Since its inception in the mid-1990s, dynamic combinatorial chemistry (DCC), the chemistry of complex systems under thermodynamic control, has proved valuable in identifying unexpected molecules with ...remarkable binding properties and in providing effective synthetic routes to complex species. Essentially, in this approach, one designs the experiment rather than the molecule. DCC has also provided us with insights into how some chemical systems respond to external stimuli. Using examples from the work of our laboratory and others, this Account shows how the concept of DCC, inspired by the evolution of living systems, has found an increasing range of applications in diverse areas and has evolved conceptually and experimentally. A dynamic combinatorial library (DCL) is a thermodynamically controlled mixture of interconverting species that can respond to various stimuli. The Cambridge version of dynamic combinatorial chemistry was initially inspired by the mammalian immune system and was conceived as a way to create and identify new unpredictable receptors. For example, an added template can select and stabilize a strongly binding member of the library which is then amplified at the expense of the unsuccessful library members, minimizing the free energy of the system. But researchers have exploited DCC in a variety of other ways: over the past two decades, this technique has contributed to the evolution of chemistry and to applications in the diverse fields of catalysis, fragrance release, and responsive materials. Among these applications, researchers have built intricate and well-defined architectures such as catenanes or hydrogen-bonded nanotubes, using the ability of complex chemical systems to reach a high level of organization. In addition, DCC has proved a powerful tool for the study of complex molecular networks and systems. The use of DCC is improving our understanding of chemical and biological systems. The study of folding or self-replicating macrocycles in DCLs has served as a model for appreciating how complex organisations such as life can emerge from a pool of simple chemicals. Today, DCC is no longer restricted to thermodynamic control, and new systems have recently appeared in which kinetic and thermodynamic control coexist. Expanding the realm of DCC to unexplored and promising new territories, these hybrid systems show that the concept of dynamic combinatorial chemistry continues to evolve.
Discovery of an Organic Trefoil Knot Ponnuswamy, Nandhini; Cougnon, Fabien B. L.; Clough, Jessica M. ...
Science (American Association for the Advancement of Science),
11/2012, Letnik:
338, Številka:
6108
Journal Article
Recenzirano
Molecular knots remain difficult to produce using the current synthetic methods of chemistry because of their topological complexity. We report here the near-quantitative self-assembly of a trefoil ...knot from a naphthalenediimide-based aqueous disulfide dynamic combinatorial library. The formation of the knot appears to be driven by the hydrophobic effect and leads to a structure in which the aromatic components are buried while the hydrophilic carboxylate groups remain exposed to the solvent. Moreover, the building block chirality constrains the topological conformation of the knot and results in its stereoselective synthesis. This work demonstrates that the hydrophobic effect provides a powerful strategy to direct the synthesis of entwined architectures.
Conventional approaches to the synthesis of molecular knots and links mostly rely on metal templation. We present here an alternative strategy that uses the hydrophobic effect to drive the formation ...of complex interlocked structures in water. We designed an aqueous dynamic combinatorial system that can generate knots and links. In this system, the self-assembly of a topologically complex macrocycle is thermodynamically favored only if an optimum packing of all its components minimizes the hydrophobic surface area in contact with water. Therefore, the size, geometry, and rigidity of the initial building blocks can be exploited to control the formation of a specific topology. We illustrate the validity of this concept with the syntheses of a Hopf link, a Solomon link, and a trefoil knot. This latter molecule, whose self-assembly is templated by halides, binds iodide with high affinity in water. Overall, this work brings a fresh perspective on the synthesis of topologically complex molecules: Solvophobic effects can be intentionally harnessed to direct the efficient and selective self-assembly of knots and links.
Achiral 2catenanes composed of rings with inequivalent sides may adopt chiral co-conformations. Their stereochemistry depends on the relative orientation of the interlocked rings and can be ...controlled by sterics or an external stimulus (e.g., a chemical stimulus). Herein, we have exploited this stereodynamic property to amplify a mechanically chiral (P)-catenane upon binding to (R)-1,1′-binaphthyl 2,2′-disulfonate, with a diastereomeric excess of 85%. The chirality of the 2catenane was ascertained in the solid state by single crystal X-ray diffraction and in solution by NMR and CD spectroscopies. This study establishes a robust basis for the development of a new synthetic approach to access enantioenriched mechanically chiral 2catenanes.
Dynamic covalent synthesis Cougnon, Fabien B. L; Stefankiewicz, Artur R; Ulrich, Sébastien
Chemical science,
01/2024, Letnik:
15, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Dynamic covalent synthesis aims to precisely control the assembly of simple building blocks linked by reversible covalent bonds to generate a single, structurally complex, product. In recent years, ...considerable progress in the programmability of dynamic covalent systems has enabled easy access to a broad range of assemblies, including macrocycles, shape-persistent cages, unconventional foldamers and mechanically-interlocked species (catenanes, knots,
etc.
). The reversibility of the covalent linkages can be either switched off to yield stable, isolable products or activated by specific physico-chemical stimuli, allowing the assemblies to adapt and respond to environmental changes in a controlled manner. This activatable dynamic property makes dynamic covalent assemblies particularly attractive for the design of complex matter, smart chemical systems, out-of-equilibrium systems, and molecular devices.
Toward organic self-synthesis using encoded synthons and programmed processes: we summarize here the design principles and the recent achievements which illustrate the power of dynamic covalent synthesis for making complex covalent architectures.
A homochiral naphthalenediimide-based building block forms in water a disulfide library of macrocycles containing topological isomers. We attempted to identify each of these isomers, and explored the ...mechanisms leading to their formation. The two most abundant species of the library were assigned as a topologically chiral Solomon link (60% of the library, as measured by high-performance liquid chromatography (HPLC)) and a topologically achiral figure eight knot (18% by HPLC), competing products with formally different geometries but remarkably similar 4-fold symmetries. In contrast, a racemic mixture of building blocks gives the near-quantitative formation of another new and more stable structure, assigned as a meso figure eight knot. Taken together, these results seem to uncover a correlation between the point chirality of the building block used and the topological chirality of the major structure formed. These and the earlier discovery of a trefoil knot also suggest that the number of rigid components in the building block may translate into corresponding knot symmetry and could set the basis of a new strategy for constructing complex topologies.
Complex molecular knots and links are still difficult to synthesize and the properties arising from their topology are mostly unknown. Here, we report on a comparative photophysical study carried out ...on a family of closely related quinolinium‐based knots and links to determine the impact exerted by topology on the molecular backbone. Our results indicate that topology has a negligible influence on the behavior of loosely braided molecules, which mostly behave like their unbraided equivalents. On the other hand, tightly braided molecules display distinct features. Their higher packing density results in a pronounced ability to resist deformation, a significant reduction in the solvent‐accessible surface area and favors close‐range π–π interactions between the quinolinium units and neighboring aromatics. Finally, the sharp alteration in behavior between loosely and tightly braided molecules sheds light on the factors contributing to braiding tightness.
Untying the knot: The topology of a molecule affects its physical and chemical properties in many ways. The built‐in quinolinium chromophore in a family of structurally related knots and links, exhibits sharp alteration in its properties depending on the braiding tightness as uncovered by UV/Vis, transient absorption and NMR spectroscopies.
Templated Dynamic Synthesis of a [3]Catenane Cougnon, Fabien B. L.; Jenkins, Nicholas A.; Pantoş, G. Dan ...
Angewandte Chemie (International ed.),
February 6, 2012, Letnik:
51, Številka:
6
Journal Article
Recenzirano
Three rings: The self‐assembly of a water‐soluble 3catenane from a library composed of two linear building blocks, both terminated by cysteine components, is promoted either by a high salt ...concentration or by the presence of spermine. The spermine‐templated synthesis of the 3catenane shows that such structures can exhibit strong binding interactions with a biologically relevant target in water under near‐physiological conditions.
A molecular Solomon link adopts different conformations in acetonitrile (1) and in water (2). Contrary to expectations, the main driving force of the transformation is not the change in medium ...polarity, but the cooperative binding of about four molecules of water, forming a tiny droplet in the central cavity of 2. Mechanistic studies reveal that the four binding sites can simultaneously switch between an inactive state (unable to bind water) and an active state (able to bind water) during the transformation. Spatial and temporal coordination of switching events is commonly observed in biological systems but has been rarely achieved in artificial systems. Here, the concerted activation of the four switchable sites is controlled by the topology of the whole molecule.
Like in a game of falling dominoes: A molecular Solomon link is presented that possesses four interdependent binding sites that can switch in a concerted way between an inactive and an active state. In the active state, each site binds one molecule of water. Binding of a total of four water molecules to this unusual receptor is highly cooperative.
The discovery through dynamic combinatorial chemistry (DCC) of a new generation of donor−acceptor 2catenanes highlights the power of DCC to access unprecedented structures. While conventional ...thinking has limited the scope of donor−acceptor catenanes to strictly alternating stacks of donor (D) and acceptor (A) aromatic units, DCC is demonstrated in this paper to give access to unusual DAAD, DADD, and ADAA stacks. Each of these catenanes has specific structural requirements, allowing control of their formation. On the basis of these results, and on the observation that the catenanes represent kinetic bottlenecks in the reaction pathway, we propose a mechanism that explains and predicts the structures formed. Furthermore, the spontaneous assembly of catenanes in aqueous dynamic systems gives a fundamental insight into the role played by hydrophobic effect and donor−acceptor interactions when building such complex architectures.
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