Constructing Hybrid Protein Zymogens through Protective Dendritic Assembly

The modulation of protein uptake and activity in response to physiological changes forms an integral part of smart protein therapeutics. We describe herein the self‐assembly of a pH‐responsive dendrimer shell onto the surface of active enzymes (trypsin, papain, DNase I) as a supramolecular protecting group to form a hybrid dendrimer–enzyme complex. The attachment is based on the interaction between boronic acid and salicyl hydroxamate, thus allowing the macromolecular assembly to respond to changes in pH between 5.0 and 7.4 in a highly reversible fashion. Catalytic activity is efficiently blocked in the presence of the dendrimer shell but is quantitatively restored upon shell degradation under acidic conditions. Unlike the native proteases, the hybrid constructs are shown to be efficiently taken up by A549 cells and colocalized in the acidic compartments. The programmed intracellular release of the proteases induced cytotoxicity, thereby uncovering a new avenue for precision biotherapeutics.     

Controlled Anchoring of (Phenylureido)sulfonamide-Based Receptor Moieties: An Impact of Binding Site Multiplication on Complexation Properties

The repetition of urea-based binding units within the receptor structure does not only lead to monomer properties multiplication. As confirmed by spectroscopic studies, UV-Vis and ¹H-NMR in classical or competitive titration mode, the attachment to a carrier allocates the active moieties to mutual positions predetermining the function of the whole receptor molecule. Bivalent receptors form self-aggregates. Dendritic receptors with low dihydrogen phosphate loadings offer a cooperative complexation mode associated with a positive dendritic effect. In higher dihydrogen phosphate concentrations, the dendritic branches act independently and the binding mode changes to 1:1 anion: complexation site. Despite the anchoring, the dendritic receptors retain the superior efficiency and selectivity of a monomer, paving the way to recyclable receptors, desirable for economic and ecological reasons.     

Supramolecular Dendrimers: Convenient Synthesis by Programmed Self‐Assembly and Tunable Thermoresponsivity

We report here the noncovalent synthesis of thermosensitive dendrimers. Short oligoguanosine strands were linked to the focal point of a dendron by using “click chemistry”, and quadruplex formation was used to drive the self‐assembly process in the presence of metal ions. The dynamic nature of these noncovalent assemblies can be exploited to create combinatorial libraries of dendrimers as demonstrated by the co‐assembly of two components. These supramolecular dendrimers showed thermoresponsive behavior that can be tuned by varying the templating cations or the number of guanines in the oligonucleotide strand.     

Self-assembly with block copolymers through metal coordination of SCS-Pd(II) pincer complexes and pseudorotaxane formation

Poly(norbornene)-based block copolymers containing side chains of palladated pincer complexes/dibenzo[24]crown-8 or palladated pincer complexes/dibenzylammonium salts were synthesized. Noncovalent functionalization was accomplished with their corresponding recognition units through simple 1:1 addition with association constants (Ka) greater than 10(5) m(-1). The self-assembly processes were monitored by using both 1H NMR spectroscopy and isothermal titration calorimetry. In all cases, we found that the self-assembly of the recognition units along each polymer block does not preclude the self-assembly processes along the other block.     

Quantitative Analysis of the Self‐Assembly Process of a Pd12L24 Coordination Sphere

The self‐assembly process of a Pd₁₂L₂₄ sphere was revealed by a quantitative approach (quantitative analysis of self‐assembly process: QASAP) quantifying all the substrates, the products, and the observable intermediates, indicating that the Pd₁₂L₂₄ sphere is produced through several pathways. Firstly, Pd_n L_2n (n= 6, 8, and 9), which are perfectly closed structures smaller than the Pd₁₂L₂₄ sphere, and a mixture of intermediates not observed by NMR ( Int ) were produced. Next, the sphere was assembled from intra‐/intermolecular reaction of a certain class of Int (path A) and from the coordination of free pyridyl groups in Int to the Pd^II center of Pd_n L_2n (n= 6, 8, and 9) (path B). While capping the free pyridyl groups in Int with Pd^II ions perfectly inhibited the sphere formation, the addition of free L to Int accelerated the formation of the sphere.     

Acid–Base‐Controlled Stereoselective Metalation of Overhanging Carboxylic Acid Porphyrins: Consequences for the Formation of Heterobimetallic Complexes

Overhanging carboxylic acid porphyrins have revealed promising ditopic ligands offering a new entry in the field of supramolecular coordination chemistry of porphyrinoids. Notably, the adjunction of a so‐called hanging‐atop (HAT) Pb^II cation to regular Pb^II porphyrin complexes allowed a stereoselective incorporation of the N‐core bound cation, and an allosterically controlled Newton’s cradle‐like motion of the two Pb^II ions also emerged from such bimetallic complexes. In this contribution, we have extended this work to other ligands and metal ions, aiming at understanding the parameters that control the HAT Pb^II coordination. The nature of the N‐core bound metal ion (Zn^II, Cd^II), the influence of the deprotonation state of the overhanging COOH group and the presence of a neutral ligand on the opposite side (exogenous or intramolecular), have been examined through ¹H NMR spectroscopic experiments with the help of radiocrystallographic structures and DFT calculations. Single and bis‐strap ligands have been considered. They all incorporate a COOH group hung over the N‐core on one side. For the bis‐strap ligands, either an ester or an amide group has been introduced on the other side. In the presence of a base, the mononuclear Zn^II or Cd^II complexes incorporate the carbonyl of the overhanging carboxylate as apical ligand, decreasing its availability for the binding of a HAT Pb^II. An allosteric effector (e.g., 4‐dimethylaminopyridine (DMAP), in the case of a single‐strap ligand) or an intramolecular ligand (e.g., an amide group), strong enough to compete with the carbonyl of the hung COO^?, is required to switch the N‐core bound cation to the opposite side with concomitant release of the COO^?, thereby allowing HAT Pb^II complexation. In the absence of a base, Zn^II or Cd^II binds preferentially the carbonyl of the intramolecular ester or amide groups in apical position rather than that of the COOH. This better preorganization, with the overhanging COOH fully available, is responsible for a stronger binding of the HAT Pb^II. Thus, either allosteric or acid–base control is achieved through stereoselective metalation of Zn^II or Cd^II. In the latter case, according to the deprotonation state of the COOH group, the best electron‐donating ligand is located on one or the other side of the porphyrin (COO^?>CONHR>COOR>COOH): the lower affinity of COOH for Zn^II and Cd^II, the higher for a HAT Pb^II. These insights provide new opportunities for the elaboration of innovative bimetallic molecular switches.     

Self‐Assembly of Tyrosine into Controlled Supramolecular Nanostructures

In the context of designing novel amino acid nanostructures, the capacity of tyrosine alone to form well‐ordered structures under different conditions was explored. It was observed that Tyr can self‐assemble into well‐defined morphologies when deposited onto surfaces for transmission electron microscopy, atomic force microscopy, and scanning electron microscopy. The influence of various parameters that can modulate the self‐assembly process, including concentration of the amino acid, aging time, and solvent, was studied. Different supramolecular architectures, including nanoribbons, branched structures, and fern‐like arrangements were also observed.     

Self‐Assembly of a Trinuclear Luminescent Europium Complex

Triangular luminescent box : Self‐assembly of a new multidentate receptor with europium cations results in the formation of trinuclear discrete complexes. X‐ray crystallography shows that nine‐coordinate cations are linked by ligands to provide a triangular complex in the solid state and in solution. Despite the coordinated solvent molecules, this topologically unusual complex exhibits remarkable luminescent properties.

     

Design, synthesis, and characterization of conifer-shaped dendritic architectures

An elongated structural design leading to more conical-shaped dendritic architectures by using a combination of 1-->3, 1-->(2+1), and 1-->(2+1 Me) C-branched monomers is presented. Synthesis of the conifer-shaped macromolecule was achieved by reaction between isocyanate 20 and amine 26 in dry CH2Cl2. A resultant extended focal adamantane-modified dendron was deprotected to generate the water-soluble product, which was subsequently complexed with beta-cyclodextrin in D2O to create the desired tree-like product. Host-guest interactions of the adamantane moiety with the beta-cyclodextrin cavity were monitored by 1H NMR spectroscopy. All monomers, key intermediates, and final products were fully characterized by 1H and 13C NMR spectroscopy, ESI or MALDI-TOF mass spectrometry, and IR spectroscopy.     

Site‐Selective Ligand Exchange on a Heteroleptic TiIV Complex Towards Stepwise Multicomponent Self‐Assembly

A series of heteroleptic [Ti 1 ₂X]^? complexes have been selectively constructed from a mixture of Ti^IV ions, a pyridyl catechol ligand (H₂ 1 ; H₂ 1 =4‐(3‐pyridyl)catechol), and various bidentate ligands (HX) in the presence of a weak base, in addition to a previously reported [Ti 1 ₂(acac)]^? (acac=acetylacetonate) complex. Comparative studies of these Ti^IV complexes revealed that [Ti 1 ₂(trop)]^? (trop=tropolonate) is much more stable than the [Ti 1 ₂(acac)]^? complex, which allows the replacement of acac with trop on the [Ti 1 ₂(acac)]^? complex. This Ti^IV‐centered site‐selective ligand exchange reaction also takes place on a heteronuclear Pd^II? Ti^IV ring complex with the preservation of the Pd^II‐centered coordination structures. Intra‐ and intermolecular linking between two Ti^IV centers with a flexible or a rigid bis‐tropolone bridging ligand provided a tetranuclear and an octanuclear Pd^II? Ti^IV complex, respectively. These higher‐order structures could be efficiently constructed only through a stepwise synthetic route.     

Metal‐Ion‐Coated Graphitic Nanotubes: Controlled Self‐Assembly of a Pyridyl‐Appended Gemini‐Shaped Hexabenzocoronene Amphiphile

The assembly line : Hexabenzocoronene amphiphiles appended with pyridyl‐terminated triethylene glycol side chains, in combination with trans‐[Pt(PhCN)₂Cl₂], lead to the formation of graphitic nanotubes. The structural features and dimensions of the nanotubes depend on the assembly conditions. A platinum(II)‐bridged cyclic dimer having two HBC units self‐assembles into a nanotubular structure.

     

Component Selection in the Self‐Assembly of Palladium(II) Nanocages and Cage‐to‐Cage Transformations

Dynamic supramolecular systems involving a tetratopic palladium(II) acceptor and three different pyridine‐ and imidazole‐based donors have been used for self‐selection by a synergistic effect of morphological information and coordination ability of ligands through specific coordination interactions. Three different cages were first synthesized by two‐component self‐assembly of individual donor and acceptor. When all four components were allowed to interact in a reaction mixture, only one out of three cages was isolated. The preferential binding affinity towards a particular partner was also established by transforming a non‐preferred cage into a preferred cage by interaction with the appropriate ligand. Computational studies further supported the fact that coordination interaction of imidazole moiety to Pd^II is enthalpically more preferred compared to pyridine, which drives the selection process. Analysis of crystal packing of both complexes indicated the presence of strong hydrogen bonds between nitrate and water molecules and also H‐bonded 3D networks of water. Both complexes exhibit promising proton conductivity (10^?5 to ca. 10^?3 S cm^?1) at ambient temperature under a relative humidity of circa 98 % with low activation energy.     

Reversible Guest Uptake/Release by Redox‐Controlled Assembly/Disassembly of a Coordination Cage

Controlling the guest expulsion process from a receptor is of critical importance in various fields. Several coordination cages have been recently designed for this purpose, based on various types of stimuli to induce the guest release. Herein, we report the first example of a redox‐triggered process from a coordination cage. The latter integrates a cavity, the panels of which are based on the extended tetrathiafulvalene unit (exTTF). The unique combination of electronic and conformational features of this framework (i.e. high π‐donating properties and drastic conformational changes upon oxidation) allows the reversible disassembly/reassembly of the redox‐active cavity upon chemical oxidation/reduction, respectively. This cage is able to bind the three‐dimensional B₁₂F₁₂^2? anion in a 1:2 host/guest stoichiometry. The reversible redox‐triggered disassembly of the cage could also be demonstrated in the case of the host–guest complex, offering a new option for guest‐delivering control.     

Calixarene amino acids; building blocks for calixarene peptides and peptide-dendrimers

A modular strategy towards receptor macromolecules is presented, which combines synthetically diverse peptide synthesis with highly functional calixarene chemistry. The design and synthesis of calix[4]arene amino acids 1a-f, calix-lysines, is described, which were used as construction blocks to assemble nanoscale, multivalent entities—calix-peptides 2 and calix-peptide-dendrimers 3.