|
Chemistry
Faculty Research Summaries | Chairman's Introduction
R. Stephen BerryDynamics of small and medium size systems. This subject has several facets. One is the exploration of the effects of correlation on the electronic structure of atoms and molecules, for example on whether the quantization is independent-particle-like or collective. Electron correlation plays a particularly important role in negative ions. We are carrying out experiments on two-photon detachment of electrons from negative atomic and molecular ions and also on detachment of electrons in collisions of negative ions with excited, neutral energy donors - "Penning detachment." Another aspect of this general area concerns the behavior of atomic and molecular clusters. An important issue here is exploring the topography of the multi-dimensional potential surfaces and relating the topography to such manifestations as dynamic equilibrium among isomers, phase equilibria, surface melting, and glass formation. For example, many kinds of clusters can exhibit solid-like and liquid-like forms that coexist in equilibrium like chemical isomers within a band of temperatures and pressures. How this coexistence behaves as the number of particles in the cluster increases has generated new insights into the nature of the melting/freezing process and into super heating and super cooling. The interpretation of topographies and dynamics on complex potential surfaces has led our group into a study of protein folding, dynamics and kinetics. This work has shown that the same general principles that determine how well a cluster finds a selective structure, such as a crystalline or polyhedral form, also determine how effectively a protein finds its active structure. This work has now led into investigations of self-assembly of proteins and of effects of mutations on structure and folding. Clusters have also proven to be useful laboratories for studying chaos and ergodicity. Very small systems actually become more ordered and less chaotic when they "melt" but the pseudo ordering process associated with a very few degrees of freedom is masked in larger clusters composed of even as few as 5-7 particles. The research on clusters has consisted of computational and theoretical studies until now. We are beginning a program of experimental work to complement the theoretical studies, especially of phase equilibria. Finite-time thermodynamics. The extension of thermodynamics to describe processes operating under constraints of finite time or nonzero rate is the goal of this work. finding natural bounds on performance of processes with time constraints is part of the objective of this work; finding the process paths that yield optimum performance is another part. Examples include finding the optimum performance of the idealized automobile engine and how existing engines could be made to operate more efficiently, and determination of the limits on performance of distillation and other heat-driven separation processes. Brice BosnichThree projects are currently in progress. The respiratory protein hemerythrin found in marine worms transports molecular oxygen by employing two iron atoms in a chemically subtle way. The mechanism of this process is currently being studied using low molecular weight analogues of the protein. In a related project, bimetallic complexes which activate molecular oxygen are being studied with a view to developing catalysts which use atmospheric oxygen for the oxygenation of organic substrates, particularly hydrocarbons. A third area of study concerns the use of supramolecular chemistry for recognition and incorporation of inorganic salts and of charged organic molecules. The supramolecular structure are such that molecular switches may be developed with these incorporated guests. Laurie J. ButlerOur research investigates the fundamental molecular dynamics and electronic energy transfer processes that determine the pathways of chemical reactions. Much of the current understanding of chemical reaction dynamics relies on the Born-Oppenheimer separation of nuclear and electronic motion; this approximation allows one to calculate, for instance, the energetic barrier to the chemical reaction from first principles quantum mechanics. Our experiments show that for wide classes of chemical reactions this approximation breaks down, reversing the expected branching between energetically allowed chemical product channels (e.g. a different bond will break than the one predicted to!). The experimental studies are designed to both provide critical comparisons with predictions of emerging quantum theories on nonadiabatic reaction dynamics in small systems where the usual approximations we make for chemical dynamics break down and to develop an intuitive framework for understanding chemical reactions in condensed phase and biological systems. Our work uses two powerful and complementary experimental techniques, polarized emission spectroscopy to study the evolution of the dynamics during the subpicosecond reaction and measurement of photofragment velocity and angular distributions by crossed laser-molecular beam methods to determine the mechanism for forming specific reaction products over several energetically allowed ones. Recent work includes studies of the dynamics and product branching in reactions important in atmospheric processes and in combustion. The photodissociation channels of nitric acid, a molecule important in reactions involving OH radicals in the atmosphere, cannot be predicted within the usual chemical reaction rate theories. Our experiments show the orientation of the radical p electron on the forming OH radical as the N-OH bond breaks results in the NO2 reaction product only being formed in excited electronic states, never in the ground electronic state. In other work, we investigated the competition between two bond fission channels in amides, molecules which link together the peptides in proteins. We are interested in understanding unexplored features of reaction dynamics coming to the forefront with recent theory and experiment, including the effect of accessing different regions of the excited potential surfaces on the ensuing dynamics and branching between possible product channels. Robert N. ClaytonMany chemical elements show variations in the abundances of their stable isotopes in extraterrestrial materials (e.g., meteorites and lunar samples) which are much greater than variations in terrestrial materials. In some instances, these variations can be traced back to processes of nucleosynthesis, both in stars and in interstellar space. In other cases, isotopic variability has been introduced by processes of evaporation and condensation in the solar nebula from which the sun and planets formed. For other elements, isotopic variability results from interactions with energetic particles from the sun (solar ?ares and solar wind) or from the galactic cosmic rays. We use a variety of mass spectrometric techniques to measure isotopic abundances of many elements: H, C, N, O, Mg, Si, K, Ca, Ti, Cr, Fe, Ni, Sr, Zr, Mo, and others. In collaboration with scientists at the Argonne National Laboratory, we use Resonance Ionization Mass Spectrometry (RIMS) for measurement of nucleosynthetic effects in minor elements present in individual interstellar grains preserved in primitive meteorites. Isotope abundance variations are also powerful tools for investigation of terrestrial natural processes. For example, the geochemical cycling of carbon and nitrogen through the Earth's crust and mantle can be traced by means of their isotopic compositions. Similarly, the movements of aqueous ?uids in the Earth's interior are studied through the isotopic ratios of hydrogen and oxygen. Philip E. EatonMy group's research interests are focused on the synthesis and examination of new ring systems specifically designed as probes into the effects of molecular geometry on bonding, reactivity, strain, etc. In the course of our work we were first to synthesize cubane, pentaprismane, [2.2.2]propellane, the [n.2.2.2]paddlanes, and many other highly strained "unnatural" compounds. These systems have given us special opportunities to study the behavior of exceptionally strained molecules vis-à-vis their propensity for rearrangement and reaction. Cubane is the most highly strained, kinetically stable ring system available in quantity. We have used it as the source of even more highly strained compounds including 1(9)-homocubene (the most highly twisted olefin), cubene, (the most highly pyramidalized olefin), and such intriguing species as 1,4-dehydrocubane, cubyl cation (the "least likely" cation), and the cubylcarbinyl radical (the fastest rearranging saturated radical). These have "record" properties and as such have proven to be of fundamental importance in developing an understanding of bonding in strained systems. We have underway now synthetic efforts to synthesize hexaprismane (2 flat cyclohexanes fused by 6 cyclobutanes), the enormously high energy "flat" carbon system of [2.2.2.2]paddlane, and hetero analogs of such unnatural ring systems, for example, azacubane. As the geometric requirements of such compounds are far from ordinary, tactical synthesis is an exceptional challenge. Much of our work, therefore, is on the development and application of new synthesis methods and techniques. Diels-Alder reactions, photochemical cyclizations, electrochemical couplings, and metal-induced transformations are of particular interest. Cubanes and other unnatural products offer interesting practical applications as diverse as anti-viral agents, explosives, high-refractive index lenses, liquid crystals, specialty polymers, and fuel additives. We are particularly interested in the construction of new materials for use in nanoarchitecture projects. For example, we are now working on the synthesis and characterization of n-[cubylcubanes] and n-[diethynylcubanes]. These are stiff, rigid rods with dimensional stability. We plan to use their derivatives for the construction of 2-dimensionally crystalline Langmuir film gratings with controlled spacing at the molecular scale level Karl F. FreedOur research interests cover several areas of theoretical chemistry, including the electronic structure of molecules, the statistical mechanics of polymers in the liquid phase, and the long time dynamics of peptides and polymers in solution. We have developed a highly correlated ab initio electronic structure method that is designed to tackle the difficult problem of describing electronic excited states of molecules, as well as the transition states for chemical reactions. The method is a multiconfigurational generalization of the widely used MPn single reference configuration methods that are available in many commercial electronic structure packages. These new ab initio methods have been applied to describe the excited states of a number of conjugated p-electron systems, where our computed energies and oscillator strengths rival in accuracy the most advanced ab initio methods. Additional applications have been made to computing two-dimensional methyl mercaptan and three-dimensional hydrogen sulfide potential energy surfaces for the electronically excited states that are accessed in non-adiabatic photodissociation experiments carried out by Professor Butler's group. (The computations have been performed by a theory-experiment student also working with Prof. Butler.) Present work is focused on computing electronic spectra of radicals in interstellar space and the electronic properties of biological chromophores in its protein environment. Our electronic structure methods are unique in enabling us to derive from first principles the true valence shell effective Hamiltonian that is mimicked by the model Hamiltonians of purely semiempirical molecular orbital theories. We have computed the first fully correlated "ab initio" p-electron Hamiltonian that demonstrates why some assumptions of semiempirical p-electron theories are correct, but our computations for small conjugated p-electron systems indicate deficiencies of these older methods along with theoretically justified methods for their improvement. We have been developing a theory for the statistical thermodynamics of polymers in the liquid state. Our analytical theory is the first and only one to describe the influence of monomer molecular structure on the thermodynamic properties of polymer mixtures. Several applications explain small angle neutron scattering and thermodynamic experiments for mixtures of polymers in the liquid state. Our theoretical predictions of a strong pressure dependence to the small angle neutron scattering intensities has been verified. Likewise, we have predicted the possibility that certain block copolymers will form nano-scale ordered self-assembled structures in the liquid phase upon heating, a bold prediction subsequently verified experimentally. Recent extensions of the theory consider random copolymers, the influence of short chain branching and chain semiflexibility on miscibilities of polymers in the liquid phase, as well as the phase behavior of liquid crystalline systems. We have also devised a density functional theory of interfaces in polymer systems. Particular examples include the interfaces between phase separated polymers and the surface segregation profiles of polymers near an impenetrable, patterned surface. A key motivation is to understand the molecular features governing the rich array of observed phenomena. Our recent theory of reversible equilibrium polymerization in poly (a-methyl styrene) is being extended to explain rather unusual findings for the polymerization of the protein actin. The actin polymerization occurs in ecariotic non-muscle cells to provide part of the cell scaffolding and to enabling cell movement. Possible extensions are under consideration to treat the kinetics of the polymerization of tubulin, which provides the "tracks" for transport within living cells. Flexible aqueous peptides and solution polymers have important dynamical processes occurring on time scales far exceeding current capabilities for computer simulations of these systems. Thus, we are developing a theory of long time protein and polymer dynamics, where input information may be taken from computer simulations. The theory successfully uses this information to provide a realistic description of the longer time dynamics. While the initial applications of the theory compare well with experiments made by Graham Fleming's group (University of California, Berkeley), current research is studying the long time dynamics of small neurotransmitting peptides to test and refine various components of the theory. Other applications use coarse grained models of a b-barrel to describe the nonequilibrium dynamics occurring during protein unfolding. We are also developing fundamental theories for the dynamical consequences of molecule-solvent interactions. Robert GomerExperimental and theoretical studies of surface diffusion of adsorbates on single crystal metal surfaces. Thermal desorption from single crystal surfaces. Electron-stimulated desorption of chemisorbed and physisorbed atoms and molecules. Ultraviolet and X-ray photoelectron spectroscopy of adsorbates on metals. Chemisorption on metal overlayers on refractory substrates, e.g., CO or O on W(110)/Cu1 or W(110)/Pd1, W(110)/Hg. Philippe Guyot-SionnestSurface nonlinear optics. The interaction of laser radiation and surfaces is studied. The polarization and spectroscopic response of surfaces prepared in Ultra-High Vacuum and in liquids is used to determine their structure and composition. Surface dynamics. The very fast energy transfer and coupling mechanisms of small molecules with surfaces are followed with time-resolved laser spectroscopy. Relaxation of excited vibrational and electronic states will be investigated. Nanoscale optics. The optical response of subwavelength structures such as semiconductor clusters or "quantum dots" will be studied and new approaches will be investigated to perform optical spectroscopy on a nanometer scale. Jack HalpernMy research encompasses the fields of coordination and organometallic chemistry, kinetics and mechanisms of inorganic and organometallic reactions, catalytic phenomena, and bioinorganic chemistry. Chemistry of vitamin B12 and related compounds. The chemical properties of certain low-spin cobalt complexes, containing liquids such as cyanide, dimethylglyoxime, and Schiff bases, exhibit striking parallels with those of vitamin B12 and its derivatives, including reactions with alkylating agents to form organometallic derivatives. I am examining the mechanisms of these reactions and their possible significance as vitamin B12 model systems. Current studies are focused on the determination of cobalt-alkyl bond energies, particularly in relation to the role of cobalt-carbon bond homolysis in coenzyme B12 dependent rearrangements. Chemistry of oxygen complexes. Although the formation of dioxygen adducts of metal complexes is well known, such complexes have thus far exhibited disappointingly limited reactivity of the coordinated oxygen and little utility as intermediates in catalytic oxidation. Our studies are directed at the preparation of new oxygen adducts, their physical and chemical characterization, and the elucidation of the mechanisms of catalytic oxidation reactions involving such adducts. Oxidative addition and reductive elimination reactions. Our studies on such reactions are concerned with the elucidation of their mechanisms and reactivity patterns and with synthetic and catalytic applications. Current research is focused particularly on intra- and intermolecular reductive elimination reactions involving C-H bond formation.
Free radical processes in organometallic chemistry. Current studies are focused on several types of reactions of metal complexes leading to the formation of free radicals, notably: LnMo + RX LnM - X + Ro; LnM - H + > C = C < LnMo + > CH - C
Mechanisms of catalytic reactions of coordination and organometallic compounds. Transition metal complexes catalyze a variety of organic reactions such as oxidation, hydrogenation, carbonylation, and decarbonylation. While it is appreciated that such reactions proceed through stepwise mechanisms involving organo-metallic intermediates, the detailed mechanisms for the most part remain to be elucidated. My studies, directed at such elucidation are currently focusing with considerable success on the mechanisms of homogeneous catalytic hydrogenation of olefins, including asymmetric catalytic hydrogenation and hydrogenation via free radical mechanisms.
We study the molecular genetics of nitrogen fixation and photosynthesis in cyanobacteria and purple bacteria. Recently, we have begun to study genes encoding the enzyme acetyl-CoA carboxylase in plants.
The cyanobacterium Anabaena grows in filaments of 100 cells or more. When starved for nitrogen, specialized cells called heterocysts differentiate from the photosynthetic vegetative cells at regular intervals along each filament. Heterocysts are anaerobic factories for nitrogen fixation; in them, the nitrogenase enzyme complex is synthesized and the components of the oxygen-evolving photosystem II are turned off. More than 1000 genes are believed to be differentially expressed during the (irreversible) development of a heterocyst from a vegetative cell. We have cloned and sequenced genes for nitrogen fixation (nif) and others encoding RuBP carboxylase, glutamine synthetase, the D1, CP-47 and water-oxidizing proteins of photosystem II, all the components of phycobilisome rods, and the sigma and core sub-units of RNA polymerase. We also constructed cDNA libraries corresponding to the mRNA populations present uniquely at particular times of heterocyst development. More than 200 clones from these stage-specific libraries have been sequenced. Finally, mutants unable to fix nitrogen aerobically have been isolated. Among these are some that have altered heterocyst morphology or an altered pattern. Four of these have been studied in detail, using a complementation system to isolate the wild-type gene defective in the mutants. One mutant fails to deposit the necessary glycolipid layer that forms part of the heterocyst envelope. A second mutant fails to make any heterocysts at all. A third makes them only at the ends of filaments. A fourth makes them too late and too frequently! In these cases, the sequences of the complementing genes are highly informative, corresponding to proteins that participate in environment-sensing regulatory cascades. The relationships among these regulatory proteins are being worked out by using the Green Fluorescent Protein from the jellyfish as a cell-specific reporter of gene expression.
The purple bacterium Rhodobacter capsulatus carries out photosynthesis and nitrogen fixation at the same time. Its chromosome is a circle containing 3.7 Mb of DNA. We have constructed a fine-structure physical map of the chromosome based on a set of overlapping cosmids that cover it completely. All of the known genes of Rhodobacter have been located on the physical map. We have begun to determine the complete sequence of the chromosomal DNA, one cosmid at a time. To date, we have sequenced 3.7 Mb, nearly the entire chromosome. The few remaining gaps are being closed by walking steps on chromosomal DNA. One of the most remarkable discoveries in the sequence is the presence of nine different prophage chromosomes embedded in the bacterial chromosome.
Several unicellular cyanobacteria provide superb experimental systems for studies of the photosynthetic apparatus. We have cloned many of the genes encoding components of the light-harvesting systems and reaction centers and used those genes as insertional mutagens, inactivating one or more of the polypeptides of the photosystems. The mutant strains are being used in studies of energy transfer and electron transfer, monitored by time-resolved fluorescence decay measurements.
Fatty acid synthesis, in plants as well as in cyanobacteria, begins with the reaction catalyzed by acetyl-CoA carboxylase (ACC). ACC in bacteria, including cyanobacteria, is comprised of four subunits: biotin carboxyl carrier protein (BCCP), biotin carboxylase (BC), and two subunits of carboxyltransferase. In chicken, rat, yeast and plants all of these domains reside in a single polypeptide. We have cloned and sequenced genes encoding BC and BCCP from two cyanobacteria and used this information to design probes for the cloning of ACC cDNA from wheat. We have complete cDNAs for the wheat cytoplasmic and chloroplast forms of the enzyme and have expressed them in yeast. Yeast using the wheat enzyme are sensitive to herbicides that target the wheat enzyme, allowing a full study of structure/function relationships for this important enzyme. The wheat/yeast system will also be useful for production of crystallizable amounts of protein for structure determinations. We recently discovered that apicomplexan parasites (malaria, toxoplasma) have an ACCase that is similar to the wheat chloroplast form of the enzyme, that is, extremely sensitive to herbicides that target the wheat enzyme. The herbicides may be fruitfully used to treat the diseases caused by these parasites.
Our research is focused on studies of the interactions of very reactive, energy-rich molecules with transition-metal complexes. In some cases, the goal is to trap unusual molecular fragments as ligands; in other cases, to use metals to prepare otherwise inaccessible, very unstable molecules so that the fundamental details of their reaction chemistry can be studied. Two projects that reflect current research interests are outlined below:
I. Oxygen Transfer Reactions of Nitrous Oxide.
Since the early metals are oxophilic, it is unlikely that useful catalytic chemistry will be uncovered here, so we are now expanding our research to include late-metal organometallics in which the M-O bonds, once formed, will not be so strong that they can't be easily broken.
II. Chemistry of Diazene, NH=NH, and Related Molecules.
The goal of our research is to design, synthesize, and study inorganic and organometallic complexes and polymers that possess interesting electronic, optical, nonlinear-optical, magnetic, and photochemical properties. Central to our research is the use of high-resolution and time-resolved spectroscopic methods. We use the information from these techniques to develop a detailed understanding of the structures, bonding, and dynamics of the ground states and electronic excited states of molecules.
This knowledge enables us to rationally design new materials with enhanced properties. One of our goals is to prepare and electronically characterize transition-metal analogues of conjugated organic compounds and polymers. Our interest in developing these materials is motivated by the expectation that incorporating optically tunable and redox-tunable metal centers into the backbones on unsaturated organic compounds will significantly enhance the technologically valuable physical properties of conjugated organic systems. We have prepared a broad array of conjugated transition-metal complexes and polymers from multiply metal-metal and metal-ligand bonded building blocks and have systematically explored the electronic and structural analogies among these species and their organic counterparts. We are presently investigating the properties of these new classes of materials, particularly with reference to their potential applications in molecular electronics.
A second major area of research centers on the photochemistry and photophysics of high-valent complexes that contain multiple metal-ligand bonds. A primary objective of this work is to develop powerful excited-state oxidants. To this end, we have discovered rare examples of d0 complexes that possess long-lived excited states in fluid solution at room temperature. We are also exploring the photochemistry alkene and alkyne metathesis catalysts, with the aims of kinetically and thermodynamically enhancing the ground-state reactivity of these species and of developing systems capable of activating inert substrates as N2.
Research at the interface of organic and physical chemistry; chemical systems that can be controlled and can perform functions; chemical complexity. We use organic chemistry to control the structure of molecules; these molecules generate function on the nanoscale (molecules that convert chemical energy into mechanical work) and on the macroscale (organic electronic materials). We use microfluidics and microfabrication to control interacting chemical reactions; these reactions detect, transmit, amplify, and analyze chemical signals. Ultimately, this research may lead to functional systems of organic molecules, materials, and reactions that interact via fluidic and electrical networks and function at the level of complexity of a living organism. We expect that our research will lead to better understanding of molecular-scale energy conversion, and of complex chemical and biochemical processes and networks.
The Jordan research group is interested in the design, synthesis, and study of reactive organotransition metal complexes and the application of these compounds in catalysis, olefin polymerization, and organic synthesis. Students develop an extensive knowledge of the structures, bonding, and reactivity of organic, inorganic, and organometallic systems and use state-of-the-art laboratory and spectroscopic methods for the manipulation and characterization of reactive materials. Our current efforts focus on olefin polymerization catalysts and organic and organometallic synthesis.
Cationic, d0 metallocene complexes Cp2M(R)+ (Cp=h -C5H5; M=Ti, Zr, Hf) have been implicated as active species in soluble Ziegler-Natta olefin polymerization catalyst systems (e.g., Cp2MX2/MAO). The group has discovered general methods for the synthesis and isolation of complexes of this type and is studying their chemistry. We have shown that cationic Cp2Zr(R)(L)+ complexes (L=labile ligand) polymerize ethylene under mild conditions in the absence of Al cocatalysts or oxide supports.
Detailed studies of Cp2Zr(R)(L)+ complexes have provided important information about insertion, b -H elimination, M-R bond hydrogenolysis, and other reactions which are important in catalytic olefin polymerization. Such studies are providing new insights about the generation, structures, and reactivity of the active species/sites of soluble and heterogeneous olefin polymerization catalysts.
The group also is exploring applications of Cp2Zr(R)+ species in organic synthesis. This effort has led to the discovery of a Zr-catalyzed process for coupling pyridines and olefins in which ortho C-H activation in a Cp2Zr(H) (pyridine)+ species is a key step. Current efforts are focused on the development of chiral catalysts for stereoselective C-H activation/C-C coupling reactions.
We have used the insights gained from our studies of cationic metallocene complexes to develop many new classes of reactive metal alkyls and olefin polymerization catalysts which contain a variety of ligand types. For example, by utilizing carboranyl ligands in place of Cp- ligands, we have constructed neutral complexes, i.e. (h -C2B9H11)(h -C 5R5) M(R), which have the same structures, electron count, and frontier orbital properties as Cp2Zr(R)+ cations.
The carboranyl systems are very active catalysts for olefin polymerization and selective alkyne dimerization. More recently we have prepared novel cationic main group alkyl species, e.g., {RC(NR')2}Al(R)+ MeB(C6F5)3- , which polymerize ethylene in the absence of transition metals. These novel compounds offer many avenues for future research.
Thermodynamics, high temperature calorimetry. Recently our work on high temperature reaction calorimetry has stressed: 1) development of calorimetric facilities for precision calorimetry above 1100o; and 2) applications of these methods and techniques in thermodynamic studies of high temperature melts and refractory materials. Recent investigations have emphasized work on 1) mixtures of the noble metals with transition metals; 2) refractory borides, silicides, and related compounds; 3) intermetallic compounds formed between early and late transition metals.
New Strategies for Organic Catalysis and Target-Oriented Synthesis. The power of chemical synthesis lies in the ability of creating entities with new molecular structure and function. Our research program is centered in the field of modern organic synthesis with an emphasis on the development of new chemical transformations and their application to addressing problems of biological and medical significance. Specifically, we are designing transition metal-catalyzed processes involving unusual types of organosilicon compounds, as a prelude to the development of an arsenal of new methods for rapid and fully stereocontrolled assembly of complex synthetic targets. In addition to the synthesis of promising bioactive natural products, we are interested in generating chemical libraries of organic compounds capable of specific and potent modulation of apoptosis, a cellular process believed to be abnormally regulated in cancer cells. Thus, starting at the level of basic research in the area of organic and organometallic synthesis, it is our ultimate goal to provide new directions for the development of effective anticancer chemotherapeutic agents.
A wide variety of diseases are results of deficient or abnormal protein-lipid interactions. The elucidation of the interactions between specific proteins and lipids, and the ability to examine and manipulate biomembranes that mimic real life systems hold the key to a better understanding of these diseases. Our research interests lie in the interdisciplinary area which can be termed as "interfacial medicine". Using two-dimensional monolayers, either at the air-water interface or transferred onto solid substrates, and supported bilayers as model systems, along with various microscopy and scattering techniques, we plan to carry out fundamental studies on the interactions between lipids and proteins to gain insights into the biophysical aspects of these diseases. Two diseases of particular interest are listed below.
A complex mixture of lipids and proteins, known as lung surfactant, forms monolayers at the alveolar air-water interface. The surfactant lowers the surface tension to near zero, and is responsible for reducing the work of breathing. A lack of surfactant, either due to immaturity in premature infants or disease or trauma in adults, can result in RDS. In spite of the serious morbidity and mortality of the disease, a firm understanding of the role of surfactant in both normal and diseased lungs is still lacking. My group is interested in developing a detailed structure-function relationship for the various components of lung surfactant. In particular, we will examine the phase behavior of various mixtures of lung surfactant components, as well as the interactions between lung surfactant specific proteins and the surrounding lipid matrix. We will explore the effect of lung surfactant proteins on monolayer collapse dynamics, and the effect of serum proteins on the normal functioning of the lung surfactant. The knowledge gained from this should lead to an understanding of the morphological consequences of monolayer phase separation and collapse, which is necessary for the continued development of positive interventions for patients suffering from RDS.
Amyloid-Beta (Ab) Peptides and Alzheimer's Disease A-beta, a self-assembling 39-43 residue peptide generated by the proteolytic processing of the amyloid precursor protein, comprises the major proteinaceous component of neuritic plaques and vascular deposits that appear in Alzheimer's disease, and is implicated as one of the causal factors in the pathology of the disease. Since the Ab peptide fragment includes 28 residues just outside the membrane plus the first 11-15 residues of the transmembrane domain, it has been shown to display properties commonly associated with surfactants. My group is interested in understanding the aggregation of the Ab peptides, and in using two-dimensional thin films (either free-standing monolayers or supported bilayers) as "templates" to explore the possibility of surface-induced aggregation. We plan to study various isoforms of Ab and examine their surface activities and their association with model membrane systems in both their monomeric and aggregated states. This can elucidate the residue length dependence of the aggregation process, and help explain why the longer Ab isoforms may be more intimately associated with Alzheimer's disease pathology than their shorter counterparts. Ab is also known to aggregate and form fibrils, though the mechanism involved is still not well understood. Since the rate of this process can be adjusted by various experimental parameters, we plan to monitor the formation process, and characterize the structure of the fibrils formed. Our goal is to provide a model for Ab aggregation.
Other research projects in the group include the insertion of antimicrobial peptide protegrin-1 into model membrane systems, structures and dynamics of monolayer and bilayer domains, membrane sealing using poloxamers, and two-dimensional ordering of rod-coil copolymers. Experimental techniques employed in these studies include optical and scanning probe microscopy as well as x-ray and neutron scattering.
Van der Waals molecules. The structures of van der Waals molecules are extracted from the rotational fine structure in the electronic spectrum. The details of internal energy transfer and photodissociation are studied using emission spectroscopy. Mode selective van der Waals chemistry has been observed.
Amino acids and peptides in the gas phase. Amino acids and peptides are injected into a supersonic molecular beam by means of laser vaporization of the solid, and the electronic spectra of these species are studied. Information on conformations and on the excited electronic states of these species is obtained.
Intramolecular energy and electron transfer. Energy and electron transfer processes are studied in molecules consisting of two different chromophores spearated by various molecular spacers. The dependence of energy transfer rates on molecular conformation are observed.
Laser desorption. The properties of laser desorbed solids are measured to provide insight into the mechanism of the laser desorption process.
Development of mathematical and advanced computational methods to solve problems in chemical physics.
Quantum theory of gas-phase atomic and molecular scattering, both for inelastic (energy transfer) and reactive processes.
State-to-state cross sections and rate constants are calculated.
Exact quantum reaction rate constants by flux-flux autocorrelation function methods.
Theory of molecule-surface collision processes including inelastic processes.
Exact quantum statics and dynamics of small polyatomic molecules including theoretical spectroscopy, intramolecular vibrational energy relaxation, pre-dissociation, and isomerization.
My research group is concerned with interface that is created when a man-made material is brought into contact with a biological fluid. Our work is characterized by the development of new synthetic strategies for tailoring the structures of interfaces and the use of these substrates in both fundamental studies of cell adhesion and technologies used for drug
discovery.
One broad effort uses surfaces that are decorated with peptide ligands to understand the mechanisms that underlie cell attachment and behavior. In tissue, cells are attached to a protein matrix that comprises a large number of peptides which influence cell behavior. The complexity of the natural matrix makes it difficult to study the roles of discreet ligands. The model substrates that we have developed, which can control entirely the ligands with which an attached cell interacts, provide an unprecedented opportunity to understand the roles of individual ligands, and hence to understand the basis of many disease processes that stem from defects in the natural protein matrix.
A second effort is developing chip-based tools for the global analysis of cellular activities. We have developed methods to pattern thousands of peptide ligands to a glass slide--where each ligand occupies an area thesize of a human hair. These peptide chips are used to analyze the protein interactions and activites that reside with in tissue cells. Our work applies these tools to fundamental studies of cell behavior and to high throughput screening of drug candidates.
A third effort in the group is developing new strategies for the fabrication of nano-structured materials--where in materials have sizes that are 1/1000th the width of a human hair. Our approach is inspired by analogous structures found in biology, and which self-assemble from protein components. We have found that certain amyloid proteins can self-assemble into fibers that are 15 nm in width and up to millimeters long, and in other cases, virus proteins can self-assemble into spheres that are 50 nm in diameter. Our focus is on devising strategies by which physical forces--including electrical and magnetic fields, microfluidic flow, and surface patterning--can direct the protein assembly into designed structures. Future work aims to prepare structures that display novel
properties.
Several distinctly different studies in biophysical and physical chemistry are being pursued. One of our ultimate goals is to understand more fully the fundamentals of the primary acts of photosynthesis. Included in our investigations are questions concerned with light absorption as well as energy conversion and storage. Photosynthetic reaction center proteins and light harvesting complexes are examined by a variety of spectroscopic probes. A major component of this work will be the development of picosecond time domain x-ray diffraction studies of the photosynthetic electron transfer reactions using intense synchrotron radiation pulses. The final major goal is the development of a single molecule, in a single molecule cage, to serve ultimately as a single molecule probe.
Natural and artificial photochemistry is explored by a variety of spectroscopic techniques specifically designed to probe mechanisms involved in photochemistry. Special modifications or perturbations, such as static and time dependent electric and magnetic fields, alter the photochemistry and spectroscopy. Implementation of these methods requires application of advanced optical and magnetic resonance spectroscopy. Of particular value is our time-domain electron paramagnetic magnetic resonance spectrometer with a time resolution of less than ten nanoseconds.
Light harvesting complexes are the principle light gathering "antenna" for the bacterial photosynthetic reaction center. Two light harvesting complexes exist in Rhodobacter sphaeroides while only one antenna complex is found in Rhodopseudomonas viridis. These complexes are an example of sophisticated integral membrane proteins with highly optimized function. The three dimensional organization of the antenna proteins results in the assembly of an unusually symmetric array of chlorophyll molecules whose function is to transfer incident light energy into the reaction center where chemical potential energy is trapped.
Important questions remain regarding these light harvesting complexes with their large arrays of "antenna" bacteriochlorophyll molecules. The mechanism of energy transfer is the subject of considerable interest. What distinguishes energy transfer and storage in antenna complexes from reaction-center protein complexes? In addition, can either the in vivo or modified antenna protein complexes be coupled to other photochemical processes in order to perform useful photochemistry?
With the goal of answering these questions as well as developing a better understanding of energy transfer and storage, normal and isotopically altered integral membrane proteins are manipulated by site directed mutagenesis via the photosynthetic bacterium Rhodopseudomonas viridis. These manipulated proteins exhibit modified chemical kinetics that are interpreted using detailed electron transfer theory. Interestingly, the core light-harvesting complex of photosynthetic bacteria yields stable radicals upon chemical oxidation. An intriguing feature of these oxidized antenna complexes is rapid electron transfer that can be uniquely explored with electron paramagnetic resonance (EPR). This aspect is intriguing because in nature these antenna are not oxidized, nor do they perform electron transfer chemistry. Consequently, exploration of a completely new facet of integral membrane proteins is possible while at the same time contributing to the better understanding of the overall process of photosynthesis. Along these lines, we have performed variable temperature EPR measurements with the aim of elucidating the mechanism of this electron transfer chemistry. The results are indicative of electron transfer among the bacteriochlorophyll molecules comprising the chromophore network of the light harvesting complex.. The available x-ray structural information makes possible the simulation the EPR spectra. A description for the temperature dependence of the electron-transfer rate constants is obtained using non-adiabatic electron transfer theory.
Finally, special probe molecules are being designed and synthesized to explore and to exploit single molecules. The fundamental idea is to modify dramatically the chemical and physical properties of single molecules or ions by insertion into another single molecule, i.e., the development of single molecule containers for single molecules. Caged molecules will necessarily possess modified chemical and physical properties in comparison to the corresponding un-caged molecules. However, to what extent the properties of caged molecules can be tailored remains to be seen and is a question to be explored in the course of these studies. This work involves the chemical synthesis of caged molecules or ions using nano-structures such as nano-bubbles and nano-tubes. The synthesis of caged molecules is interesting quite apart from any potential application. Eventually, one of the goals is to employ these caged molecules as single molecule probes of other systems such as membranes, gels, living cells, etc.
We combine the technique of high resolution high sensitivity laser infrared spectroscopy and plasma chemistry to observe laboratory spectra of fundamental molecular ions such as H3+, CH3+, CH2+, C2H2+, C2H3+, CH5+ , NH2+, NH3+, NH4+, H3O+ etc. We then use these spectra as fingerprints to search for the molecular ions in astronomical objects by infrared telescopes. Those molecular ions are assumed to play pivotal roles in interstellar chemistry and thus in star formation.
Our work has contributed to identify the intense and pure H3+ infrared emission lines that were observed in Jupiter. The V2 fundamental spectrum we observed in 1990 has become a powerful tool to study morphology and temporal variation of plasma activities in planetary ionospheres. In 1996 we detected the absorption spectrum of interstellar H3+ towards young stellar objects that are deeply embedded in molecular clouds. This has given a most direct support to the currently accepted mechanism of the ion-neutral reaction scheme in which H3+ is the cornerstone. Our observation in 1998 of a large amount of H3+ towards a visible star and the galactic center brought a surprise since it clearly demonstrates abundance of H3+ also in diffuse clouds, where density is predicted to be very low because of its recombination with abundant electrons. The enigma brought up by this observation will be studied intensively in the next several years.
My group is using the methods of statistical mechanics to study the dynamics of phase transitions, in particular the rates of nucleation and growth for new phases. Applications include gas-to-liquid transitions (and the reverse), the freezing of liquids and melting of solids, transitions to mesophases such as liquid crystals and plastic crystals, and the formation of micelles and vesicles in amphiphilic fluids.
We have applied our new theoretical approach to study the nucleation of liquids from the vapor, both for pure substances and for gas mixtures, including the highly non-ideal mixtures of water and sulfuric acid that dominate in polar stratospheric cloud formation. The reverse process of bubble formation in superheated, stretched, or supersaturated liquids is also being studied.
When a liquid is cooled, it can crystallize, form a glass, or pass through a mesophase such as a plastic crystal or liquid crystal. Information from theory and diffraction experiments on the structure of the liquid (packing of atoms and molecules, positional and orientational correlations) is being used to predict which outcome is seen in a given situation. Colloidal suspensions provide a useful test case in which crystallization dynamics can be monitored on a particle-by-particle basis, while alloy crystallization provides an important arena for application of the theory. The crystallization of proteins from solution is a particularly timely application. Predictions of rates of growth of crystals from the melt are also being made through a dynamical extension of the equilibrium statistical theory of freezing.
We are studying amphiphilic fluid mixtures, which provide models for biological membranes. Such molecules can cluster together to form micelles, vesicles, and bilayer membranes, or they can organize into entire lyotropic liquid crystal phases. Equilibrium and kinetic aspects of these processes are being studied.
My research efforts are directed toward the design of new chemical reactions and strategies for the synthesis of compounds, both natural and unnatural, that possess a unique, challenging architecture. The research projects that we are currently pursuing chemical problems in several different areas of organic chemistry, including: (1) exploration of the high reactivity of strained-ring compounds and applying this chemistry to the synthesis of medically important compounds, such as cardiac steroids and triquinane natural products (2) development of new, highly efficient routes to indole alkaloids, such as those of the strychnos and aspidosperma families, (3) development of methods for asymmetric synthesis, and (4) exploration of aspects of biomimetic chemistry and design of effective catalysts for asymmetric synthesis. Our study of these problems has already resulted in the discovery and development of several new bond-forming strategies.
My research interests are currently in two broad areas: active control of quantum dynamical processes, the properties of interfaces, and other quasi-two-dimensional systems.
In the first category, the goal is to develop theoretical understanding of methods to achieve control of selectivity of product formation in a chemical reaction. At present the focus of the research effort is on developing a general formalism for the control of quantum dynamical systems, on understanding the limitations to the use of optimally shaped time dependent fields to control the evolution of a molecule, extending the theory of control to reactions in condensed media, and developing a version of the general theory that is useful when applied to large molecules.
In the second category, the aim is to understand the properties of inhomogeneous liquids (e.g. the structure of the liquid-vapor and liquid-solid interfaces) in terms of the molecular interactions in the system. Among the questions of interest are: How does the structure of the inhomogeneous interface of a metallic alloy depend on the electronic structure of the species? How does the structure of the interface depend on the structure of the contact medium? What determines the concentration profile of a component that segregates at a liquid-x interface? What kinds of phases can exist in such a system and what are the structures of such phases? What are the dynamical properties of two-dimensional liquids? Is the surface of a liquid effectively two-dimensional or not? Typical studies involve the development of theoretical models, the utilization of computer simulations of model systems, the use of grazing incidence X-ray diffraction to study the interface structure in the plane, and of X-ray reflection to study the density distribution of the inhomogeneous system along the normal, to the interface, the use of evanescent wave dynamical light scattering to study motion in the interface, and video microscope studies of phase transitions and diffusion in quasi-two- dimensional
colloid suspensions.
Our research involves the direct time-domain study of the microscopic dynamics associated with chemical reactions and photophysical processes in condensed media and at interfaces on all chemically and biologically-relevant timescales (femtoseconds to seconds). Many of the investigations involve collaborations with groups in Biology, Chemistry and Physics.
We are interested in how chemical reactions (e.g. dissociation and electron-transfer) involve interactions with the surrounding environment (liquid, solid, protein). We are examining the intra-protein charge transfer dynamics and protein fluctuations that affect these dynamics in photosynthetic systems, blue-copper proteins, photoactive yellow protein and redox cofactor proteins by ensemble and single molecule methods. (See the Institute for Biophysical Dynamics Website http://ibd.bsd.uchicago.edu/ and the IBD section of PSD Research in Progress for further elaboration). We are embarking on new research to examine dynamics in two-dimensional systems including the dynamics of biological membranes, the vibrational dynamics of hydration water at interfaces, and membrane-bound proteins.
We are also working on novel spatially localized microscopy methods in conjunction with (femtosecond) laser methods for scanning probe microscopy and nanometer-scale photonic structures and devices. This effort involves fundamental research on plasmon propagation in metal nano-structures; from single particles to complex arrays and photonic crystal films. Computer simulations complement many of these experiments.
Four state-of-the-art laser labs relevant to addressing the issues mentioned above are currently in use or development within the group: (1) novel photon echo methods to probe optical coherence decay of chromophores and reactions; (2) pump-probe and polarization spectroscopy to probe the dynamics of reactions in solution and in protein environments; (3) polarizability probing of optically-induced reactions in solution and protein environments; and (4) a unique apparatus allowing spatially localized examination of physical processes using pulsed laser techniques and scanning probe microscopy. We also have established two "single molecule" labs to examine dynamics by fluorescence and picoNewton force fluctuation approaches-the latter of single ligand-protein complexes.
Our research interests currently center on using experimental and theoretical techniques to address fundamental questions in the fields of surface chemistry and catalysis, nanoscience,surface physics, and materials research. In particular, we are using a variety of molecular beam, laser spectroscopic, and scanning probe microscopy techniques, as well as computational tools such as molecular dynamics, to examine issues central to our understanding of surface chemical dynamics. Illustrative topics include: surface chemical kinetics and reaction dynamics, heterogeneous combustion and catalysis, surface photochemistry, metallic oxidation and corrosion, self-organization of atomically structured thin films, atomic-scale interfacial chemistry, supersonic molecular beam growth of electronic materials including diamond, thin film polymer dynamics, and most recently, the cell-wall structure of infectious bacteria. Our newest endeavor centers on examining how highly energetic reagents, such as atomic oxygen, interact with materials, a topic of fundamental importance to materials chemistry, including reactions in the low-earth-orbit space environment. These studies are being conducted under ultra-high vacuum conditions, with recent extension to electrochemical environments. They are motivated by a desire to understand and control surface chemical processes at the molecular level, and by the increasing need to understand the physical properties of low-dimensional interfacial systems. More details can be found at our extensive group web page: http://sibener-group.uchicago.edu.
In the area of planetary exploration, the instrument that Thanasis Economou and I have helped the Germans to design is on its way to Mars. The scheduled landing is July 4, 1997. The instrument will provide a chemical analyses of Martian rocks and soil. The original alpha weathering and proton production modes have been supplemented by an x-ray mode. This will provide a more detailed analysis for chemical elements heavier than silicon.
We have received samples of uranium from Vienna that have been stored since World War II. It is important to repeat the double beta decay experiment on U238.
Photochemistry. Our current interest in photochemistry concerns the inter-actions between excited state groups and other groups through sigma-bonds, C-C and Si-Si bonds. We have found both electron-transfer interactions and exciton interactions through these bonds, and they occur both in solution and in gas phase. The latter work, in collaboration with Professor Donald Levy, was performed in a supersonic jet. The kinetics of the interactions in solution will be carried out in collaboration with Professor Norbert Scherer. The interactions through Si-Si bonds were more distinctive than those through C-C bonds. Our interest in this area also extends into the possible applications of our compounds in material sciences.
Chemistry of Synthetic Proteins. Amphiphilic peptides self-associate to form well-defined oligomers. These peptides may exhibit polymorphism under different experimental conditions, including their associations with membrane-mimetics. Our peptides form well defined supramolecular complexes with organic ligands and metal ions. They were characterized by fluorescence, X-ray crystallography, multi-dimensional NMR spectrometry, and other physical techniques. We are exploring the relationships between primary structures of synthetic proteins and their foldings into different secondary structures. Some of our peptides exhibit anti-microbial activities higher than Magainins, a group of natural occuring antibiotics. Our aims are to design and synthesize oligo-peptides in order (1) to explore their foldings into different secondary structures, and (2) to study their structure: anti- microbial-activity relationship.
My research is focused on the interfacial area between organic chemistry and materials science. This area has rich opportunities for organic chemists both in fundamental science and practical technologies. There are five current projects in the group.
Polymerization Methodology. Since many new polymers and functional materials are designed, preparation of many of them needs new chemical approaches. We are especially interested in exploring reactions that require mild reaction conditions. Typical examples include: a). Palladium-mediated coupling reactions (The Heck reaction, the Stille coupling reaction) for the preparation of conjugated polymers; b). The Mitsunobu reactions for the preparation of electro-optic polymers; c). Living ring-opening polymerization for the synthesis of biocompatible polyesters; d). Chemoselective ligation for the preparation of biocompatible diblock copolymers; e). Orthogonal approach for the synthesis of well-defined oligophenylenevinylenes.
Conjugated Diblock Copolymers. It is well known that the extended ?-electronic systems of conjugated polymers give the materials numerous physical properties, which resemble those of a typical inorganic semiconductor. For example, high electric conductivity after chemical doping, optical nonlinearity and electroluminescence have been demonstrated in the past decades. It will be very interesting if one can synthesize conjugated diblock copolymers. A fundamental question can be asked: what kind of electronic and structural properties will these rod-rod types of diblock copolymers exhibit? For example, if an electron-deficient conjugated block is coupled together with an electron-rich block, will the resultant diblock molecule behave like molecular p-n junction? The exploration these diblock copolymers, their self-assembly behavior, and associated physical properties may lead to new physical phenomena, such as rectifying effect and optical switching. Careful engineering of these molecules, both in their amphiphilic properties and electronic properties will allow us to organize these molecules into large area monolayers that may prove to be crucial for the realization of molecular electronic devices. These materials present the unlimited opportunity to further fundamental knowledge of the electronic and structural properties of organic electroactive materials.
Supramolecular Assembly of Nanostructured Materials. Research on nanostructured materials is the frontier area in materials science. A challenging task in this area is to manipulate nanostructured materials and assemble them into desired structural forms-one, two or three-dimensional structures so that the unique physical properties associated with nanostructured materials can be harvested. Organic chemistry plays a crucial role in the development of nanoscience and nanotechnlogy. Supramolecular assembly of nanostructured materials is the key to the success. We are developing new supramolecular approaches to assemble nanoclusters into one, two or three-dimensional structures.
Photorefractive and Electro-Optic Polymers. The pursuit of research of photorefractive polymers is driven by both the fundamental challenge in identifying the basic synthetic principles of these multi-functional polymers and their potential for practical applications, such as for optical signal processing and information storage. Organic photorefractive (PR) materials are a new kind of electro-optic materials, which possess both electro-optic effect and photoconductivity. It is a challenge to integrate these properties into a single polymer system that will exhibit this PR effect. This project involves a great deal of organic synthesis of new polymer structures. These new structures are designed based on our current understanding and synthesized and characterized to test our new hypothesis.
Functional polymers containing metal complexes. Metal complexes exhibit rich electro-magnetic and optical properties, which can be explored for electro-optic materials. One of our projects is to combine organic conjugated polymers with transition metal complexes to investigated new physical properties. Introduction of transition metal ions into p-conjugated polymers provides enormous opportunities to tune the physical properties of the resulting materials. From the strong interaction between transition metal complexes and conducting polymer backbones, unique photophysical, photochemical and electrochemical properties are expected to evolve, leading to materials with a wide range of interesting physical properties, such as photorefractive effects, photoconductivity and novel redox property. These polymers exhibit promising potential for applications in solar energy conversion, sensor, polymer-supported electrode, nonlinear optics, photorefraction and electroluminescence.
|
 |
|
Division of the Physical Sciences - 5747 S. Ellis Ave., Chicago, IL 60637 - |