Aaron Sattler

Cleaving carbon-carbon bonds by inserting tungsten into unstrained aromatic rings.

The cleavage of C–H and C–C bonds by transition metal centres is of fundamental interest and plays an important role in the synthesis of complex organic molecules from petroleum feedstocks. But while there are many examples for the oxidative addition of C–H bonds to a metal centre, transformations that feature oxidative addition of C–C bonds are rare. The paucity of transformations that involve the cleavage of C–C rather than C–H bonds is usually attributed to kinetic factors arising from the greater steric hindrance and the directional nature of the spn hybrids that form the C–C bond, and to thermodynamic factors arising from the fact that M–C bonds are weaker than M–H bonds. Not surprisingly, therefore, most examples of C–C bond cleavage either avoid the kinetic limitations by using metal compounds in which the C–C bond is held in close proximity to the metal centre, or avoid the thermodynamic limitations by using organic substrates in which the cleavage is accompanied by either a relief of strain energy or the formation of an aromatic system. Here, we show that a tungsten centre can be used to cleave a strong C–C bond that is a component of an unstrained 6-membered aromatic ring. The cleavage is enabled by the formation of an unusual chelating di(isocyanide) ligand, which suggests that other metal centres with suitable ancillary ligands could also accomplish the cleavage of strong C–C bonds of aromatic substrates and thereby provide new ways of functionalizing such molecules.

Shape-shifting in contorted dibenzotetrathienocoronenes

We detail a general method for the synthesis of dibenzotetrathienocoronenes and elucidate their solid state structures in crystals and co-crystals. The contorted dibenzotetrathienocoronene (c-DBTTC) is a tetrathiophene-fused version of the previously studied contorted hexabenzocoronenes (c-HBC). The synthesis detailed here is simple and provides easy access to this important class of materials. We have found that these materials display molecular flexibility and tunable supramolecular self-assembly properties in the solid state by shifting molecular conformations between two different conformations. Depending on the conditions under which a c-DBTTC-containing material crystallizes, the c-DBTTC adopts either the “up-down” or the “butterfly” conformation. When grown from the vapor phase, crystals of the unsubstituted c-DBTTC show the molecule only in the up-down conformation, and it packs into dense crystals containing columnar arrays with close intracolumnar packing. The packing is controlled by the inherent molecular corrugation of the three-dimensional core and sulfur–sulfur interactions. When grown as co-crystals with electron acceptors from solution, the butyl-substituted c-DBTTC either adopts the butterfly conformation when the electron acceptor is small enough to be completely enveloped (TCNQ) or the up-down conformation when the electron acceptor is relatively large (C60). When grown from organic solvent crystals of the butyl-substituted c-DBTTC contain molecules of the solvent as the only guest, and we observe both conformations of the c-DBTTC. Controlling the supramolecular structure is the key to developing these materials for electronic applications.

Searching for New Chemotherapies for Tropical Diseases: Ruthenium-Clotrimazole Complexes Display High in vitro Activity Against Leishmania major and Trypanosoma cruzi and Low Toxicity Toward Normal Mammalian Cells

Eight new ruthenium complexes of clotrimazole (CTZ) with high antiparasitic activity have been synthesized, cis,fac-[Ru(II)Cl(2)(DMSO)(3)(CTZ)] (1), cis,cis,trans-[Ru(II)Cl(2)(DMSO)(2)(CTZ)(2)] (2), Na[Ru(III)Cl(4)(DMSO)(CTZ)] (3), Na[trans-Ru(III)Cl(4)(CTZ)(2)] (4), [Ru(II)(η(6)-p-cymene)Cl(2)(CTZ)] (5), [Ru(II)(η(6)-p-cymene)(bipy)(CTZ)][BF(4)](2) (6), [Ru(II)(η(6)-p-cymene)(en)(CTZ)][BF(4)](2) (7), and [Ru(II)(η(6)-p-cymene)(acac)(CTZ)][BF(4)] (8) (bipy = bipyridine; en = ethlylenediamine; acac = acetylacetonate). The crystal structures of compounds 4-8 are described. Complexes 1-8 are active against promastigotes of Leishmania major and epimastigotes of Trypanosoma cruzi. Most notably, complex 5 increases the activity of CTZ by factors of 110 and 58 against L. major and T. cruzi, with no appreciable toxicity to human osteoblasts, resulting in nanomolar and low micromolar lethal doses and therapeutic indexes of 500 and 75, respectively. In a high-content imaging assay on L. major-infected intraperitoneal mice macrophages, complex 5 showed significant inhibition on the proliferation of intracellular amastigotes (IC(70) = 29 nM), while complex 8 displayed some effect at a higher concentration (IC(40) = 1 μM).

Photovoltaic Universal Joints: Ball‐and‐Socket Interfaces in Molecular Photovoltaic Cells

A new approach toward higher efficiency organic photovoltaic devices (OPVs) is described. Complementarity in shape between the donor (contorted hexabenzocoronene, see picture) and acceptor (buckminsterfullerene) molecules results in OPVs that perform surprisingly well. This exploitation of host-guest chemistry at the organic/organic interface demonstrates a new direction for OPV device design.

Metal-drug synergy: new ruthenium(II) complexes of ketoconazole are highly active against Leishmania major and Trypanosoma cruzi and nontoxic to human or murine normal cells.

In our ongoing search for new metal-based chemotherapeutic agents against leishmaniasis and Chagas disease, six new ruthenium–ketoconazole (KTZ) complexes have been synthesized and characterized, including two octahedral coordination complexes—cis,fac-[RuIICl2(DMSO)3(KTZ)] (1) and cis-[RuIICl2(bipy)(DMSO)(KTZ)] (2) (where DMSO is dimethyl sulfoxide and bipy is 2,2′-bipyridine)—and four organometallic compounds—[RuII(η6-p-cymene)Cl2(KTZ)] (3), [RuII(η6-p-cymene)(en)(KTZ)][BF4]2 (4), [RuII(η6-p-cymene)(bipy)(KTZ)][BF4]2 (5), and [RuII(η6-p-cymene)(acac)(KTZ)][BF4] (6) (where en is ethylenediamine and acac is acetylacetonate); the crystal structure of 3 is described. The central hypothesis of our work is that combining a bioactive compound such as KTZ and a metal in a single molecule results in a synergy that can translate into improved activity and/or selectivity against parasites. In agreement with this hypothesis, complexation of KTZ with RuII in compounds 3–5 produces a marked enhancement of the activity toward promastigotes and intracellular amastigotes of Leishmania major, when compared with uncomplexed KTZ, or with similar ruthenium compounds not containing KTZ. Importantly, the selective toxicity of compounds 3–5 toward the leishmania parasites, in relation to human fibroblasts and osteoblasts or murine macrophages, is also superior to the selective toxicities of the individual constituents of the drug. When tested against Trypanosoma cruzi epimastigotes, some of the organometallic complexes displayed activity and selectivity comparable to those of free KTZ. A dual-target mechanism is suggested to account for the antiparasitic properties of these complexes.

Carbon—Sulfur Bond Cleavage and Hydrodesulfurization of Thiophenes by Tungsten

The reactions of W(PMe(3))(4)(η(2)-CH(2)PMe(2))H, W(PMe(3))(5)H(2), W(PMe(3))(4)H(4) and W(PMe(3))(3)H(6) towards thiophenes reveal that molecular tungsten compounds are capable of achieving a variety of transformations that are relevant to hydrodesulfurization. For example, sequential treatment of W(PMe(3))(4)(η(2)-CH(2)PMe(2))H with thiophene and H(2) yields the butanethiolate complex, W(PMe(3))(4)(SBu(n))H(3), which eliminates but-1-ene at 100 °C. Likewise, sequential treatment of W(PMe(3))(4)(η(2)-CH(2)PMe(2))H with benzothiophene and H(2) yields W(PMe(3))(4)(SC(6)H(4)Et)H(3), which releases ethylbenzene at 100 °C. Moreover, W(PMe(3))(4)(η(2)-CH(2)PMe(2))H desulfurizes dibenzothiophene to form a dibenzometallacyclopentadiene complex, [(κ(2)-C(12)H(8))W(PMe(3))](μ-S)(μ-CH(2)PMe(2))(μ-PMe(2))[W(PMe(3))(3)].

Multiple Modes for Coordination of Phenazine to Molybdenum: Ring Fusion Promotes Access to η4-Coordination, Oxidative Addition of Dihydrogen and Hydrogenation of Aromatic Nitrogen Compounds

Mo(PMe(3))(6) reacts with phenazine (PhzH) to give (eta(6)-C(6)-PhzH)Mo(PMe(3))(3), (mu-eta(6),eta(6)-PhzH)[Mo(PMe(3))(3)](2) and (eta(4)-C(4)-PhzH)(2)Mo(PMe(3))(2), each of which displays previously unknown coordination modes for phenazine. Both mononuclear (eta(6)-C(6)-PhzH)Mo(PMe(3))(3) and dinuclear (mu-eta(6),eta(6)-PhzH)[Mo(PMe(3))(3)](2) react with H(2) at room temperature to give the respective dihydride complexes, (eta(4)-C(4)-PhzH)Mo(PMe(3))(3)H(2) and (mu-eta(6),eta(4)-PhzH)[Mo(PMe(3))(3)][Mo(PMe(3))(3)H(2)]. A comparison of (eta(6)-C(6)-PhzH)Mo(PMe(3))(3) with the anthracene (AnH) and acridine (AcrH) counterparts, (eta(6)-AnH)Mo(PMe(3))(3) and (eta(6)-C(6)-AcrH)Mo(PMe(3))(3), indicates that oxidative addition of H(2) is promoted by incorporation of nitrogen substituents into the central ring. Furthermore, comparison of (eta(6)-C(6)-PhzH)Mo(PMe(3))(3) with the quinoxaline (QoxH) analogue, (eta(6)-C(6)-QoxH)Mo(PMe(3))(3), indicates that ring fusion also promotes oxidative addition of H(2). The mononitrogen quinoline (QH) and acridine compounds, (eta(6)-C(6)-QH)Mo(PMe(3))(3) and (eta(6)-C(6)-AcrH)Mo(PMe(3))(3), which respectively possess two and three fused six-membered rings, exhibit a similar trend, with the former being inert towards H(2), while the latter reacts rapidly to yield (eta(4)-C(4)-AcrH)Mo(PMe(3))(3)H(2). Ring fusion also promotes hydrogenation of the heterocyclic ligand, with (eta(6)-C(6)-AcrH)Mo(PMe(3))(3) releasing 9,10-dihydroacridine upon treatment with H(2) in benzene at 95 degrees C. Furthermore, catalytic hydrogenation of acridine to a mixture of 9,10-dihydroacridine and 1,2,3,4-tetrahydroacridine may be achieved by treatment of (eta(6)-C(6)-AcrH)Mo(PMe(3))(3) with acridine and H(2) at 95 degrees C.

Synthesis of polynitroxides based on nucleophilic aromatic substitution.

The scope and limitations of the synthesis of polynitroxides by nucleophilic substitution of electron-deficient fluorinated aromatic compounds are described. The method provides a facile route to the formation of polynitroxides exhibiting strong electron exchange between nitroxide groups.

Electronic Excited States of Tungsten(0) Arylisocyanides.

W(CNAryl)6 complexes containing 2,6-diisopropylphenyl isocyanide (CNdipp) are powerful photoreductants with strongly emissive long-lived excited states. These properties are enhanced upon appending another aryl ring, e.g., W(CNdippPh(OMe2))6; CNdippPh(OMe2) = 4-(3,5-dimethoxyphenyl)-2,6-diisopropylphenylisocyanide (Sattler et al. J. Am. Chem. Soc. 2015, 137, 1198-1205). Electronic transitions and low-lying excited states of these complexes were investigated by time-dependent density functional theory (TDDFT); the lowest triplet state was characterized by time-resolved infrared spectroscopy (TRIR) supported by density functional theory (DFT). The intense absorption band of W(CNdipp)6 at 460 nm and that of W(CNdippPh(OMe2))6 at 500 nm originate from transitions of mixed ππ*(C≡N-C)/MLCT(W → Aryl) character, whereby W is depopulated by ca. 0.4 e(-) and the electron-density changes are predominantly localized along two equatorial molecular axes. The red shift and intensity rise on going from W(CNdipp)6 to W(CNdippPh(OMe2))6 are attributable to more extensive delocalization of the MLCT component. The complexes also exhibit absorptions in the 300-320 nm region, owing to W → C≡N MLCT transitions. Electronic absorptions in the spectrum of W(CNXy)6 (Xy = 2,6-dimethylphenyl), a complex with orthogonal aryl orientation, have similar characteristics, although shifted to higher energies. The relaxed lowest W(CNAryl)6 triplet state combines ππ* excitation of a trans pair of C≡N-C moieties with MLCT (0.21 e(-)) and ligand-to-ligand charge transfer (LLCT, 0.24-0.27 e(-)) from the other four CNAryl ligands to the axial aryl and, less, to C≡N groups; the spin density is localized along a single Aryl-N≡C-W-C≡N-Aryl axis. Delocalization of excited electron density on outer aryl rings in W(CNdippPh(OMe2))6 likely promotes photoinduced electron-transfer reactions to acceptor molecules. TRIR spectra show an intense broad bleach due to ν(C≡N), a prominent transient upshifted by 60-65 cm(-1), and a weak down-shifted feature due to antisymmetric C≡N stretch along the axis of high spin density. The TRIR spectral pattern remains unchanged on the femtosecond-nanosecond time scale, indicating that intersystem crossing and electron-density localization are ultrafast (<100 fs).

Functionalizing molecular wires: a tunable class of α,ω-diphenyl-μ,ν-dicyano-oligoenes

We describe the synthesis and characterization of a new class of cyano-functionalized oligoenes and their derivatives. We have made the vinylogous series of α,ω-diphenyl-μ,ν-dicyano-oligoenes (DPDCn) comprised of each odd-numbered member from 3 to 13 linear conjugated olefins. Installing cyano groups onto the oligoene backbone lowers HOMO and LUMO energies by up to ∼0.7 eV, thereby stabilizing the molecule with respect to oxidative decomposition; this exemplifies a new approach to the stabilization of conjugated oligoenes. UV-vis absorption spectra and redox potentials across the DPDCn series reveal that the molecular band gap ranges from 2.80 to 1.75 eV. This gap can be further tuned by the facile installation of a variety of aryl end-groups. The choice of end-groups also greatly affects the physical properties such as solubility and the solid-state packing. We also present the longest oligoene crystal structure reported to date. Moreover, we find that the prototypical linear structure makes oligoenes suitable as molecular wires and connectors in the bottom-up construction of nanoscale architectures. As a proof of concept, carboxylic acid terminated oligoenes were used to position 10-nm Fe3O4 nanoparticles on a GaAs (100) substrate.