Showing papers in "Accounts of Chemical Research in 1997"

Synthetic supramolecular chemistry

Abstract: For many decades, the construction of organic compounds in the laboratory has relied on the remarkable abilities of the 20th century ‘alchemists’ — namely, synthetic organic chemists — to make and break covalent bonds. Careful selection of functional groups and reaction conditions, in conjunction with protection/deprotection protocols, constitute the ‘secrets’ and ‘tricks’ of their ‘art’ which is commensurate with ‘traditional’ organic synthesis [1,2]. Indeed, relying on multistep reaction sequences, the total syntheses of structurally intricate molecular compounds which are constructed entirely using covalent bonds — e.g., brevetoxin B [3], palytoxin [4], and the calichearubicins [5] — have been realized in recent times. These very elegant and successful syntheses have required enormous intellectual and hands-on effort by large teams of chemists over rather long periods of time — very often, several years. Moreover, these extremely complex, and often particularly beautiful, examples represent close to state-of-the-art as far as ‘traditional’ organic synthesis is concerned. Alas, they also highlight the difficulties and limitations associated with classical organic syntheses — specifically, that the multistep aspect of such syntheses can be extremely laborious and time-consuming. With the possible exception of some dendritic structures [6], it is becoming apparent that the construction of nanoscopic structures, of the same complexities as those found in biological systems, using these classical methods is out of the reach of even the most talented and optimistic of the 20th century chemists!

New Developments in the Photonic Applications of Conjugated Polymers

Abstract: I. Semiconducting Polymers as Materials for “Plastic” Photonics Devices Solid-state photonic devices are a class of devices in which the quantum of light, the photon, plays a role. Because the interband optical transition (absorption and/or emission) is involved in photonic phenomena and because photon energies from near-infrared to near-ultraviolet are of interest, the relevant materials are semiconductors with band gaps in the range from 1 to 3 eV. Typical inorganic semiconductors used for photonic devices are Si, Ge, and Group III-V and Group II-VI alloys.1 Conjugated polymers are a novel class of semiconductors that combine the optical and electronic properties of semiconductors with the processing advantages and mechanical properties of polymers. Important examples of polymers within this class include poly(p-phenylenevinylene) (PPV), poly(p-phenylene) (PPP), and polyfluorene (PF) derivatives whose molecular structures are shown in Figure 1. The relative simplicity with which high photoluminescence (PL) efficiency polymers of different colors can be achieved is in stark contrast to inorganic semiconductors, where, for example, bright blue light emitting diodes (LEDs) were not available until recently because of the difficulties in growing InGaN films.2 Most of the photonic phenomena known in conventional inorganic semiconductors have been observed in these semiconducting polymers. The dream of using such materials in high-performance “plastic” photonic devices is rapidly becoming reality: high-performance photonic devices fabricated from conjugated polymers have been demonstrated, including diodes,3 light-emitting diodes,4 photodiodes,5 field-effect transistors,6 polymer grid triodes,7 light-emitting electrochemical cells,8 and optocouplers,9 i.e., all the categories that characterize the field of photonic devices. These polymer-based devices have reached performance levels comparable to or even better than those of their inorganic counterparts. For a recent review of progress in plastic photonic devices fabricated with semiconducting polymers, see ref 10.

Nitridomanganese(V) Complexes: Design, Preparation, and Use as Nitrogen Atom-Transfer Reagents

Abstract: Oxidation of organic substrates by direct oxygen-atom transfer from transition-metal complexes is of fundamental importance and has been subject to intensive investigation. Highly selective methods for alkene epoxidation and dihydroxylation have been described and are commonly employed in synthesis. By contrast, significantly fewer reagents and protocols are available for the analogous nitrogen-atom-transfer process, despite the enormous potential utility of such methodology. Recent efforts by other groups to develop general olefin amination strategies have led to impressive advances in both metalcatalyzed hydroxyamination and aziridination. Our interest in this area has resulted in the preparation and characterization of novel nitridomanganese complexes which may be activated for nitrogen-atom transfer. Pivotal to the success of this research has been the development of new protocols for the construction of these manganese nitride (Mn≡N) reagents. These systems have proven to be versatile and effective aminating agents with different classes of olefins which include both silyl enol ethers and glycals (eq 1). The following account documents these findings and highlights the unique chemistry of these complexes as nitrogen-atom-transfer reagents.

Novel Multinuclear Catalysts for the Electroreduction of Dioxygen Directly to Water

Abstract: The electroreduction of O_2 to H_2O in aqueous acid at potentials close to the thermodynamically permitted value remains a daunting challenge for designers of superior fuel cells and batteries that utilize dioxygen as the reducible reactant. The four-electron reduction of O_2, which involves the rupture of the O-O bond and the formation of four O-H bonds, requires the use of catalysts to obtain useful rates at cathode potentials of interest in practical applications. The standard potential of the O_2/H_2O couple in solutions containing 1 M H^+ and saturated with O_2 at 1 atm is ca. 1.0 V (vs the saturated calomel electrode, SCE), but the highest cathode potentials achievable with currently available catalysts are closer to 0.55 V. (Molecules, functional groups, or metallic deposits that accelerate the rates of electrode reactions when they are confined to the surfaces of electrodes are often called electrocatalysts, a terminology that will be adopted in this Account.) Finely divided platinum supported on high area carbon is the electrocatalyst employed most frequently to achieve the electroreduction of O_2 to H_2O in presently available fuel cells. However, this type of electrocatalyst suffers from the disadvantages of high cost and gradual loss in catalytic activity as the surface area of the active platinum particles decreases because of sintering, dissolution, physical dislodgment, and/or adsorption of impurities. Searches for superior electrocatalysts for the reduction of O2 have often focused on cobalt porphyrins which are well-known to exhibit electrocatalytic activity toward the reduction of O_2, although H_2O_2 instead of H_2O is the usual product. However, it was discovered in recent years that a variety of molecular catalysts consisting of dimeric cofacial cobalt porphyrins adsorbed on the surface of graphite electrodes are able to catalyze the direct four-electron electroreduction of O_2 without passing through H_2O_2 as an intermediate. Both dimeric and monomeric iridium por phyrins have also been found to accomplish the electroreduction of O_2 to H_2O at unusually positive potentials. The mechanisms through which dimeric electrocatalysts are believed to operate involve the simultaneous interaction of both metal centers with the two oxygen atoms of the O_2 molecule as the O-O bond is severed. The ideas and strategies that underlay the development of these electrocatalysts have been described.

From Qinghao, marvelous herb of antiquity, to the antimalarial trioxane Qinghaosu - And some remarkable new chemistry

Abstract: The famous Qing Dynasty novel Honglou Meng or The Dream of Red Mansions by Xao Xueqin provides a wonderful insight into the extraordinarily sophisticated political and social life led by upper class Chinese in the late 16th and early 17th centuries. In one memorable sequence, as recorded in Chapter 51 of David Hawkes’s distinguished translation of the novel,1 a physician is called in to diagnose the malady of a maid-servant of Master Bao-Yu, who because of the cold weather, is ensconced in Master Bao-Yu’s bedroom. The physician, young and inexperienced, conducts the consultation with the patient concealed behind the bed curtain, and prescribes a decoction containing herbal constituentssperilla, kikio root, wind-shield, nepeta seed, thorny lime, ephedra, and others. However, Master Bao-Yu is not happy with the prescription, and in contrast to a prevailing acceptance of diagnosis and prescription today, is able to sum up sufficient courage to query the wisdom of the young physician in prescribing such harsh decongestants as thorny lime (Citrus spp.) and ephedra (Ephedra spp.) to a young lady. He calls for a re-examination by a physician of more established repute. The latter, of considerably greater age than the first, actually presents quite a similar prescription, although the thorny lime and ephedra are now replaced by the more gentle angelica (probably Angelica dahurica), bitter peel (Citrus spp.), and white peony root (probably Paeonia lactiflora). Bao-Yu thereupon orders the decoction to be prepared immediately within his household, “for the scent of boiling herbs is the finest in the world, far superior to the perfume of any flower...”. The knowledge which led Bao-Yu to question the prescription of the first physician is indicative of the sophistication of Chinese medicine at the time, and contrasts markedly with contemporaneous European practice. Knowledge was accessible to the wealthy household through detailed, carefully, and elegantly scripted pharmacopoeia. One herb which also was featured prominently in these pharmacopoeia, especially in relation to decoctions used to treat fever, was qinghao, the “bluegreen” herb (Artemisia annua). Recorded use of qinghao spans over 2000 years, with written descriptions first appearing in 168 B.C. in the Mawangdui Han Dynasty Wu Shi Er Bing Fang Lun (Treatments for 52 Sicknesses), and as late as 1798 in the Wen Bing Tiao Bian (Book of Fevers). The most detailed description appears in the mammoth Ben Cao Gang Mu (Compendium of Materia Medica) compiled in 1596 by the great Ming Dynasty physician Li Shi-Zen, and which is still printed in China today.2 With this background of use, qinghao was a prominent target for investigation in a Chinese program, involving Chinese chemists, pharmacologists, and botanists, designed to isolate and identify possible new antimalarial drugs.3 In 1972, after activity-guided bioassay involving ether extracts, there was isolated a remarkable new compound which the Chinese called qinghaosu (compound 1), the “active principle of qinghao”. The compound was demonstrated to have substantial antimalarial activity. Chinese chemists then embarked on a major program which entailed both derivatization of qinghaosu to provide compounds with better formulation characteristics and clinical trials on qinghaosu and selected derivatives.3 Within this program, the Chinese prepared the oil-soluble artemether (2) and arteether (3) and the water-soluble artesunate (4). The program was noteworthy for its success in demonstrating to the world the advent of a new antimalarial drug and its derivatives, which structurally are entirely unrelated to the classical antimalarials based on quinine and synthetic analogues. Qinghaosu, artemether, and artesunate are now used for treatment of severe malaria, and with sanction and support from the World Health Organization, Geneva, it may be said that

Construction and Design of β-Sheets

Abstract: Introduction De novo protein design and architecture both focus on the construction and design of three-dimensional structures. Although these disciplines work on vastly different scales, they nevertheless share two requirements: a structural design and an understanding of the physical properties which govern the stability of that structure. Our knowledge of physics and engineering has allowed architects to devise magnificent buildings that can be stably constructed to serve the intended purpose. Protein designers, on the other hand, have a greater challenge realizing their intended structures because accurately predicting a protein’s stability is not yet possible. Although it is well-documented that a protein’s folded threedimensional structure is encoded by its amino acid sequence, currently that folded structure cannot be predicted from sequence information alone. Therefore, the studies of protein stability, protein secondary structure, and de novo protein design are intimately interconnected. Stability studies provide insight for the design of proteins that will fold into predetermined structures and perform specified functions. Protein design, on the other hand, provides an opportunity to test our grasp of the rules that underlie protein structure and stability. Understanding â-sheet formation is the key to a host of problems and applications involving protein folding and design. For example, the formation of a â-hairpin has a profound effect on reducing the conformational space and defining the long-range interactions for a folding protein. Although the characterization and de novo design of R-helical structures have dominated the field in the past, interest in â-sheet stability and design has intensified for several reasons. Recent studies have emphasized that there are many proteins in which â-sheets play functionally important roles. â-Sheets can provide the key element in protein-DNA,1 protein-RNA,2 and protein-protein recognition.3 Several of these interactions are based upon direct, edge-on â-sheet contacts, which can often be mimicked by peptides, for example, the dimerization of HIV protease4 and P pilin binding to the PapD chaperone.5 Even the behavior of the hormone erythropoetin can be mimicked by disulfide-linked â-hairpin peptides.6 Aggregated protein fibrils exhibiting predominantly â-structure have been implicated in amyloid diseases.7 Recently, several groups have begun to quantify the energetics of the interactions that stabilize â-structure in simple model systems and to formulate guidelines which will allow the structure and stability of â-sheets to be manipulated in a rational fashion.

Working against Time: Rapid Radiotracer Synthesis and Imaging the Human Brain

Abstract: In this Account, the authors describe some advances in radiotracer chemistry which have made it possible to probe the chemical anatomy of the human brain while working within a very restricted time scale. Though we highlight research from our laboratory, it is important to emphasize that advances in PET brain imaging have come from many laboratories throughout the world. Thus, for a more comprehensive treatment of PET technology the reader is referred to textbooks and review articles cited in this Account. Since many of the milestones in delineating biochemical transformations and the movement of drugs in the human brain have involved radiosynthesis with carbon-11 and fluorine-18, we focus on these two isotopes. 50 refs., 6 figs., 1 tab.