Unveiling the nature of supramolecular crown ether–C60 interactions

A series of exTTF-(crown ether)₂ receptors, designed to host C₆₀, has been prepared. The size of the crown ether and the nature of the heteroatoms have been systematically changed to fine tune the association constants. Electrochemical measurements and transient absorption spectroscopy assisted in corroborating charge transfer in the ground state and in the excited state, leading to the formation of radical ion pairs featuring lifetimes in the range from 12 to 21 ps. To rationalize the nature of the exTTF-(crown ether)₂·C₆₀ stabilizing interactions, theoretical calculations have been carried out, suggesting a synergetic interplay of donor–acceptor, π–π, n–π and CH···π interactions, which is the basis for the affinity of our novel receptors towards C₆₀.     

A catalytic asymmetric total synthesis of (–)-perophoramidine

We report a catalytic asymmetric total synthesis of the ascidian natural product perophoramidine. The synthesis employs a molybdenum-catalyzed asymmetric allylic alkylation of an oxindole nucleophile and a monosubstituted allylic electrophile as a key asymmetric step. The enantioenriched oxindole product from this transformation contains vicinal quaternary and tertiary stereocenters, and is obtained in high yield along with high levels of regio-, diastereo-, and enantioselectivity. To install the second quaternary stereocenter in the target, the route utilizes a novel regio- and diastereoselective allylation of a cyclic imino ether to deliver an allylated imino ether product in near quantitative yield and with complete regio- and diastereocontrol. Oxidative cleavage and reductive amination are used as final steps to access the natural product.     

Bypassing the lack of reactivity of endo-substituted norbornenes with the catalytic rectification–insertion mechanism

The catalytic 1,2-insertion polymerization of polar norbornenes (NBEs) leads to the formation of functional rigid macromolecules with exceptional thermal, optical and mechanical properties. However, this remarkable reaction is plagued by the low reactivity of the polar monomers, and most notably of those bearing a functional group in endo position. We have examined the polymerization mechanism of NBEs bearing one or two CO₂Me groups either in exo or endo position catalyzed by the so-called naked allyl Pd⁺ SbF₆^– catalyst (1). Although endo dimethyl ester of 5-norbornene-2,3-dicarboxylic acid (NBE(CO₂Me)₂) is polymerized by 1, two endo units are never inserted consecutively along the polymer chain. Indeed, 1 is a tandem catalyst which not only catalyzes the insertion of the monomer but also the isomerization of endo and exo isomers. Thus, the polymerization of endo monomers proceeds via a novel mechanism, coined rectification–insertion mechanism, whereby half of the endo monomers are rectified into exo ones prior insertion, leading to the formation of an alternating endo–exo copolymer using an endo only feedstock. With this mechanism, the lack of reactivity of endo norbornenes is bypassed, and the polymerization of predominantly endo polar NBEs bearing a variety of functionalities such as esters, imides, acids, aldehydes, alcohols, anhydrides, or alkyl bromides proceeds with catalyst loadings as low as 0.002 mol%.     

Thorium–ligand multiple bonds via reductive deprotection of a trityl group

Reaction of [Th(I)(NR₂)₃] (R = SiMe₃) (2) with KECPh₃ (E = O, S) affords the thorium chalcogenates, [Th(ECPh₃)(NR₂)₃] (3, E = O; 4, E = S), in moderate yields. Reductive deprotection of the trityl group from 3 and 4 by reaction with KC₈, in the presence of 18-crown-6, affords the thorium oxo complex, [K(18-crown-6)][Th(O)(NR₂)₃] (6), and the thorium sulphide complex, [K(18-crown-6)][Th(S)(NR₂)₃] (7), respectively. The natural bond orbital and quantum theory of atoms-in-molecules approaches are employed to explore the metal–ligand bonding in 6 and 7 and their uranium analogues, and in particular the relative roles of the actinide 5f and 6d orbitals.     

Long-lived charge carrier generation in ordered films of a covalent perylenediimide–diketopyrrolopyrrole–perylenediimide molecule

The photophysics of a covalently linked perylenediimide–diketopyrrolopyrrole–perylenediimide acceptor–donor–acceptor molecule (PDI–DPP–PDI, 1) were investigated and found to be markedly different in solution versus in unannealed and solvent annealed films. Photoexcitation of 1 in toluene results in quantitative charge separation in τ = 3.1 ± 0.2 ps, with charge recombination in τ = 340 ± 10 ps, while in unannealed/disordered films of 1, charge separation occurs in τ < 250 fs, while charge recombination displays a multiexponential decay in ∼6 ns. The absence of long-lived, charge separation in the disordered film suggests that few free charge carriers are generated. In contrast, upon CH₂Cl₂ vapor annealing films of 1, grazing-incidence X-ray scattering shows that the molecules form a more ordered structure. Photoexcitation of the ordered films results in initial formation of a spin-correlated radical ion pair (electron–hole pair) as indicated by magnetic field effects on the formation of free charge carriers which live for ∼4 μs. This result has significant implications for the design of organic solar cells based on covalent donor–acceptor systems and shows that long-lived, charge-separated states can be achieved by controlling intramolecular charge separation dynamics in well-ordered systems.     

Small molecule antagonists of cell-surface heparan sulfate and heparin–protein interactions

Surfen, bis-2-methyl-4-amino-quinolyl-6-carbamide, was previously reported as a small molecule antagonist of heparan sulfate (HS), a key cell-surface glycosaminoglycan found on all mammalian cells. To generate structure–activity relationships, a series of rationally designed surfen analogs was synthesized, where its dimeric structure, exocyclic amines, and urea linker region were modified to probe the role of each moiety in recognizing HS. An in vitro assay monitoring inhibition of fibroblast growth factor 2 binding to wild-type CHO cells was utilized to quantify interactions with cell surface HS. The dimeric molecular structure of surfen and its aminoquinoline ring systems was essential for its interaction with HS, and certain dimeric analogs displayed higher inhibitory potency than surfen and were also shown to block downstream FGF signaling in mouse embryonic fibroblast cells. These molecules were also able to antagonize other HS–protein interactions including the binding of soluble RAGE to HS. Importantly, selected molecules were shown to neutralize heparin and other heparinoids, including the synthetic pentasaccharide fondaparinux, in a factor Xa chromogenic assay and in vivo in mice. These results suggest that small molecule antagonists of heparan sulfate and heparin can be of therapeutic potential for the treatment of disorders involving glycosaminoglycan–protein interactions.     

Mechanical and optical properties of ultralarge flakes of a metal–organic framework with molecular thickness

The isolation of 2D-materials is already a success for graphene, graphene oxide, boron nitride and a few clays or metal chalcogenides, however despite the fact that some of them show very interesting physical properties, they lack useful functionalities. Metal–Organic Frameworks (MOFs) are multifunctional materials showing a wide range of physical and chemical properties that can be structurally designed by suitable selection of their building-blocks. This strategy may allow the production of layers with a variety of useful electronic and molecular recognition functionalities. Herein we isolate 2D-MOF flakes with areas of hundreds of square microns and an excellent control of the molecular thickness (from single up to ca. 50 layers). The samples exhibit such good photoluminescence and mechanical properties as to allow free-standing characterization of few layers’ flakes.     

Copper-catalyzed intermolecular C(sp3)–H bond functionalization towards the synthesis of tertiary carbamates

We describe the development of an intermolecular unactivated C(sp³)–H bond functionalization towards the direct synthesis of tertiary carbamates. The transformation proceeded using a readily available, abundant first-row transition metal catalyst (copper), and isocyanates as the source of the amide moiety. This is a novel strategy for direct transformation of a variety of unactivated hydrocarbon feedstocks to N-alkyl-N-aryl and N,N-dialkyl carbamates without pre-functionalization or installation of a directing group. The reaction had a broad substrate scope with 3° > 2° > 1° site selectivity. The reaction proceeded even on a gram scale, and a corresponding free amine was directly obtained when the reaction was performed at high temperature. Kinetic studies suggested that radical-mediated C(sp³)–H bond cleavage was the rate-determining step.     

Counterion influence on the N–I–N halogen bond

A detailed investigation of the influence of counterions on the [N–I–N]⁺ halogen bond in solution, in the solid state and in silico is presented. Translational diffusion coefficients indicate close attachment of counterions to the cationic, three-center halogen bond in dichloromethane solution. Isotopic perturbation of equilibrium NMR studies performed on isotopologue mixtures of regioselectively deuterated and nondeuterated analogues of the model system showed that the counterion is incapable of altering the symmetry of the [N–I–N]⁺ halogen bond. This symmetry remains even in the presence of an unfavorable geometric restraint. A high preference for the symmetric geometry was found also in the solid state by single crystal X-ray crystallography. Molecular systems encompassing weakly coordinating counterions behave similarly to the corresponding silver(i) centered coordination complexes. In contrast, systems possessing moderately or strongly coordinating anions show a distinctly different behavior. Such silver(i) complexes are converted into multi-coordinate geometries with strong Ag–O bonds, whereas the iodine centered systems remain linear and lack direct charge transfer interaction with the counterion, as verified by ¹⁵N NMR and DFT computation. This suggests that the [N–I–N]⁺ halogen bond may not be satisfactorily described in terms of a pure coordination bond typical of transition metal complexes, but as a secondary bond with a substantial charge-transfer character.     

Phase diagram of the selenium–sulfur system in the pressure range 1 × 10<Superscript>–5</Superscript>–1 × 10<Superscript>–1</Superscript> MPa

The partial pressures of the components in the saturated vapor of the Se–S system were determined and presented as the temperature–concentration dependences. Based on these data, the boundaries of the melt–vapor phase transition at atmospheric pressure and in vacuum (1350, 100, and 10 Pa) were calculated. A complete phase diagram was constructed, which included the vapor–liquid equilibrium fields at atmospheric and low pressures, whose boundaries allowed us to determine the behavior of sulfur and selenium during distillation separation.     

Electromagnetic properties of zinc–nickel ferrites in the frequency range of 0.05–10 GHz

Zn_x-1Ni_xFe₂O₄ samples have been synthesized by solid-state reactions. Data on the chemical composition and the surface morphology of the samples have been obtained using a scanning electron microscope. X-ray powder diffractometer has been used to establish the phase purity and to determine the unit cell parameters. It has been found that the obtained samples had the spinel structure with Fd-3m (No. 227) space group. The unit cell parameters decrease with increasing nickel concentration. The magnetic characteristics of the obtained samples are determined and discussed. The Curie point of obtained samples varies in the range of 803.5–572.7 K. The maximum spontaneous magnetization of ~74.6 emu/g at room temperature was fixed for the solid solution with x = 0.6. The maximum value of the μ^/real part of ~12 and μ^//imaginary part of 6 of the permeability in the frequency range of 50 MHz–10 GHz is observed for the composition with x = 0.3. The composite samples for microwave study were prepared by mixing the ferrite powders with molten paraffin wax. The largest value of the μ^/ real part of ~3 and μ^// imaginary part of 0.63 of permeability is found for the x = 0.4 composite. The formation of the composite significantly reduces permeability.     

Structure–activity relationship studies of cyclopropenimines as enantioselective Br?nsted base catalysts

We recently demonstrated that chiral cyclopropenimines are viable Brønsted base catalysts in enantioselective Michael and Mannich reactions. Herein, we describe a series of structure–activity relationship studies that provide an enhanced understanding of the effectiveness of certain cyclopropenimines as enantioselective Brønsted base catalysts. These studies underscore the crucial importance of dicyclohexylamino substituents in mediating both reaction rate and enantioselectivity. In addition, an unusual catalyst CH···O interaction, which provides both ground state and transition state organization, is discussed. Cyclopropenimine stability studies have led to the identification of new catalysts with greatly improved stability. Finally, additional demonstrations of substrate scope and current limitations are provided herein.     

Asymmetric C–H functionalization of cyclopropanes using an isoleucine-NH2 bidentate directing group

The systematic investigation of substrate-bound α-amino acid auxiliaries has resulted in catalytic asymmetric C–H functionalization of cyclopropanes enabled by amino acid amides as chiral bidentate directing groups. The use of an Ile-NH₂ auxiliary embedded in the substrate provided excellent levels of asymmetric induction (diastereomeric ratio of up to 72 : 1) in the Pd(ii)-catalyzed β-methylene C(sp³)–H bond activation of cyclopropanes and cross-coupling with aryl iodides.     

Cytocompatible in situ cross-linking of degradable LbL films based on thiol–exchange reaction

Formation of both mechanically durable and programmably degradable layer-by-layer (LbL) films in a biocompatible fashion has potential applications in cell therapy, tissue engineering, and drug-delivery systems, where the films are interfaced with living cells. In this work, we developed a simple but versatile method for generating in situ cross-linked and responsively degradable LbL films, based on the thiol–exchange reaction, under highly cytocompatible conditions (aqueous solution at pH 7.4 and room temperature). The cytocompatibility of the processes was confirmed by coating individual yeast cells with the cross-linked LbL films and breaking the films on demand, while maintaining the cell viability. In addition, the processes were applied to the controlled release of an anticancer drug in the HeLa cells.     

Consecutive C–F bond activation and C–F bond formation of heteroaromatics at rhodium: the peculiar role of FSi(OEt)3

C–F activation of 2,3,5,6-tetrafluoropyridine at [Rh{Si(OEt)₃}(PEt₃)₃] (1) yields [Rh{2-(3,5,6-C₅F₃HN)}(PEt₃)₃] (2) and FSi(OEt)₃, but in an unprecedented consecutive reaction FSi(OEt)₃ acts as a fluoride source to give [Rh(4-C₅F₄N)(PEt₃)₃] (4) by regeneration of the C–F bond and C–H activation. Analogous refluorination steps were observed for other 2-pyridyl rhodium complexes. NMR spectroscopic studies revealed a delicate balance between the feasibility for C–F bond formation accompanied by a C–H activation and the occurrence of competing reactions such as hydrodefluorinations induced by the intermediary presence of H₂.     

Enantioselective installation of adjacent tertiary benzylic stereocentres using lithiation–borylation–protodeboronation methodology. Application to the synthesis of bifluranol and fluorohexestrol

1,2-Diaryl ethanes bearing 1,2-stereogenic centres show interesting biological activity but their stereocontrolled synthesis has not been reported forcing a reliance of methods involving diastereomer and enantiomer separation. We have found that this class of molecules can be prepared with very high stereocontrol using lithiation–borylation methodology. The reaction of an enantioenriched benzylic lithiated carbamate with an enantioenriched benzylic secondary pinacol boronic ester gave a tertiary boronic ester with complete diastereo- and enantiocontrol. It was essential to use MgBr₂/MeOH after formation of the boronate complex, both to promote the 1,2-migration and to trap any lithiated carbamate/benzylic anion that formed from fragmentation of the ate complex, anions that would otherwise racemise and re-form the boronate complex eroding both er and dr of the product. When the benzylic lithiated carbamate and benzylic secondary pinacol boronic ester were too hindered, boronate complex did not even form. In these cases, it was found that the use of the less hindered neopentyl boronic esters enabled successful homologation to take place even for the most hindered reaction partners, with high stereocontrol and without the need for additives. Protodeboronation of the product boronic esters with TBAF gave the target 1,2-diaryl ethanes bearing 1,2-stereogenic centres. The methodology was applied to the stereocontrolled synthesis of bifluranol and fluorohexestrol in just 7 and 5 steps, respectively.     

A carbon–carbon hybrid – immobilizing carbon nanodots onto carbon nanotubes

The thrust of this work is to integrate small and uniformly sized carbon nanodots (CNDs) with single-walled carbon nanotubes (SWCNT) of different diameters as electron donors and electron acceptors, respectively, and to test their synergetic interactions in terms of optoelectronic devices. CNDs (denoted pCNDs, where p indicates pressure) were prepared by pressure-controlled microwave decomposition of citric acid and urea. pCNDs were immobilized on single-walled carbon nanotubes by wrapping the latter with poly(4-vinylbenzyl trimethylamine) (PVBTA), which features positively charged ammonium groups in the backbone. Negatively charged surface groups on the CNDs lead to attractive electrostatic interactions. Ground state interactions between the CNDs and SWCNTs were confirmed by a full-fledged photophysical investigation based on steady-state and time-resolved techniques. As a complement, charge injection into the SWCNTs upon photoexcitation was investigated by ultra-short time-resolved spectroscopy.     

Synthesis of (diarylmethyl)amines using Ni-catalyzed arylation of C(sp3)–H bonds

The first nickel catalyzed deprotonative cross coupling between C(sp³)–H bonds and aryl chlorides is reported, allowing the challenging arylation of benzylimines in the absence of directing group or stoichiometric metal activation. This methodology represents a convenient access to the (diarylmethyl)amine moiety, which is widespread in pharmaceutically relevant compounds.     

Heterometallic titanium–gold complexes inhibit renal cancer cells in vitro and in vivo

Following recent work on heterometallic titanocene–gold complexes as potential chemotherapeutics for renal cancer, we report here on the synthesis, characterization and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = S–C₆H₄–COO^–) bound to gold(i)-phosphane fragments through a thiolate group [(η-C₅H₅)₂TiMe(μ-mba)Au(PR₃)]. The compounds are more stable in physiological media than those previously reported and are highly cytotoxic against human cancer renal cell lines. We describe here preliminary mechanistic data involving studies on the interaction of selected compounds with plasmid (pBR322) DNA used as a model nucleic acid, and with selected protein kinases from a panel of 35 protein kinases having oncological interest. Preliminary mechanistic studies in Caki-1 renal cells indicate that the cytotoxic and anti-migration effects of the most active compound 5 [(η-C₅H₅)₂TiMe(μ-mba)Au(PPh₃)] involve inhibition of thioredoxin reductase and loss of expression of protein kinases that drive cell migration (AKT, p90-RSK, and MAPKAPK3). The co-localization of both titanium and gold metals (1 : 1 ratio) in Caki-1 renal cells was demonstrated for 5 indicating the robustness of the heterometallic compound in vitro. Two compounds were selected for further in vivo studies on mice based on their selectivity in vitro against renal cancer cell lines when compared to non-tumorigenic human kidney cell lines (HEK-293T and RPTC) and the favourable preliminary toxicity profile in C57BL/6 mice. Evaluation of Caki-1 xenografts in NOD.CB17-Prkdc SCID/J mice showed an impressive tumor reduction (67%) after treatment for 28 days (3 mg per kg per every other day) with heterometallic compound 5 as compared with the previously described [(η-C₅H₅)₂Ti{OC(O)-4-C₆H₄-P(Ph₂)AuCl}₂] 3 which was non-inhibitory. These findings indicate that structural modifications on the ligand scaffold affect the in vivo efficacy of this class of compounds.     

Three-phase junction for modulating electron–hole migration in anatase–rutile photocatalysts

The heterophase solid–solid junction as an important type of structure unit has wide applications for its special mechanics and electronic properties. Here we present a first three-phase atomic model for the anatase–rutile TiO₂ heterophase junction and determine its optical and electronic properties, which leads to resolution of the long-standing puzzles on the enhanced photocatalytic activity of anatase–rutile photocatalysts. By using a set of novel theoretical methods, including crystal phase transition pathway sampling, interfacial strain analysis and first principles thermodynamics evaluation of holes and electrons, we identify an unusual structurally ordered three-phase junction, a layer-by-layer “T-shaped” anatase/TiO₂-II/rutile junction, for linking anatase with rutile. The intermediate TiO₂-II phase, although predicted to be only a few atomic layers thick in contact with anatase, is critical to alleviate the interfacial strain and to modulate photoactivity. We demonstrate that the three-phase junction acts as a single-way valve allowing the photogenerated hole transfer from anatase to rutile but frustrating the photoelectron flow in the opposite direction, which otherwise cannot be achieved by an anatase–rutile direct junction. This new model clarifies the roles of anatase, rutile and the phase junction in achieving high photoactivity synergistically and provides the theoretical basis for the design of better photocatalysts by exploiting multi-phase junctions.