Adam J. Matzger - US grants

Abstract
CHE-0316250
Matzger/Michigan

Professor Matzger and his coworkers at the University of Michigan are examining the spontaneous self-assembly of physisorbed monolayers for the formation of two-dimensional crystal structures. With the support of the Analytical and Surface Chemistry Program, this group is combining computational design, organic synthesis, and scanning probe microscopic characterization to produce surfaces patterned at the nanoscale. This approach is applied to the formation of polymer monolayers by reaction of these self-assembled monolayer surfaces. These surfaces are used for heterogenous catalysis, lubrication, and corrosion resistance applications.

With the support of the Analytical and Surface Chemistry Program, Professor Matzger and coworkers at the University of Michigan are examining the structures of physisorbed monolayers. Using scanning probe microscopy to characterize these adsorbed layers, routes to the formation of robust polymerized monolayers are developed. These layers promise application in many areas of tribology and catalysis.

Abstract
CHE-0616487
Matzger/Michigan

Professor Matzger and his coworkers in the Department of Chemistry at the University of Michigan, are developing a systematic understanding of self-assembly at the liquid-solid interface by examining the structures of organic molecules adsorbed on planar substrates. Using scanning tunneling microscopy coupled with judicious choice (or synthesis) of molecular adsorbate, they are probing a wide range of two-dimensional crystallization motifs. With the support of the Analytical and Surface Chemistry Program, the results of these structural studies, combined with work in the literature, will result in a public two dimensional crystallographic data base of use to a broad range of researchers. The fundamental understanding of self-assembly will have impact on a range of technologies, from molecular electronics to corrosion inhibition strategies.

Two dimensional crystal structures are being examined by Professor Matzger and his coworkers, in order to develop an understanding of the self-assembly of large molecule structures at the liquid-solid interface. A data base categorizing and classifying new and existent structures is an expected output of this work. A fundamental understanding of the process of self-assembly will impact a broad range of important technologies.

[unreadable] DESCRIPTION (provided by applicant): The role of solid-state form in determining the properties of Pharmaceuticals is a critical issue in drug delivery. The ability of a solid to exist as more than 1 polymorph, supramolecular isomers that differ only in packing and not constitution, creates a situation where each crystal form may have different bioavailability and stability. Only by discovering the presence of new polymorphs and their unique properties can the most efficacious form for a solid dosage be found. This proposal outlines a method for studying and controlling this important aspect of crystal growth. Specific Aim 1-Develop a general methodology for producing new polymorphs. We will create libraries of polymers that can heteronucleate crystallization of solids. It is proposed that varying the functional groups on the surface of the polymer and the orientation and density of these functional groups will allow kinetic access to new polymorphs by creating novel heteronucleation events. Specific Aim 2-lnvestigate the relationship between polymer structure and crystal polymorph obtained. Though it has been established that the majority of crystallizations on a macroscopic scale proceed through heteronucleation events, there is little information about the influence of the substrate on crystallization events. Using the approach developed in Specific Aim 1 to find polymers that create novel polymorphs, we will determine which characteristics are important for controlling polymorph production. Specific Aim 3-Determine the properties of novel polymorphs. With the ultimate goal of finding more efficacious forms of existing and new Pharmaceuticals, the determination of several key properties of the new polymorphs will be undertaken including stability, equilibrium solubility and dissolution rate. Brief description of public health relevance: The effectiveness of a drug substance is not solely related to its chemical composition but also to how the molecules arrange in the solid. This proposal offers a method for optimizing this important aspect of drug delivery and will lead to the development of more effective forms of current and future therapeutic agents. [unreadable] [unreadable] [unreadable]

The Department of Chemistry at the University of Michigan will upgrade a 600 MHz nuclear magnetic resonance (NMR) spectrometer and equip it with solid state NMR capabilities with support from the Chemistry Research Instrumentation and Facilities: Multi User (CRIF:MU) program. The instrument will be employed in several biophysical and biomaterials and synthetic chemistry projects requiring high field SSNMR including: The high field SSNMR will be used in studies of polymorphic organic compounds, nanomaterials, reactive intermediates, interactions of small molecules with phospholipid bilayers, molecular organization of bone materials, molecular dynamics of proteins in nanocrystals and fuel cell membranes.

Nuclear Magnetic Resonance (NMR) spectroscopy is the most powerful tool available to chemists for the elucidation of the structure of molecules. It is used to identify unknown substances, to characterize specific arrangements of atoms within molecules, and to study the dynamics of interactions between molecules in solution. Access to state-of-the-art NMR spectrometers is essential to chemists who are carrying out frontier research. The results from these NMR studies will have an impact in synthetic organic chemistry, organometallic chemistry, biophysical chemistry and materials chemistry.

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).

With this award from the Chemistry Research Instrumentation and Facilities Multiuser Program (CRIF:MU), Professor Carol A. Fierke from the University of Michigan and colleagues Adam J. Matzger, John Montgomery, Vincent L. Pecoraro and Melanie S. Sanford will acquire a single crystal X-ray diffractometer with a strong copper source to obtain high-resolution structural information in diverse fields including synthetic organic chemistry, materials science and inorganic chemistry. This instrument will support education and research in complexes from metallacrowns producing soft materials; determination of absolute and relative stereochemistry of molecules important in catalytic reactions; in synthesis and characterization of biological properties of fluorinated proteins; in mechanistic studies of late metal complexes with high oxidation states; and in metal-organic frameworks.

An X-ray diffractometer allows accurate and precise measurements of the full three dimensional structure of a molecule, including bond distances and angles, and provides accurate information about the spatial arrangement of a molecule relative to neighboring molecules. The studies described here will impact a number of areas, including chemistry, materials chemistry and biochemistry. This instrument will be an integral part of teaching as well as research.

Abstract

PI Name: Phillip Savage
Institution: University of Michigan
Proposal Number: 0937992

EFRI-HyBi: The Science and Engineering of Microalgae Hydrothermal Processing

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)

Intellectual Merit
Two major barriers in conventional approaches for converting microalgae to liquid fuels on a large scale are the needs to cultivate algae with high oil content and to dry the algae and extract the oil components. The PIs propose to develop the scientific and engineering knowledge needed to implement a different approach that shatters both barriers. This approach involves integrated hydrothermal-catalytic-microbial processing. The hydrothermal (elevated pressure and temperature, aqueous phase) process is not limited to converting only algae with high oil content. It can also convert the biomass carbohydrates and proteins into bio-oil. Algae with high oil content are not required. Secondly, with this hydrothermal process, no algae drying or oil extraction is needed. The biomass is processed as a whole in its high-moisture state. The research contains four broad objectives. The PIs will determine the reaction products, pathways, kinetics, and mechanisms operative during hydrothermal conversion of microalgae to molecules that constitute a crude bio-oil. This task will include the use of Raman spectroscopy for the first in situ analysis of these chemical changes. They will work at the molecular level to develop and design heterogeneous catalysts for engineering the molecular composition of the liquid hydrocarbons. Thus, significant progress will be made in adapting heterogeneous catalysis for oil upgrading under hydrothermal conditions. The PIs will also make scientific advances in the use of microbial pathways for utilization of solid and aqueous-phase byproducts from hydrothermal processing. Finally, they will maintain a systems perspective throughout and couple chemical process design, economic evaluation, and life cycle assessment to screen alternate process configurations and guide the research. The broader sustainability performance of hydrothermal processing options will be studied through life cycle modeling of upstream algae production and downstream biosolids and wastewater processing/utilization. The proposed research could overcome key barriers in the algae-to-hydrocarbons field and potentially transform the landscape for commercialization of this promising biomass feedstock.

Broader Impacts
A new technological approach for producing drop-in renewable transportation fuels from microalgae could be an outcome of this research. The strategy could also be used for processing other types of high-moisture biomass. Thus, the research could play a major role in our transition toward energy independence and reduced CO2 emissions from the energy sector. Five PhD students will be trained by an interdisciplinary team working on cutting edge research on a topic of intense international interest. These students will be involved in lab rotations to ensure their training will be interdisciplinary. Upon graduation, they will be well prepared for leadership positions in industry, government, or academia. Master?s students will see aspects of this research integrated into the curriculum of the Engineering Sustainable Systems dual degree program between the College of Engineering and the School of Natural Resources and Environment. Students in graduate elective courses in sustainability and in industrial ecology (which are taught by two of the PIs) will work on projects related to the research. Moreover, each PI will include undergraduate students in their laboratories. They will engage undergraduates in the research, and they will participate in the University?s UROP and WISE programs, which provide mentoring and research experiences for underrepresented minorities and women students, respectively. They will also participate in the College of Engineering outreach to science and math students in a local high school that has a high percentage of underrepresented minority and socio-economically disadvantaged students. Thus, the project integrates research and teaching and contributes to human resource development. The results obtained from the research will be disseminated via participation of project personnel in conferences and via publications in scholarly journals.

TECHNICAL SUMMARY:

The over-arching goal of this research is to develop a detailed, molecular level understanding of an emerging class of ultrahigh performance sorbents named Microporous Coordination Polymers (MCPs). MCP sorbent performance derives from their high fractional volume (porosity) of tiny, nanometer-sized pores resulting in exceedingly high specific surface areas. An understanding of how these materials can adsorb such enormous amounts of gases and the chemical/physical basis for selective uptake are the major thrusts of the proposed research. In particular, the fundamental role of pore size, pore architecture, and pore interconnectedness will be observed for the first time during the actual processes of gas adsorption and solvent removal. Enabling this unique viewpoint is the first use in MCPs of positron annihilation lifetime spectroscopy, an antimatter probe of porous materials recently developed to characterize microporous thin film dielectric insulators in microelectronic devices. Adoption of this technique has the potential to transform how researchers probe porosity in sorbents. Only by understanding how changes on the microscale and nanoscale exert an effect on apparent porosity can the best modes of exploiting existing MCPs be realized. Ultimately these results will be of practical use to guide the synthesis of new materials. MCP?s are expected to find broad application in energy research (gas storage) and environmental research (gas purification) and since MCPs are now being commercialized they are at the point where direct impact on society can and will be felt.

NON-TECHNICAL SUMMARY

This research brings together chemists and physicists in an effort to transform the study of ultrahigh performance sorbents?the nanomaterials that are themselves transforming the field of chemical separations. This unique collaboration seeks to use powerful antimatter probe techniques recently developed to study newly engineered porous insulators in microchips to provide unprecedented structural characterization. These highly porous sorbents are expected to find broad application in alternative energy (gas storage) and industrial processes (gas purification) and since they are now beginning to be commercialized they are at the point where direct impact on society will be felt. The impact of this research is totally dependent on the successful interaction of chemists and physicists. Graduate and undergraduate students will cross discipline boundaries to learn in a broadly diverse and collaborative environment involving frequent interaction with industry. For these reasons the potential for obtaining transformative research results is high. However, this will only be possible if the properties of the materials are sufficiently well understood to allow widespread deployment in new more efficient processes. It is clear that sorbent technology has not yet achieved this point, but the proposed research will do much to enable reaching this goal.

DESCRIPTION (provided by applicant): The most common and desirable way to deliver active pharmaceutical ingredients (APIs) is in the crystalline form. APIs can be formulated in pure form, as salts, or as multicomponent (solvate, cocrystal) solids and these offer due to stability and processing advantages over other formulations. The choice among these forms depends very much on the specific chemical properties of the drug molecule as well as factors such as solubility. However, there is the pervasive issue of crystal polymorphism to consider: a given composition is not constrained to crystallize in a predictable way and multiple packing motifs of the same unit possess different thermodynamic stabilities that can influence bioavailability. The proposed program will develop more rapid and comprehensive techniques to control the crystallization of bioactive organic molecules while being less material intensive. Thi will enable early stage screening of potential drugs to determine which form has the appropriate solubility and stability to be formulated into a bioavailable dosage. Three interconnected aims are designed to develop and deploy more efficient and robust polymorph discovery methodology. Aim 1 adapts the polymer-induced heteronucleation (PIHn) approach towards solid form discovery so that it functions in a high throughput manner suitable for polymorph discovery. Two of the key advances proposed are miniaturization of the technology and automation of the solid form screening, which together will make the PIHn method much better suited for the screening of preclinical drug candidates. Aim 2 addressed the issue of crystal polymorphism outside of the well-studied realm of neutral molecular compounds. Because solvates, salts, and cocrystals are increasingly the solid forms of choice for drugs entering the clinic, there is a pressing need for understanding solid form diversity in such APIs. The methodology proposed in Aim 1 is perfectly suited to polymorph discovery in solvates, salts, and cocrystals because it can generate solid form diversity even under the relatively narrow sets of conditions employed in multicomponent crystal formation. Finally, in Aim 3 a new strategy for identifying targeted inhibitors of crystal forms will be introduced. The approach involves a new paradigm, based on the mechanistic understanding of how PIHn accelerates nucleation, redeployed for creating soluble polymeric nucleation inhibitors.

DESCRIPTION (provided by applicant): The most common and desirable way to deliver active pharmaceutical ingredients (APIs) is in the crystalline form. APIs can be formulated in pure form, as salts, or as multicomponent (solvate, cocrystal) solids and these offer due to stability and processing advantages over other formulations. The choice among these forms depends very much on the specific chemical properties of the drug molecule as well as factors such as solubility. However, there is the pervasive issue of crystal polymorphism to consider: a given composition is not constrained to crystallize in a predictable way and multiple packing motifs of the same unit possess different thermodynamic stabilities that can influence bioavailability. The proposed program will develop more rapid and comprehensive techniques to control the crystallization of bioactive organic molecules while being less material intensive. Thi will enable early stage screening of potential drugs to determine which form has the appropriate solubility and stability to be formulated into a bioavailable dosage. Three interconnected aims are designed to develop and deploy more efficient and robust polymorph discovery methodology. Aim 1 adapts the polymer-induced heteronucleation (PIHn) approach towards solid form discovery so that it functions in a high throughput manner suitable for polymorph discovery. Two of the key advances proposed are miniaturization of the technology and automation of the solid form screening, which together will make the PIHn method much better suited for the screening of preclinical drug candidates. Aim 2 addressed the issue of crystal polymorphism outside of the well-studied realm of neutral molecular compounds. Because solvates, salts, and cocrystals are increasingly the solid forms of choice for drugs entering the clinic, there is a pressing need for understanding solid form diversity in such APIs. The methodology proposed in Aim 1 is perfectly suited to polymorph discovery in solvates, salts, and cocrystals because it can generate solid form diversity even under the relatively narrow sets of conditions employed in multicomponent crystal formation. Finally, in Aim 3 a new strategy for identifying targeted inhibitors of crystal forms will be introduced. The approach involves a new paradigm, based on the mechanistic understanding of how PIHn accelerates nucleation, redeployed for creating soluble polymeric nucleation inhibitors.