study uptake and release properties of crystal violet (CV) and methylene blue (MB) from ultrasound nano-CuBTC MOF in comparison with mechanosynthesis method (bulk structure). The ultrasound-assisted methods give a decrease in the surface area as calculated from the reduced nitrogen adsorption capability. In comparison, the uptake of guest molecules on ultrasound nano-CuBTC is remarkable and clearly exceeds that of bulk structure in the aqueous solution of guests. In bulk compound the channel length is increased so that the amount of adsorption is decreased a little. The small guest enters and leaves the cavity rapidly, whereas larger guests enter slowly due to their size relative to the size of the gaps in the capsule. As a result, the uptake and release of MB from CuBTC is faster than that of CV.