Molecular self-assembly is the spontaneous association of molecules under equilibrium conditions into stable, structurally well-defined aggregates joined by noncovalent bonds. Molecular self-assembly is ubiquitous in biological systems and underlies the formation of a wide variety of complex biological structures. Understanding self-assembly and the associated noncovalent interactions that connect complementary interacting molecular surfaces in biological aggregates is a central concern in structural biochemistry. Self-assembly is also emerging as a new strategy in chemical synthesis, with the potential of generating nonbiological structures with dimensions of 1 to 10(2) nanometers (with molecular weights of 10(4) to 10(10) daltons). Structures in the upper part of this range of sizes are presently inaccessible through chemical synthesis, and the ability to prepare them would open a route to structures comparable in size (and perhaps complementary in function) to those that can be prepared by microlithography and other techniques of microfabrication.

Molecular self-assembly and nanochemistry: A chemical strategy for the synthesis of nanostructures

Covalent organic frameworks (COFs) represent an exciting new type of porous organic materials, which are ingeniously constructed with organic building units via strong covalent bonds. The well-defined crystalline porous structures together with tailored functionalities have offered the COF materials superior potential in diverse applications, such as gas storage, adsorption, optoelectricity, and catalysis. Since the seminal work of Yaghi and co-workers in 2005, the rapid development in this research area has attracted intensive interest from researchers with diverse expertise. This critical review describes the state-of-the-art development in the design, synthesis, characterisation, and application of the crystalline porous COF materials. Our own opinions on further development of the COF materials are also presented for discussion (155 references).

Covalent organic frameworks (COFs): from design to applications

Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.

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Designing hydrogels for controlled drug delivery.

The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Synthetic molecular motors and mechanical machines.

Covalent organic frameworks (COFs) are a class of crystalline porous polymers that allow the atomically precise integration of organic units to create predesigned skeletons and nanopores. They have recently emerged as a new molecular platform for designing promising organic materials for gas storage, catalysis, and optoelectronic applications. The reversibility of dynamic covalent reactions, diversity of building blocks, and geometry retention are three key factors involved in the reticular design and synthesis of COFs. This tutorial review describes the basic design concepts, the recent synthetic advancements and structural studies, and the frontiers of functional exploration.

Covalent organic frameworks

Dynamic covalent chemistry relates to chemical reactions carried out reversibly under conditions of equilibrium control. The reversible nature of the reactions introduces the prospects of "error checking" and "proof-reading" into synthetic processes where dynamic covalent chemistry operates. Since the formation of products occurs under thermodynamic control, product distributions depend only on the relative stabilities of the final products. In kinetically controlled reactions, however, it is the free energy differences between the transition states leading to the products that determines their relative proportions. Supramolecular chemistry has had a huge impact on synthesis at two levels: one is noncovalent synthesis, or strict self-assembly, and the other is supramolecular assistance to molecular synthesis, also referred to as self-assembly followed by covalent modification. Noncovalent synthesis has given us access to finite supermolecules and infinite supramolecular arrays. Supramolecular assistance to covalent synthesis has been exploited in the construction of more-complex systems, such as interlocked molecular compounds (for example, catenanes and rotaxanes) as well as container molecules (molecular capsules). The appealing prospect of also synthesizing these types of compounds with complex molecular architectures using reversible covalent bond forming chemistry has led to the development of dynamic covalent chemistry. Historically, dynamic covalent chemistry has played a central role in the development of conformational analysis by opening up the possibility to be able to equilibrate configurational isomers, sometimes with base (for example, esters) and sometimes with acid (for example, acetals). These stereochemical "balancing acts" revealed another major advantage that dynamic covalent chemistry offers the chemist, which is not so easily accessible in the kinetically controlled regime: the ability to re-adjust the product distribution of a reaction, even once the initial products have been formed, by changing the reaction's environment (for example, concentration, temperature, presence or absence of a template). This highly transparent, yet tremendously subtle, characteristic of dynamic covalent chemistry has led to key discoveries in polymer chemistry. In this review, some recent examples where dynamic covalent chemistry has been demonstrated are shown to emphasise the basic concepts of this area of science.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820020503%2941%3A9%3C1460%3A%3AAID-ANIE11111460%3E3.0.CO%3B2-N

Dynamic covalent chemistry.

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 A3, lined with 12 oxygen atoms.

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Molecular borromean rings.

Multivalent interactions, which rely upon noncovalent bonds, are essential ingredients in the mediation of biological processes, as well as in the construction of complex (super)structures for materials applications. A fundamental understanding of multivalency in supramolecular chemistry is necessary not only to construct motors and devices on the nanoscale but also to synthesize model systems to provide insight into how biological processes work. This Account focuses on the application of multivalency to supramolecular chemistry in particular and the nanosciences in general.

Multivalency and cooperativity in supramolecular chemistry.

For many decades, the construction of organic compounds in the laboratory has relied on the remarkable abilities of the 20th century ‘alchemists’ — namely, synthetic organic chemists — to make and break covalent bonds. Careful selection of functional groups and reaction conditions, in conjunction with protection/deprotection protocols, constitute the ‘secrets’ and ‘tricks’ of their ‘art’ which is commensurate with ‘traditional’ organic synthesis [1,2]. Indeed, relying on multistep reaction sequences, the total syntheses of structurally intricate molecular compounds which are constructed entirely using covalent bonds — e.g., brevetoxin B [3], palytoxin [4], and the calichearubicins [5] — have been realized in recent times. These very elegant and successful syntheses have required enormous intellectual and hands-on effort by large teams of chemists over rather long periods of time — very often, several years. Moreover, these extremely complex, and often particularly beautiful, examples represent close to state-of-the-art as far as ‘traditional’ organic synthesis is concerned. Alas, they also highlight the difficulties and limitations associated with classical organic syntheses — specifically, that the multistep aspect of such syntheses can be extremely laborious and time-consuming. With the possible exception of some dendritic structures [6], it is becoming apparent that the construction of nanoscopic structures, of the same complexities as those found in biological systems, using these classical methods is out of the reach of even the most talented and optimistic of the 20th century chemists!

Synthetic supramolecular chemistry

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3757%2820020503%29114%3A9%3C1528%3A%3AAID-ANGE11111528%3E3.0.CO%3B2-Z

Stuart Cantrill

Papers

Dynamic covalent chemistry.

Molecular borromean rings.

Multivalency and cooperativity in supramolecular chemistry.

Synthetic supramolecular chemistry

Dynamische kovalente Chemie