Maarten M. J. Smulders

Pathway complexity in supramolecular polymerization

Self-assembly provides an attractive route to functional organic materials, with properties and hence performance depending sensitively on the organization of the molecular building blocks. Molecular organization is a direct consequence of the pathways involved in the supramolecular assembly process, which is more amenable to detailed study when using one-dimensional systems. In the case of protein fibrils, formation and growth have been attributed to complex aggregation pathways that go beyond traditional concepts of homogeneous and secondary nucleation events. The self-assembly of synthetic supramolecular polymers has also been studied and even modulated, but our quantitative understanding of the processes involved remains limited. Here we report time-resolved observations of the formation of supramolecular polymers from π-conjugated oligomers. Our kinetic experiments show the presence of a kinetically favoured metastable assembly that forms quickly but then transforms into the thermodynamically favoured form. Quantitative insight into the kinetic experiments was obtained from kinetic model calculations, which revealed two parallel and competing pathways leading to assemblies with opposite helicity. These insights prompt us to use a chiral tartaric acid as an auxiliary to change the thermodynamic preference of the assembly process. We find that we can force aggregation completely down the kinetically favoured pathway so that, on removal of the auxiliary, we obtain only metastable assemblies.

How to distinguish isodesmic from cooperative supramolecular polymerisation

To study the supramolecular polymerisation mechanisms of a self-assembling system, concentration- and temperature-dependent measurements can both be used to probe the transition from the molecular dissolved state to the aggregated state. In this report, both methods are evaluated to determine their effectiveness in identifying and quantifying the self-assembly mechanism for isodesmic and cooperative self-assembling systems. It was found that for a rapid and unambiguous determination of the self-assembly mechanism and its thermodynamic parameters, temperature-dependent measurements are more appropriate. These studies allow the acquisition of a large data set leading to an accurate determination of the self-assembly mechanism and quantification of the different thermodynamic parameters that describe the supramolecular polymerisation. For a comprehensive characterisation, additional concentration-dependent measurements can be performed.

Anion-induced reconstitution of a self-assembling system to express a chloride-binding Co10L15 pentagonal prism

Biochemical systems are adaptable, capable of reconstitution at all levels to achieve the functions associated with life. Synthetic chemical systems are more limited in their ability to reorganize to achieve new functions; they can reconfigure to bind an added substrate (template effect) or one binding event may modulate a receptors affinity for a second substrate (allosteric effect). Here we describe a synthetic chemical system that is capable of structural reconstitution on receipt of one anionic signal (perchlorate) to create a tight binding pocket for another anion (chloride). The complex, barrel-like structure of the chloride receptor is templated by five perchlorate anions. This second-order templation phenomenon allows chemical networks to be envisaged that express more complex responses to chemical signals than is currently feasible.

Asymmetrically Substituted Benzene‐1,3,5‐tricarboxamides: Self‐Assembly and Odd–Even Effects in the Solid State and in Dilute Solution

Molecular organization: Chiral benzene tricarboxamides with methyl substituents at defined positions self-assemble into supramolecular polymers of preferred helicity by three-fold alpha-helical-type hydrogen bonding. The odd-even effect is operative and all derivatives are liquid crystalline showing a Col(ho) phase (see figure).Asymmetric benzene-1,3,5-tricarboxamides (aBTAs) comprising two n-octyl and one chiral methyl-alkyl side chain were synthesised and characterised. The influence of the position and the configuration of the chiral methyl group (methyl at the alpha, beta or gamma position) in the aliphatic side chains on the liquid-crystalline properties and the aggregation behaviour of the aBTAs was systematically studied and compared to symmetrical benzene-1,3,5-tricarboxamides (sBTAs). Solid-state characterisation (polarised optical microscopy, IR spectroscopy, X-ray diffraction and differential scanning calorimetry) revealed that all aBTAs show threefold, alpha-helical-type intermolecular hydrogen bonding between neighbouring molecules and exhibit a columnar hexagonal organisation from room temperature to well above 200 degrees C. Moving the chiral methyl group closer to the amide group stabilises the liquid-crystalline state, as evidenced by a higher clearing temperature and corresponding enthalpy. The self-assembly of dilute solutions of the aBTAs in methylcyclohexane ( approximately 10(-5) mol L(-1)) was investigated with circular dichroism (CD) spectroscopy. The sign of the Cotton effect demonstrated a pronounced odd-even effect, whereas the value of the molar ellipticity, Deltaepsilon, in the aBTAs was independent of the position of the methyl group. Subsequent temperature-dependent CD measurements showed that the aggregation of all aBTAs can quantitatively be described by the nucleation-growth model and that the stability of the aggregates increases when the chiral methyl group is closer to the amide moiety. The results presented herein illustrate that even small changes in the molecular structure of substituted benzene-1,3,5-tri-carboxamides affect their solid-state properties and their self-assembly behaviour in dilute solutions.

Integrative Self‐Sorting Synthesis of a Fe8Pt6L24 Cubic Cage

The many different chemical processes associated with life run in parallel within the cytoplasm of a cell. These processes are not spatially separated by membranes, yet they do not interfere with each other. The biomolecular agents of these processes can be said to undergo self-sorting, which is defined as “the high-fidelity recognition of self from nonself”, into the locally organized systems that achieve individual functions. The goal of creating synthetic self-sorting systems is thus inspired in part by the prospect of synthesizing functional supramolecular systems that carry out different processes together in solution. Self-assembled metal–organic capsules have been shown to be useful for a variety of applications, including guest binding and separation, cavity-controlled catalysis, generation of unusual reaction products, and stabilization of reactive intermediates. New strategies have been explored to prepare more complex, metal–organic capsules so as to achieve new functions. The potential of self-sorting has only recently been acknowledged by researchers as a method for preparing such capsules. One strategy pursued by researchers to create progressively more-complex metal–organic architectures has been the preparation of heteroleptic species. This method relies on the combination of at least two types of homotopic ligands and a single metal ion for the construction of a metal–organic complex. An alternative method to create complexity, employed herein, entails the use of a single heterotopic ligand and more than one metal ion, wherein the fidelity of the self-assembly relies on integrative self-sorting. Our construction method relies on two different metal ions and coordination environments: in addition to the tris(pyridylimine)iron(II) moiety, widely employed in the subcomponent self-assembly of complex structures, we have introduced a second coordination motif, the tetrakis(pyridine)platinum(II) moiety. To this end, ditopic ligand 1 (Scheme 1), was selected as a ligand that can coordinate to both Fe (as a tris(pyridylimine) complex) and Pt ions (through its terminal pyridine group). Based on the fourfold symmetry of the tetrakis(pyridine)platinum(II) moiety and the threefold symmetry of the tris(pyridylimine)iron(II) moiety, we envisioned the possibility of preparing a heterometallic cubic capsule: after synthesis of the square-planar Pt complex 2, this intermediate could be incorporated into heterometallic cube 3 by formation of Fe-stabilized pyridylimine bonds (Scheme 1, right). Self-sorting could be validated within such a system by starting with the free subcomponents and metal ions, and allowing each to find its proper place within the final product structure (Scheme 1, left). For this selfassembly process to work, the two different kinds of sphybridized nitrogen donors must bind to the correct metal ions, without scrambling. Herein we employ integrative self-sorting in the synthesis of the heterometallic Fe8Pt6L24 cube 3 (Scheme 1). A one-pot synthesis of cube 3 from four different components, in which a total of 62 building blocks are brought together, was found to be possible, thus demonstrating both the potential of selfScheme 1. The two-step synthesis of cube 3 via the square-planar Pt intermediate 2 and the one-pot synthesis of 3 starting from free subcomponents and metal ions. For clarity, the chemical structure of only one of the six faces of the cube is shown.

Selective anion binding by a “Chameleon” capsule with a dynamically reconfigurable exterior

A new class of tetrahedral metal–organic capsules that can incorporate up to twelve different externally-directed amine residues is reported, allowing for very large dynamic libraries to be formed from mixtures of amines. Selectivity is observed both externally—more electron-rich amines are incorporated in favour of electron-poor amines—and internally—PF6− is bound in preference to CF3SO3− or BF4−.

Thermodynamics of Supramolecular Naphthalenediimide Nanotube Formation: The Influence of Solvents, Side Chains, and Guest Templates

Amino-acid functionalized naphthalenediimides self-assemble into hydrogen-bonded supramolecular helical nanotubes via a noncooperative, isodesmic process; the self-assembly of ordered helical systems is usually realized through a cooperative process. This unexpected behavior was rationalized as a manifestation of entropy-enthalpy compensation. Fundamental insights into the thermodynamics governing this self-assembly were obtained through the fitting of the isodesmic model to (1)H NMR spectrometry and circular dichroism spectroscopy measurements. Furthermore, we have extended the application of this mathematical model, for the first time, to quantitatively estimate the effect of guests, solvents, and side chains on the stability of the supramolecular nanotube; most significantly, we demonstrate that C(60) acts as a template to stabilize the nanotube assembly and thereby substantially increase the degree of polymerization.

Generation of a Dynamic System of Three-Dimensional Tetrahedral Polycatenanes

Seven of the best: A dynamic combinatorial library of polycatenated tetrahedra was prepared by complexation between a dynamic Fe4L6 tetrahedral cage, constructed from ligands containing an electron‐deficient naphthalenediimide core, and an electron‐rich aromatic crown ether, 1,5‐dinaphtho[38]crown‐10. The highest order species in the library is the tetrahedral [7]catenane.WILEY-VCH

Probing the Limits of the Majority-Rules Principle in a Dynamic Supramolecular Polymer

By systematic variation of the chemical structure of benzene-1,3,5-tricarboxamide (BTA) derivatives, the effect of chemical structure on the amplification of chirality was studied and quantified. In combination with temperature-dependent amplification experiments, the limits of the majority-rules principle were also investigated. For all BTA derivatives a high, constant helix reversal penalty was determined, which is related to the intermolecular hydrogen bonds that are present in all studied derivatives. For asymmetrically substituted BTA derivatives an odd-even effect was found in the degree of chiral amplification when changing the position of the stereogenic center with respect to the amide functionality. It was found that the mismatch penalty could be directly related to the number of stereocenters present in the molecules. Increasing this number from one to three resulted in an increase in this energy penalty while leaving the helix reversal penalty unaffected. For the majority-rules principle this implies that a single stereocenter present in the molecule contains sufficient chiral information at the molecular level to result in a chirally amplified state at the supramolecular level. Further evidence that the mismatch penalty is directly related to the number of stereocenters was obtained from mixed majority-rules experiments where two BTA derivatives with different numbers of stereocenters with opposite stereoconfiguration were studied in a majority-rules experiment. Finally, the ultimate limits of chiral amplification for the majority-rules principle were investigated, revealing that, given a certain helix reversal penalty, there is an optimum to which the mismatch penalty can be reduced while also enhancing the degree of chiral amplification. Temperature-dependent majority-rules experiments could indeed confirm these simulations. These findings show the relevance of both energy penalties when trying to enhance the degree of chiral amplification for the majority-rules principle in a one-dimensional helical supramolecular polymer.

Self‐Assembly of Ureido‐Pyrimidinone Dimers into One‐Dimensional Stacks by Lateral Hydrogen Bonding

Ureido-pyrimidinone (UPy) dimers substituted with an additional urea functionality self-assemble into one-dimensional stacks in various solvents through lateral non-covalent interactions. (1)H NMR and DOSY studies in CDCl(3) suggest the formation of short stacks (<10), whereas temperature-dependent circular dichroism (CD) studies on chiral UPy dimers in heptane show the formation of much larger helical stacks. Analysis of the concentration-dependent evolution of chemical shift in CDCl(3) and the temperature-dependent CD effect in heptane suggest that this self-assembly process follows an isodesmic pathway in both solvents. The length of the aggregates is influenced by substituents attached to the urea functionality. In sharp contrast, UPy dimers carrying an additional urethane group do not self-assemble into ordered stacks, as is evident from the absence of a CD effect in heptane and the concentration-independent chemical shift of the alkylidene proton of the pyrimidinone ring in CDCl(3).