Post-assembly Modification Research Articles

A metal–carbene template approach enables efficient synthesis of a functionalized cage-annulated crown ether

A novel flexible intramolecular cage-annulated crown ether organic imidazolium cation with potentially large cavities was constructed through a kind of post-assembly modification strategy, photochemical [2+2] cycloaddition reaction.

Peptide Modification via N-Terminal-Residue-Directed γ-C(sp3)-H Arylation.

Postassembly modification of peptides via C(sp3)-H functionalization provides an efficient way to prepare functionalized peptides for biological study and pharmaceutical development. In this work, we developed a new method for γ-C(sp3)-H functionalization of aliphatic side chains of N-terminus-unprotected peptides. With the N-terminal residues as directing groups, a wide range of di-, tri-, tetra-, and pentapeptides underwent C-H arylation of the residues (Val, Ile, Tle) at the +2 position from the N-terminus.

Covalent Post-Assembly Modification: A Synthetic Multipurpose Tool in Supramolecular Chemistry.

The use of covalent post-assembly modification (PAM) in supramolecular chemistry has grown significantly in recent years, to the point where PAM is now a versatile synthesis tool for tuning, modulating, and expanding the functionality of self-assembled complexes and materials. PAM underpins supramolecular template-synthesis strategies, enables modular derivatization of supramolecular assemblies, permits the covalent 'locking' of unstable structures, and can trigger controlled structural transformations between different assembled morphologies. This Review discusses key examples of PAM spanning a range of material classes, including discrete supramolecular complexes, self-assembled soft nanostructures and hierarchically ordered polymeric and framework materials. As such, we hope to highlight how PAM has continued to evolve as a creative and functional addition to the synthetic chemist's toolbox for constructing bespoke self-assembled complexes and materials.

Polymeric Nanoparticles Integrated from Discrete Organoplatinum(II) Metallacycle by Stepwise Post-assembly Polymerization for Synergistic Cancer Therapy

Post-assembly modification is a useful tool for producing discrete metallasupramolecular structures. However, the simple structural transformation by facile covalent reactions greatly impedes the d...

Single-Step Enantioselective Synthesis of Mechanically Planar Chiral [2]Rotaxanes Using a Chiral Leaving Group Strategy.

We report a one-step enantioselective synthesis of mechanically planar chiral [2]rotaxanes. Previous studies of such molecules have generally involved the separation of enantiomers from racemic mixtures or the preparation and separation of diastereomeric intermediates followed by post-assembly modification to remove other sources of chirality. Here, we demonstrate a simple asymmetric metal-free active template rotaxane synthesis using a primary amine, an activated ester with a chiral leaving group, and an achiral crown ether lacking rotational symmetry. Mechanically planar chiral rotaxanes are obtained directly in up to 50% enantiomeric excess. The rotaxanes were characterized by NMR spectroscopy, high-resolution mass spectrometry, chiral HPLC, single crystal X-ray diffraction, and circular dichroism. Either rotaxane enantiomer could be prepared selectively by incorporating pseudoenantiomeric cinchona alkaloids into the chiral leaving group.

On/off porosity switching and post-assembly modifications of Cu4L4 metal-organic polyhedra.

Synthetic porous materials composed of metal–organic polyhedra (MOPs) have found application in topical areas such as gas storage, separation and catalysis. Control over their physical properties (e.g. porosity) has typically been achieved through ligand design or judicious choice of metal ions. Here, we demonstrate pore-size control and on/off porosity in Cu4L4 MOPs by exploiting their structural non-rigidity. We report an aldehyde-functionalised MOP (1) that can be isolated in five distinct solvatomorphs, each exhibiting different structural flexibility. When soaked in MeOH, two of these solvatomorphs undergo a rapid transformation to a thermodynamically favoured phase, whilst in acetone they template the crystallisation of an entirely new crystal packing. We support these findings by single and powder X-ray diffraction and rationalise the observed phase transformations by lattice energy calculations. Of the five solvatomorphs, three can be obtained as solvent-exchanged pseudo-polymorphs with distinct porosities in their activated form (SABET = 35–455 m2 g−1). Further control over the crystal packing of MOPs is achieved through covalent post-assembly modifications, which promote the crystallisation of isoreticular 2-D sheet-like structures.

A substituent-induced post-assembly modification cascade of a metallosupramolecular imine-type Co-complex.

Here, we report a reaction cascade employing the substituent-induced post-assembly modification of a Co(iii) complex. Unexpectedly, we found that the (triisopropylsilyl)alkynyl moiety introduced to the Sonogashira reaction with the bromo-functionalized Co(iii) assembly plays a "Trojan horse" role, triggering a subsequent, second step of the cascade, i.e. Co(iii) to Co(ii) reduction. The reported substituent-activated Sonogashira-redox cascade reaction might set a new direction in the construction of specific chemical sensors.

Post-assembly Modification of Phosphine Cages Controls Host-Guest Behavior.

We report the design, synthesis, and post-assembly modification of a new phosphine-paneled supramolecular cage framework, the anion binding ability of which can be modified rationally through selective post-assembly functionalization. The parent phosphine-paneled cage can be modified in situ through oxidation, methylation, or auration. These covalent and coordinative modifications to the exterior of the cage strongly influence the guest-binding properties of the host.

Advanced Approaches to Post-Assembly Modification of Peptides by Transition-Metal-Catalyzed Reactions

We have summarized diverse synthetic approaches for the modification of peptides by employing transition-metal-catalyzed reactions. These methods can deliver unusual peptides suitable for peptidomimetics. To this end, several popular reactions such as Diels–Alder, 1,3-dipolar cycloaddition, [2+2+2] cyclotrimerization, metathesis, Suzuki­–Miyaura cross-coupling, and Negishi coupling have been used to assemble modified peptides by post-assembly chemical modification strategies. 1 Introduction 2 Synthesis of a Cyclic α-Amino Acid Derivative via a Ring-Closing Metathesis Protocol 3 Peptide Modification Using a Ring-Closing Metathesis Strategy 4 Peptide Modification via a [2+2+2] Cyclotrimerization Reaction 5 Peptide Modification by Using [2+2+2] Cyclotrimerization and Suzuki Coupling 6 Peptide Modification via a Suzuki–Miyaura Cross-Coupling 7 Peptide Modification via Cross-Enyne Metathesis and a Diels–Alder­ Reaction as Key Steps 8 Peptide Modification via 1,3-Dipolar Cycloaddition Reactions 9 Modified Peptides via Negishi Coupling 10 A Modified Dipeptide via Ethyl Isocyanoacetate 11 Conclusions

Advanced Approaches to Post-Assembly Modification of Peptides by Transition-Metal-Catalyzed Reactions

We have summarized diverse synthetic approaches for the modification of peptides by employing transition-metal-catalyzed reactions. These methods can deliver unusual peptides suitable for peptidomimetics. To this end, several popular reactions such as Diels–Alder, 1,3-dipolar cycloaddition, [2+2+2] cyclotrimerization, metathesis, Suzuki­–Miyaura cross-coupling, and Negishi coupling have been used to assemble modified peptides by post-assembly chemical modification strategies.1 Introduction2 Synthesis of a Cyclic α-Amino Acid Derivative via a Ring-Closing Metathesis Protocol3 Peptide Modification Using a Ring-Closing Metathesis Strategy4 Peptide Modification via a [2+2+2] Cyclotrimerization Reaction5 Peptide Modification by Using [2+2+2] Cyclotrimerization and Suzuki Coupling6 Peptide Modification via a Suzuki–Miyaura Cross-Coupling7 Peptide Modification via Cross-Enyne Metathesis and a Diels–Alder­ Reaction as Key Steps8 Peptide Modification via 1,3-Dipolar Cycloaddition Reactions9 Modified Peptides via Negishi Coupling10 A Modified Dipeptide via Ethyl Isocyanoacetate11 Conclusions

Designed Conformation and Fluorescence Properties of Self-Assembled Phenazine-Cored Platinum(II) Metallacycles.

A series of platinum(II) metallacycles were prepared via the coordination-driven self-assembly of a phenazine-cored dipyridyl donor with a 90° Pt(II) acceptor and various dicarboxylate donors in a 1:1:2 ratio. While the metallacycles display similar absorption profiles, they exhibit a trend of blue-shifted fluorescence emission with the decrease in the bite angles between the carboxylate building blocks. Comprehensive spectroscopic and dynamic studies as well as a computational approach were conducted, revealing that the difference in the degree of constraint imposed on the excited-state planarization of the phenazine core within these metallacycles results in their distinct photophysical behaviors. As such, a small initial difference in the dicarboxylate building blocks is amplified into distinct photophysical properties of the metallacycles, which is reminiscent of the efficient functional tuning observed in natural systems. In addition to the pre-assembly approach, the photophysical properties of a metallacycle can also be modulated using a post-assembly modification to the dicarboxylate building block, suggesting another strategy for functional tuning. This research illustrated the potential of coordination-driven self-assembly for the preparation of materials with precisely tailored functionalities at the molecular level.

Strongly luminescent 5d/4f heterometal-organic macrocycles with open metal sites: post-assembly modification and sensing.

A series of strongly luminescent 5d/4f heterometal-organic macrocycles formulated as Ln2(Pt-L)2 have been constructed from a preformed cis-blocked alkynylplatinum metalloligand (Pt-L) and lanthanide (Ln = LaIII, EuIII, LuIII) ions. Open metal sites on the lanthanide centres of the heterometal-organic macrocycles facilitate not only the post-assembly modification leading to great enhancement of the luminescence, but also the displacement sensing toward toxic thiophosphonates.

Process-tracing study on the post-assembly modification of poly-NHC-based metallosupramolecular cylinders with tunable aggregation-induced emission.

In this work, we demonstrate the design and fabrication of a series of cylinder-like, hexazido-terminated MI-CNHC (M = Ag, Au) complexes. Moreover, we present for the first time a process-tracing and aggregation-induced emission (AIE) study of a covalent postassembly modification (PAM) process of the AuI-CNHC cylinders, highlighting the excellent versatility and complexity of functionalised poly-NHC compounds as a new type of molecular platform for novel applications.

Post-assembly modification of polymeric composite membranes using spin drying for fuel cell applications

A spin-drying process is simply adopted during fabrication of reinforced polymer composite membranes.

Functional Capsules via Subcomponent Self-Assembly.

Coordination-driven self-assembly can produce large, symmetrical, hollow cages that are synthetically easy to access. The functions provided by these aesthetically attractive structures provide a driving force for their development, enabling practical applications. For instance, cages have provided new methods of molecular recognition, chirality sensing, separations, stabilization of reactive species, and catalysis. We have fruitfully employed subcomponent self-assembly to prepare metal-organic capsules from simple building blocks via the simultaneous formation of dynamic coordinative (N→metal) and covalent (N═C) bonds. Design strategies employ multidentate pyridyl-imine ligands to define either the edges or the faces of polyhedral structures. Octahedral metal ions, such as FeII, CoII, NiII, ZnII, and CdII, constitute the vertices. The generality of this technique has enabled the preparation of capsules with diverse three-dimensional structures. This Account highlights how fundamental investigations into the host-guest chemistry of capsules prepared through subcomponent self-assembly have led to the design of useful functions and new applications. We start by discussing simple host-guest systems involving a single capsule and continue to systems that include multiple capsules and guests, whose interactions give rise to complex functional behavior. Many of the capsules presented herein bind varied neutral guests, including aromatic or aliphatic molecules, biomolecules, and fullerenes. Binding selectivity is influenced by solvent effects, weak non-covalent interactions between hosts and guests, and the size, shape, flexibility, and degree of surface enclosure of the inner spaces of the capsules. Some hosts are able to adaptively rearrange structurally or express a different ratio of cage diastereomers to optimize the guest binding ability of the system. In other cases the bound guest can be either protected from degradation or catalytically transformed through encapsulation. Other capsules bind anions, most often in organic solvents and occasionally in water. Complexation is usually driven by a combination of electrostatic interactions, hydrogen bonding, and coordination to additional metal centers. Anion binding can also induce cage diastereomeric reconfiguration in a similar manner to some neutral guests, illustrating the general ability of subcomponent self-assembled capsules to respond to stimuli due to their dynamic nature. Capsules have been developed as supramolecular extractants for the selective removal of anions from water and as channels for transporting anions through planar lipid bilayers and into vesicles. Different capsules may work together, allowing for functions more complex than those achievable within single host-guest systems. Incorporation of stimuli-responsive capsules into multicage systems allows individual capsules within the network to be addressed and may allow signals to be passed between network members. We first present strategies to achieve selective guest binding and controlled guest release using mixtures of capsules with varied affinities for guests and different stabilities toward external stimuli. We then discuss strategies to separate capsules with encapsulated cargos via selective phase transfer, where the solvent affinities of capsules change as a result of anion exchange or post-assembly modification. The knowledge gained from these multicage systems may lead to the design of synthetic systems that can perform complex tasks in biomimetic fashion, paving the way for new supramolecular technologies to address practical problems.

Covalent Post-assembly Modification Triggers Multiple Structural Transformations of a Tetrazine-Edged Fe4L6 Tetrahedron.

Covalent post-assembly modification (PAM) reactions are useful synthetic tools for functionalizing and stabilizing self-assembled metal-organic complexes. Recently, PAM reactions have also been explored as stimuli for triggering supramolecular structural transformations. Herein we demonstrate the use of inverse electron-demand Diels-Alder (IEDDA) PAM reactions to induce supramolecular structural transformations starting from a tetrazine-edged FeII4L6 tetrahedral precursor. Following PAM, this tetrahedron rearranged to form three different architectures depending on the addition of other stimuli: an electron-rich aniline or a templating anion. By tracing the stimulus-response relationships within the system, we deciphered a network of transformations that mapped different combinations of stimuli onto specific transformation products. Given the many functions being developed for self-assembled three-dimensional architectures, this newly established ability to control the interconversion between structures using combinations of different stimulus types may serve as the basis for switching the functions expressed within a system.

Preparation and Post-Assembly Modification of Metallosupramolecular Assemblies from Poly( N-Heterocyclic Carbene) Ligands.

Although the coordination chemistry of N-heterocyclic carbenes (NHCs) with transition metals has been explored for half a century, only in the past ten years has the chemistry of metallosupramolecular assemblies based on poly-NHC ligands been studied more extensively. Remarkable discrete assemblies featuring poly-NHC ligands including two-dimensional metallacycles and three-dimensional metallaprisms/cages have since emerged. These assemblies are mostly obtained starting from various imidazolium or benzimidazolium salts. Driven by the increasing interest in new supramolecular architectures from carbon donor ligands, design, and construction of poly-NHC metal assemblies has become a rapidly growing area of research. The metal-carbene bond length is fixed to approximately 2.0 Å in linear NHC-M-NHC complexes. This allows the use of such complexes bearing olefin-substituted NHC ligands as templates for subsequent photochemical [2 + 2] cycloaddition reactions. The postassembly modification of such assemblies has been actively explored in recent years. In this review, we focus on the synthetic methods, characterization, structural features, and postassembly modifications of metallosupramolecular assemblies obtained from poly-NHC ligands.

Metal Organic Polyhedra: A Click-and-Clack Approach Toward Targeted Delivery.

Mixed self-assembly of ligands 1 and 2, PXDA (3), and Pd(NO3)2 afforded metal organic polyhedra (MOP 1 - MOP 3) which bear 24 covalently attached CB[7] and cyclooctyne moieties. Post assembly modification (PAM) of MOP 3 by covalent strain promoted alkyne azide click reaction provided MOP 4 R bearing covalently attached functionality (PEG, sulfonate, biotin, c-RGD, fluorescein and cyanine). Orthogonal CB[7] guest mediated non-covalent PAM of MOP 4 R with Ad-FITC afforded MOP 5 RGD Ad-FITC and MOP 5 biotin 0020Ad-FITC. Flow cytometry analysis of the uptake of MOP 5 RGD Ad-FITC toward U87 cells demonstrated improved uptake relative to control MOP lacking c-RGD ligands. These results suggest a broad applicability of orthogonally functionalizable (covalent and non-covalent) MOPs in targeted drug delivery and imaging applications.

Process-Tracing Study on the Postassembly Modification of Highly Stable Zirconium Metal-Organic Cages.

Metal-organic cages (MOCs) are discrete molecular assemblies formed by coordination bonds between metal nodes and organic ligands. The application of MOCs has been greatly limited due to their poor stability, especially in aqueous solutions. In this work, we thoroughly investigate the stability of several Zr-MOCs and reveal their excellent stability in aqueous solutions with acidic, neutral, and weak basic conditions. In addition, we present for the first time a process-tracing study on the postassembly modification of one MOC, ZrT-1-NH2, highlighting the excellent stability and versatility of Zr-MOCs as a new type of molecular platform for various applications.

Post-assembly polymerization of discrete organoplatinum(II) metallacycles via dimerization of coumarin pendants

The post-assembly modification provides a powerful strategy for constructing functional polymeric materials by the selection of suitable functional groups or external stimuli. Herein, we took advantage of photodimerization of coumarins to link the pendent coumarin functional groups of hexagonal metallacycles 1 and 2 to give metallacycle-cored supramolecular polymers 1p and 2p under UV irradiation at 365 nm.