Size‐Tunable Micron‐Bubbles Based on Fluorous–Fluorous Interactions of Perfluorinated Dendritic Polyglycerols

This paper describes the behavior of various generations of polyglycerol dendrimers that contain a perfluorinated shell. The aggregation in organic solvents is based on supramolecular fluorous–fluorous interactions, which can be described by means of ¹⁹F NMR spectroscopy. In order to study the interaction and aggregation phenomena of dendrimers with perfluorinated shell and perfluoro‐tagged guest molecules we investigated [G3.5]‐dendrimer with a perfluorinated shell in the presence of perfluoro‐tagged disperse red. Noteworthy, the interaction intensities varied in an unexpected manner depending on the equivalents of perfluoro‐tagged guest molecules added to the dendrimers in solution which then formed supramolecular complexes based on fluorous–fluorous interactions. We found that these complexes aggregated around residual air in the solvent to form stable micron‐sized bubbles. Their sizes correlated with the interaction intensities measured for certain dendrimer–guest molecule ratios. Degassing of the solutions led to a quasi phase separation between organic and fluorous phase, whereby the dendrimers formed the fluorous phases. Regassing the sample with air afforded bubbles of the initial size again.     

Water-soluble pH-responsive dendritic core-shell nanocarriers for polar dyes based on poly(ethylene imine)

A simple general synthetic concept to build dendritic core-shell architectures with pH-labile linkers based on hyperbranched PEI cores and biocompatible PEG shells is presented. Using these dendritic core-shell architectures as nanocarriers, the encapsulation and transport of polar dyes of different sizes is studied. The results show that the acid-labile nanocarriers exhibit much higher transport capacities for dyes than unfunctionalized hyperbranched PEI. The cleavage of imine bonds and controlled release of the polar dyes revealed that weak acidic condition (pH approximately 5.0) could cleave the imine bonds linker and release the dyes up to five times faster than neutral conditions (pH = 7.4).     

Hyperbranched‐upon‐dendritic macromolecules as unimolecular hosts for controlled release

Novel amphiphilic hyperbranched‐upon‐dendritic polymers with a dendritic polyester core, a linear poly(ε‐caprolactone) (PCL) inner shell, and a hyperbranched polyglycerol outer shell have been prepared. The structures of the hyperbranched‐upon‐dendritic polymers were characterized by using NMR spectra. The critical aggregating concentrations (CACs) of those amphiphilic hyperbranched‐upon‐dendritic polymers were measured by using pyrene as the polarity probe. To study the encapsulation performances of those hyperbranched‐upon‐dendritic polymers as unimolecular hosts, inter‐molecular encapsulation was carefully prevented by controlling the host concentrations below their CACs and by washing with good organic solvents. The study on encapsulation of two model guest molecules, pyrene and indomethacin, was performed. The amounts of encapsulated molecules were dependent mainly on the size of inner linear shells. About three pyrene molecules or five indomethacin molecules were encapsulated in hyperbranched‐upon‐dendritic polymers with average PCL repeating units of two but different hyperbranched polyglycerol outer shells, whereas about five pyrene molecules or about 12 indomethacin molecules were encapsulated in those with PCL repeating units of nine. The encapsulated molecules could be released in a controlled manner. Thus, the hyperbranched‐upon‐dendritic polymers could be used as unimolecular nanocarriers with controllable molecular encapsulation dosage for controlled release. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 4013–4019, 2010     

Beta-alanine-based dendritic beta-peptides: dendrimers possessing unusually strong binding ability towards protic solvents and their self-assembly into nanoscale aggregates through hydrogen-bond interactions

A series of poly(beta-alanine) dendrimers 1-4 with Boc-carbamate as the surface functionality, beta-alanine as the dendritic branch, 3,5-diaminobenzoic acid as the branching agent, and 1,2diaminoethane as the interior core has been synthesized by a solution-phase peptide-coupling method. The structural identities and purities of the products have been fully characterized by spectroscopic and chromatographic methods. 1H NMR studies on the dendrimers indicated that the Boc-carbamate surface groups exist as a mixture of syn and anti rotamers in solution, and that the dendrimers adopt an open structure in polar solvents; this allows the free interaction of the interior core functionality with solvent molecules. Due to the cooperative effect of a large number of carbamate and amide groups, the dendrimers exhibit an unusually strong binding ability towards protic solvents and behave as H-bond sponges. As a result, the H/D exchange rates of the N-H protons are significantly enhanced in such dendritic structures, as compared to those of nondendritic carbamates and amides. These dendritic peptide dendrimers also exhibit a strong tendency to form nanoscopic aggregates in nonpolar or polar aprotic solvents through intermolecular H-bond interactions.     

Synthesis of carbosilane dendritic wedges and their use for the construction of dendritic receptors

A divergent route for the synthesis of carbosilane wedges that contain either a bromine or amine as focal point has been developed. These new building blocks enable the construction of various core-functionalized carbosilane dendrimers. As a typical example carbosilane dendrimers up to the third generation containing a N,N',N'-1,3,5-benzenetricarboxamide core (G1-G3) have been synthesized. This new class of molecules has been studied as host molecules and they have been found to bind protected amino acids as guest molecules via hydrogen bonding interactions. A decrease in the association constants was observed for the higher generation dendritic hosts, which is attributed to the increased steric hindrance around the core where the binding site is located. The binding properties of the dendritic host molecules can be tuned by modifying the binding motif at the core of the carbosilane dendrimers. A higher association constant for N-CBZ-protected glutamic acid 1-methyl ester (5) was observed when the third generation N,N',N'-1,3,5-tris(L-alaninyl)benzenetricarboxamide core-functionalized carbosilane dendrimer (G3') was used as the host molecule compared to G3. Different association constants for the formation of the diastereomeric G3'.L-5(K=295 M(-1)) and G3'.(D-5)(2) (K=236 M(-1)) host-guest complexes were observed, pointing to a small enantioselective recognition effect. The difference between the association constants for the formation of the G3'.(L-5)(2) and G3'.(D-5)(2) host-guest complexes was much more pronounced, K=37 M(-1)versus K=10 M(-1), respectively.     

Synthesis and properties of new thiourea-functionalized poly(propylene imine) dendrimers and their role as hosts for urea functionalized guests

Five generations of poly(propylene imine) dendrimers have been modified by palmityl and adamantyl endgroups via a thiourea linkage. The synthesis of the thiourea dendrimers DAB-dendr-(NHCSNHAd)(n) and DAB-dendr-(NHCSNHC(16)H(33))(n) (n = 4, 8, 16, 32, 64) proceeds smoothly via the amino-terminated DAB dendrimer and the adamantyl and palmityl isothiocyanates, respectively. The properties of the thiourea dendrimers have been studied by IR and (1)H NMR, including relaxation (T1, T2) measurements. The thiourea dendrimers are used as multivalent hosts for a number of guest molecules containing a terminal urea-glycine unit in organic solvents. The host-guest interactions have been investigated using 1D- and NOESY-NMR. These investigations show that the guest molecules bind to the dendritic host via thiourea (host)-urea (guest) hydrogen bonding, and ionic bonding between the terminal guest carboxylate moiety and the outer shell tertiary amines of the dendrimer. The ability to bind guest molecules of the adamantyl- and palmitylthiourea dendrimers has been compared with their respective urea containing dendrimer analogues, by NMR-titration, and competition experiments. Upon complexation, the thiourea dendrimer hosts show a larger downfield NH shift than the corresponding urea dendrimer hosts, indicative of stronger hydrogen bonding in the complexed state. Furthermore, microcalorimetry has been used to determine binding constants for formation of the host-guest complexes; the binding constants are typically in the order of 10(4) M(-1). Both NMR and microcalorimetric studies show that the thiourea dendrimers bind the urea containing guests with somewhat higher affinity than the corresponding urea dendrimers.     

Multiarm star nanocarriers containing a poly(ethylene imine) core and polylactide arms

Star polymers (SPs) containing a hyperbranched poly(ethylene imine) (PEI; number‐average molecular weight = 10,000) core and polylactide arms were synthesized via the ring‐opening polymerization of lactide. PEI was used as a multifunctional macroinitiator for the ring‐opening polymerization of lactide. Different lactide monomer/amino‐functional group (LA/NH_n; n = 1 or 2) ratios were used for preparing SPs with different molecular weights. SPs were able to encapsulate small guest molecules such as Rose Bengal; they also transported small, hydrophilic molecules from water to the organic phase. The transport capacity of all the nanocarriers depended on the LA/NH_n ratio used for synthesizing the SPs. Nanocarriers with a higher LA/NH_n ratio had higher transport capacities. The size of all the nanocarriers depended on the type of solvent. In chloroform, these nanoparticles had several sizes that were related to the self‐assembly of these nanocarriers, but in acetone, they were monodisperse, and their size was smaller than that in chloroform. Also, the transport of polar dyes from water to the chloroform phase was possible. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5740–5749, 2006     

氟两相催化反应的进展

对氟两相催化反应作一介绍。氟两相体系是一种新的相分离和固定化技术,全氟溶剂与大多数有机溶剂不互溶,而在催化剂分子中引入适当数量、大小和形状的氟尾能使之优先溶于全氟溶剂,在氟两相体系中进行催化反应就使催化剂的回收再用产物的纯化都变得极为方便。     

Polycationic (mixed) core-shell dendrimers for binding and delivery of inorganic/organic substrates

The convergent synthesis of a series of polycationic aryl ether dendrimers has been accomplished by a convenient procedure involving quantitative quaternarization of aryl(poly)amine core molecules. The series has been expanded to the preparation of the first polycationic, mixed core-shell dendrimer. All these dendrimers consist of an apolar core with a peripheral ionic layer which is surrounded by a less polar layer of dendritic wedges. These cationic, macromolecular species have been investigated for their ability to form assemblies with (anionic) guest molecules. The results obtained from UV/Vis and NMR spectroscopies, and MALDI-TOF-MS demonstrate that all the cationic sites throughout the dendrimer core are involved in ion pair formation with anionic guests giving predefined guest/host ratios up to 24. The large NMR spectroscopic shifts of resonances correlated with the groupings located in the core of the dendrimers, together with the relaxation time data indicate that the anionic guests are associated with the cationic core of these dendrimers. The X-ray molecular structure of the octacationic, tetra-arylsilane model derivative [Si(C6H3[CH2NMe3](2)-3,5)4]8+. 8I- shows that the iodide counterions are primarily located near the polycationic sphere. The new polycationic dendrimers have been investigated for their catalytic phase-transfer behavior and substrate delivery over a nanofiltration membrane.     

Using a Multi‐Shelled Hollow Metal–Organic Framework as a Host to Switch the Guest‐to‐Host and Guest‐to‐Guest Interactions

A bio‐inspired design of using metal–organic framework (MOF) microcrystals with well‐defined multi‐shelled hollow structures was used as a matrix to host multiple guests including molecules and nanoparticles at separated locations to form a hierarchical material, mimicking biological structures. The interactions such as energy transfer (ET) between different guests are regulated by precisely fixing them in the MOF shells or encapsulating them in the cavities between the MOF shells. The proof‐of‐concept design is demonstrated by hosting chromophore molecules including rhodamine 6G (R6G) and 7‐amino‐4‐(trifluoromethyl)coumarin (C‐151), as well as metal nanoparticles (Pd NPs) into the multi‐shelled hollow zeolitic imidazolate framework‐8 (ZIF‐8). We could selectively establish or diminish the guest‐to‐framework and guest‐to‐guest ET. This work provides a platform to construct complex multifunctional materials, especially those need precise separation control of multi‐components.     

Disassembly via an environmentally friendly and efficient fluorous phase constructed with dendritic architectures

Traditionally the fluorous phase is generated with perfluorinated alkyl groups that are usually perfluorooctyl or longer and are bioaccummulative and biopersistent and therefore, are considered environmentally unfriendly. Here we report a new concept for the construction of the fluorous phase. This concept is based on the amplification of the fluorous effect with the help of dendritic architectures containing very short semifluorinated groups on their periphery. This new concept was demonstrated by the convergent synthesis of the first and second generation AB₃ and AB₂ benzyl ether dendrons functionalized on their periphery via catalytic nucleophilic addition of their phenolates to perfluoropropyl vinyl ether. The resulting dendrons are liquids. Their fluorous phase affinity was analyzed and demonstrated that the dendritic architecture amplifies the fluorous phase at a specific generation by the number of functional groups on the dendron periphery, and at different generations by increasing their generation number. Therefore, this concept is very efficient for the design and synthesis of new fluorous materials. In addition, by contrast with dendrons containing perfluoroalkyl groups on their periphery, the current dendrons mediate the disassembly of their parent building blocks but do not mediate the self‐assembly in a supramolecular architecture. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2498–2508, 2010     

Structure and conformation of DAB dendrimers in solution via multidimensional NMR techniques.

NOESY-HSQC 3D-NMR and NOESY 2D-NMR techniques have been used on a 750 MHz spectrometer to study the chain conformations of different generation DAB dendrimers (poly[propylene imine] dendrimers) in chloroform and benzene solutions. The high-field multidimensional NMR techniques provided the chemical shift dispersion needed to resolve all of the unique resonances in the dendrimers. By studying the NOE interactions among dendritic chain protons, information about through space interactions between protons on different parts of the dendrimer chain is obtained, which is directly related to the conformation of the dendrimer. These experiments also give further proof of the chemical shift assignments obtained from the HMQC-TOCSY 2D and 3D NMR experiments. The concentration effects on chemical shifts have also been observed, revealing information about the interactions between solvent and different parts of dendrimer molecules. These studies clearly show for DAB dendrimers, that folded chain conformations can occur in nonpolar solvents such as benzene and extended chain conformations are predominant in polar solvents such as chloroform.     

Oligosaccharide Shells as a Decisive Factor for Moderate and Strong Ionic Interactions of Dendritic Poly(ethylene imine) Scaffolds under Shear Forces

For better understanding and improving the non‐covalent interactions of dendritic core–shell, we evaluated the interactions of hyperbranched poly(ethylene imine) (PEI) decorated with various oligosaccharide shells with water‐soluble B vitamins, an estradiol derivative and pantoprazole. Depending on the different properties of the analyte molecules, dendritic core–shell glyco architectures showed (very) weak, moderate and strong interactions with the analyte molecules. Thus, ionic interactions are the strongest driving force for the formation of host–guest complexes. The core–shell glyco architecture is a necessary prerequisite for stable analyte/PEI complexes; the pure hyperbranched PEI did not show any sufficiently strong interactions with neutral, cationic or anionic analytes under the shear forces applied during ultrafiltration of pure aqueous solution without an adjusted pH. Thus, only robust non‐covalent interactions between analytes and the dendritic polyamine scaffold of the glycopolymer structure survive this separation step and allow isolation of stable host–guest complexes in aqueous solution.     

Selective peptide binding using facially amphiphilic dendrimers

Amphiphilic dendrimers, which contain both hydrophobic and hydrophilic groups in every repeat unit, exhibit environment-dependent assemblies both in hydrophilic solvent, water, and in lipophilic solvent, toluene. Upon investigating the status of these assemblies in a mixture of immiscible solvents, these dendrimers were found to be kinetically trapped in the solvent in which they are initially assembled. This property has been exploited to selectively extract peptides from aqueous solution into an organic phase, where the peptides bind to the interior functionalities of the dendritic inverse micelles. While the corresponding small molecule surfactant does not exhibit any selective binding toward peptides, all dendrons (G1-G3) are capable of this selective binding. We show that the inverse micelle-type assembly itself is crucial for the binding event and that the assembly formed by the G1 dendron has a greater capability for binding compared to the G2 or G3 dendrons. We have also shown that the average apparent pKa of the carboxylic acid functionalities varies with generation, and this could be the reason for the observed differences in binding capacity.     

Multistep Parallel Synthesis of Quinazoline‐2,4‐diones by a Fluorous Biphasic Concept without Perfluorinated Solvents

Based on perfluoro‐tagged benzyl alcohol adsorbed via fluorous–fluorous interactions on fluorous reversed‐phase silica gel (FRPSG), we have performed a multistep synthesis leading finally to a small library of quinazoline‐2,4‐diones. The whole reaction sequence runs without isolation of intermediates and most importantly, without the need of perfluorinated solvents.     

Sugar‐Decorated Dendritic Nanocarriers: Encapsulation and Release of the Octahedral Rhenium Cluster Complex [Re6S8(OH)6]4−

The encapsulation of a nanometer‐sized octahedral anionic rhenium cluster complex with six terminal hydroxo ligands [Re₆S₈(OH)₆]^4? in maltose‐decorated poly(propylene amine) dendrimers (POPAM, generation 4 and 5) has been investigated. Ultrafiltration experiments showed that maximal loading capacity of the dendrimers with the cluster complex is achieved after about ten hours in aqueous solution. To study the inclusion phenomena, three different methods have been applied: UV/Vis, time‐resolved laser‐induced fluorescence spectroscopy (TRLFS), and laser‐induced liquid bead ion desorption mass spectrometry (LILBID‐MS). From the results obtained, it could be concluded that: a) the hydrolytic stability of the rhenium cluster complex is significantly enhanced in the presence of dendritic hosts; b) the cluster anions are preferentially bound inside the dendrimers; c) the number of cluster complexes encapsulated in the dendrimers increases with rising dendrimer generation. On average, four to five cluster anions can preferentially be captured in the interior of sugar‐coated dendritic carriers. An asymptotic progression of the release of cluster complexes from the loaded dendrimers was observed under physiologically relevant conditions (isotonic sodium chloride solution: approximately 93 % within 4 days for loaded POPAM‐G4‐maltose; approximately 86 % within 4 days for loaded POPAM‐G5‐maltose). These encapsulation and release properties of maltose‐decorated nanocarriers imply the possibility for the development of the next generation of dendritic nanocarriers with specific targeting of destined tissue for therapeutic treatments.     

Generation‐Dependent Host–Guest Interactions: Solution States of Polyglycerol Dendrimers of Generations 3 and 4 Modulate the Localization of a Guest Molecule

Host–guest interactions between polyglycerol dendrimers of generations 3 and 4 (PGD‐G3 and G4) and 4‐amino‐3‐hydroxynapthalene‐2‐sulphonic acid (AHSA) were investigated by fluorescence spectroscopy, isothermal titration calorimetry (ITC), and dynamic light scattering (DLS). PGD‐G3 molecules were found to form an associated state with an average diameter of 82.7 nm in aqueous solution, in which PGD‐G3 provided a much more polar microenvironment than glycerol. PGD‐G3 and AHSA interacted attractively, showing a binding constant of 5.3×10⁵ M ^?1 with a 2:1 stoichiometry. On the other hand, AHSA interacted with the periphery of PGD‐G4, the majority of which existed as a unimer, forming a less polar microenvironment. The driving force of the interactions for PGD‐G3 and ‐G4 were mainly enthalpically and entropically driven, respectively. The generation‐dependent host–guest interactions were described in conjunction with thermodynamic parameters.     

Enhancement of entrapping ability of dendrimers by a cubic silsesquioxane core

We report that a polyhedral oligomeric silsesquioxane (POSS) core can enhance the entrapping ability of dendrimers. Compared to the G2 PAMAM dendrimer, the G2 POSS-core dendrimer can entrap a larger amount of guest molecules without loss of affinity, and consequently, the water solubility of the entrapped guest molecules can be increased. In addition, we demonstrated that a fluorophore entrapped in the G2 POSS-core dendrimer was prevented from undergoing fluorescence photobleaching.     

Multicomponent host-guest chemistry of carboxylic acid and phosphonic acid based guests with dendritic hosts: an NMR study

A new way to analyze supramolecular dendritic architectures is reported by making use of (13)C NMR and (31)P NMR. Two ethylene glycol guest molecules have been synthesized containing a (13)C labeled carboxylic acid headgroup (2) and a phosphonic acid headgroup (3). The binding of these guests to urea-adamantyl modified poly(propylene imine) dendrimers has been investigated with (13)C NMR and (31)P NMR next to 1D and 2D (1)H NMR techniques. Different amounts of guest 2 have been added to fifth generation dendrimer 1e, and the observed chemical shift values in (13)C NMR were fitted to a model that assumes 1:1 binding between guest and binding site. An association constant of 400 +/- 95 M(-)(1) is obtained for guest 2 with 41 binding sites per dendrimer. When different amounts of phosphonic acid guest 3 are added to dendrimer 1e, two different signals are observed in (31)P NMR. Deconvolution gives the fractions of free and bound guest, resulting in an association constant of (4 +/- 3) x 10(4) M(-)(1) and 61 +/- 1 binding sites. A statistical analysis shows that guest 2 forms a "polydisperse supramolecular aggregate", while guest 3 is able to form a "monodisperse supramolecular aggregate" when the amount of guest is high enough. The NMR results are compared with dynamic light scattering experiments, and a remarkable agreement is found. Phosphonic acid guest 3 is able to exchange with guest 2, which is in agreement with the obtained association constants, and shows that these techniques can be used to analyze multicomponent dendritic aggregates.     

Porous alumina-based fluorous liquid membranes: Dependence of transport on fluorous solvent

We report here the properties of supported fluorous liquid membranes based on porous alumina. The alumina is first rendered compatible with fluorous solvents by surface modification with an oligomeric perfluoropropylene oxide-based carboxylic acid, Krytox 157FSH. After modification, simply dipping the porous alumina membrane into a perfluorinated solvent results in a supported liquid membrane with high selectivity for fluorous compounds. Two homologous series of compounds differing in the number of -CF₂- groups were investigated, namely esters of cinnamyl alcohol and the analogous naphthyl derivative with 2H,2H,3H,3H-perfluoroalkanoic acids (HOOC-(CH₂)₂-(CF₂)_m−1CF₃, m = 2, 4, 6 and 8). Four perfluorinated membrane solvents (FC-77, PF-5080, FC-3283 and FC-43) were investigated. In FC-3283, the permeabilities, which are the products of a diffusion coefficient and a partition coefficient in the solution-diffusion model, of cinnamyl alcohol derivatives are 3.62 ± 0.36 times greater than those of the analogous naphthyl compounds for the solutes containing the same perfluorinated chain. Permeability, P, increases as the perfluorinated chain length increases in all of the perfluorinated solvents. Values of log(P) vs m are linear with a slope of 0.147 ± 0.002 but with different intercepts for the various solvents. Independent measurements of the partition coefficients of the solutes between the source/receiving phase solvent, ethanol, and the fluorous solvents reveal that the selectivity behavior is dominated by partitioning rather than diffusion. The free energy of transfer of a -CF₂- group (ethanol to perfluorinated solvents) is −1.1 kJ/mol. Despite the fact that the solvents are mixtures, not pure liquids, the partition coefficients are well correlated with values calculated based on group contributions with ‘mobile order and disorder’ theory. The diffusion coefficients of four solutes in four membrane solvents were also determined based on the solution-diffusion model. The Stoke-Einstein equation shows satisfactory estimation of experimental results.