The Effects of Microenvironment Polarity and Dendritic Branching of Aliphatic Hydrocarbon Dendrons on the Self‐Assembly of 2‐Ureido‐4‐pyrimidinones

Two series of aliphatic hydrocarbon‐based G1–G3 dendritic 2‐ureido‐4‐pyrimidinones (UPy) ( S‐Gn )₂ and ( L‐Gn )₂, differing from one another by the distance between the branching juncture to the urea end, were prepared and characterized. These hydrocarbon dendrons were also appended to a p‐aminonitrobenzene solvatochromic chromophore in order to probe their microenvironment polarity. While positive solvatochromism was observed which indicated the chromophore was solvent accessible, there was no significant difference between the microenvironment polarities on going from the G1 to the G3 dendrons. The self‐assembling behavior and tautomeric preference of the dendritic UPy derviatives were examined by ¹H NMR spectroscopy. The dimerization constants (K_dim*) of the DDAA tautomers were unchanged at 10⁷ M ^?1 in CDCl₃ at both 25 and 50 °C, which were comparable to those of UPy compounds bearing other nonpolar substitutents. Furthermore, the lower limits on the K′_dim* of the DADA tautomeric forms of the ( S‐Gn )₂ and ( L‐Gn )₂ series were determined to be 10⁶ and 10⁵ M ^?1 in CDCl₃, respectively. It was found that a closer proximity of the dendron branching juncture to the UPy unit could lead to a destabilization effect on the dimeric states. Hence, the ( L‐Gn )₂ dimers are more stable than those of ( S‐Gn )₂ in the DDAA form, but the latter are more stable than the former in the tautomeric DADA state. This study showed that both the highly nonpolar microenvironment and the proximity of the dendritic branching juncture to the UPy motif could alter the strength and profile of the hydrogen bond‐mediated self‐assembling process.     

Super-tough and rapidly self-recoverable multi-bond network hydrogels facilitated by 2-ureido-4[1H]-pyrimidone dimers

Multi-bond network(MBN) hydrogels contain hierarchical dynamic bonds with different bond association energy as energy dissipation units,enabling super-tough mechanical properties.In this work,we copolymerize a protonated 2-ureido-4[1 H]-pyrimidone(UPy)-contained monomer with acrylic acid in HCl solution.After removing excess HCl,UPy motifs are deprotonated and from dimers,thus generating an UPy-contained MBN hydrogel.The obtained MBN hydrogels(75 wt% watercontent) exhibit super-tough mechanical properties(0.39 MPa to 2.51 MPa tensile strength),with tremendous amount of energy(1.68 MJ/m³ to 11.1 MJ/m³) dissipated by the dissociation of UPy dimers.The introduction of ionic bonds can further improve the mechanical properties.Moreover,owing to their dynamic nature,both UPy dimers and ionic bonds can re-associate after being dissociated,resulting in excellent self-recovery ability(around 90% recovery efficiency within only 1 h).The excellent self-recovery ability mainly originates from the re-association of UPy dimers based on the high dimerization constant of UPy motifs.     

Interplay of fidelity, binding strength, and structure in supramolecular polymers

In studies of a supramolecular network of polymers formed by self-association of UPy or UG recognition units displayed along a poly(butyl methacrylate) (PBMA) backbone, it was unexpectedly found that the more weakly dimerizing (Kdimer approximately 200 M-1) UG unit produced more assembly than did the very strongly dimerizing UPy unit (Kdimer = 2 x 107 M-1). Likewise, in examining supramolecular blends mediated by the heterocomplexation of DAN and UPy, which occurs upon the mixing of polystyrene containing the DAN unit (PS-DAN) and PBMA-UPy, increasing the mol % of UPy did not produce increased viscosity. 1H NMR showed that both observations can be explained by the intramolecular recognition of UPy. Structural studies show that the length of the chain linking the UPy unit to the backbone is critical, with longer linkers favoring intermolecular dimers. An interplay of linker chain length, polymer Mw, recognition unit mol %, and fidelity determines the extent of network growth.     

Self‐Assembly of Ureido‐Pyrimidinone Dimers into One‐Dimensional Stacks by Lateral Hydrogen Bonding

Ureido‐pyrimidinone (UPy) dimers substituted with an additional urea functionality self‐assemble into one‐dimensional stacks in various solvents through lateral non‐covalent interactions. ¹H NMR and DOSY studies in CDCl₃ suggest the formation of short stacks (<10), whereas temperature‐dependent circular dichroism (CD) studies on chiral UPy dimers in heptane show the formation of much larger helical stacks. Analysis of the concentration‐dependent evolution of chemical shift in CDCl₃ and the temperature‐dependent CD effect in heptane suggest that this self‐assembly process follows an isodesmic pathway in both solvents. The length of the aggregates is influenced by substituents attached to the urea functionality. In sharp contrast, UPy dimers carrying an additional urethane group do not self‐assemble into ordered stacks, as is evident from the absence of a CD effect in heptane and the concentration‐independent chemical shift of the alkylidene proton of the pyrimidinone ring in CDCl₃.     

A Well-defined Hierarchical Hydrogen Bonding Strategy to Polyureas with Simultaneously Improved Strength and Toughness

A well-defined quadruple hydrogen bonding strategy involving dimerization of 2-ureido-4[1H]-pyrimidone(UPy) units is innovatively designed to prepare polyureas with high overall mechanical properties. Three polyureas containing different amounts of UPy units were synthesized by replacing a portion of isophorone diisocyanate(IPDI) with a UPy-derived diisocyanate. The formation of quadruple hydrogen bonds in hard segments via UPy dimers was confirmed by nuclear magnetic resonance(NMR) and Fourier transform infrared spectroscopy(FTIR). The mechanical properties of the polyureas were evaluated by uniaxial tensile testing. Compared to the polyurea without UPy units, remarkable improvements in Young's modulus, tensile strength, and toughness were simultaneously achieved when UPy units were incorporated. The mechanism behind the strong strengthening effect rooted in the stronger intermolecular forces among hard segments brought by the quadruple hydrogen bonds, which were stronger than the inherent bidentate and monodentate hydrogen bonds among urea groups, and the slower soft segmental dynamics reaveled by both increased Tg and relaxation time of the soft segments. The mechanism behind the strong toughening effect was ascribed to more effective energy dissipation brought by the quadruple hydrogen bonds that served as stronger sacrificial bonds upon deformation. This work may offer new insight into the design of polyurea elastomers with comprehensively improved mechanical properties.     

Self‐assembly and morphology of polydimethylsiloxane supramolecular thermoplastic elastomers

Functionalization of polydimethylsiloxanes (PDMS) polymers with hydrogen‐bonding ureidopyrimidinone (UPy) groups leads to supramolecular thermoplastic elastomers. In previous studies, no lateral stacking of UPy dimers was observed in UPy‐functionalized polymers, unless additional urethane or urea groups were built into the hard block. However, we have shown that when PDMS is used as the soft block, this lateral aggregation of UPy dimers does take place, since long fibers could be observed in the atomic force microscopy (AFM) phase image. Also in bulk, the presence of these interactions was proven by oscillatory shear experiments. We attribute this aggregation to the incompatibility of soft block and hard block, leading to phase separation. Moreover, we have shown that additional urethane or urea groups in the hard block do lead to materials with more fibers and higher melting points. For the UPy‐urea functionalized PDMS even single fibers are observed with AFM when dropcasted from a very diluted solution. When the length of the soft block is increased, the morphology changes from fibrous to spherical. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3877–3885, 2008     

An Unconventional Approach to Induce Liquid‐Crystalline Phases of Triazine‐Based Dendrons by Breaking Their Self‐Assembly into Dimers

Three triazine‐based dendrons ( 1 a – c ) were successfully prepared in 70–83 % yields. These newly prepared dendrons are found to be liquid crystalline (LC). Computational investigations on molecular conformations and dipoles of triazine‐based dendrons reveal that the substituent on the central triazine unit interrupts strong dipole or H‐bond interactions to avoid dimeric formation. The obtained dendrons, not favouring self‐assembly into dimers but showing LC behaviours, provides evidence for an approach contrary to the conventional method of inducing LC behaviours of dendrons by dimer or trimer formation, mostly through H‐bond interactions.     

Stretchable alkaline quasi-solid-state electrolytes created by super-tough,fatigue-resistant and alkali-resistant multi-bond network hydrogels

Hydrogel-based quasi-solid-state electrolytes (Q-SSEs) swollen with electrolyte solutions are important components in stretchable supercapacitors and other wearable devices. This work fabricates a super-tough, fatigue-resistant, and alkali-resistant multi-bond network (MBN) hydrogel aiming to be an alkaline Q-SSE. To synthesize the hydrogel, a 2-ureido-4[1H]-pyrimidone (UPy) motif is introduced into a poly(acrylic acid) polymer chain. The obtained MBN hydrogels with 75 wt% water content exhibit tensile strength as high as 2.47 MPa, which is enabled by the large energy dissipation ability originated from the dissociation of UPy dimers due to their high bond association energy. Owing to the high dimerization constant of UPy motifs, the dissociated UPy motifs are able to partially re-associate soon after being released from external forces, resulting in excellent fatigue-resistance. More importantly, the MBN hydrogels exhibit excellent alkali-resistance ability. The UPyGel-10 swollen with 1 mol/L KOH display a tensile strength as high as ～1.0 MPa with elongation at break of ～550%. At the same time, they show ionic conductivity of ～17 mS/cm, which do not decline even when the hydrogels are stretched to 500% strain. The excellent mechanical property and ionic conductivity of the present hydrogels demonstrate potential application as a stretchable alkaline Q-SSE.     

Supramolecular Macrostructures of UPy‐Functionalized Carbon Nanotubes

Carbon nanotubes (CNTs) are considered excellent materials for the construction of flexible displays due to their nanoscale dimensions and unique physical and chemical properties. By using the recognition properties of 2‐ureido‐4[1H]pyrimidinone (UPy), a versatile and simple methodology was demonstrated for the construction of macroscopic structures based on UPy‐CNT/polymer composites prepared by a combination of two functionalization approaches: 1) covalent attachment of UPy pendants on the multiwalled CNT surface ( UPy‐MWCNTs ) and 2) directed self‐assembly of UPy‐MWCNTs within polymers bearing UPy pendants ( Bis‐UPy 1 and Bis‐UPy 2 ) by quadruple complementary DDAA–AADD hydrogen‐bond recognition (D=donor, A=acceptor).     

A Supramolecular Polymer Network of Graphene Quantum Dots

Graphene quantum dot (GQD)–organic hybrid compounds (GQD‐ 2 b – e ) were prepared by introducing 3,4,5‐tri(hexadecyloxy)benzyl groups (C16) and linear chains terminated with a 2‐ureido‐4‐[1H]‐pyrimidinone (UPy) moiety onto the periphery of GQD‐ 1 . GQD‐ 2 b – e formed supramolecular assemblies through hydrogen bonding between the UPy units. GPC analysis showed that GQDs with high loadings of the UPy group formed larger assemblies, and this trend was confirmed by DOSY and viscosity measurements. AFM images showed the polymeric network structures of GQD‐ 2 e on mica with flat structures (ca. 1.1 nm in height), but no such structures were observed in GQD‐ 2 a , which only carries the C16 group. GQD‐ 2 c and GQD‐ 2 d formed organogels in n‐decanol, and the gelation properties can be altered by replacing the alkyl chains in the UPy group with ethylene glycol chains (GQD‐ 3 ). GQD can thus be used as a platform for supramolecular polymers and organogelators by suitable chemical functionalization.     

Development of Non‐Cell Adhesive Vascular Grafts Using Supramolecular Building Blocks

Cell‐free approaches to in situ tissue engineering require materials that are mechanically stable and are able to control cell‐adhesive behavior upon implantation. Here, the development of mechanically stable grafts with non‐cell adhesive properties via a mix‐and‐match approach using ureido‐pyrimidinone (UPy)‐modified supramolecular polymers is reported. Cell adhesion is prevented in vitro through mixing of end‐functionalized or chain‐extended UPy‐polycaprolactone (UPy‐PCL or CE‐UPy‐PCL, respectively) with end‐functionalized UPy‐poly(ethylene glycol) (UPy‐PEG) at a ratio of 90:10. Further characterization reveals intimate mixing behavior of UPy‐PCL with UPy‐PEG, but poor mechanical properties, whereas CE‐UPy‐PCL scaffolds are mechanically stable. As a proof‐of‐concept for the use of non‐cell adhesive supramolecular materials in vivo, electrospun vascular scaffolds are applied in an aortic interposition rat model, showing reduced cell infiltration in the presence of only 10% of UPy‐PEG. Together, these results provide the first steps toward advanced supramolecular biomaterials for in situ vascular tissue engineering with control over selective cell capturing.

     

Self‐Healing Gelatin Hydrogels Cross‐Linked by Combining Multiple Hydrogen Bonding and Ionic Coordination

Self‐healing hydrogels have been studied by many researchers via multiple cross‐linking approaches including physical and chemical interactions. It is an interesting project in multifunctional hydrogel exploration that a water soluble polymer matrix is cross‐linked by combining the ionic coordination and the multiple hydrogen bonds to fabricate self‐healing hydrogels with injectable property. This study introduces a general procedure of preparing the hydrogels (termed gelatin‐UPy‐Fe) cross‐linked by both ionic coordination of Fe³⁺ and carboxyl group from the gelatin and the quadruple hydrogen bonding interaction from the ureido‐pyrimidinone (UPy) dimers. The gelatin‐UPy‐Fe hydrogels possess an excellent self‐healing property. The effects of the ionic coordination of Fe³⁺ and quadruple hydrogen bonding of UPy on the formation and mechanical behavior of the prepared hydrogels are investigated. In vitro drug release of the gelatin‐UPy‐Fe hydrogels is also observed, giving an intriguing glimpse into possible biological applications.

     

Dendron-containing tetraphenylethylene compounds: dependence of fluorescence and photocyclization reactivity on the dendron generation

The synthesis and characterization of four dendron-containing tetraphenylethylenes (TPEs), 1(1)-1(4), were synthesized, along with a TPE compound that contained four OCH(2) Ph groups (referred to as 1(0)) for comparison. Photophysical studies revealed that the TPE core became emissive after linking dendrons onto its periphery. Moreover, the fluorescence intensity was significantly enhanced when high-generation dendrons were linked onto the TPE core; the fluorescence intensity increased in the following order: 1(1)<1(2)<1(3)<1(4). This phenomenon was tentatively attributed to an enhancement in the energy barrier for internal rotation and torsion of the TPE core to which four dendrons were connected. In addition, the photocyclization of the TPE core into the respective 9,10-diphenylphenanthrene was facilitated when high-generation dendrons were linked to the TPE core. Again, the photocycliztion reactivity increased in the following order: 1(1)<1(2)<1(3)<1(4). We found that the fluorescence and photocyclization reactivity of TPE could be modulated by covalent interactions with dendrons, and such modulation was strongly dependent on the dendron-generation.     

主链含四重氢键基元聚氨酯的合成与性能

合成了一种新型含有UPy(2-ureido-4[1H]-pyrimidone)基团的二羟基化合物,以此二羟基化合物作扩链剂,通过与聚氨酯预聚体进行的扩链反应,制备了一系列主链含UPy的聚氨酯(PU-UPy).傅里叶红外光谱(FTIR)、氢核磁共振(1H-NMR)等测试结果表明,在聚氨酯主链中确实含有UPy链段.同时,热性能及力学性能测试表明,聚氨酯中的UPy二聚体会集聚而形成微晶,熔点在60℃附近.在聚氨酯主链中引入UPy,能大幅提高聚氨酯的力学性能,调整软段的分子量,以及在主链中UPy含量可改变聚氨酯弹性体的断裂伸长率和抗张强度.     

Supramolecular ordering of amide dendrons in lyotropic and thermotropic conditions

Self-assembled superstructures of amide dendrons, from first to third generation including monodendrons and covalently linked dimers, were extensively examined, and the supramolecular ordering processes in thermotropic and lyotropic conditions were compared. The superstructures as determined by X-ray diffraction and DSC revealed that the first and second generation dendrons showed nearly identical superstructures regardless of the assembly conditions. But, the third generation dendrons showed a more sensitive self-organizing behavior. The structure obtained from the gel state was lamellar with a more extended conformation, while the structure from the melt state revealed the columnar superstructures of contracted branches. The superstructure formed from the gel state also showed a structural change upon raising the temperature and assumed a structure similar to the thermotropically driven one, implying that the structure formed from the gel is thermodynamically unstable. The formation of lamellar- or cylinder-type superstructures from amide dendrons was primarily dependent on the shape of dendrons, which is associated with the branch size (generation) and the surrounding conditions.     

Investigation of the association and flexibility of cationic lipidic peptide dendrons by NMR spectroscopy

The cationic peptide dendrons synthesized and studied are lower generation polylysine-based partial dendrimers with or without lipid chains in the core. The dendrons with lipidic chains can be utilized as protein and liposomal mimics because of their unique structural properties. The full assignments of three different dendrons (L)7(NH2)8, (C14)1(L)7(NH2)8 and (C14)3(L)7(NH2)8 were obtained in D2O and H2O/D2O using a 500 MHz NMR spectrometer. The hydrophobic lipidic core of branched polylysine dendrons was found to induce aggregation upon increasing concentration. Because non-lipidic dendrons do not self-assemble, the behaviour and internal structural features of two different dendrons with one and three C14 hydrocarbon chains were explored. The critical association concentration clearly depends on the number of core hydrophobic residues and the association starts at 0.025 mM for (C14)1(L)7(NH2)8 and 0.05 mM for (C14)3(L(7(NH2)8. Chemical shift analysis also revealed that the hydrophobic chains of the dendrons associate in the core, whereas the polar head groups (NH2) are mainly located at the surfaces of the aggregates. The T1 relaxation time measurements showed that the mobility of the hydrocarbon chain is greater with the monomeric form of dendron (C14)1(L)7(NH2)8) than that of monomer (C14)3(L)7(NH2)8. The inter-chain hydrophobic interactions restrict the flexibility of the dendron with three hydrocarbon chains. As expected, the flexibility of the monomeric form is higher than that of the aggregated state for both of the dendrons.     

Synthesis and chiroptical analysis of optically active chiral shell dendrons

We have prepared a series of chiral dendrons (1-4) in which chiral subunits are placed in individual generational shells at varying distances from the focal point. The optical activity of these chiral dendritic structures is successfully modeled using structurally similar low-molecular weight model compounds. In dendrons 1a and 1b a chiral subunit is directly adjacent to the focal point, whereas in dendrons 2, 3, and 4a,b the chiral subunits are incorporated in the interior of the dendron. A marked difference in optical activity between the former 1a and 1b) and latter (2, 3, 4a,b) dendrons is mirrored in the optical activities of model compounds 12a, 12b, 19a, and 19b. These model compounds directly mimic the surrounding constitution of the chiral subunits in the dendrons. This successful analysis of the chiroptical data using low-molecular weight model compounds suggests that these dendrons do not possess conformational order in solution.     

A highly directional fourfold hydrogen-bonding motif for supramolecular structures through self-assembly of fullerodendrimers

Supramolecular dendrimers resulting from the dimerization of fullerene-functionalized dendrons through a quadruple hydrogen-bonding motif were prepared. The synthetic strategy is based on the esterification of a tert-butoxycarbonyl (Boc)-protected 2-ureido-4-[1H]pyrimidinone precursor possessing an alcohol function with fullerodendrons bearing a carboxylic acid unit at the focal point. Subsequent acidic treatment to cleave the protecting group and reaction of the resulting amine with octylisocyanate affords the targeted compounds. As demonstrated by the results of MALDI-TOF mass spectrometry and 1H NMR spectroscopy, both of the 2-ureido-4-[1H]pyrimidinone derivatives form self-assembled dimers spontaneously through hydrogen-bonding interactions, thus leading to supramolecular structures containing two or ten fullerene moieties.     

Expanding the structural diversity of self-assembling dendrons and supramolecular dendrimers via complex building blocks

The design and synthesis of the first examples of AB4 and AB5 dendritic building blocks with complex architecture are reported. Structural and retrostructural analysis of supramolecular dendrimers self-assembled from hybrid dendrons based on different combinations of AB4 and AB5 building blocks with AB2 and AB3 benzyl ether dendrons demonstrated that none of these new hybrid dendrons exhibit the previously encountered conformations of libraries of benzyl ether dendrons. These hybrid dendrons enabled the discovery of some highly unusual tapered and conical dendrons generated by the intramolecular back-folding of their repeat units and of their apex. The new back-folded tapered dendrons have double thickness and self-assemble into pine-tree-like columns exhibiting a long-range 7/2 helical order. The back-folded conical dendrons self-assemble into spherical dendrimers. Non-back-folded truncated conical dendrons were also discovered. They self-assemble into spherical dendrimers with a less densely packed center. The discovery of dendrons displaying a novel crown-like conformation is also reported. Crown-like dendrons self-assemble into long-range 5/1 helical pyramidal columns. The long-range 7/2 and 5/1 helical structures were established by applying, for the first time, the helical diffraction theory to the analysis of X-ray patterns obtained from oriented fibers of supramolecular dendrimers.     

Synthesis and retrostructural analysis of libraries of AB3 and constitutional isomeric AB2 phenylpropyl ether-based supramolecular dendrimers

We report the synthesis of methyl esters of 3-(4-hydroxyphenyl)propionic, 3-(3,4-dihydroxyphenyl)propionic, 3-(3,5-dihydroxyphenyl)propionic, and 3-(3,4,5-trihydroxyphenyl)propionic acids and their use in a convergent iterative strategy to prepare up to four generations of three libraries, one of 3,4,5- and two of constitutional isomeric 3,4- and 3,5-substituted 3-phenylpropyl dendrons. Each library contains 3-[3,4,5-tris(dodecyl-1-oxy)phenyl]propyl-, 3-[3,4-bis(dodecyl-1-oxy)phenyl]propyl-, 3-{3,4-bis[3-(4-dodecyl-1-oxyphenyl)propyl-1-oxy]phenyl}propyl-, and 3-{3,4,5-tris[3-(4-dodecyl-1-oxyphenyl)propyl-1-oxy]phenyl}propyl ether first-generation dendrons on their periphery and -CO2CH3, -COOH, and -CH2OH groups at their apex. Regardless of their generation number and their periphery, internal, and apex structures, these dendrons self-assemble into supramolecular dendrimers that self-organize into all periodic and quasi-periodic assemblies encountered previously and in several unencountered with architecturally related benzyl ether-based supramolecular dendrimers. A variety of porous columnar lattices that were previously obtained only from dendritic dipeptides and hollow supramolecular spheres were also discovered from these building blocks. The more flexible and less compact 3-phenylpropyl ether repeat units are stable under acidic conditions, facilitate a simpler synthetic strategy, provide faster dynamics of self-assembly into higher-order supramolecular structures of larger dimensions, exhibit lower transition temperatures than the corresponding benzyl ether homologues, and demonstrate the generality of the self-assembly concept based on amphiphilic dendrons.