Research Structure and Reactivity Solvation Variable Spin Molecules Phosphorus Project Dossiers

Interests and Future Plans

Present military doctrine calls for field decontamination of bulk amounts of organophosphorus chemical warfare agents to be accomplished either by hydrolysis in organic/aqueous media, or via bioremediation, either using live bacteria, or immobilized and encapsulated enzymes. Detailed mechanistic understanding of the chemical and biochemical pathways involved is for the most part lacking. We are taking advantage of newly available computational models that (i) accurately represent enzymatic environments and (ii) efficiently include the effects of bulk solvation to perform a systematic study of reagents and reaction conditions in order to clarify critical microscopic details. Particularly with respect to bioremediative systems, computation provides a cost-effective method to explore enzymatic modifications designed to enhance catalytic efficiency, substrate specificity, etc.

Accomplishments

With a central theme of better understanding the mechanistic details associated with various schemes for the detoxification of phosphorus-containing chemical weapons, we have carried out a variety of studies on open- and closed-shell molecules containing this pnictogen. Of particular note, we have:

• developed and calibrated theoretical models for the successful prediction of electron spin resonance hyperfine coupling constants in radicals containing phosphorus. We demonstrated second-order perturbation theory to be particularly robust (comparing to experimental data) for radicals containing hydrogen, boron, carbon, nitrogen, oxygen, fluorine, aluminum, phosphorus, sulfur, chlorine and copper. We also evaluated more efficient levels of theory and established the degree of accuracy lost when one resorts to them because of molecular size. We have in particular examined density functional theory. Although the MP2 level of theory is more trustworthy than DFT, we have demonstrated the latter level of theory to be adequate for radicals containing hydrogen, oxygen, fluorine, phosphorus, sulfur, and chlorine. We showed that one of the key drawbacks of the DFT procedure is its failure to accurately predict molecular geometries in many phosphoranyl radicals. (See Publications 11, 12, 13, 37, and 59.)

• characterized the structure, energetics, and stereodynamics of a number of hydroxylated phosphoranyl radicals (these molecules occur biologically via catabolism of organophosphorus derivatives and from radiation damage of genetic material). We identified a new stereopermutational pathway open to presumably all trigonal bipyramidal radicals that localize their unpaired spin-density so as to mimic a substituent. This pathway, termed pseudoinversion, was shown to be lower in energy than pseudorotation. (See Publications 10, 27, 31, and 44.)

  
  
  

  
  
  
• explored both computationally and spectroscopically the structures, energetics, and dynamics of synthetically important phosphorus-stabilized allyl anions. We illustrated how hyperconjugation controls the structure of these carbanions, explained the observed reaction-product stereochemistries and magnetic resonance spectra, and made predictions for increasing the stereoselectivity of the synthetic process. (See Publications 6 and 32.)

• identified the key role of hyperconjugation in determining the overall substitution pattern in trigonal bipyramidal molecular systems (a finding of wide general import). We demonstrated that hyperconjugation can overwhelm the energetic preferences typically associated with apicophilicity for some electronegative substituents. (See Publications 10, 27, 31, 44, 51, 57, and 107.)

• demonstrated that Escherichia coli biodegradation of organophosphonates is more likely to take place via a low-energy reductive pathway than via an oxidative pathway characterized by an activation energy about 9 kcal/mol higher. (See Publication 86.)

  
  
  

  
  
  
• investigated a number of possible mechanisms for the solvolysis of a VX model compound with either hydroxide anion or perhydroxide anion acting as the nucleophile. Addition-elimination, proceeding through stable trigonal bipyramidal intermediates, is the preferred pathway for both nucleophiles. (See Publication 91.)