China Science

Despite many advances in recent years, crystal engineering remains a risky venture. A successful outcome requires manipulation of the noncovalent bonding and properties such as size, shape, repulsion, attraction, polarity, and chirality. In this Account, we describe the interplay of crystal engineering and synthetic organic chemistry required to develop the family of helical tubuland diol hosts, the members of which exhibit a wide range of tube dimensions and inclusion properties. Certain alicyclic dialcohols crystallize with a hydrogen-bonded network structure, termed the helical tubuland lattice, in space group P3121 (or its enantiomorph P3221). Double helices of diol molecules surround parallel tubes that contain guest molecules, which are included on the basis of size and shape rather than functional group. The crystal structure of (diol)3·(chloroacetic acid)1.2 is illustrative. These chiral helical tubulate lattice inclusion compounds are formed when the racemic host diol is allowed to crystallize from solution. Complete enantiomer separation occurs during this process, producing a 1:1 mixture of pure (+)- and pure (?)-crystals (a conglomerate). The challenge of creating this family of compounds required the development of much synthetic chemistry, in particular new pathways to alicyclic ring systems with specific substitution patterns. It was also necessary to understand and control the supramolecular properties of the diol molecules. What makes the original compound tick, and why did it behave in this remarkable manner, when most of its structural neighbors crystallize totally differently? The synthesis of new helical tubuland diols requires not just preparation of a new molecular structure but also a transplant of the original unchanged hydrogen-bonding supramolecular synthon. Synthesis of the specific crystal space group is necessary. This was achieved by defining structural characteristics, termed molecular determinants, which are essential for the helical tubuland structure to occur. If these requirements were met, then the target molecule had a high probability of success. This investigation has close conceptual parallels with the search for pharmacophore properties of bioactive molecules. In both situations, parts of a molecule with little or no chemical reactivity may actually play vital supramolecular roles. The review illustrates how crystal engineering is based on specific supramolecular properties that can be uncovered and then exploited by synthetic chemists.

Roger Bishop
School of Chemistry, The University of New South Wales, UNSW Sydney, NSW 2052, Australia

The burgeoning field of nanoscience has stimulated an intense interest in properties that depend on particle size. For transition metal particles, one important property that depends on size is catalytic reactivity, in which bonds are broken or formed on the surface of the particles. Decreased particle size may increase, decrease, or have no effect on the reaction rates of a given catalytic system. This Account formulates a molecular theory of the structure sensitivity of catalytic reactions based on the computed activation energies of corresponding elementary reaction steps on transition metal surfaces. Recent progress in computational catalysis, surface science, and nanochemistry has significantly improved our theoretical understanding of particle-dependent reactivity changes in heterogeneous catalytic systems. Reactions that involve the cleavage or formation of molecular ?-bonds, as in CO or N2, must be distinguished from reactions that involve the activation of ?-bonds, such as CH bonds in methane. The activation of molecular ?-bonds requires a reaction center with a unique configuration of several metal atoms and step-edge sites, which can physically not be present on transition metal particles less than 2 nm. This is called class I surface sensitivity, and the rate of reaction will sharply decrease when particle size decreases below a critical size. The activation of ? chemical bonds, in which the activation proceeds at a single metal atom, displays a markedly different size relationship. In this case, the dependence of reaction rate on coordinative unsaturation of reactive surface atoms is large in the forward direction of the reaction, but the activation energy of the reverse recombination reaction will not change. Dissociative adsorption with cleavage of a CH bond is strongly affected by the presence of surface atoms at the particle edges. This is class II surface sensitivity, and the rate will increase with decreasing particle size. Reverse reactions such as hydrogenation typically show particle-size-independent behavior. The rate-limiting step for these class III reactions is the recombination of an adsorbed hydrogen atom with the surface alkyl intermediate and the formation of a ?-type bond. Herein is our molecular theory explaining the three classes of structure sensitivity. We describe how reactions with rates that are independent of particle size and reactions with a positive correlation between size and rate are in fact complementary phenomena. The elucidation of a complete theory explaining the size dependence of transition metal catalysts will assist in the rational design of new catalytic systems and accelerate the evolution of the field of nanotechnology.

Rutger A. Van Santen
Schuit Institute of Catalysis, Laboratory of Inorganic Chemistry and Catalysis, P.O Box 513, 5600 MB Eindhoven, Eindhoven University of Technology, The Netherlands

As master craftsmen, modern synthetic chemists are challenged to achieve remarkable feats of efficiency and elegance toward molecular targets. The nature of this pursuit necessitates the collection of synthetic repertoires that are tried and true. With methodologies and pathways increasingly scrutinized, the adept chemist must seek out propitious tools to incorporate into the arsenal. With this in mind, this Account highlights the versatility of alkoxyallenes as precursors to valuable heterocyclic building blocks for such efforts as natural product synthesis. Accessed by the etherification of either propargyl alcohols or propargylic halides, alkoxyallenes are obtained after base-catalyzed isomerizations of the propargylic ethers. A host of umpolung synthons are available through this scheme after metalation, generating C3 nucleophiles synthetically equivalent to vital anionic and zwitterionic synthons. Reactions with a diverse set of heteroatomic electrophiles yield carbohydrates, spiroketals, alkaloids, and heteroaromatics via [3 + 2] or [3 + 3] cyclizations. By employing lithiated alkoxyallenes into transformation routes, the natural product chemist can utilize this methodology as a viable resource in stereoselective synthesis. A survey of our own utilization of alkoxyallenes along synthetic pathways toward natural product targets reveals their suitability for generating advantageous precursors. A set of four stereoisomeric 2,6-dideoxyhexoses were stereoselectively obtained after an initial lithiated alkoxyallene and lactaldehyde cyclization, followed by the oxidative ring opening of the dihydrofurans. Through the addition of a lithiated alkoxyallene to a functionalized benzaldehyde, an essential spiroketal diastereomer was rapidly achieved in a few steps. We greatly benefitted from alkoxyallenes in the construction of complex nitrogen-containing synthetic targets, whether pyrrolidine alkaloids, substituted imidazole derivatives, or functionalized pyridines. A pinnacle example of their utility came from the coupling of alkoxyallenes to nitrones affording 1,2-oxazines, which served as a gateway to an array of novel polyfunctionalized compounds such as aminopolyols, hydroxylated pyrrolidines, or carbohydrate mimetics. Alkoxyallenes have proven themselves to be powerful C3 building blocks toward complex molecular targets, revealing novel pathways to a variety of desirable highly functionalized heterocycles. In our view, the full extent of their synthetic utility has yet to be truly realized.

Malte Brasholz?Hans-Ulrich Reissig?Reinhold Zimmer
Freie Universitt Berlin, Institut fr Chemie and Biochemie, Takustrasse 3, D-14195 Berlin, Germany

Unlike normal chemical bonds, hydrogen bonds (H-bonds) characteristically feature binding energies and contact distances that do not simply depend on the donor (D) and acceptor (:A) nature. Instead, their chemical context can lead to large variations even for a same donor?acceptor couple. As a striking example, the weak HO?H···OH2 bond in neutral water changes, in acidic or basic medium, to the 6-fold stronger and 15% shorter [H2O···H···OH2]+ or [HO···H···OH]? bonds. This surprising behavior, sometimes called the H-bond puzzle, practically prevents prediction of H-bond strengths from the properties of the interacting molecules. Explaining this puzzle has been the main research interest of our laboratory in the last 20 years. Our first contribution was the proposal of RAHB (resonance-assisted H-bond), a new type of strong H-bond where donor and acceptor are linked by a short ?-conjugated fragment. The RAHB discovery prompted new studies on strong H-bonds, finally leading to a general H-bond classification in six classes, called the six chemical leitmotifs, four of which include all known types of strong bonds. These studies attested to the covalent nature of the strong H-bond showing, by a formal valence-bond treatment, that weak H-bonds are basically electrostatic while stronger ones are mixtures of electrostatic and covalent contributions. The covalent component gradually increases as the difference of donor?acceptor proton affinities, ?PA, or acidic constants, ?pKa, approaches zero. At this limit, the strong and symmetrical D···H···A bonds formed can be viewed as true three-center-four-electron covalent bonds. These results emphasize the role PA/pKa equalization plays in strengthening the H-bond, a hypothesis often invoked in the past but never fully verified. In this Account, this hypothesis is reconsidered by using a new instrument, the pKa slide rule, a bar chart that reports in separate scales the pKa’s of the D?H proton donors and :A proton acceptors most frequently involved in D?H···:A bond formation. Allowing the two scales to shift so to bring selected donor and acceptor molecules into coincidence, the ruler permits graphical evaluation of ?pKa and then empirical appreciation of the D?H···:A bond strength according to the pKa equalization principle. Reliability of pKa slide rule predictions has been verified by extensive comparison with two classical sources of H-bond strengths: (i) the gas-phase dissociation enthalpies of charged [X···H···X]? and [X···H···X]+ bonds derived from the thermodynamic NIST Database and (ii) the geometries of more than 9500 H-bonds retrieved from the Cambridge Structural Database. The results attest that the pKa slide rule provides a reliable solution for the long-standing problem of H-bond-strength prediction and represents an efficient and practical tool for making such predictions directly accessible to all scientists.

Paola Gilli?Loretta Pretto?Valerio Bertolasi?Gastone Gilli
Dipartimento di Chimica and Centro di Strutturistica Diffrattometrica, Universitdi Ferrara, I-44100 Ferrara, Italy

The selective detection of the anion pyrophosphate (PPi) is a major research focus. PPi is a biologically important target because it is the product of ATP hydrolysis under cellular conditions, and because it is involved in DNA replication catalyzed by DNA polymerase, its detection is being investigated as a real-time DNA sequencing method. In addition, within the past decade, the ability to detect PPi has become important in cancer research. In general, the sensing of anions in aqueous solution requires a strong affinity for anions in water as well as the ability to convert anion recognition into a fluorescent or colorimetric signal. Among the variety of methods for detecting PPi, fluorescent chemosensors and colorimetric sensors for PPi have attracted considerable attention during the past 10 years. Compared with the recognition of metal ions, it is much more challenging to selectively recognize anions in an aqueous system due to the strong hydration effects of anions. Consequently, the design of PPi sensors requires the following: an understanding of the molecular recognition between PPi and the binding sites, the desired solubility in aqueous solutions, the communicating and signaling mechanism, and most importantly, selectivity for PPi over other anions such as AMP and ADP, and particularly phosphate and ATP. This Account classifies chemosensors for PPi according to topological and structural characteristics. Types of chemosensors investigated and reported in this study include those that contain metal ion complexes, metal complexes combined with excimers, those that function with a displacement approach, and those based on hydrogen-bonding interaction. Thus far, the utilization of a metal ion complex as a binding site for PPi has been the most successful strategy. The strong binding affinity between metal ions and PPi allows the detection of PPi in a 100% aqueous solution. We have demonstrated that carefully designed receptors can distinguish between PPi and ATP based on their different total anionic charge densities. We have also demonstrated that a PPi metal ion complex sensor has a bioanalytical application. This sensor can be used in a simple and quick, one-step, homogeneous phase detection method in order to confirm DNA amplification after polymerase chain reaction (PCR).

Sook Kyung Kim#8224?Dong Hoon Lee#8225?Jong-In Hong#8225?Juyoung Yoon#8224?

Targeting the minor groove of DNA through binding to a small molecule has long been considered an important molecular-recognition strategy in biology. A wide range of synthetic heterocyclic molecules bind noncovalently in the minor groove of the double helix and are also effective against a number of human and animal diseases. A classic structural concept, the isohelicity principle, has guided much of this work: such heterocyclic molecules require a shape that complements the convex surface of the minor groove. Researchers have used this principle to design molecules that can read DNA sequences. This principle also predicts that molecules that lack the complementary shape requirement would only bind weakly to DNA. Recently, however, researchers have unexpectedly found that some essentially linear compounds, which do not have this feature, can have high DNA affinity. In this Account, we discuss an alternative recognition concept based on these new findings. We demonstrate that highly structured water molecules can play a key role in mediating between the ligand and DNA minor groove without loss of binding affinity. Combined structural and thermodynamic approaches to understanding the behavior of these molecules have shown that there are different categories of bound water in their DNA complexes. For example, application of this water-bridging concept to the phenylamidine platform has resulted in the discovery of molecules with high levels of biological activity and low nonspecific toxicity. Some of these molecules are now in advanced clinical trials.

Binh Nguyen#8224?Stephen Neidle#8225?W. David Wilson#8224?

The structural blue color of a Morpho butterfly originates from the diffraction of light and interference effects due to the presence of the microstructures on the wing of the butterfly. Structural color on the surface of a damselfish reversibly changes between green and blue. Inspired by these creatures, we have been trying to prepare high-quality and functional structural color films. We describe our efforts in this Account. A useful technique to prepare such structural color films in colloidal solution is a “lifting” method, which allows us to quickly fabricate brilliant colloidal crystal films. The thicknesses of the films can be controlled by precisely adjusting the particle concentration and the lifting speed. Moreover, in order to prepare a complicated structure, we have used template methods. Indeed, we have successfully prepared the inverse structure of the wing of a Morpho butterfly with this technique. Initially, however, our structural color films had a whitish appearance due to the scattering of light by defects in the colloidal crystal film. Later, we were able to prepare a non-whitish structural color film by doping an appropriate dye in the colloidal particles to absorb the scattering light. In addition to the structural blue color, the wing of the Morpho butterfly has superhydrophobic properties. According to Wenzel’s equation, the hydrophobic and hydrophilic properties are enhanced when the roughness of the hydrophobic and hydrophilic surface is increased, respectively. Based on this mechanism, we have successfully prepared structural color films with superhydrophobic properties, as well as with superhydrophilic properties. Another important property that can be seen in nature is tunable structural color, such as the color change that can be seen on the surface of a damselfish. In order to mimic such color change, we have developed several tunable structural color films. In particular, we have successfully prepared phototunable photonic crystals using photoresponsive azobenzene derivatives. In order to apply these structural color films, we developed a technique for patterning them by taking advantage of the wettability of the substrate surface. These materials can be used in the future for self-cleaning pigments and tunable photonic crystals.

Osamu Sato#8224?Shoichi Kubo#8225?Zhong-Ze Gu§

In spite of being sheared along the so-called pseudo-twinning direction, ?-TiAl undergoes true twinning under zero pressure or hydrostatic tension by means of a specific combination of , and shears in two consecutive (1 1 1) matrix planes allowing the adjacent twin to thicken over one (1 1 1) atomic layer. The corresponding total shear strain of is four times as large as that generated by conventional deformation twinning or during the L10 to L11 transformation by or shears, respectively. This shear is substantially more effective in accommodating stress concentration and high strain rate than conventional deformation twinning. The conditions under which twinning by dislocations operates are interpreted based on a modified gamma-surface and discussed in terms of zonal partial dislocations.

Dongsheng XuaEmail:dsxu@imr.ac.cn?Hao Wanga?Rui Yanga?Patrick Veyssièreb
[a]Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, China;[b]LEM, CNRS-ONERA, BP 72, 92322 Chatillon, France

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