Coordination-Cage-Catalysed Hydrolysis of Organophosphates: Cavity- or Surface-Based?

The hydrophobic central cavity of a water-soluble M8 L12 cubic coordination cage can accommodate a range of phospho-diester and phospho-triester guests such as the insecticide "dichlorvos" (2,2-dichlorovinyl dimethyl phosphate) and the chemical warfare agent analogue di(isopropyl) chlorophosphate. The accumulation of hydroxide ions around the cationic cage surface due to ion-pairing in solution generates a high local pH around the cage, resulting in catalysed hydrolysis of the phospho-triester guests. A series of control experiments unexpectedly demonstrates that-in marked contrast to previous cases-it is not necessary for the phospho-triester substrates to be bound inside the cavity for catalysed hydrolysis to occur. This suggests that catalysis can occur on the exterior surface of the cage as well as the interior surface, with the exterior-binding catalysis pathway dominating here because of the small binding constants for these phospho-triester substrates in the cage cavity. These observations suggest that cationic but hydrophobic surfaces could act as quite general catalysts in water by bringing substrates into contact with the surface (via the hydrophobic effect) where there is also a high local concentration of anions (due to ion pairing/electrostatic effects).

Photophysics of Cage/Guest Assemblies: Photoinduced Electron Transfer between a Coordination Cage Containing Osmium(II) Luminophores, and Electron-Deficient Bound Guests in the Central Cavity.

A heterometallic octanuclear coordination cage [Os4Zn4(Lnap)12]X16 (denoted Os•Zn; X = perchlorate or chloride) has been prepared (Lnap is a bis-bidentate bridging ligand containing two pyrazolyl-pyridine chelating units separated by a 1,5-naphthalenediyl spacer group). The {Os(NN)3}2+ units located at four of the eight vertices of the cube have a long-lived, phosphorescent 3MLCT excited state which is a stronger electron donor than [Ru(bipy)3]2+. The chloride form of Os•Zn is water-soluble and binds in its central cavity the hydrophobic electron-accepting organic guests 1,2,4,5-tetracyanobenzene, 1,4-naphthoquinone and 1-nitronaphthalene, with binding constants in the range 103-104 M-1, resulting in quenching of the phosphorescence arising from the Os(II) units. A crystal structure of an isostructural Co8 cage containing one molecule of 1,2,4,5-tetracyanobenzene as a guest inside the cavity has been determined. Ultrafast transient absorption measurements show formation of a charge-separated Os(III)/guest•- state arising from cage-to-guest photoinduced electron transfer; this state is formed within 13-21 ps, and decays on a time scale of ca. 200 ps. In the presence of a competing guest with a large binding constant (cycloundecanone) which displaces each electron-accepting quencher from the cage cavity, the charge-separated state is no longer observed. Further, a combination of mononuclear {Os(NN)3}2+ model complexes with the same electron-accepting species showed no evidence for formation of charge-separated Os(III)/guest•- states. These two control experiments indicate that the {Os(NN)3}2+ chromophores need to be assembled into the cage structure to bind the electron-accepting guests, and for PET to occur. These results help to pave the way for use of photoactive coordination cages as hosts for photoredox catalysis reactions on bound guests.

Qualitative colorimetric analysis of a Ir(iii)/Eu(iii) dyad in the presence of chemical warfare agents and simulants on a paper matrix.

The addition of G- and V-series organophosphorus chemical warfare agents and simulants to a paper-based assay of a dual-luminescent Ir(iii)/Eu(iii) dyad generated different emissive responses between the classes and compound types. The emission responses are complex and based not only on altering the balance between red Eu(iii)-based and blue Ir(iii)-based luminescent components, but also incorporate other factors such as analyte volatility, concentration and UV absorption. The extent of this emission colour change was analysed colorimetrically and related to the change in RGB output over time.

Catalysis in a Cationic Coordination Cage Using a Cavity-Bound Guest and Surface-Bound Anions: Inhibition, Activation, and Autocatalysis.

The Kemp elimination (reaction of benzisoxazole with base to give 2-cyanophenolate) is catalyzed in the cavity of a cubic M8L12 coordination cage because of a combination of (i) benzisoxazole binding in the cage cavity driven by the hydrophobic effect, and (ii) accumulation of hydroxide ions around the 16+ cage surface driven by ion-pairing. Here we show how reaction of the cavity-bound guest is modified by the presence of other anions which can also accumulate around the cage surface and displace hydroxide, inhibiting catalysis of the cage-based reaction. Addition of chloride or fluoride inhibits the reaction with hydroxide to the extent that a new autocatalytic pathway becomes apparent, resulting in a sigmoidal reaction profile. In this pathway the product 2-cyanophenolate itself accumulates around the cationic cage surface, acting as the base for the next reaction cycle. The affinity of different anions for the cage surface is therefore 2-cyanophenolate (generating autocatalysis) > chloride > fluoride (which both inhibit the reaction with hydroxide but cannot deprotonate the benzisoxazole guest) > hydroxide (default reaction pathway). The presence of this autocatalytic pathway demonstrates that a reaction of a cavity-bound guest can be induced with different anions around the cage surface in a controllable way; this was confirmed by adding different phenolates to the reaction, which accelerate the Kemp elimination to different extents depending on their basicity. This represents a significant step toward the goal of using the cage as a catalyst for bimolecular reactions between a cavity-bound guest and anions accumulated around the surface.

Binding of Hydrophobic Guests in a Coordination Cage Cavity is Driven by Liberation of "High-Energy" Water.

The cavity of an M8 L12 cubic coordination cage can accommodate a cluster of ten water molecules in which the average number of hydrogen bonds per water molecule is 0.5 H-bonds less than it would be in the bulk solution. The presence of these "hydrogen-bond frustrated" or "high-energy" water molecules in the cavity results in the hydrophobic effect associated with guest binding being predominantly enthalpy-based, as these water molecules can improve their hydrogen-bonding environment on release. This contrasts with the classical form of the hydrophobic effect in which the favourable entropy change associated with release of ordered molecules from hydrophobic surfaces dominates. For several guests Van't Hoff plots showed that the free energy of binding in water is primarily enthalpy driven. For five homologous pairs of guests related by the presence or absence of a CH2 group, the incremental changes to ΔH and TΔS for guest binding-that is, ΔΔH and TΔΔS, the difference in contributions arising from the CH2 group-are consistently 5(±1) kJ mol-1 for ΔΔH and 0(±1) kJ mol-1 for TΔΔS. This systematic dominance of ΔH in the binding of hydrophobic guests is consistent with the view that guest binding is dominated by release of "high energy" water molecules into a more favourable solvation environment, as has been demonstrated recently for some members of the cucurbituril family.

Coordination mode-induced isomeric cyclometalated [Ir(tpy)(nbi)Cl](PF6) complexes: distinct luminescence, self-assembly and cellular imaging behaviors.

Two isomeric Ir(iii) complexes Ir-O and Ir-R arising from the different coordination mode of a naphthalene-containing ligand, show distinct luminescence, self-assembly ability and cellular imaging behaviors.

Highly selective CO2vs. N2 adsorption in the cavity of a molecular coordination cage.

Two M8L12 cubic coordination cages, as desolvated crystalline powders, preferentially adsorb CO2 over N2 with ideal selectivity CO2/N2 constants of 49 and 30 at 298 K. A binding site for CO2 is suggested by crystallographic location of CS2 within the cage cavity at an electropositive hydrogen-bond donor site, potentially explaining the high CO2/N2 selectivity compared to other materials with this level of porosity.

Photoinduced energy- and electron-transfer from a photoactive coordination cage to bound guests.

In a coordination cage which contains an array of twelve naphthyl chromophores surrounding a central cavity, photoinduced energy or electron-transfer can occur from the chromophore array to the bound guest in supramolecular host/guest complexes.

Geometric isomerism in coordination cages based on tris-chelate vertices: a tool to control both assembly and host/guest chemistry.

This 'Perspective' article summarises recent work from the authors' research group on the exploitation of the simple fac/mer geometric isomerism of octahedral metal tris-chelates as a tool to control the chemistry of coordination cages based on bis(pyrazolyl-pyridine) ligands, in two different respects. Firstly this geometric isomerism plays a major role in controlling the guest binding properties of cages because a fac tris-chelate arrangement of pyrazolyl-pyridine chelates around a metal ion vertex results in formation of a convergent set of inwardly-directed C-H protons in a region of high positive electrostatic potential close to a metal cation. This collection of δ+ protons therefore provides a charge-assisted hydrogen-bond donor site, which interacts with the electron-rich regions of guest molecules that are of the correct size and shape to occupy the cage cavity, and the strength of this hydrogen-bonding interaction plays a major role in guest recognition in non-aqueous solvents. Secondly the ability to prepare mononuclear complexes with either a fac or mer arrangement of ligands provides an entry into the controlled, stepwise assembly of heterometallic cages based on a combination of kinetically inert and kinetically labile metal ions at different sites. This has allowed introduction of useful physical properties such as redox activity or luminescence, commonly associated with inert metal ions which are not amenable to participation in thermodynamic self-assembly processes, to be incorporated in a predictable way into the superstructures of coordination cages at specific sites.

Synthesis and photophysical properties of Ir(iii)/Re(i) dyads: control of Ir→Re photoinduced energy transfer.

A series of dinuclear Ir(iii)/Re(i) complexes has been prepared based on a family of symmetrical bridging ligands containing two bidentate N,N'-chelating pyrazolyl-pyridine termini, connected by a central aromatic or aliphatic spacer. The Ir(iii) termini are based on {Ir(F2ppy)2}(+) units (where F2ppy is the cyclometallating anion of a fluorinated phenylpyridine) and the Re(i) termini are based on {Re(CO)3Cl} units. Both types of terminus are luminescent, with the Ir-based unit showing characteristic strong, structured phosphorescence in the blue region (maximum 452 nm) with a triplet excited state energy of 22 200 cm(-1) and the Re-based unit showing much weaker and lower-energy phosphorescence (maximum 530 nm) with a triplet excited state energy of 21 300 cm(-1). The energy gradient between the two excited states allows for partial Ir→Re photoinduced energy-transfer, with substantial (but incomplete) quenching of the higher-energy Ir-based emission component and sensitised emission - evidenced by an obvious grow-in component - on the lower-energy Re-based emission. The Ir→Re energy-transfer rate constants vary over the range 1-8 × 10(7) s(-1) depending on the bridging ligand: there is no simple correlation between bridging ligand structure and energy-transfer rate, possibly because this will depend substantially on the conformation of these flexible molecules in solution. To test the role of ligand conformation further, we investigated a complex in which the bridging chain is a (CH2CH2O)6 unit whose conformation is known to be solvent-polarity dependent, with such chains adopting an open, elongated conformation in water and more compact, folded conformations in organic solvents. There was a clear link between the rate and extent of Ir→Re energy-transfer which reduced in polar solvents as the chain became elongated and the Ir/Re separation was larger; and increased in less polar solvents as the chain adopted a more compact conformation and the Ir/Re separation was reduced.

Imposing control on self-assembly: rational design and synthesis of a mixed-metal, mixed-ligand coordination cage containing four types of component.

Retrosynthetic analysis of a [M16L24]32+ coordination cage shows how it can be assembled rationally, in a stepwise manner, using a combination of kinetically inert and kinetically labile components. Combination of the components of fac-[Ru(Lph)3](PF6)2, Cd(BF4)2 and Lnaph in the necessary 4 : 12 : 12 stoichiometry afforded crystals of [Ru4Cd12(Lph)12(Lnaph)12]X32 (X = a mono-anion) in which the location of the two types of metal ion [Ru(ii) or Cd(ii)] at specific vertices in the metal-ion array, and the two types of bridging ligand (Lph and Lnaph) along specific edges, is completely controlled by the synthetic strategy. The incorporation of four different types of component at pre-determined positions in a coordination cage superstructure represents a substantial advance in imposing control on the self-assembly of complex metallosupramolecular entities.

Stepwise assembly of mixed-metal coordination cages containing both kinetically inert and kinetically labile metal ions: introduction of metal-centred redox and photophysical activity at specific sites.

Stepwise preparation of the heterometallic octanuclear coordination cages [(M(a))4(M(b))4L12](16+) is reported, in which M(a) = Ru or Os and M(b) = Cd or Co (all in their +2 oxidation state). This requires initial preparation of the kinetically inert mononuclear complexes [(M(a))L3](2+) in which L is a ditopic ligand with two bidentate chelating pyrazolyl-pyridine units: in the complexes [(M(a))L3](2+) one terminus of each ligand is bound to the metal ion, such that the complex has three pendant bidentate sites at which cage assembly can propagate by coordination to additional labile ions M(b) in a separate step. Thus, combination of four [(M(a))L3](2+) units and four [M(b)](2+) ions results in assembly of the complete cages [(M(a))4(M(b))4L12](16+) in which a metal ion lies at each of the eight vertices, and a bridging ligand spans each of the twelve edges, of a cube. The different types of metal ion necessarily alternate around the periphery with each bridging ligand bound to one metal ion of each type. All four cages have been structurally characterised: in the Ru(ii)/Cd(ii) cage (reported in a recent communication) the Ru(ii) and Cd(ii) ions are crystallographically distinct; in the other three cages [Ru(ii)/Co(ii), Os(ii)/Cd(ii) and Os(ii)/Co(ii), reported here] the ions are disordered around the periphery such that every metal site refines as a 50 : 50 mixture of the two metal atom types. The incorporation of Os(ii) units into the cages results in both redox activity [a reversible Os(ii)/Os(iii) couple for all four metal ions simultaneously, at a modest potential] and luminescence [the Os(ii) units have luminescent (3)MLCT excited states which will be good photo-electron donors] being incorporated into the cage superstructure.

Stepwise assembly of an adamantoid Ru4Ag6 cage by control of metal coordination geometry at specific sites.

The geometrically pure 'complex ligand' fac-[Ru(L(ph))3](2+), in which three pendant bidentate binding sites are located on one face of the complex, reacts with Ag(I) ions to form the adamantoid decanuclear cage [{Ru(L(ph))3}4Ag6](PF6)14 which contains a 6-coordinate Ru(II) ion at each vertex of a large tetrahedron and a 4-coordinate Ag(I) ion along each edge.

Stepwise synthesis of a Ru4Cd4 coordination cage using inert and labile subcomponents: introduction of redox activity at specific sites.

The kinetically inert mononuclear complex [RuL3](PF6)2 (1 : 3 mixture of fac and mer isomers), with three pendant binding sites, reacts with labile Cd(II) ions to complete the assembly of a Ru4Cd4 cubic coordination cage in which reversible redox behaviour has been introduced at the Ru(II) sites.

Fac and mer isomers of Ru(II) tris(pyrazolyl-pyridine) complexes as models for the vertices of coordination cages: structural characterisation and hydrogen-bonding characteristics.

We have prepared a series of mononuclear fac and mer isomers of Ru(II) complexes containing chelating pyrazolyl-pyridine ligands, to examine their differing ability to act as hydrogen-bond donors in MeCN. This was prompted by our earlier observation that octanuclear cube-like coordination cages that contain these types of metal vertex can bind guests such as isoquinoline-N-oxide (K = 2100 M(-1) in MeCN), with a significant contribution to binding being a hydrogen-bonding interaction between the electron-rich atom of the guest and a hydrogen-bond donor site on the internal surface of the cage formed by a convergent set of CH2 protons close to a 2+ metal centre. Starting with [Ru(L(H))3](2+) [L(H) = 3-(2-pyridyl)-1H-pyrazole] the geometric isomers were separated by virtue of the fact that the fac isomer forms a Cu(I) adduct which the mer isomer does not. Alkylation of the pyrazolyl NH group with methyl iodide or benzyl bromide afforded [Ru(L(Me))3](2+) and [Ru(L(bz))3](2+) respectively, each as their fac and mer isomers; all were structurally characterised. In the fac isomers the convergent group of pendant -CH2R or -CH3 protons defines a hydrogen-bond donor pocket; in the mer isomer these protons do not converge and any hydrogen-bonding involving these protons is expected to be weaker. For both [Ru(L(Me))3](2+) and [Ru(L(bz))3](2+), NMR titrations with isoquinoline-N-oxide in MeCN revealed weak 1 : 1 binding (K ≈ 1 M(-1)) between the guest and the fac isomer of the complex that was absent with the mer isomer, confirming a difference in the hydrogen-bond donor capabilities of these complexes associated with their differing geometries. The weak binding compared to the cage however occurs because of competition from the anions, which are free to form ion-pairs with the mononuclear complex cations in a way that does not happen in the cage complexes. We conclude that (i) the presence of fac tris-chelate sites in the cage to act as hydrogen-bond donors, and (ii) exclusion of counter-ions from the central cavity leaving these hydrogen-bonding sites free to interact with guests, are both important design criteria for future coordination cage hosts.