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Peptide [4]Catenane by Folding and Assembly
Angewandte Chemie International Edition
Abstract
A topologically complex peptide [4]catenane with the crossing number of 12 was synthesized by a folding and assembly strategy wherein the folding and metal-directed self-assembly of a short peptide fragment occur simultaneously. The latent Ω-looped conformation of the Pro-Gly-Pro sequence was found only when pyridines at the C- and N-termini coordinatively bind metal ions (Ag(I) or Au(I) ). Crystallographic studies revealed that the Ω-looped motifs formed four M3 L3 macrocycles that were intermolecularly entwined to generate an unprecedented peptide [4]catenane topology.
... For references on knot theory and its applications, see [10][11][12][13][14][15], for example. In [18,19], two topologically different metal-peptide interlocking molecules with entangled structures of 4 rings and 12 crossings were synthesized, and in [20], another interlocking molecule with 6 rings and 24 crossings was synthesized. See Section 3 for details. ...
... The topological structures of molecules in [18][19][20] can be considered as polyhedral links [19,20]. The topological aspects of polyhedral links have been studied, for example, in [25][26][27]. ...
... In [18][19][20], the interlocking molecules of metal-peptide rings with complex topology have been synthesized. For details, see those papers. ...
Knots and links are ubiquitous in chemical systems. Their structure can be responsible for
a variety of physical and chemical properties, making them very important in materials development. In this article, we analyze the topological structures of interlocking molecules composed of metal-peptide rings using the concept of polyhedral links. To that end, we discuss the topological classification of alternating polyhedral links.
... 78 Later, Gagné and co-workers 79 and Trabolsi and co-workers 80 reported the stereoselective self-assembly of [2]catenanes from chiral building blocks, including the absolute stereochemistry of a crystallized product by comparison with a covalent stereogenic unit as an internal reference. 72 (ii) Fujita's tetra-interlocked metallo- [4]catenane [Ag 12 (18) 12 ] 12+ , which expresses conditional and unconditional topological chirality, 73 and (iii) Fujita's metallo- [2] catenane [Ag 8 (19) 8 ] 8+ , which contains four crossing points (8 2 1 link) and expresses both conditional and unconditional topological chirality. 74 (C) Biasing of co-conformational stereogenic units using non-covalent interactions: (i) a diastereomeric ion pair based on a helically chiral coconformation of Stoddart's cationic catenane 20 4+ and chiral phosphate anion 21 À75 and (ii) a diastereomeric ion pair based on Credi's coconformationally mechanically planar chiral rotaxane 22 and camphor sulfonate (23) (R = CH2-3-pyrenyl). ...
... Perhaps the most impressive examples of chiral derivatization in the stereoselective synthesis of mechanically chiral catenanes under thermodynamic control have been reported by Fujita and co-workers 73,74,81,82 beginning in 2016 with the report of a metallo- [4]catenane. 83 Catenane [Ag 12 (18) 12 ] 12+ , formed by the self-assembly of 12 equivalents of short peptide 18 and 12 Ag + cations, crystallized from the reaction mixture over 9 weeks (Figure 4B, ii). ...
... 83 Catenane [Ag 12 (18) 12 ] 12+ , formed by the self-assembly of 12 equivalents of short peptide 18 and 12 Ag + cations, crystallized from the reaction mixture over 9 weeks (Figure 4B, ii). 73 Single-crystal X-ray diffraction (SCXRD) revealed [Ag 12 (18) 12 ] 12+ to be composed of four oriented macrocycles linked together to generate a tetra-interlocked structure that has 12 crossing points and expresses unconditional topological chirality. In addition, the rings themselves are oriented, resulting in conditional topological stereogenic units. ...
Mechanically interlocked molecules, such as rotaxanes and catenanes, are composed of two or more covalent subcomponents threaded through one another such that they cannot be separated without breaking a covalent bond. This arrangement can allow the covalent subcomponents to undergo large-amplitude relative motion, and this property of the mechanical bond has been widely exploited in the design and synthesis of molecular machines. Another less well-known property of the mechanical bond is that it can give rise to chirotopic stereogenic units that do not rely on covalent stereogenic elements. Although the study of such “mechanically chiral” molecules is expanding, their synthesis in enantiopure form remains challenging. In this Perspective, we review the strategies available, highlighting key examples along the way, and suggest future areas for development.
... Here, we control the formation of these structural isomers using the folding-and-assembly strategy. [12][13][14][15][16][17][18][19][20] To do this, we incorporate pyridyl-appended residues into the octapeptide sequence of 1, and induce simultaneous folding and assembly of the two peptide strands into the specific isomers of the ds-β-helix through metal coordination ( Figure 2). These results aid our understanding of the structures of the transitory species in the as-yet unexplained folding-and-assembly pathways of short peptides and facilitate the rational design of ds-βhelix-based peptidic frameworks for nanoscale peptide engineering. ...
... The crystal structure revealed a Type II antiparallel ds-β-helix (Figure 4c, Supporting information Figures S13c, S22 and Table S2), in which the orientation of the two strands is opposite to that in the Type I helix (Figure 1a). Because the same number (14) of interstrand amide hydrogen bonds is involved in both the Type I and Type II helices (Supporting information Figures S1 and S16), their stabilities should be comparable and, thus, both presumably exist in solution state. However, the Type II helix has not yet been noticed or characterized. ...
Short peptides with sequences of alternating l‐ and d‐residues are known to form antiparallel double β‐helical structures, but their equilibrium structures have not been characterized in detail. Here, we use metal coordination of a simple octapeptide, ‐(l‐Val‐d‐Val)4‐, modified with two coordinating side chains at the (i, j)‐th residues to uncover these elusive structures. When (i, j) = (3, 5), complexation with ZnI2 induces a parallel double β‐helix, which is not commonly seen. In contrast, when (i, j) = (5, 7), a commonly occurring antiparallel double β‐helix (Type I) is formed. Interestingly, complexation of the peptide with (i, j) = (3, 7) gives another antiparallel double β‐helix, the unknown Type II structure, which has an inverted orientation of the two strands. Complexation of a monotopic peptide (i = 3) with trans‐PdCl2 yields a Pd(II)‐linked dimeric bundle of two antiparallel β‐helices. These results demonstrate that metal coordination can induce even as‐yet unrecognized structures in the folding and assembly pathways of short peptides.
Key points
Structural elucidation of elusive peptide nanostructures
Precise structural control of double helical molecules
Fusion of peptide folding and metal‐directed self‐assembly
... Recently, the formation of giant structures from peptide ligands has also been explored by other groups. Their approaches can be summarized in two ways: formation of a discrete complex using an interlocking structure [58][59][60][61][62], [62]. However, it is still difficult to predict the our design for developing giant multicomponent crystalline systems in the future. ...
Biological systems display a range of sophisticated functions that cannot be performed by artificial systems, through intricate cooperative structural changes involving multiple functional units. The designability and structural flexibility of peptides are demonstrated by biological systems that display cooperative structural changes; these properties also make them well-suited for the formation of artificial systems that display such changes. The problem with the use of peptide frameworks is that long peptide residues, which are not suitable for gram-scale use, are required for the formation of stable ordered structures. However, if ordered structures containing peptides could be constructed by coordinating them to metal ions, peptides could be widely used to develop sophisticated functional materials. Crystal packing can be used for the design of functional materials made from simple molecules because it provides a way to place the components relative to each other. Although crystalline systems have been reported in which the small size of the cavities has been attributed to the flexibility of the peptide, recently, large systems with giant cavities have been developed with flexible peptides. In this review, we summarize the formation of cooperative multicomponent systems in the crystalline state using metal complexes of simple peptides, along with recent advances in the construction of giant artificial systems using short peptides.
... Supramolecular self-assembly, inspired by the precise organization of bio-macromolecules in living systems, allows for the spontaneous formation of ordered complexes from a chaos state. 1 Among various noncovalent driving forces, metal-ligand coordination plays a vital role in the selfassembly of structurally and functionally sophisticated metallo-supramolecules, benefitting from the high direct ionality and predictable feature of coordination bonds. [2][3][4][5][6] As a result, metallo-supramolecular chemistry has witnessed an explosion in constructing a myriad of artificial supramolecular architectures, including polygons, [7][8][9][10][11] knots, [12][13][14][15] links, [16][17][18][19] fractals, [20][21][22] as well as Platonic, [23][24][25][26][27] Archimedean, [28][29][30][31][32][33][34] Goldenberg polyhedrons, 35,36 and so on. And these complexes show great potentials among different fields, including catalysis, [37][38][39][40][41][42][43][44][45][46] nano-electronics, 47,48 stabili-diagnosis and therapy, [52][53][54][55][56][57] and so on. ...
... The synthesis of small hybrid systems from biomolecules usually requires synthetic support structures, such as crown ether-ammonium ion or metal coordination complexes, that remain in the structure. Rotaxanes [27][28][29][30][31] , catenanes [32][33][34][35][36][37] and molecular knots 38,39 with hybrid structures have been reported in which amino acids are incorporated into such supports. However, the synthesis of such MIPs without artificial supports has been found difficult owing to the lack of recognition motifs in peptides for template-directed synthesis in polar solvents 29 , which makes the construction of even simple MIPs, for example, peptide [2]catenanes, synthetically challenging. ...
Mechanically interlocked molecules (MIMs), such as rotaxanes and catenanes, have captured the attention of chemists both from a synthetic perspective and because of their role as simple prototypes of molecular machines. Although examples exist in nature, most synthetic MIMs are made from artificial building blocks and assembled in organic solvents. The synthesis of MIMs from natural biomolecules remains highly challenging. Here, we report on a synthesis strategy for interlocked molecules solely made from peptides, that is, mechanically interlocked peptides (MIPs). Fully peptidic, cysteine-decorated building blocks were self-assembled in water to generate disulfide-bonded dynamic combinatorial libraries consisting of multiple different rotaxanes, catenanes and daisy chains as well as more exotic structures. Detailed NMR spectroscopy and mass spectrometry characterization of a [2]catenane comprising two peptide macrocycles revealed that this structure has rich conformational dynamics reminiscent of protein folding. Thus, MIPs can serve as a bridge between fully synthetic MIMs and those found in nature.
... 21 In the F&A strategy, we employ short peptide fragments that possess metal-coordination sites (typically, pyridine rings, hereafter referred to as py) at both the N and C termini. [21][22][23][24][25][26][27][28] Upon metal coordination, the F&A of the oligopeptide fragments take place simultaneously (Figure 1). Importantly, the two processes are not independent but help each other to generate well-defined nanostructures that can neither be addressed by peptide engineering 10-13,29-32 nor coordination self-assembly. ...
Folding and assembly are intra- and inter-molecular processes, respectively, for spontaneously generating predetermined, well-defined molecular structures. Though the cooperative processes of these mechanisms have been studied in coiled coils and β-sheets, they have been seldom utilized simultaneously in the synthetic fields. We have been developing a new folding-and-assembly (F&A) strategy, in which the folding and metal-directed self-assembly of a short peptide fragment occur simultaneously by helping and inducing the processes of each other. Depending on the sequence design, each short peptide ligand exhibits a specific conformation during metal coordination and simultaneously assembles into an advanced nanostructure, which has been hardly achieved by known synthetic strategies. The concepts, examples of the F&A strategy, the function of the obtained structures as well as future directions are disclosed in this perspective.
Mechanical stereochemistry arises when the interlocking of stereochemically trivial covalent subcomponents results in a stereochemically complex object. Although this general concept was identified in 1961, the stereochemical description of these molecules is still under development to the extent that new forms of mechanical stereochemistry are still being identified. Here, we present a simple analysis of rotaxane and catenane stereochemistry that allowed us to identify the final missing simple mechanical stereogenic unit, an overlooked form of rotaxane geometric isomerism, and demonstrate its stereoselective synthesis.
Although the synthesis of mechanically interlocked molecules has been extensively researched, selectively constructing homogeneous linear [4]catenanes remains a formidable challenge. Here, we selectively constructed a homogeneous linear metalla[4]catenane in a one‐step process through the coordination‐driven self‐assembly of a bidentate benzothiadiazole derivative ligand and a binuclear half‐sandwich rhodium precursor. The formation of metalla[4]catenanes was facilitated by cooperative interactions between strong sandwich‐type π‐π stacking and non‐classical hydrogen bonds between the components. Moreover, by modulating the aromatic substituents on the binuclear precursor, two homogeneous metalla[2]catenanes were obtained. The molecular structures of these metallacatenanes were unambiguously characterized by single‐crystal X‐ray diffraction analysis. Additionally, reversible structural transformation between metal‐catenanes and the corresponding metallarectangles could be achieved by altering their concentration, as confirmed by mass spectrometry and NMR spectroscopy studies.
Although the synthesis of mechanically interlocked molecules has been extensively researched, selectively constructing homogeneous linear [4]catenanes remains a formidable challenge. Here, we selectively constructed a homogeneous linear metalla[4]catenane in a one‐step process through the coordination‐driven self‐assembly of a bidentate benzothiadiazole derivative ligand and a binuclear half‐sandwich rhodium precursor. The formation of metalla[4]catenanes was facilitated by cooperative interactions between strong sandwich‐type π‐π stacking and non‐classical hydrogen bonds between the components. Moreover, by modulating the aromatic substituents on the binuclear precursor, two homogeneous metalla[2]catenanes were obtained. The molecular structures of these metallacatenanes were unambiguously characterized by single‐crystal X‐ray diffraction analysis. Additionally, reversible structural transformation between metal‐catenanes and the corresponding metallarectangles could be achieved by altering their concentration, as confirmed by mass spectrometry and NMR spectroscopy studies.
Peptides are very interesting biomolecules that upon self-association form a variety of thermodynamically stable supramolecular structures of nanometric dimension e.g. nanotubes, nanorods, nanovesicles, nanofibrils, nanowires and many others. Herein, we report six peptide molecules having a general chemical structure, H-Gaba-X-X-OH (Gaba: γ-aminobutyric acid, X: amino acid). Out of these six peptides, three are aromatic and the others are aliphatic. Atomic force microscopic (AFM) studies reveal that except peptide 6 (H-Gaba-Trp-Trp-OH), all the reported peptides adopt nanofibrillar morphology upon aggregation in aqueous medium. These supramolecular assemblies can recognize amyloid-specific molecular probe congo red (CR) and thioflavine t (ThT) and exhibit all the characteristic properties of amyloids. The MTT cell viability assay reveals that the toxicity of both aliphatic and aromatic peptides increases with increasing concentration of the peptides to both cancer (HeLa) and non-cancer (HEK 293) cells. Of note, the aromatic peptides show a slightly higher cytotoxic effect compared to the aliphatic peptides. Overall, the studies highlight the self-assembling nature of the de novo designed aliphatic and aromatic peptides and pave the way towards elucidating the intricacies of pathogenic amyloid assemblies.
Using the strategy of ligand fine-tuning by steric hindrance, we successfully obtained Solomon links (\(4_1^2\)) and figure-eight knots (41) with half-sandwich organometallic unit and amino-acid embedded ligands. The two curved bidentate ligands exhibit subtle differences, whereas they result in totally distinct entanglement modes. An alcoholysis reaction with the ligands leads to the formation of a molecular tweezer. Notably, unsymmetrical ligands were utilized in the self-assembly process to explore the formation of directional molecules, and the reactions exhibited selectivity due to comprehensive π interactions and multiple hydrogen bonds. The topologies and behavior of the above structures were confirmed through single-crystal X-ray diffraction, nuclear magnetic resonance techniques and mass spectrometry.
To clarify the design strategy for achieving functionality in crystalline multi-component systems comprising cyclic complexes of flexible short peptides, crystalline Ni(II) cyclic complexes were synthesized using two novel dipeptides (2 and 3) possessing different functional groups at the N-terminus of dipeptide 1. X-ray single-crystal structural analysis revealed that 2 and 3 formed tetranuclear cyclic complexes ([Ni4L4]8+), which were also observed for 1. The crystalline packing structure of the cyclic complexes of dipeptide 2 was almost the same as that of the cyclic complexes of dipeptide 1, whereas that of 3 had a different packing structure. The cooperative opening/closing of the crystalline heterogeneous cavity, which demonstrates humidity-responsive cooperative binding in the cyclic complexes of 1, was not observed for the complexes of 2, plausibly because of the decrease in crystalline voids of the latter. In contrast, the amounts for water and alcohol vapor adsorbed at room temperature were almost the same for the open forms of the cyclic complexes of 1 and 2, which was supported by the expansion of the flexible cavities in the crystalline cyclic complexes of 2.
Metal‐peptide networks (MPNs), which are assembled from short peptides and metal ions, are considered one of the most fascinating metal‐organic coordinated architectures because of their unique and complicated structures. Although MPNs have considerable potential for development into versatile materials, they have not been developed for practical applications because of several underlying limitations, such as designability, stability, and modifiability. In this review, we summarise several important milestones in the development of crystalline MPNs and thoroughly analyse their structural features, such as peptide sequence designs, coordination geometries, cross‐linking types, and network topologies. In addition, potential applications such as gas adsorption, guest encapsulation, and chiral recognition are introduced. We believe that this review is a useful survey that can provide insights into the development of new MPNs with more sophisticated structures and novel functions.
Entangling strands in a well-ordered manner can produce useful effects, from shoelaces and fishing nets to brown paper packages tied up with strings. At the nanoscale, non-crystalline polymer chains of sufficient length and flexibility randomly form tangled mixtures containing open knots of different sizes, shapes and complexity. However, discrete molecular knots of precise topology can also be obtained by controlling the number, sequence and stereochemistry of strand crossings: orderly molecular entanglements. During the last decade, substantial progress in the nascent field of molecular nanotopology has been made, with general synthetic strategies and new knotting motifs introduced, along with insights into the properties and functions of ordered tangle sequences. Conformational restrictions imparted by knotting can induce allostery, strong and selective anion binding, catalytic activity, lead to effective chiral expression across length scales, binding modes in conformations efficacious for drug delivery, and facilitate mechanical function at the molecular level. As complex molecular topologies become increasingly synthetically accessible they have the potential to play a significant role in molecular and materials design strategies. We highlight particular examples of molecular knots to illustrate why these are a few of our favourite things.
Catenanes composed of two achiral rings that are oriented (Cnh symmetry) because of the sequence of atoms they contain are referred to as topologically chiral. Here, we present the synthesis of a highly enantioenriched catenane containing a related but overlooked "co-conformationally 'topologically' chiral" stereogenic unit, which arises when a bilaterally symmetric Cnv ring is desymmetrized by the position of an oriented macrocycle.
From being an aesthetic molecular object to a building block for the construction of molecular machines, catenanes and related mechanically interlocked molecules (MIMs) continue to attract immense interest in many research areas. Catenane chemistry is closely tied to that of rotaxanes and knots, and involves concepts like mechanical bonds, chemical topology and co-conformation that are unique to these molecules. Yet, because of their different topological structures and mechanical bond properties, there are some fundamental differences between the chemistry of catenanes and that of rotaxanes and knots although the boundary is sometimes blurred. Clearly distinguishing these differences, in aspects of bonding, structure, synthesis and properties, between catenanes and other MIMs is therefore of fundamental importance to understand their chemistry and explore the new opportunities from mechanical bonds.
Transition metal-mediated templating and self-assembly have shown great potential to construct mechanically interlocked molecules. Herein, we describe the formation of the bimetallic [3]catenane and [4]catenane based on neutral organometallic scaffolds via the orthogonality of platinum-to-oxygen coordination-driven self-assembly and copper(I) template–directed strategy of a [2]pseudorotaxane. The structures of these bimetallic [3]catenane and [4]catenane were characterized by multinuclear NMR {¹H and ³¹P} spectroscopy, electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS), and PM6 semiempirical molecular orbital theoretical calculations. In addition, single-crystal X-ray analyses of the [3]catenane revealed two asymmetric [2]pseudorotaxane units inside the metallacycle. It was discovered that tubular structures were formed through the stacking of individual [3]catenane molecules driven by the strong π–π interactions.
Supramolecular helices from helical building blocks represent an emerging analogue of the α-helix. In cases where the helicity of the helical building block is well propagated, the head-to-tail intermolecular interactions that lead to the helix could be enhanced to promote the formation and the stability of the supramolecular helix, wherein homochiral elongation dominates and functional helical channel structures could also be generated. This feature article outlines the supramolecular helices built from helical building blocks, i.e., helical aromatic foldamers and helical short peptides that are held together by intermolecular π-π stacking, hydrogen/halogen/chalcogen bonding, metal coordination, dynamic covalent bonding and solvophobic interactions, with emphasis on the influence of efficient propagation of helicity during assembly, favouring homochirality and channel functions.
A branched [8]catenane from an efficient one‐pot synthesis (72% HPLC yield, 59% isolated yield) featuring the simultaneous use of three kinds of templates and cucurbit[6]uril‐mediated azide‐alkyne cycloaddition (CBAAC) for ring‐closing is reported. Design and assembly of the [8]catenane precursors are unexpectedly complex that can involve cooperating, competing and non‐influencing interactions. Due to the branched structure, dynamics of the [8]catenane can be modulated in different extent by rigidifying/loosening the mechanical bonds at different regions by using solvent polarity, acid‐base and metal ions as the stimuli. This work not only highlights the importance of understanding the delicate interplay of the weak and non‐obvious supramolecular interactions in the synthesis of high‐order [n]catenane, but also demonstrates a complex control of dynamics and flexibility for exploiting [n]catenanes applications.
A branched [8]catenane from an efficient one‐pot synthesis (72 % HPLC yield, 59 % isolated yield) featuring the simultaneous use of three kinds of templates and cucurbit[6]uril‐mediated azide–alkyne cycloaddition (CBAAC) for ring‐closing is reported. Design and assembly of the [8]catenane precursors are unexpectedly complex that can involve cooperating, competing and non‐influencing interactions. Due to the branched structure, dynamics of the [8]catenane can be modulated in different extent by rigidifying/loosening the mechanical bonds at different regions by using solvent polarity, acid‐base and metal ions as the stimuli. This work not only highlights the importance of understanding the delicate interplay of the weak and non‐obvious supramolecular interactions in the synthesis of high‐order [n]catenane, but also demonstrates a complex control of dynamics and flexibility for exploiting [n]catenanes applications.
Despite the frequent occurrence of knotted frameworks in protein structures, the latent potential of peptide strands to form entangled structures is rarely discussed in peptide chemistry. Here we report the construction of highly entangled molecular topologies from Ag(I) ions and tripeptide ligands. The efficient entanglement of metal–peptide strands and the wide scope for design of the amino acid side chains in these ligands enabled the construction of metal–peptide 91 torus knots and 101² torus links. Moreover, steric control of the peptide side chain induced ring opening and twisting of the torus framework, which resulted in an infinite toroidal supercoil nanostructure.
Two novel compounds, a molecular trefoil knot and a Solomon link, were constructed successfully through the cooperation of multiple π-π stacking interactions. A reversible transformation between the trefoil knot and the corresponding [2 + 2] macrocycle could be achieved by solvent- and guest-induced effects. However, the Solomon link maintains its stability in different concentrations, solvents and guest molecules. Single-crystal X-ray crystallographic data, NMR spectroscopic experiments and ESI-MS support the synthesis and structural assignments. These synthesis methods open the door to the further development of smart materials, which will push the advancement of rational design of biomaterials.
Supramolecular one-step self-assembly of dimanganese decacarbonyl, diaryl diselenide, and linear dipyridyl ligands (L
= pyrazine (pz), 4,4′-bipyridine (bpy), and trans-1,2-bis(4-
pyridyl)ethylene (bpe)) has resulted in the formation of
selenolato-bridged manganese(I)-based metallorectangles. The
synthesis of tetranuclear Mn(I)-based metallorectangles
[{(CO)3Mn(μ-SeR)2Mn(CO)3}2(μ-L)2] (1−6) was facilitated
by the oxidative addition of diaryl diselenide to dimanganese
decacarbonyl with the simultaneous coordination of linear
bidentate pyridyl linker in an orthogonal fashion. Formation of
metallorectangles 1−6 was ascertained using IR, UV−vis, NMR
spectroscopic techniques, and elemental analyses. The molecular mass of compounds 2, 4, and 6 were determined by ESI-mass
spectrometry. Solid-state structural elucidation of 2, 3, and 6 by single-crystal X-ray diffraction methods revealed a rectangular
framework wherein selenolato-bridges and pyridyl ligands define the shorter and longer edges, respectively. Also, the guest binding
capability of metallorectangles 3 and 5 with different aromatic guests was studied using UV−vis absorption and emission
spectrophotometric titration methods that affirmed strong host−guest binding interactions. The formation of the host−guest
complex between metallorectangle 3 and pyrene has been explicitly corroborated by the single-crystal X-ray structure of 3•pyrene.
Moreover, select metallorectangles 1−4 and 6 were studied to explore their anticancer activity, while CO-releasing ability of
metallorectangle 2 was further appraised using equine heart myoglobin assay.
Construction of entangled nanostructures from molecular rings or strands has long attracted chemists, yet synthetic approaches for highly entangled nanostructures remain unexplored to date. Here, we introduce our recent achievements in construction of such nanostructures by utilization of metal–peptide strands. Our folding-and-assembly strategy, that is based on a cooperative processes of peptide self-folding and metal-induced self-assembly, has afforded unprecedented topological nanostructures through threading of multiple metal–peptide rings. Starting from the initial design of the system, we discuss remarkable examples such as polyhedral links, torus knots, and a poly[n]catenane, and state the perspectives in this account review.
The construction of cooperative systems comprising several units is an essential challenge for artificial systems toward the development of sophisticated functions comparable to those found in biological systems. Flexible frameworks possessing various functional groups that can form weak intra/intermolecular interactions similar to those observed in biological systems have promising design features for artificial systems used to control cooperative systems. However, it is difficult to construct multiple component systems >1 nm using these flexible units by controlling the arrangement of functional units, beginning with the precise control of the cooperative switching of multiple units. In general, it is difficult for oligopeptides to form stable conformations by themselves, although they have designability and structural features suitable for the development of cooperative systems. Increasing the number of coordination bonds in peptides, which are stronger than hydrogen bonds, can be used to control the assembled peptide structures and stabilize their structures owing to the variety of coordination bonds and selective binding affinity. Thus, metal complexes of artificial short peptides have great potential for the development of multicomponent cooperative systems. Based on this concept, we have developed a series of novel metal complexes of flexible peptides and have achieved, to date, cooperative systems, the formation of giant structures, and precise control over the functional units that are the essential bases for designable multifunctional systems that can be regarded as artificial enzymes. In this feature article, we summarize these results and discuss the principal/essential design of artificial systems.
Two quadrilateral metallacycles were prepared by coordination-driven self-assembly of a 90° platinum(ii) receptor 6 with a flexible donor 1,3-bis(4,4′-bipyridinium)propane 1a or 1,1-bis(4,4′-bipyridinium)methane 1b, respectively. Three [3]catenanes (3, 4 and 5) were further prepared by in situ addition of crown ethers (DB24C8 or DB30C10) to the yielded metallacycles. By comparing the crystal structures of 1a and 4, it was found that the bite angle change of the flexible bidentate donor 1a (111.0° to 112.3°) is much smaller than that of rigid platinum(ii) receptor 6 (90.0° to 83.2°) during metalla-cyclization. The multicomponent [3]catenanes were stabilized by multiple supramolecular interactions, including metal coordination, π-π stacking, charge transfer, and hydrogen bonding.
We describe a janusarene derivative PyJ, which forms micrometer-scale one-dimensional metallo-supramolecular polymer through coordination driven self-assembly. PyJ is a well-preorganized dodecatopic pyridyl ligand built on a hexaphenylbenzene platform. The two-face structural feature of PyJ allows for a delicate control over multiple Py-Ag⁺-Py coordination interactions, leading to assembled structure of PyJ-Ag⁺, which was characterized by dynamic light scattering, atomic force microscopy, and transmission electron microscopy.
The folding propensity of ortho -phenylene foldamers dictates the outcome of their self-assembly into macrocycles.
Ring-linear blends composed of complexes bearing multiple rings are promising candidates for soft devices, and understanding the penetration of linear chains into rings is essential for enhancing their mechanical properties. Coarse-grained molecular dynamics simulations of ring-linear blends composed of bonded rings or polycatenanes bearing two or three rings were performed for revealing the conformations in blends. To investigate the relationship between the conformations of ring polymers and penetration of linear chains, we considered linear-rich systems with fring = 0.05 and 0.1, where fring is the fraction of ring complex. The number of linear chains penetrating rings (nP) was estimated from the Gauss linking number for all the pairs of ring polymers and linear chains. Dependence of penetration on the ring size was determined from the probability distributions of nP. Average nP (nP) of the systems with polycatenanes was slightly higher than those of the systems with bonded rings. For fring = 0.1, nPof the single ring was 3.41 when number of beads per a ring was Nring = 160. nP of the bonded two-ring system and poly-[2]-catenane with Nring = 80 was 2.60 and 2.87, respectively, while nPof the bonded three-ring system and poly-[3]-catenane with Nring = 80 was 3.63 and 3.87, respectively, which were slightly higher than that of the single ring with Nring = 160. Since the ring complexes had multiple chains penetrating even for low Nring, mechanical properties of the crosslinked ring-linear blend were expected to be controlled by the ring complexes instead of the single ring.
A pair of radial [4]catenane isomers interlocked with two CB[6]s and one β-CD is reported. Due to the different positions of the tightly bound CB[6]s, shuttling dynamics of the β-CD between the two biphenyl stations are different in the isomers.
Reaction of N,Nʺ-ethylene-1,2-diylbis(3-pyridin-3-ylurea) (L) with AgNO3 in a variety of solvents gives a total of five 2-D Borromean weave coordination polymer networks that adopt three structural types depending on the interactions to the solvent pocket. The Borromean network is of formula [Ag2(L)3](NO3)2 ·solvent where the solvent is either a cluster of water molecules, mixtures of water and acetonitrile, water and methanol or chloroform and methanol. The Borromean structure is a thermodynamic sink and under fast crystallization conditions an alternative 2 + 2 metallomacrocycle forms that can result in metallogel formation. The metallogel structure transforms into the crystalline Borromean network over time.
Effect of topological catenation on dimensional and shape properties of a single linear polycatenane (or [n]catenane), a polymer composed entirely of interlocking rings (macrocycles) arranged in a linear architecture, have been investigated by molecular dynamics simulation. The specific role of topological catenation in a polycatenane is revealed through comparing conformational properties of polycatenane to those obtained in a linear bonded-ring polymer, in which the same number of rings with the same ring size are connected via covalent bonds instead. We find that the mean-square radii of gyration of a polycatenane and a bonded-ring polymer obey the same scaling laws with a linear chain with respect to chain length, i.e., ⟨Rg2⟩~N2ν with ν≈3/5, but topological catenation makes dimension of a polycatenane smaller than the corresponding bonded-ring polymer. On properties of ring dimensions, it is found that dimensions of the middle rings along a linear polycatenane are larger than those of the two edge rings located at two chain ends. Furthermore, the dimensional ratio of the middle to the edge rings remains a constant, i.e., independent of the number of rings along the chain, n, and the ring length. In contrast, rings along a bonded-ring polymer have the same dimensions, and their values remain approximately unchanged from the dimensions of the rings in isolation. Shape properties of the whole polycatenane and bonded-ring polymer are solely determined by their chain topologies and the number of rings along the chain, while the ring length doesn't play a role. Conclusion is that topological catenation makes shape of polycatenane chains more isotropic than their bonded-ring polymer counterparts. For instance, in the regime of n being small (e.g. n<10), ratios of the average eigenvalues of gyration tensors, ⟨λ1⟩/⟨λ3⟩, ⟨λ1⟩/⟨λ2⟩ and the mean asphericity, ⟨A⟩, and the mean prolateness, ⟨P⟩ of polycatenanes are smaller than those of bonded-ring polymers. In regime of n~10 or larger, these quantities approximately recover corresponding values of linear polymers. On shape properties of rings along a polycatenane, it is concluded that all the middle rings become more prolate than those edge rings, which isn't seen in the case of bonded-ring polymer.
Two dynamic slider-on-deck assemblies, i.e. a two-component threefold degenerate (k298 = 34.9 kHz) and a catenated three-component ninefold degenerate (k298 = 27.9 kHz) system, were quantitatively interconverted. Inspection of their computed structures revealed an allosteric effect on the sliding rates due to the spatial interaction between the components.
The construction of synthetic protein mimics is a central goal in chemistry. A known approach for achieving this goal is the self‐assembly of synthetic biomimetic sequences into supramolecular structures. Obtaining different 3D structures via a simple sequence modification, however, is still challenging. Herein we present the design and synthesis of biomimetic architectures, via the self‐assembly of distinct copper‐peptoid duplexes. We demonstrate that changing only one non‐coordinating side‐chain within the peptoids—sequence‐specific N‐substituted glycine oligomers—leads to different supramolecular structures. Four peptoid trimers incorporating 2,2’‐bipyridine and pyridine ligands, and a non‐coordinating but rather a structure‐directed bulky group were synthesized, and their solutions were treated with Cu²⁺ in a 1:1 ratio. Single‐crystal X‐ray analysis of the products revealed the self‐assembly of each peptoid into a metallopeptoid duplex, followed by the self‐assembly of multiple duplexes and their packing into a three‐dimensional supramolecular architecture via hydrogen bonding and π–π interactions. Tuning the non‐coordinating side‐chain enables to regulate both the final structure being either a tightly packed helical rod or a nano‐channel, and the pore width of the nano‐channels. Importantly, all the metallopeptoids structures are stable in aqueous solution as verified by cryo‐TEM measurements and supported by UV/Vis and EPR spectroscopies and by ESI‐MS analysis. Thus, we could also demonstrate the selective recognition abilities of the nano‐channels towards glycerol.
Photochromic coordinative cages containing dynamic C=N imine bonds are assembled from dithienylethene-based aldehyde and tris-amine precursors via metallo-component self-assembly. The resulting metal-templated cages are then reduced and demetalated into pure covalent-organic cages (COCs), which are otherwise difficult to prepare via de novo organic synthesis. Both of the obtained coordinative and covalent cages can be readily interconverted between the ring-open (o-isomer) and the one-lateral ring-closed (c-isomer) forms by UV/vis light irradiation, demonstrating distinct absorption, luminescence and photoisomerization dynamics. Specifically, the ring-closed c-COCs show blue-shifted absorption band compared with analogous metal-templated cages, which can be applied in photoluminescence (PL) color-tuning of upconversion materials in different way, showing potentials to construct multi-readout logic gate systems.
A crystalline metal–peptide pore entraps chiral alcohols and ketones in a single‐crystal‐to‐single‐crystal manner. Crystallographic analyses revealed their chemical structures, chiral conformations, and even an unstable equilibrium product.
Abstract
Porous metal complexes enable single‐crystal X‐ray crystallographic observation of included guests or reaction intermediates through simple soaking with the guests/substrates. Previous studies on this technique have often encountered difficulties in the observation of chiral structures because the host frameworks had no chirality. We synthesized a new metal–peptide porous complex through a folding‐and‐assembly strategy and utilized the chiral pore for trapping chiral guests. Chiral alcohols and ketones were successfully included within the pore. Crystallographic analyses clearly revealed not only their chemical structures but also chiral transformation events within the pore such as fixed conformations or an unstable hemiacetal formation.
Porous metal complexes enable single‐crystal X‐ray crystallographic observation of included guests or reaction intermediates through simple soaking with the guests/substrates. Previous studies on this technique have often encountered difficulties in the observation of chiral structures because the host frameworks had no chirality. We synthesized a new metal–peptide porous complex through a folding‐and‐assembly strategy and utilized the chiral pore for trapping chiral guests. Chiral alcohols and ketones were successfully included within the pore. Crystallographic analyses clearly revealed not only their chemical structures but also chiral transformation events within the pore such as fixed conformations or an unstable hemiacetal formation.
Since the emergence of the concept of chemical topology, interlocked molecular assemblies have graduated from academic curiosities and poorly defined species to become synthetic realities. Coordination-directed synthesis provides powerful, diverse, and increasingly sophisticated protocols for accessing interlocked molecules. Originally, metal ions were employed solely as templates to gather and position building blocks in entwined or threaded arrangements. Recently, metal centers have increasingly featured within the backbones of the integral structural elements, which in turn use noncovalent interactions to self-assemble into intricate topologies. By outlining ingenious recent examples as well as seminal classic cases, this Review focuses on the role of metal-ligand paradigms in assembling molecular links. In addition, the ever-evolving approaches to efficient assembly, the structural features of the resulting architectures, and their prospects for the future are also presented.
A one-pot reaction is used to make a series of [5]rotaxanes. The protocol involves simultaneous threading-followed-by-stoppering to trap a macrocycle (dibenzo[24]crown 8, DB24C8) on an axle to form a mechanically interlocked molecule (MIM) – in this case a rotaxane – and the condensation of an aldehyde with a pyrrole to form a porphyrin precursor. For each [5]rotaxane, a different combination of recognition site and stoppering group was used; the protonation state of the [5]rotaxane can be used to generate different co-conformational states for each [5]rotaxane making these systems potential multi-state switches for further study in solution or the solid-state.
Engineering of supramolecular topologies offers potential opportunities for tailoring their properties to various function and applications. However, synthesis of interlocked or intertwined compounds‒catenanes, links or knots, is a challenge. Previously, we used coordination‒driven self‒assembly and non-covalent interactions (NCIs) between metal‒based acceptors and multi‒pyridyl donors to create supramolecular topologies with increasing complexity. Self‒assembling components of fixed length and geometry have been utilized for the production of topologies such as Borromean rings, Solomon links, Hopf’s link, “rectangle in rectangle”, and an 818 molecular knot. However, recent synthesis of a linear [3]catenane by us witnessed the importance of flexible ligand along with coordination‒driven self‒assembly and NCIs in self‒assembling units. This flexibility provides distinctive angularity for the recognition of various NCIs and thus offers tremendous possibilities for realizing complex supramolecular topologies. This study proposed a selective and quantitative synthesis, and also the first X‒ray characterization of a closed three‒link chain (a prime link of [3]catenane with 6 crossings) via two component coordination‒driven self‒assembly. The experiments based upon concentration, guest template and solvent effects were systematically presented. Furthermore, the experimental finding was supported by density functional theory calculations which highlighted the necessity of the multiple NCIs along with appropriate geometry of the [2+2] rings.
Equilibrium conformational properties of a ring polymer (named by ‘inner ring’) simultaneously concatenated with a varying number of outer rings in a ‘flower’-shaped polymer catenane are explored by molecular dynamics simulations. Two different cases have been considered. In Case I, the excluded volume interactions between the outer rings are absent in a polymer catenane, while they are present in Case II. Results demonstrate that, compared to an isolated ring polymer, size and shape properties of the same, inner ring in a polymer catenane can be greatly modified by the catenation topology in both Cases. It is concluded that the topological catenation can induce a swelling of the inner ring in a catenane compared to the same ring in isolation. Importantly, scaling relationships between the swelling degree, fsw, of the inner ring and number of the outer rings, n, have been established in both Case I and Case II, fsw=anα, where the prefactor a and scaling exponent α are all predominantly dependent on molecular-weight ratio of the inner to outer rings in catenane. Besides, swelling of inner ring in a catenane of Case II is more pronounced than the same inner ring in a catenane of Case I. The mean asphericity of the inner ring is slightly increased due to the catenation topology, while its mean prolateness is remarkably modified by the catenation topology. The inner ring in a catenane becomes more oblate, compared to the same ring in isolation, with increasing either number or molecular weight of the outer rings in the catenane. Profiles of the mean prolateness changes of the inner ring from those of the same isolated ring with respect to number of the outer rings are also mainly controlled by the molecular-weight ratio of the inner to outer rings.
Half a century after Schill and Lüttringhaus carried out the first directed synthesis of a [2]catenane, a plethora of strategies now exist for the construction of molecular Hopf links (singly interlocked rings), the simplest type of catenane. The precision and effectiveness with which suitable templates and/or noncovalent interactions can arrange building blocks has also enabled the synthesis of intricate and often beautiful higher order interlocked systems, including Solomon links, Borromean rings, and a Star of David catenane. This Review outlines the diverse strategies that exist for synthesizing catenanes in the 21st century and examines their emerging applications and the challenges that still exist for the synthesis of more complex topologies.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
The protein topology database KnotProt, http://knotprot.cent.uw.edu.pl/, collects information about protein structures with open polypeptide chains forming knots or slipknots. The knotting complexity
of the cataloged proteins is presented in the form of a matrix diagram that shows users the knot type of the entire polypeptide
chain and of each of its subchains. The pattern visible in the matrix gives the knotting fingerprint of a given protein and
permits users to determine, for example, the minimal length of the knotted regions (knot's core size) or the depth of a knot,
i.e. how many amino acids can be removed from either end of the cataloged protein structure before converting it from a knot
to a different type of knot. In addition, the database presents extensive information about the biological functions, families
and fold types of proteins with non-trivial knotting. As an additional feature, the KnotProt database enables users to submit
protein or polymer chains and generate their knotting fingerprints.
In the last decade, a new class of proteins has emerged that contain a topological knot in
their backbone. Although these structures are rare, they nevertheless challenge our
understanding of protein folding. In this review, we provide a short overview of
topologically knotted proteins with an emphasis on newly discovered structures. We discuss
the current knowledge in the field, including recent developments in both experimental and
computational studies that have shed light on how these intricate structures fold.
A rigid dinitrile ligand was synthesized from two xanthene units condensed to a naphthalene-1,4,5,8-diimide spacer. The rigidity and C shape of the ligand gave exclusively trans complexes with Pd(II), Ag(I), and Au(I). Evidence for complexation, coordination geometry, and stoichiometry was provided by a combination of 1H NMR, 19F NMR, and IR spectroscopy. The AuBF4 and PdCl2 complexes were shown to have a 1:1 (metal-to-ligand) stoichiometry and the AgBF4 complex was shown to have a 1:2 stoichiometry in solution. The preorganization of the dinitrile ligand resulted in complexes much more stable than their monodentate counterparts.
The crystal structure of the double-stranded DNA bacteriophage HK97 mature empty capsid was determined at 3.6 angstrom resolution.
The 660 angstrom diameter icosahedral particle contains 420 subunits with a new fold. The final capsid maturation step is
an autocatalytic reaction that creates 420 isopeptide bonds between proteins. Each subunit is joined to two of its neighbors
by ligation of the side-chain lysine 169 to asparagine 356. This generates 12 pentameric and 60 hexameric rings of covalently
joined subunits that loop through each other, creating protein chainmail: topologically linked protein catenanes arranged
with icosahedral symmetry. Catenanes have not been previously observed in proteins and provide a stabilization mechanism for
the very thin HK97 capsid.
Directed chemical synthesis can produce a vast range of molecular structures, but the intended product must be known at the outset. In contrast, evolution in nature can lead to efficient receptors and catalysts whose structures defy prediction. To access such unpredictable structures, we prepared dynamic combinatorial libraries in which reversibly binding building blocks assemble around a receptor target. We selected for an acetylcholine receptor by adding the neurotransmitter to solutions of dipeptide hydrazones [proline-phenylalanine or proline-(cyclohexyl)alanine], which reversibly combine through hydrazone linkages. At thermodynamic equilibrium, the dominant receptor structure was an elaborate [2]-catenane consisting of two interlocked macrocyclic trimers. This complex receptor with a 100 nM affinity for acetylcholine could be isolated on a preparative scale in 67% yield.
A crystal structure is reported for the C168S mutant of a typical 2-Cys peroxiredoxin III (Prx III) from bovine mitochondria at a resolution of 3.3 A. Prx III is present as a two-ring catenane comprising two interlocking dodecameric toroids that are assembled from basic dimeric units. Each ring has an external diameter of 150 A and encompasses a central cavity that is 70 A in width. The concatenated dodecamers are inclined at an angle of 55 degrees, which provides a large contact surface between the rings. Dimer-dimer contacts involved in toroid formation are hydrophobic in nature, whereas the 12 areas of contact between interlocked rings arise from polar interactions. These two major modes of subunit interaction provide important insights into possible mechanisms of catenane formation.
Phytochromes are red/far-red light photoreceptors that direct photosensory responses across the bacterial, fungal and plant kingdoms. These include photosynthetic potential and pigmentation in bacteria as well as chloroplast development and photomorphogenesis in plants. Phytochromes consist of an amino-terminal region that covalently binds a single bilin chromophore, followed by a carboxy-terminal dimerization domain that often transmits the light signal through a histidine kinase relay. Here we describe the three-dimensional structure of the chromophore-binding domain of Deinococcus radiodurans phytochrome assembled with its chromophore biliverdin in the Pr ground state. Our model, refined to 2.5 A resolution, reaffirms Cys 24 as the chromophore attachment site, locates key amino acids that form a solvent-shielded bilin-binding pocket, and reveals an unusually formed deep trefoil knot that stabilizes this region. The structure provides the first three-dimensional glimpse into the photochromic behaviour of these photoreceptors and helps to explain the evolution of higher plant phytochromes from prokaryotic precursors.
The mutual molecular recognition between different structural components in large rings has led to the template-directed synthesis of a wide range of catenanes composed of from two to five interlocked rings. The molecular self-assembly processes rely upon the recognition between (i) π-electron rich and π-electron deficient aromatic units and (ii) hydrogen bond donors and acceptors, in the different components. In order to increase our knowledge of the factors involved in such molecular self-assembly processes, a homologous series of [2]catenanes has been constructed using macrocyclic polyethers of the bis(p-phenylene)-(3n+4)-crown-n (n = 9-14) type as templates for the formation of the tetracationic cyclophane, cyclobis(paraquat-p-phenylene). Increasing the size of the tetracationic cyclophane to cyclobis(paraquat-4,4′-bitolyl) allows the simultaneous entrapment of two hydroquinone ring-containing macrocyclic polyethers affording a series of [3]catenanes, and one [4]catenane incorporating a cyclic dimer of the expanded cyclophane and three bis(p-phenylene)-34-crown-10 components. By analogy, increasing the number of hydroquinone rings in the macrocyclic polyether permits the self-assembly of more than one tetracationic cyclophane around the templates present in the macrocyclic polyether. In this context, the template-directed synthesis of two [3]catenanes, incorporating two cyclobis(paraquat-p-phenylene) components and either (i) tris(p-phenylene)-51-crown-15 or (ii) tetrakis(p-phenylene)-68-crown-20, has been achieved and is reported. A combination of these two approaches has led to the successful self-assembly, in two steps, of a linear [4]catenane, together with a small amount of a [5]catenane. The creation of these intricate molecular compounds lends support to the contention that self-assembly is a viable paradigm for the construction of nanometer-scale molecular architectures incorporating a selection of simple components.
Borromean rings or links are topologically complex assemblies of three entangled rings where no two rings are interlinked in a chain-like catenane, yet the three rings cannot be separated. We report here a metallacycle complex whose crystalline network forms the first example of a new class of entanglement. The complex is formed from the self-assembly of CuBr2 with the cyclotriveratrylene-scaffold ligand (±)-tris(iso-nicotinoyl)cyclotriguaiacylene. Individual metallacycles are interwoven into a two-dimensional chainmail network where each metallacycle exhibits multiple Borromean-ring-like associations with its neighbours. This only occurs in the solid state, and also represents the first example of a crystalline infinite chainmail two-dimensional network. Crystals of the complex were twinned and have an unusual hollow tubular morphology that is likely to result from a localized dissolution-recrystallization process.
Ein halbes Jahrhundert nach der ersten gerichteten Synthese eines [2]Catenans durch Schill und Lüttringhaus existiert heutzutage eine Vielzahl an Strategien zur Synthese von Hopf-Verschlingungen (einfach verzahnten Ringen), der einfachsten Klasse der Catenane. Die Präzision und Effektivität, mit der geeignete Template und/oder nichtkovalente Wechselwirkungen Bausteine anordnen können, ermöglichten die Synthese komplizierter – und häufig schöner – verzahnter Systeme höherer Ordnung, darunter Salomonische Verschlingungen, Borromäische Ringe und ein Davidstern-Catenan. In diesem Aufsatz werden die zahlreichen Strategien, die im 21. Jahrhundert zur Synthese von Catenanen zur Verfügung stehen, vorgestellt und potenzielle Anwendungen untersucht. Des Weiteren werden die Herausforderungen bei der Synthese noch komplizierterer Topologien aufgezeigt.
A simple self-assembled [Pd2L4] coordination cage consisting of four carbazole-based ligands was found to dimerize into the interpenetrated double cage [3 X@Pd4L8] upon the addition of 1.5 equivalents of halide anions (X=Cl−, Br−). The halide anions serve as templates, as they are sandwiched by four PdII cations and occupy the three pockets of the entangled cage structure. The subsequent addition of larger amounts of the same halide triggers another structural conversion, now yielding a triply catenated link structure in which each PdII node is trans-coordinated by two pyridine donors and two halide ligands. This simple system demonstrates how molecular complexity can increase upon a gradual change of the relative concentrations of reaction partners that are able to serve different structural roles.
Ein einfacher selbstorganisierter [Pd2L4]-Koordinationskäfig bestehend aus vier Carbazol-basierten Liganden dimerisiert nach Zugabe von 1.5 Äquivalenten eines Halogenidions (X=Cl−, Br−) zu einem verflochtenen Doppelkäfig [3 X@Pd4L8]. Die Halogenidionen agieren als Template, eingelagert in den drei Taschen der verschlungenen Käfigstruktur und umgeben von vier PdII Kationen. Zugabe höherer Mengen desselben Halogenidions bewirkt eine weitere strukturelle Umwandlung, die in einer dreifach verschlungenen Verbindung resultiert. Letztere enthält trans-koordinierte PdII-Zentren, die von zwei Pyridin-Donor- und zwei Halogenidliganden umgeben sind. Dieses einfache System zeigt eindrucksvoll, wie molekulare Komplexität aus der graduellen Änderung der relativen Konzentrationen einer geringen Zahl an Reaktionspartnern erwachsen kann, insbesondere, wenn diese unterschiedliche strukturelle Rollen einnehmen können.
Zwischen 1990 und 2000 wuchs in der Goldchemie das Interesse an aurophilen Wechselwirkungen, nachdem man festgestellt hatte, dass diese eine Vielzahl struktureller und anderer physikalischer Eigenschaften von Gold(I)-Verbindungen nennenswert beeinflussen. Die Aufmerksamkeit, die man diesem kontraintuitiven inter- und intramolekularen Typ von Bindung zwischen Metallzentren mit scheinbar abgeschlossener Elektronenschale entgegenbrachte, hat sich schnell auch auf die Chemie des Silbers ausgeweitet. Hunderte von Untersuchungen widmeten sich seither dem Phänomen der Argentophilie. Dieser Aufsatz gibt einen Überblick über diese Entwicklung mit Hauptaugenmerk auf molekularen Systemen mit zwei oder mehr in engem Kontakt stehenden Silber(I)-Zentren, was zu spezifischen strukturellen sowie zu einer Vielzahl neuartiger physikalischer Eigenschaften führt. Diese schließen vor allem stark veränderte LigandMetall-Ladungstransferprozesse ein, aber auch eine überdimensionale thermische Kontraktion auf der einen und eine beispiellose negative lineare Kompressibilität von Kristallparametern auf der anderen Seite.
The decade 1990-2000 saw a growing interest in aurophilic interactions in gold chemistry. These interactions were found to influence significantly a variety of structural and other physical characteristics of gold(I) compounds. The attention paid to this unusual and counterintuitive type of intra- and intermolecular bonding between seemingly closed-shell metal centers has rapidly been extended to also include silver chemistry. Hundreds of experimental and computational studies have since been dedicated to the argentophilicity phenomenon. The results of this development are reviewed herein focusing on molecular systems where two or more silver(I) centers are in close contact leading to specific structural characteristics and a variety of novel physical properties. These include strongly modified ligand-to-metal charge-transfer processes observed in absorption and emission spectroscopy, but also colossal positive and negative thermal expansion on the one hand and unprecedented negative linear compressibility of crystal parameters on the other.
We describe the synthesis of a [2]catenane that consists of two triply entwined 114-membered rings, a molecular link. The woven scaffold is a hexameric circular helicate generated by the assembly of six tris(bipyridine) ligands with six iron(II) cations, with the size of the helicate promoted by the use of sulfate counterions. The structure of the ligand extension directs subsequent covalent capture of the catenane by ring-closing olefin metathesis. Confirmation of the Star of David topology (two rings, six crossings) is provided by NMR spectroscopy, mass spectrometry and X-ray crystallography. Extraction of the iron(II) ions with tetrasodium ethylenediaminetetraacetate affords the wholly organic molecular link. The self-assembly of interwoven circular frameworks of controlled size, and their subsequent closure by multiple directed covalent bond-forming reactions, provides a powerful strategy for the synthesis of molecular topologies of ever-increasing complexity.
Short peptide helices have attracted attention as suitable building blocks for soft functional materials, but they are rarely seen in crystalline materials. A new artificial nanoassembly of short peptide helices in the crystalline state is presented in which peptide helices are arranged three-dimensionally by metal coordination. The folding and assembly processes of a short peptide ligand containing the Gly-Pro-Pro sequence were induced by silver(I) coordination in aqueous alcohol, and gave rise to a single crystal composed of polyproline II helices. Crystallographic studies revealed that this material possesses two types of unique helical nanochannel; the larger channel measures more than 2 nm in diameter. Guest uptake properties were investigated by soaking the crystals in polar solutions of guest molecules; anions, organic chiral molecules, and bio-oligomers are effectively encapsulated by this peptide-folded porous crystal, with moderate to high chiral recognition for chiral molecules.
Short peptide helices have attracted attention as suitable building blocks for soft functional materials, but they are rarely seen in crystalline materials. A new artificial nanoassembly of short peptide helices in the crystalline state is presented in which peptide helices are arranged three-dimensionally by metal coordination. The folding and assembly processes of a short peptide ligand containing the Gly-Pro-Pro sequence were induced by silver(I) coordination in aqueous alcohol, and gave rise to a single crystal composed of polyproline II helices. Crystallographic studies revealed that this material possesses two types of unique helical nanochannel; the larger channel measures more than 2 nm in diameter. Guest uptake properties were investigated by soaking the crystals in polar solutions of guest molecules; anions, organic chiral molecules, and bio-oligomers are effectively encapsulated by this peptide-folded porous crystal, with moderate to high chiral recognition for chiral molecules.
[2]Rotaxanes consisting of butadiyne-linked porphyrin dimers threaded through a phenanthroline-containing macrocycle, can be synthesised by an active-metal template directed copper-mediated Glaser coupling, in yields of up to 61%, without requiring a large excess of the macrocycle. The crystal structure of one of these rotaxanes confirms that the macrocycle is clasped around the centre of the porphyrin dimer. A radial hexa-pyridyl template was used to convert the alkyne-terminated [2]rotaxane into a [4]catenane cyclic porphyrin hexamer in 62% yield, via palladium-catalysed Glaser coupling. The related [7]catenane porphyrin dodecamer complex was also isolated as a by-product of this cyclisation, in 6% yield. These results illustrate the scope of template-directed synthesis for creating complex interlocked structures directly from simple starting materials.
Synthese d'une sorte de catenane formant des helices a partir de bis-[hydroxy-4 phenyl]-9,9' tetramethylene-2,2' bis-phenanthroline-1,10 et du derive diiodo de l'hexaethyleneglycol en presence de [Cu(CH 3 CN) 4 ] +
Molecular knots have long been the subject of speculation. Now, for the first time, it has been possible to synthesize a “knotted” molecule having the topological chirality of a trefoil knot. Compound 1 was synthesized via a double‐helix complex by exploiting the template effect of CuI ions. The chirality of 1 could be demonstrated by ¹H NMR spectroscopy. The “unraveled” topological isomer of 1 was also synthesized. (Figure Presented.)
Supermolecules consisting of interlinked ring-like molecules (catenanes) are an interesting target for chemical synthesis both for their intrinsic interest as non-covalently bound but robust assemblies and because of the perspective they offer on materials chemistry. Catenanes have been prepared by metal-ion templating, and self-assembly through other non-covalent interactions,,,,,,,. Here we report the synthesis of a catenane composed not of two interlocking rings but of two cages. This structure is prepared by metal-mediated self-assembly,,. The framework of each cage is assembled from five components: two tridentate ligands held together with three metal ions. Because each cage framework can bind an aromatic ring, two cage units will bind one another during their assembly process through the formation of a quadruple aromatic stack, giving rise to the ten-component interlocked supermolecule,.
Seven of the best: A dynamic combinatorial library of polycatenated tetrahedra was prepared by complexation between a dynamic Fe4 L6 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.
The selectivity of formation of organometallic rings or [2]catenanes [{X(4-C6H4OCH2CCAu)2(μ-Ph2PZPPh2)}n], n =1 or 2, respectively, has been studied as a function of the hinge group X and the diphosphine ligand [X = O, S, SO2, CH2, CMe2, CPh2, C(CF3)2, C6H10; Z = (CH2)m with m = 2−5]. When Z = (CH2)3, mixing of pairs of compounds with different C2v-symmetrical hinge groups (X, X‘ = SO2, CH2, CMe2, CPh2, C(CF3)2, C6H10) led to formation of an equilibrium mixture containing the unsymmetrical [2]catenanes [{X(4-C6H4OCH2CCAu)2(μ-Ph2PZPPh2)}{X‘(4-C6H4OCH2CCAu)2(μ-Ph2PZPPh2)], as identified by NMR spectroscopy. The complexes with Z = (CH2)4 exist in solution predominantly as the macrocycles and so do not form analogous mixed diacetylide complexes. When the hinge group contained a prochiral carbon center (X = CHMe, CMePh, 1,1-indanylidene), only achiral macrocycles [X(4-C6H4OCH2CCAu)2(μ-Ph2PZPPh2)] were formed in solution when Z = (CH2)4, but mixtures containing both achiral macrocycles and chiral [2]catenane were formed when Z = (CH2)3. In several cases, the solid-state structures of the isolated complexes were not representative of the structures in solution, with macrocycles being dominant in solution and [2]catenanes formed preferentially during crystallization.
Using dynamic combinatorial chemistry, mixtures of dipeptide monomers were combined to probe how the structural elements of a family of self-assembled [2]-catenanes affect their equilibrium stability versus competing non-catenated structures. Of particular interest were experiments to target the effects of CH-π interactions, inter-ring hydrogen bonds, and β-turn types on [2]-catenane energetics. The non-variant core of the [2]-catenane was shown only to adopt type II' and type VIII turns at the β-2 and β-4 positions, respectively. Monomers were designed to delineate how these factors contribute to [2]-catenane equilibrium speciation/stability. Dipeptide turn adaptation studies, including three-component dynamic self-assembly experiments, suggested that stability losses are localized to the mutated sites, and that the turn types for the core β-2 and β-4 positions, type II' and type VIII, respectively, cannot be modified. Mutagenesis studies on the core Aib residue involved in a seemingly key CH-π-CH sandwich reported on how CH-π interactions and inter-ring hydrogen bonds affect stability. The interacting methyl group of Aib could be replaced with a range of alkyl and aryl substituents with monotonic affects on stability, though polar heteroatoms were disproportionately destabilizing. The importance of a key cross-ring H-bond was also probed by examining an Aib for l-Pro variant. Inductive affects and the effect of CH donor multiplicity on the core proline-π interaction also demonstrated that electronegative substituents and the number of CH donors can enhance the effectiveness of a CH-π interaction. These data were interpreted using a cooperative binding model wherein multiple non-covalent interactions create a web of interdependent interactions. In some cases, changes to a component of the web lead to compensating effects in the linked interactions, while in others, the perturbations create a cascade of destabilizing interactions that lead to disproportionate losses in stability.
Under acidic conditions (50 equiv of TFA), combinations of hydrazide A-B monomers self-assemble into octameric [2]-catenanes with high selectivity for [1(3)2](2), where 1 is a D-Pro-X (X = Aib, Ac(4)c, Ac(6)c, L-4-Cl-PhGly)-derived monomer and 2 is an L-Pro'-L-arylGly (Pro' = Pro, trans-F-Pro, trans-HO-Pro, aryl = naphthyl, phenyl)-derived monomer. Five different combinations of monomers were studied by X-ray crystallography. In each case, the unique aryl glycine unit is located in the core of the structure where the aryl ring templates a CH-π-CH sandwich. Analysis of metrical parameters indicates that this core region is highly conserved, while the more peripheral zones are flexible. (1)H NMR spectroscopy indicate that the solid-state structures are largely retained in solution, though several non-C(2)-symmetric compounds have a net C(2)-symmetry that indicates accessible dynamic processes. Catenane dynamic processes were additionally probed through H/D exchange, with the core being inflexible relative to the peripheral structure. Mass spectrometry was utilized to identify the constitutional isomerism in the minor asymmetric [1(5)2(3)] catenanes.
A growing number of organisms have been discovered inhabiting extreme environments, including temperatures in excess of 100 degrees C. How cellular proteins from such organisms retain their native folds under extreme conditions is still not fully understood. Recent computational and structural studies have identified disulfide bonding as an important mechanism for stabilizing intracellular proteins in certain thermophilic microbes. Here, we present the first proteomic analysis of intracellular disulfide bonding in the hyperthermophilic archaeon Pyrobaculum aerophilum. Our study reveals that the utilization of disulfide bonds extends beyond individual proteins to include many protein-protein complexes. We report the 1.6 A crystal structure of one such complex, a citrate synthase homodimer. The structure contains two intramolecular disulfide bonds, one per subunit, which result in the cyclization of each protein chain in such a way that the two chains are topologically interlinked, rendering them inseparable. This unusual feature emphasizes the variety and sophistication of the molecular mechanisms that can be achieved by evolution.
The role of covalent, coordinative, and supramolecular interactions utilized by chemists and biochemists, when they are assembling molecular knots and links, are presented. The Trefoil Knot comprises a simple overhand knot where the two ends have been connected and can exist in left-handed and right-handed forms. A molecular Trefoil Knot displays inherent topological chirality and any representation of its graph cannot be deformed in 3D space to its mirror image, and exists as two enantiomers. A significant increase in knot yields is achieved by replacing the polymethylene linker with a meta-phenylene bridge, a change of design that resulted in the quantitative assembly of the precursor double helical complex. Alkene metathesis is particularly suited to macrocyclizations involving Cu(I)-templated species as it is a thermodynamically controlled reaction. It also avoids the need for addition of destabilizing bases, such as NaH, which are required when alkylation is the final step in the reaction sequence.
Closed circular mitochondrial DNA molecules which are catenated, or connected like the links in a chain, have been identified in extracts of HeLa cells.
Omega (omega-) loops, a nonregular secondary structure found in globular proteins, are characterized by a polypeptide chain that follows a loop-shaped course in three-dimensional space. They do not contain repeating backbone dihedral angles or regular patterns of hydrogen bonding; however, many omega-loops contain a large number of hydrogen bonds, therefore it is not correct to think of omega-loops as structures lacking in hydrogen bonds. omega-Loops are found almost exclusively at the protein surface and exhibit amino acid preferences consistent with this observation. Since the first description of omega-loops in 1986, experiments have been conducted to probe the role of these structures in protein function, stability, and folding. It has become clear that omega-loops are often involved in protein function and molecular recognition. One motif, an omega-loop lid, that is flexible and mobile until substrate or inhibitor is bound and which probably plays a role in one or more steps of enzymatic catalysis, has been described in a variety of enzymes. Because they lack the periodic hydrogen bonding patterns of the regular secondary structures, some omega-loops are well suited for such functional roles in proteins. However, loops with a higher-than-average number of hydrogen bonds or hydrophobic contacts may play roles in protein stability or folding. Rather than determining further geometric definitions of loops, it may be instructional to group them according to their roles in protein structure, i.e., as categories of functional omega-loops, stability omega-loops, and folding omega-loops.
The search for knots in protein has uncovered little that would cause Alexander the Great to reach for his sword. Excluding knots formed by post-translational crosslinking, the few proteins considered to be knotted form simple trefoil knots with one end of the chain extending through a loop by only a few residues, ten in the 'best' example. A knot in an open chain (as distinct from a closed circle) is not rigorously defined and many weak protein knots disappear if the structure is viewed from a different angle. Here I describe a computer algorithm to detect knots in open chains that is not sensitive to viewpoint and that can define the region of the chain giving rise to the knot. It characterizes knots in proteins by the number of residues that must be removed from each end to abolish the knot. I applied this algorithm to the protein structure database and discovered a deep, figure-of-eight knot in the plant protein acetohydroxy acid isomeroreductase. I propose a protein folding pathway that may explain how such a knot is formed.
This paper reports an efficient strategy to synthesize molecular necklaces, in which a number of small rings are threaded onto a large ring, utilizing the principles of self-assembly and coordination chemistry. Our strategy involves (1) threading a molecular "bead" with a short "string" to make a pseudorotaxane and then (2) linking the pseudorotaxanes with a metal complex with two cis labile ligands acting as an "angle connector" to form a cyclic product (molecular necklace). A 4- or 3-pyridylmethyl group is attached to each end of 1,4-diaminobutane or 1,5-diaminopentane to produce the short "strings" (C4N4(2+), C4N3(2+), C5N4(2+), and C5N3(2+)), which then react with a cucurbituril (CB) "bead" to form stable pseudorotaxanes (PR44(2+), PR43(2+), PR54(2+), and PR53(2+), respectively). The reaction of the pseudorotaxanes with Pt(en)(NO(3))(2) (en = ethylenediamine) produces a molecular necklace [4]MN, in which three molecular "beads" are threaded on a triangular framework, and/or a molecular necklace [5]MN, in which four molecular "beads" are threaded on a square framework. Under refluxing conditions, the reaction with PR44(2+) or PR54(2+) yields exclusively [4]MN (MN44T or MN54T, respectively), whereas that with PR43(2+) or PR53(2+) produces exclusively [5]MN (MN43S or MN53S, respectively). The products have been characterized by various methods including X-ray crystallography. At lower temperatures, on the other hand, the reaction with PR44(2+) or PR54(2+) affords both [4]MN and [5]MN. The supermolecules reported here are the first series of molecular necklaces obtained as thermodynamic products. The overall structures of the molecular necklaces are strongly influenced by the structures of pseudorotaxane building blocks, which is discussed in detail on the basis of the X-ray crystal structures. The temperature dependence of the product distribution observed in this self-assembly process is also discussed.
The antibacterial peptide microcin J25 (MccJ25) inhibits bacterial transcription by binding within, and obstructing, the nucleotide-uptake channel of bacterial RNA polymerase. Published covalent and three-dimensional structures indicate that MccJ25 is a 21-residue cycle. Here, we show that the published covalent and three-dimensional structures are incorrect, and that MccJ25 in fact is a 21-residue "lariat protoknot", consisting of an 8-residue cyclic segment followed by a 13-residue linear segment that loops back and threads through the cyclic segment. MccJ25 is the first example of a lariat protoknot involving a backbone-side chain amide linkage.
The realization of the Borromean link in a wholly synthetic molecular form is reported. The self-assembly of this link, which is topologically achiral, from 18 components by the template-directed formation of 12 imine and 30 dative bonds, associated with the coordination of three interlocked macrocycles, each tetranucleating and decadentate overall, to a total of six zinc(II) ions, is near quantitative. Three macrocycles present diagonally in pairs, six exo-bidentate bipyridyl and six endo-diiminopyridyl ligands to the six zinc(II) ions. The use, in concert, of coordination, supramolecular, and dynamic covalent chemistry allowed the highly efficient construction, by multiple cooperative self-assembly processes, of a nanoscale dodecacation with an approximate diameter of 2.5 nanometers and an inner chamber of volume 250 A(3), lined with 12 oxygen atoms.
Among proteins of known three-dimensional structure, only a few possess complex topological features such as knotted or interlinked (catenated) protein backbones. Such unusual proteins offer potentially unique insights into folding pathways and stabilization mechanisms. They also present special challenges for both theorists and computational scientists interested in understanding and predicting protein-folding behavior. Here, we review complex topological features in proteins with a focus on recent progress on the identification and characterization of knotted and interlinked protein systems. Also, an approach is described for designing an expanded set of knotted proteins.
(Figure Presented) Making up a foursome: Self-assembly of 4,4′-(3-pyridinemethoxy)benzophenone (L) and Pd(NO3) 2 resulted in the quantitative formation of a quadruply stranded metallohelicate [Pd2(L)4], which undergoes spontaneous dimerization to an unprecedented chiral interlocked metallohelicate [Pd 2(L)4]2 (see X-ray structure; C black, H white, N blue, O red).
Angew. Chem. 2015, 127, 756–797