Molecular hospitality: Self‐assembled molecular containers provide a very specific geometric as well as chemical environment for a bound guest, which allows for selective guest binding or the ...stabilization of unstable molecules or unstable conformations within the capsule (see scheme). The geometric constraints imposed by the container can even change the outcome of a chemical reaction.
Through their unique and specific interactions with various metal ions, naturally occurring proteins control structures and functions of many biological processes and functions in organisms. Inspired ...by natural metallopeptides, chemists have developed artificial peptides which coordinate with metal ions through their functional groups either for introducing a special reactivity or for constructing nanostructures. However, the design of new coordination peptides requires a deep understanding of the structures, assembly properties, and dynamic behaviours of such peptides. This review briefly discusses strategies of peptide self-assembly induced by metal coordination to different natural and non-natural binding sites in the peptide. The structures and functions of the obtained aggregates are described as well. We also highlight some examples of a metal-induced peptide self-assembly with relevance to biotechnology applications.
This review summarizes the recent development of structures, functions, as well as strategies of a peptide self-assembly induced by metal ions.
In general, self-assembly in polar solutions requires a combination of several non-covalent interactions within one binding motif. Besides the combination of H-bonds and hydrophobic or aromatic ...stacking interactions, in the last few years H-bonded ion pairs have been proven useful in this context. Also the molecular rigidity and the extent of intra- versus intermolecular interactions within the monomer play an important role in determining the self-assembling properties of a given monomer. We present some general guidelines and illustrative examples of various approaches that have been pursued in the literature before finally concentrating on a case study from our own work, the dimerization of a guanidiniocarbonyl pyrrole carboxylate zwitterion. This zwitterion forms stable dimers with K > 10(9) M(-1) in DMSO and >10(2) M(-1) even in water and can not only be used to study the importance of various non-covalent interactions for self-assembly in polar solvents but also to construct large nanostructures.
Herein, a novel cationic peptide gemini amphiphile containing diacetylene motifs (DA2P) is presented, which self‐assembles into novel tadpole‐ and bola‐shaped nanostructures at low concentrations and ...nanofibers at higher concentrations. Interestingly, the DA2P assemblies can be polymerized into a fluorescent red phase but only during incubation with HeLa cells, most likely owing to the reorganization of the diacetylene chains of DA2P upon interaction with the cell membrane. The red‐fluorescent polymerized DA2P assemblies can serve as a novel cell imaging probe. However, only vesicles, tadpole‐ and bola‐shaped DA2P assemblies can be translocated into HeLa cells, whereas the nanofiber‐like DA2P assemblies are trapped by the cell membranes and do not enter the cells. Hence, morphology‐dependent cell imaging is observed.
Novel nanostructure: A peptide gemini amphiphile containing diacetylene motifs self‐assembles into novel tadpole‐ and bola‐shaped nanostructures at low concentrations, as well as nanofibers at higher concentrations. Interestingly, morphology‐dependent cell imaging is achieved owing to the polymerization of the diacetylenes upon interaction with the cell membrane.
The water‐soluble tweezer receptor 1 with two symmetric peptidic arms, which are connected by an aromatic scaffold and contain lysine, phenylalanine, and a guanidinium‐based anion‐binding site as ...headgroup, has been synthesized. UV/Vis‐derived Job plots show that the receptor forms 1:1 complexes with nucleotides and phosphate in buffered water at neutral pH. Binding constants have been determined by fluorescence and UV/Vis spectroscopy. All nucleotides tested were bound very efficiently, even in pure water, with binding constants between 104 and 105 M−1. Interestingly, all mononucleotides were bound much stronger than phosphate by a factor of at least 5 to 10. Furthermore 1 favors the binding of adenosine monophosphate (AMP) over adenosine diphosphate (ADP) and adenosine triphosphate (ATP), which is unprecedented for artificial nucleotide receptors reported so far. According to NMR spectroscopy and molecular modeling studies, the efficient binding is a result of strong electrostatic contacts supported by π–π interactions with the nucleobase within the cavity‐shaped receptor.
Nucleotides preferred: The symmetric peptide‐based tweezer receptor 1 forms stable 1:1 complexes with nucleotides in water (pH 7). The host prefers nucleotides over phosphate and mononucleotides over di‐ or trinucleotides (see scheme). Hence, complex formation is due also to π‐stacking interactions with the nucleobase.
Herein we introduce a new guest, the guanidiniocarbonyl pyrrole cation (GCP), for host–guest chemistry with cucurbit8uril. Macromodel calculations as well as isothermal titration calorimetry (ITC), ...showed that CB8 can entrap two GCP molecules inside its hydrophobic cavity. Using this 1:2‐complex formation, we further show that CB8 can induce crosslinking of a flexibletetracationic guanidiniocarbonyl pyrrole. An extended supramolecular cross‐linked 3D network was observed at pH 4.1 where all GCP groups in guanidiniocarbonyl pyrrole are protonated. At pH 6.5, the GCP groups are only partially protonated nanostructures with a more globular vesicle‐like shape.
Cucurbituril8 is an efficient host for two GCP cations. Addition of CB8 to a tetra‐GCP compound 1 thus induces supramolecular polymerization. Depending on the pH and the protonation state of the GCP cation different types of aggregates are formed.
The synthesis and binding properties of a new tricationic guanidiniocarbonyl pyrrole receptor 7 are described. Receptor 7 binds citrate 9 and other tricarboxylates such as trimesic acid ...tricarboxylate 8 with unprecedented high association constants of K assoc > 105 M-1 in water as determined by UV and fluorescence tritration studies. According to NOESY experiments and molecular modeling calculations, the tricarboxylates are bound within the inner cavity of receptor 7 by ion pairing between the carboxylate groups and the guanidiniocarbonyl pyrrole moieties, favored by the nonpolar microenvironment of the cavity. Hence, receptor 7 can be regarded as a molecular flytrap. In the case of the aromatic tricarboxylate 8, additional aromatic interactions further strengthen the complex. The complexes with the tricarboxylates are so strong that even the presence of a large excess of competing anions or buffer salts does not significantly affect the association constant. For example, the association constant for citrate changes only from K assoc = 1.6 × 105 M-1 in pure water to K assoc = 8.6 × 104 M-1 in the presence of a 170-fold excess of bis-tris buffer and a 1000-fold excess of chloride. This makes 7 one of the most efficient receptors for the binding of citrate in aqueous solvents reported thus far.
A series of guanidiniocarbonyl pyrrole receptors has been synthesized which bind carboxylates by ion pairing in combination with multiple hydrogen bonds. Their binding properties with various ...carboxylates have been investigated using NMR titration studies in 40 % water/water (v/v). The best receptor has association constants which are in the order of K≈103 mol−1 and hence some 30 times larger than with the simple acetyl guanidinium cation. Through a systematic variation of the receptor structure, semiquantitative estimates for the energetic contributions of the individual binding interactions could be derived. These data show that the various hydrogen bonds are not equally important for the binding but differ significantly in their energetic contribution to the overall complexation process. Furthermore, the receptor can be made chiral and shows selectivity upon binding of enantiomeric amino acid carboxylates. Molecular modeling was used to obtain structural information for the various receptor carboxylate complexes and served as a basis to explain the observed differences in binding constants.
Guanidiniocarbonylpyrrol‐Rezeptoren bilden mit Carboxylaten Ionenpaare, die zusätzlich durch mehrere Wasserstoffbrückenbindungen stabilisiert werden. Eine Reihe solcher Rezeptoren wurde synthetisiert und ihre Bindungseigenschaften mit verschiedenen Carboxylaten durch NMR Titrationen in 40 % Wasser/Wasser (v/v) untersucht. Der beste Rezeptor weist Assoziationskonstanten in der Größenordnung von K≈103 mol−1 auf, die somit ca. 30 mal größer sind als mit der Stammverbindung, dem Acetylguanidinium‐Kation. Durch systematische Variation der Rezeptorstruktur konnten die energetischen Beiträge der einzelnen Wechselwirkungen zur Gesamtkomplexbildung abgeschätzt werden. Hierbei zeigte sich, daß die verschiedenen Wasserstoffbrückenbindungen nicht alle gleich wichtig sind, sondern sich erheblich in ihrer Stärke unterscheiden. Einer der hier vorgestellten Rezeptoren ist chiral und bindet enantiomere Aminosäurecarboxylate stereoselektiv. Die Diskussion der beobachteten Unterschiede im Komplexierungsverhalten der verschiedenen Rezeptoren erfolgt auf der Basis der mit Hilfe von Kraftfeldrechnungen ermittelten Strukturen der Komplexe.
Guanidiniocarbonyl receptors stereoselectively bind carboxylates with association constants which are significantly higher than with the parent acetyl guanidinium cation. Systematic binding studies showed that the various hydrogen bonds do not contribute equally to the overall association process. Shown here (in kJ mol−1) are their estimated semiquantitative contributions for the binding of N‐acetyl‐L‐alanyl carboxylate in 40 % water/water (v/v).
Supramolecular nanoassemblies are gaining increasing importance as promising new materials with considerable potential for novel and promising applications. Within supramolecular nanoassemblies the ...connectivity of the monomeric units is based on reversible noncovalent interactions, like van der Waals interactions, hydrogen bonding, or ionic interactions. As the strength of these interactions depends on the molecular surrounding, the formation of nanoassemblies in principle can be controlled externally by changing the environment and/or the molecular shape of the underlying monomer. This way it is not only possible to switch the self‐assembly on or off, but also to change between different aggregation states. In this minireview we present some recent selected approaches to supramolecular stimuli‐responsive nanoassemblies.
Switch over: Different approaches are presented that allow external switching of self‐assembled nanostructures between different aggregation states and morphologies. There are multiple stimuli that can be applied to supramolecular oligomers, and first examples for useful applications can already be found in materials science.
