Chemistry Grants

Dasan M. Thamattoor, 2018-2020, Fulbright Global Scholar Award: A Globally Integrated Research and Teaching Collaboration on Reactive Intermediates (Fulbright Foreign Scholarship Board)

Under the auspices of this award Das will spend the summer of 2018 in Japan (research at Hiroshima University), the summer of 2019 in the Czech Republic (research at Masaryk University), and January/February of 2020 in Singapore (teaching at Yale-NUS College).

Dasan M. Thamattoor, 07/01/2018, ACS-PRF: New Photochemical Approaches to Cyclopropylidenes from Phenanthrene-based Spiropentanes (PRF# 58437-UR4)

Intense scrutiny by theoreticians and experimentalists, as well as advances in technology, have led to considerable progress in carbene chemistry over the years. Much work still remains to be done, however, to better understand cyclopropylidenes, the smallest cyclic carbenes containing the divalent carbon as part of a three-membered ring. It is noteworthy that techniques such as time-resolved laser flash photolysis and matrix isolation spectroscopy, which have played critical roles in helping elucidate the structures and reactivities of carbenes, have had very little impact on the study of cyclopropylidenes primarily due to the lack of suitable photochemical precursors to these important intermediates. To address this conspicuous void in the carbene literature, this proposal seeks to undertake fundamental research projects, appropriate for undergraduates, to study cyclopropylidenes that are photochemically generated from new and versatile phenanthrene-based spiropentanes. Experimental work such as the synthesis, purification, and characterization of precursors; steady state photolysis in solution with and without traps; product analysis; and time-resolved laser flash photolysis, will be also accompanied by detailed computational studies using modern methods. The proposed projects will provide undergraduate students with a multi-faceted research experience, engage them as partners in the discovery process, and serve them well in their post-graduate scientific careers.

Jeffrey Katz, 07/05/2017, NSF, RUI: Synthesis of Heterohelicenes Using Acetylene-Activated SNAr Reactions (CHE-1664549)

The Chemical Synthesis Program of the Chemistry Division supports this project by Professor Jeffrey Katz, a faculty member in the Department of Chemistry at Colby College. He is investigating chemical methods that allow for the synthesis of chemical compounds called helicenes. Helicenes are unusual molecules that possess a rigid helical (screw-like) shape. The primary goal of the funded research is the development of technology that allows access to previously unknown helicenes containing nitrogen, oxygen, sulfur, and selenium atoms on terminal positions of the molecules. Compounds of this type have potential applications as chemical sensors, organic electronics, and new polymeric materials. Students working on this project are obtaining experience in organic chemical synthesis and materials chemistry. Professor Katz is highly active in the recruitment and retention of underrepresented minority students into chemistry and other scientific fields. He serves as co-Director of the Colby Achievement Program in the Sciences (CAPS), a summer bridge program at Colby College for entering first-year students from underrepresented backgrounds that fosters a climate of success and leadership within the minority student science population.

Helicenes and their heteroaromatic variants are a promising compound class for use as chiral ligands, supramolecular building blocks, polymerization monomers, liquid crystals, optoelectronic materials, and components of molecular machines. A wide variety of [n]heterohelicenes are being accessed using acetylene-activated SNAr/anionic cyclization chemistry as the key diversifying transformation, a reaction cascade recently developed in the Katz laboratory. The cascade approach is efficient, highly modular, and allows for structural diversification at the final stages of the synthetic sequence. Further, the investigations target the production of non-racemic heterohelicenes through the use of chiral nucleophiles in the SNAr step of the cascade sequence, as well as adaptation of the method to produce heteroarene-terminated phenacenes. Undergraduate students working with Professor Katz travel to scientific conferences to present their research. Professor Katz leverages his attendance at these meetings by organizing and moderating Undergraduate Context Sessions, which support the educational environment for all attending undergraduate students. Such Sessions are included in the general programs of several major conferences in organic chemistry and have helped undergraduate students to become an increasingly recognized focus of the program structures.

Dasan M. Thamattoor, 07/01/2017, NSF RUI: Strained Cycloalkynes

In this project funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Dasan Thamattoor of the Department of Chemistry at Colby College is developing new approaches to small-ring compounds containing a triple bond. As the triple bond prefers a linear geometry, incorporating this feature inside a small ring can lead to considerable strain. Investigating such strained molecules can teach us about structure, bonding, energetics, and chemical reactivity. It can lead to the design of new reactions for the preparations of pharmaceuticals and energetic materials. The project, which integrates elements of synthetic, mechanistic, and computational organic chemistry, is designed to provide undergraduates with a wholesome research experience, and engage them as partners in the scientific enterprise. In addition, several initiatives to promote the delivery of high quality education in Science, Technology, Engineering, and Mathematics (STEM) in the local schools (K-12) will be pursued. This includes providing summer research opportunities for high school students and partnering with educators in the elementary, middle, and junior high schools to enhance STEM offerings.

Reuben Hudson, Jeffrey Katz, Maine Technology Institute, TechStart Grants 5/13/2016, 6/28/2016 (TS0612, TS0623)

Keith Russell, Jeffrey Katz, 2/10/2016, NSF: The TIM Consortium: A Dispersed REU Site in Theoretically Interesting Molecules (CHE-1559886)

This award funded by the Division of Chemistry Research Experience for Undergraduates (REU) Sites Program supports a dispersed REU site led by Professor K. C. Russell at Northern Kentucky University. The site also includes senior researchers and their undergraduate students at Grand Valley State University, the University of Richmond, the University of San Diego, and Colby College. Research projects supported in this site are focused on the study of “theoretically interesting molecules” in the fields of synthetic organic, physical organic, organometallic, and materials chemistry. The REU site supports eleven undergraduate research students per summer in a ten-week program. Broader impacts are addressed through the recruitment of students from local two-year colleges and from four-year institutions that lack significant opportunities for undergraduate research. The site seeks to prepare the diverse student cohort participating for further study in the chemical sciences and graduate school, with eventual employment as part of the country’s technical workforce.

Undergraduate research projects include: (1) the exploration of calcium-catalyzed addition reactions (Prof. Kristine Nolin, University of Richmond); (2) the synthesis and characterization of novel [12]- and [14]-annulenes (Prof. K. C. Russell, Northern Kentucky University); (3) the synthesis and evaluation of extraction agents for Ln-Ln and Ln-An separations (Shannon Biros, Grand Valley State University); (4) the synthesis of self-assembled architectures from end-functionalized polysaccharides (Prof. Peter Iovine, University of San Diego); and (5) the synthesis of rigid oxacalixarene scaffolds (Prof. Jeffrey Katz, Colby College). In addition to research activities, the student participants take part in an integrated ethics curriculum that includes training modules and case studies based on current events within the scientific community.

King, Cole, Nyhus, Bevier, Rueger, Fleming, Donihue, Bruesewitz, Dissanayake, BRCA, MSL, and MLRC, 9/1/2013, NSF-Maine EPSCoR. Modeling Resilience and Adaptation in the Belgrade Lakes Watershed (NSF-EPS0904155).

Modeling Resilience and Adaptation in the Belgrade Lakes Watershed A dynamic group of academic researchers and students in collaboration with conservation partners in the Belgrade Lakes watershed are investigating how communities build ecological and societal resilience to sustain healthy lake ecosystems, and the specific influence of information on conservation behavior. Maine’s lakes contribute over five percent to the state’s gross domestic product and are central to the state’s national image as “Vacation Land”. Maine has some of the most progressive shoreland zoning standards in the country, a comprehensive volunteer lake monitoring program, hundreds of citizen-based lake conservation organizations, and supports extensive academic and government lake research. Nevertheless, the US EPA lists over ten percent of Maine lakes as impaired, with many additional lakes showing declines in water quality. Maine citizens are simply “loving their lakes to death.” Over the last four years, we have used the Belgrade Lakes watershed as a model for understanding the dynamics of human-coupled lake ecosystems because it provides a unique laboratory to study the complex relationships among environmental, biogeochemical, and socio-economic systems.
In Year 5, our proposed work focuses on capstone activities that document the last four years of work in a range of professional and public venues, that solidify an already dynamic and collaborative research team from academia and the conservation community, and that facilitate submission of a major research proposal to NSF to investigate how reciprocal information flow in this coupled human natural system influences stakeholder-based actions and conservation behaviors.

Dasan Thamattoor, 09/01/2013, NSF, RUI: Experimental and Theoretical Investigation of Alkylidenecarbenes from Methylenecyclopropanes

The Chemical Structure, Dynamics, and Mechanisms – B Program of the Division of Chemistry supports Professor Dasan M. Thamattoor of Colby College, in an undergraduate-driven research program, to investigate alkylidenecarbenes generated from new photochemical sources based on cyclopropanated phenanthrene and indan systems. The program includes the study of acyclic alkylidenecarbenes with alkyl and aryl substituents, the investigation of cycloalkylidenecarbenes, with a particular emphasis on their ability to generate small- and medium-ring cycloalkynes, the study of dihalovinylidenes, and the domino generation of two alkylidenecarbenes from a single precursor and the formation of C2.
This research program provides a research experience for undergraduate students, which trains them in the synthesis of organic molecules and in the physical methods used to characterize these molecules and determine their structures. The work will continue an outreach program that provides research opportunities to high school students over the summer months. Also, the implementation of new partnerships with math and science teachers at local elementary and middle schools, to deliver quality instruction in STEM subjects, will be sought and existing ones strengthened.

Jeffrey Katz, 08/01/2012, NSF, RUI: Developing Acetylene-Activated SNAr Reactions

With an RUI Award from the Chemical Structure, Dynamics and Mechanisms Program, Professor Jeffrey L. Katz of Colby College will research the merging of the synthetically powerful carbon-carbon triple bond, with a classic organic transformation, the nucleophilic aromatic substitution (SNAr) reaction. The Katz group has found ethynyl groups to be sufficient for activating fluorobenzenes toward nucleophilic substitution. Such acetylene-activated SNAr reactions will be pursued in three areas. First, through kinetics measurements and experiments of reaction scope, students in the Katz laboratory will study the electronic nature of acetylene functional groups with respect to aromatic substitution processes. Second, acetylene-activated SNAr chemistry will be exploited for the rapid synthesis of complex heterocycles, and heterocyclic arylethynyl-substituted luminophores. Finally, acetylene-substituted SNAr reactions will be applied to the synthesis of oxacalix[4]arene macrocycles, and the formed oxacalix[4]arenes bearing acetylene groups will be studied as a new class of bifunctional molecular receptors.

This RUI award will also support students working with Professor Katz as part of a research-based mentoring program for underrepresented minority students in chemistry at Colby College. Professor Katz is the creator and Director of the Colby Research Scholars (CRS) Program, an academic-year program for minority students to pursue independent research projects with faculty in the sciences as early as their freshman year. Professor Katz also serves as co-Director of the Colby Achievement Program in the Sciences (CAPS), a summer bridge program for entering first-year students from underrepresented backgrounds. In conjunction, these programs seek to recruit and retain minority students into chemistry and other scientific disciplines. Students participating in the CRS and CAPS programs in the Katz laboratory will have active roles in the proposed research, participate in research group meetings, attend and present posters at local and national meetings, and interact academically and socially with other student-scientists.

Keith Russell, Jeffrey Katz, 5/10/2011, NSF: The TIM Consortium: A Dispersed REU Site in Theoretically Interesting Molecules

This award from the Division of Chemistry (CHE) supports a distributed Research Experience for Undergraduates (REU) site led by K. C. Russell at Northern Kentucky University. Besides, Northern Kentucky University, the site also includes senior researchers and their undergraduate students at Colby College, Trinity University, Macalester College, Grand Valley State University and the University of San Diego. The research projects supported in this site are focused on the study of “theoretically interesting molecules.” Undergraduates will be recruited to this site primarily from local two-year colleges and other institutions without significant opportunities for undergraduate research. The site will continue a fruitful collaboration with students and faculty from Central Connecticut State University. The site will support twelve undergraduate research students per summer in a ten week program. A sample of the projects that researchers will work on include: (1) the study of an interesting family of antiaromatic dications and dianions (Prof. Nancy Mills, Trinity University); (2) the synthesis and characterization of push-pull [14]-annulene compounds (Prof. K. C. Russell, Northern Kentucky University) ; (3) the synthesis and study of oxacalixarenes and poly (meta-phenelene oxides) (Prof. Jeffrey Katz, Colby College); (4) the synthesis nad characterization of hetero-boroxines and novel boroxine containing macrocycles (Prof. Peter Iovine, University of San Diego); (5) the study of Cu-catalyzed azide/alkyne click chemistry for the synthesis of novel fluorophores (Prof. Ronald Brisbois, Macalester College); and (6) the development of new multidentate chelators of Gd(III) for potential use in MRI contrast agents (Shannon Biros, Grand Valley State University). In addition to conducting research during the summer, the students participating in this program will participate in a number of professional development activities.

Young scientists need exposure to modern research methods and tools as part of their training. This REU site aims to provide students without significant research experience a chance to conduct cutting-edge research in the chemical sciences with close, individual supervision by dedicated faculty mentors at these primarily undergraduate institutions. The diverse student cohort participating in research at this site will be well-prepared for further study in the chemical sciences, and graduate school, with eventual employment as part of the country’s technical workforce.

Jeffrey Katz, 2010, Henry Dreyfus Teacher-Scholar Award, The Development and Quantitative Measurement of Acetylene-Activated SNAr Reactions and Their Application for Complex Macrocycle Synthesis.
Dasan Thamattoor, 09/15/2010, NSF: RUI: Syntheses, Structures, and Reactions of Strained Cyclic Allenes

This award from the Chemical Structure, Dynamics and Mechanism Program of the Division of Chemistry supports Professor Dasan M. Thamattoor of the Chemistry Department at Colby College in Waterville, ME in his exploration of the following topics: 1) Generation of strained allene compounds via novel decomposition of spiropentanes; 2) Synthesis of derivatives of 1,2 cycloheptadiene and 1,2 cyclooctadiene that are stable enough to form crystals suitable for x-ray diffraction, and 3) Development of pyrolysis methods for converting cycloalkenylcarbenes to strained cyclic allenes. Computational studies using Density Functional Theory (DFT) would be done in parallel with the experiments to provide insight into product stabilities and reaction pathways. The proposed work, which integrates elements of synthetic, mechanistic, and computational organic chemistry, is designed to provide undergraduates with a wholesome research experience, and enable them to make original contributions to scientific knowledge.

Among the most important broader impacts of this research, as mentioned above, is the mentoring of undergraduate researchers and training them as future scientists in a predominantly undergraduate institution. A number of ideas for melding research and education, based on approaches that have already met with success, will be implemented. This is exemplified, for instance, by the incorporation of research-like projects and new pedagogical experiments in the introductory organic chemistry laboratory course. The proposal also seeks to continue Prof. Thamattoor’s highly successful program that provides research opportunities to high school students over the summer months. Women, minorities, and students from disadvantaged backgrounds will also be recruited to participate in summer research activities. In addition, there will be new initiative that forges partnerships with elementary school teachers to specifically strengthen the science curriculum in the K-3 level. Finally, it is expected that a number of important fundamental chemical reaction pathways will be elucidated.

David Emerson, D. Whitney King, 4/15/2010, NSF: Microbial Systems in the Biosphere: Unraveling the Lifestyles of Dominant Freshwater Fe-oxidizing Bacteria

Bacteria are remarkable for their metabolic diversity and ability to utilize seemingly unpalatable food sources. The Fe-oxidizing bacteria (FeOB) are a prime example, since they gain energy for growth by oxidizing ferrous iron to ferric iron (rust). These bacteria are prolific and easily recognized by abundant rust-colored precipitates that form whereever ferrous iron is present in natural waters, or in domestic and industrial water distribution systems. The work funded by this proposal will investigate the systematics, ecology, and physiology of a particular group of freshwater FeOB. The systematics are important because we do not know the true identity of some of the most important FeOB; without knowing who they are it is impossible to reliably identify them. The ecology is important because we know different types of FeOB have very specific habitat requirements. Figuring out those requirements may provide an easy way to determine aspects of water quality that are specific for a given group of FeOB. This could be a good diagnostic tool for assessing water quality. The physiology studies are important because we actually know very little about how, or even why, bacteria oxidize iron. By answering these questions we can learn about an important fundamental biological process. This may allow better control over it, or allow us to harness it for beneficial purposes. To investigate these questions we will employ a host of modern microbiological and chemical techniques that allow us to study cells in their natural environments at the microscale, as well as reproduce those controlled conditions in the laboratory.

Ultimately this work will improve our understanding of a long recognized, but poorly understood group of microbes, of significant environmental importance, both as nuisance organisms that cause biofouling and corrosion, and as beneficial organisms that can remove metals and other pollutants from water.

Kevin Rice, 05/01/2009, NIH / NIGMS / Institutional Development Award, “Identification of the role of carbamoylating activity from antineoplastic sulfonylhydrazines and nitrosoureas”

This project focuses on the mechanism of action of Laromustine, a sulfonylhydrazine anticancer prodrug currently in clinical trials for acute myelogenous leukemia and glioblastoma multiforme. These efforts will also include the nitrosoureas, a related class of compounds that are actively used in the clinic. The activity of Laromustine is a function of two reactive electrophiles that are generated upon base-catalyzed activation in situ: a 2-chloroethylating species and methylisocyanate. The 2-chloroethylating species ultimately forms cytotoxic, interstrand DNA crosslinks, and the carbamoylating activity of methylisocyanate synergizes with the 2-chloroethylating activity, resulting in significant cytotoxicity to neoplastic cells. These in situ chemical processes are similar to those of other anticancer compounds, including nitrosoureas. This project will involve an investigation of several enzymes as targets likely to be modified with a carbamoyl group from methylisocyanate so as to explain the synergistic cytotoxicity. In addition, the effects of exposure to studied agents on gene expression and signaling pathways will be elucidated. The proposed research will greatly enhance the understanding of the relationship between the chemical reactivity of these compounds and their observed pre-clinical and clinical effects, which potentially could lead to more effective chemotherapeutic strategies. This grant supports undergraduate students in research and a laboratory manager for 5 years.

D. Whitney King, 10/01/2008, NSF: Collaborative Research: A Nanostructure Sensor for Measuring Dissolved Iron and Copper Concentrations in Coastal and Offshore Seawater

Iron and Copper serve as key co-constituents for numerous enzymes in a wide range of biological systems, and their elevated or impoverished levels in aqueous systems have dramatic consequences at organismal, ecosystem, and human health scales. Over the last decade these effects have increasingly been recognized to be important in ocean systems. Identifying sites and times where these metals cause negative environmental outcomes is greatly hampered by their comparatively sparse datasets. This problem is a direct consequence of the analytical challenge of obtaining accurate Fe and Cu determinations in saline waters at very low (trace) concentrations, and the limitations of ship-dependent sampling regimes. The PI’s request funding to build on research and technology advances in the Tripp, Wells and King laboratories to develop active nanostructures that can serve as platforms amenable for detection of a wide range of environmentally important dissolved metals in seawater. Preliminary work has validated a biologically-inspired sensor platform in the subarctic N. Pacific, providing the first demonstration of dissolved Fe measurements at very low (<50 pM) concentrations in oceanic waters by a solid state sensor. The proposed work will 1) optimize this prototype sensor by tuning the active nanostructures to measure dissolved Fe and Cu, and 2) develop a detection device that migrates the current ship-board method to operate on rosette profiling platforms as well as on moorings and autonomous vehicles.

Broader Impacts: This project has the potential to further develop a sensor that will provide unique information about the chemical speciation of the biologically important metals Fe and Cu. The work proposed here fills an important need for high spatial and temporal resolution data of these metals identified as priority by researchers in marine chemistry and marine biogeochemistry. This interdisciplinary approach has the potential to fill an analytical void for data that continues to stymie efforts to understand how and Cu and more specifically Fe availability in the oceans modulates the cycling of carbon and nitrogen in the marine environment. The proposal is well balanced in its goal of marrying nanotechnology with IR spectroscopy to address a analytical void while providing specific support for the training of students at the undergraduate and graduate levels. The PIs plan to develop minority student involvement in their research. This will have the most important impact, since bringing smart students into our field and stimulating young students to consider careers in science is essential for the continued growth of our national science capabilities.

Dasan Thamattoor, 08/01/2007, NSF: RUI: Experimental and Theoretical Investigation into the Reactions of Atomic Carbon with Organic Substrates

This RUI award to Professor Dasan M. Thamattoor of the Chemistry Department at Colby College in Waterville, ME has as its goal the production of arc generated carbon atoms and the study of their reactions. Interesting divalent carbon intermediates (carbenes) will be generated by reactions with a variety of organic chemical substrates. More specifically, these organic substrates include alkenes, alkynes, azulene, acid chlorides, 1,2-dicarbonyl compounds and molecules with highly strained single carbon-carbon bonds. The chemistry of these intermediates and the pathways by which they are formed and consumed will be investigated experimentally and by modern computational techniques. The proposed work, which integrates elements of synthetic, mechanistic, and computational organic chemistry, is designed to provide undergraduates with a wholesome research experience, and enable them to make original contributions to scientific knowledge.

Jeffrey Katz, , 03/15/2007, NSF: CAREER: Molecular design through oxacalixarenes: synthetic methods, molecular receptors, and chemical sensors

With a CAREER Award from the Organic and Macromolecular Chemistry Program, Professor Jeffrey L. Katz of Colby College is developing methods for the synthesis of oxacalix[n]arenes and exploring applications of these compounds as molecular receptors and chemical sensors. A new single-step synthesis of oxacalixarenes by nucleophilic aromatic substitution of meta-diphenols with meta-dihalogenated aromatics allows access to an array of oxacalix[n]arenes bearing diverse functional groups. Naphthyridine-containing oxacalixarenes are found to act as receptors (molecular tweezers) for neutral aromatic compounds bearing hydrogen bond donors, and the optical properties of these receptors makes them potential chemical sensors for neutral organic analytes.

With the support of the CAREER award, Professor Katz will initiate a research-based mentoring program for the recruitment and retention of minority students into chemistry and other scientific disciplines. As an integral part their freshmen year and continuing throughout their undergraduate education, minority students at Colby College will have active roles in the proposed research, participate in research group meetings, attend and present posters at local and national meetings, and interact academically and socially with other student-scientists.

Julie Millard, 2006, Petroleum Research Fund: Epihalohydrin Cross-Linking of DNA
The goal of this project is to characterize the potential DNA cross-linking of the suspect carcinogen epichlorohydrin (ECH) and related compounds. Specific aims include the following:

Determination of sequence preferences for cross-linking.
Examination of the stereospecificity of the ECH cross-linking reaction.
Assessment of DNA bending by ECH-indued interstrand cross-links.
Determination of the structure-function relationship for cross-linking
by ECH in comparison to (1-chloroethenyl) oxirane.
Characterization of the mechanism of cell death induced by ECH and
related compounds in 6C2 chicken erythroid cells.

Julie Millard, 2004, Camille and Henry Dreyfus Foundation, Henry Dreyfus Teacher-Scholar Award: Small Molecule-DNA Interactions with
an Emphasis on the Mechanism of Anti-Cancer Activity

With a Henry Dreyfus Award, Professor Julie T. Millard and her research team at Colby College are investigating of the activities of DNA cross-linking agents within cells. Dr. Fred LaRiviere spent a year in the group helping to develop methods for quantitative PCR to monitor the reactivity of cross-linkers within a 6C2 chicken erythroid cell line and within human HL60 cells. The team is monitoring damage at different loci to determine whether DNA accessibility modulates cross-linker reactivity. Prof. Millard and Dr. LaRiviere also developed a new service-learning course (CH151) during the January term in which Colby students designed and implemented hands-on activities for local elementary school children.

Dasan Thamattoor, Jeffrey Katz, Shari Dunham, Catherine Bevier, Julie Millard, 08/01/2004, NSF: MRI: Acquisition of a Preparative HPLC system for Undergraduate Research Training in Chemistry and Biology

With this award from the Major Research Instrumentation (MRI) Program, the Department of Chemistry at Colby College will acquire a preparative high performance liquid chromatography (HPLC) system. This equipment will enhance research in a number of areas including a) purification of precursors used to synthesize carbenes; b) synthesis of natural products; c) synthesis of aza- and oxocalixarene macrocycles and diheterocalixarene cage compounds; c) studies of the interactions of small molecules with DNA; d) investigations on the covalent interactions between duplex DNA and small transition metal compounds; and e) analysis of frog skin secretions.

High performance liquid chromatography (HPLC) is an extremely powerful technique used for the separation and analysis of complex mixtures. The results from these studies will have an impact in a number of areas including synthetic chemistry and biochemistry.

Mark Wells, D. Whitney King, Carl Tripp, Karen Orcutt, 08/15/2003, NSF: NIRT: Developing a Nanoscale Sensing Device for Measuring the Supply of Iron to Phytoplankton in Marine Systems

Intellectual Merit of the Proposed Activity: This proposal was received in response to NSE NSF-02-148. There is increasing evidence that Fe has a singularly unique role in marine ecosystems, both regulating total phytoplankton production in high nitrate, low chlorophyll regions of the world, and influencing the predominant composition of the phytoplankton assemblages found in others. It is remarkable then that there is no agreement about how to define biologically available Fe, in contrast to the macronutrients nitrogen, phosphorous or silicon. Current attempts to attain predictive insights to how ocean ecosystems will influence the magnitude of climate change are blocked in large part by this question, along with an extreme shortage of data on Fe distributions in the oceans. There is recent evidence that Fe availability can be regulated in bulk seawater incubations by small additions of the fungal siderophore desferrioximine B (DFB). The Fe-DFB complex is not readily available to eukaryotic phytoplankton, so that if the quantity of Fe complexed by DFB were measured and calibrated to Fe uptake by phytoplankton it could yield a novel first order measure of Fe availability. Building from our current research we have developed liposomes that specifically acquire DFB-bound Fe from solution. These devices, 100 nm in diameter, open the way to applying nanotechnology to create a new breed of Fe biosensors in marine waters.

The project goals are to 1) optimize these nanodevices by improving their physical robustness, identifying the size/functionality relationship, and examining the efficacy of other DFB-Fe transporter molecules, 2) develop self-reporting capabilities for quantifying Fe uptake by these nanodevices, and 3) to calibrate the capture of Fe by these nanodevices to the Fe uptake by various phytoplankton species. The anticipated final product will be a calibrated nanoscale biosensor for laboratory-scale use that could then be adapted for deploying on remote vehicles.

Broader Impacts Resulting from the Proposed Activity: The two institutions involved in this project (U. Maine and Colby College) have a strong track record for involving undergraduate and graduate students in cutting edge research in marine science and chemistry, and this project will continue this process.

Dasan Thamattoor, Thomas Shattuck, D. Whitney King, 08/01/2003, NSF: MRI/RUI: Acquisition of a Time-Resolved Laser Flash Photolysis System for Undergraduate Research and Training in Chemistry

With this award from the Major Research Instrumentation (MRI) Program, the Department of Chemistry at Colby College will acquire a time-resolved laser flash photolysis system for undergraduate research and training in chemistry. This equipment will enhance research studies in a) carbene chemistry and b) the aquatic photochemistry of iron.

This instrumentation will bring laser based techniques into the undergraduate education (both teaching and research) of Chemistry majors, and further strengthen the quality of undergraduate research and education at Colby College.

Dasan Thamattoor, 07/15/2003, NSF: RUI: Enhancing Undergraduate Chemical Education Through Research: The Experimental and Theoretical Investigation of Unusual Carbenes

Carbene-like products obtained from nitrogen-containing precursors may in fact come from the excited state of the precursors themselves. In addition, many nitrogenous precursors can be hazardous to handle or may simply not be synthetically available to generate carbenes of interest – e.g., a convenient and widely applicable method of generating a-hydroxycarbenes is currently unavailable. This proposal describes an undergraduate-oriented research program designed to study unusual carbenes generated from various cyclopropanated aromatics instead of conventional sources such as diazo compounds and diazirines. These non-nitrogenous precursors provide a safe, viable, and alternative route to carbene generation. Specific projects include the investigation a-hydroxycarbenes and novel heterocyclopropylcarbenes (including oxiranyl- and aziridinyl carbenes) and the generation of a-ketocarbenes to address key mechanistic issues in Wolff rearrangement processes. Electron spin resonance spectroscopy, time-resolved laser flash photolysis, and advanced computational methods will be brought to bear on the investigations as well.

With this Research at Undergraduate Institutions Award, the Organic and Macromolecular Chemistry Program supports the research of Professor Dasan M. Thamattoor, of the Department of Chemistry at Colby College. Professor Thamattoor and his students are exploring, via theory and wet chemistry, the preparation, structure, and reactivity of unusual electron-deficient species known as carbenes. These unusual species play central roles in a wide variety of chemical processes, and development of a detailed understanding of their structure and reaction chemistry will lead to the development of better predictive tools for the control of chemical reactivity. Whereas other routes to some of the targeted carbenes are known, Professor Thamattoor’s studies address serious questions about the structure and reactivity of the carbenes generated via these other routes, and in addition offer promise for the generation of new, previously unavailable carbenes. Through a partnership with the Maine Research Internships for Teachers and Students (MERITS) program, Professor Thamattoor will enhance the educational experience provided by this research program by including high school teachers and students.

Julie Millard, 2003, National Cancer Institute, AREA: Diepoxide Cross-Linking of DNA II.

The goal this project is to further the understanding of the role of DNA dama induced by diepoxybutane (DEB) and related compounds in carcinogenicity and anti-tumor potential. The specific long-term goals in this grant proposal were as follows:

To characterize DEB reactivity within whole cells.

To assess diepoxide interstrand cross-links for bending, as well as recognition by proteins that recognize bent DNA.

To assess whether the related compound epichlorohydrin (ECH) forms DNA interstrand cross-links.
Julie Millard, 2002, Research Corporation: In Vivo Mapping of Diepoxybutane Damage using a Ligation-Mediated Polymerase Chain Reaction

The goal of our research is to further the understanding of the role of DNA damage induced by diepoxybutane (DEB) and related compounds in carcinogenicity and anti-tumor potential. DEB results from mammalian detoxification of butadiene by cytochrome P450 and has been linked to increased mortality from lymphatic and hematopoietic cancers among workers in the butadiene industry. We are interested in how DNA packaging affects the reaction sites of DEB in whole cells. Establishing the mutational spectrum of DEB directly impacts the understanding of the potentially adverse human health effects of butadiene exposure. Recent polymerase chain reaction (PCR) techniques have been developed that allow specific regions of DNA to be amplified and examined for chemical damage. We are using chicken cells as a model system to develop experimental strategies that could later be applied to human cells.

Stephen Dunham, Paul Greenwood, Dasan Thamattoor, 08/01/2002, NSF: MRI/RUI: Acquisition of Isothermal Titration and Differential Scanning MicroCalorimeters for Chemistry and Biology Research

With support from the Major Research Instrumentation (MRI) Program, Stephen Dunham, Paul Greenwood and Dasan Thamattoor of Colby College will acquire an isothermal titration calorimeter (ITC) and differential scanning microcalorimeters (DSC) for chemistry and biology research. Research projects that will exploit this equipment include a) structural studies of modified oligonucleotides; b) metal ion binding affinities and stabilities of modified DNA aptamers; c) binding affinities of DNA aptamers to biological targets; d) ion binding affinities and structural characterization of proteins in nematocysts; e) ion binding selectivity of polyoxa[n]peristylanes; f) computer aided molecular design and guest-host chemistry of H2-antagonists; and g) structural analysis of RNase mutants that allow self-fertilization in plants.

Calorimetry is an extremely useful tool in modern analytical chemistry. Calorimetric analysis is used to measure the thermal energy (heat) exchange that occurs during molecular interactions and reactions. Thus it can provide a very reliable and sensitive method for determining the thermodynamic properties of materials such as changes in heat capacity of liquid and solid samples. Colby College is an undergraduate institution, and the availability of these instruments will have a strong impact on undergraduate research. In addition, commercial ITC and DSC microcalorimeters are currently not available in the state of Maine.

D. Whitney King, 04/01/2002, NSF: (SGER): Exploratory Geochemistry Field Program for Minority Students

This small grant for exploratory research supports a geochemistry summer program for underrepresented minority students to be based at Colby College. The goal is to expose two high school juniors to the excitement of geoscience research while building their formal mathematics, chemistry, and earth science skills. The program is unique from past programs in that the students and their high school teacher are all participants in the program. Students will be selected from the High School for Engineering Professions program or the College preparatory Magnet program at Scotlandville Magnet High School in Baton Rouge, LA. The students will be part of ongoing research at Colby investigating the geochemistry of the Belgrade lakes watershed. The summer program will be the launching point for the students senior-year advanced science courses. This experimental program may serve as a model for other partnerships between under resourced high schools and four-year colleges and universities.

Rebecca Conry, Alice Bruce, Richard Broene, Rachel Austin, Henry Tracy, 08/15/2001, NSF: MRI: Acquisition of a CCD Single Crystal X-ray Diffraction System for a Partnership of Maine Institutions

With support from the Major Research Instrumentation (MRI) Program, the Department of Chemistry at Colby College will acquire a X-ray diffractometer with CCD detector for small molecule diffractometry. This equipment will be used by five educational institutions in Maine: Colby College, Bates College, Bowdoin College, the University of Southern Maine and the University of Maine. The X-ray CCD diffractometer will enhance research in a number of areas including 1) studies of copper-arene chemistry; 2) development of new synthetic methods of selected natural products; 3) synthesis of polycyclic cage compounds with unusual architecture; 4) structure-function relationships in metalloenzymes and metalloenzymes mimics; and 5) production of C-2 symmetric lanthanocene catalyst systems and their utility in the construction of chiral molecules.

The X-ray diffractometer allows accurate and precise measurements of the full three dimensional structure of a molecule, including bond distances and angles, and it provides accurate information about the spatial arrangement of the molecule relative to the neighboring molecules. These studies will have an impact in a number of areas, including organic and natural products synthesis plus biological, organometallic and materials areas of inorganic chemistry. The instrument will play a major supporting role in the research efforts of all of the participating institutions, which range from bachelor’s level to Ph.D.-granting schools. In addition, the diffraction system will be used for the formal education of students in advanced chemistry courses utilizing the capability of the diffractometer to be run off site.

Thomas Shattuck, Bradford Mundy, Stephen Dunham, Dasan Thamattoor, Shari Dunham, 02/01/2001, NSF: Biochemical, Organic, Physical, Analytical, and Inorganic Mass Spectrometry

Chemistry (12) Teaching through research is a guiding principle in the institution’s NSF-AIRE recognized program. A requested ion trap mass spectrometer with electrospray and atmospheric pressure chemical ionization interfaces (LC/MS) prepares the students at this institution to be creative, independent, and well-trained scientists. This instrument provides a novel linkage and enhancement of the full chemistry curriculum using experiments some of which are adapted from standard literature. Mass spectrometry is used in general chemistry for characterization of transition metal complexes. In organic chemistry students do natural products isolation and structure characterization. In physical chemistry proton affinities in gas phase and solution are studied. In Instrumental Analysis the fundamentals of the ionization and mass analysis processes are discussed. Biochemistry students use LC/MS in protein sequencing. These LC/MS-enhanced curricular components allow the introduction of exciting and important new approaches to chemistry, including combinatorial chemistry, solid-phase synthesis, and computer aided molecular design. The program in combinatorial chemistry links the Organic, Physical, Instrumental, and Biochemistry courses to map the active site of the proteolytic enzyme papain. Students in the Organic Chemistry course use solid-phase synthesis to make resin-bound combinatorial mixtures of papain substrates. These mixtures are analyzed in Instrumental Analysis for structure and purity, and in Biochemistry in a kinetic assay. The results of the papain assay are used for QSAR and receptor modeling studies in Physical Chemistry. Beyond curricular developments, the instrument is used to significantly enhance student/faculty research opportunities.

Stephen Dunham, Thomas Shattuck, Rebecca Conry, Dasan Thamattoor, Shari Dunham, 08/01/2000, NSF: Upgrade of a 400-MHz NMR Spectrometer Vital for Chemistry Research and Education

With support from the Major Research Instrumentation (MRI) Program, the Department of Chemistry at Colby College will upgrade a 400 MHz NMR Spectrometer. This equipment will enable researchers to carry out studies on a) the isolation and identification of natural products; b) synthesis and reactivity of carbenes; c) antitumor agent development; d) nucleic acid and peptide structure/function relationships; and e) organometallic synthesis.

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 spectrometry is essential to chemists who are carrying out frontier research. The results from these NMR studies will have an impact in a number of areas including drug development and biochemistry.