"Click"-Like η6 -Metalation/Demetalation of Aryl Iodides as a Means of Turning "ON/OFF" Halogen Bond Donor Functionality.

η6 -Metalated aryl halides are recognized as a class of halogen bond (XB) donors. Click-like η6 -metalation/demetalation of aryl iodides by cyclopentadienylruthenium(II) ([CpRuII ]+ ) is shown to turn ON/OFF (amplify/suppress) XB donor functionality. [CpRu(MeCN)3 ][PF6 ] is shown to react quantitatively with iodobenzenes (ArIn , n=1,2) to yield [CpRu(η6 -ArIn )][PF6 ] compounds. Photochemical demetalation (405 nm) quantitatively reverts these compounds to ArIn and [CpRu(MeCN)3 ][PF6 ]. Crystal structures of [CpRu(ArXn )]+ salts show that the [CpRu(ArIn )]+ cations are strong, charge-assisted XB donors analogous to iodopyridinium cations. XB-induced association of [CpRu(C6 H5 I)]+ with diazobicyclo[2.2.2]octane (DABCO) is established by NMR spectroscopy. [CpRu(C6 H5 I)][BPh4 ] and [CpRu(1,4-C6 H4 I2 )][BPh4 ] co-crystallize with DABCO and the structure of [CpRu(1,4-C6 H4 I2 )][BPh4 ]⋅DABCO⋅Et2 O is reported. DFT calculations support amplification of the XBing capabilities of aryl iodides upon [CpRu]+ -metalation.

Palladium-catalyzed cascade cyclizations involving C-C and C-X bond formation: strategic applications in natural product synthesis.

Palladium-catalyzed cascade cyclizations (PCCs) are powerful synthetic tools that enable rapid assembly of polycyclic scaffolds. Palladium complexes can promote a variety of carbon-carbon and carbon-heteroatom bond-forming reactions with high chemo-, enantio-, and diastereoselectivity. The combination of multiple ring-forming elementary steps into a single cascade sequence can allow complex structures to be accessed with high step economy. This strategy has been employed to access natural products in several distinct classes, including the mitomycins, dragmacidins, isoryanodane diterpenes, and ergot alkaloids. In this tutorial review, we demonstrate how PCCs have expedited natural product synthesis by enabling the formation of both C-C and C-X (X = O, N) bonds in a single synthetic operation.

Exploring the Scope of Macrocyclic "Shoe-last" Templates in the Mechanochemical Synthesis of RHO Topology Zeolitic Imidazolate Frameworks (ZIFs).

The macrocyclic cavitand MeMeCH2 is used as a template for the mechanochemical synthesis of 0.2MeMeCH2@RHO-Zn16(Cl2Im)32 (0.2MeMeCH2@ZIF-71) and RHO-ZnBIm2 (ZIF-11) zeolitic imidazolate frameworks (ZIFs). It is shown that MeMeCH2 significantly accelerates the mechanochemical synthesis, providing high porosity products (BET surface areas of 1140 m2/g and 869 m2/g, respectively). Templation of RHO-topology ZIF frameworks constructed of linkers larger than benzimidazole (HBIm) was unsuccessful. It is also shown that cavitands other than MeMeCH2-namely MeHCH2, MeiBuCH2, HPhCH2, MePhCH2, BrPhCH2, BrC5CH2-can serve as effective templates for the synthesis of x(cavitand)@RHO-ZnIm2 products. The limitations on cavitand size and shape are explored in terms of their effectiveness as templates.

Microporosity of a Guanidinium Organodisulfonate Hydrogen-Bonded Framework.

Guanidinium organosulfonates (GSs) are a large and well-explored archetypal family of hydrogen-bonded organic host frameworks that have, over the past 25 years, been regarded as nonporous. Reported here is the only example to date of a conventionally microporous GS host phase, namely guanidinium 1,4-benzenedisulfonate (p-G2 BDS). p-G2 BDS is obtained from its acetone solvate, AcMe@G2 BDS, by single-crystal-to-single-crystal (SC-SC) desolvation, and exhibits a Type I low-temperature/pressure N2 sorption isotherm (SABET =408.7(2) m2 g-1 , 77 K). SC-SC sorption of N2 , CO2 , Xe, and AcMe by p-G2 BDS is explored under various conditions and X-ray diffraction provides a measurement of the high-pressure, room temperature Xe and CO2 sorption isotherms. Though p-G2 BDS is formally metastable relative to the "collapsed", nonporous polymorph, np-G2 BDS, a sample of p-G2 BDS survived for almost two decades under ambient conditions. np-G2 BDS reverts to zCO2 @p-G2 BDS or yXe@p-G2 BDS (y,z=variable) when pressure of CO2 or Xe, respectively, is applied.

Manometric real-time studies of the mechanochemical synthesis of zeolitic imidazolate frameworks.

We demonstrate a simple method for real-time monitoring of mechanochemical synthesis of metal-organic frameworks, by measuring changes in pressure of gas produced in the reaction. Using this manometric method to monitor the mechanosynthesis of the zeolitic imidazolate framework ZIF-8 from basic zinc carbonate reveals an intriguing feedback mechanism in which the initially formed ZIF-8 reacts with the CO2 byproduct to produce a complex metal carbonate phase, the structure of which is determined directly from powder X-ray diffraction data. We also show that the formation of the carbonate phase may be prevented by addition of excess ligand. The excess ligand can subsequently be removed by sublimation, and reused. This enables not only the synthesis but also the purification, as well as the activation of the MOF to be performed entirely without solvent.

Use of a "Shoe-Last" Solid-State Template in the Mechanochemical Synthesis of High-Porosity RHO-Zinc Imidazolate.

We report the first use of a nonionic solid (NIS) as a template in mechanosynthesis of a metal-organic framework. Through eight intermolecular C-H···O hydrogen bonds, the macrocyclic MeMeCH2 template predictably functions as a "shoe-last" for the assembly of double-eight rings in the liquid-assisted reaction of ZnO and imidazole (ImH). The resulting new form of ZnIm2 (namely xMeMeCH2@RHO-Zn16Im32) is available in multigram amounts, highly porous, and thermally stable.

Reproducible Synthesis and High Porosity of mer-Zn(Im)2 (ZIF-10): Exploitation of an Apparent Double-Eight Ring Template.

Reproducible synthesis of the elusive merlinoite (mer) topology of zinc imidazolate (mer-Zn(Im)2, or ZIF-10) has been achieved by employing a simple macrocyclic solute-MeMeCH2-as a kinetic template. The corresponding phase-pure material, mer-MeMeCH2@Zn16(Im)32, is confirmed to be porous and exhibits one of the highest experimental surface areas (1893 m(2)/g, BET) yet reported for any ZIF. The X-ray single crystal structure of mer-MeMeCH2@Zn16(Im)32·xsolvent reveals the role of the macrocyle as an 8-fold hydrogen bond acceptor in templating the requisite double-eight rings (d8r) of the mer framework.

Enclathration and Confinement of Small Gases by the Intrinsically 0D Porous Molecular Solid, Me,H,SiMe2.

The stable, guest-free crystal form of the simple molecular cavitand, Me,H,SiMe2, is shown to be intrinsically porous, possessing discrete, zero-dimensional (0D) pores/microcavities of about 28 Å(3). The incollapsible 0D pores of Me,H,SiMe2 have been exploited for the enclathration and room temperature (and higher) confinement of a wide range of small gases. Over 20 isostructural x(gas/guest)@Me,H,SiMe2 (x ≤ 1) clathrates (guest = H2O, N2, Ar, CH4, Kr, Xe, C2H4, C2H6, CH3F, CO2, H2S, CH3Cl, CH3OCH3, CH3Br, CH3SH, CH3CH2Cl, CH2Cl2, CH3I, CH3OH, BrCH2Cl, CH3CH2OH, CH3CN, CH3NO2, I2), and a propyne clathrate (CH3CCH@Me,H,SiMe2·2CHCl3), have been prepared and characterized, and their single crystal structures determined. Gas enclathration is found to be highly selective for gases that can be accommodated by the predefined, though slightly flexible 0D pore. The structure determinations provide valuable insight, at subangstrom resolution, into the factors that govern inclusion selectivity, gas accommodation, and the kinetic stability of the clathrates, which has been probed by thermal gravimetric analysis. The activation (emptying) of several clathrates (guest = H2O, N2, CO2, Kr, CH3F) is shown to occur in a single-crystal-to-single-crystal (SC → SC) fashion, often requiring elevated temperatures. Akin to open pore materials, water vapor and CO2 gas are shown to be taken up by single crystals of empty Me,H,SiMe2 at room temperature, but sorption rates are slow, occurring over weeks to months. Thus, Me,H,SiMe2 exhibits very low, but measurable, gas permeability, despite there being no obvious dynamic mechanism to facilitate gas uptake. The unusually slow exchange kinetics has allowed the rates of gas (water vapor and CO2) sorption to be quantified by single crystal X-ray diffraction. The data are well fit to a simple three-dimensional diffusion model.

Extreme confinement of xenon by cryptophane-111 in the solid state.

Solids that sorb, capture and/or store the heavier noble gases are of interest because of their potential for transformative rare gas separation/production, storage, or recovery technologies. Herein, we report the isolation, crystal structures, and thermal stabilities of a series of xenon and krypton clathrates of (±)-cryptophane-111 (111). One trigonal crystal form, Xe@111⋅y(solvent), is exceptionally stable, retaining xenon at temperatures of up to about 300 °C. The high kinetic stability is attributable not only to the high xenon affinity and cage-like nature of the host, but also to the crystal packing of the clathrate, wherein each window of the molecular container is blocked by the bridges of adjacent containers, effectively imprisoning the noble gas in the solid state. The results highlight the potential of discrete molecule materials exhibiting intrinsic microcavities or zero-dimensional pores.

Synthesis and structure-activity relationship studies of small molecule disruptors of EWS-FLI1 interactions in Ewing's sarcoma.

EWS-FLI1 is an oncogenic fusion protein implicated in the development of Ewing's sarcoma family tumors (ESFT). Using our previously reported lead compound 2 (YK-4-279), we designed and synthesized a focused library of analogues. The functional inhibition of the analogues was measured by an EWS-FLI1/NR0B1 reporter luciferase assay and a paired cell screening approach measuring effects on growth inhibition for human cells containing EWS-FLI1 (TC32 and TC71) and control PANC1 cell lines devoid of the oncoprotein. Our data revealed that substitution of electron donating groups at the para-position on the phenyl ring was the most favorable for inhibition of EWS-FLI1 by analogs of 2. Compound 9u (with a dimethylamino substitution) was the most active inhibitor with GI50 = 0.26 ± 0.1 µM. Further, a correlation of growth inhibition (EWS-FLI1 expressing TC32 cells) and the luciferase reporter activity was established (R(2) = 0.84). Finally, we designed and synthesized a biotinylated analogue and determined the binding affinity for recombinant EWS-FLI1 (Kd = 4.8 ± 2.6 µM).

Rim-functionalized cryptophane-111 derivatives via heterocapping, and their xenon complexes.

Capping of cyclotriphenolene (3a) by the more available cyclotriguaiacylene (3c) or trisbromocyclotriphenolene (3b) gives the first rim-functionalized cryptophane-111 derivatives. Crystal structures of the xenon complexes reveal high cavity packing coefficients and unprecedentedly short Xe···C contacts.

Methyl 2-(but-3-en-yl)-4-hy-droxy-1,1-dioxo-2H-1λ(6),2-benzothia-zine-3-carboxyl-ate.

In the title compound, C(14)H(15)NO(5)S, the thia-zine ring adopts a sofa conformation and an intra-molecular O-H⋯O hydrogen bond forms an S(6) ring. In the crystal, molecules are linked viaC-H⋯O inter-actions.

Methyl 4-hy-droxy-1,1-dioxo-2-(2-phenyl-eth-yl)-2H-1λ,2-benzothia-zine-3-carboxyl-ate.

In the title compound, C(18)H(17)NO(5)S, the thia-zine ring adopts a half-chair conformation and the dihedral angle between the aromatic rings is 79.41 (6)°. An intra-molecular O-H⋯O hydrogen bond generates an S(6) ring. In the crystal, mol-ecules are linked by weak C-H⋯O inter-actions resulting in infinite sheets along the b and c axes.

N-(2-Bromo-phen-yl)-4-methyl-N-(4-methyl-phen-ylsulfon-yl)benzene-sulfonamide.

In the title compound, C(20)H(18)BrNO(4)S(2), the mean planes formed by the toluene substituents are inclined at a dihedral angle of 45.34 (8)°. The bromo-benzene group is disordered over two positions with an occupancy ratio of 0.74:0.26, resulting in two conformations of the ring; the two rings are oriented at a dihedral angle of 6.6 (6)° with each other. In the crystal structure, weak C-H⋯O inter-actions connect the mol-ecules in a zigzag manner along the a axis.

Miniemulsion synthesis of metal-oxo cluster containing copolymer nanobeads.

Hybrid nanobeads containing either a manganese-oxo or manganese-iron-oxo cluster have been prepared via the miniemulsion polymerization technique. Two new ligand substituted oxo clusters, Mn(12)O(12)(VBA)(16)(H(2)O)(4) and Mn(8)Fe(4)O(12)(VBA)(16)(H(2)O)(4) (where VBA = 4-vinylbenzoate), have been prepared and characterized. Polymerization of the functionalized metal-oxo clusters with styrene under miniemulsion conditions produced monodispersed polymer nanoparticles as small as ~60 nm in diameter. The metal-oxo polymer nanobeads were fully characterized in terms of synthetic parameters, composition, structure, and magnetic properties.

Methyl 4-hy-droxy-2-isopropyl-1,1-dioxo-2H-1,2-benzothia-zine-3-carboxyl-ate.

In the crystal structure of the title mol-ecule, C(13)H(15)NO(5)S, the S and N atoms of the thia-zine ring exihibit the maximum deviations from the least-squares plane of 0.3008 (6) and 0.3280 (7) Å, respectively. The ring therefore adopts a half chair conformation. The thia-zine ring is twisted by an angle of 13.29 (7)° with respect to the aromatic ring. The isopropyl substituent is oriented at a dihedral angle of 53.2 (12)° with respect to the thia-zine ring. An intra-molecular O-H⋯O hydrogen bond occurs. Inter-molecular hydrogen bonding is observed in the crystal structure.

Reversible phase transitions within self-assembled fibrillar networks of (R)-18-(n-alkylamino)octadecan-7-ols in their carbon tetrachloride gels.

The CCl(4) gel phases of a series of low-molecular-mass organogelators, (R)-18-(n-alkylamino)octadecan-7-ols (HSN-n, where n = 0-5, 18 is the alkyl chain length), appear to be unprecedented in that the fibrillar networks of some of the homologues undergo thermally reversible, gel-to-gel phase transitions, and some of those transitions are evident as opaque-transparent changes in the appearance of the samples. The gels have been examined at different concentrations and temperatures by a wide variety of spectroscopic, diffraction, thermal, and rheological techniques. Analyses of those data and data from the neat gelators have led to an understanding of the source of the gel-to-gel transitions. IR and SANS data implicate the expulsion (on heating the lower-temperature gel) or the inclusion (on cooling the higher-temperature gel) of molecules of CCl(4) that are interspersed between fibers in bundles. However, the root cause of the transitions is a consequence of changes in the molecular packing of the HSN-n within the fibers. This study offers opportunities to design new gelators that are capable of behaving in multiple fashions without entering the sol/solution phase, and it identifies a heretofore unknown transformation of organogels.

A cubic, 12-connected, microporous metal-organometallic phosphate framework sustained by truncated tetrahedral nodes.

A rare example of a microporous metal-organic phosphate, [Co(12)(L)(6)(µ(3)-PO(4))(4)(µ(3)-F)(4)(µ-H(2)O)(6)][NO(3)](2) (1), is synthesized by the reaction of a [(η(5)-C(5)H(5))Fe(II)](+)-functionalized terephthalate ligand with Co(NO(3))(2)·6H(2)O and phosphate and fluoride ions generated from the in situ hydrolysis of hexafluorophosphate. 1 is a cubic, 12-connected, face-centered cubic framework sustained by the linear connection of unprecedented, dodecanuclear truncated tetrahedral coordination clusters.

A water-soluble Xe@cryptophane-111 complex exhibits very high thermodynamic stability and a peculiar (129)Xe NMR chemical shift.

The known xenon-binding (±)-cryptophane-111 (1) has been functionalized with six [(η(5)-C(5)Me(5))Ru(II)](+) ([Cp*Ru](+)) moieties to give, in 89% yield, the first water-soluble cryptophane-111 derivative, namely [(Cp*Ru)(6)1]Cl(6) ([2]Cl(6)). [2]Cl(6) exhibits a very high affinity for xenon in water, with a binding constant of 2.9(2) × 10(4) M(-1) as measured by hyperpolarized (129)Xe NMR spectroscopy. The (129)Xe NMR chemical shift of the aqueous Xe@[2](6+) species (308 ppm) resonates over 275 ppm downfield of the parent Xe@1 species in (CDCl(2))(2) and greatly broadens the practical (129)Xe NMR chemical shift range made available by xenon-binding molecular hosts. Single crystal structures of [2][CF(3)SO(3)](6)·xsolvent and 0.75H(2)O@1·2CHCl(3) reveal the ability of the cryptophane-111 core to adapt its conformation to guests.