To explain the remarkable regioselective de-O-benzylating properties of diisobutylaluminium hydride (DIBAL-H) and triisobutylaluminium (TIBAL) towards polybenzylated sugars or cyclodextrins, we propose a plausible mechanistic rationale critically involving the kinetic formation of a product-generating 2:1 Al-benzylated sugar complex. For the reaction to occur, one pair of adjacent oxygen atoms should first be able to form a chelation complex with the first equivalent of aluminium reagent, either a highly fluxional complex with tetracoordinate aluminium species or a pentacoordinate one. The second equivalent then induces the regioselectivity of the de-O-alkylation by coordinating preferentially to one of the oxygen atoms of the selected pair.

We report the synthesis and characterisation of photosensitive cationic surfactants with various hydrophobic tail lengths. These molecules, called AzoCx, are used as photosensitive nucleic acid binders (pNABs) and are applied to the photocontrol of DNA conformation. All these molecules induce DNA compaction in a photodependent way, originating in the photodependent polarity of their hydrophobic tails. We show that increasing hydrophobicity strongly enhances the compaction efficiencies of these molecules, but reduces the possibility of reversible photocontrol of a DNA conformation. Optimal performance was achieved with AzoC5, which allowed reversible control of DNA conformation with light at a concentration seven times smaller than previously reported.

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....

Fluorinated carbohydrates have become indispensable in glycosciences. This contribution provides an overview of how fluorine introduction modifies physical and chemical properties of carbohydrates along with selected examples of its applications.

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 enzymatic hydrolysis of alpha-L-fucosides is of importance in cancer, bacterial infections, and fucosidosis, a neurodegenerative lysosomal storage disorder. Here we show a series of snapshots along the reaction coordinate of a glycoside hydrolase family GH29 alpha-L-fucosidase unveiling a Michaelis (ES) complex in a (1)C(4) (chair) conformation and a covalent glycosyl-enzyme intermediate in (3)S(1) (skew-boat). First principles metadynamics simulations on isolated alpha-L-fucose strongly support a (1)C(4)<-->(3)H(4)<-->(3)S(1) conformational itinerary for the glycosylation step of the reaction mechanism and indicate a strong "preactivation" of the (1)C(4) complex to nucleophilic attack as reflected by free energy, C1-O1/O5-C1 bond length elongation/reduction, C1-O1 bond orientation, and positive charge development around the anomeric carbon. Analysis of an imino sugar inhibitor is consistent with tight binding of a chair-conformed charged species.

Fluoro-C-glycosides and fluoro-carbasugars are a particular subclass of hydrolytically stable glycomimetics that are expected to have different, hopefully improved properties thanks to the stereoelectronic features of the fluoroalkyl moiety. This review summarizes the studies devoted to the synthesis of such structures as well as the studies regarding their conformational behaviour and their potential as carbohydrate analogues.

It has been well established that the regulation of gene activity is strongly dependent on the higher-order structure of genomic DNA molecules.[1] Several strategies have thus been developed to control the higher-order structure of long DNA molecules. Most of them have been based on the use of chemical compounds that bind to DNA to neutralize its charge, such as polyamines, multivalent metal cations, cationic surfactants, cationic polymers, nanoparticles, or crowding agents such as hydrophilic polymers.[2] Depending on the concentration of these additives, DNA exhibits a folded or unfolded conformation. Nevertheless, with all these strategies, it is impossible to act in a reversible way on the DNA higher-order structure under a constant chemical composition.Moreover, for transfection applications, compacting DNA is an essential step to allow the entry of DNA into the cell. In most cases, however, DNA remains in a compact conformation inside the cell, which can significantly alter the DNA gene expression. Using an external stimulus to control DNA higherorder structure within a cell-sized compartment has thus became an important challenge.On the other hand, motivated by the perspective of DNA vectorization, [3] preparation of artificial cells [4] or biochemical microreactors, [5] many scientists have attempted to encapsulate DNA into cell-like microcompartments, for example, cellsized liposomes [6] or phospholipid-coated microdroplets. [7] Consequently, various successful strategies have been proposed to prepare DNA-liposome complexes [8] or encapsulate DNA inside liposomes.[9] In most cases encapsulated DNA molecules were typically smaller than a few thousands base pairs. However, in nature, genomic DNA molecules can be much larger, up to hundreds of kbp (kilo base pairs). To the best of our knowledge, no method has been proposed to encapsulate efficiently, in a controlled way, and without degradation, DNA molecules that are larger than 1 kbp into cell-sized liposomes. One paper reported the encapsulation of T4 DNA molecules, but the data were not sufficient to draw conclusions about the integrity of encapsulated DNA chains.[10] Another strategy was to encapsulate DNA in a compact state, but DNA molecules remained in their compact state once they were encapsulated. [11] Very recently, Le Ny and Lee made a breakthrough by proposing a system where DNA higher-structure can be controlled by light in a reversible manner. [12] This was achieved by adding to a DNA solution a photosensitive cationic surfactant, azobenzene trimethylammonium bromide surfactant (AzoTAB). The apolar tail of the surfactant contains an azo group, which is mainly in the trans (more hydrophobic) conformation under visible conditions. Under UV illumination (365 nm), the azo group photoisomerizes into the cis (more hydrophilic) conformation. They demonstrated that there exists an AzoTAB concentration range for which DNA is in the compact state under dark/visible conditions but in the unfolded state under UV illumination, that is, DNA higher-orde...