The Chemical Catalysis Program supports the efforts of Professor Louis Y. Kuo of Lewis and Clark College in the study of phosphonothioate hydrolysis using molybdocene complexes in the presence of either gold or silver nanoparticles or polymer resins. This project focuses on improving the turnover of phosphonothioate hydrolysis while developing an understanding of the stereochemical, electronic and steric factors associated with selective P-S scission and the rate acceleration provided by the molybdocene catalysts. The structures of the various molybdocenes are compared with their catalytic activities to determine the important relationships that impact reactivity and selectivity.

The detoxification of phosphonothioates, compounds found in insecticides and chemical weapons, is of practical importance. The molybdocene compounds used in this study are among the first to destroy these potential environmental poisons, in water and under very mild conditions and temperatures. The experiments included in this program are well-integrated into the undergraduate curriculum. Several of the molybdenum complexes and nanoparticles are synthesized either in the general chemistry laboratory or by the upper level inorganic chemistry students. Professor Kuo participates in the award-winning "Saturday Academy", a program that enables high school students to conduct summer internships in his research group.

Project Report

Some organophosphates are neurotoxins that have found applications as agricultural pesticides. A subset of these compounds a sulfur-containing organophosphates known as phosphonothioates of the form R1P(O)(OR2)(SR3). The most notorious phosphonothioate is the VX chemical warfare agent which is the most potent neurotoxin known. Our investigation looks at organometallic complexes that degrade these phosphonothioates through hydrolytic means. Specifically we look at molybdenum metallocenes that are water stable and were reported as the first organometallic compound that hydrolyzed organophosphates. Therefore, the broader societal value of this fundamental investigation affects environmental chemistry (i.e. pesticide hydrolysis) as well as the chemistry for combatting chemical warfare agents. The title compound of this investigation was a phosphonothioate containing both a P-S and P-O bond. We developed the basic chemical mechanism of how a molybdenum metallocene of the form (C5H5)2MoCl2 hydrolyzed only the P-S linkage to yield a phosphonate that contained no P-S functionality. This work was published in Organometallics. The selective hydrolysis is important because P-O scission yields another phosphonothioate that is usually just as toxic. In this process we also understood why this reaction yields no turnover of the phosphonothioate hydrolysis by the molybdenum metallocene. This was due to the sulfur-containing byproduct ("leaving group") which binds to the molybdenum reagent in a strong and irreversible manner. As such, the molybdenum metallocene was "poisoned" by the very hydrolytic product it formed from phosphonothioate hydrolysis. To this end, we also proposed and carried out a protocol to promote turnover with the addition of thiophilic nanoparticles. The addition of silver nanoparticles allowed the regeneration of the active molybdenum metallocene to degrade another equivalent of the phosphonothioate neurotoxin. Hypothetical routes for this modest turnover were also presented in an Organometallics paper that reported this work. This was the first publication of an organometallic-nanoparticle hybrid that degraded phosphonothioate neurotoxins. Another publication (Inorganic Chemistry) reported a mechanistic investigation on how methanol degrades the phosphonothioates (i.e. methanolysis). There were computational calculations that showed a particular low-energy pathway involving a trigonal bipyramid intermediate in the methanolysis of phosphonothioates. In our hands we found this reaction was a concerted process in the presence of a lanthunum metal ion. It was the first experimental work to establish this mechanism using an optically pure form of the phosphonothioate neurotoxin. Finally, the molybdenum metallocene we worked with was in the +4 oxidation state. The tail end of the investigation looked at higher oxidation state molybdenum metallocenes, specifically the +5 metallocene. Tangential to the investigation of phosphonothioate hydrolysis was another finding on how a +5 molybdenum metallocene reduces to the +4 counterpart in water. This reduction only occured in water and it was the first case where water served as a reducing reagent as well as the solvent. This work also appeared in the journal Organometallics. In terms of broader impacts and intellectual merit, a 2010 Chemical Review article mentioned this work "represents a turning point for organometallic systems," for it found a new non-traditional application of this class of metal complexes. This RUI award involved five undergraduates and two high school students and resulted in four publications in peer-reviewed, specialty journals. All five undergraduates did their senior theses on this project, and four of them (as well as both high school students) were coauthors on the four publications. In addition, a patent directly related to this work was awarded in 2011 and another was submitted in 2013. Elements of the phosphonothioate synthesis were incorporated in an upper level teaching lab at the College, and all seven students presented the results of their work either at local poster sessions or talks at national American Chemical Society meetings (spring 2010 and 2011).

Agency
National Science Foundation (NSF)
Institute
Division of Chemistry (CHE)
Type
Standard Grant (Standard)
Application #
0956740
Program Officer
Carol Bessel
Project Start
Project End
Budget Start
2010-05-01
Budget End
2014-04-30
Support Year
Fiscal Year
2009
Total Cost
$180,000
Indirect Cost
Name
Lewis and Clark College
Department
Type
DUNS #
City
Portland
State
OR
Country
United States
Zip Code
97219