Showing papers in "Accounts of Chemical Research in 2000"
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TL;DR: A historical perspective on the application of molecular dynamics to biological macromolecules is presented and recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed for the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories.
Abstract: A historical perspective on the application of molecular dynamics (MD) to biological macromolecules is presented. Recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed us to reach the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories. We illustrate such applications on nucleic acid duplexes, RNA hairpins, protein folding trajectories, and protein−ligand, protein−protein, and protein−nucleic acid interactions.
3,965 citations
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TL;DR: The present state of the rapidly emerging field of monolayer-protected cluster (MPC) molecules with regard to their synthesis andmonolayer functionalization, their core and monolayers structure, their composition, and their properties is evaluated.
Abstract: In this report, we evaluate the present state of the rapidly emerging field of monolayer-protected cluster (MPC) molecules with regard to their synthesis and monolayer functionalization, their core and monolayer structure, their composition, and their properties. Finally, we canvass some of the important remaining research opportunities involving MPCs.
2,326 citations
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TL;DR: A comparison of traditional solid-state devices to molecular systems is described and issues of cost and ease of manufacture are outlined, along with the syntheses and testing of molecular wires and devices.
Abstract: Molecular electronics involves the use of single or small packets of molecules as the fundamental units for computing. While initial targets are the substitution of solid-state wires and devices with molecules, long-range goals involve the development of novel addressable electronic properties from molecules. A comparison of traditional solid-state devices to molecular systems is described. Issues of cost and ease of manufacture are outlined, along with the syntheses and testing of molecular wires and devices.
1,170 citations
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TL;DR: Chiral phosphinooxazolines (PHOX ligands) as discussed by the authors coordinate to a metal center with a N-and a P-atom, allowing effective enantiocontrol in a variety of metal-catalyzed reactions.
Abstract: Chiral phosphinooxazolines (PHOX ligands), which coordinate to a metal center with a N- and a P-atom, allow effective enantiocontrol in a variety of metal-catalyzed reactions. They are readily synthesized, and because of their modular structure, the steric and electronic properties can be tailored for a specific application by variation of the oxazoline ring, the backbone, and the phosphine moiety.
1,116 citations
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TL;DR: A search for a practical method for the kinetic resolution reaction led to the discovery of highly enantiomer-selective hydrolytic ring-opening using the corresponding (salen)Co(III) catalyst, which displays extraordinary substrate generality, and allows practical access to enantiopure terminal epoxides on both laboratory and industrial scales.
Abstract: The discovery of the metal salen-catalyzed asymmetric ring-opening (ARO) of epoxides is chronicled. A screening approach was adopted for the identification of catalysts for the addition of TMSN3 to meso-epoxides, and the chiral (salen)CrN3 complex was identified as optimal. Kinetic and structural studies served to elucidate the mechanism of catalysis, which involves cooperative activation of both epoxide and azide by two different metal centers. Covalently linked bimetallic complexes were constructed on the basis of this insight, and shown to catalyze the ARO with identical enantioselectivity but 1−2 orders of magnitude greater reactivity than the monomeric analogues. Extraordinarily high selectivity is observed in the kinetic resolution of terminal epoxides using the (salen)CrN3/TMSN3 system. A search for a practical method for the kinetic resolution reaction led to the discovery of highly enantiomer-selective hydrolytic ring-opening using the corresponding (salen)CoIII catalyst. This system displays ext...
1,064 citations
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TL;DR: Recent research on lead salt quantum dots is reviewed, which suggests that lead salt nanostructures may be the only materials in which the electronic energies are determined primarily by quantum confinement.
Abstract: Nanocrystals or quantum dots of the IV−VI semiconductors PbS, PbSe, and PbTe provide unique properties for investigating the effects of strong confinement on electrons and phonons. The degree of confinement of charge carriers can be many times stronger than in most II−VI and III−V semiconductors, and lead salt nanostructures may be the only materials in which the electronic energies are determined primarily by quantum confinement. This Account briefly reviews recent research on lead salt quantum dots.
1,057 citations
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TL;DR: The present analysis is based on studies of transition metals under idealized conditions, and several recent reports imply that TSR is by no means confined to the gas phase.
Abstract: It is proposed that spin-crossing effects can dramatically affect reaction mechanisms, rate constants, branching ratios, and temperature behaviors of organometallic transformations. This phenomenon is termed two-state reactivity (TSR) and involves participation of spin inversion in the rate-determining step. While the present analysis is based on studies of transition metals under idealized conditions, several recent reports imply that TSR is by no means confined to the gas phase. In fact, participation of more than a single spin surface in the reaction pathways is proposed as a key feature in organometallic chemistry.
1,017 citations
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TL;DR: In this paper, the main achievements in the field of excited-state properties of fullerene derivatives are reviewed, and the photosensitizing and electron-acceptor features of some relevant classes of functionalized materials are highlighted.
Abstract: This Account reviews our main achievements in the field of excited-state properties of fullerene derivatives. The photosensitizing and electron-acceptor features of some relevant classes of functionalized fullerene materials are highlighted, considering the impact of functionalization on fullerene characteristics. In addition, the unique optimization in terms of redox potentials, water-solubility, and singlet oxygen generation is presented for several novel fullerene-based materials.
1,010 citations
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TL;DR: This Account highlights recent developments in the Biginelli reaction in areas such as solid-phase synthesis, combinatorial chemistry, and natural product synthesis.
Abstract: In 1893, P. Biginelli reported the synthesis of functionalized 3, 4-dihydropyrimidin-2(1H)-ones (DHPMs) via three-component condensation reaction of an aromatic aldehyde, urea, and ethyl acetoacetate. In the past decade, this long-neglected multicomponent reaction has experienced a remarkable revival, mainly due to the interesting pharmacological properties associated with this dihydropyrimidine scaffold. In this Account, we highlight recent developments in the Biginelli reaction in areas such as solid-phase synthesis, combinatorial chemistry, and natural product synthesis.
971 citations
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TL;DR: The anion ligated to the palladium(0) affects the kinetics of the oxidative addition to ArI as well as the structure and reactivity of the arylpalladium(II) complexes produced in this reaction.
Abstract: The anions of PdCl(2)L(2) and Pd(OAc)(2), precursors of palladium(0) used in cross-coupling and Heck reactions, play a crucial role in these reactions. Tricoordinated anionic complexes Pd(0)L(2)Cl(-) and Pd(0)L(2)(OAc)(-) are the effective catalysts instead of the usually postulated Pd(0)L(2) complex. The anion ligated to the palladium(0) affects the kinetics of the oxidative addition to ArI as well as the structure and reactivity of the arylpalladium(II) complexes produced in this reaction. Thus, pentacoordinated anionic complexes are formed, ArPdI(Cl)L(2)(-) or ArPdI(OAc)L(2)(-), the precursor of neutral trans-ArPd(OAc)L(2), instead of the usually postulated trans-ArPdIL(2) complex (L = PPh(3)).
923 citations
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TL;DR: X-ray crystallography of the chiral complexes reveals a propensity for the formation of distorted square planar or square pyramidal geometries in catalyzed processes that exhibit excellent temperature-selectivity profiles.
Abstract: A bis(oxazoline) (box) copper(II) complex and its hydrated counterpart (1 and 2) function as enantioselective Lewis acid catalysts for carbocyclic and hetero Diels−Alder, aldol, Michael, ene, and amination reactions with substrates capable of chelation through six- and five-membered rings. X-ray crystallography of the chiral complexes reveals a propensity for the formation of distorted square planar or square pyramidal geometries. The sense of asymmetric induction is identical for all the processes catalyzed by [Cu((S,S)-t-Bu-box)](X)2 complexes 1 and 2 (X = OTf and SbF) resulting from the intervention of a distorted square planar catalyst-substrate binary complex. These catalyzed processes exhibit excellent temperature−selectivity profiles. Reactions catalyzed by [Cu(S,S-Ph-pybox)](SbF6)2 and their derived chelation complexes are also discussed.
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TL;DR: The development of materials that are capable of releasing macromolecules such as proteins and peptides, intelligent delivery systems based on magnetism or microchip technology, new degradable materials such as polyanhydrides, and noninvasive approaches for delivering molecules through the skin and lungs are discussed.
Abstract: This Account reviews our laboratory's research in biomaterials. In one area, drug delivery, we discuss the development of materials that are capable of releasing macromolecules such as proteins and peptides, intelligent delivery systems based on magnetism or microchip technology, new degradable materials such as polyanhydrides, and noninvasive approaches for delivering molecules through the skin and lungs. A second area, tissue engineering, is also discussed. New polymer systems for creating cartilage, blood vessels, nerves, and other tissues are examined.
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TL;DR: A mechanism for long-range charge transport in DNA that depends on its spontaneous structural distortion, which is called phonon-assisted polaron hopping is described, which provides a framework for understanding the reactions and charge-transport properties of DNA.
Abstract: Damage to DNA is often caused by oxidative reactions. In one such process, an electron is lost from a base, forming its radical cation. Further reaction of the radical cation can lead to permanent change, which results in mutation. This Account is a report on oxidative damage to DNA caused by irradiation of anthraquinone derivatives, which are either randomly bound to the DNA or attached to it covalently at specific locations. Radical cations introduced in the DNA by the excited quinone cause damage both near to it and far away. We describe a mechanism for long-range charge transport in DNA that depends on its spontaneous structural distortion, which we call phonon-assisted polaron hopping. This mechanism, and its extension, provides a framework for understanding the reactions and charge-transport properties of DNA.
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TL;DR: It is shown that the spin density maps give a precise description of the ground state of such molecular magnetic species as 3d or 4f metal ions, organic radicals, and ferromagnetic species.
Abstract: The building of multidimensional magnetic materials obtained with the molecular precursor [Cu(opba)]2- is described. The reaction with other paramagnetic species (3d or 4f metal ions, organic radicals) yielded one-dimensional, two-dimensional, and interlocked networks. The magnetic properties of these systems are reviewed using polarized neutron diffraction and magnetic measurements. It is shown that the spin density maps give a precise description of the ground state of such molecular magnetic species. Moreover, different long-range magnetic orderings (antiferro-, ferri-, and ferromagnetic) have been obtained.
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TL;DR: The breakthrough is presented using chiral phosphoramidite ligands for copper-catalyzed dialkylzinc additions for enantioselective carbon-carbon bond formation by 1,4-addition of organometallic reagents to enones.
Abstract: The development of an efficient catalytic system for enantioselective carbon−carbon bond formation by 1,4-addition of organometallic reagents (organolithium, Grignard, and organozinc reagents) to enones is a major challenge in organic synthesis. This Account presents the breakthrough realized in this field using chiral phosphoramidite ligands for copper-catalyzed dialkylzinc additions. Applications in catalytic routes to cycloalkanones as well as tandem and annulation procedures with excellent enantioselectivities are discussed.
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TL;DR: Long-distance charge transport from a guanine radical cation (G(+*)) to a G-rich sequence is of biological importance and was studied by selective charge injection into a G, monitoring the charge transport to aGGG sequence by competing H(2)O-trapping.
Abstract: Long-distance charge transport from a guanine radical cation (G(+*)) to a G-rich sequence is of biological importance. This reaction was studied by selective charge injection into a G, monitoring the charge transport to a GGG sequence by competing H(2)O-trapping. The efficiency of the charge transport diminished dramatically with increasing number of A:T base pairs between G(+*) and GGG. But in DNA strands where G's are located between the G(+*) and GGG sequence, long-distance charge transport occurred by a multistep hopping mechanism.
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TL;DR: This Account focuses on the recent and systematic effort in the development of generic scanning probe lithography (SPL)-based methodologies to produce nanopatterns of self-assembled monolayers (SAMs) and the principle of these procedures and the critical steps in controlling local tip-surface interactions are discussed.
Abstract: This Account focuses on our recent and systematic effort in the development of generic scanning probe lithography (SPL)-based methodologies to produce nanopatterns of self-assembled monolayers (SAMs). The key to achieving high spatial precision is to keep the tip−surface interactions strong and local. The approaches used include two AFM-based methods, nanoshaving and nanografting, which rely on the local force, and two STM-based techniques, electron-induced diffusion and desorption, which use tunneling electrons for fabrication. In this Account we discuss the principle of these procedures and the critical steps in controlling local tip−surface interactions. The advantages of SPL will be illustrated through various examples of production and modification of SAM nanopatterns and their potential applications.
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TL;DR: It is shown, inter alia, that reproducible and transferable crystal synthesis strategies based on charge-assisted hydrogen bonds can be devised to build periodical supermolecules.
Abstract: The utilization of noncovalent interactions to construct molecular crystals is evaluated in the context of inorganic and organometallic crystal engineering. The attention is focused on hydrogen-bonding interactions involving metal complexes in which the metal atoms participate in the bonding either directly or as ancillary systems. The role of ionic charges is discussed. It is shown, inter alia, that reproducible and transferable crystal synthesis strategies based on charge-assisted hydrogen bonds can be devised to build periodical supermolecules.
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TL;DR: Using recently developed techniques, one can quickly obtain highly specific research reagents that act on defined intracellular targets in the context of the living cell and their use as in vivo modulators of cellular physiology is facilitated.
Abstract: Aptamers are nucleic acid ligands which are isolated from combinatorial oligonucleotide libraries by in vitro selection. They exhibit highly complex and sophisticated molecular recognition properties and are capable of binding tightly and specifically to targets ranging from small molecules to complex multimeric structures. Besides their promising application as molecular sensors, many aptamers targeted against proteins are also able to interfere with the proteins' biological function. Recently developed techniques facilitate the intracellular application of aptamers and their use as in vivo modulators of cellular physiology. Using these approaches, one can quickly obtain highly specific research reagents that act on defined intracellular targets in the context of the living cell.
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TL;DR: Chiral monophosphines have been prepared from enantiomerically pure 2, 2'-dihydroxy-1,1'-binaphthyl and demonstrated to be highly efficient chiral ligands for transition-metal-catalyzed organic transformations, especially for reactions where chelating bisphosphine ligands cannot be used.
Abstract: Chiral monophosphines, whose chirality is due to biaryl axial chirality, have been prepared from enantiomerically pure 2, 2'-dihydroxy-1,1'-binaphthyl and demonstrated to be highly efficient chiral ligands for transition-metal-catalyzed organic transformations, especially for reactions where chelating bisphosphine ligands cannot be used. The high efficiency is observed in palladium-catalyzed asymmetric hydrosilylation of a wide variety of olefins such as alkyl-substituted terminal olefins and in asymmetric reactions via pi-allylpalladium intermediates represented by asymmetric reduction of allylic esters with formic acid.
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TL;DR: Current understanding of cycloaddition reactions of organic molecules with semiconductor surfaces is summarized and the rates and mechanisms of the surface reactions show some distinct differences from those of their organic counterparts.
Abstract: Recent investigations have shown that cycloaddition reactions, widely used in organic chemistry to form ring compounds, can also be applied to link organic molecules to the (001) surfaces of crystalline silicon, germanium, and diamond. While these surfaces are comprised of SiSi, GeGe, and CC structural units that resemble the CC bonds of organic alkenes, the rates and mechanisms of the surface reactions show some distinct differences from those of their organic counterparts This article reviews recent studies of [2 + 2], [4 + 2] Diels−Alder, and other cycloaddition reactions of organic molecules with semiconductor surfaces and summarizes the current understanding of the reaction pathways.
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TL;DR: The catalytic generation of transition-metal metalloenolates and alkynilides under conditions compatible with electrophilic reaction partners provides fresh avenues for the development of new efficient asymmetric processes leading to C-C bond formation.
Abstract: There have been great strides in expanding the scope, application, and versatility of known reaction types (i.e., Mukaiyama aldol). It is interesting to speculate that limitations in the number of such known basic reaction types constitute the greatest barrier in the development of practical processes. The catalytic generation of transition-metal metalloenolates and alkynilides under conditions compatible with electrophilic reaction partners provides fresh avenues for the development of new efficient asymmetric processes leading to C−C bond formation.
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TL;DR: This Account outlines the preparation and application of a class of phosphine ligands based upon the trans-2,5-disubstituted phospholane moiety and highlights the versatility of highly efficient bis(phospholane)rhodium catalysts that allow enantioselective hydrogenation to produce a diverse range of compounds containing C-N, C-O, and C-C stereogenic centers.
Abstract: This Account outlines the preparation and application of a class of phosphine ligands based upon the trans-2,5-disubstituted phospholane moiety. The modular nature of these ligands has allowed facile variation of both phospholane substituent and backbone structure, thus providing access to a series of ligands. Bidentate bis(phospholane) ligands have been found to be very useful in asymmetric catalytic hydrogenation reactions. In particular, we highlight the versatility of highly efficient bis(phospholane)rhodium catalysts that allow enantioselective hydrogenation to produce a diverse range of compounds containing C−N, C−O, and C−C stereogenic centers.
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TL;DR: The earlier tremendous interest in molybdenum blue solutions-an enigma for generations of chemists-became even more pronounced when it turned out that the basic building units correspond to giant wheel-shaped clusters with nanostructured cavities, displaying exceptional aesthetic beauty.
Abstract: The earlier tremendous interest in molybdenum blue solutions-an enigma for generations of chemists-became even more pronounced when it turned out that the basic building units correspond to giant wheel-shaped clusters with nanostructured cavities, displaying exceptional aesthetic beauty. This discovery will stimulate new ideas in supramolecular chemistry, colloid chemistry, and materials science. The giant wheels represent nanosensors and nanoreactors, enabling the initiation of chemical processes at different positions, like a "structured landscape", and can even be used as robust synthons for the construction of compounds with typical solid-state structure, a situation comparable to crystal engineering.
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TL;DR: The design and synthesis of a new family of chiral nucleophilic catalysts, specifically, planar-chiral heterocycles are described, which provide good levels of enantiomeric excess in the addition of alcohols to ketenes, the rearrangement of O-acylated azlactones, and the kinetic resolution of secondary alcohols.
Abstract: Although Lewis bases (e.g., tertiary phosphines, tertiary amines, and pyridines) serve as nucleophilic catalysts for a wide array of reactions, there have been relatively few reports of enantioselective nucleophilic catalysts. In this Account, we describe the design and synthesis of a new family of chiral nucleophilic catalysts, specifically, planar-chiral heterocycles. These complexes provide good levels of enantiomeric excess in the addition of alcohols to ketenes, the rearrangement of O-acylated azlactones, and the kinetic resolution of secondary alcohols.
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TL;DR: The new mixed-valent configurations, as obtained through various chemical approaches, display different stabilities and spectroscopic characteristics in relation to the Creutz-Taube ion; the analysis of these results serves to provide a better understanding of fundamental aspects of molecule-mediated metal-metal interaction.
Abstract: Starting from the Creutz-Taube ion as the prototype of a molecule-bridged mixed-valent complex, a number of related systems are presented in which the metal, the co-ligands, the molecular bridge, the d electron configuration, the medium, the charge, the coordination mode, or the nuclearity have been modified. The new mixed-valent configurations, as obtained through various chemical approaches, display different stabilities and spectroscopic characteristics in relation to the Creutz-Taube ion; the analysis of these results serves to provide a better understanding of fundamental aspects of molecule-mediated metal−metal interaction.
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TL;DR: Ligand K-edge X-ray absorption spectroscopy is a new experimental probe of the covalency of a metal-ligand bond and provides important electronic structure insight into function.
Abstract: Ligand K-edge X-ray absorption spectroscopy (XAS) is a new experimental probe of the covalency of a metal−ligand bond. The intensity of the ligand pre-edge feature is proportional to the mixing of ligand orbitals into the metal d orbitals. The methodology to determine covalencies in one-electron (hole) and many-electron systems is described and demonstrated for a series of metal tetrachlorides [MCl4]n-, metal tetrathiolates [M(SR)4]n-, and dimeric iron−sulfur (Fe−S) clusters [Fe2S2(SR)4]2-. It is then applied to blue Cu proteins, the CuA site, hydrogen bonding in Fe−S clusters, and the delocalization behavior in [2Fe-2S] vs [4Fe-4S] clusters. The covalencies determined in these studies provide important electronic structure insight into function.
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TL;DR: Structural and mutational analysis allowed us to explore the determinants of native protein structure and these determinants were then applied to the design of a dinuclear metal-binding protein that can now serve as a model for this important class of proteins.
Abstract: De novo protein design has proven to be a powerful tool for understanding protein folding, structure, and function. In this Account, we highlight aspects of our research on the design of dimeric, four-helix bundles. Dimeric, four-helix bundles are found throughout nature, and the history of their design in our laboratory illustrates our hierarchic approach to protein design. This approach has been successfully applied to create a completely native-like protein. Structural and mutational analysis allowed us to explore the determinants of native protein structure. These determinants were then applied to the design of a dinuclear metal-binding protein that can now serve as a model for this important class of proteins.
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TL;DR: This account outlines work primarily from the author's laboratory on the development of nickel-catalyzed multicomponent coupling processes, an overview of new synthetic methods, a discussion of potential mechanisms, and a description of applications in complex-molecule synthesis are provided.
Abstract: Transition-metal-catalyzed processes that allow the efficient coupling of three reactive components in a chemoselective and stereoselective fashion are particularly useful in the synthesis of complex organic molecules from simple, readily available substrates. This account outlines work primarily from the author's laboratory on the development of nickel-catalyzed multicomponent coupling processes. An overview of new synthetic methods, a discussion of potential mechanisms, and a description of applications in complex-molecule synthesis are provided.