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The First Book about Geodesic Polyarenes, Carbon Nanorings, and Aromatic Hydrocarbon Belts
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The book Fragments of Fullerenes and Carbon Nanotubes: Designed Synthesis, Unusual Reactions, and Coordination Chemistry grew out of a very successful symposium on the same topic that was held in conjunction with the 2008 national meeting of the American Chemical Society in Philadelphia. Shortly after that meeting, an editor from John Wiley & Sons approached Professor Lawrence T. Scott and Professor Marina Petrukina from the University at Albany, who had coorganized the symposium, about publishing a book on this burgeoning branch of chemistry. The two agreed to accept the challenge, and each contributed a chapter to the book from their own research. The other chapters in this edited monograph were written by prominent experts in the field from all over the world, many of whom had spoken in the symposium. The chapter written by Professor Scott on “Hemispherical Geodesic Polyarenes: Attractive Templates for the Chemical Synthesis of Uniform Diameter Armchair Nanotubes” reports previously unpublished results from the Ph.D. thesis of former BC graduate student Anthony Belanger, as well as contributions from the undergraduate research of former BC chemistry major and Scholar of the College Katherine Mirica and early groundwork by former postdoctoral fellow Dr. James Mack. The front cover of the book is adapted from “La Tricoteuse,” a painting by William Adolphe Bouguereau (1825-1905), digitally modifed to show the girl knitting a scarf in the likeness of a carbon nanotube.
For a video interview with Professor Scott about this book, go to:
http://www.bc.edu/sites/libraries/facpub//scott-fragments
For more details and a list of chapters, go to:
http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470569085,subjectCd-CH72.html
(03.21.12)
The First Chemical Synthesis of a Short, Rigid, Structurally Pure Carbon Nanotube
The discovery of carbon nanotubes in 1991 almost instantly inspired dreams among scientists and engineers about how these light weight, super strong, heat resistant, ultra thin nanowires could someday be used to miniaturize electronic devices down to the nanometer scale, well beyond the limits of what can ever be achieved by lithography on silicon chips. Unfortunately, not all carbon nanotubes (CNTs) are alike. Some are semiconductors, whereas others are highly conductive, like metals, with current carrying capacities up to 1000 times greater than that of copper wire. Despite two decades of extensive experimentation worldwide, however, all known preparation methods still yield mixtures of different types of CNTs that are virtually impossible to separate into their individual components in useful amounts. Stimulated by the challenge to address this long-standing problem, Professor Lawrence Scott and his students began exploring a revolutionary new production strategy involving the controlled elongation of small hydrocarbon templates, such as hemispherical nanotube end-caps, prepared by bottom-up chemical synthesis; the diameter and rim structure encoded in the template would dictate the diameter and chirality of the resulting CNT. Toward that objective, the Scott laboratory has succeeded in synthesizing a short CNT by chemical methods in just three steps from corannulene, a readily available starting material. The new C50H10 geodesic polyarene has been isolated, purified, crystallized, and fully characterized by NMR spectroscopy, UV-vis absorption spectroscopy, high resolution mass spectrometry, and X-ray crystallography. With this advance, a major obstacle to the rational synthesis of structurally uniform CNTs has been overcome. Only now that a small hydrocarbon template such as this is finally available can methods for elongating it into uniform CNTs be tested or invented. Work on this final phase is currently in progress. Financial support was provided by the National Science Foundation and the Department of Energy.
To read the article, go to:
http://pubs.acs.org/doi/abs/10.1021/ja209461g
To read other accounts of this work, go to:
http://pubs.acs.org/doi/pdf/10.1021/ja212036w
(01.01.12)
A Practical and Catalytic Method that Provides Access to Many Biologically Active Molecules
A large number of biologically active macrocycles contain a C–C double bond through which various other derivatives are prepared; the stereochemical identity of the alkene or the resulting moieties can be critical to the beneficial properties of such molecules. Catalytic ring-closing metathesis (RCM) is a widely employed method for the synthesis of large unsaturated rings; however, cyclizations often proceed without control of alkene stereochemistry. Such shortcoming is particularly costly with complex molecules when cyclization is performed after a long sequence of transformations. In the most recent issue of Nature (2011, 479, 88–93; doi:10.1038/nature10563), Professor Amir Hoveyda, graduate student Miao Yu and postdoctoral fellow Chenbo Wang disclose a practical and general approach for efficient and highly stereoselective synthesis of macrocyclic alkenes by catalytic RCM; transformations deliver up to 97% Z selectivity due to control induced by a tungsten-based alkylidene. The exceptional utility of the method is demonstrated by stereoselective preparation of highly potent anti-cancer agents epothilone C and nakadomarin A, previously reported syntheses of which have been marred by late-stage non-selective RCM. The team reports that the tungsten alkylidene can be manipulated in air, promoting reactions carried out in a fume hood to deliver products in useful yields and high Z selectivity. As a result of efficient RCM and re-incorporation of side products into the catalytic cycle with minimal alkene isomerization, desired cyclizations proceed in preference to alternative pathways even under relatively high concentration (0.1 molar). The research, conceived and largely performed in the Boston College laboratories by Wang and Yu, is in collaboration with Professors Richard Schrock (MIT) as well as Professor Darren Dixon (Oxford) and two members of his team. Financial support was provided by the National Institutes of Health and the UK ESPRC.
To read the article, go to:
http://www.nature.com/nature/journal/v479/n7371/pdf/nature10563.pdf
(11.04.11)
Novel Imaging Agents of Cell Death
Essentially all anticancer drugs work by directly or indirectly inducing apoptosis of cancer cells, the programmed cell death pathway. Therefore, noninvasive imaging of apoptotic cells should enable prompt evaluation of the efficacy of cancer therapeutics. In principle, apoptotic cell death can be reliably detected by targeting the lipid molecule phosphatidylserine (PS), which in healthy cells is completely confined to the cytosolic side of the plasma membrane. In apoptosis, the distribution asymmetry is lost, resulting in PS exposure on the surfaces of dying cells. Natural PS-binding proteins are less than ideal as imaging agents of apoptosis for multiple reasons, including their large size, low stability, difficulty of labeling, and their poor tissue penetration. Small molecule ligands that specifically target PS may circumvent these problems and thereby serve as powerful imaging tools for cancer research and treatment. In their recent paper in the Journal of the American Chemical Society, Professor Jianmin Gao and coworkers report a new class of PS-targeting molecules that enables facile imaging of apoptotic cells. These PS-imaging agents are developed by using a biomimetic approach: the PS-binding epitope of the milk protein lactadherin are grafted onto a cyclic peptide scaffold; rational optimization using unnatural amino acids results in the cyclic lactadherin mimics (cLacs) that preferentially associate with PS-presenting membranes. The cLac design also benefits from the intrinsic membrane impermeability of peptides, which allows cLacs to target surface-exposed PS. A fluorophore labeled cLac effectively detects apoptotic cells under a fluorescence microscope. Given the small size and ease of synthesis and labeling, cLacs hold great promise for noninvasive imaging of cell death in living animals and ultimately in patients.
To read the article, go to:
http://pubs.acs.org/doi/pdf/10.1021/ja205911n
(09.12.11)
Kantrowitz Lab uses X-ray Crystallography to Provide a Molecular Level Description of Each of the Steps in the Catalytic Cycle of a Critical Metabolic Enzyme
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Graduate students Katharine Harris and Gregory Cockrell, along with undergraduate David Puleo, working with Professor Evan Kantrowitz have used protein crystallography and theoretical studies to provide a detailed mechanism of the reaction catalyzed by the enzyme aspartate transcarbamoylase. This enzyme catalyzes one of the first reactions in the biosynthesis of the pyrimidine nucleotides, the building blocks of DNA and RNA. This enzyme also helps to control the rate of the entire pathway and has become the target for the development of drugs that can be used to fight cancer and malaria. This work is important because it provides details on the molecular level of the active site of the enzyme and the steps involved in the catalytic reaction, which are critical for drug design. By combining data from three high-resolution X-ray crystal structures of the enzyme in the absence of ligands, in the presence of one of the enzyme’s two substrates, and in the presence of the bisubstrate/transition state analog with theoretical studies involving in silico docking and electrostatic calculations, the Kantrowitz Lab has been able to visualize each step in the catalytic cycle of ATCase, from the ordered binding of the substrates, to the formation and decomposition of the tetrahedral intermediate, to the ordered release of the products from the active site. These results provide a molecular level portrait of how this critical metabolic enzyme functions.
To read the article, go to:
http://dx.doi.org/10.1016/j.jmb.2011.05.036
(08.22.11)
Tan Lab Extends Its Scaffolding Catalysis Strategy To a Metal-free System for the Enantioselective Desymmetrization of 1,2-Diols
Students working with Professor Kian Tan have recently developed a new non-metal catalyst that uses reversible covalent bonding between catalyst and substrate in order to enhance both reactivity and selectivity. Graduate students Xixi Sun and Amanda Worthy disclosed in Angew. Chem., Int. Ed. that these scaffolding catalysts are highly effective for the enantioselective desymmetrization of 1,2-diols. For most synthetic catalysts, reversible covalent bonding is used to form a reactive intermediate, thereby affording enhanced rate of reaction. In this case reversible covalent bonding is implemented to transiently tether reagents. A key aspect of this mode of catalysis is that a part of the acceleration arises from the entropic advantage gained through intramolecularity. This mode of catalysis is infrequently used in synthetic catalyst designs but holds great promise as a general method for accelerating reactions.
To read the article, go to:
http://onlinelibrary.wiley.com/doi/10.1002/anie.201103470/pdf
(08.09.11)
Snapper Lab Builds Polycyclic Lactones by Powerful Tandem Catalytic Reaction Sequences
David F. Finnegan, working in Professor Marc L. Snapper’s laboratory developed a new ruthenium-catalyzed tandem reaction sequence that generates polycyclic compounds from acyclic precursors in one reaction flask. The process uses a single ruthenium additive to catalyze the two mechanistically distinct transformations; a ring closing metathesis followed by a hetero-Pauson-Khand cycloaddition. The key to developing this tandem process was to learn how to convert in situ the metathesis active ruthenium alkylidene into a hetero-Pauson-Khand cycloaddition catalyst. This was accomplished by treating the metathesis active ruthenium complex with CO to remove the alkylidene functionality, followed by a reductant (methoxide) and more CO to generate the active ruthenium (0) carbonyl complex that catalyzes the desired cycloaddition. This work was published as a “Feature Article” in the Journal of Organic Chemistry. The National Science Foundation provided financial support for these studies.
To read the article, go to:
http://pubs.acs.org/doi/pdf/10.1021/jo200359c
(07.12.11)
A Boron-Based Synthesis of the Natural Product (+)-trans-Dihydrolycoricidine
A synthesis of the natural product trans-dihydrolycoricidine has been accomplished through the aid of new boron-based chemical reactions developed in the laboratory of Professor James Morken. Postdoctoral fellow Dr. Sarah Poe (now at the Warner-Babcock Institute for Green Chemistry) developed a diastereoselective diboration reaction that converts cyclic dienes to single isomer cyclohexendiols (Eq. 1, above). This reaction occurs with excellent levels of stereoselectivity and can accomplish oxidations that have not been possible with singlet oxygen-based methods. Dr. Poe then employed this reaction along with catalytic allylboration reactions that the Morken group has also developed to provide an efficient synthesis of the target molecule. The work has been published in Angewandte Chemie.
To read the article, go to:
http://onlinelibrary.wiley.com/doi/10.1002/anie.201007135/pdf
(05.16.11)
Enantioselective Conjugate Addition of SiMe2Ph Catalyzed by a Chiral N-Heterocyclic Carbene
Research in the laboratory of Professor Amir Hoveyda has resulted in the development of the first catalytic method for forming carbon–silicon bonds that does not require an organometallic complex as the catalyst. This accomplishment is based on a discovery made two years ago in the Hoveyda group, illustrating that achiral N-heterocyclic carbenes (NHCs) – in the absence of a metal salt – can activate a B–B bond to catalyze efficient, but non-enantioselective, boronate conjugate additions to α,β-unsaturated carbonyl compounds. In a recent communication in the Journal of the American Chemical Society, Hoveyda and graduate student Jamie O’Brien disclose a metal-free method for enantioselective conjugate addition of the versatile dimethylphenylsilyl group to a wide variety of α,β-unsaturated carbonyl compounds. Transformations are catalyzed by a chiral N-heterocyclic carbene (NHC) and are performed in an aqueous solution, which makes them operationally simpler to perform than the NHC–Cu-catalyzed variant. The chiral catalyst, also originally developed in the Hoveyda group, is generated from a readily accessible enantiomerically pure imidazolinium salt (prepared in three steps) and a common organic amine base. NHC-catalyzed processes proceed with 5.0-12.5 mol % catalyst loading at room temperature within 1-12 hours, affording the desired products in up to >98:2 enantiomeric ratio and in up to >98% yield. Cyclic enones or lactones and acyclic α,β-unsaturated ketones, esters as well as aldehydes can be used as substrates.
To read the article, go to:
http://pubs.acs.org/doi/pdf/10.1021/ja203031a
(05.11.11)
Catalytic Z-Selective Olefin Cross-Metathesis for Natural Product Synthesis
Alkenes are found in a great number of biologically active molecules and are employed in numerous transformations in organic chemistry. Many olefins exist as E or higher energy Z isomers. Catalytic procedures for the stereoselective formation of alkenes are therefore valuable; nonetheless, methods for synthesizing 1,2-disubstituted Z olefins remain scarce. In an Article published in Nature, Professor Amir Hoveyda and his team report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and allylic amides, which have been employed until now only in E-selective processes; the resulting disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. The new transformations are promoted by catalysts that contain the highly abundant and inexpensive molybdenum, and are amenable to gram-scale operations. The Article introduces the use of reduced pressure as a simple and effective strategy for achieving high stereoselectivity. The utility of the new discovery was demonstrated by syntheses of anti-oxidant C18 (plasm)-16:0 (PC), found in electrically active tissues and implicated in Alzheimer’s disease, and the potent immunostimulant KRN7000. The research was performed by postdoctoral fellow Dr. Simon J. Meek, graduate student Robert V. O’Brien, and visiting scholar Josep Llaveria, from Spain, as part of the longstanding collaboration with Professor Richard Schrock at MIT. Funding was provided by the NIH (joint grant to Hoveyda and Schrock) as well as an NSF grant to Hoveyda; O’Brien is a LaMattina graduate fellow, and Llaveria was funded by the Spanish Ministry of Education.
For more details, see also:
http://www.nature.com/nature/journal/v471/n7339/full/471452a.html
To read the article, go to:
http://www.nature.com/nature/journal/v471/n7339/pdf/nature09957.pdf
(04.04.11)
Nature’s Clever Use of Thermal Fluctuations
Recent research published in the Proceedings of the National Academy of Sciences by Professor Udayan Mohanty has advanced our understanding of the clever ways the molecular machinery of life uses fluctuations and dissipation and the large role that thermal fluctuations between structures plays in enzymatic function.
With the advent of single molecule methods, scientists have begun to get a glimpse into how nature has developed its molecular machinery not only to deal with fluctuations, but even to use them to advantage. Single molecule experiments indicate that large and rare thermal fluctuations of the ribosome are essential to rotate the ternary complex into a position so as to facilitate stable contacts with the GTPase activated center (GAC) and the sarcin-ricin loop (SRC) in the large subunit.
In collaboration with Professor Steven Chu at U.C. Berkeley, Professor Mohanty and his students have explored how large, rare thermal fluctuations of the ribosome aid in the functioning of the ribosome. Their theoretical findings establish that configurations, which make significant contribution to the probability of the rare process, have the inherent property that they are localized tightly around the most likely configuration. Small variations in the re-positioning of cognate relative to near-cognate complexes lead to significant rate enhancement.
The protein functional groups, the structural positioning of the RNA, and the inner-sphere coordination of the protein atoms to them, create several unique motifs for the binding of Mg2+ ions in the large subunit of H. marismortuni and E. coli ribosomes. The paper examines over a dozen unique structural motifs of magnesium binding sites to further elucidate the interplay between structure, dynamics and function within the ribosome and to provide insights into how site-bound magnesium ions contribute to its structural stability.
To read the article, go to:
http://www.pnas.org/content/early/2011/02/15/1100671108.full.pdf+html
(02.28.11)
Zinc(II)-Catalysis of Keteniminium Ion Formation Enables a New Approach to Four-Membered Rings
The Ghosez synthesis of cyclobutanones based on keteniminium salts is a useful variant of the classic ketene–olefin [2+2] cycloaddition reaction. Each process generates four-carbon ring strain and formally accomplishes the vicinal carbofunctionalization of an alkene. Professor Jason Kingsbury and graduate student Jamie O’Brien have now published a full article in The Journal of Organic Chemistry that describes, for the first time, catalysis of keteniminium–alkene cyclocondensation. The new transformations take place with complete regiochemical control at room temperature in the absence of solvent, giving functional cycloadducts with hindered all-carbon-substituted stereocenters. Their studies also include the results of extensive ab initio calculations carried out in collaboration with recent graduate Dr. Adil Zhugralin to help elucidate the reaction mechanism. The authors hope that their work can inspire modern enantioselective entries to substituted cyclobutanones, since prior strategies have relied exclusively on pyrrolidine-based chiral auxiliaries.
To read the article, go to:
http://pubs.acs.org/articlesonrequest/AOR-SGQ6arihxvf5DaJSAZ5j
(02.18.11)
Professor Kian Tan's synthesis of beta-amino-aldehydes
The synthesis of beta-amino-aldehydes has been achieved through enantioselective hydroformylation of PMP-protected allylic amines. The reaction is accomplished by using a scalemic scaffolding ligand that covalently and reversibly binds to the substrate. These ligands behave like chiral auxiliaries because they are covalently attached to the substrate during hydroformylation; however, similar to traditional asymmetric ligands, they can be used in catalytic quantities. The directed hydroformylation of disubstituted olefins occurs under mild conditions (35 °C and 50 psi CO/H2), and Z-olefins afford excellent enantioselectivities (up to 93% ee).
To read the article, go to: http://pubs.acs.org/doi/abs/10.1021/ja107433h
To read a published commentary on the article, go to: http://onlinelibrary.wiley.com/doi/10.1002/anie.201006489/abstract
(02.07.11)
Professor Lawrence Scott’s article highlighted on the cover of Journal of Materials Chemistry
Carbon nanotubes have been widely touted for their potential to fulfill dreams in materials science and nanotechnology. Despite intense scrutiny by scientists and engineers worldwide for two decades, however, these fascinating carbon-rich materials are still being made today by poorly understood empirical methods that produce inseparable mixtures of tubes, the properties of which vary widely as a function of tube diameter and chirality. This inhomogeneity has seriously impeded realization of numerous applications envisioned in molecular scale electronics that require single-walled nanotubes (SWNTs) with uniform properties. Only those tubes that exhibit metallic properties can serve as electrically conductive nanowires, for example.
Professor Scott and graduate student Eric H. Fort have recently demonstrated that nitroethylene can serve as a highly reactive “masked acetylene” for converting aromatic hydrocarbon bay regions into new, unsubstituted benzene rings by a one-pot Diels-Alder cycloaddition/rearomatization reaction sequence, and this new methodology holds great promise as a strategy for the metal-free growth of single-diameter, single-chirality carbon nanotubes from small hydrocarbon templates (see doi/pdf/10.1021/ja907802g and doi/10.1002/anie.201002859/pdf). In their recently highlighted J. Mater. Chem. article, Fort and Scott report molecular orbital calculations on the Diels–Alder reactivity of aromatic belts and hemispherical end-caps of varying dimensions, and their results offer strong support for the feasibility of this strategy. Bay regions on the rim of a [10,10]nanotube end-cap are predicted to exhibit Diels–Alder reactivity comparable to that of bay regions in planar polyarenes that have already been successfully transformed into new benzene rings by nitroethylene. Some hurdles still remain, but the day is drawing nearer when SWNTs of predefined diameter and chirality will be “made to order” by chemical methods in the laboratory.
To read the article, go to:
http://pubs.rsc.org/en/Content/ArticleLanding/2011/JM/C0JM02517H
(01.01.11)
Atmospheric Research at Boston College
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Figure: Measured Cloud Condensation Activity (k) as a function of measured oxygen to carbon (O/C) ratio for a range of aerosol materials (listed in the inset).
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Research in the Davidovits laboratory focuses on the climate effects of atmospheric aerosol particles. Such particles are produced by both biogenic and human activities and play key roles in the development of cloud cover. All cloud droplets contain an aerosol particle that acts as a center for the condensation of water vapor. Only hydrophilic aerosols can serve as cloud condensation nuclei (CCN). Thus aerosol particles affect cloud cover and cloud stability, thereby impacting radiation balance.
The composition of aerosol is highly complex and subject to continual change in the atmosphere. Inadequate representations of aerosol cloud formation (CCN) activity and the resulting effects on cloud albedo and cloud lifetime represent particularly large sources of uncertainty in current climate models. A central aim of Professor Davidovits’s research is to obtain a simple, reliable characterization of the CCN activity of organic aerosol.
A single parameter formulation of CCN activity has recently been introduced and designated as k. This CCN activity parameter incorporates the initial (dry) particle size and the critical supersaturation of water vapor required to form cloud droplets. However, k also depends on particle composition. Thus, in principle, if the particle composition and size are known, CCN activity can be extracted from the k value.
A critical challenge to the success of this approach has been finding a way to represent simply the complex composition of organic aerosols. In recent work from the Davidovits laboratory, it has been found, within experimental accuracy, that k correlates linearly (or nearly so) with the aerosol (O/C) ratio, possibly independent of particle composition, particle diameter, or method of oxidation for a wide range of atmospherically-relevant organic aerosol precursors (see figure). Such a simple general correlation as this represents a significant step toward the goal of more accurately climate modeling.
This work was performed at Boston College as a joint project involving researchers from Boston College, Aerodyne, and two research groups from Finland.
Publication:
“Relationship between aerosol oxidation level and hygroscopic properties of laboratory generated secondary organic aerosol (SOA) particles.” Massoli, P., A.T. Lambe, A.T. Ahern, L. R. Williams, M. Ehn, J. Mikkilä, M. R. Canagaratna, W. H. Brune, T. B. Onasch, J. T. Jayne, T. Petäjä, M. Kulmala, A. Laaksonen, C. E. Kolb, P. Davidovits, and D. R. Worsnop.. Geophys. Res. Lett. 37, L 24801, doi:10.1029/2010GL045258, 2010.
To read the article, go to:
http://www.agu.org/pubs/crossref/2010/2010GL045258.shtml
(12.27.10)
Homegrown Catalyst Provides a Solution to a Problem in Synthesis
Discovery and development of catalytic methods for enantioselective conjugate additions of easily accessible C-based nucleophiles to unsaturated carbonyls faciliates the synthesis of a large assortment of enantiomerically enriched biologically active molecules and are therefore of great significance. Nevertheless, notable shortcomings persist in this area, particularly in the context of reactions furnishing quaternary carbon stereogenic centers. One deficiency relates to the paucity of protocols for catalytic conjugate additions of vinyl groups. Recent research in the Hoveyda group, reported in a recent Communication in the Journal of the American Chemical Society and performed by graduate students Tricia L. May and Jennifer A. Dabrowski, puts forward an exciting new method for enantioselective conjugate addition of silyl-substituted vinylaluminum reagents to five- and six-membered b-substituted cyclic ketones. Reactions are catalyzed by a chiral bidentate N-heterocyclic carbene-copper catalysts, originally designed and developed in the Hoveyda laboratories and used for a wide range of other important transformations such as enantioselective olefin metathesis, allylic substitutions, hydroboration and diboration reactions. The new catalyst is derived from air stable and commercially available CuCl2•2H2O, affording the desired products in up to 95% yield and >98:2 enantiomeric ratio. The resulting enantiomerically enriched vinylsilanes can be protodesilylated, converted to the corresponding vinyl halides, or oxidized to b-acyl-substituted enones in high efficiency. The utility of the NHC–Cu-catalyzed reaction has been demonstrated through a concise enantioselective total synthesis of natural product riccardiphenol B.
To read the article, go to:
http://pubs.acs.org/doi/pdf/10.1021/ja110054q
(12.10.10)
New Water Splitting Electrodes Developed
One key challenge in materials research is how to tailor certain aspects of the intrinsic properties of a material without adversely altering others. This problem has made it extremely difficult to progress at a meaningful pace in several critical fields, such as efficient energy storage and high-capacity energy storage. In a recent study, Assistant Professor Dunwei Wang, demonstrates that this challenge can be addressed, at least in part, by forming heteronanostructures. Differing from simple nanostructures, heteronanostructures consist of multiple parts, each of which may be selected or tailored independently. When combined, they contribute to offering a collection of property features that are not found in simple nanostructures, thus making high-efficiency solar water splitting possible. An important step to this goal is recently reported in Angew. Chem. Int. Ed. (doi: 10.1002/anie.201004801), in which the Wang group achieved WO3-based photoelectrodes that are stable in neutral solutions (pH 7) and exhibit high catalytic activities. The discovery was enabled by the introduction of two material components – a TiSi2 nanonets for effective charge transport and an oxygen evolving catalyst (provided by their collaborator, Assistant Professor Harvey Hou, at the University of Massachusetts at Dartmouth) for fast charge transfer. Building on this success, the Wang group is presently applying similar design concepts to construct electrodes that will permit practical water splitting as a form of energy harvesting and storage.
To read the article, go to:
http://dx.doi.org/10.1002/ange.201004801
(12.10.10)
The total synthesis of sclerophytin A by the Morken Group
The oxygenated cembrane diterpenes are a large class of natural products comprising cladiellins, briarellins, asbestinins, and sarcodictyins. Their intricate chemical structures have captivated many in the synthetic chemistry community. In addition to intriguing structures, these compounds also tend to possess potent biological activity. Amongst the cladiellins, sclerophytin A is a particularly striking compound; it was isolated from the marine soft coral Sclerophytum capitalis and found to exhibit remarkable potency against mouse leukemia cells (cytotoxic at 1 ng/ml versus L1210 cell line), yet its original structural formulation was incorrect. Total syntheses by the Paquette and Overman groups established the correct formulation of sclerophytin A to be that depicted in Scheme 1. As a means to examine the utility of the stereoselective Oshima-Utimoto reaction in chemical synthesis, Professor James Morken's research group has been attracted to the target sclerophytin A and its structural relatives. In this study, we show that (-)-sclerophytin A can be constructed in 13 steps from geranial. Highlights from the synthesis are a stereoselective Oshima-Utimoto reaction, a Shibata-Baba indium-promoted radical cyclization, and a novel stereoconvergent epoxide hydrolysis.
To read the article, go to:
http://pubs.acs.org/doi/abs/10.1021/ja108185z
This work was highlighted in Nature Chemistry. See: http://www.nature.com/nchem/reshigh/2010/1110/full/nchem.927.html
(10.4.10)
Professor Larry McLaughlin's research featured in Chemical & Engineering News
To control the expression products from unwanted genes including those from oncogenes, transformed cells and viral infections, it would be very valuable to target and inhibit the process of RNA transcription. Gene-specific pharmaceuticals would result. This process begins with the ability to recognize specific double-stranded DNA sequences. The natural processes for such recognition and control relies typically with proteins (suppressors and repressors) binding to DNA and selectively preventing transcription. Our understanding of the recognition processes between proteins and specific DNA sequences is not sufficient to design and prepare a protein product to target a unique double-stranded sequence.
The use of a single strand of DNA to target duplexes is feasible, but to date the one residue to one base pair format (resulting in DNA triplexes) has been limited to polypurine sequences; targets that are not biologically very prevalent, particularly in the DNA sequences of interest. We are developing a fundamentally new type of recognition format in which a third strand of DNA (or the related peptide nucleic acid, PNA) inserts itself between two Watson-Crick faces of the base pairs of the target duplex. The resulting Janus-Wedge (J-W) triplex (Janus after the Roman god often depicted with two faces) can be generalized to any duplex target. The success of this project will lead to a new generation of gene-specific pharmaceuticals.
To read the article, go to:
http://pubs.acs.org/cen/email/html/8839sci1.html
(10.4.10)
The Gao Group Publishes a VIP in Angewante Chemie
The latest research of the Gao group, appearing as a VIP article in Angewante Chemie, has ushered a new modality of molecular recognition into protein design. VIP (Very Important Paper) designation in Angewante Chemie represents the highest recommendation that a manuscript may receive in peer review. According to the journal, less than 5% of their manuscripts receive this distinction.
Well-programmed assembly of biomolecules serves as the foundation of the complex and hierarchical organization of biology. The exquisite specificity of molecular assembly is driven by a collection of noncovalent forces, including the well-characterized hydrogen bonding and electrostatic interactions. The report by Professor Jianmin Gao and his student Hong Zheng demonstrates for the first time that the quadrupolar interaction between aromatic rings can be utilized to program the specific assembly of protein molecules.
Aromatic compounds – benzene, for example – display an electronegative center and electropositive edge. This uneven electron distribution gives zero dipole, yet a big quadrupole moment. Perfluorinated benzene exhibits an opposite quadrupole and tends to bind benzene in a face-to-face geometry. To evaluate the potential of this unique noncovalent interaction in protein design, Gao and Zheng replaced all four aromatic residues in the core of a homodimeric protein with the perfluorinated variants. Structured as a homodimer on its own, the fluorinated mutant disrupts the native dimeric fold of the wild type protein to form heterodimers exclusively. The homodimer to heterodimer conversion is attributed to the cross affinity of aromatic side chains and the perfluorinated analogues. The authors further quantified the energetic scale of the quadrupole interaction between phenyl and perfluorophenyl moieties to be ~1.0 kcal/mol, comparable to that of weak hydrogen bonds.
The report by Gao and Zheng clearly demonstrates the aromatic quadrupolar interaction can direct protein-protein interactions in water. This new recognition element greatly expands our toolbox for programming protein assemblies in order to achieve novel materials for biomedical applications.
To read the paper, go to:
http://onlinelibrary.wiley.com/doi/10.1002/anie.201002860/abstract
(8.18.10)
Professor Kian Tan's Research is Highlighted in Chemical & Engineering News
A bifunctional amine-phosphine ligand designed to simultaneously bind the substrate and catalyst in hydroformylation reactions is proving to be a versatile directing group for organic syntheses, report Professor Kian L. Tan and coworkers of Boston College (J. Am. Chem. Soc., DOI: 10.1021/ja1036226). Tan’s group has previously shown how this so-called scaffolding ligand’s amine group helps bind an olefin substrate and the phosphine group helps bind a rhodium catalyst, leading to regio- and stereoselective hydroformylation of mono- or disubstituted olefins. Stoichiometric amounts of phosphorus-based directing groups were previously required to carry out such reactions, but by reversibly binding the substrate and catalyst, only a catalytic amount of the scaffolding ligand is needed. Tan, Xixi Sun, and Kwame Frimpong have now demonstrated that the scaffolding ligand selectively directs formation of a quaternary carbon, rather than preferentially forming a lactone, in the hydroformylation of styrene-based substrates (reaction shown, R = aryl groups). A general method of using hydroformylation to create highly substituted carbon centers in olefins had been lacking, the researchers note. The synthesis “demonstrates the power of directing groups to overturn inherent selectivities of reactions,” they write.
(8.18.10)
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