Over the last several years, the Canary laboratory has discovered bistable molecules that can be electrically switched between two distinct states. These substances are complexes of copper with three-armed organic ligands that exhibit a molecular propeller-like twist, the pitch of which can be modulated or inverted. Mechanistic investigations revealed that oxidation/reduction of the central copper ion led to exchange of the atoms bound to the metal which in turn resulted in dramatic changes in the conformation and shape of the organic portion of the complex.

In this grant cycle, electron-induced changes in conformation of the organic ligand will be applied to three problems. First, the reorientation of two of the arms in the three-arm complexes will be used to study take-up and release of neurotransmitter-like guest molecules and electrically controlled catalysis of organic reactions. Such technology could enable electronic control of chemical signaling, catalysis, or open new strategies for redox-mediated drug delivery. Second, ligand reorganization will be used to construct a molecule that can be extended or retracted with an electrical trigger, affording a nanometer-scale electromechanical transducer whose properties will be probed by atomic force microscopy (AFM). Such materials could be of interest for valves and constrictors in nanodevices. Third, the principles used to develop the three-arm copper complexes will be applied to the design of peptides that reversibly convert between alpha-helical and beta-sheet secondary structures upon electronic stimulation. Besides potential materials applications, such peptide transitions may be relevant to processes associated with redox stress in biological systems or neurodegenerative disease.

This research project will be undertaken by undergraduate and graduate students and postdoctoral fellows, including individuals from underrepresented groups, who will learn valuable synthetic and physical skills that will enable them to become productive contributors to our nation?s research enterprise. Summers will include participation by faculty from predominantly undergraduate institutions as well as New York City high school students. The members of the research team will participate in annual outreaches at public museums and other K-12 activities. The project leader will serve the scientific community by organizing and facilitating interdisciplinary conferences and discussion groups.

Project Report

Research outcomes and significance. The Canary laboratory has developed a set of copper complexes that exhibit dramatic reconfiguration of the organic ligand upon addition or removal of an electron to or from a central copper atom. One interesting system (synthesized from the amino acid, L-methionine) results in the inversion of the helicity of the complex upon electro-reconfiguration. The overall shapes of the copper(I) and copper(II) complexes are nearly mirror image right- and left-handed propeller structures and give nearly equal and opposite interactions with polarized light. This electron-induced inversion of handedness is essentially unique to this system. At the heart of the system is a molecular ratchet that twists the overall shape of the molecule between right and left-handed. The copper atom may select between ligation by oxygen or sulfur atoms in the organic ligand. Addition of an electron selects for sulfur; removal selects for oxygen. When sulfur is selected, the complex is left-handed; oxygen give a right-handed configuration. During this grant period, the lab attached catalytic groups to the periphery of the invertible redox switch to produce a new catalyst for a reaction capable of producing mirror image products. The right-handed catalyst gave mainly product of (S)-configuration, while the left-handed catalyst gave formation of mainly (R)-product. Control experiments indicate that the helicity of the catalyst governs the stereochemical outcome of the reaction: The key structural change between the two catalyst states is the mirror image steric environment of the catalytic groups and their orientation with respect to one another. Rinsing with simple oxidants or reductants switches the "ambidextrous" catalyst between two states to produce whichever enantiomer is desired in the reaction. This was the first example of electron-mediated "dial-in" inversion of the stereoselectivity of a catalyst. The system is amenable to dynamic "on the fly" switching, so that one can imagine opening up new avenues of stereoselective synthesis of polymers like polypropylene where the configuration of chiral centers along the backbone greatly affects the properties of the material. A second major advance was the development of a peptide that switches between α-helical and β-sheet secondary structures using similar oxidation/reduction chemistry. The design uses the same sulfur/oxygen switching principles discussed above. Highly reversible aggregation and disaggregation of the peptides was observed, which is relevant both in terms of modeling plaque formation and considering applications such as redox-responsive peptidic materials. The mechanism of metal-mediated aggregation may be similar to the means by which plaque forms in neurodegenerative diseases like Alzheimers, although in the diseases the plaque formation is irreversible and difficult to study. Broader impacts/Contributions to resources in science and engineering. During the past funding period, three students graduated with Ph.D. degrees, including one from an underrepresented minority group. Two former students obtained academic positions at colleges, and three former students earned tenure (Florida State, Doane College, and Pace University). A minority student that earned a B.S./M.S. in my lab moved on to the M.D./Ph.D. program at Stanford. Nine undergraduates and four high school students (three underrepresented minorities) worked in my lab. A faculty member from a local college lacking a graduate program in chemistry worked 2-3 days/week in my lab, allowing him and his 5 students and one high school student to interact with NYU researchers and access NYU’s excellent research. An undergraduate female coworker started the Ph.D. in Chemistry program at UC Berkeley funded by a NSF Predoctoral Fellowship. Last year, we began an outreach to bring students from a high school in the Bronx to visit the lab and discuss vocations in chemistry. Each of the last three years, my group participated in an outreach to the public (with many K-12 students) at the New York Hall of Science (Queens, NY) providing hands-on activities related to molecular chirality. This event was organized by the New York Section of the American Chemical Society in celebration of National Chemistry Week. With the help of vendor Maruzen International, Inc. (where I serve as a Scientific Advisory Board member), we also provided large DNA and protein molecular models plus "hands-on" models for the visitors to use. These efforts and others were recognized by the award of the 2011 Outstanding Service Award from the New York Section of the American Chemical Society. In 2013, I was recognized by the same organization on the national level by being selected as a Fellow of the American Chemical Society.

Agency
National Science Foundation (NSF)
Institute
Division of Chemistry (CHE)
Application #
0848234
Program Officer
Tyrone D. Mitchell
Project Start
Project End
Budget Start
2009-07-01
Budget End
2013-06-30
Support Year
Fiscal Year
2008
Total Cost
$540,000
Indirect Cost
Name
New York University
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10012