Supramolecular control of selectivity in transition-metal catalysis through substrate preorganization

Supramolecular chemistry exploits multiple weak intermolecular interactions to assemble nano-sized molecular architectures, providing new possibilities for (transition metal) catalyst development. In this Perspective we focus on the application of such weak (directional) interactions between a substrate molecule and a (bifunctional) catalyst for structural preorganization prior to the catalytic reaction. As we discuss, such effects together with the confinement properties of the nano-space of the 'active sites' play a crucial role for the exceptional selectivities and activities of natural enzymes. We will elaborate on the application of such supramolecular strategy to the more traditional transition-metal catalysis, and we will compare it with the traditional substrate preorganization methods. Subsequently, literature examples of such bifunctional catalyst systems will be described in which the function of weak interactions was carefully designed a priori, as well as, the serendipitously found catalysts in which the presence of supramolecular effects was recognized post factum. The discussed examples demonstrate the power of the strategy for the control of selectivity in various types of metal catalyzed reactions, and the observation of the serendipitous findings can help to generate new leads for more efficient catalyst design

Synthesis and evaluation of fluorimetric and colorimetric chemosensors for anions based on (oligo)thienyl-thiosemicarbazones

A family of heterocyclic thiosemicarbazone dyes (3a-d) containing thienyl groups has been synthesized, characterized and their chromo-fluorogenic response in acetonitrile in the presence of selected anions studied. Acetonitrile solutions of 3a-d show absorption bands in the 338-425 nm range which are modulated by the groups attached to the thiosemicarbazone moiety. The fluoride, chloride, bromide, iodide, dihydrogen phosphate, hydrogen sulfate, nitrate, acetate and anions were used in the recognition studies. Only sensing features were observed for fluoride, cyanide, acetate and dihydrogen phosphate anions. Two different chromogenic responses were found, (i) a small shift of the absorption band due to coordination of the anions with the thiourea protons and (ii) the appearance of a new red shifted band due to deprotonation of the receptor. For the latter process changes in the color solutions from pale-yellow to orange-red were observed. Fluorescence studies showed a different emission behavior according to the number of thienyl rings in the π-conjugated bridges. Stability constants for the two processes (complex formation + deprotonation) for receptors 3a-d in the presence of fluoride and acetate anions were determined from spectrophotometric titrations using the HypSpec program. The interaction of 3d with fluoride was also studied through 1H NMR titrations. Semiempirical calculations to evaluate the hydrogen-donating ability of the receptors were also performed.Fundação para a Ciência e a Tecnologia (FCT) , Acções Integradas Luso-Espanholas/CRUP, Generalitat Valenci

Enantioselective, intermolecular benzylic C–H amination catalysed by an engineered iron-haem enzyme

C–H bonds are ubiquitous structural units of organic molecules. Although these bonds are generally considered to be chemically inert, the recent emergence of methods for C–H functionalization promises to transform the way synthetic chemistry is performed. The intermolecular amination of C–H bonds represents a particularly desirable and challenging transformation for which no efficient, highly selective, and renewable catalysts exist. Here we report the directed evolution of an iron-containing enzymatic catalyst—based on a cytochrome P450 monooxygenase—for the highly enantioselective intermolecular amination of benzylic C–H bonds. The biocatalyst is capable of up to 1,300 turnovers, exhibits excellent enantioselectivities, and provides access to valuable benzylic amines. Iron complexes are generally poor catalysts for C–H amination: in this catalyst, the enzyme's protein framework confers activity on an otherwise unreactive iron-haem cofactor

A study of anion binding behaviour of 1,3-alternate thiacalix[4]arene-based receptors bearing urea moieties

© 2016 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique. Three novel thiacalix[4]arene receptors 4 a-c each with a 1,3-alternate conformation and possessing two urea moieties linking various phenyl groups substituted with either para electron-donating or -withdrawing groups have been synthesized. The binding properties of these receptors were investigated by means of 1 H NMR spectroscopy and UV-vis absorption titration experiments using various anions. The structures and complexation energies were also studied by density functional theory (DFT) methods. The results suggested that receptor 4 c , which possesses two p-(trifluoromethyl)phenyl ureido moieties, can complex most efficiently in the urea cavity and exhibits high selectivity towards F - and AcO - ions

Supramolecular Catalysis in the Synthesis of Substituted 1H-Tetrazoles from Isonitriles by a Self-Assembled Hexameric Capsule

The synthesis of substituted 1H-tetrazoles from aliphatic or aromatic isonitriles and trimethylsilyl azide can be efficiently promoted by the hexameric capsule of resorcin[ 4]arene as a supramolecular self-assembled catalyst. The reaction is sensitive to the size and nature of the substrate and is driven by encapsulation of the reagents within the cavity of the supramolecular catalyst.The synthesis of substituted 1H-tetrazoles from aliphatic or aromatic isonitriles and trimethylsilyl azide can be efficiently promoted by the hexameric capsule of resorcin[4]arene as a supramolecular self-assembled catalyst. The reaction is sensitive to the size and nature of the substrate and is driven by encapsulation of the reagents within the cavity of the supramolecular catalyst

High iso aldehyde selectivity in the hydroformylation of short-chain alkenes

The authors thank the Eastman Chemical Company for funding (LI, and later JAF) and permission to publish. The EPSRC (EP/M003868/1) is also acknowledged for funding (JAF).The hydroformylation of propene to give predominantly iso‐butanal has been achieved; class‐leading selectivity is possible even at higher temperatures that deliver fast conversion. Racemic rhodium complexes of bidentate phospholane phosphites derived from tropos‐biphenols and unusual solvent systems are the key to the selectivity observed.PostprintPeer reviewe

A Shape‐Adaptable Organometallic Supramolecular Coordination Cage for the Encapsulation of Fullerenes

The development of three‐dimensional supramolecular coordination complexes (SCCs), with cavities suitable for guest binding, is of great interest because these materials are useful in a large number of applications. Herein, a nickel‐conjoined organometallic molecular prism is described, which has been fully characterized. The X‐ray diffraction structure of the molecule reveals that the cage possesses an internal cavity with a volume of 1028 Å3, thus suitable for the encapsulation of large 3D‐molecules, such as fullerenes. This cage shows highly selective complexation of C70 over C60, thus being potentially useful for fullerene separation and purification. The combined experimental and computational studies suggest that the complexation process is largely entropically‐driven, and DFT calculations suggest that the cage is flexible and can adapt the size and the shape of the cavity to maximize the face‐to‐face interaction with the fullerenes

Positive and negative allosteric effects of thiacalix[4]arene-based receptors having urea and crown-ether moieties

Heteroditopic receptors (4ₐ₋ₑ) based on a thiacalix[4]arene in the 1,3-alternate conformation, which have two urea moieties linking various phenyl groups substituted with either electron-donating or -withdrawing groups at their m-, or p-positions with a crown-ether moiety at the opposite side of the thiacalix[4]arene cavity, have been synthesized. The two examples with p-CH₃– (4b) and p-NO₂-substituted (4ₑ) phenyl groups have been characterized by X-ray crystallography. The binding properties of receptor 4ₑ were investigated by means of ¹H NMR spectroscopic and absorption titration experiments in CHCl₃–DMSO (10:1, v/v) solution in the presence of K⁺ ions and various anions. Interestingly, it was found that receptor 4ₑ, which possesses two p-nitrophenyl ureido moieties, can complex most efficiently in the urea cavity or the crown-ether moiety; and the plausible allosteric effect of receptor 4ₑ was also studied

Directed Evolution of an Artificial Imine Reductase

Artificial metalloenzymes, resulting from incorporation of a metal cofactor within a host protein, have received increasing attention in the last decade. The directed evolution is presented of an artificial transfer hydrogenase (ATHase) based on the biotin-streptavidin technology using a straightforward procedure allowing screening in cell-free extracts. Two streptavidin isoforms were yielded with improved catalytic activity and selectivity for the reduction of cyclic imines. The evolved ATHases were stable under biphasic catalytic conditions. The X-ray structure analysis reveals that introducing bulky residues within the active site results in flexibility changes of the cofactor, thus increasing exposure of the metal to the protein surface and leading to a reversal of enantioselectivity. This hypothesis was confirmed by a multiscale approach based mostly on molecular dynamics and protein-ligand dockings

Synthesis and evaluation of thiosemicarbazones functionalized with furyl moieties as new chemosensors for anion recognition

A family of heterocyclic thiosemicarbazone dyes (3a-f and 4) containing furyl groups were synthesized in good yields, characterized and their response in acetonitrile in the presence of selected anions was studied. Acetonitrile solutions of 3a-f and 4 show absorption bands in the 335-396 nm range which are modulated by the electron donor or acceptor strength of the heterocyclic systems appended to the thiosemicarbazone moiety. Fluoride, chloride, bromide, iodide, dihydrogen phosphate, hydrogen sulphate, nitrate, acetate and cyanide anions, were used in recognition studies. From these anions, only sensing features were seen for fluoride, cyanide, acetate and dihydrogen phosphate. Two clearly different chromo-fluorogenic behaviours were observed, (i) a small shift of the absorption band due to the coordination of the anions with the thiourea protons and (ii) the appearance of a new red shifted band due to deprotonation. For the latter effect, a change in the colour solution from pale yellow to purple was observed. Fluorescence studies were also in agreement with the different effects observed in the UV/Vis titrations. In this case, hydrogen bonding interactions were visible through the enhancement of the emission band, whereas deprotonation induced the appearance of a new red-shifted emission. Logarithms of stability constants for the two processes (complex formation + deprotonation) for receptors 3a-f in the presence of fluoride and acetate anions were determined from spectrophotometric titrations using the HypSpec V1.1.18 program. Semi-empirical calculations to evaluate the hydrogen-donating ability of the receptors and a prospective electrochemical characterization of compound 3b in the presence of fluoride were also performed.Fundação para a Ciência e a Tecnologia (FCT), Acções Integradas Luso-espanholas/CRUP, Generalitat Valenciana