We describe the use of dynamic combinatorial chemistry to discover a new series of linear hydrazone-based receptors that bind multiple dihydrogen phosphate ions. Through the use of a template-driven, ...selection-based approach to receptor synthesis, dynamic combinatorial chemistry allows for the identification of unexpected host structures and binding motifs. Notably, we observed the unprecedented selection of these linear receptors in preference to competing macrocyclic hosts. Furthermore, linear receptors containing up to nine building blocks and three different building blocks were amplified in the dynamic combinatorial library. The receptors were formed using a dihydrazide building block based on an amino acid-disubstituted ferrocene scaffold. A detailed study of the linear pentamer revealed that it forms a helical ditopic receptor that employs four acylhydrazone hydrogen-bond donor motifs to cooperatively bind two dihydrogen phosphate ions.
Amino-acid functionalized naphthalenediimides self-assemble into hydrogen-bonded supramolecular helical nanotubes via a noncooperative, isodesmic process; the self-assembly of ordered helical systems ...is usually realized through a cooperative process. This unexpected behavior was rationalized as a manifestation of entropy–enthalpy compensation. Fundamental insights into the thermodynamics governing this self-assembly were obtained through the fitting of the isodesmic model to 1H NMR spectrometry and circular dichroism spectroscopy measurements. Furthermore, we have extended the application of this mathematical model, for the first time, to quantitatively estimate the effect of guests, solvents, and side chains on the stability of the supramolecular nanotube; most significantly, we demonstrate that C60 acts as a template to stabilize the nanotube assembly and thereby substantially increase the degree of polymerization.
We present the first polymorph interconversion study that uses solid-state dynamic covalent chemistry (DCC). This system exhibits unexpected and rich behavior, including the observation that under ...appropriate conditions the polymorph interconversion of a heterodimer proceeds through reversible covalent chemistry intermediates, and this route is facilitated by one of the two disulfide homodimers involved in the reaction. Furthermore, we demonstrate experimentally that in all cases a dynamic equilibrium is reached, meaning that changing the milling conditions affects the free energy difference between the two polymorphs and thus their relative stability. We suggest that this effect is due to the surface solvation energy combined with the high surface to volume ratio of the nanocrystalline powder.
We here explore how ball-mill-grinding frequency affects the kinetics of a disulfide exchange reaction. Our kinetic data show that the reaction progress is similar at all the frequencies studied ...(15-30 Hz), including a significant induction time before the nucleation and growth process starts. This indicates that to start the reaction an initial energy accumulation is necessary. Other than mixing, the energy supplied by the mechanical treatment has two effects: (i) reducing the crystal size and (ii) creating defects in the structure. The crystal-breaking process is likely to be dominant at first becoming less important later in the process when the energy supplied is stored at the molecular level as local crystal defects. This accumulation is taken here to be the rate-determining step. We suggest that the local defects accumulate preferentially at or near the crystal surface. Since the total area increases exponentially when the crystal size is reduced by the crystal-breaking process, this can further explain the exponential dependence of the onset time on the milling frequency.
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.
Templated Dynamic Synthesis of a [3]Catenane Cougnon, Fabien B. L.; Jenkins, Nicholas A.; Pantoş, G. Dan ...
Angewandte Chemie (International ed.),
February 6, 2012, Volume:
51, Issue:
6
Journal Article
Peer reviewed
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.
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.
We report the first dynamic combinatorial synthesis in water of an all-acceptor 2catenane and of different types of donor–acceptor 2 and 3catenanes. Linking two electron-deficient motifs within one ...building block using a series of homologous alkyl chains provides efficient and selective access to a variety of catenanes and offers an unprecedented opportunity to explore the parameters that govern their synthesis in water. In this series, catenane assembly is controlled by a fine balance between kinetics and thermodynamics and subtle variations in the building block structure, such as the linker length and building block chirality. A remarkable and unexpected odd–even effect with respect to the number of atoms in the alkyl linker is reported.
Abstract
Self-assembly of multiple building blocks via hydrogen bonds into well-defined nanoconstructs with selective binding function remains one of the foremost challenges in supramolecular ...chemistry. Here, we report the discovery of a enantiopure nanocapsule that is formed through the self-assembly of eight amino acid functionalised molecules in nonpolar solvents through 48 hydrogen bonds. The nanocapsule is remarkably robust, being stable at low and high temperatures, and in the presence of base, presumably due to the co-operative geometry of the hydrogen bonding motif. Thanks to small pore sizes, large internal cavity and sufficient dynamicity, the nanocapsule is able to recognize and encapsulate large aromatic guests such as fullerenes C
60
and C
70
. The structural and electronic complementary between the host and C
70
leads to its preferential and selective binding from a mixture of C
60
and C
70
.
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