Highly Strong and Tough Supramolecular Polymer Networks Enabled by Cryptand-Based Host-Guest Recognition.

Supramolecular polymer networks (SPNs) demonstrate great potential in the development of smart materials owing to their attractive dynamic properties. However, as they suffer from the inherent weak bonding of most noncovalent cross-links, it remains a significant challenge to construct SPNs with outstanding mechanical performance. Herein, we exploit the cryptand/paraquat host-guest recognition motifs as cross-links to prepare a class of highly strong and tough SPNs. Unlike those supramolecular cross-links with relatively weak binding abilities, the cryptand-based host-guest interactions have a high association constant and steady complexing structure, which effectively stabilizes the network and resists mechanical deformation under external force. Such favorable structural stability endows our SPNs with greatly enhanced mechanical performance, compared with the control-1 cross-linked by the weakly complexed crown ether/secondary ammonium salt motif (tensile strength: 21.1±0.5 vs 2.8±0.1 MPa; Young's modulus: 102.6±4.8 vs 2.1±0.3 MPa; toughness: 90.4±2.0 vs 10.8±0.6 MJ m-3 ). Moreover, our SPNs also retain abundant dynamic properties including good abilities in energy dissipation, reprocessability, and stimuli-responsiveness. These findings provide novel insights into the preparation of SPNs with enhanced mechanical properties, and promote the development of high-performance intelligent supramolecular materials.

Viologen-Based Rotaxanes from Dibenzo-30-crown-10.

Three [2]rotaxanes (4, 7, and 12) and one [3]rotaxane (8) were synthesized based on the dibenzo-30-crown-10/viologen binding motif. To the best of our knowledge, these are the first rotaxanes formed from dibenzo-30-crown-10 and viologens. The rotaxanes were all characterized by 1H NMR, 13C NMR, and HRMS. An X-ray crystal structure of one of the [2]rotaxanes (7) was obtained. This work demonstrates for the first time that dibenzo-30-crown-10 does form pseudorotaxane complexes with viologens in solution.

Supramolecular Pseudorotaxane Polymers from Biscryptands and Bisparaquats.

Five new bis(dibenzo-30-crown-10-based cryptand)s were synthesized, two of which (16 and 17) had long (12-atom), flexible spacers that led to cooperative complexation of dibenzyl paraquat TFSI ( Kave = 4.36 × 105 M-1 for 17•2b). Self-assembly of 16 and 17 with bisparaquats with similar spacers (18, 21, and 23) led to high molecular weight supramolecular pseudorotaxane polymers in solution. Continuous, flexible fibers were drawn from concentrated solutions. 17 with C10-linked bisparaquat 23 in dichloromethane (DCM) produced a log-log viscosity vs concentration plot with a limiting slope of 3.55, confirming high molecular weight; at 37 mM, the degree of polymerization was estimated to be 126 and Mn = 407 kDa. These are the first truly polymeric pseudorotaxane-type AA/BB supramolecular polymers.

Pseudocryptand Hosts for Paraquats and Diquats.

H-bonding interaction of acidic moieties (CH2OH, COOH) at the 5- and 5'-positions of bis(1,3-phenylene)-32-crown-10 (1) with di- or tritopic anions leads to enhanced formation of inclusion complexes with N,N'-dialkyl-4,4'-bipyridinium salts ("paraquats", 2); the enforced folding of the crown ethers into pseudocryptands thus leads to pseudo-pseudorotaxanes. Strikingly, in the presence of the most effective anion (trifluoroacetate, TFA), the apparent bimolecular association constants for crown-paraquat complexation increase by more than an order of magnitude and approach those for covalent cryptands derived from the crown ether. Even though they may form pseudocryptands, the picolinate, nicotinate, and isonicotinate diesters 6 of cis-(4,4')-bis(hydroxymethyl)dibenzo-30-crown-10 do not exhibit enhanced binding of either diquat or paraquat relative to the starting diol in contrast to the picolinate ester of isomeric 5,5'-bis(hydroxymethyl)bis(m-phenylene)-32-crown-10, which displayed a higher binding constant than the starting diol. The results for the analogous reverse esters 7 derived from cis-(4,4')-dicarboxydibenzo-30-crown-10 and pyridylmethanols reveal weaker complexes with diquat than the normal esters 6; however, surprisingly, two reverse esters 7 complex paraquat more strongly than isomers 6.

High-Yielding Syntheses of Crown Ether-Based Pyridyl Cryptands.

Pyridinium bis(trifluoromethylsulfonyl)imide (PyTFSI)-templated syntheses of 2,6-pyridyl cryptands of cis(4,4')-dibenzo-30-crown-10 (3a), the p-bromobenzyloxy derivative 3b, bis(m-phenylene)-32-crown-10 (5), cis(4,4')-dibenzo-27S-crown-9 (7), cis(4,4')-dibenzo-27L-crown-9 (9), and cis(4,4')-dibenzo-24-crown-8 (11) are reported. Here we provide a fast (12 h), high-yielding (89%, 74%, 80%, and 62% for 3a, 3b, 5, and 9, respectively) templation method without the use of a syringe pump. The yields for 7 (19%) and 11 (26%) were lower than with the previous pseudo-high-dilution method, indicating ineffective templation in these cases. Coupled with our previously developed templated syntheses of dibenzo crown ethers, this protocol makes powerful cryptand hosts readily available in gram quantities in good yields from methyl 4(or 3)-hydroxy-3(or 4)-benzyloxybenzoate.

The Long and the Short of It: Regiospecific Syntheses of Isomers of Dicarbomethoxydibenzo-27-crown-9 and Binding Abilities of Their Pyridyl Cryptands.

The two isomers 6 and 9 of cis(4,4'-)-dicarbomethoxydibenzo-27-crown-9 with tri- and tetra-(ethyleneoxy) linkages transposed were synthesized regiospecifically in high yields (94 and 92%, respectively) by the Wang-Pederson-Wessels (WPW) protocol and were converted via the corresponding diols 7 and 10 to the corresponding pyridyl cryptands 3 and 4 by reaction with pyridine-2,6-dicarbonyl chloride. As expected from Corey-Pauling-Koltun (CPK) models, the cryptand with the tri(ethyleneoxy) arm para to the ester linkages, "short-armed" cryptand 3, did display a higher binding constant (Ka = 2.4 × 105 M-1) with paraquats than the analogous dibenzo-30-crown-10-based cryptand previously studied; however, the effect was only twofold. Its binding to diquat was reduced by an order of magnitude (1.5 × 105 M-1), as expected on the basis of its narrower cavity. Also as expected, the cryptand with the tetra(ethyleneoxy) arm para to the ester linkages, "long-armed" cryptand 4, possessed diminished binding with both paraquats and diquat relative to the 30-crown-based analogue; in these systems, 2:1 H:G complexes were also detected by mass spectrometry. A crystal structure is reported for 3·DQ(PF6)2.

Stimuli-responsive host-guest systems based on the recognition of cryptands by organic guests.

CONSPECTUS: As the star compounds in host-guest chemistry, the syntheses of crown ethers proclaimed the birth of supramolecular chemistry. Crown ether-based host-guest systems have attracted great attention in self-assembly processes because of their good selectivity, high efficiency, and convenient responsiveness, enabling their facile application to the "bottom-up" approach for construction of functional molecular aggregates, such as artificial molecular machines, drug delivery materials, and supramolecular polymers. Cryptands, as preorganized derivatives of crown ethers, not only possess the above-mentioned properties but also have three-dimensional spatial structures and higher association constants compared with crown ethers. More importantly, the introduction of the additional arms makes cryptand-based host-guest systems responsive to more stimuli, which is crucial for the construction of adaptive or smart materials. In the past decade, we designed and synthesized crown ether-based cryptands as a new type of host for small organic guests with the purpose of greatly increasing the stabilities of the host-guest complexes and preparing mechanically interlocked structures and large supramolecular systems more efficiently while retaining or increasing their stimuli-responsiveness. Organic molecules such as paraquat derivatives and secondary ammonium salts have been widely used in the fabrication of functional supramolecular aggregates. Many host molecules including crown ethers, cyclodextrins, calixarenes, cucurbiturils, pillararenes, and cryptands have been used in the preparation of self-assembled structures with these guest molecules, but among them cryptands exhibit the best stabilities with paraquat derivatives in organic solvents due to their preorganization and additional and optimized binding sites. They enable the construction of sophisticated molecules or supramolecules in high yields, affording a very efficient way to fabricate stimuli-responsive functional supramolecular systems. This Account mainly focuses on the application of cryptands in the construction of mechanically interlocked molecules such as rotaxanes and catenanes, and stimuli-responsive host-guest systems such as molecular switches and supramolecular polymers due to their good host-guest properties. These cryptands are bicyclic derivatives of crown ethers, including dibenzo-24-crown-8, bis(m-phenylene)-26-crown-8, dibenzo-30-crown-10, and bis(m-phenylene)-32-crown-10. The length of the third arm has a very important influence on the binding strength of these cryptands with organic guests, because it affects not only the size fit between the host and the guest but also the distances and angles that govern the strengths of the noncovalent interactions between the host and the guest. For example, for bis(m-phenylene)-32-crown-10-based cryptands, a third arm of nine atoms is the best. The environmental responsiveness of these cryptand-based host-guest systems arises from either the crown ether units or the third arms. For example, a dibenzo-24-crown-8 unit introduces potassium cation responsiveness and an azobenzene group on the third arm imbues photoresponsiveness. We believe that studies on stimuli-responsive host-guest systems based on cryptands and organic guests will contribute significantly to future research on molecular devices, supramolecular polymers, and other functional supramolecular materials.

Cation and anion transport in a dicationic imidazolium-based plastic crystal ion conductor.

Here we investigate the organic ionic plastic crystal 1,2-bis[N-(N'-hexylimidazolium-d2(4,5))]ethane 2PF6(-) in one of its solid plastic crystal phases by means of multinuclear solid-state (SS) NMR and pulsed-field-gradient NMR diffusometry. We quantify distinct cation and anion diffusion coefficients as well as the Arrhenius diffusion activation energies (Ea) in this dicationic imidazolium-based plastic crystal. Our studies suggest a change in transport mechanism for the cation upon varying thermal and magnetic treatment (9.4 T), evidenced by differences in cation and anion Ea. Moreover, variable temperature (2)H SSNMR line shapes support a change in local molecular environment upon slow cooling in B0. We quantify the percentage of mobile anions as a function of temperature with (19)F SSNMR, wherein two distinct spectral features are present. We also comment on the Arrhenius pre-exponential factor for diffusion (D0), giving insight into the number of degrees of freedom for transport for both cation and anion as a function of thermal treatment. Given the breadth and depth of our measurements, we propose that bulk ion transport is dominated by anion diffusion in ionic-liquid-like domain boundaries separating crystallites. This study elucidates fundamental properties of this plastic crystal, and allows for a more general and deeper understanding of ion transport within such materials.

Contrasting biscryptand/dimethyl paraquat [3]pseudorotaxanes: statistical vs. anticooperative complexation behavior.

Via the self-assembly of two bis(meta-phenylene)-32-crown-10-based cryptands, bearing covalent and metal complex (ferrocene) linkages, with dimethyl paraquat, novel [3]pseudorotaxanes were formed statistically and anticooperatively, respectively.

Pseudocryptand-type [3]pseudorotaxane and "hook-ring" polypseudo[2]catenane based on a bis(m-phenylene)-32-crown-10 derivative and bisparaquat derivatives.

The first pseudocryptand-type supramolecular [3]pseudorotaxane was designed and prepared via the self-assembly of a bispicolinate BMP32C10 derivative and a bisparaquat. The complexation behavior was cooperative. In addition, the complex comprised of the BMP32C10 derivative and a cyclic bisparaquat demonstrated strong binding; interestingly, a poly[2]pseudocatenane structure was formed in the solid state for the first time.

Pseudocryptand-type [2]pseudorotaxanes based on bis(meta-phenylene)-32-crown-10 derivatives and paraquats with remarkably improved association constants.

The first dual component pseudocryptand-type [2]pseudorotaxanes were designed and prepared via the self-assembly of synthetically easily accessible bis(meta-phenylene)-32-crown-10 pyridyl, quinolyl, and naphthyridyl derivatives with paraquat. The formation of the pseudocryptand structures in the complexes remarkably improved the association constant by forming the third pseudobridge via H-bonding with the guest and π-stacking of the heterocyclic units.

The first [2]pseudorotaxane and the first pseudocryptand-type poly[2]pseudorotaxane based on bis(meta-phenylene)-32-crown-10 and paraquat derivatives.

By the self-assembly of a bis(meta-phenylene)-32-crown-10 bearing two electron-donating groups (carbazoles) with electron-accepting paraquat derivatives, the first [2]pseudorotaxane and the first pseudocryptand-type poly[2]pseudorotaxane based on bis(meta-phenylene)-32-crown-10 were isolated as crystalline solids as shown by X-ray analyses.

Supramolecular AA-BB-type linear polymers with relatively high molecular weights via the self-assembly of bis(m-phenylene)-32-crown-10 cryptands and a bisparaquat derivative.

Two novel bis(m-phenylene)-32-crown-10-based cryptands, one bearing covalent linkages and the other metal-complex linkages, were designed and prepared. By self-assembly of these biscryptands, which can be viewed as AA monomers, and a bisparaquat, which can be viewed as a BB monomer, AA-BB-type linear supramolecular polymers with relatively high molecular weights were successfully prepared.

Complexation equilibria involving salts in non-aqueous solvents: ion pairing and activity considerations.

Complexation of anions, cations and even ion pairs is now an active area of investigation in supramolecular chemistry; unfortunately it is an area fraught with complications when these processes are examined in low polarity organic media. Using a pseudorotaxane complex as an example, apparent K(a2) values (=[complex]/{[salt](o)-[complex]}{[host](o)-[complex]}) for pseudorotaxane formation from dibenzylammonium salts (2-X) and dibenzo-[24]crown-8 (1, DB24C8) in CDCl(3)/CD(3)CN 3:2 vary with concentration. This is attributable to the fact that the salt is ion paired, but the complex is not. We report an equilibrium model that explicitly includes ion pair dissociation and is based upon activities rather than molar concentrations for study of such processes in non-aqueous media. Proper analysis requires both a dissociation constant, K(ipd), for the salt and a binding constant for interaction of the free cation 2(+) with the host, K(a5); K(a5) for pseudorotaxane complexation is independent of the counterion (500 M(-1)), a result of the complex existing in solution as a free cation, but K(ipd) values for the salts vary by nearly two orders of magnitude from trifluoroacetate to tosylate to tetrafluoroborate to hexafluorophosphate anions. The activity coefficients depend on the nature of the predominant ions present, whether the pseudorotaxane or the ions from the salt, and also strongly on the molar concentrations; activity coefficients as low as 0.2 are observed, emphasizing the magnitude of their effect. Based on this type of analysis, a method for precise determination of relative binding constants, K(a5), for multiple hosts with a given guest is described. However, while the incorporation of activity coefficients is clearly necessary, it removes the ability to predict from the equilibrium constants the effects of concentration on the extent of binding, which can only be determined experimentally. This has serious implications for study of all such complexation processes in low polarity media.

In vitro and in vivo studies of single-walled carbon nanohorns with encapsulated metallofullerenes and exohedrally functionalized quantum dots.

Single-walled carbon nanohorns (SWNHs) are new carbonaceous materials. In this paper, we report the first successful preparation of SWNHs encapsulating trimetallic nitride template endohedral metallofullerenes (TNT-EMFs). The resultant materials were functionalized by a high-speed vibration milling method and conjugated with CdSe/ZnS quantum dots (QDs). The successful encapsulation of TNT-EMFs and external functionalization with QDs provide a dual diagnostic platform for in vitro and in vivo biomedical applications of these new carbonaceous materials.

Structure and properties of N,N-alkylene bis(N'-alkylimidazolium) salts.

A series of N,N-alkylene bis(N'-alkylimidazolium) salts with various anions was prepared and characterized. The hydrogen-bonding abilities and ion-pairing strengths of the salts in solution were varied by changing the solvent and anion. Qualitatively, the extent of ion pairing of the 1,2-bis[N-(N'-butylimidazolium)]ethane salts with different anions was determined in acetone-d(6) by (1)H NMR spectroscopy. Thermal properties of the imidazolium salts were related not only to the nature of anions but also to the spacer length between imidazolium cations. Exceptionally high melting points of 1,2-bis[N-(N'-alkylimidazolium)]ethane bis(hexafluorophosphate)s can be explained by multiple hydrogen bonds observed in the X-ray crystal structures. Moreover, a trans conformation of the ethylene spacer of 1,2-bis[N-(N'-alkylimidazolium)]ethane bis(hexafluorophosphate)s allows good stacking structure in the crystals.

High relaxivity trimetallic nitride (Gd3N) metallofullerene MRI contrast agents with optimized functionality.

Water-soluble poly(ethylene glycol) (PEG) functionalized and hydroxylated endohedral trimetallic nitride metallofullerene derivatives, Gd(3)N@C(80)[DiPEG(OH)(x)], have been synthesized and characterized. The (1)H MRI relaxivities in aqueous solution were measured for the derivatives with four different molecular weights of PEG (350-5000 Da) at 0.35, 2.4, and 9.4 T. The 350/750 Da PEG derivatives have the highest relaxivities among the derivatives, 237/232 mM(-1) s(-1) for r(1) and 460/398 mM(-1) s(-1) for r(2) (79/77 mM(-1) s(-1) and 153/133 mM(-1) s(-1) based on Gd(3+) ion), respectively, at a clinical-range magnetic field of 2.4 T. These represent some of the highest relaxivities reported for commercial or investigational MRI contrast agents. Dynamic light scattering results confirm a larger average size for 350/750 Da PEGs derivatives (95/96 nm) relative to longer chain length derivatives, 5000 Da PEG derivatives (37 nm). Direct infusion of the optimized 350 Da PEG derivatives into live tumor-bearing rat brains demonstrated an initial uniform distribution, and hence, the potential for effective brachytherapy applications when the encapsulated Gd(3+) ions are replaced with radioactive (177)Lu.

Encapsulation of a radiolabeled cluster inside a fullerene cage, (177)Lu(x)Lu((3-x))N@C(80): an interleukin-13-conjugated radiolabeled metallofullerene platform.

In this communication, we describe the successful encapsulation of (177)Lu into the endohedral metallofullerene (177)Lu(x)Lu(3-x)N@C(80) (x = 1-3) starting with (177)LuCl(3) in a modified quartz Kraschmer-Huffman electric generator. We demonstrate that the (177)Lu (beta-emitter) in this fullerene cage is not significantly released for a period of up to at least one-half-life (6.7 days). We also demonstrate that this agent can be conjugated with an interleukin-13 peptide that is designed to target an overexpressed receptor in glioblastoma multiforme tumors. This nanoparticle delivery platform provides flexibility for a wide range of radiotherapeutic and radiodiagnostic multimodal applications.