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.European Research Council (695009), UK Engineering and Physical Sciences Research Council (EPSRC, EP/P027067/1

Metal-peptidic cages—Helical oligoprolines generate highly anisotropic nanospaces with emergent isomer control

The self-assembly of metal-organic cages enables the rapid creation of atomically defined, three-dimensional, nanoscale architectures reminiscent of proteins. However, existing metal-organic cages are almost exclusively built from rigid and flat aromatic panels, limiting binding selectivity and, often, water solubility. Herein, we disclose a new class of cages—metal-peptidic cages—which utilize water-soluble, chiral, and helical oligoproline strands of varying lengths to generate highly anisotropic nanospaces. Further, we find that the formation of the cis isomer of the cage is strongly favored and is an emergent property of using complex and chiral building blocks in the formation of defined nanospaces. We demonstrate that the use of peptidic building blocks allows us to rapidly tune the size of the nanospace formed, from c. 1 to 4 nm, and that the use of biologically relevant components enables targeted binding of therapeutic molecules, highlighting the potential of these systems for selective drug delivery.</p

Anion Pairs Template a Trigonal Prism with Disilver Vertices.

Here we describe the formation of a trigonal prismatic cage, utilizing 2-formyl-1,8-naphthyridine subcomponents to bind pairs of silver(I) ions in close proximity. This cage is the first example of a new class of subcomponent self-assembled polyhedral structures having bimetallic vertices, as opposed to the single metal centers that typically serve as structural elements within such cages. Our new cage self-assembles around a pair of anionic templates, which are shown by crystallographic and solution-phase data to bind within the central cavity of the structure. Many different anions serve as competent templates and guests. Elongated dianions, such as the strong oxidizing agent peroxysulfate, also serve to template and bind within the cavity of the prism. The principle of using subcomponents that have more than one spatially close, but nonchelating, binding site may thus allow access to other higher-order structures with multimetallic vertices.European Research Council (695009) and the UK Engineering and Physical Sciences Re‐ search Council (EPSRC, EP/P027067/1). European Union's Horizon 2020 research and innovation program, Marie Sklodowska‐Curie Grant (642192)

A Double-Walled Tetrahedron with AgI 4 Vertices Binds Different Guests in Distinct Sites

A double-walled tetrahedral metal-organic cage assembled in solution from silver(I), 2-formyl-1,8-naphthyridine, halide, and a threefold-symmetric triamine. The AgI 4 X clusters at its vertices each bring together six naphthyridine-imine moieties, leading to a structure in which eight tritopic ligands bridge four clusters in an (AgI 4 X)4 L8 arrangement. Four ligands form an inner set of tetrahedron walls that are surrounded by the outer four. The cage has significant interior volume, and was observed to bind anionic guests. The structure also possesses external binding clefts, located at the edges of the cage, which bound small aromatic guests. Halide ions bound to the silver clusters were observed to exchange in a well-defined hierarchy, allowing modulation of the cavity volume. The principles uncovered here may allow for increasingly more sophisticated cages with silver-cluster vertex architectures, with post-assembly tuning of the interior cavity volume enabling targeted binding behavior

Palladium-catalyzed enolate arylation as a key C-C bond-forming reaction for the synthesis of isoquinolines.

The palladium-catalyzed coupling of an enolate with an ortho-functionalized aryl halide (an α-arylation) furnishes a protected 1,5-dicarbonyl moiety that can be cyclized to an isoquinoline with a source of ammonia. This fully regioselective synthetic route tolerates a wide range of substituents, including those that give rise to the traditionally difficult to access electron-deficient isoquinoline skeletons. These two synthetic operations can be combined to give a three-component, one-pot isoquinoline synthesis. Alternatively, cyclization of the intermediates with hydroxylamine hydrochloride engenders direct access to isoquinoline N-oxides; and cyclization with methylamine, gives isoquinolinium salts. Significant diversity is available in the substituents at the C4 position in four-component, one-pot couplings, by either trapping the in situ intermediate after α-arylation with carbon or heteroatom-based electrophiles, or by performing an α,α-heterodiarylation to install aryl groups at this position. The α-arylation of nitrile and ester enolates gives access to 3-amino and 3-hydroxyisoquinolines and the α-arylation of tert-butyl cyanoacetate followed by electrophile trapping, decarboxylation and cyclization, C4-functionalized 3-aminoisoquinolines. An oxime directing group can be used to direct a C-H functionalization/bromination, which allows monofunctionalized rather than difunctionalized aryl precursors to be brought through this synthetic route

The mechanical bond in biological systems

The field of mechanically interlocked molecules (MIMs) has advanced rapidly in recent years, with much work focused on their use in materials, sensing, and catalysis. However, the use of MIMs in biology and biomedicine has been limited, despite the identification of naturally occurring MIMs in DNA and proteins and the potential advantages of the mechanical bond in fields such as nanomedicine and tissue engineering. Difficulties in the synthesis of MIMs, along with their limited solubility and stability in biological media, have until recently impeded their wider application in biology. Contemporary advances have, however, enabled a broader integration of the mechanical bond in biology; the mechanical interlocking endows these systems with unique functional advantages. Herein, we summarize recent advances in the application of small-molecule, biologically derived, and polymeric MIMs in biology, highlighting synergies ripe for future exploration.</p

Selective Anion Binding Drives the Formation of AgI8L6 and AgI12L6 Six-Stranded Helicates.

Here we describe the formation of an unexpected and unique family of hollow six-stranded helicates. The formation of these structures depends on the coordinative flexibility of silver and the 2-formyl-1,8-napthyridine subcomponent. Crystal structures show that these assemblies are held together by Ag4I, Ag4Br, or Ag6(SO4)2 clusters, where the templating anion plays an integral structure-defining role. Prior to the addition of the anionic template, no six-stranded helicate was observed to form, with the system instead consisting of a dynamic mixture of triple helicate and tetrahedron. Six-stranded helicate formation was highly sensitive to the structure of the ligand, with minor modifications inhibiting its formation. This work provides an unusual example of mutual stabilization between metal clusters and a self-assembled metal-organic cage. The selective preparation of this anisotropic host demonstrates new modes of guiding selective self-assembly using silver(I), whose many stable coordination geometries render design difficult

Beyond Platonic: How to Build Metal-Organic Polyhedra Capable of Binding Low-Symmetry, Information-Rich Molecular Cargoes.

The field of metallosupramolecular chemistry has advanced rapidly in recent years. Much work in this area has focused on the formation of hollow self-assembled metal-organic architectures and exploration of the applications of their confined nanospaces. These discrete, soluble structures incorporate metal ions as 'glue' to link organic ligands together into polyhedra.Most of the architectures employed thus far have been highly symmetrical, as these have been the easiest to prepare. Such high-symmetry structures contain pseudospherical cavities, and so typically bind roughly spherical guests. Biomolecules and high-value synthetic compounds are rarely isotropic, highly-symmetrical species. To bind, sense, separate, and transform such substrates, new, lower-symmetry, metal-organic cages are needed. Herein we summarize recent approaches, which taken together form the first draft of a handbook for the design of higher-complexity, lower-symmetry, self-assembled metal-organic architectures.European Research Council Leverhulme Trust The Isaac Newton Trust Sidney Sussex College, Cambridg

A complementary pair of enantioselective switchable organocatalysts

A pair of enantioselective switchable bifunctional catalysts are shown to promote a range of conjugate addition reactions in up to 95 : 5 e.r. and 95% conversion.</p