Frank Cheng, ifcheng@uidaho.edu Destruction of Organophosphorus Nerve Agent Analogues by Activation of O2 under Aqueous Room Temperature and Atmospheric Pressure Conditions Christina Noradoun, Ryan Hutcheson, Edmund Wong, I. Francis Cheng* University of Idaho, Department of Chemistry, Moscow, ID 83844-2343 ifcheng@uidaho.edu; 208-885-6387 November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu Overall Goal The destruction or neutralization of xenobiotics. Inexpensive & Safe Processes. Room Temperature and Pressure Conditions (RTP) Common Reagents – Long Term Storage No Specialized Catalysts Yang, Y.-C., Chemical Detoxification of Chemical Nerve Agent VX, Accounts of Chemical Research, 1999, 32, 109-115. November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu Oxidative Pathways -Most attractive oxidant - O2 from air -CxHyXz + O2 = CO2 + H2O + HX (unbalanced) G<0 -Room temperature oxidations by air are kinetically slow -enzymatic or enzyme-mimics -Partially reduced O2 (Reactive Oxygen Species) November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu Reactive Oxygen Forms G •O=O• b.o. = 2  120 kcal/mol +4e- +4H+ 2H2O •O-O• b.o. = 1.5  80 kcal/mol +e- +2e- +2H+ HO-OH b.o. = 1  50 kcal/mol November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Partially Reduced Oxygen E0reduction O2 + e-  O2.- -0.45 volts O2 + 2H+ + 2e-  H2O2 +0.30 volts O2 + 4H+ + 4e-  H2O +1.23 volts November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

That Last Step: The Fenton Reaction -Reduction of HO-OH H2O2 + FeII = FeIII + HO- + HO. HO. + e- = HO- Eo = 1.8 volts -HO. reacts with organics with diffusion limited kinetics -Possible Roles for O2.- 2O2.- + 2H+  H2O2 + O2 O2.- + FeIII  O2 + FeII November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu The Proposed System Red = reducing agent, consumed MII/III = O2 activation redox catalyst M’II/III = Fenton’s Reagent November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Putting the System Together –The Reducing Agent Considerations -Costs -Kinetics -Environmental Ered0 Zero-valent metals Fe  Fe2+ + 2e- -0.44 volts Ascorbate Ascorbate  dehydroxyascorbate + 2e- 0.154 volts (pH 4) November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Putting the System Together – Oxygen Activation Agents RTP O2 activation Biological Systems: -cytochrome p450…. Chemical Systems: -non-heme iron complexes (cost?) Que, L. JACS 2003, 125, 2113-2128 -FeIIEDTA oxidation by O2 Van Eldik, R. Inorg. Chem, 1997, 36, 4115-4120 November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Putting the System Together – Fenton’s Reagent H2O2 + e-  HO- + HO Ered0 = 0.26(pH 6) to 0.08(pH 3) V FeIIIEDTA + e-  FeIIEDTA Ered0 = 0.1 V FeII/IIIEDTA is a classic Fenton’s Reagent Used in DNA footprinting studies Can FeII/IIIEDTA do both O2 activation and the Fenton reaction? November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Summary of Van Eldik Study FeIIEDTAH(H2O) + O2  FeIIEDTAH(O2) + H2O FeIIEDTAH(O2)  FeIIIEDTAH(O2-) FeIIIEDTAH(O2-) + FeIIEDTAH(H2O)  FeIIIEDTAH(O22-)FeIIIEDTAH + H2O FeIIIEDTAH(O22-)FeIIIEDTAH + H2O + 2H+  2FeIIIEDTAH(H2O) + H2O2 2FeIIEDTAH(H2O) + H2O2  2FeIIIEDTAH(H2O) + H2O *Proposes H2O2 as intermediate *Saw no evidence of H2O2 Van Eldik, R. Inorg. Chem, 1997, 36, 4115-4120 November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu Our System System Consists of Fe(0) 20 mesh, EDTA, Air & Water Proposed dioxygen activation schemes. Heterogeneous activation at the Fe(0) surface. Homogeneous activation by Fe(EDTA). Reaction stoichiometries are not balanced and only representative of likely processes. Heterogeneous activation producing ferryl. November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Method for Detection of Facile Oxidant from O2 Actiavtion Thiobarbituric acid-reactive substances (TBARS) assay Nonselective detection of oxidizing species. HO·, FeIV=O Malonaldehyde bis(dimethyl acetal) TBARS Deoxyribose 532 nm November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu TBARS Results Results of HO· radical trapping by deoxyribose/thiobarbituric acid system forming a chromgen (532 nm). The conditions were 30 minutes of reaction time with 0.1 g 40-70 mesh Fe(0), under aerobic conditions. Other conditions stated below.   Absorbance Units at 532 nm Control 1 – 0 mM deoxyribose, 2.39 mM EDTA 0.0 Control 2 – 3.18 mM deoxyribose, 0 mM EDTA, - also N2 flow, -No Fe(0) 0.149 3.18 mM deoxyribose, 2.39 mM EDTA 0.846 November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Summary of the New System Consists of Fe(0), EDTA, Air, and Water Fulfills Several Requirements *Inexpensive Reagents – Long Shelf Life *Nontoxic *No Precious Metal Catalysts *No Special Reaction Vessels *RTP *Possibility for Portability – Field Destruction November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Xenobiotic Oxidation Studies H2O2 O2 + 2H+ + EDTA Iron particles 0.1-1 mm Fe2+ FeIIEDTA FeIIIEDTA + HO- + HO. Aqueous Xenobiotic CO2 + H2O November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Xenobiotic Oxidation Studies *Chlorophenols – recalcitrant and oxidatively stable *Malathion – Surrogate for organophosphorous compounds Kinetics Intermediates Final Products -50/50 Ethyl Acetate/Hexane GC-FID -Direct Aqueous LC-GC -Ion Chromatography November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Oxidation of Chlorophenols 0.5 g of 40-70 mesh Fe(0) 10 mL of solution 0.32 mM EDTA 140 ppm 4-chlorophenol 4 hour reaction time GC and LC-MS RTP November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Reaction Vessel pH 5.5 – 6.5, unbuffered. Air flow 2.0 mL 50/50 hexane/ethyl acetate (extraction only) 10.0 mL water pH 5.5 – 6.5, unbuffered. 0.44mM EDTA 0.44mM Xenobiotic Stir bar 0.5g Fe; 20 or 40-70 mesh November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

4-CP Degradation Kinetic Studies Pseudo first-order rate constant = -1.11 /hr. 0.5-g 40-70 mesh Fe(0) 0.72 mM EDTA 0.54 mM 4-chlorophenol Aerobic conditions November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Summary of the degradation of the chlorophenols in this study . All runs included 0.5 g of 40-70 mesh Fe(0) in 10 mL of solution.     I) 0.32 mM EDTA Aerobic II) 0.0 mM EDTA III) 0.32 mM EDTA Anaerobic (N2 purge) IV) dark conditions 0.32 mM EDTA aerobic 140 ppm 4-chlorophenol Complete degradation after 4 h. (GC-FID) No reaction after 4 h. Complete degradation after 4 h. 162 ppm Penta-chlorophenol suspension Complete degradation after 70 h. (GC-FID) No reaction after 70 h. N/A November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Organophosphorous Agents Malathion VX Sarin, GB November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu Control Studies Control experiments conducted using: No EDTA No O2 No Fe0 showed no malathion degradation. Post reaction extractions of the iron solids using Ethyl acetate Toluene Butanol Hexane showed the absence of any organics absorbed to the iron surface. November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Summary of Identified Intermediates DES malathion max: 4-6 hrs unknown product max: 2-3 hrs malaoxon PO43- + SO42- November 23, 2018 Frank Cheng, ifcheng@uidaho.edu Max: 7 hrs

Kinetics of Malathion Degradation Diethyl Succinate (DES) GC/FID chromatograph, error bars indicate the standard deviation between three measurements of each sample. November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu Malaoxon 5000 10000 15000 20000 25000 3.3 6.6 10 13.3 16.7 time (hours) peak area November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Unidentified Intermediate MW = 410 g/mol November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Ion Chromatography of other Ionic Products and Intermediates -2.000 0.000 2.000 4.000 6.000 8.000 10.000 12.000 10 20 30 Time (hours) conc (ppm) Nitrate Phosphate Sulfate November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Summary of Intermediates Time: 0 2 hrs 4 hrs 12hrs rxn complete Malathion 0.44 mM 0.0199 mM (4.5%) 6.8e-3 mM (1.5%) Below detection limit of GC/FID Unknown 410 -- Peak 7 hours Diethyl Succinate 0 mM 0.0524 mM (12% yield) 0.167 mM (38% yield) SO42- 3.75e-3 mM 8.42e-3 mM 0.0593mM (14% yield) (24hrs) PO43- 0.0102 mM 9.61e-3 mM 0.0825 mM (19 % yield) November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu Kinetically stable organic species in the presence of aqueous Fe(0)/EDTA/O2. 24 hour products for the degradation of -EDTA -Malathion -4-chlorophenol -pentachlorophenol -phenol November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

pH Control and Possible Role *Self Buffering at pH 5.5 – production of organic acids *Optimal pH range 3-6 November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu Technical Summary Ability to degrade organic pollutants Under room temperature, atmospheric pressure conditions Inexpensive Reagents – Iron particles, water, air & EDTA Unspecialized reactors Process is easily transportable, iron particles & EDTA Strong possibility of scale-up Example of a “Green Oxidant” November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu Scientific Summary First example of abiotic RTP activation of O2 able to oxidize destructively organics Control experiments indicate process is dependent on Fe(0), EDTA, air, and water November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Future Investigations Mechanisms – Understanding the process, C balance Kinetics – Speeding up the process Homogeneous Systems Search for an oxidatively stable iron chelate/organic solvent Basic organic chemistry – oxidizable and nonoxidizable functional groups Application & Scale-up November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu Desorption Studies Step 1 Starting Mixture 0.5-g 40-70 mesh Fe(0) 0.72 mM EDTA 0.54 mM 4-chlorophenol Aerobic conditions Step 2 Corrosion products observed Reaction Time 4 hours No detectable 4-chlorophenol by GC-FID Step 3 Begin N2 purge Addition of 0.54 mM 4-chlorophenol Step 4 N2 purge Reaction time 4 hours 0.54 mM 4-chlorophenol detected by GC-FID Step 5a Aerobic Conditions Addition of 0.72 mM EDTA No 4-chlorophenol detected by GC-FID Step 5b Approx. 50% of 4-chlorophenol detected by GC-FID Step 5c November 23, 2018 Frank Cheng, ifcheng@uidaho.edu

Frank Cheng, ifcheng@uidaho.edu Time: 0 hrs EDTA Malathion Reaction Conditions 0.44mM Malathion 0.44mM EDTA 0.5g FeO O2 HCO3- propionic acid oxalate Time: 13 hrs Iminodiacetic Acid November 23, 2018 Frank Cheng, ifcheng@uidaho.edu