Post-synthetic Modification Reactions Research Articles

Tuning the electrostatic energy landscape within the pores of covalent organic frameworks: post-synthetic modification reactions and structural imperfections

Polar substituents decorating the pore walls of covalent organic frameworks can be used to control the electrostatic potential within the pores and to tune the alignment of the electronic states in guest molecules and the COF scaffold.

Disulfide-driven Pore Functionalization of Metal-organic Frameworks.

Post-synthetic modification (PSM) imparts additional functionality to metal-organic frameworks (MOFs) that is often difficult to access using solvothermal synthesis. As such, expanding the repertory of PSM reactions available to the practitioner is of increased importance for the generation of materials tailored for desired applications. Herein, we describe a method for the protecting group-free installation of diverse functional groups within the pores of a MIL-53(Al) analogue via disulfide bond formation. The majority of the reactions proceed with thiol-to-disulfide conversions ranging from high to nearly quantitative. The disulfide bonds are stable in various solvents and can be cleaved in the presence of a reducing agent.

Gradient Channel Segmentation in Covalent Organic Framework Membranes with Highly Oriented Nanochannels.

Covalent organic frameworks (COFs) offer an exceptional platform for constructing membrane nanochannels with tunable pore sizes and tailored functionalities, making them promising candidates for separation, catalysis, and sensing applications. However, the synthesis of COF membranes with highly oriented nanochannels remains challenging, and there is a lack of systematic studies on the influence of postsynthetic modification reactions on functionality distribution along the nanochannels. Herein, we introduced a "prenucleation and slow growth" approach to synthesize a COF membrane featuring highly oriented mesoporous channels and a high Brunauer-Emmett-Teller surface area of 2230 m2 g-1. Functional moieties were anchored to the pore walls via "click" reactions and coordinated with Cu ions to serve as segmentation functions. This led to a remarkable H2/CO2 separation performance that surpassed the Robeson upper bound. Moreover, we found that the functionalities distributed along the nanochannels could be influenced by functionality flexibility and postsynthetic reaction rate. This strategy paved the way for the accurate design and construction of COF-based artificial solid-state nanochannels with high orientation and precisely controlled channel environments.

Construction of novel benzoxazine-linked covalent organic framework with antimicrobial activity via postsynthetic cyclization

Organic framework materials have shown increasingly promising applications in biomedicine, such as drug delivery and release. In this work, we first synthesized a new hydroxyl-containing imine-linked two-dimensional covalent organic framework (COF) through solvothermal synthesis. Then, the imine group was converted into a benzoxazine group using a cyclization reaction. The results show that the postsynthetic modification did not change the basic framework of the original COF and did not affect the basic properties of the original COF. At the same time, the new benzoxazine group obtained by cyclization gave the COF good antibacterial activity against Escherichia coli and Staphylococcus aureus. The COF efficiency after cyclization was improved, and its antibacterial activity against both bacteria was over 90% compared with the imine-linked COF. Moreover, the benzoxazine-linked COF crystal structure and pore structures were retained, leaving the drug delivery and release functions unaffected. A benzoxazine-linked COF has never been reported because it cannot be synthesized by a direct reaction method. The work in this paper shows that the COFs that cannot be directly synthesized can be obtained through specific postsynthetic modification reactions. This means that more functional COFs can be obtained based on existing COFs, and the diversity of COF types and their potential applications can be further enriched and expanded.

Complete and Versatile Post‐Synthetic Modification on Iron‐Triazole Spin Crossover Complexes: A Relevant Material Elaboration Method

AbstractIn this paper we study the post‐synthetic modification (PSM) reaction on solid spin crossover (SCO) [Fe(NH2trz)3]X2 (X=NO3, OTs, Cl, SO4, BF4) complexes with different substrates. The wide access to a diversity of functionalized complexes with imine, amide and carbamide groups from the same amino parent compound demonstrates the synthetic approach value of this method. The as‐obtained post‐synthetic complexes were studied by IR, solid NMR, elemental analyses, and powder X‐ray diffraction, and compared to the corresponding compounds obtained by direct synthesis (DS) routes. Moreover, after digestion of the complexes obtained by PSM reactions, the free ligands were characterized by NMR in solution, which allowed us to indirectly confirm the formation of complexes we wished to synthesize. The study reveals in numerous cases that a complete post‐synthetic modification is possible despite the structural cohesion that is established between the 1D coordination chains within these materials. Spin crossover properties of some complexes obtained by both methods are also reported and compared.

Reagent Reactivity and Solvent Choice Determine Metal-Organic Framework Microstructure during Postsynthetic Modification.

The spatial distribution of MOF functionalization reveals that postsynthetic modification (PSM)-derived microstructures can range from uniform to core-shell, affected by reagent reactivity and solvent choice. A suite of isocyanate reagents with varying reactivity were employed to study the effect of kinetics and experimental conditions on microstructure during PSM. Exploiting the difference in reactivity between chloroacetyl isocyanate and 4-bromophenyl isocyanate, a one-pot PSM reaction produces a dual-functionalized core-shell structure. Furthermore, a triple-functionalized Matryoshka structure is formed in a two-step PSM procedure using trifluoroacetyl isocyanate followed by a self-sorting reaction with chloroacetyl isocyanate and 4-bromophenyl isocyanate, demonstrating that a better understanding of the dynamics of PSM can support the design of MOFs with increasingly sophisticated architectures.

Tailoring the breathing behavior of functionalized MIL-53(Al,M)-NH2 materials by using the mixed-metal concept

Abstract Mixed-metal metal-organic frameworks with two or more metals distributed over crystallographically equivalent sites are gaining growing attention in various research areas. We have extended the range of available mixed-metal frameworks of the MIL-53-NH2 family by combining aluminum with scandium, vanadium, chromium or iron. In contrast to other already reported mixed-metal MIL-53 materials, the developed MIL-53(Al,M)-NH2 materials (M = Sc, V, Cr, Fe), which contain 2-aminoterephthalate as linker instead of terephthalate, will enable subsequent post-synthetic modifications. All developed materials have been thoroughly characterized with standard methods as well as X-ray absorption spectroscopy to prove the exclusive incorporation of the employed metals into the MIL-53-NH2 framework structure and to verify the absence of impurity phases. Nitrogen physisorption measurements revealed that the choice of the metal combinations and ratios had a strong influence on the breathing behavior. Furthermore, post-synthetic modification reactions of the amine groups with maleic anhydride showed that the metal combination had a dramatic impact on the resulting modification degrees. Thus, the flexibility of the pore systems can be tailored by a careful selection of suitable metal combinations for these materials.

The introduction of functional side groups and the application of the mixed-linker concept in divalent MIL-53(Ni) materials.

Metal-organic framework materials with functional side groups are commonly used for various purposes like post-synthetic modification reactions or the tuning of pore geometries. Additionally, the mixed-linker concept, in which different linkers are statistically distributed over equivalent lattice positions, is a versatile approach to adjust the number of functional groups within the framework. However, neither functional side groups nor the mixed-linker approach have been used in MIL-53 materials with divalent metal ions yet. In the present work, we report on the synthesis of MIL-53(Ni)-Br(100), which contains only 2-bromoterephthalate as a linker molecule, and mixed-linker MIL-53(Ni)-Br(50) containing both terephthalate and 2-bromoterephthalate. These two materials represent the first functionalized and mixed-linker MIL-53 materials in combination with a divalent metal. Consequently, the possibilities to tailor the properties of the still rarely used divalent MIL-53 materials were expanded.

Amidation, Esterification, and Thioesterification of a Carboxyl-Functionalized Covalent Organic Framework.

Three new post-synthetic modification reactions, namely amidation, esterification, and thioesterification, were demonstrated on a novel highly crystalline two-dimensional covalent organic framework (COF), COF-616, bearing pre-installed carboxyl groups. The strategy can be used to introduce a large variety of functional groups into COFs and the modifications can be carried out under mild reaction conditions, with high yields, and an easy work-up protocol. As a proof of concept, various chelating functionalities were successfully incorporated into COF-616 to yield a family of adsorbents for efficient removal of several contaminants in the water.

Multistep Solid-State Organic Synthesis of Carbamate-Linked Covalent Organic Frameworks.

Herein, we demonstrate the first example of a multistep solid-state organic synthesis, in which a new imine-linked two-dimensional covalent organic framework (COF-170, 1) was transformed through three consecutive postsynthetic modifications into porous, crystalline cyclic carbamate and thiocarbamate-linked frameworks. These linkages are previously unreported and inaccessible through de novo synthesis. While not altering the overall connectivity of the framework, these chemical transformations induce significant conformational and structural changes at each step, highlighting the key importance of noncovalent interactions and conformational flexibility to COF crystallinity and porosity. These transformations were assessed using 15N multiCP-MAS NMR spectroscopy, providing the first quantitation of yields in COF postsynthetic modification reactions, as well as of amine defect sites in imine-linked COFs. This multistep COF linkage postsynthetic modification represents a significant step toward bringing the precision of organic solution-phase synthesis to extended solid-state compounds.

Insights into Functionalization of Metal-Organic Frameworks Using In Situ NMR Spectroscopy

Postsynthetic reactions of metal-organic frameworks (MOFs) are versatile tools for producing functional materials, but the methods of evaluating these reactions are cumbersome and destructive. Here we demonstrate and validate the use of in situ NMR spectroscopy of species in the liquid state to examine solvent-assisted ligand exchange (SALE) and postsynthetic modification (PSM) reactions of metal-organic frameworks. This technique allows functionalization to be monitored over time without decomposing the product for analysis, which simplifies reaction screening. In the case of SALE, both the added ligand and the ligand leaving the framework can be observed. We demonstrate this in situ method by examining SALE and PSM reactions of the robust zirconium MOF UiO-67 as well as SALE with the aluminum MOF DUT-5. In situ NMR spectroscopy provided insights into the reactions studied, and we expect that future studies using this method will permit the examination of a variety of MOF–solute reactions.

From Highly Crystalline to Outer Surface-Functionalized Covalent Organic Frameworks--A Modulation Approach.

Crystallinity and porosity are of central importance for many properties of covalent organic frameworks (COFs), including adsorption, diffusion, and electronic transport. We have developed a new method for strongly enhancing both aspects through the introduction of a modulating agent in the synthesis. This modulator competes with one of the building blocks during the solvothermal COF growth, resulting in highly crystalline frameworks with greatly increased domain sizes reaching several hundreds of nanometers. The obtained materials feature fully accessible pores with an internal surface area of over 2000 m2 g–1. Compositional analysis via NMR spectroscopy revealed that the COF-5 structure can form over a wide range of boronic acid-to-catechol ratios, thus producing frameworks with compositions ranging from highly boronic acid-deficient to networks with catechol voids. Visualization of an −SH-functionalized modulating agent via iridium staining revealed that the COF domains are terminated by the modulator. Using functionalized modulators, this synthetic approach thus also provides a new and facile method for the external surface functionalization of COF domains, providing accessible sites for post-synthetic modification reactions. We demonstrate the feasibility of this concept by covalently attaching fluorescent dyes and hydrophilic polymers to the COF surface. We anticipate that the realization of highly crystalline COFs with the option of additional surface functionality will render the modulation concept beneficial for a range of applications, including gas separations, catalysis, and optoelectronics.

Synthesis and post-synthetic modification of amine-, alkyne-, azide- and nitro-functionalized metal-organic frameworks based on DUT-5.

Functionalized 4,4'-biphenyldicarboxylic acid molecules with additional amine, alkyne, azide or nitro groups were prepared and applied in the synthesis of novel metal-organic frameworks and mixed-linker metal-organic frameworks isoreticular to DUT-5. The properties of the frameworks could be tuned by varying the number of functional groups in the materials and the amine groups were employed in post-synthetic modification reactions without changing the framework structure or significantly decreasing the porosity of the materials.

Design of Highly Porous Single‐Site Catalysts through Two‐Step Postsynthetic Modification of Mixed‐Linker MIL‐53(Al)

AbstractDefined mixed‐linker metal–organic frameworks based on MIL‐53‐NH2(Al) were successfully synthesized under ambient pressure, thus, enabling easy scaling up of the synthesis. The two‐step postsynthetic modification reaction of these materials with, first, maleic anhydride and, second, palladium(II) acetate resulted in immobilized palladium(II) complexes at the side chain of the linker molecules. The high porosity of the mixed‐linker materials was retained throughout the modification process, which was in contrast to a previous study with pure MIL‐53‐NH2(Al). The novel palladium‐containing materials were applied in Heck‐type CC coupling reactions of bromo‐ or chlorobenzene with styrene, in which they exhibited high catalytic activity and selectivity.

Postsynthetic modification of coordination networks

The postsynthetic modification (PSM) of coordination networks was initially reported over a decade ago independently by Stephen Lee (Cornell U., U.S.A.) and Kimoon Kim (POSTECH, Korea). PSM involves the chemical modification of a coordination network in a heterogeneous fashion on the already-formed solid network by an external reagent that is present in the solution or gas phase. Retention of structure and crystallinity with respect to the original material is an essential feature of most useful PSM reactions. Since those first reports, and particularly in the last past five years, PSM has grown into an important tool for the manipulation of coordination network materials, and for the preparation of frameworks containing functionalised pores. While the archetypical PSM reaction involves an organic transformation involving functional groups or ‘tags’ on the linkers, the PSM strategy is not limited to this and can involve transformation of the 'inorganic' parts of the network or other framework changes. In addition, chemical, photolytic, or thermal treatment can lead to postsynthetic deprotection reactions, and the unmasking of reactive functional groups that would have been likely to interfere with the coordination network synthesis.

Transgenic bioreactors

1. 1. Although many human therapeutic proteins are currently produced in microbial fermentors using recombinant DNA techniques, it is obvious that microbial processing is not suitable for a large number of bioactive proteins owing to the inability of bacteria to carry out postsynthetic modification reactions required for full biological activity. 2. 2. This disadvantage does not apply to animal cell bioreactors that can generate biologically fully active entities, yet the use of large-scale animal cell cultures for production purposes is prohibitively expensive. 3. 3. With the advent of transgenic technology, the production of valuable human pharmaceuticals in large farm animals (pig, sheep, goat and dairy cattle) has become more and more attractive as a high-quantity, low-cost alternative. By employing targeted gene transfer, e.g. using mammary gland-specific regulatory sequences fused with the desired production genes, it is possible to govern the expression to occur exclusively in the mammary gland and hence the gene product is being ultimately secreted into the milk. 4. 4. While reviewing the remarkable progress in this field that has even led to commercial exploitations, we will outline in somewhat greater detail our strategy for the use of dairy cattle as a bioreactor for valuable proteins of pharmaceutical interest.