Load–Collapse–Release Cascades of Amphiphilic Guest Molecules in Charged Dendronized Polymers through Spatial Separation of Noncovalent Forces

The ability to pack guest molecules into charged dendronized polymers (denpols) and the possibility to release these guest molecules from subsequently densely aggregated denpols in a load–collapse–release cascade is described. Charged denpols, which constitute molecular objects with a persistent, well‐defined envelope and interior, are capable of incorporating large amounts of amphiphilic guest molecules. Simultaneously, multivalent ions can coordinate to the surfaces of charged denpols, leading to counterion‐induced aggregation of the already guest‐loaded host structures. Thus, although the local guest concentration in denpol‐based molecular transport might already be initially high due to the dense guest packing inside the dendritic denpol scaffolding, the “local” guest concentration can nonetheless be further increased by packing (through aggregation) of the host–guest complexes themselves. Subsequent release of guest compounds from densely aggregated dendronized polymers is then possible (e.g., through increasing the solution concentration of imidazolium‐based ions). Augmented with this release possibility, the concept of twofold packing of guests, firstly through hosting itself and secondly through aggregation of the hosts, gives rise to a load–collapse–release cascade that strikingly displays the high potential of dendronized macromolecules for future molecular transport applications.     

Nanoporosity,Inclusion Chemistry,and Spin Crossover in Orthogonally Interlocked Two‐Dimensional Metal–Organic Frameworks

[Fe(tvp)₂(NCS)₂] ( 1 ) (tvp=trans‐(4,4′‐vinylenedipyridine)) consists of two independent perpendicular stacks of mutually interpenetrated two‐dimensional grids. This uncommon supramolecular conformation defines square‐sectional nanochannels (diagonal≈2.2 nm) in which inclusion molecules are located. The guest‐loaded framework 1@guest displays complete thermal spin‐crossover (SCO) behavior with the characteristic temperature T_1/2 dependent on the guest molecule, whereas the guest‐free species 1 is paramagnetic whatever the temperature. For the benzene–guest derivatives, the characteristic SCO temperature T_1/2 decreases as the Hammet σ_p parameter increases. In general, the 1@guest series shows large entropy variations associated with the SCO and conformational changes of the interpenetrated grids that leads to a crystallographic‐phase transition when the guest is benzonitrile or acetonitrile/H₂O.     

A Polyaromatic Gemini Amphiphile That Assembles into a Well‐Defined Aromatic Micelle with Higher Stability and Host Functions

A gemini‐type amphiphilic molecule, constituted of two V‐shaped polyaromatic amphiphiles linked by a linear acetylene spacer, was synthesized. The gemini amphiphile assembles into a well‐defined aromatic micelle (ca. 2 nm in core diameter), providing higher stability in water even at low concentration (0.09 mm ) and high temperature (>130 °C). Unlike common gemini amphiphiles with aliphatic chains, the present amphiphile and its micellar assembly emit green and orange fluorescence (Φ_F=33 and 9 %), respectively. Despite strong and multiple π‐stacks of the polyaromatic panels of the amphiphiles, the water‐soluble gemini aromatic micelle incorporates medium‐size to large hydrophobic compounds into the frameworks. Interestingly, the guest binding capability toward large planar molecules was enhanced by more than two times through the pre‐encapsulation of spherical molecules in the cavity.     

Orientational order of guest molecules in aligned liquid crystal as measured by EPR and UV–vis techniques

Orientational order of guest molecules in aligned liquid crystal 4-cyano-4′-pentylbiphenyl (5CB) is studied via optical dichroism and electron paramagnetic resonance (EPR) spectra measurements. The guest molecules used are bifunctional molecules bearing paramagnetic nitroxide group and photochromic azobenzene moiety. The bifunctional probe with rigidly bonded nitroxide and azobenzene moieties was found to align as a whole, while flexible long spacer between the moieties provides independent alignment for the nitroxide and azobenzene parts. Intermolecular interactions responsible for the alignment of azobenzene and nitroxide moieties of the probe molecules are discussed. The molecules with cis-configuration of azobenzene moiety are able to align in the liquid-crystalline medium, but to a lesser extent than the molecules with trans-configuration. Directions of orientational axes and characteristics of rotational mobility of spin probes are determined. Second, fourth and, in some cases, sixth rank order parameter values are found.     

Photoresponsive nanocarriers based on PAMAM dendrimers with a o‐nitrobenzyl shell

Gn (n = 3, 4, and 5) poly(amidoamine) (PAMAM) dendrimers were synthesized and peripherally modified with photocleavable o‐nitrobenzyl (NB) groups by reacting o‐nitrobenzaldehyde with the terminal amine groups of PAMAM dendrimers, followed by reducing the imine to amine groups with NaBH₄. The NB‐modified dendrimers, Gn‐NB (n = 3, 4, and 5), were characterized by nuclear magnetic resonance and fourier transform infrared spectroscopy. The results showed that the NB groups were successfully attached on the periphery of the dendrimers with near 100% grafting efficiency. Such a photosensitive NB shell could be cut off on irradiation with 365 nm ultraviolet (UV) light. The encapsulation and release of guest molecules, that is, salicylic acid (SA) and adriamycin (ADR), by Gn‐NB were explored. The encapsulation capability of these dendrimers was found to increase as the guest molecular size was decreased and have dependence on the generation of dendrimers as well. For both of SA and ADR, the average encapsulation numbers per dendrimer decreased in the order of G4‐NB > G5‐NB > G3‐NB, indicating that the fourth generation dendrimer was a better container for the guest molecules. The rate of SA release was found to be greater with UV irradiation than that without, suggesting that the NB‐shelled PAMMAM dendrimers could function as a molecular container/box with photoresponsive characteristics. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 551–557, 2010     

Clicked Isoreticular Metal–Organic Frameworks and Their High Performance in the Selective Capture and Separation of Large Organic Molecules

Three highly porous metal–organic frameworks (MOFs) with a uniform rht‐type topological network but hierarchical pores were successfully constructed by the assembly of triazole‐containing dendritic hexacarboxylate ligands with Zn^II ions. These transparent MOF crystals present gradually increasing pore sizes upon extension of the length of the organic backbone, as clearly identified by structural analysis and gas‐adsorption experiments. The inherent accessibility of the pores to large molecules endows these materials with unique properties for the uptake of large guest molecules. The visible selective adsorption of dye molecules makes these MOFs highly promising porous materials for pore‐size‐dependent large‐molecule capture and separation.     

Study of degradation behavior of besifloxacin,characterization of its degradation products by LC–ESI–QTOF–MS and their in silico toxicity prediction

Knowledge and understanding of the stability profile of a drug is important as it affects its safety and efficacy. In the present work, besifloxacin, a new, fourth‐generation fluoroquinolone antibiotic, was subjected to different forced‐degradation conditions as per International Conference on Harmonization (ICH) guidelines such as hydrolysis (acid, base and neutral), oxidation, thermal and photolysis. The drug degraded under acidic, basic, oxidative and photolytic conditions while it was found to be stable under dry heat and neutral hydrolytic conditions. In total, five degradation products (DPs) were formed under different conditions—DP1 and DP2 (photolysis), DP3 (oxidation), DP4 (acidic), DP3 and DP5 (basic). The chromatographic separation of besifloxacin and its degradation products was achieved on a Sunfire C₁₈ (250 mm × 4.6 mm, 5 μm) column with 0.1% aqueous formic acid–acetonitrile as a mobile phase. The gradient RP‐HPLC method was developed and validated as per ICH guidelines. The degradation products were characterized with the help of LC–ESI–QTOF mass spectrometric studies and the most likely degradation pathway of the drug was proposed. In silico toxicity assessment of the drug and its degradation products was carried out, which indicated that DP3 and DP4 carry a mutagenicity alert.     

Star‐Shaped Conjugated Molecules with Oxa‐ or Thiadiazole Bithiophene Side Arms

Star‐shaped conjugated molecules, consisting of a benzene central unit symmetrically trisubstituted with either oxa‐ or thiadiazole bithiophene groups, were synthesized as promising molecules and building blocks for application in (opto)electronics and electrochromic devices. Their optical (E_g(opt)) as well as electrochemical (E_g(electro)) band gaps depended on the type of the side arm and the number of solubilizing alkyl substituents. Oxadiazole derivatives showed E_g(opt) slightly below 3 eV and by 0.2 eV larger than those determined for thiadiazole‐based compounds. The presence of alkyl substituents in the arms additionally lowered the band gap. The obtained compounds were efficient electroluminophores in guest/host‐type light‐emitting diodes. They also showed a strong tendency to self‐organize in monolayers deposited on graphite, as evidenced by scanning tunneling microscopy. The structural studies by X‐ray scattering revealed the formation of supramolecular columnar stacks in which the molecules were organized. Differences in macroscopic alignment in the specimen indicated variations in the self‐assembly mechanism between the molecules. The compounds as trifunctional monomers were electrochemically polymerized to yield the corresponding polymer network. As shown by UV/Vis‐NIR spectroelectrochemical studies, these networks exhibited reversible electrochromic behavior both in the oxidation and in the reduction modes.     

PEO‐b‐PCL Block Copolymers: Synthesis,Detailed Characterization,and Selected Micellar Drug Encapsulation Behavior

Summary: A series of poly(ethylene glycol)‐block‐poly(ε‐caprolactone) diblock copolymers was synthesized and fully characterized. In particular, MALDI‐TOF MS results revealed interesting new insights into their molecular architecture. Small and defined micelles could be prepared from these block copolymers. Utilizing a high‐throughput screening approach, it was observed that these micelles are able to encapsulate/solubilize different guest molecules (e.g. drugs) depending on the solubility of the guest in water. Furthermore, it could be proven that a guest is located within a micelle and that these micelles can be utilized as transport vehicles for the encapsulated guest molecules.

PEO‐b‐PCL diblock copolymers can encapsulate small guest molecules in the core of the polymeric micelles.     

A highly porous metal-organic framework: structural transformations of a guest-free MOF depending on activation method and temperature

A doubly interpenetrating porous metal–organic framework ( SNU‐77 ) has been synthesized from the solvothermal reaction of the extended carboxylic acid tris(4′‐carboxybiphenyl)amine (H₃TCBPA) and Zn(NO₃)₂ ? 6H₂O in N,N‐dimethylacetamide (DMA). SNU‐77 undergoes single‐crystal‐to‐single‐crystal transformations during various activation processes, such as room‐temperature evacuation, supercritical CO₂ drying, and high temperature evacuation, to afford SNU‐77R , SNU‐77S , and SNU‐77H , respectively. These guest‐free MOFs exhibited different fine structures with different window shapes and different effective window sizes at room temperature. Variable‐temperature synchrotron single‐crystal X‐ray analyses reveal that the guest‐free structure is also affected by changes in temperature. Despite the different fine structures, SNU‐77R , SNU‐77S , and SNU‐77H show similar gas sorption properties due to the nonbreathing nature of the framework and an additional structural change upon cooling to cryogenic gas sorption temperature. SNU‐77H exhibits a large surface area (BET, 3670 m² g^?1), a large pore volume (1.52 cm³ g^?1), and exceptionally high uptake capacities for N₂, H₂, O₂, CO₂, and CH₄ gases.     

Distribution of Butane in the Host Water Cage of Structure II Clathrate Hydrates

To understand host–guest interactions of hydrocarbon clathrate hydrates, we investigated the crystal structure of simple and binary clathrate hydrates including butane (n‐C₄H₁₀ or iso‐C₄H₁₀) as the guest. Powder X‐ray diffraction (PXRD) analysis using the information on the conformation of C₄H₁₀ molecules obtained by molecular dynamics (MD) simulations was performed. It was shown that the guest n‐C₄H₁₀ molecule tends to change to the gauche conformation within host water cages. Any distortion of the large 5¹²6⁴ cage and empty 5¹² cage for the simple iso‐C₄H₁₀ hydrate was not detected, and it was revealed that dynamic disorder of iso‐C₄H₁₀ and gauche‐nC₄H₁₀ were spherically extended within the large 5¹²6⁴ cages. It was indicated that structural isomers of hydrocarbon molecules with different van der Waals diameters are enclathrated within water cages in the same way owing to conformational change and dynamic disorder of the molecules. Furthermore, these results show that the method reported herein is applicable to structure analysis of other host–guest materials including guest molecules that could change molecular conformations.     

Remarkably stable amphiphilic random copolymer assemblies: A structure–property relationship study

Synthesis of a library of amphiphilic random copolymers from a single reactive pre‐polymer and their self‐assembly is reported. Post‐polymerization modifications of the parent polymer containing pendant N‐hydroxy succinimide (NHS) ester groups with various oligooxyethylene (OE) amines produce amphiphilic random copolymers with same degree of polymerization and equal extent of randomness. ¹H‐NMR and FT‐IR data indicate quantitative substitution in all cases. The critical aggregation concentration (CAC) for all the polymers is estimated to be in the range of 10^?5 M. Stability of these nano‐aggregates is studied by photoluminescence using time dependent F—rster Resonance Energy Transfer (FRET) between co‐encapsulated lipophilic dyes namely DiO and DiI in the hydrophobic pocket of the aggregates. These studies suggest remarkably high stability for all systems. However those with shorter hydrophilic pendant chains are found to be even more robust. Morphology is examined by high resolution transmission electron microscopy (HRTEM) which reveals multi‐micellar clusters and vesicles for polymers containing short and longer OE segments, respectively. Encapsulation efficacy is tested with both hydrophobic and hydrophilic guest molecules. All of them can encapsulate hydrophobic guest pyrene while a hydrophilic dye Calcein can be sequestered only in vesicle forming polymers. Lower critical solution temperature (LCST) is exhibited by only one polymer that contains the shortest OE chains. All polymers exhibit excellent cell viability as determined by MTT assay. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4932–4943     

Two-Dimensional Polymer Networks Locking on Inorganic Nanoparticles

Two-dimensional polymers (2DPs), single-layer networks of covalently linked monomers, show perspectives as membranes and in electronics. However, 2D polymerization of monomers in orthogonal directions limited the formation of 2DPs on nanoparticles (NPs) with high surface curvatures. Here we propose a high-curvature 2D polymerization to form a single-layer 2DP network as a non-contacting ligand on the surface of NPs for their stabilization and functionalization. The high-curvature 2D polymerization of amphiphilic Gemini monomers was conducted in situ on surfaces of NPs with various sizes, shapes, and materials, forming highly cross-linked 2DPs. Selective etching of core–shell NPs led to 2DPs as a non-contact ligand of yolk-shell structures with excellent shape retention and high NP-surface accessibility. In addition, by copolymerization, the 2DP ligands can covalently link to other functional molecules. This work promotes the development of 2DPs on NPs for their functional modification.     

Amphiphilic Block‐Graft Copolymers Poly(ethylene glycol)‐b‐(polycarbonates‐g‐palmitate) Prepared via the Combination of Ring‐Opening Polymerization and Click Chemistry

Amphiphilic block‐graft copolymers mPEG‐b‐P(DTC‐ADTC‐g‐Pal) were synthesized by ring‐opening polymerization of 2,2‐dimethyltrimethylene carbonate (DTC) and 2,2‐bis(azidomethyl)trimethylene carbonate (ADTC) with poly(ethylene glycol) monomethyl ether (mPEG) as an initiator, followed by the click reaction of propargyl palmitate and the pendant azido groups on the polymer chains. Stable micelle solutions of the amphiphilic block‐graft copolymers could be prepared by adding water to a THF solution of the polymer followed by the removal of the organic solvent by dialysis. Dynamic light scattering measurements showed that the micelles had a narrow size distribution. Transmission electron microscopy images displayed that the micelles were in spherical shape. The grafted structure could enhance the interaction of polymer chains with drug molecules and improve the drug‐loading capacity and entrapment efficiency. Further, the amphiphilic block‐graft copolymers mPEG‐b‐P(DTC‐ADTC‐g‐Pal) were low cytotoxic and had more sustained drug release behavior. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Constructing novel double‐bond‐containing well‐defined amphiphilic graft copolymers via successive Ni‐catalyzed living coordination polymerization and SET‐LRP

A series of polyallene‐based well‐defined amphiphilic graft copolymers, poly(6‐methyl‐1,2‐heptadiene‐4‐ol)‐g‐poly(2‐(diethylamino)ethyl methacrylate) (PMHDO‐g‐PDEAEMA), was synthesized through the grafting‐from technique. First, double‐bond‐containing PMHDO backbone bearing pendant hydroxyls was prepared via [(η³‐allyl)NiOCOCF₃]₂‐initiated living coordination polymerization of 6‐methyl‐1,2‐heptadiene‐4‐ol (MHDO). The pendant hydroxyls in the homopolymer were then reacted with 2‐chloropropionyl chloride to give PMHDO‐Cl macroinitiator. Finally, hydrophilic PDEAEMA side chains were formed by single electron transfer‐living radical polymerization (SET‐LRP) of 2‐(diethylamino)ethyl methacrylate (DEAEMA) in THF/H₂O initiated by the macroinitiator using CuCl/Me₆TREN as catalytic system to afford PMHDO‐g‐PDEAEMA graft copolymers. The narrow molecular weight distributions (M_w/M_n ≤ 1.35) and kinetics experiment showed the controllability of SET‐LRP graft copolymerization of DEAEMA. The critical micelle concentration (cmc) of PMHDO‐g‐PDEAEMA amphiphilic graft copolymer in aqueous media was determined by fluorescence probe technique and the relationships between cmc and pH or salinity were also investigated. Micellar morphologies were preliminarily explored using transmission electron microscopy. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

The structural and dynamic properties of 1‐bromodecane in urea inclusion compounds investigated by solid‐state 1H, 13C and 2H NMR spectroscopy

For asymmetric guest molecules in urea, the end‐groups of two adjacent guest molecules may arrange in three different ways: head–head, head–tail and tail–tail. Solid‐state ¹H and ¹³C NMR spectroscopy is used to study the structural properties of 1‐bromodecane in urea. It is found that the end groups of the guest molecules are randomly arranged. The dynamic characteristics of 1‐bromodecane in urea inclusion compounds are probed by variable‐temperature solid‐state ²H NMR spectroscopy (line shapes, spin–spin relaxation: T₂, spin‐lattice relaxation: T_1Z and T_1Q) between 120 K and room temperature. The comparison between the simulation and experimental data shows that the dynamic properties of the guest molecules can be described in a quantitative way using a non‐degenerate three‐site jump process in the low‐temperature phase and a degenerate three‐site jump in the high‐temperature phase, in combination with the small‐angle wobbling motion. The kinetic parameters can be derived from the simulation. Copyright © 2011 John Wiley & Sons, Ltd.     

Amphiphilic Inclusion Spaces for Various Guests and Regulation of Fluorescence Intensity of 1,8‐Bis(4‐aminophenyl)anthracene Crystals

A host framework for inclusion of various guest molecules was investigated by preparation of inclusion crystals of 1,8‐bis(4‐aminophenyl)anthracene (1,8‐BAPA) with organic solvents. X‐ray crystallographic analysis revealed construction of the same inclusion space incorporating 1,8‐BAPA and eight guest molecules including both non‐polar (benzene) and polar guests (N,N‐dimethylformamide, DMF). Fluorescence efficiencies varied depending on guest molecule polarity; DMF inclusion crystals exhibited the highest fluorescence intensity (Φ_F=0.40), four times as high as that of a benzene inclusion crystal (Φ_F=0.10). According to systematic investigations of inclusion phenomena, strong host–guest interactions and filling of the inclusion space led to a high fluorescence intensity. Temperature‐dependent fluorescence spectral measurements revealed these factors effectively immobilised the host framework. Although hydrogen bonding commonly decreases fluorescence intensity, the present study demonstrated that such strong interactions provide excellent conditions for fluorescence enhancement. Thus, this remarkable behaviour has potential application toward sensing of highly polar molecules, such as biogenic compounds.     

Preparation of amphiphilic diblock copolymers with pendant hydrophilic phosphorylcholine and hydrophobic dendron groups and their self‐association behavior in water

Generation 3.5 poly(amido amine) dendron (G3.5) with 16 n‐butyl terminal groups containing an acrylamide monomer (AaUG3.5) was prepared by condensation between an amino focal group in G3.5 and 11‐acrylamidoundecanoic acid. AaUG3.5 was polymerized using poly(2‐methacryloyloxyethyl phosphorylcholine) (pMPC)‐based macro‐chain transfer agent via reversible addition‐fragmentation chain transfer (RAFT) radical polymerization to obtain amphiphilic diblock copolymers with different compositions. The diblock copolymers (P_mD_n) were composed of a hydrophilic pMPC block and hydrophobic pendant dendron‐bearing block, where P and D represent pMPC and pAaUG3.5, respectively, and m and n represent the degree of polymerization for each block, respectively. P₂₉₆D₁ and P₉₈D₃ formed vesicles and large compound micelles and vesicles, respectively, which was confirmed by light scattering measurements and transmission electron microscopic (TEM) observations. The large compound micelles formed from P₉₈D₃ could not incorporate hydrophilic guest polymer molecules, because the aggregates did not have a hydrophilic hollow core. In contrast, the vesicles formed from P₂₆₉D₁ could incorporate hydrophilic guest polymer molecules into the hollow core. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4923–4931     

Effect of Guest–Host Hydrogen Bonding on the Structures and Properties of Clathrate Hydrates

To provide improved understanding of guest–host interactions in clathrate hydrates, we present some correlations between guest chemical structures and observations on the corresponding hydrate properties. From these correlations it is clear that directional interactions such as hydrogen bonding between guest and host are likely, although these have been ignored to greater or lesser degrees because there has been no direct structural evidence for such interactions. For the first time, single‐crystal X‐ray crystallography has been used to detect guest–host hydrogen bonding in structure II (sII) and structure H (sH) clathrate hydrates. The clathrates studied are the tert‐butylamine (tBA) sII clathrate with H₂S/Xe help gases and the pinacolone + H₂S binary sH clathrate. X‐ray structural analysis shows that the tBA nitrogen atom lies at a distance of 2.64 Å from the closest clathrate hydrate water oxygen atom, whereas the pinacolone oxygen atom is determined to lie at a distance of 2.96 Å from the closest water oxygen atom. These distances are compatible with guest–water hydrogen bonding. Results of molecular dynamics simulations on these systems are consistent with the X‐ray crystallographic observations. The tBA guest shows long‐lived guest–host hydrogen bonding with the nitrogen atom tethered to a water HO group that rotates towards the cage center to face the guest nitrogen atom. Pinacolone forms thermally activated guest–host hydrogen bonds with the lattice water molecules; these have been studied for temperatures in the range of 100–250 K. Guest–host hydrogen bonding leads to the formation of Bjerrum L‐defects in the clathrate water lattice between two adjacent water molecules, and these are implicated in the stabilities of the hydrate lattices, the water dynamics, and the dielectric properties. The reported stable hydrogen‐bonded guest–host structures also tend to blur the longstanding distinction between true clathrates and semiclathrates.     

Ultrasound‐Driven Secondary Self‐Assembly of Amphiphilic β‐Cyclodextrin Dimers

The controlled secondary self‐assembly of amphiphilic molecules in solution is theoretically and practically significant in amphiphilic molecular applications. An amphiphilic β‐cyclodextrin (β‐CD) dimer, namely LA‐(CD)₂, has been synthesized, wherein one lithocholic acid (LA) unit is hydrophobic and two β‐CD units are hydrophilic. In an aqueous solution at room temperature, LA‐(CD)₂ self‐assembles into spherical micelles without ultrasonication. The primary micelles dissociates and then secondarily form self‐assemblies with branched structures under ultrasonication. The branched aggregates revert to primary micelles at high temperature. The ultrasound‐driven secondary self‐assembly is confirmed by transmission electron microscopy, dynamic light scattering, ¹H NMR spectroscopy, and Cu²⁺‐responsive experiments. Furthermore, 2D NOESY NMR and UV/Vis spectroscopy results indicate that the formation of the primary micelles is driven by hydrophilic–hydrophobic interactions, whereas host–guest interactions promote the formation of the secondary assemblies. Additionally, ultrasonication is shown to be able to effectively destroy the primary hydrophilic–hydrophobic balances while enhancing the host–guest interaction between the LA and β‐CD moieties at room temperature.