Daniel E. Falvey - US grants

This investigation will deal with spectroscopic and kinetic evaluation of the generation of arylnitrenium ions. Although the initial phase of the project will involve the photolysis of anthranilium salts, it is expected that several new photochemical methods for the general production of arylnitrenium ions will eventually emerge. The study will center on the use of nanosecond laser flash photolysis, low temperature ESR spectroscopy, and molecular orbital calculations to provide unequivocal identification of arylnitrenium ions. A highlight of the work will be to define the spin-multiplicity of the nitrenium ions generated and the products formed from each spin state. The question of the existence of a singlet-triplet equilibrium will be answered and the consequences for final product distribution will be delineated. The role of arylnitrenium ions in DNA damaging reactions will also be investigated by trapping of arylnitrenium ions with guanine to simulate carcinogenetic reactivity. %%% This new grant from the Organic Dynamics Program supports the work of Professor Daniel A. Falvey at the University of Maryland. The investigation will seek to analyze the reactivity of very short lived molecules called nitrenium ions. Nitrenium ions, which possess a nitrogen with a positive charge, have received little attention and yet represent a potential class of reactive species with widespread utility in chemical processes induced by light. By using an instrument designed to take snap-shot ultraviolet absorption "pictures" of transient chemical species which live a few billionths of a second, it will be possible to confirm the existence of arylnitrenium ions which have been implicated as the primary entities involved in the DNA damaging process of arylamines.

This award from the Chemistry Research Instrumentation Program will assist the Department of Chemistry at the University of Maryland in the purchase of an upgrade for an electron spin resonance (ESR) spectrometer. This upgrade is essential if the PI's are to make much more effective of the present equipment. The research projects that will be enhanced by the acquisition of this equipment include: 1) Studies of the electronic structure of organometallic 15-electron complexes, 2) Formation and electonic structure studies of 17 electron dihydride complexes, 3) Photochemical and electrochemical generation of arylnitrenium (Ar-N-R+) ions, probable intermediates in chemical carcinogenesis, and the study of their electronic structure, 4) ESR studies of organometallic and molecular-based inorganic polymers with bulk ferromagnetism and low dimensional conductivity, 5) ESR studies of enzyme-stablized radicals in biological processes. %%% An electron spin resonance (ESR) spectrometer provides information about the electronic structure of molecules and can detect the presence of "free radicals" which play an important in many chemical and biological interactions.

This award is made in the Organic Dynamics Program in the support of the research of Prof. Daniel Falvey at the University of Maryland. The research deals with chemical and spectroscopic studies of nitrenium ions, photochemically generated from N-aminopyridinium salts. Two specific areas will be addressed: (1) the solution reactivity of nitrenium ions, particularly with nucleophiles, and (2) defining the structural features of nitrenium ions which control their singlet-triplet energy gaps. The former will be probed by laser flash photolysis and photothermal beam deflection calorimetry and the latter by low temperature electron paramagnetic resonance spectroscopy. Experimental studies will be complemented by semi-empirical and ab initio calculations. Nitrenium ions, as reactive intermediates in organic reactions, have not been well explored. This study of the structural features which control their singlet-triplet energy gaps, will provide fundamental information which will aid in the design of new magnetic materials. Additionally, the study of the reactivity of nitrenium ions towards nucleophiles will shed light on their role in DNA damage and carcinogenesis.

With this award Professor Falvey will continue his work on the chemical and spectroscopic studies of nitrenium ions and related electron deficient nitrogen species. A variety of experimental techniques will be used to elucidate the chemical and physical properties of nitrenium ions. The chemistry of aryl nitrenium ions will be studied in detail in the course of this work. Aryl nitrenium ions are generated in biological systems through enzyme catalyzed metabolism of aromatic amines. These nitrenium ions are electrophilic and hence very reactive so the production of these species in living organisms is believed to be mutagenic and/or carcinogenic. Aryl nitrenium ions are also implicated as intermediates in the synthesis of polyanilines, a conducting polymer. Aniline oxidation will be used to generate nitrenium ions and their reactions with a variety of electron rich arenes will be studied. Professor Falvey and his group will also work to prepare and study ground state triplet nitrenium ions since theory predicts they will have different chemical reactivities than the ground state singlet nitrenium ions outlined in the first part of this proposal.

With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Daniel E. Falvey of the Department of Chemistry at the University of Maryland, College Park. Dr. Falvey will work on the generation and study of a family of reactive molecules known as nitrenium ions. These molecules contain an electron deficient and hence chemically reactive nitrogen atom as part of their molecular structure. Nitrenium ions are generated in biological systems through enzyme catalyzed metabolism of aromatic amines. The production of these species in living organisms is believed to be mutagenic and/or carcinogenic. Nitrenium ions are also implicated as intermediates in the synthesis of polyanilines, a conducting polymer. A thorough understanding of how these species are generated and how they react should contribute to a better understanding of the fundamental chemistry involved in both of the processes outlined above. Students trained during the course of this work will gain skills needed by the speciality chemicals industry and the pharmaceutical industry.

With support from the Chemistry Research Instrumentation and Facilities (CRIF) Program, the Department of Chemistry at the University of Maryland in College Park will acquire instrumentation for time correlated single photon counting. This equipment will enhance research in a number of areas including the following: a) single-molecule studies of protein-induced DNA conformational populations; b) measurement of fluorescence lifetimes from short-lived low quantum yield species; c) studies of complex fluorescence kinetics and reorientation of new molecular surfactants adsorbed to liquid/liquid interfaces; and d) investigations of radical chemistry in environmental systems.
Measuring time resolved fluorescence affords researchers direct insight into the local environment and dynamics around a probe. Techniques developed to monitor time resolved fluorescence have been broadly applied to established fields such as photobiology as well as newly emerging areas in materials chemistry.

With this award, the Organic and Macromolecular Chemistry Program supports the work of Professor Daniel E. Falvey, of the Chemistry Department at University of Maryland, College Park, MD. This research will involve studies of the electronic and chemical properties of nitrenium ions and ion diradicals and investigate new photochemical routes to polyaniline. Both experiment and theory will be used in these studies in which a series of short-lived cationic intermediates, including nitrenium ions, carbenium ions, and oxenium ions, will be generated and their electronic properties elucidated. Recent computational studies in the PI's lab predict that appropriate substitutions in these intermediates will lead to structures that have high-spin triplet ground states. A combination of laser flash photolysis, chemical, trapping experiments, low-temperature EPR spectroscopy, SQUID magnetometry and electronic structure calculations will be employed in these investigations, which have the long term goal of identifying persistent or stable high-spin triplet species. In addition, a new photochemical route to polyaniline will be explored.

These studies, directed toward the synthesis of stable high-spin molecules, will aid in the design of organic materials that have useful magnetic and electronic properties. The development of a well characterized photochemical method for synthesizing polyaniline will aid in the fabrication of nano and microscale electronic devices that make use of this polymer. Graduate and undergraduate students involved in this project will gain valuable experience in organic synthesis, polymer chemistry, computational chemistry and photochemistry.

Professors Michael P. Doyle, Jeffrey T. Davis, Daniel E. Falvey, Lyle D. Issacs and Herman O. Sintim of the University of Maryland have submitted a proposal in response to the CRIF: MU solicitation to acquire a high resolution double sector mass spectrometer. The research projects it will support are related to a variety of studies including: (i) synthesis and application of unnatural amino acids; (ii) characterization of small molecule intermediates used in supramolecular chemistry, molecular recognition, and the assembly of receptors for transmembrane ion-transport; (iii) development of highly selective and efficient catalytic processes for the synthesis of biologically relevant compounds; (iv) the study of photo induced electron transfer reactions and the generation of novel high spin organic species; (v) development of small molecule probes for electron and electrophile migration along strands of DNA; and, (vi) total synthesis of antibiotics of the family of Platensimycin.

Mass spectrometry (MS) is used to identify the chemical composition of a sample and determine its purity. A high resolution mass spectrometer has the capability of performing accurate elemental composition analysis of compounds. This makes it a powerful tool for identification of known and unknown or new compounds. This acquisition will benefit undergraduate and graduate students in their research and in a new experimental course to be developed. Students and faculty at Howard University Virginia State University and Catholic University will also use it to analyze samples.

The Chemical Structure, Dynamics and Mechanisms Program in the Chemistry Division at the National Science Foundation supports Professor Daniel Falvey of the University of Maryland- College Park, for the development of new molecular systems with controllable photochemical release of one or more functional groups. The goal of the project is to develop donor-acceptor systems that will undergo electron transfer sensitized reactions that release stable molecules such as carboxylic acids. An innovative feature of Professor Falvey's approach is that the molecules will be designed to undergo these reactions after absorbing two photons, so that low energy visible light can be employed. These reactions are important to many fields as they allow for both temporal and spatial control of the movement of molecules.

Broader impacts of the research include the potential for improved control of 3D nanofabrication processes, and for imaging and biomedical applications. Professor Falvey is recognized for his breadth of knowledge across several disciplines (organic synthesis, spectroscopy, kinetics, and computational chemistry), which makes his laboratory effective in tackling difficult research problems. He has been successful in recruiting and mentoring underrepresented groups to his laboratory at the University of Maryland, and he is an advisor to the International Chemistry Olympiad.

Chemistry (12) "Transforming Advanced Chemistry Laboratories to Prepare Students for Challenges in Nanotechnology, Energy and the Environment" at the University of Maryland is testing the hypothesis that extended and repeated exposure to modern instrumentation is effective for teaching upper-level chemistry laboratories. Current scientific problems are increasingly complex and solving them requires the use of increasingly sophisticated instrumentation. As the number and complexity of modern tools for chemical measurements increases, it is increasingly impractical to train undergraduates on every possible technique they might encounter in the workplace or in postgraduate studies. The intellectual merit is to develop methods to (a) enable students to become sophisticated at accomplishing open-ended, problem-based exercises and (b) provide transferable skills that allow students to quickly master new instrumentation in later laboratory courses. The project outcomes include (a) improving students' understanding of the concepts of physical and analytical chemistry, (b) providing aspiring chemists and biochemists with problem solving skills that will enable them to answer modern experimental problems, (c) fostering an appreciation of the experimental basis of chemical and biochemical knowledge and (d) introducing students to modern interdisciplinary problems in relevant areas. The innovations that prove most effective will serve as the basis for designing an advanced laboratory curriculum in chemistry. The project results will have broad impact by serving as a model for enhancing student learning that can be adapted to other university-level chemistry programs. The results will be disseminated throughout the chemical education community and are likely to be of use to the broader STEM community.

The ability to create devices with finer features over larger areas is crucial to technological innovation in both mature and emerging industries. In the semiconductor industry, progress in increasing circuit density has been maintained by using light of ever shorter wavelengths to produce circuit patterns, but this method is expensive and further improvements are nearing their limit. This Scalable NanoManufacturing (SNM) project will use three beams of visible light of different wavelengths to produce nanoscale features with the improved resolution required to produce high density integrated circuits. Because visible light is inexpensive to produce, propagate and manipulate, the method promises to lower the cost of cutting-edge nanomanufacturing by a factor of 10 or more. The project team will collaborate with major industrial developers and end-users to transfer the technology to practice, providing a major boost to American competitiveness in scalable nanomanufacturing. The ever more compact and powerful devices that this technology will produce have the potential to impact virtually every imaginable aspect of technology and every member of our society.

The project team has researched and proven 2-color approaches to photolithography that have made possible the creation of high-resolution features using visible light. The basis of these techniques is that one color of light is used to initiate chemistry and a second color is used to inhibit it. However, these methods are not yet capable of producing the resolution needed to satisfy the requirements of the next node of the Semiconductor Roadmap. The stumbling block for 2-color approaches has been that initiation of chemistry competes with deactivation. The proposed 3-color approaches circumvent this problem. One color of light pre-activates chemistry, a second color of light deactivates the molecules, and a third color of light transforms pre-activated molecules into activated molecules that then undergo chemistry. This approach provides a viable path to attaining sub-20-nm resolution for scalable nanomanufacturing in 2 and 3 dimensions. The project team combines expertise in photolithography, photochemistry, spectroscopy and pattern transfer to realize this vision. The team will work closely with industrial collaborators who have expertise in commercial photoresists, photolithographic tool components and photolithographic simulation methods to ensure that the research methods and materials used are compatible with the needs and processes of the semiconductor industry and other consumer product industries.

This award is supported by the Major Research Instrumentation and the Chemistry Research Instrumentation programs. Professor Peter Nemes from the University of Maryland College Park and colleagues Daniel Falvey, Lyle Isaacs, Lisa Taneyhill and Scott Juntti are acquiring a high-resolution, high-pressure liquid chromatograph mass spectrometer with electrospray ionization capabilities (HR-HPLC-ESI-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. In the electrospray technique a high voltage is applied to a liquid to create an aerosol. This voltage is useful to produce ions from large molecules by avoiding the propensity of macromolecules to fragment when ionized. 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. The acquisition also provides training opportunities to many undergraduate and graduate students as well as postdoctoral fellows at this institution. The new capability to measure both small biological and organic molecules in a shared Mass Spectrometry Facility has a broad impact on scientists and students in the District of Columbia-Maryland-Virginia region through workshops as well as curriculum modernization and collaborations with Bowie State University.


The award of the mass spectrometer is aimed at enhancing research and education at all levels. It especially impacts studies of metabolic effectors of embryonic development and hormone metabolite activity in nervous system functions. The instrumentation is also used for research on mitochondrial metabolism in the liver as well as molecular mechanisms in neural crest and dental placode cells. In addition, the MS provides information useful for the search of the next generation enzymatic kinetic isotope effects and for studying binders for the valosine-containing protein (VCP) that segregate protein molecules from large cellular structures. The mass spectrometer is also used to inform the design of efficient syntheses for molecular guest compounds. It is also utilized in investigations of electrophilic nitrogen containing species and their reactivity with proteins and nucleic acids.

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.