Supramolecular chemistry with ureido-benzoic acids

The controlled self-assembly of multiple molecules into predefined architectures requires highly directional and controllable non-covalent interactions with a high association constant. Here, we introduce the self-complementary ureido-benzoic acid (UBA) quadruple hydrogen-bonding motif. The dimerization constant is of the order of 109 M-1 in chloroform, which makes it an excellent candidate for supramolecular chemistry in dilute conditions. The self-complementary quadruple hydrogen bonding was confirmed in the solid state by a crystal structure. The applicability of the motif in supramolecular polymers was evaluated by bis-UBA telechelic poly(ethylene-butylene) polymers, which showed a dramatic increase in mechanical properties upon functionalization. The potential of the UBA motif in supramolecular chemistry was further evaluated in solution. One of the synthesized UBA molecules revealed hydrogen bonding to NaPy at high concentrations in chloroform. However, upon dilution, the UBA:NaPy hydrogen bonding is disrupted and UBA homodimers are obtained. This shows the potential of NaPy as a supramolecular protective group for the UBA molecule, which can be deprotected upon dilution. Furthermore, the dimerization of the UBA motif was reversibly switched between the 'off' and 'on' states using base and acid, demonstrating an alternative method of influencing the UBA dimerization. Switching of a UBA molecule in the presence of UPy revealed that UBA dimerization can be selectively switched 'off' and 'on' in the presence of UPy dimers. These results show the applicability and great potential of the self-complementary quadruple hydrogen-bonding UBA motif for supramolecular chemistry

Supramolecular chemistry with ureido-benzoic acids

The controlled self-assembly of multiple molecules into predefined architectures requires highly directional and controllable non-covalent interactions with a high association constant. Here, we introduce the self-complementary ureido-benzoic acid (UBA) quadruple hydrogen-bonding motif. The dimerization constant is of the order of 109 M-1 in chloroform, which makes it an excellent candidate for supramolecular chemistry in dilute conditions. The self-complementary quadruple hydrogen bonding was confirmed in the solid state by a crystal structure. The applicability of the motif in supramolecular polymers was evaluated by bis-UBA telechelic poly(ethylene-butylene) polymers, which showed a dramatic increase in mechanical properties upon functionalization. The potential of the UBA motif in supramolecular chemistry was further evaluated in solution. One of the synthesized UBA molecules revealed hydrogen bonding to NaPy at high concentrations in chloroform. However, upon dilution, the UBA:NaPy hydrogen bonding is disrupted and UBA homodimers are obtained. This shows the potential of NaPy as a supramolecular protective group for the UBA molecule, which can be deprotected upon dilution. Furthermore, the dimerization of the UBA motif was reversibly switched between the 'off' and 'on' states using base and acid, demonstrating an alternative method of influencing the UBA dimerization. Switching of a UBA molecule in the presence of UPy revealed that UBA dimerization can be selectively switched 'off' and 'on' in the presence of UPy dimers. These results show the applicability and great potential of the self-complementary quadruple hydrogen-bonding UBA motif for supramolecular chemistry

From Molecular Structure to Macromolecular Organization: Keys to Design Supramolecular Biomaterials

In the past decade, significant progress has been made in the field of biomaterials, for potential applications in tissue engineering or drug delivery. We have recently developed a new class of thermoplastic elastomers, based on ureidopyrimidinone (UPy) quadruple hydrogen bonding motifs. These supramolecular polymers form nanofiber-like aggregates initially <i>via</i> the dimerization of the UPy units followed by lateral urea-hydrogen bonding. Combined kinetic and thermodynamic studies unravel the pathway complexity in the formation of these polymorphic nanofibers and the subtlety of the polymer’s design, while these morphologies are so critically important when these materials are used in combination with cells. We also show that the cell behavior directly depends on the length and shape of the nanofibers, illustrating the key importance of macromolecular and supramolecular organization of biomaterials. This study leads to new design rules that determine what factors are decisive for a polymer to be a good candidate as biomaterial

Bioengineering of living renal membranes consisting of hierarchical, bioactive supramolecular meshes and human tubular cells

Maintenance of polarisation of epithelial cells and preservation of their specialized phenotype are great challenges for bioengineering of epithelial tissues Mimicking the basement membrane and underlying extracellular matrix (ECM) with respect to its hierarchical fiber-like morphology and display of bioactive signals is prerequisite for optimal epithelial cell function in vitro We report here on a bottom-up approach based on hydrogen-bonded supramolecular polymers and ECM-peptides to make an electro-spun bioactive supramolecular mesh which can be applied as synthetic basement membrane The supramolecular polymers used self-assembled into nano-meter scale fibers while at micro-meter scale fibers were formed by electro-spinning We introduced bioactivity into these nano-fibers by intercalation of different ECM-peptides designed for stable binding Living kidney membranes were shown to be bioengineered through culture of primary human renal tubular epithelial cells on these bioactive meshes Even after a long-term culturing period of 19 days we found that the cells on bioactive membranes formed tight monolayers while cells on non-active membranes lost their monolayer integrity Furthermore the bioactive membranes helped to support and maintain renal epithelial phenotype and function Thus incorporation of ECM-peptides Into electro-spun meshes via a hierarchical supramolecular method is a promising approach to engineer bioactive synthetic membranes with an unprecedented structure This approach may in future be applied to produce living bioactive membranes for a I:no-artificial kidney (C) 2010 Elsevier Ltd All rights reserve