Self-Assembly of Rod-Coil Bottlebrush Copolymers into Degradable Nanodiscs with a UV-Triggered Self-Immolation Process.

Polymer nanodiscs, especially with stimuli-responsive features, represent an unexplored frontier in the nanomaterial landscape. Such 2D nanomaterials are considered highly promising for advanced biomedicine applications. Herein, we designed a rod-coil copolymer architecture based on an amphiphilic, tadpole-like bottlebrush copolymer, which can directly self-assemble into core-shell nanodiscs in an aqueous environment. As the bottlebrush side chains are made of amorphous, UV-responsive poly(ethyl glyoxylate) (PEtG) chains, they can undergo rapid end-to-end self-immolation upon light irradiation. This triggered nanodisc disassembly can be used to boost small molecule release from the nanodisc core, which is further aided by a morphological change from discs to spheres.

Tailored Biocompatible Polyurethane-Poly(ethylene glycol) Hydrogels as a Versatile Nonfouling Biomaterial.

Polyurethane-based hydrogels are relatively inexpensive and mechanically robust biomaterials with ideal properties for various applications, including drug delivery, prosthetics, implant coatings, soft robotics, and tissue engineering. In this report, a simple method is presented for synthesizing and casting biocompatible polyurethane-poly(ethylene glycol) (PU-PEG) hydrogels with tunable mechanical properties, nonfouling characteristics, and sustained tolerability as an implantable material or coating. The hydrogels are synthesized via a simple one-pot method using commercially available precursors and low toxicity solvents and reagents, yielding a consistent and biocompatible gel platform primed for long-term biomaterial applications. The mechanical and physical properties of the gels are easily controlled by varying the curing concentration, producing networks with complex shear moduli of 0.82-190 kPa, similar to a range of human soft tissues. When evaluated against a mechanically matched poly(dimethylsiloxane) (PDMS) formulation, the PU-PEG hydrogels demonstrated favorable nonfouling characteristics, including comparable adsorption of plasma proteins (albumin and fibrinogen) and significantly reduced cellular adhesion. Moreover, preliminary murine implant studies reveal a mild foreign body response after 41 days. Due to the tunable mechanical properties, excellent biocompatibility, and sustained in vivo tolerability of these hydrogels, it is proposed that this method offers a simplified platform for fabricating soft PU-based biomaterials for a variety of applications.

Post-synthetic 'Click' Synthesis of RAFT Polymers with Pendant Self-immolative Triazoles.

Self-immolative linkers offer efficient mechanisms for deprotecting 'caged' functional groups in response to specific stimuli. Herein we describe a convenient 'click' chemistry method for introducing pendant self-immolative linkers to a polymer backbone through post-polymerization modification. The introduced triazole rings serve both to anchor the stimuli-cleavable trigger groups to the polymer backbone, while also forming a functional part of the self-immolation cascade. We investigate the polymerization kinetics, post-synthetic modification, and self-immolation mechanism of a model polymer system, and discuss avenues for future studies on poly-pendant self-immolative triazoles as a modular, stimuli-responsive macromolecule platform.

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.

Dynamic pH responsivity of triazole-based self-immolative linkers.

Gating the release of chemical payloads in response to transient signals is an important feature of 'smart' delivery systems. Herein, we report a triazole-based self-immolative linker that can be reversibly paused or slowed and restarted throughout its elimination cascade in response to pH changes in both organic and organic-aqueous solvents. The linker is conveniently prepared using the alkyne-azide cycloaddition reaction, which introduces a 1,4-triazole ring that expresses a pH-sensitive intermediate during its elimination sequence. Using a series of model compounds, we demonstrate that this intermediate can be switched between active and dormant states depending on the presence of acid or base, cleanly gating the release of payload in response to a fluctuating external stimulus.

Multivalent Crown Ether Receptors Enable Allosteric Regulation of Anion Exchange in an Fe4 L6 Tetrahedron.

We report a strategy for regulating the rate of internally bound anion exchange within an Fe4 L6 metal-organic tetrahedron through external coordination of tripodal tris(alkylammonium) cations. The cage features three flexible 18-crown-6 receptors at each of its FeII vertices, facilitating strong tritopic interactions with tris(ammonium) cations to "cap" the vertices of the tetrahedron. This capping mechanism restricts the flexibility of the cage framework, thereby reducing the rate of anion exchange within its central cavity by 20-fold. Thus, we demonstrate the first use of an externally bound multivalent effector to allosterically control internal guest binding in a molecular cage.

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.

Covalent post-assembly modification in metallosupramolecular chemistry.

A growing variety of covalent reactions have been employed to achieve the post-assembly modification (PAM) of self-assembled metallosupramolecular complexes. Covalent PAM enables the late-stage derivatisation of pre-assembled parent complexes in a modular fashion, thus expanding the chemical space available for supramolecular synthesis. The oldest and most widespread implementation of covalent PAM is in metal-preorganised covalent synthesis. Recent work, however, has broadened the scope of covalent PAM to include: protocols for efficiently grafting new functionalities onto supramolecular architectures, reactions that permanently 'lock-down' metastable complexes, and covalent bond-forming stimuli that trigger controlled structural transformations between distinct supramolecular species. This review highlights key examples of each of these distinct kinds of covalent PAM in metallosupramolecular chemistry, before providing a perspective upon future challenges and opportunities.

Perfluorinated Ligands Induce Meridional Metal Stereochemistry to Generate M8L12, M10L15, and M12L18 Prisms.

Meridional (mer) coordination promotes the generation of larger and lower-symmetry prismatic metallosupramolecular structures, in contrast with the facial (fac) coordination common to smaller and higher-symmetry polyhedra. Here, we describe a general route to the selective formation of large metallosupramolecular prisms that contain exclusively mer-coordinated metal vertices. The use of 2-formylpyridine subcomponents that contain perfluorophenylene substituents at their 5-positions resulted in stereoselective formation of the iron(II) complexes from these subcomponents. Only mer vertices were observed, as opposed to the statistical fac/mer mixture otherwise generated. This mer-selective self-assembly could be used to prepare tetragonal (M8L12), pentagonal (M10L15), and hexagonal (M12L18) prisms by taking advantage of the subtle selectivities imposed by the different anilines and counterions employed. The equilibrium between the tetragonal and pentagonal prism followed a linear free-energy relationship, with the ratio between structures correlating with the Hammett σp(+) parameter of the incorporated aniline. The contrasting preferences of the fluorinated and nonfluorinated ligands to generate prisms and tetrahedra, respectively, were quantified energetically, with the destabilization increasing linearly for each "incorrect ligand" incorporated into either structure.

A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine--Tertiary Isocyanate Coupling for Polymer Ligation.

Click reactions have provided access to an array of remarkably complex polymer architectures. However, the term "click" is often applied inaccurately to polymer ligation reactions that fail to respect the criteria that typify a true "click" reaction. With the purpose of providing a universal way to benchmark polymer-polymer coupling efficiency at equimolarity and thus evaluate the fulfilment of click criteria, we report a simple one-pot methodology involving the homodicoupling of α-end-functionalized polymers using a small-molecule bifunctional linker. A combination of SEC analysis and chromatogram deconvolution enables straightforward quantification of the coupling efficiency. We subsequently employ this methodology to evaluate an overlooked candidate for the click reaction family: the addition of primary amines to α-tertiary isocyanates (α-(t)NCO). Using our bifunctional linker coupling strategy, we show that the amine-(t)NCO reaction fulfills the criteria for a polymer-polymer click reaction, achieving rapid, chemoselective, and quantitative coupling at room temperature without generating any byproducts. We demonstrate that amine-(t)NCO coupling is faster and more efficient than the more common amine-tertiary active ester coupling under equivalent conditions. Additionally, we show that the α-(t)NCO end group is unprecedentedly stable in aqueous media. Thus, we propose that the amine-(t)NCO ligation is a powerful new click reaction for efficient macromolecular coupling.

Dual stimuli-induced formation of a µ-hydroxido bridged [Zn9L5(µ-OH)6]12+ half-pipe.

Low-symmetry metal-organic architectures that feature unusual binding motifs are useful for exploring new modes of guest recognition. Such structures remain difficult to create using current rational design principles. One approach to constructing such architectures is to employ ligands with coordination vectors oriented to preclude the formation of simple, low nuclearity molecular assemblies upon complexation to metal ions. Here we report two new supramolecular assemblies generated from such a ligand: a simple metastable [Zn3L3]6+ assembly, which was observed to convert to a more complex [Zn9L5(µ-OH)6]12+ twisted half-pipe architecture. Two chemically distinct stimuli-an anionic template and a base-must be applied for the conversion to occur. Perchlorate, perrhenate, trifluoromethanesulfonate and 2-naphthalenesulfonate were found to act as competent templates for the [Zn9L5(µ-OH)6]12+ structure.

Stacking Interactions Drive Selective Self-Assembly and Self-Sorting of Pyrene-Based M(II)4L6 Architectures.

Subcomponent self-assembly of two isomeric bis(3-aminophenyl)pyrenes, 2-formylpyridine and the metal ions Fe(II), Co(II), and Zn(II) led to the formation of two previously unidentified structure types: a C2-symmetric M(II)4L6 assembly with meridionally coordinated metal centers, and a C3-symmetric self-included M(II)4L6 assembly with facially coordinated metal centers. In both structures the meta linkages within the ligands facilitate π-stacking between the pyrene panels of the ligands. A C2h-symmetric M(II)2L2 box was also obtained, which was observed to selectively bind electron-deficient aromatic guests between two parallel pyrene subunits. Similar donor-acceptor interactions drove the selective self-assembly of a singular M(II)4L4L'2 architecture incorporating both a pyrene-containing diamine and an electron-deficient NDI-based diamine. This heteroleptic architecture was shown to be thermodynamically favored over the corresponding homoleptic M(II)4L6 and M(II)4L'6 complexes, which were nonetheless stable in each others' absence. By contrast, an isomeric pyrene-based diamine was observed to undergo narcissistic self-sorting in the presence of the NDI-based diamine.

Post-assembly Modification of Tetrazine-Edged Fe(II)4L6 Tetrahedra.

Post-assembly modification (PAM) is a powerful tool for the modular functionalization of self-assembled structures. We report a new family of tetrazine-edged Fe(II)4L6 tetrahedral cages, prepared using different aniline subcomponents, which undergo rapid and efficient PAM by inverse electron-demand Diels-Alder (IEDDA) reactions. Remarkably, the electron-donating or -withdrawing ability of the para-substituent on the aniline moiety influences the IEDDA reactivity of the tetrazine ring 11 bonds away. This effect manifests as a linear free energy relationship, quantified using the Hammett equation, between σ(para) and the rate of the IEDDA reaction. The rate of PAM can thus be adjusted by varying the aniline subcomponent.

Selective endo and exo binding of mono- and ditopic ligands to a rhomboidal diporphyrin prism.

Copper(I) can preferentially form heteroleptic complexes containing two phosphine and two nitrogen donors due to steric factors. This preference was employed to direct the self-assembly of a porphyrin-faced rhomboidal prism having two parallel tetrakis(4-iminopyridyl)porphyrinatozinc(II) faces linked by eight 1,4-bis(diphenylphosphino)benzene pillars. The coordination preferences of the Cu(I) ions and geometries of the ligands come together to generate a slipped-cofacial orientation of the porphyrinatozinc(II) faces. This orientation enables selective encapsulation of 3,3'-bipyridine (bipy), which bridges the Zn(II) ions of the parallel porphyrins, whereas 4,4'-bipy exhibits weaker external coordination to the porphyrin faces. Reaction with 2,2'-bipy, by contrast, results in the displacement of the tetratopic porphyrin ligand and formation of [{(2,2'-bipy)Cu(I) }2 (diphosphine)2 ]. The differing strengths of interactions of bipyridine isomers with the system allows for a hierarchy to be deciphered, whereby 4,4'-bipy may be displaced by 3,3'-bipy, which in turn is displaced by 2,2'-bipy.

Molecular containers in complex chemical systems.

Over the last decade molecular containers have been increasingly studied within the context of complex chemical systems. Herein we discuss selected examples from the literature concerning three aspects of this field: complex host-guest behaviour, adaptive transformations of molecular containers and reactivity modulation within them.

Post-assembly modification of kinetically metastable Fe(II)2L3 triple helicates.

We report the covalent post-assembly modification of kinetically metastable amine-bearing Fe(II)2L3 triple helicates via acylation and azidation. Covalent modification of the metastable helicates prevented their reorganization to the thermodynamically favored Fe(II)4L4 tetrahedral cages, thus trapping the system at the non-equilibrium helicate structure. This functionalization strategy also conveniently provides access to a higher-order tris(porphyrinatoruthenium)-helicate complex that would be difficult to prepare by de novo ligand synthesis.

Tunable self-assembly of triazole-linked porphyrin-polymer conjugates.

The convergence of supramolecular chemistry and polymer science offers many powerful approaches for building functional nanostructures with well-defined dynamic behaviour. Herein we report the efficient "click" synthesis and self-assembly of AB2 - and AB4 -type multitopic porphyrin-polymer conjugates (PPCs). PPCs were prepared using the copper(I)-catalysed azide-alkyne cycloaddition (CuAAC) reaction, and consisted of linear polystyrene, poly(butyl acrylate), or poly(tert-butyl acrylate) arms attached to a zinc(II) porphyrin core via triazole linkages. We exploit the presence of the triazole groups obtained from CuAAC coupling to direct the self-assembly of the PPCs into short oligomers (2-6 units in length) via intermolecular porphyrinatozinc-triazole coordination. By altering the length and grafting density of the polymer arms, we demonstrate that the association constant of the porphyrinatozinc-triazole complex can be systematically tuned over two orders of magnitude. Self-assembly of the PPCs also resulted in a 6 K increase in the glass transition temperature of the bulk material compared to a non-assembling PPC. The modular synthesis and tunable self-assembly of the triazole-linked PPCs thus represents a powerful supramolecular platform for building functional nanostructured materials.

Synthesis and ultrafast excited-state dynamics of zinc and palladium triply fused diporphyrins.

We report the synthesis and ultrafast excited-state dynamics of two new meso-meso, ß-ß, ß-ß triply fused diporphyrins, Zn-3DP and Pd-3DP. Both compounds were found to have short excited-state lifetimes: Zn-3DP possessed an average S1 lifetime of 14 ps before nonradiative deactivation to the ground state, whereas Pd-3DP displayed a longer average S1 lifetime of 18 ps before crossing to the T1 state, which itself possessed a very short triplet lifetime of 1.7 ns. The excited-state dynamics of Zn-3DP, compared to similar zinc(II) diporphyrins reported in the literature, suggests that a conical intersection of the S1 and S0 potential energy surfaces plays a major role as a deactivation pathway of these molecules. Furthermore, the short triplet lifetime of Pd-3DP, compared to other diporphyrins that also exploit the intramolecular heavy atom effect, reveals that the position of the heavy atom within the diporphyrin framework influences the strength of spin-orbit coupling. The implications for employing triply fused diporphyrins as NIR-absorbing triplet sensitizers are discussed.

Spectroscopy of the free phenalenyl radical.

After benzene and naphthalene, the smallest polycyclic aromatic hydrocarbon bearing six-membered rings is the threefold-symmetric phenalenyl radical. Despite the fact that it is so fundamental, its electronic spectroscopy has not been rigorously scrutinized, in spite of growing interest in graphene fragments for molecular electronic applications. Here we used complementary laser spectroscopic techniques to probe the jet-cooled phenalenyl radical in vacuo. Its spectrum reveals the interplay between four electronic states that exhibit Jahn-Teller and pseudo-Jahn-Teller vibronic coupling. The coupling mechanism has been elucidated by the application of various ab initio quantum-chemical techniques.