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Heteromultivalency, which involves the simultaneous interactions of more than one type of ligand with more than one type of receptor, is ubiquitous in living systems and provides a powerful strategy to improve the binding efficiency of heterotopic species such as proteins and membranes. However, the design and development of artificial heteromultivalent receptors is still challenging owing to tedious synthesis processes and the need for precise control over the spatial arrangement of the binding sites. Here, we have designed a heteromultivalent platform by co-assembling cyclodextrin and calixarene amphiphiles, so that two orthogonal, non-covalent binding sites are distributed on the surface of the co-assembly. Binding with model peptides shows a synergistic effect of the two receptors, (hetero)multivalency and self-adaptability. The co-assembly shows promise for inhibition of the fibrillation of amyloid-β peptides and the dissolution of amyloid-β fibrils, substantially reducing amyloid cytotoxicity. This self-assembled heteromultivalency concept is easily amenable to other ensembles and targets, so that versatile biomedical applications can be envisaged.

Water-soluble supramolecular assemblies of redox-active ferrocenyl-decorated (Fc) poly(propylene imine) (PPI) dendrimers and -cyclodextrin (CD) were adsorbed at self-assembled monolayers (SAMs) of CD (“molecular printboards”). The dendrimers form a stable monolayer at the CD SAM owing to multivalent host−guest interactions. In the present study, dendrimers of generation 1 (4 Fc end groups) up to generation 5 (64 Fc end groups) were investigated. The immobilization of the dendrimers at the CD SAM can be under electrochemical control since Fc forms stable inclusion complexes with CD, whereas the oxidized ferrocenium (Fc) does not. The redox-dependent adsorption process was studied by potential-dependent electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Detailed information was obtained on the adsorption and desorption kinetics, the diffusion constants, and the conformation of the guest dendrimers adsorbed at the host surface.

Redox-active ferrocenyl (Fc)-functionalized poly(propylenimine) (PPI) dendrimers solubilized in aqueous media by complexation of the Fc end groups with -cyclodextrin (CD) were immobilized at monolayers of CD on glass (“molecular printboards”) via multiple host-guest interactions. The directed immobilization of the third-generation dendrimer-CD assembly G3-PPI-(Fc)16-(CD)16at the printboard was achieved by supramolecular microcontact printing. The redox activity of the patterned dendrimers was mapped by scanning electrochemical microscopy (SECM) in the positive feedback mode using IrCl63-as a mediator. Local oxidation of the Fc-dendrimers by the microelectrode-generated IrCl62-resulted in an effective removal of the Fc-dendrimers from the host surface since the oxidation of Fc to the oxidized form (Fc) leads to a concomitant loss of affinity for CD. Thus, SECM provided a way not only to image the surface, but also to control the binding of the Fc-terminated dendrimers at the molecular printboard. Additionally, the electrochemical desorption process could be monitored in time as the dendrimer patterns were gradually erased upon multiple scans.

Poly(propylene imine) dendrimers with dialkyl sulfide end groups were prepared and developed as inks for positive microcontact printing (()CP) on gold. Long (C10H21−S−C10H20−), medium (C3H7−S−C4H8−), and short (CH3−S−CH2−) dialkyl sulfide end groups were attached to second- and third-generation PPI dendrimers to create a family of dendritic sulfides. The dendritic inks flatten upon adsorption and form monolayers on gold. ()CP was performed on gold using commercially available poly(dimethylsiloxane) as stamp material and n-octadecanethiol as etch resist. The gold beneath the dendrimers was selectively etched away with an acidic Fe(NO3)3/thiourea solution to give the positive copy of the original master pattern. The multivalent sulfide attachment and the relatively high molecular mass of these dendrimers ensured minimal lateral ink spreading and thus optimal feature reproducibility. Contact times were varied to analyze the spreading rates of the dendritic inks. The spreading rates of the dendritic inks were found to be much lower than that of pentaerythritol tetrakis(3-mercaptopropionate). ()CP with the new inks was extended to submicrometer features. Optical microscopy, scanning electron microscopy, and atomic force microscopy were used to characterize the etched samples. Lines with a width of 100 nm were faithfully replicated with the third-generation dendrimers bearing medium (C3−S−C4−) end groups.