Metal centers associated with cavities have attracted much attention, mainly because of their resemblance to metalloenzymes.[1] Among concave molecules with a cavity, cyclodextrins (CDs) are unique owing to their natural occurrence, their hydrosolubility, and the structure of their cavity. Unlike any other cavity, in particular those based on aromatic rings, their interior is carpeted with hydrogen atoms, which confer hydrophobicity and introduce additional van der Waals interactions. Therefore, CDs are widely used to host hydrophobic molecules in polar solvents. The possibility of converting cyclodextrins into enzyme mimics very soon attracted the interest of scientists.[2] More specifically, for CDs to be used to mimic metalloenzymes, a metal must be attached to the CD scaffold. [3] Owing to the size of the cavity, two different ways to append the metal can be considered for the study of two different phenomena. First, the metal can be positioned at the entrance of the cavity to exploit the inclusion ability of the cavity in its interaction with a substrate and mimic the binding pocket of an enzyme (Figure 1 a).Second, the metal can be encapsulated inside the cavity to study the effect of confinement on its coordination sphere and chemical properties; this arrangement mimics the environment of a metal buried deeply within a folded protein (Figure 1 b).The first kind of design has been widely studied, often with the attachment of a metal-ligand unit through a single linkage.[3] Such structures can be used in a multitude of applications, for example, in catalysis.[4] However, for the metal center to be fixed directly above the cavity, double linkage of the metal was necessary. In the resulting so-called metal-capped CDs, [5,6] the metal ion is located right on top of the CD cavity.[7] The deepest position in which the metal has been placed so far intercepts the plane defined by the C-6 atoms of the sugar units. [8,9] This metal position leaves the cavity available for the inclusion of guests. The cavity can thus serve as a host for substrates (the interaction of which with the metal center can lead to an acceleration of the reaction rate [10] in analogy with an enzymatic reaction), as a probe for ligand exchange, [8] or as a second coordination sphere through C À H···X À M interactions. [11] For metallocyclodextrins of the second kind, in which the metal center occupies the middle of the cavity like an included guest, typically at the level of the H-5 atoms, only noncovalent inclusion complexes of metal ions have been described so far. Their electrochemical properties have been studied thoroughly, and electron transfer is thought not to involve the included complex, but the free portion of nonincluded metallic guest ions.[12] In other words, no studies on cyclodextrin complexes in which the metal ion is forced through covalent bonding to be included deep inside the Figure 1. In a metal-capped cyclodextrin, the cavity interacts either a) with the substrate or b) with the metal, depending on the depth of inclusion....

International audienceIntroduced in the late sixties, non-innocent (or redox) ligands have been extensively studied for their unusual and intriguing chemical behavior. Their ability to delocalize and/or provide electrons to the metal center of organometallic complexes confers them undisputable chemical interest and has proved valuable in the development of novel synthetic methodologies. This review will focus on the chemistry and applications of low-valent iron complexes bearing potentially non-innocent ligands. Because of the elusive nature of these ligands, and whenever possible, theoretical calculations and analysis of spectroscopic data will be presented in an effort to provide insights into the catalytic activity of the complexes

A series of capped metallo-cyclodextrins were synthesized, affording a variety of artificial chiral metallo-pockets through modulation of the space around the metal. Carbene ligands were used as caps for placing a silver, gold, or copper center at a well-defined location inside the cyclodextrin cavity. Multiple weak interactions involving the d 10 metal center and intra-cavity hydrogen atoms, including anagostic interactions, were observed in solution. Thus, the metal was used as a probe for assessing intra-cavity metal-H distances for building 3D models, revealing the very different shapes of capped a-, band nd g-cyclodextrins and the helical shape of the chiral pocket of some modified cyclodextrins. This series of N-heterocyclic-carbene-based cyclodextrins were compared in gold-catalyzed cycloisomerization reactions, for which the 3D models were used to rationalize the observed regio-and stereoselectivities.

The well-established oxidative addition -reductive elimination pathway is the most followed one in transition metal catalyzed cross coupling reactions. While readily occurring with a series of transition metals, it does not take place with gold(I) complexes which have shown some reluctance to undergo oxidative addition unless special sets of ligands on gold(I), reagents or reaction conditions are used. A new possibility to overcome this hurdle has been devised. Upon visible light irradiation, an iridium photocatalyst triggers via triplet sensitization the oxidative addition of an alkynyliodide onto a vinylgold(I) intermediate to deliver Csp 2 -Csp coupling products after reductive elimination. Mechanistic and modeling studies support that an energy transfer takes place and not a redox pathway. This novel mode of activation in gold homogenous catalysis was applied in several dual catalytic processes. Alkynylbenzofuran derivatives were obtained from o-alkynylphenols and iodoalkynes in the presence of catalytic gold(I) and iridium(III) complexes under blue LED irradiation.Over the last two decades, homogeneous gold catalysis has been extensively used to efficiently and selectively promote a variety of cyclization processes. [1][2][3] The typical casting involves bifunctional substrates bearing an unsaturation prompt to electrophilic activation and a judiciously positioned internal nucleophile. A protodemetalation of the organogold intermediates to afford hydrofunctionalized products generally terminates the catalytic cycles. 4 Pursuing the step economy principle and also aiming at higher level of molecular complexity, some in situ post-functionalization reactions of the organogold 5 intermediate have been devised such as electrophilic halogenation or cross-coupling reactions. Although palladium catalyzed cross coupling from an organogold(I) intermediate has been

A comparison of the oxidations of diclofenac with microsomes of yeasts expressing various human liver cytochromes P450 showed that P450 2C9 regioselectively led to 4'-hydroxy diclofenac (4'-OHD) whereas P450 3A4 only led to 5-hydroxy diclofenac (5-OHD). P450 2C19, 2C18, and 2C8 led to the simultaneous formation of 4'-OHD and 5-OHD (respective molar ratios of 1.3, 0.37, and 0.17), and P450 1A1, 1A2, 2D6, and 2E1 failed to give any detectable hydroxylated metabolite under identical conditions. P450 2C9 was found to be much more efficient for diclofenac hydroxylation than all the other P450s tested (k(cat)/K(M) of 1.6 min(-1) microM(-1) instead of 0.025 for the second more active P450), mainly because of markedly lower K(M) values (15 +/- 8 instead of values between 170 and 630 microM). Oxidation of diclofenac with chemical model systems of cytochrome P450 based on iron porphyrin catalysts exclusively led to the quinone imine derived from two-electron oxidation of 5-OHD, in an almost quantitative yield. Two derivatives of diclofenac lacking its COO(-) function were then synthesized; their oxidation by recombinant human P450 2Cs always led to a major product coming from their 5-hydroxylation. Substrate 2, which derives from reduction of the COO(-) function of diclofenac to the CH(2)OH function, was studied in more detail. All the P450s tested (1A1, 1A2, 2C8, 2C9, 2C18, 2C19, 2D6, and 3A4) almost exclusively led to its 5-hydroxylation. P450s of the 2C subfamily were found to be the most efficient catalysts for this reaction, with k(cat)/K(M) values between 0.2 and 1.6 min(-1) microM(-1). Oxidation of 2 with an iron porphyrin-based chemical model of cytochrome P450 also led to a product derived from the oxidation of 2 at position 5. These results show that oxidation of diclofenac and its derivative 2, either with chemical model systems of cytochrome P450 or with recombinant human P450s, generally occurs at position 5. This position, para to the NH group on the more electron-rich aromatic ring of diclofenac derivatives, is thus, as expected, the privileged site of reaction of electrophilic, oxidant species. The most spectacular exception to this chemoselective 5-oxidation of diclofenac derivatives was found for oxidation of diclofenac itself with P450 2C9 (and P450 2C19 and 2C18 to a lesser extent), which only led to 4'-OHD. A likely explanation for this result is a strict positioning of diclofenac in the P450 2C9 active site, via its COO(-) function, to completely orientate its hydroxylation toward position 4', which is not chemically preferred. P450 2C19, 2C18, and 2C8 would not lead to such a strict positioning as they give mixtures of 4'-OHD and 5-OHD. The above results show that diclofenac derivatives are interesting tools to compare the active site topologies of human P450 2Cs.

A new method for the arylative cyclization of o-alkynylphenols with aryldiazonium salts via dual photoredox/gold catalysis is described. The reaction proceeds smoothly at room temperature in the absence of base and/or additives and offers an efficient approach to benzofuran derivatives. The scope of the transformation is wide, and the limitations are discussed. The reaction is proposed to proceed through a photoredox-promoted generation of a vinylgold(III) intermediate that undergoes reductive elimination to provide the heterocyclic coupling adduct.

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A series of new secondary phosphine oxide (SPO)–gold(I) complexes have been synthesized and characterized by X-ray crystallography. Complexes exhibited dimeric structures interconnected by O–H···Cl hydrogen bonds. Their first use in homogeneous catalysis is reported and suggests a broad field of application in prototypical enyne cycloisomerization and hydroxy- and methoxycyclization reactions.