Boris Breiner

White Phosphorus Is Air-Stable Within a Self-Assembled Tetrahedral Capsule

Molecular Fire Quencher Cage-shaped molecular assemblies can regulate the reactivity of smaller molecules trapped within them. Mal et al. (p. 1697) extend this approach to enable the protection of elemental white phosphorus (P4), a substance that rapidly ignites on contact with oxygen. The tetrahedral cages self-assemble in aqueous solution through coordination of six ligands to four iron ions, and efficiently capture phosphorus from a suspension. The water-soluble host-guest constructs were stable in air for at least 4 months, but released intact P4 rapidly on displacement by added benzene. A molecular cage keeps phosphorus from igniting in air, yet releases it easily for reactions when benzene is added. The air-sensitive nature of white phosphorus underlies its destructive effect as a munition: Tetrahedral P4 molecules readily react with atmospheric dioxygen, leading this form of the element to spontaneously combust upon exposure to air. Here, we show that hydrophobic P4 molecules are rendered air-stable and water-soluble within the hydrophobic hollows of self-assembled tetrahedral container molecules, which form in water from simple organic subcomponents and iron(II) ions. This stabilization is not achieved through hermetic exclusion of O2 but rather by constriction of individual P4 molecules; the addition of oxygen atoms to P4 would result in the formation of oxidized species too large for their containers. The phosphorus can be released in controlled fashion without disrupting the cage by adding the competing guest benzene.

A Self‐Assembled M8L6 Cubic Cage that Selectively Encapsulates Large Aromatic Guests

Biological encapsulants such as ferritin, lumazine synthase, and viral capsids achieve their selective separation and sequestration of substrates by providing: 1) a guest microenvironment isolated from the surroundings, 2) favorable interactions complementing a size and shape match with the encapsulated guests, and 3) sufficient flexibility to allow guests to be incorporated and released. These biological hosts self-assemble from multiple copies of identical protein subunits, the symmetries and connection properties of which dictate the hollow polyhedral structures of the encapsulant. In order to create abiological molecular systems that are capable of expressing functions of similar complexity to biological systems and to explore new applications of synthetic hosts, there is a need to create synthetic capsules capable of tightly and selectively binding large substrates. Taking inspiration from natural systems and from other previously reported metal–organic capsules, we report the design and synthesis of a series of metallo-supramolecular cage molecules capable of selectively encapsulating large aromatic guests. The necessary features to achieve this function are: 1) small pore sizes to isolate guests from the environment, 2) large cavity sizes to ensure sufficient volume for the guests of interest, 3) enough flexibility and lability to allow guests to enter and exit the host, and 4) regions of the cage walls rich in p-electron density to provide favorable interactions with targeted guests. The selective encapsulation of large aromatic molecules is an attractive goal since their physicochemical properties are similar, which can render their separation difficult. The higher fullerenes represent particularly attractive targets because their potential applications remain difficult to explore because of the challenges associated with their separation, despite recent advances. Employing principles of geometric analysis, we determined that combination of the C4-symmetric tetrakis-bidentate ligand shown in Figure 1 with the C3-symmetric iron(II) tris(pyridylimine) center would result in the formation of an O-symmetric cubic structure of general formula M8L6, in which the corners of the cube are defined by the metal centers and the faces by the ligands (Figure 1). This cage represents the first example of a new class of closed-face metallosupramolecular cubic hosts to be synthesized. In order to provide favorable binding sites for our target guests we incorporated porphyrin moieties, which have previously been demonstrated to interact with large aromatic molecules, into our design. This design also provides for small pore sizes and the potential to create new chemical functionality through the introduction of different metal ions into the centers of the N4 macrocycle and by substituting these metals axial ligands. We chose to employ labile iron(II) centers with pyridylimine ligands as chelating agents to allow for the formation of the ligand in situ through the subcomponent self-assembly approach. The reaction between tetrakis(4-aminophenyl)porphyrin (H2-tapp), 2-formylpyridine, and iron(II) trifluoromethanesulfonate (triflate, OTf ) in DMF produced cage [H21]·16OTf (Figure 1) as the uniquely observed product, as verified by NMR spectroscopy (Figure 3b), electrospray mass spectrometry (ESI-MS), and elemental analysis. Substitution of nickel(II) tetrakis(4-aminophenyl)porphyrin (Ni-tapp) or zinc(II) tetrakis(4-aminophenyl)porphyrin (Zn-tapp) for H2tapp under identical conditions yielded the nickel-containing (Ni-1) and zinc-containing (Zn-1) congeners of H2-1 (Figures S2a and S3a in the Supporting Information), respectively, suggesting the formation of such capsules to be a general feature of tetrakis(4-aminophenyl) porphyrins (Figure 1). Vapor diffusion of diethyl ether into a DMF/acetonitrile solution of Ni-1 resulted in the isolation of block-shaped dark purple crystals. Single-crystal X-ray diffraction revealed a solid-state structure (Figure 2) consistent with the O-symmetric NMR spectra recorded in solution. Each face of Ni-1 is covered by one porphyrin ligand and each corner is defined by a six-coordinate low-spin Fe ion. All of the Fe centers within each cage adopt the sameL or D configuration; both enantiomers of Ni-1 are present in the crystal lattice. The Ni–Ni distance between opposite faces is 15 , and the internal cavity volume is 1340 3 (Figure S2e). [*] W. Meng, Dr. B. Breiner, Prof. J. D. Thoburn, Dr. J. K. Clegg, Dr. J. R. Nitschke University of Cambridge, Department of Chemistry Lensfield Road, Cambridge, CB2 1EW (UK) E-mail: jrn34@cam.ac.uk Homepage: http://www-jrn.ch.cam.ac.uk/

Anion-induced reconstitution of a self-assembling system to express a chloride-binding Co10L15 pentagonal prism

Biochemical systems are adaptable, capable of reconstitution at all levels to achieve the functions associated with life. Synthetic chemical systems are more limited in their ability to reorganize to achieve new functions; they can reconfigure to bind an added substrate (template effect) or one binding event may modulate a receptors affinity for a second substrate (allosteric effect). Here we describe a synthetic chemical system that is capable of structural reconstitution on receipt of one anionic signal (perchlorate) to create a tight binding pocket for another anion (chloride). The complex, barrel-like structure of the chloride receptor is templated by five perchlorate anions. This second-order templation phenomenon allows chemical networks to be envisaged that express more complex responses to chemical signals than is currently feasible.

Selective anion binding by a “Chameleon” capsule with a dynamically reconfigurable exterior

A new class of tetrahedral metal–organic capsules that can incorporate up to twelve different externally-directed amine residues is reported, allowing for very large dynamic libraries to be formed from mixtures of amines. Selectivity is observed both externally—more electron-rich amines are incorporated in favour of electron-poor amines—and internally—PF6− is bound in preference to CF3SO3− or BF4−.

Subcomponent self-assembly and guest-binding properties of face-capped Fe4L48+ capsules

A general method for preparing Fe(4)L(4) face-capped tetrahedral cages through subcomponent self-assembly was developed and has been demonstrated using four different C(3)-symmetric triamines, 2-formylpyridine, and iron(II). Three of the triamines were shown also to form Fe(2)L(3) helicates when the appropriate stoichiometry of subcomponents was used. Two of the cages were observed to have nearly identical Fe-Fe distances in the solid state, which enabled their ligands to be coincorporated into a collection of mixed cages. Only one of the cages combined a sufficiently large cavity with the sufficiently small pores required for guest binding, taking up a wide variety of guest species in size- and shape-selective fashion.

A stimuli responsive system of self-assembled anion-binding Fe4L68+ cages

A new cationic Fe4L6 cage molecule was synthesised from 4,4′-diaminobiphenyl, 2-formylpyridine and iron(II). The cage exists as a system of interconverting diastereomers in solution. The system adapts to the addition of anionic guest molecules, expressing a new combination of diastereomers that synergistically bind the guest molecules. Not only do the cage diastereomers interconvert, the volume of the individual cages adapts physically through the rotation of bonds, providing a tailored binding pocket for the guest lined with hydrogen-bond donors. A model for the resulting complex network of species was developed that allowed the system to be fully described. The anion binding constants and the kinetics of both diastereomer interconversion and guest exchange were measured.

C-lysine conjugates: pH-controlled light-activated reagents for efficient double-stranded DNA cleavage with implications for cancer therapy

Double-stranded DNA cleavage of light-activated lysine conjugates is strongly enhanced at the slightly acidic pH (<7) suitable for selective targeting of cancer cells. This enhancement stems from the presence of two amino groups of different basicities. The first amino group plays an auxiliary role by enhancing solubility and affinity to DNA, whereas the second amino group, which is positioned next to the light-activated DNA cleaver, undergoes protonation at the desired pH threshold. This protonation results in two synergetic effects which account for the increased DNA-cleaving ability at the lower pH. First, lysine conjugates show tighter binding to DNA at the lower pH, which is consistent with the anticipated higher degree of interaction between two positively charged ammonium groups with the negatively charged phosphate backbone of DNA. Second, the unproductive pathway which quenches the excited state of the photocleaver through intramolecular electron transfer is eliminated once the donor amino group next to the chromophore is protonated. Experiments in the presence of traps for diffusing radicals show that reactive oxygen species do not contribute significantly to the mechanism of DNA cleavage at the lower pH, which is indicative of tighter binding to DNA under these conditions. This feature is valuable not only because many solid tumors are hypoxic but also because cleavage which does not depend on diffusing species is more localized and efficient. Sequence-selectivity experiments suggest combination of PET and base alkylation as the chemical basis for the observed DNA damage. The utility of these molecules for phototherapy of cancer is confirmed by the drastic increase in toxicity of five conjugates against cancer cell lines upon photoactivation.

Synthesis of selectively deuterated fulvenes and indenes from enediynes.

A facile enediyne--> fulvene--> indene transformation provides a route to all possible isotopomers of substituted fulvenes and indenes.

DNA damage-site recognition by lysine conjugates

Simple lysine conjugates are capable of selective DNA damage at sites approximating a variety of naturally occurring DNA-damage patterns. This process transforms single-strand DNA cleavage into double-strand cleavage with a potential impact on gene and cancer therapy or on the design of DNA constructs that require disassembly at a specific location. This study constitutes an example of DNA damage site recognition by molecules that are two orders of magnitude smaller than DNA-processing enzymes and presents a strategy for site-selective cleavage of single-strand nucleotides, which is based on their annealing with two shorter counterstrands designed to recreate the above duplex damage site.

Reversible anion-templated self-assembly of [2+2] and [3+3] metallomacrocycles containing a new dicopper(I) motif

A new dicopper(I) complex is reported that can be incorporated into extended architectures through multitopic carboxylate linkers; reversible carboxylate templation under pH control led to the formation of [2+2] and [3+3] metallomacrocycles.