While a great deal of knowledge on the roles of hydrogen bonding and hydrophobicity in proteins have resulted in the creation of rationally designed and functional peptidic structures, the roles of these forces on purely synthetic supramolecular architectures in water have proven difficult to ascertain. Focusing on a 1,3,5-benzenetricarboxamide (BTA) based supramolecular polymer, we have designed a molecular modeling strategy to dissect the energetic contributions involved in the self-assembly (electrostatic, hydrophobic, etc.) upon growth of both ordered BTA stacks and random BTA aggregates. Utilizing this set of simulations, we have unraveled the cooperative mechanism for polymer growth, where a critical size must be reached in the aggregates before emergence and amplification of order into the experimentally observed fibers. Furthermore, we have found that the formation of ordered fibers is favored over disordered aggregates solely on the base of electrostatic interactions. Detailed analysis of the simulation data suggests that H-bonding is a major source of this stabilization energy. Experimental and computational comparison with a newly synthesized 1,3,5-benzenetricarboxyester (BTE) derivative, lacking the ability to form the H-bonding network, demonstrated that this BTE variant is also capable of fiber formation, albeit at a reduced persistence length. This work provides unambiguous ev-idence for the key 1D driving force of hydrogen bonding in enhancing the persistency of monomer stacking and amplifying the lev-el of order into the growing supramolecular polymer in water. Our computational approach provides an important relationship di-rectly linking the structure of the monomer to the structure and properties of the supramolecular polymer.

Dendrimers are well-defined macromolecules whose highly branched structure is reminiscent of many natural structures, such as trees, dendritic cells, neurons or the networks of kidneys and lungs. Nature has privileged such branched structures for increasing the efficiency of exchanges with the external medium; thus, the whole structure is of pivotal importance for these natural networks. On the contrary, it is generally believed that the properties of dendrimers are essentially related to their terminal groups, and that the internal structure plays the minor role of an ‘innocent' scaffold. Here we show that such an assertion is misleading, using convergent information from biological data (human monocytes activation) and all-atom molecular dynamics simulations on seven families of dendrimers (13 compounds) that we have synthesized, possessing identical terminal groups, but different internal structures. This work demonstrates that the scaffold of nanodrugs strongly influences their properties, somewhat reminiscent of the backbone of proteins.

The construction of hierarchical materials through controlled self-assembly of molecular building blocks (e.g., dendrimers) represents a unique opportunity to generate functional nanodevices in a convenient way. Transition-metal compounds are known to be able to interact with cationic dendrimers to generate diverse supramolecular structures, such as nanofibers, with interesting collective properties. In this work, molecular dynamics simulation (MD) demonstrates that acetate ions from dissociated Cd(CH(3)COO)(2) selectively generate cationic PPI-dendrimer functional fibers through hydrophobic modification of the dendrimer's surface. The hydrophobic aggregation of dendrimers is triggered by the asymmetric nature of the acetate anions (AcO(-)) rather than by the precise transition metal (Cd). The assembling directionality is also controlled by the concentration of AcO(-) ions in solution. Atomic force (AFM) and transmission electron microscopy (TEM) prove these results. This well-defined directional assembly of cationic dendrimers is absent for different cadmium derivatives (i.e., CdCl(2), CdSO(4)) with symmetric anions. Moreover, since the formation of these nanofibers is controlled exclusively by selected anions, fiber disassembly can be consequently triggered via simple ionic competition by NaCl salt. Ions are here reported as a simple and cost-effective tool to drive and control actively the assembly and the disassembly of such functional nanomaterials based on dendrimers.

We use monodisperse dendrons that allow control over functional group presentation to investigate the influence of the location of a ligand on protein-induced disassembly and release of encapsulated small molecules. Based on both experiments and molecular dynamics simulations, we demonstrate that ligand location greatly influences release of guest molecules from the dendron-based supramolecular assembly. We show that a ligand moiety grafted to the dendron periphery is more accessible for the target protein in aqueous solution. On the other hand, the ligand moiety placed at the focal point or at the intermediate layer within the dendritic scaffold is less accessible, since it is surrounded by an environment rich in PEG chains, which hinders binding and even influences nonspecific interactions. We also demonstrate that the specific binding between one ligand and the target protein can destabilize the dendritic assembly. Furthermore, if more ligands are available, multivalent interactions are also possible with extravidin, which speed up disassembly and trigger the release of hydrophobic guests.

Fully consistent X-ray data and molecular dynamics simulations on new star-shaped liquid crystals yield two nanosegregated architectures with a coaxial stacking of two functional discotic units: tris(triazolyl)triazine and triphenylene. Analysis of lattice order along the principal axes reveals preferential staggered arrangement of the stacked molecules in the columnar assembly.