Hydrogen-Bonds-Mediated Nanomedicine: Design, Synthesis, and Applications.

Among the various challenges in medicine, diagnosis, complete cure, and healing of cancers remain difficult given the heterogeneity and complexity of such a disease. Differing from conventional platforms with often unsatisfactory theranostic capabilities, the contribution of supramolecular interactions, such as hydrogen-bonds (H-bonds), to cancer nanotheranostics opens new perspectives for the design of biomedical materials, exhibiting remarkable properties and easier processability. Thanks to their dynamic characteristics, a feature generally observed for noncovalent interactions, H-bonding (macro)molecules can be used as supramolecular motifs for yielding drug- and diagnostic carriers that possess attractive features, arising from the combination of assembled nanoplatforms and the responsiveness of H-bonds. Thus, H-bonded nanomedicine provides a rich toolbox that is useful to fulfill biomedical needs with unique advantages in early-stage diagnosis and therapy, demonstrating the promising potential in clinical translations and applications. Here the design and synthetic routes toward H-bonded nanomedicines, focus on the growing understanding of the structure-function relationship for efficient cancer treatment are summarized. A guidance for designing new H-bonded intelligent theranostic agents is proposed, to inspire more successful explorations of cancer nanotheranostics and finally to promote potential clinical translations.

Hydrogen-Bonded Supramolecular Polymer Adhesives: Straightforward Synthesis and Strong Substrate Interaction.

High-performance adhesives are of great interest in view of industrial demand. We herein identify a straightforward synthetic strategy towards universal hydrogen-bonded (H-bonded) polymeric adhesives, using a side-chain barbiturate (Ba) and Hamilton wedge (HW) functionalized copolymer. Starting from a rubbery copolymer containing thiolactone derivatives, Ba and HW moieties are tethered as pendant groups via an efficient one-pot two-step amine-thiol-bromo conjugation. Hetero-complementary Ba/HW interactions thus yield H-bonded supramolecular polymeric networks. In addition to an enhanced polymeric network integrity induced by specific Ba/HW association, the presence of individual Ba or HW moieties enables strong binding to a range of substrates, outstanding compared to commercial glues and reported adhesives.

Polyether Sulfone-Based Epoxy Toughening: From Micro- to Nano-Phase Separation via PES End-Chain Modification and Process Engineering.

The toughness of a high-performance thermosetting epoxy network can be greatly improved by generating polyether sulfone-based macro- to nano-scale morphologies. Two polyethersulfones (PES) which only differ by their chain-end nature have been successively investigated as potential tougheners of a high-Tg thermoset matrix based on a mixture of trifunctional and difunctional aromatic epoxies and an aromatic diamine. For a given PES content, morphologies and toughness of the resulting matrices have been tuned by changing curing conditions and put into perspective with PES chain-end nature.

Routes to Hydrogen Bonding Chain-End Functionalized Polymers.

The contribution of supramolecular chemistry to polymer science opens new perspectives for the design of polymer materials exhibiting valuable properties and easier processability due to the dynamic nature of non-covalent interactions. Hydrogen bonding polymers can be used as supramolecular units for yielding larger assemblies that possess attractive features, arising from the combination of polymer properties and the responsiveness of hydrogen bonds. The post-polymerization modification of reactive end-groups is the most common procedure for generating such polymers. Examples of polymerizations mediated by hydrogen bonding-functionalized precursors have also recently been reported. This contribution reviews the current synthetic routes toward hydrogen bonding sticker chain-end functionalized polymers.

'All-supramolecular' nanocapsules from low-molecular weight ureas through interfacial addition reaction in miniemulsion.

This contribution presents a new strategy for preparing nanocapsules with a shell made of a supramolecular polymer which repeating units are held together by reversible interactions rather than covalent bonds. These nanocapsules were prepared in classical miniemulsion through interfacial addition reaction of a diisocyanate (IPDI) and a monoamine (iBA), forming low-molecular weight bis-ureas moieties which are strong self-complementary interacting molecules through hydrogen-bonding. The nanocapsules present a diameter around 100 nm, and MALDI-TOF MS and (1)H NMR analyses confirm the expected molecular characteristics for the shell. This strategy opens the scope of a new type of nanomaterials exhibiting stimuli-responsiveness due to the reversible interaction linking the repeating units.

Design of Heterocomplementary H-Bonding RAFT Agents - Towards the Generation of Supramolecular Star Polymers.

Supramolecular poly(vinyl acetate) PVAc 3-arms stars were successfully generated by Reversible Addition-Fragmentation chain Transfer (RAFT)-polymerized chains bearing hydrogen-bonding heterocomplementary associating units. Chain Transfer Agents (CTA) bearing thymine- and diaminopyridine-based units were first synthesized and proved to mediate efficiently the polymerization of VAc. The binding ability of the chains in solution was then demonstrated by (1) H NMR and GPC measurements, proving the formation of the supramolecular stars.

Thickness transition of a rigid supramolecular polymer.

A low molecular weight bisurea in nonpolar solvents is shown to self-assemble by hydrogen bonding into two distinct high molecular weight structures. At low temperature and high concentration, the most stable structure is a thick cylindrical assembly, responsible for the very high viscosity of the solution. At higher temperature or lower concentration, the thick filaments disappear in favor of thinner filaments, leading to a lower viscosity. The reversible transition occurs over a temperature range of 5 degrees C only, showing that it is highly cooperative. The structural switch can also be triggered by changing the nature of the solvent or the composition in the case of a mixture of two bisureas. The high cooperativity and the tunability of this transition are useful for the design of responsive materials.

N,N'-disubstituted ureas: influence of substituents on the formation of supramolecular polymers.

Symmetrical N,N'-disubstituted ureas have been synthesized and characterized. Among them, the branched dialkylureas prepared are highly soluble in organic media. Moreover, the solutions obtained are very viscous in heptane, if the branched alkyl groups are not too bulky (i.e. a methyl group on the alpha carbon, or an ethyl group on the beta carbon). Due to the strong, bifurcated hydrogen bonds between the urea moieties, linear supramolecular polymers are formed. The degree of association of these supramolecular polymers has been determined by FTIR spectroscopy.