Dynamic covalent chemistry

Last updated

Dynamic covalent chemistry (DCvC) is a synthetic strategy employed by chemists to make complex supramolecular assemblies from discrete molecular building blocks. [1] DCvC has allowed access to complex assemblies such as covalent organic frameworks, molecular knots, polymers, and novel macrocycles. [2] Not to be confused with dynamic combinatorial chemistry, DCvC concerns only covalent bonding interactions. As such, it only encompasses a subset of supramolecular chemistries.


The underlying idea is that rapid equilibration allows the coexistence of a variety of different species among which molecules can be selected with desired chemical, pharmaceutical and biological properties. For instance, the addition of a proper template will shift the equilibrium toward the component that forms the complex of higher stability ( thermodynamic template effect ). After the new equilibrium is established, the reaction conditions are modified to stop equilibration. The optimal binder for the template is then extracted from the reactional mixture by the usual laboratory procedures. The property of self-assembly and error-correcting that allow DCvC to be useful in supramolecular chemistry rely on the dynamic property.

Dynamic systems

Dynamic systems are collections of discrete molecular components that can reversibly assemble and disassemble. Systems may include multiple interacting species leading to competing reactions.

Thermodynamic control

Figure 1: Thermodynamic versus Kinetic Control KTC Super.png
Figure 1: Thermodynamic versus Kinetic Control

In dynamic reaction mixtures, multiple products exist in equilibrium. Reversible assembly of molecular components generates products and semi-stable intermediates. Reactions can proceed along kinetic or thermodynamic pathways. Initial concentrations of kinetic intermediates are greater than thermodynamic products because the lower barrier of activation (ΔG‡), compared to the thermodynamic pathway, gives a faster rate of formation. A kinetic pathway is represented in figure 1 as a purple energy diagram. With time, the intermediates equilibrate towards the global minimum, corresponding to the lowest overall Gibbs free energy (ΔG°), shown in red on the reaction diagram in figure 1. The driving force for products to re-equilibrate towards the most stable products is referred to as thermodynamic control. The ratio of products to at any equilibrium state is determined by the relative magnitudes of free energy of the products. This relationship between population and relative energies is called the Maxwell-Boltzmann distribution.

Thermodynamic template effect

The concept of a thermodynamic template is demonstrated in scheme 1. A thermodynamic template is a reagent that can stabilize the form of one product over others by lowering its Gibb's free energy (ΔG°) in relation to other products. cyclophane C2 can be prepared by the irreversible highly diluted reaction of a diol with chlorobromomethane in the presence of sodium hydride. The dimer however is part of series of equilibria between polyacetal macrocycles of different size brought about by acid catalyzed (triflic acid) transacetalization. [4] Regardless of the starting material, C2, C4 or a high molar mass product, the equilibrium will eventually produce a product distribution across many macrocycles and oligomers. In this system it is possible to amplify the presence of C2 in the mixture when the transacetalisation catalyst is silver triflate because the silver ion fits ideally and irreversibly in the C2 cavity.

Scheme 1: Thermodynamic Template in macrocycle synthesis Silver Templated .pdf
Scheme 1: Thermodynamic Template in macrocycle synthesis

Synthetic methods

Reactions used in DCvC must generate thermodynamically stable products to overcome the entropic cost of self-assembly. The reactions must form covalent linkages between building blocks. Finally, all possible intermediates must be reversible, and the reaction ideally proceeds under conditions that are tolerant of functional groups elsewhere in the molecule.

Reactions that can be used in DCvC are diverse and can be placed into two general categories. Exchange reactions involve the substitution of one reaction partner in an intermolecular reaction for another with an identical type of bonding. Some examples of this are shown in schemes 5 and 8, in an ester exchange, and disulfide exchange reactions. The second type, formation reactions, rely on the formation of new covalent bonds. Some examples include Diels–Alder and aldol reactions. In some cases, a reaction can pertain to both categories. For example, Schiff base formation can be categorized as a forming new covalent bonds between a carbonyl and primary amine. However, in the presence of two different amines the reaction becomes an exchange reaction where the two imine derivatives compete in equilibrium.

Exchange and formation reactions can be further broken down into three categories:

  1. Bonding between carbon–carbon
  2. Bonding between carbon–heteroatom
  3. Bonding between heteroatom–heteroatom


Bond formation between carbon atoms forms very thermodynamically stable products. Therefore, they often require the use of a catalyst to improve kinetics and ensure reversibility.

Aldol reactions

Aldol reactions are commonly used in organic chemistry to form carbon-to-carbon bonds. The aldehyde-alcohol motif common to the reaction product is ubiquitous to synthetic chemistry and natural products. The reaction utilizes two carbonyl compounds to generate a β-hydroxy carbonyl. Catalysis is always necessary because the barrier of activation between kinetic products and starting materials makes the dynamic reversible process too slow. Catalysts that have been successfully employed include enzymatic aldolase and Al2O3 based systems. [5]

Scheme 2: Aldol formation from a ketone and an aldehyde Aldol reaction.tif
Scheme 2: Aldol formation from a ketone and an aldehyde


Scheme 3: [4+2] cycloaddition between furan and maleimide Diels-Alder Reaction (Furan-Maleimide).tif
Scheme 3: [4+2] cycloaddition between furan and maleimide

[4+2] cycloadditions of a diene and an alkene have been used as DCvC reactions. These reactions are often reversible at high temperatures. In the case of furanmaleimide adducts, the retro-cycloaddition is accessible at temperatures as low as 40 °C. [6]


Scheme 4: Olefin Metathesis via Grubb's catalyst Olefin Metathesis.tif
Scheme 4: Olefin Metathesis via Grubb's catalyst

Olefin and alkyne metathesis refers to a carbon–carbon bond forming reaction. In the case of olefin metathesis, the bond forms between two sp2-hybridized carbon centers. In alkyne metathesis it forms between two sp-hybridized carbon centers. [7] Ring opening metathesis polymerization (ROMP) can be used in polymerization and macrocycle synthesis. [1]


A common dynamic covalent building motif is bond formation between a carbon center and a heteroatom such as nitrogen or oxygen. Because the bond formed between carbon and a heteroatom is less stable than a carbon-carbon bond, they offer more reversibility and reach thermodynamic equilibrium faster than carbon bond forming dynamic covalent reactions.

Ester exchange

Scheme 5: Ester exchange with an alcohol Ester-exchange .tif
Scheme 5: Ester exchange with an alcohol

Ester exchange takes place between an ester carbonyl and an alcohol. Reverse esterification can take place via hydrolysis. This method has been used extensively in polymer synthesis. [8]

Imine and aminal formation

Bond forming reactions between carbon and nitrogen are the most widely used in dynamic covalent chemistry. They have been used more broadly in materials chemistry for molecular switches, covalent organic frameworks, and in self-sorting systems. [1]

Imine formation takes place between an aldehyde or ketone and a primary amine. Similarly, aminal formation takes place between an aldehyde or ketone and a vicinal secondary amine. [8] Both reactions are commonly used in DCvC. [1] While both reactions can initially be categorized as formation reactions, in the presence of one or more of either reagent, the dynamic equilibrium between carbonyl and amine becomes an exchange reaction.

Scheme 6: Schiff base formation between an aldehyde and an amine Schiff-base (aldehyde and 1-amine).tif
Scheme 6: Schiff base formation between an aldehyde and an amine
Scheme 7: Aminal formation between a ketone and two secondary amines Aminal formaiton.tif
Scheme 7: Aminal formation between a ketone and two secondary amines


Dynamic heteroatom bond formation, presents useful reactions in the dynamic covalent reaction toolbox. Boronic acid condensation (BAC) and disulfide exchange constitute the two main reactions in this category. [1]

Disulfide exchange

Disulfides can undergo dynamic exchange reactions with free thiols. The reaction is well documented within the realm of DCvC, and is one of the first reactions demonstrated to have dynamic properties. [1] [9] The application of disulfide chemistry has the added advantage of being a biological motif. Cysteine residues can form disulfide bonds in natural systems. [1]

Scheme 8: Disulfide exchange between asymmetric disulfides Disulfide Exchange.tif
Scheme 8: Disulfide exchange between asymmetric disulfides

Boronic acid

Boronic acid self-condensation or condensation with diols is a well-documented dynamic covalent reaction. The boronic acid condensation has the characteristic of forming two dynamic bonds with various substrates. This is advantageous when designing systems where high rigidity is desired, such as 3-D cages and COFs. [10]

Scheme 9: Boronic acid condensation Boronic Acids.tif
Scheme 9: Boronic acid condensation


Dynamic covalent chemistry has allowed access to a wide variety of supramolecular structures. Using the above reactions to link molecular fragments, higher order materials have been made. These materials include macrocycles, COFs, and molecular knots. The applications of these products have been used in gas storage, catalysis, and biomedical sensing, among others. [1]

Dynamic signaling cascades

Dynamic covalent reactions have recently been used in Systems chemistry to initiate signaling cascades by reversibly releasing protons. The dynamic nature of the reactions provides a suitable "on-off" switch-like nature to the cascade systems. [11]


Many examples exist that demonstrate the utility of DCvC in macrocycle synthesis. This type of chemistry is effective for large macrocycle synthesis because the thermodynamic template effect is well suited to stabilize ring structures. Furthermore, the error-correcting ability inherent to DCvC allows large structures to be made without flaws. [12] [13]

Covalent organic frameworks

All current methods of covalent organic framework (COF) synthesis use DCvC. Boronic acid dehydration, as demonstrated by Yaghi et al. is the most common type of reaction used. [14] COFs have been used in gas storage, catalysis, . Possible morphologies include infinite covalent 3D frameworks, 2D polymers, or discrete molecular cages.

Molecular knots

DCvC has been used to make molecules with complex topological properties. In the case of Borromean rings, DCvC is used to synthesize a three ring interlocking system. Thermodynamic templates are used to stabilize interlocking macrocycle growth.

See also

Related Research Articles

<span class="mw-page-title-main">Organometallic chemistry</span> Study of organic compounds containing metal(s)

Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, and sometimes broadened to include metalloids like boron, silicon, and selenium, as well. Aside from bonds to organyl fragments or molecules, bonds to 'inorganic' carbon, like carbon monoxide, cyanide, or carbide, are generally considered to be organometallic as well. Some related compounds such as transition metal hydrides and metal phosphine complexes are often included in discussions of organometallic compounds, though strictly speaking, they are not necessarily organometallic. The related but distinct term "metalorganic compound" refers to metal-containing compounds lacking direct metal-carbon bonds but which contain organic ligands. Metal β-diketonates, alkoxides, dialkylamides, and metal phosphine complexes are representative members of this class. The field of organometallic chemistry combines aspects of traditional inorganic and organic chemistry.

<span class="mw-page-title-main">Rotaxane</span> Interlocked molecular structure resembling a dumbbell

In chemistry, a rotaxane is a mechanically interlocked molecular architecture consisting of a dumbbell-shaped molecule which is threaded through a macrocycle. The two components of a rotaxane are kinetically trapped since the ends of the dumbbell are larger than the internal diameter of the ring and prevent dissociation (unthreading) of the components since this would require significant distortion of the covalent bonds.

<span class="mw-page-title-main">Micelle</span> Group of fatty molecules suspended in liquid by soaps and/or detergents

A micelle or micella is an aggregate of surfactant amphipathic lipid molecules dispersed in a liquid, forming a colloidal suspension. A typical micelle in water forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single-tail regions in the micelle centre.

Supramolecular chemistry refers to the branch of chemistry concerning chemical systems composed of a discrete number of molecules. The strength of the forces responsible for spatial organization of the system range from weak intermolecular forces, electrostatic charge, or hydrogen bonding to strong covalent bonding, provided that the electronic coupling strength remains small relative to the energy parameters of the component. While traditional chemistry concentrates on the covalent bond, supramolecular chemistry examines the weaker and reversible non-covalent interactions between molecules. These forces include hydrogen bonding, metal coordination, hydrophobic forces, van der Waals forces, pi–pi interactions and electrostatic effects.

<span class="mw-page-title-main">Catenane</span> Molecule composed of two or more intertwined rings

In macromolecular chemistry, a catenane is a mechanically interlocked molecular architecture consisting of two or more interlocked macrocycles, i.e. a molecule containing two or more intertwined rings. The interlocked rings cannot be separated without breaking the covalent bonds of the macrocycles. They are conceptually related to other mechanically interlocked molecular architectures, such as rotaxanes, molecular knots or molecular Borromean rings. Recently the terminology "mechanical bond" has been coined that describes the connection between the macrocycles of a catenane. Catenanes have been synthesised in two different ways: statistical synthesis and template-directed synthesis.

<span class="mw-page-title-main">Macrocycle</span> Molecule with a large ring structure

Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry.

<span class="mw-page-title-main">Molecular Borromean rings</span> Molecule composed of three interlocked rings

In chemistry, molecular Borromean rings are an example of a mechanically-interlocked molecular architecture in which three macrocycles are interlocked in such a way that breaking any macrocycle allows the others to dissociate. They are the smallest examples of Borromean rings. The synthesis of molecular Borromean rings was reported in 2004 by the group of J. Fraser Stoddart. The so-called Borromeate is made up of three interpenetrated macrocycles formed through templated self assembly as complexes of zinc.

Ring-closing metathesis (RCM) is a widely used variation of olefin metathesis in organic chemistry for the synthesis of various unsaturated rings via the intramolecular metathesis of two terminal alkenes, which forms the cycloalkene as the E- or Z- isomers and volatile ethylene.

<span class="mw-page-title-main">Cyclic compound</span> Molecule with a ring of bonded atoms

A cyclic compound is a term for a compound in the field of chemistry in which one or more series of atoms in the compound is connected to form a ring. Rings may vary in size from three to many atoms, and include examples where all the atoms are carbon, none of the atoms are carbon, or where both carbon and non-carbon atoms are present. Depending on the ring size, the bond order of the individual links between ring atoms, and their arrangements within the rings, carbocyclic and heterocyclic compounds may be aromatic or non-aromatic; in the latter case, they may vary from being fully saturated to having varying numbers of multiple bonds between the ring atoms. Because of the tremendous diversity allowed, in combination, by the valences of common atoms and their ability to form rings, the number of possible cyclic structures, even of small size numbers in the many billions.

In chemistry, mechanically-interlocked molecular architectures (MIMAs) are molecules that are connected as a consequence of their topology. This connection of molecules is analogous to keys on a keychain loop. The keys are not directly connected to the keychain loop but they cannot be separated without breaking the loop. On the molecular level, the interlocked molecules cannot be separated without the breaking of the covalent bonds that comprise the conjoined molecules; this is referred to as a mechanical bond. Examples of mechanically interlocked molecular architectures include catenanes, rotaxanes, molecular knots, and molecular Borromean rings. Work in this area was recognized with the 2016 Nobel Prize in Chemistry to Bernard L. Feringa, Jean-Pierre Sauvage, and J. Fraser Stoddart.

<span class="mw-page-title-main">Thorpe–Ingold effect</span>

The Thorpe–Ingold effect, gem-dimethyl effect, or angle compression is an effect observed in chemistry where increasing steric hindrance favours ring closure and intramolecular reactions. The effect was first reported by Beesley, Thorpe, and Ingold in 1915 as part of a study of cyclization reactions. It has since been generalized to many areas of chemistry.

<span class="mw-page-title-main">Boronic acid</span> Organic compound of the form R–B(OH)2

A boronic acid is an organic compound related to boric acid in which one of the three hydroxyl groups is replaced by an alkyl or aryl group. As a compound containing a carbon–boron bond, members of this class thus belong to the larger class of organoboranes.

The term "polymer" refers to large molecules whose structure is composed of multiple repeating units and the prefix "supra" meaning "beyond the limits of". Supramolecular polymers are a new category of polymers that can potentially be used for material applications beyond the limits of conventional polymers. By definition, supramolecular polymers are polymeric arrays of monomeric units that are connected by reversible and highly directional secondary interactions–that is, non-covalent bonds. These non-covalent interactions include van der Waals interactions, hydrogen bonding, Coulomb or ionic interactions, π-π stacking, metal coordination, halogen bonding, chalcogen bonding, and host–guest interaction. The direction and strength of the interactions are precisely tuned so that the array of molecules behaves as a polymer in dilute and concentrated solution, as well as in the bulk.

Physical organic chemistry, a term coined by Louis Hammett in 1940, refers to a discipline of organic chemistry that focuses on the relationship between chemical structures and reactivity, in particular, applying experimental tools of physical chemistry to the study of organic molecules. Specific focal points of study include the rates of organic reactions, the relative chemical stabilities of the starting materials, reactive intermediates, transition states, and products of chemical reactions, and non-covalent aspects of solvation and molecular interactions that influence chemical reactivity. Such studies provide theoretical and practical frameworks to understand how changes in structure in solution or solid-state contexts impact reaction mechanism and rate for each organic reaction of interest.

Molecular binding is an attractive interaction between two molecules that results in a stable association in which the molecules are in close proximity to each other. It is formed when atoms or molecules bind together by sharing of electrons. It often, but not always, involves some chemical bonding.

Covalent organic frameworks (COFs) are a class of materials that form two- or three- dimensional structures through reactions between organic precursors resulting in strong, covalent bonds to afford porous, stable, and crystalline materials. COFs emerged as a field from the overarching domain of organic materials as researchers optimized both synthetic control and precursor selection. These improvements to coordination chemistry enabled non-porous and amorphous organic materials such as organic polymers to advance into the construction of porous, crystalline materials with rigid structures that granted exceptional material stability in a wide range of solvents and conditions. Through the development of reticular chemistry, precise synthetic control was achieved and resulted in ordered, nano-porous structures with highly preferential structural orientation and properties which could be synergistically enhanced and amplified. With judicious selection of COF secondary building units (SBUs), or precursors, the final structure could be predetermined, and modified with exceptional control enabling fine-tuning of emergent properties. This level of control facilitates the COF material to be designed, synthesized, and utilized in various applications, many times with metrics on scale or surpassing that of the current state-of-the-art approaches.

Jeremy Keith Morris Sanders is a British chemist and Emeritus Professor in the Department of Chemistry at the University of Cambridge. He is also Editor-in-Chief of Royal Society Open Science. He is known for his contributions to many fields including NMR spectroscopy and supramolecular chemistry. He served as the Pro-Vice-Chancellor for Institutional Affairs at the University of Cambridge, 2011–2015.

<span class="mw-page-title-main">Dynamic combinatorial chemistry</span>

Dynamic combinatorial chemistry (DCC); also known as constitutional dynamic chemistry (CDC) is a method to the generation of new molecules formed by reversible reaction of simple building blocks under thermodynamic control. The library of these reversibly interconverting building blocks is called a dynamic combinatorial library (DCL). All constituents in a DCL are in equilibrium, and their distribution is determined by their thermodynamic stability within the DCL. The interconversion of these building blocks may involve covalent or non-covalent interactions. When a DCL is exposed to an external influence, the equilibrium shifts and those components that interact with the external influence are stabilised and amplified, allowing more of the active compound to be formed.

<span class="mw-page-title-main">Two-dimensional polymer</span>

A two-dimensional polymer (2DP) is a sheet-like monomolecular macromolecule consisting of laterally connected repeat units with end groups along all edges. This recent definition of 2DP is based on Hermann Staudinger's polymer concept from the 1920s. According to this, covalent long chain molecules ("Makromoleküle") do exist and are composed of a sequence of linearly connected repeat units and end groups at both termini.

<span class="mw-page-title-main">Polyrotaxane</span>

Polyrotaxane is a type of mechanically interlocked molecule consisting of strings and rings, in which multiple rings are threaded onto a molecular axle and prevented from dethreading by two bulky end groups. As oligomeric or polymeric species of rotaxanes, polyrotaxanes are also capable of converting energy input to molecular movements because the ring motions can be controlled by external stimulus. Polyrotaxanes have attracted much attention for decades, because they can help build functional molecular machines with complicated molecular structure.


  1. 1 2 3 4 5 6 7 8 Jin, Yinghua; Yu, Chao; Denman, Ryan J.; Zhang, Wei (2013-08-21). "Recent advances in dynamic covalent chemistry". Chemical Society Reviews. 42 (16): 6634–6654. doi:10.1039/c3cs60044k. ISSN   1460-4744. PMID   23749182.
  2. Jin, Yinghua; Wang, Qi; Taynton, Philip; Zhang, Wei (2014-05-20). "Dynamic Covalent Chemistry Approaches Toward Macrocycles, Molecular Cages, and Polymers". Accounts of Chemical Research. 47 (5): 1575–1586. doi:10.1021/ar500037v. ISSN   0001-4842. PMID   24739018.
  3. "Thermodynamic versus kinetic control" by Nick024 - Own work. Licensed under CC0 via Commons - https://commons.wikimedia.org/wiki/File:Thermodyamic_versus_kinetic_control.png#/media/File:Thermodyamic_versus_kinetic_control.png
  4. This particular type of transacetalization goes by the name of formal metathesis because it is reminiscent of olefin metathesis but then with formaldehyde.
  5. Zhang, Yan; Vongvilai, Pornrapee; Sakulsombat, Morakot; Fischer, Andreas; Ramström, Olof (2014-03-24). "Asymmetric Synthesis of Substituted Thiolanes through Domino Thia-Michael–Henry Dynamic Covalent Systemic Resolution using Lipase Catalysis". Advanced Synthesis & Catalysis. 356 (5): 987–992. doi:10.1002/adsc.201301033. ISSN   1615-4150. PMC   4498465 . PMID   26190961.
  6. Boutelle, Robert C.; Northrop, Brian H. (2011-10-07). "Substituent effects on the reversibility of furan-maleimide cycloadditions". The Journal of Organic Chemistry. 76 (19): 7994–8002. doi:10.1021/jo201606z. ISSN   1520-6904. PMID   21866976.
  7. Vougioukalakis, Georgios C.; Grubbs, Robert H. (2010-03-10). "Ruthenium-Based Heterocyclic Carbene-Coordinated Olefin Metathesis Catalysts". Chemical Reviews. 110 (3): 1746–1787. doi:10.1021/cr9002424. ISSN   0009-2665. PMID   20000700.
  8. 1 2 Bozdemir, O. Altan; Barin, Gokhan; Belowich, Matthew E.; Basuray, Ashish N.; Beuerle, Florian; Stoddart, J. Fraser (2012-09-26). "Dynamic covalent templated-synthesis of [c2]daisy chains". Chemical Communications. 48 (84): 10401–10403. doi:10.1039/C2CC35522A. PMID   22982882 . Retrieved 2015-11-17.
  9. Kim, Jeehong; Baek, Kangkyun; Shetty, Dinesh; Selvapalam, Narayanan; Yun, Gyeongwon; Kim, Nam Hoon; Ko, Young Ho; Park, Kyeng Min; Hwang, Ilha (2015-02-23). "Reversible Morphological Transformation between Polymer Nanocapsules and Thin Films through Dynamic Covalent Self-Assembly". Angewandte Chemie International Edition. 54 (9): 2693–2697. doi:10.1002/anie.201411842. ISSN   1521-3773. PMID   25612160.
  10. Nishiyabu, Ryuhei; Kubo, Yuji; James, Tony D.; Fossey, John S. (2011-01-28). "Boronic acid building blocks: tools for self assembly". Chemical Communications. 47 (4): 1124–1150. doi:10.1039/c0cc02921a. ISSN   1364-548X. PMID   21113558.
  11. Ren, Yulong; You, Lei (2015-11-11). "Dynamic Signaling Cascades: Reversible Covalent Reaction-Coupled Molecular Switches". Journal of the American Chemical Society. 137 (44): 14220–14228. doi:10.1021/jacs.5b09912. ISSN   0002-7863. PMID   26488558.
  12. Cacciapaglia, Roberta; Di Stefano, Stefano; Mandolini, Luigi (2005-10-05). "Metathesis reaction of formaldehyde acetals: an easy entry into the dynamic covalent chemistry of cyclophane formation". Journal of the American Chemical Society. 127 (39): 13666–13671. doi:10.1021/ja054362o. ISSN   0002-7863. PMID   16190732.
  13. Kornienko, Nikolay; Zhao, Yingbo; Kley, Christopher S.; Zhu, Chenhui; Kim, Dohyung; Lin, Song; Chang, Christopher J.; Yaghi, Omar M.; Yang, Peidong (2015-10-28). "Metal–Organic Frameworks for Electrocatalytic Reduction of Carbon Dioxide". Journal of the American Chemical Society. 137 (44): 14129–14135. doi:10.1021/jacs.5b08212. PMID   26509213.
  14. Bunck, David N.; Dichtel, William R. (2012-02-20). "Internal Functionalization of Three-Dimensional Covalent Organic Frameworks". Angewandte Chemie International Edition. 51 (8): 1885–1889. doi:10.1002/anie.201108462. ISSN   1521-3773. PMID   22249947.