Martin L. Kirk, Ph.D. - US grants

9316557 Kirk This award is the starter grant increment of Dr. Kirk's Postdoctoral Reseaerch Fellowship in Chemistry. The main thrust of the research is a combined experimental and theoretical study of oxygen transfer by Group VI metals in both biological and inorganic systems. A combined spectroscopic approach utilizing variable-temperature, variable-field magnetic circular dichroism, single crystal polarized absorption, and resonance Raman spectroscopies will probe the Mo(V) state of xanthine oxidase catalytic intermediates. These enzyme studies will be complemented by parallel investigations of relevant model compounds which display structural features believed to be present at the enzyme active site. Excited state spectral studies will be used in order to evaluate the results of detailed bonding calculations including self-consistent field scattered wave calculations, transition-state calculations, and density functional methods incorporating Slater or Gaussian-type basis functions. %%% Group VI metals, specifically molybdenum and tungsten are catalytically active towards oxygen transfer in both enzymatic and inorganic systems. These studies will provide a wealth of information concerning the mode of substrate binding to the metal and will directly probe the initial steps in oxo transfer from metal to substrate. ***

XAS studies are proposed for the trinuclear sites present in the multicopper oxidases. The fully reduced, fully oxidized and oxygen intermediate forms of native and type 1 mercury substituted laccase (Lc) will be investigated by EXAFS to probe for possible metal-metal interactions which would indicate oxygen bridging at the trinuclear site and to determine if a short Cu-O interaction is present in the first shell data on the intermediates. We will quantify the amount of Cu(I) present in both intermediates using the Cu K-edge structure. Peroxide and azide bound forms of T1Hg Lc, native Lc, and ascorbate oxidase (AO) will also be systematically studied by EXAFS and X-ray absorption edge methods to correlate spectroscopic results with crystallographic data on ligand bound forms of AO. These experiments are of critical importance in developing an understanding of the role of the trinuclear site in the four electron reduction of dioxygen to water. Finally XAS studies will be directed to ceruloplasmin (Cp) to probe the oxidation state of the coppers in the unusual (i.e. EPR nondetectable) trinuclear copper cluster which appears to be present in the resting form of this enzyme in rapid preparations and to elucidate the possible interactions among the trinuclear coppers as compared with other multicopper oxidases.

DESCRIPTION (provided by applicant): The combined model and enzyme studies proposed in this project are directed toward developing a detailed electronic structure description pyranopterin molybdenum active sites, and how their unique electronic structures relate to their mechanism of activity. Computational studies will provide a valence bond description of these active sites, and aid in our understanding of enzyme-substrate interactions and the nature of the transition state. The specific aims of the project are toe 1) provide insight into the nature of the xanthine oxidase (XO) 'Very Rapid' intermediate, and assess the proposal that this intermediate is an product bound species, 2) determine the effect of terminal sulfido protonation on Mo-S bond covalency, and how this might facilitate electron transfer regeneration of the XO active site, 3) incorporate selenide into the XO site and perform spectroscopic studies on the chemically modified form of the enzyme, 4) use spectroscopically calibrated bonding calculations to probe the reaction coordinate for XO mediated hydroxylation of aldehyde and heterocyclic substrates, 5) determine whether the unique geometry of the oxidized sulfite oxidase (SO) active site directs a specific oxo ligand for transfer to substrate in the reductive half reaction, effectively lowering the energy of the transition state, 6) ascertain the role of the coordinated cysteine and ene-1,2-dithiolate donors in the oxidative half reaction of SO, 7) understand how the A208D mutation in human SO affects Mo-S-Cys bonding in SOox and/or SOred, 8) determine the role of the ene-l,2-dithiolate chelates in the electron transfer (reductive) half reaction of DMSO reductase (DMSOR), and 9) understand the role of the coordinated serine in catalysis, and probe the nature of the DMSOR transition state. The enzymes XO, aldehyde oxidase (AO), and SO are found in humans, and their importance with respect to human health is exemplified by the fact that individuals suffering from molybdenum cofactor deficiency display severe neurological symptoms and early childhood death. Enzymes of the XO family have recently been implicated in pro-drug activation, drug metabolism, and under specific conditions NO synthase activity, and AO has recently been shown to metabolize famciclovir to the potent antiviral penciclovir, which has been found to be effective against such viral infections as herpes simplex, varicella zoster, Epstein-Barr, and hepatitis B. Individuals who suffer from isolated sulfite oxidase deficiency, which derives from specific mutations in the SO gene, display a variety of deliterious effects including neurological abnormalities, dislocation of the ocular lens, mental retardation, and even attenuated brain growth.

With this renewal award, the Chemistry Division supports a Research Experiences for Undergraduates (REU) site directed by Dr. Lorraine M. Deck and four co-principal investigators in the Department of Chemistry at the University of New Mexico (UNM). The ten participants, recruited regionally and from UNM, will take part in a program that offers an intensive and comprehensive research experience. The conclusion of the research experience will include a final seminar, a scientifically written research report and a poster. The opportunity will also be afforded for students to participate in the writing of a paper for publication and/or travel to a professional meeting to make a presentation.

With support from the Major Research Instrumentation (MRI) Program, Martin Kirk and colleagues at the University of New Mexico will acquire a combined X-band/Q-band CW EPR/ENDOR spectrometer. Projects that will exploit this instrument include a) studies of molybdoenzymes and relevant model complexes; b) research on thermally induced charge transfer materials; c) the use of cobalt as a spectroscopic probe of zinc sites in metalloproteins; d) spectroscopic studies of high symmetry cobalt coordination compounds; and e) biophysical studies of photosynthetic water oxidation and iron regulation.

An electron paramagnetic resonance (EPR) spectrometer is an instrument used to obtain information about the molecular and electronic structure of molecules. It may also be used to obtain information about the lifetimes of free radicals which are often essential for the initiation of tumor growth and/or a variety of chemical reactions. These studies will have an impact in a number of areas, in particular biological chemistry.

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports research by Professor Martin L. Kirk at the University of New Mexico to study the electronic structure of donor-acceptor (D-A) and D-bridge-A biradicals related to molecular electronic applications through a combined spectroscopic and magnetic approach. The D-A systems are ground state analogues of the charge separated state generated in photoinduced electron transfer processes, and have direct relevance to various magnetic electron transport conduits, including molecular rectifiers and spintronic devices. The focus is on the use of D-A biradicals to facilitate strong donor-acceptor electronic coupling and ferromagnetic exchange interactions. The primary goals are to: (1) understand excited state contributions to the electronic structure of donor-acceptor biradicals, (2) determine the magnitude of Hab as a function of the bridge fragment, and evaluate the potential of D-A biradicals as key components in PET, molecular electron transport, and molecular recification systems, and (3) probe the degree of valence delocalization in high-spin, mixed-valent, valence tautomeric metalloorganic systems. These systems possess mixed-valent ligands, display intervalent ligand-to-ligand charge transfer transitions, and will provide a fundamental understanding of highly efficient, long-range electron transfer phenomena in metallo-organic conduits.

The goals and objectives of this proposal will contribute to a more detailed understanding of complex D-A bonding interactions, which should aid in the design of multifunctional supramolecular systems that may function as vital components in magnetic, photoactive, conducting, electroactive, switchable, and spintronic devices. UNM represents a wide cross-section of cultures and backgrounds, with minority enrollment representing 49.3% of the student body. The Inorganic Cluster at UNM has recruited and retained a proportionately high degree of minority and under-represented students. The combination of spectroscopy, magnetism, synthesis, and theory provide a fertile learning and training experience for undergraduates, graduates, and postdoctorals. Interactions with Los Alamos (LANL) enhances the learning and training potential by exposing students to specialized facilities and an alternative research environment.

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

With support from the Chemistry Research Instrumentation and Facilities:Multiuser program (CRIF:MU), the Department of Chemistry and Chemical Biology at the University of New Mexico will upgrade the console of a 300 MHz nuclear magnetic resonance spectrometer that will be used for solids and solution analyses. It will be employed in research projects that span many areas of chemistry including, a) the development of reliable protocols for the assessment of structure and bonding in high-spin Co(II) systems; b) the discovery of new catalytic reactions and efficient assembly of diverse and medicinally important chemical structures; c) investigation of Donor-Bridge-Acceptor systems as potential components of molecular wire devices; d) development of novel synthetic methods for biomedically interesting targets; e) understanding the mechanism of carbon dioxide reacting with main group amides to generate organic isocyanates; f) characterization of early stage molecular precursor chemistry for the development of new families of "doped" materials that become novel gas adsorbents, once converted to solid-state forms; g) strategies for the rational design of inhibitors for enzymes connected to diseases; h) characterization of carbon fibers used in cathodes of high power microwave sources with potential military applications; and i) characterization of bacterial communities in cave pools and their role in formation of caverns.

Multinuclear NMR spectroscopy is an essential tool in modern chemical research. NMR spectra enable researchers to identify reaction products including targeted substances, reaction intermediates and unexpected products. Structural information, i.e. information on the connectivity of the atoms in molecules and materials is obtained by detecting transitions between energy levels arising from the nuclear spin properties of atoms. The instruments will be used to support research projects of undergraduates, graduate students, and postdoctoral researchers, including traditionally underrepresented minority groups that make up approximately half of the enrollment at the university.

The Chemical Structure, Dynamics and Mechanisms Program supports Professor Martin Kirk at the University of New Mexico who will use a combined spectroscopic, magnetic, and computational approach to understand the electronic structure of new donor-acceptor (D-A) biradicals and (py)2M(dioxolene-A)2 (dioxolene = semiquinone/catecholate) extended arrays that possess organic mixed-valency. The proposed D-A systems are ground state analogues of charge separated states generated in photoinduced electron transfer processes, and therefore have direct relevance to various magnetic electron transport conduits, including molecular rectifiers and spintronic devices. The overarching focus of this work is the use of D-A biradicals to facilitate strong D-A electronic coupling and ferromagnetic exchange interactions over great distances. The proposal represents a concise research plan directed toward the achievement of broader long-range goals of adding to the molecular electron transport knowledge base. This will occur through the development of a complete electronic structure description of strong electronic coupling in D-B-A biradicals and through understanding the origin of long-range ferromagnetic exchange mediated by delocalized electrons.

With the support of the Chemical Structure, Dynamics and Mechanisms Program in the Chemistry Division at the National Science Foundation, Dr. Martin Kirk is performing research in an area of enormous interest. Phenomena such as long-range charge and energy transport in organic and metallo-organic systems are relevant to solar-energy conversion, electronics, and information processing. This work will contribute to the design of new multifunctional supramolecular systems that may function as vital components in magnetic, conducting, electroactive, photoactive, and spintronic devices. Broader impacts will involve teaching, training and learning through collaborative interactions with undergraduate programs at New Mexico Tech and San Jose State University. The diverse culture at the University of New Mexico, with approximately 50% underrepresented persons, has allowed Professor Kirk's group to be represented by students of African, African American, Pacific Island, Chinese, European, and Indian heritage. Approximately half of these have been women and some have been supported through NM-AGEP, an NSF program aimed at increasing the number of minority Ph.D.'s in science and technology.

With this award from the Chemistry Research Instrumentation and Facilities: Departmental Multi-User Instrumentation program (CRIF:MU), Professors Martin L. Kirk, Richard Kemp, Patrick S. Mariano, Robert T. Paine and Wei Wang from the Department of Chemistry and Chemical Biology at the University of New Mexico will acquire a low-field (300 MHz) multinuclear NMR spectrometer. The instrument will be used to support research activities such as: 1) synthetic methodologies that allow for step by-step (atom-by-atom) assembly of new families of main group element ring and polycyclic cage compounds rich in Group 13, 14 and 15 elements; 2) activation and fixing of small molecules such as carbon dioxide, COS, carbon disulfide, and oxygen to produce more valuable products; 3) homogeneous catalytic routes to epoxides and other partially-oxidized organics using late transition metal pincer complexes; 4) characterization of structures and stereochemistry of synthetic intermediates and natural and non-natural products; 5) rational design of Giardia lamblia growth inhibitors as well as study of phosphoproteins; 6) study of donor-bridge-acceptor systems as potential components of molecular wire devices and, 7) synthesis of new inhibitors of the proteins cholesterol esterase, lactate dehydrogenase, NfKB, urokinase, aldose reductase, HIV protease and Abeta aggregates.

Multinuclear NMR spectroscopy is an essential analytical tool in chemistry and biochemistry research. The spectra enable researchers to identify unknown substances and to provide information on the atom arrangement and structures in species ranging from small molecules to large proteins by detecting transitions between energy levels arising from the nuclear spin properties of atoms. This spectrometer will enhance many research activities of investigators and students, many of whom are from underrepresented groups.

The Chemical Structure, Dynamics and Mechanisms B Program supports Professor Martin Kirk of the University of New Mexico for a project entitled "Donor-Acceptor Interactions, Long-Range Electron Correlation, and Dynamic Spin Manipulation: Relationship To Molecular Electronics." The project focuses on electronic structure contributions to the ground state properties of magnetic donor-bridge-acceptor biradicals. The primary goals of the research are to understand excited state contributions to bridge mediated electronic coupling, understand how open-shell excited state singlet configurations promote long-range electron correlation, and develop new platforms for spin control of excited state dynamics in photoexcited donor-acceptor molecules. The research project is achieving these goals by adding to the electron/spin transport knowledge base and providing new insight into electronic structure contributions to molecular electronic materials, particularly as they relate to switchable electron transfer/transport conduits, spin-polarized electron transport, and the control of quantum interference effects.

These research activities broadly impact our understanding of how molecular and molecule-based systems can advance new technologies based on molecular electronics. The project advances discovery and understanding while promoting teaching, training, and learning through incorporation of research advancements in the classroom, student research presentations at international meetings, and mentoring undergraduate and high school students who are involved in the research. Broader participation is emphasized through New Mexico's Experimental Program to Stimulate Competitive Research (NM EPSCoR) projects, The University of New Mexico (UNM) Nanoscience and Microsystems program, mentoring students from underrepresented groups, and mentoring early career faculty members at UNM. Infrastructure for research and education is being enhanced through an association with the Center for Integrated Nanotechnologies, sharing spectroscopy facilities with collaborating scientists and UNM junior faculty, and contributing to improved computing infrastructure at UNM. New research results are constantly being injected into the classroom environment, which contributes to the broad dissemination of research results. Finally, potential benefits to society derive from the ability to transform the results of the basic research to an increased understanding of electron and spin transport, long-range interactions, and excited state dynamics in molecular electronic systems at the nanoscale.

? DESCRIPTION (provided by applicant): There exists a fundamental gap in the knowledge base regarding molybdenum cofactor sulfurase C-terminal (MOSC) domain protein structure and function, as well as the role of the complex pyranopterin dithiolene ligand in the catalytic cycles of all pyranopterin molybdenum enzymes. Our long-term goal is to develop a molecular electronic structure understanding of pyranopterin molybdenum enzyme mechanism and function in order to have a positive impact on the quality of human health. Our primary objectives are to determine 1) electronic structure contributions to pyranopterin dithiolene function, 2) geometric and electronic structure contributions to the reactivity of MOSC domain proteins, and 3) why dimethyl sulfoxide reductase family enzymes require two pyranopterin dithiolenes in order to function. We will accomplish these objectives by using a combined spectroscopic approach (electronic absorption, MCD, Raman, XAS, EPR, etc.) augmented by vibrational, spectroscopic, bonding, and reaction coordinate computations to probe the pyranopterin and catalytic mechanisms. Parallel studies on judiciously chosen small molecule analogs will complement this approach. The central hypothesis is that Mo site geometric and electronic structure, coupled with the nature of the pyranopterin dithiolene, contributes to the unique function of these enzymes. The rationale for this research is that a comprehensive understanding of MOSC family proteins and the complex interplay between the Mo ion and the pyranopterin dithiolene will provide new insights into disease states and have a positive impact on human health. We will test our central hypothesis in order to accomplish the stated objective of this proposal through the successful pursuit of three Specific Aims 1) Determine how the pyranopterin contributes to electron transfer and redox processes in xanthine oxidase and sulfite oxidase family enzymes, 2) Understand structural and mechanistic relationships between MOSC domain proteins that define their function, and 3) Develop an understanding of how coordination number and the cooperative relationship between two different pyranopterins contribute to catalysis in dimethyl sulfoxide reductase family enzymes. Our contribution is expected to provide a detailed understanding of MOSC mediated catalysis at the molecular level, the link between pyranopterin dithiolene oxidation state and the role of the pyranopterin dithiolene in catalysis, and the relationship between coordination environment and the need for two pyranopterin dithiolenes in dimethyl sulfoxide reductase family enzymes. The proposed research is significant since it will advance our understanding of post-translational sulfuration processes and molybdenum cofactor trafficking, mechanisms of prodrug activation and xenobiotic detoxification, and the electronic flexibility of the pyranopterin dithiolene in molybdoenzyme catalysis.

In this project funded by the Chemical Structure, Dynamics and Mechanism B Program of the Chemistry Division, Professor Martin L. Kirk of the Department of Chemistry and Chemical Biology at the University of New Mexico is studying how electronically active molecules can be used in molecular electronics and other molecule-based technologies. Prof. Kirk is studying (1) how electrons flow through the molecules and can be controlled, (2) how the structures of the molecules affect their absorption of light, and (3) the nature of the molecules' excited states after light has been absorbed. The research is interdisciplinary and positioned at the interface of organic, inorganic, and physical chemistry and is providing enhanced opportunities for the education and training of next generation scientists. Professor Kirk is involved in teaching, training and mentoring student researchers, including those from underrepresented groups. He is also participating in outreach projects in New Mexico including those associated with the Albuquerque Explora! Museum and NanoDays.

The project goals focus on using creatively designed magnetic exchange coupled Donor-Bridge-Acceptor biradical systems to explore (1) molecular quantum interference and molecular rectification, (2) anisotropic covalency induced spin orbit coupling contributions to excited state lifetimes, and (3) how excited state magnetic exchange interactions affect magneto-optical activity, spin polarization, and excited state relaxation pathways. The project utilizes a combined spectroscopic approach augmented by theory and computations to address these problems. Regarding molecular electron transport phenomena, Donor-Bridge-Acceptor electronic coupling in the context of molecular conductance is studied in order to test recent theoretical hypotheses and compare results to those that have been obtained under device conditions. This work could directly impact the molecular electronics field. Modulation of spin orbit coupling through anisotropic covalency impacts the ability to control relaxation rates and pathways in photoexcited states. Work using magnetic circular dichroism and transient spectroscopies reveals the nature of complex multi-spin excited state magnetic exchange interactions that derive from photoexcitation. The research contributes to a greater understanding of excited state magnetism, exciton-polaron coupling, and solar energy conversion. The project advances knowledge and understanding in the field of donor-acceptor interactions and contribute substantially to the understanding of molecular electronics, atom level control of excited state lifetimes, and spin effects on excited state processes.

This award is supported by the Major Research Instrumentation (MRI), the Chemistry Research Instrumentation (CRIF) Programs as well as the Established Program to Stimulate Competitive Research (EPSCoR). Professor Martin Kirk from University of New Mexico and colleagues Victor Acosta, Daniel Feezell, Francesca Cavallo and Abdelghani Laraoui have acquired a magnetic property measurement system (MPMS.) The instrument, also known as a magnetometer, is a very sensitive device to measure magnetic fields. It is used to measure the magnetic properties of molecules, molecule-based materials, solid state materials and devices. These magnetic properties are important in many applications. For example, the instrument is ideally suited for characterizing background impurity applications in transistors. This will help improve the performance of higher power and higher frequency transistors. The instrument serves as a resource for the New Mexico region beyond UNM's campus. Faculty at four additional Hispanic serving institutions use the instrument (Western New Mexico University, New Mexico Tech, New Mexico Highlands, and New Mexico State University). Undergraduate and graduate research students receive training on this state-of-the-art instrument.

The award is aimed at enhancing research and education at all levels. Research is conducted of cell-bound biomarkers with magnetic nanoparticles to enable their detection non-invasively using ultrasensitive diamond magnetic microscopy. Studies are underway to quantify impurity concentrations and differential resistance in wide-band-gap vertical power transistors, vertical-cavity surface-emitting lasers, and light-emitting diodes. Investigations are conducted of Groups III-V materials for lasers, detectors, and transistors, and carrying out magnetic and transport studies for paramagnetic sensors and superconducting electronics. Nanoscale probing of condensed matter physics phenomena with magnetometry based on nitrogen-vacancy centers in diamond is also carried out.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

In this project, funded by the Chemical Structure, Dynamics and Mechanisms-B Program of the Chemistry Division, Professor Martin L. Kirk of the Department of Chemistry and Chemical Biology at the University of New Mexico is developing and studying new molecular electron donor-acceptor systems. These novel systems will enhance our knowledge and understanding of the emerging field of molecular electronics and develop new insights into technologically-relevant processes that occur in solar energy conversion devices, optoelectronics, photochemistry, and photonics. The long-term goal of this research is to understand how molecular design principles can be used to affect molecular electron transport and excited state lifetimes and processes. The project is interdisciplinary and involves organic and inorganic chemistry concepts that are interrelated with physics and materials chemistry. This research team is located at a Hispanic Serving and Minority Serving Institute and thus, the research activities include broad participation by underrepresented minority students. Professor Kirk and his team advance discovery and understanding while promoting teaching, training and learning by engaging undergraduate and high school students in research projects through their relationships with international universities, the Albuquerque Academy, and New Mexico Tech. Professor Kirk gives public lectures at New Mexico museums,, co-organizes a Telluride Science Research Center meeting (Molecules and Mechanisms for Quantum Information Processing), and give lectures to the general public (Energy Prospects for New Mexico) and to undergraduates (The Molecular Highway: How Molecules Direct Electron Traffic). Potential benefits to society result include advances in quantum device technologies.

Donor-Acceptor systems provide a convenient platform to address technologically-relevant questions in molecular electronics and excited state processes. The donor-acceptor molecules that are studied possess novel electronic structures that define their ground state properties and excited state photophysics. In this project, chemical synthesis and spectroscopic approaches are augmented by theory and computations to understand the interrelationships between molecular and more complex, extended systems. The project goals focus on using well designed donor-acceptor molecules, including magnetic exchange coupled Donor-Bridge-Acceptor biradical systems, to bridge critical knowledge gaps and explore the relationship between computed molecular conductance values and experimental spectroscopic and magnetic data. Such experiments may provide new insight into single-molecule conductance and molecular rectification. The project also tackles vibronic spin-orbit coupling and anisotropic covalency contributions to excited state lifetimes; and the complexity of multiple pairwise spin exchange interactions in electronic excited states.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

This award is supported by the Major Research Instrumentation and the Chemical Instrumentation Programs. Professor Jeffrey Rack from the University of New Mexico and colleagues Martin Kirk and Yang Qin are acquiring an ultra high-pressure, quadrupole, time-of-flight mass spectrometer (UPLC-QTof-MS). In general, mass spectrometry (MS) is one of the key analytical methods used to identify and characterize small quantities of chemical species embedded in complex samples. In a typical experiment, the components flow into a mass spectrometer where they are ionized into ions and the ions' masses are measured. This highly sensitive technique allows the structure of molecules in complex mixtures to be studied. An instrument with a liquid chromatograph can separate mixtures of compounds before they reach the mass spectrometer. Using the time-of-flight method of mass spectrometry, the mass-to-charge ratio of an ion is determined by the way of a time measurement in which ions are accelerated by an electric field of known strength. This acceleration results in an ion having the same kinetic energy as any other ion that has the same charge. The acquisition strengthens the research infrastructure at the University and regional area. The instrument broadens participation by involving diverse groups of students in research and research training using this modern analytical technique and supports many users and underrepresented students. It also provides training opportunities to undergraduate students, many of whom are first-generation students. The instrument gives students experience using vital instrumentation that they carry with them into their careers.

The award of this mass spectrometer is aimed at enhancing research and education at all levels. It is especially useful for developing photoactive compounds and materials and for designing support magnetic materials for molecular electronics. The instrument is also employed in evaluating polychalcogenylene vinylene conjugated polymers for flexible optoelectronic applications and for developing platforms for screening libraries of bioactive species. The mass spectrometer is also utilized for the characterization of generic architectures that may be related to the Niemann-Pick C1 metabolic pathway associated with liver and spleen disorders and for deciphering the conformational control of nitric oxide synthases as well as labeling potential drugs with stable isotopes

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.