Two‐Dimensional Assembly Based on Flow Supramolecular Chemistry: Kinetic Control of Molecular Interactions Under Solvent Diffusion

Self‐assembly of porphyrin molecules can be controlled kinetically to form structures with lengths extending from the nano‐ to the micrometer scale, through a programmed solvent‐diffusion process in designed microflow spaces. Temporal solvent structures generated in the microflow were successfully transcribed into molecular architectures.     

Metal Recognition Driven by Weak Interactions: A Case Study in Solvent Extraction

Tuning the affinity of a medium for a given metallic cation with the sole modification of weak interactions is a challenge for molecular recognition. Solvent extraction is a key technique employed in the recovery and purification of valuable metals, and it is facing an increased complexity of metal fluxes to deal with. The selectivity of such processes generally relies on the use of specific ligands, designed after their coordination chemistry. In the present study, we illustrate the possibility to employ the sole control of weak interactions to achieve the selective extraction of Pd^II over Nd^III: the control over selectivity is obtained by tuning the self‐assembly of the organic phase. A model is proposed, after detailed experimental analysis of molecular (XRD, NMR) and supra‐molecular (SAXS) features of the organic phases. We thus demonstrate that Pd^II extraction is driven by metal coordination, whereas Nd^III extraction requires aggregation of the extractant in addition to metal coordination. These results are of general interest for the applications which rely on the stabilization of metals in organic phases.     

Very Facile Polarity Umpolung and Noncovalent Functionalization of Inorganic Nanoparticles: A Tool Kit for Supramolecular Materials Chemistry

The facile assembly of shell‐by‐shell (SbS)‐coated nanoparticles [TiO₂?PAC₁₆]@shell 1 – 7 (PAC₁₆=hexadecylphosphonic acid), which are soluble in water and can be isolated as stable solids, is reported. In these functional architectures, an umpolung of dispersibility (organic apolar versus water) was accomplished by the noncovalent binding of ligands 1 – 7 to titania nanoparticles [TiO₂?PAC₁₆] containing a first covalent coating with PAC₁₆. Ligands 1 – 7 are amphiphilic and form the outer second shell of [TiO₂?PAC₁₆]@shell 1 – 7 . The tailor‐designed dendritic building blocks 3 – 5 contain negative and positive charges in the same molecule, and ligands 6 and 7 contain a perylenetetracarboxylic acid dimide (PDI) core ( 6 / 7 ) as a photoactive reporter component. In the redox and photoactive system [TiO₂?PAC₁₆]@shell 7 , electronic communication between the inorganic core to the PDI ligands was observed.     

Switching the Mechanism of NADH Photooxidation by Supramolecular Interactions

A series of three Ru(II) polypyridine complexes was investigated for the selective photocatalytic oxidation of NAD(P)H to NAD(P)⁺ in water. A combination of (time-resolved) spectroscopic studies and photocatalysis experiments revealed that ligand design can be used to control the mechanism of the photooxidation: For prototypical Ru(II) complexes a ¹O₂ pathway was found. Rudppz ([(tbbpy)₂Ru(dppz)]Cl₂, tbbpy=4,4'-di-tert-butyl-2,2'-bipyridine, dppz=dipyrido[3,2-a:2′,3′-c]phenazine), instead, initiated the cofactor oxidation by electron transfer from NAD(P)H enabled by supramolecular binding between substrate and catalyst. Expulsion of the photoproduct NAD(P)⁺ from the supramolecular binding site in Rudppz allowed very efficient turnover. Therefore, Rudppz permits repetitive selective assembly and oxidative conversion of reduced naturally occurring nicotinamides by recognizing the redox state of the cofactor under formation of H₂O₂ as additional product. This photocatalytic process can fuel discontinuous photobiocatalysis.     

Paramagnetic DOSY: An Accurate Tool for the Analysis of the Supramolecular Interactions between Lanthanide Complexes and Proteins

Diffusion ordered NMR is implemented to determine accurately the mobility of paramagnetic tris‐dipicolinate lanthanide complexes that are versatile probes of protein structure. It is shown that diffusion coefficient ratios can be measured with an accuracy of 1 % using a standard BPPLED pulse sequence, which allows for observing significant, though weak, variations when different species are interacting with the paramagnetic compound. We demonstrate that this approach is complementary to classical chemical shift titration experiments, and that it can be applied successfully to probe the supramolecular dynamic interactions between lanthanide complexes and small molecules on the one hand, or to determine rapidly their affinity for a targeted protein.     

Bioinspired Therapeutic Dendrimers as Efficient Peptide Drugs Based on Supramolecular Interactions for Tumor Inhibition

Bioinspired tryptophan‐rich peptide dendrimers (TRPDs) are designed as a new type of dendritic peptide drugs for efficient tumor therapy. The TRPDs feature a precise molecular structure and excellent water solubility and are obtained in a facile process. Based on the unique features of peptide dendrimers, including highly branched structures, abundant terminal groups, and globular‐protein‐like architectures, the therapeutic dendrimers show significant supramolecular interactions with DNA through the tryptophan residues (indole rings and amino groups). Further experimental results indicate that TRPDs are efficient antitumor agents both in vitro and in vivo.     

Effect of an Aromatic Solvent on Hydrogen-Bond-Directed Supramolecular Polymerization Leading to Distinct Topologies

Beyond phenomenon, self-assembly of synthetic molecules, is now becoming an essential tool to design supramolecular materials not only in the thermodynamically stable state but also in kinetically trapped states. However, an approach to design complex self-assembly processes comprising different types of self-assembled states remains elusive. Herein, an example of such systems is demonstrated based on a unique supramolecular polymer mediated by supermacrocyclization of hydrogen-bonding π-conjugated molecules. By adding an aromatic solvent into nonpolar solutions of the monomer, spontaneous nucleation triggered by supermacrocyclization was suppressed so that isothermal supramolecular polymerization could be achieved from kinetically formed topological variants and amorphous agglomerates to afford helicoidal structures hitherto obtainable only with very slow cooling of a hot solution. By increasing the proportion of aromatic solvent further, another self-assembly path was found, based on competing extended hydrogen-bonded motifs affording crystalline nanowires.     

A pH-Induced Reversible Conformational Switch Able to Control the Photocurrent Efficiency in a Peptide Supramolecular System

External stimuli are potent tools that Nature uses to control protein function and activity. For instance, during viral entry and exit, pH variations are known to trigger large protein conformational changes. In Nature, also the electron transfer (ET) properties of ET proteins are influenced by pH-induced conformational changes. In this work, a pH-controlled, reversible 3₁₀-helix to α-helix conversion (from acidic to highly basic pH values and vice versa) of a peptide supramolecular system built on a gold surface is described. The effect of pH on the ability of the peptide SAM to generate a photocurrent was investigated, with particular focus on the effect of the pH-induced conformational change on photocurrent efficiency. The films were characterized by electrochemical and spectroscopic techniques, and were found to be very stable over time, also in contact with a solution. They were also able to generate current under illumination, with an efficiency that is the highest recorded so far with biomolecular systems.     

Influence of the Solvent and the Enantiomeric Purity on the Transition between Different Supramolecular Polymers

The self‐assembly of two enantiomerically pure hexa(oligo (p‐phenylene vinylene))‐substituted benzenes having 24 stereocenters was studied in pure methylcyclohexane (MCH) and in a mixture of MCH/toluene (4:1). Irrespective of the solvent a cooperative supramolecular polymerization mechanism was determined for these star‐shaped molecules by using temperature‐dependent CD and UV/Vis spectroscopy. Quite remarkably, a transition from one helical supramolecular state (A) to a second more thermodynamically stable supramolecular helical assembly (B) was observed. The rate of the A→B transition was strongly dependent on the nature of the solvent; being faster in the solvent mixture than in pure MCH. By using size exclusion chromatography we could relate the increased rate to a decreased stability of the supramolecular A state in the solvent mixture. Next, we mixed the two enantiomerically pure hexa‐substituted benzene derivatives in a so‐called majority‐rules experiment, which lead to the anitcipated chiral amplification in the A state. More importantly it appeared that the A→B transition was significantly hampered in these mixed systems. Furthermore, the absence of chiral amplification in the B state revealed the formation of separated enantiomerically pure assemblies. Therefore, by using a wide variety of spectroscopic and chromatographic techniques we determined the influence of solvent and enantiomeric purity on the transition between different supramolecular states.     

Supramolecular Stabilization of Metastable Tautomers in Solution and the Solid State

This work presents a successful application of a recently reported supramolecular strategy for stabilization of metastable tautomers in cocrystals to monocomponent, non‐heterocyclic, tautomeric solids. Quantum‐chemical computations and solution studies show that the investigated Schiff base molecule, derived from 3‐methoxysalicylaldehyde and 2‐amino‐3‐hydroxypyridine ( ap ), is far more stable as the enol tautomer. In the solid state, however, in all three obtained polymorphic forms it exists solely as the keto tautomer, in each case stabilized by an unexpected hydrogen‐bonding pattern. Computations have shown that hydrogen bonding of the investigated Schiff base with suitable molecules shifts the tautomeric equilibrium to the less stable keto form. The extremes to which supramolecular stabilization can lead are demonstrated by the two polymorphs of molecular complexes of the Schiff base with ap . The molecules of both constituents of molecular complexes are present as metastable tautomers (keto anion and protonated pyridine, respectively), which stabilize each other through a very strong hydrogen bond. All the obtained solid forms proved stable in various solid‐state and solvent‐mediated methods used to establish their relative thermodynamic stabilities and possible interconversion conditions.     

A Synthetic Supramolecular Receptor for the Hydrosulfide Anion

Hydrogen sulfide (H₂S) has emerged as a crucial biomolecule in physiology and cellular signaling. Key challenges associated with developing new chemical tools for understanding the biological roles of H₂S include developing platforms that enable reversible binding of this important biomolecule. The first synthetic small molecule receptor for the hydrosulfide anion, HS^?, using only reversible, hydrogen‐bonding interactions in a series of bis(ethynylaniline) derivatives, is reported. Binding constants of up to 90 300±8700 m ^?1 were obtained in MeCN. The fundamental science of reversible sulfide binding, in this case featuring a key CH???S hydrogen bond, will expand the possibility for discovery of sulfide protein targets and molecular recognition agents.     

Synthesis of Supramolecular Nanocapsules Based on Threading of Multiple Cyclodextrins over Polymers on Gold Nanoparticles

The CD ' s stuck : Poly(ethylene glycol) chains anchored onto gold nanoparticles (AuNPs) are threaded by multiple α‐cyclodextrin (α‐CD) rings to form a supramolecular outer layer composed of pseudopolyrotaxane columns perpendicular to the nanoparticle surface. Capping the polymer ends confines α‐CD on the nanoparticle surface, cross‐linking the α‐CD rings and then removing the AuNP cores produces supramolecular nanocapsules.

     

Carbohydrate Recognition through Noncovalent Interactions: A Challenge for Biomimetic and Supramolecular Chemistry

Carbohydrates are not always as “sticky” as one might expect . Even in organic solvents they are difficult targets for the supramolecular chemist, due to their complex, three-dimensional structures. In their natural environment (water) they are especially elusive, presenting challenges which will occupy synthetic and theoretical chemists for some time to come. The complex of an octaamide supramolecular receptor with β-D -glucopyranose, which binds through apolar and polar contacts, is shown.