Phosphonothioate Hydrolysis Turnover by ... - ACS Publications

Jul 26, 2012 - Louis Y. Kuo*, Anne K. Bentley, Yusef A. Shari'ati, and Curtis P. Smith ... of phosphonothioates with selective P–S scission in a sto...
0 downloads 0 Views 764KB Size
Download PDF
Article pubs.acs.org/Organometallics

Phosphonothioate Hydrolysis Turnover by Cp2MoCl2 and Silver Nanoparticles Louis Y. Kuo,* Anne K. Bentley, Yusef A. Shari’ati, and Curtis P. Smith Department of Chemistry, Lewis & Clark College, Portland, Oregon 97219, United States S Supporting Information *

ABSTRACT: The metallocene bis(cyclopentadienyl)molybdenum(IV) dichloride (Cp2MoCl2; Cp = η5-C5H5) is the first organometallic compound to promote the hydrolysis of phosphonothioates with selective P−S scission in a stoichiometric fashion. This report shows that silver nanoparticles capped with borohydride ions promote turnover in this hydrolytic process, as indicated by 31P NMR studies on the reaction of O,S-diethyl phenylphosphonothioate (DEPP) with Cp2MoCl2 (pH 7). This is the first example of the joint use of nanoparticles and molybdenum metallocenes to promote phosphonothioate hydrolysis. Initial results indicate the turnover may be due to free Ag+(aq) ions present in the solution that arise either from the slow dissolution of the nanoparticles or from interactions with the Ag nanoparticle surface.

■

Therefore, there is an incentive to find reactions that selectively cleave the P−S bond of phosphonothioates. Such hydrolytic strategies have applications in the degradation of pesticides containing P−S and P−O linkages such as fonofos,22 demeton-S,20 and ethion.23,24 Examples of such strategies are oxidative hydrolytic cleavage of phosphonothioates with oxone25 and micellar complexes.26 To this end we reported the first case of an organometallic compound that promoted the hydrolysis of phosphonothioates with specific P−S scission. 27 The metallocene bis(cyclopentadienyl)molybdenum(IV) dichloride (Cp2MoCl2; Cp = η5-C5H5)28 was found to specifically cleave the P−S bond of phosphonothioates. The compound O,S-diethyl phenylphosphonothioate (DEPP)26 was used to probe the product composition of phosphonothioate hydrolysis. DEPP is significantly less toxic than VX but demonstrates a very similar fraction of P−S scission products under alkaline hydrolysis.26 It was found that Cp2MoCl2 under extremely mild anaerobic conditions (pH 7, 25 °C) hydrolyzed DEPP to yield only ethyl phenylphosphonate (O-EPP), as shown in eq 2.27 DEPP is a convenient analogue to probe the product composition in hydrolytic studies. Moss and co-workers have also used DEPP to show that various iodosobenzoates (IBA) promote specific P−S scission of the phosphonothioate in water.29 The chemoselectivity and mild aqueous conditions of this hydrolytic process prompted further investigations to

INTRODUCTION Phosphonothioates,1,2 [RP(O)(SR1)(OR2)], have LD50 values that make them some of the most toxic synthetic compounds.3 These organophosphates are used as chemical warfare agents. Current methods to degrade phosphonothioates include incineration,4 alkaline hydrolysis,5 perhydrolysis,6−12 methanolysis,13−16 and adsorption.17−19 There is a treaty-bound deadline of 2012 to eliminate stockpiled warfare organophosphates.20 However, a fundamental quandary exists for the alkaline hydrolysis of phosphonothioates, which proceeds through either P−S or P−O bond scission to yield the respective phosphonate [RP(O)(OH)(OR2)] or phosphonothioate [RP(O)(SR1)(OH)] product. The P−O scission pathway generates another form of the toxic phosphonothioate.20 One dramatic example of this problem is the alkaline hydrolysis (0.1 M NaOH) of the chemical warfare agent VX, which yields both P−O (13%) and P−S (87%) scission wherein the phosphonothioate product (EA 2192) is as toxic as the parent VX (eq 1).21

Received: March 27, 2012 Published: July 26, 2012 © 2012 American Chemical Society

5294

dx.doi.org/10.1021/om300251w | Organometallics 2012, 31, 5294−5301

Organometallics

Article

Innovative Technology System One Glovebox or with standard Schlenk techniques. Additionally, all H2O was purified to 18 MΩ with a Lab 5 Excel Water Systems filter. All solvents used in the hydrolysis studies were purged with Ar. Stock solutions of Cp2MoCl2 in D2O containing 300 mM MOPS (pH 7.0) were made prior to kinetic measurements. Prior to the nanoparticle synthesis, all glassware was cleaned with aqua regia (3/1 v/v HCl/HNO3), rinsed with copious amounts of water, and dried. The borohydride-capped silver nanoparticles (Ag NPs) were made according to the procedure of Solomon and coworkers,42 where a 10 mL solution of aqueous AgNO3 (1.0 mM) solution was added dropwise to 30 mL of aqueous NaBH4 (2.0 mM) that was chilled on ice and vigorously stirred. The solution’s initial light yellow color became brighter after all the AgNO3 solution was added. These Ag NPs had the characteristic plasmon absorbance at 410 nm. Characterization Methods. TEM grids were prepared by dropping ∼7.5 μL of the nanoparticle solution onto a holey carboncoated copper TEM grid (SPI Supplies) and left to dry overnight. TEM images were acquired using a FEI Technai F-20 TEM instrument operating at 200 kV accelerating voltage. Size distributions were determined by measuring 999 nanoparticle diameters using Image J software. The silver nanoparticles were found to be 2.3 ± 1.8 nm in diameter (see Figure S1 in the Supporting Information). Absorption spectra (300−800 nm) were collected using an Agilent 8453 UV−vis spectrophotometer. Synthesis of Molybdocene Compounds 1 and 3. A degassed 1 mL aqueous solution of sodium ethanethiolate (32 mg, 0.38 mmol) was added to an aqueous 2 mL Cp2MoCl2 solution (50 mg, 0.17 mmol) under a nitrogen flush. The solution immediately turned red, and after 15 min a red precipitate formed. After the mixture was stirred for 16 h, the red precipitate was washed with degassed water and dried in vacuo. 13C NMR (CDCl3): δ 19.0, 31.5, 96.9. 1H NMR (CDCl3): δ 1.26 (t, 3H), 2.26 (q, 2H), 5.18 (s, 10H). Anal. Calcd for C14H20MoS2·1.6H2O: C, 44.58; H, 6.20. Found: C, 44.73; H, 6.20. Compound 3 (Cp2Mo(SCH3)2) was made in an identical manner but with 30 mg (0.38 mmol) of sodium methanethiolate. 13C NMR (CDCl3): δ 18.0, 96.7. 1H NMR (CDCl3): δ 1.99 (s, 3H), 5.19 (s, 10H). Anal. Calcd for C12H16MoS2·0.45H2O: C, 43.88; H, 5.19. Found: C, 44.24; H, 5.61. Synthesis of Phosphonothioates 6 and 7. The synthesis of the phosphonothioates O,S-diethyl phenylphosphonothioate (DEPP, 6), and O-ethyl-S-methyl phenylphosphonothioate (MEPP, 7) followed the procedure of DeBruin and co-workers43 with minor modifications. In this protocol, a solution of ethanol (22.1 mL, 540 mmol), pyridine (26.2 mL, 325 mmol), and toluene (36 mL) was added dropwise over 30 min to a solution of dichlorophenylphosphine (34 mL, 250 mmol) in toluene (175 mL). The mixture was stirred for 1.5 h and allowed to sit without stirring for 1 day. The solution and resulting white solid were washed with saturated sodium bicarbonate (80 mL), and the aqueous layer was back-extracted with methylene chloride (70 mL). The toluene and methylene chloride layers were combined, dried over magnesium sulfate, filtered, and then concentrated down to the Oethyl hydrogen phenylphosphinate (4) oil product (29.94 g, 176 mmol) with a 70% yield. Elemental sulfur (6.15 g, 190 mmol) was added to a solution of 4 (29.94 g, 176 mmol) and dicyclohexylamine (34.45 g, 190 mmol) in diethyl ether (300 mL) slowly over 30 min and then stirred for 4 h. The resulting solid was filtered and dried. The solid was then recrystallized with ethyl acetate. The resulting dicyclohexylammonium salt of the O-ethylphosphonothioate (PhP(O)(OEt)S−) 5 was obtained (44.3 g, 120 mmol) with a 63% yield. In the final step, 5 (5.0 g, 13 mmol) was slowly added to a stirred solution of distilled toluene (100 mL) and iodoethane (2.4 mL, 30 mmol). The mixture was stirred for 3 days. The resulting suspension was filtered and washed with anhydrous hexanes, which were concentrated under reduced pressure. This oil was washed repeatedly with a minimal amount of anhydrous hexanes to remove residual salt. The hexane washes were concentrated down to the resulting 6 (DEPP) oil (1.5 g, 6.3 mmol). Kugelrohr distillation was used if hexanes extraction did

improve phosphonothioate hydrolysis by this molybdenum metallocene. Two drawbacks to using Cp2MoCl2(aq) are its aqueous speciation and thiophilic chemistry. In water both chlorides rapidly dissociate from Cp2MoCl2 to form pH-sensitive aquated species (Cp2Mo(aq)) that exist in a dimer−monomer equilibrium. Only the monomeric form (Cp2Mo(H2O)22+) is active in DEPP hydrolysis.30 More importantly, Cp2Mo2+(aq) readily reacts with the ethanethiolate leaving group of DEPP (eq 3) to form bis(ethanethiolato)molybdocene (1), which quenches any further hydrolytic activity. As such, the next critical goal is to promote turnover in eq 2.

To this end, we have embarked on a strategy that recovers the DEPP-cleaving hydrolytic reagent through a nonoxidative process, as the Mo(IV) in Cp2MoCl2 is air sensitive. Our method takes advantage of the thiophilicity of gold31,32 and silver33,34 nanoparticles to bind the ethanethiolate product. Nanoparticles are stabilized in solution by steric and/or electrostatic effects arising from capping molecules on the surface of the metal particles. Thiol molecules have been shown to bind with high affinity to gold and silver nanoparticles, displacing existing capping agents.35−41 Specifically, BH4−capped silver nanoparticles (AgNPs) 42 were added to

Cp2MoCl2 + DEPP (excess) reactions as shown in eq 4, and 31 P NMR was used to monitor the hydrolysis process. The silver nanoparticles are easily suspended in water (pH 7 MOPS buffer) and show no evidence of reactivity with DEPP for up to 2 weeks at 55 °C (vide infra). They are readily synthesized and characterized, and the rich nanoparticle literature makes them a convenient platform for further characterization.35−41 While gold nanoparticles have an extensive literature associated with their synthesis, this study focuses specifically on results from silver nanoparticles, due to their inexpensive cost and ease of dissolution in water.

■

EXPERIMENTAL SECTION

31

P and 1H NMR spectra were obtained on a Bruker Avance-300 spectrometer at 121 and 300 MHz, respectively. The compound Cp2MoCl2 was purchased from Strem Chemical Co. (Newburyport, MA), and all reagents and solvents for the synthesis of phosphonothioates were purchased from TCI (Portland, OR) and used without further purification. All other chemicals were purchased from Sigma-Aldrich. Manipulations with Cp2MoCl2 were done in an 5295

dx.doi.org/10.1021/om300251w | Organometallics 2012, 31, 5294−5301

Organometallics

Article

not remove impurities. 1H NMR (CDCl3): δ 1.3 (t, 3H, OCH2CH3), 1.4 (t, 3H, SCH2CH3), 2.8 (q, 2H, SCH2CH3), 4.2 (q, 2H, OCH2CH3), 7.5 (m, 3H, meta and para), 7.9 (d, 2H, ortho). 13C NMR (CDCl3): δ 16.6 (d, JPC = 5.9 Hz, SCH2CH3), 16.8 (d, JPC = 6.9 Hz, OCH2CH3), 25.3 (d, JPC = 3.1 Hz, SCH2CH3), 62.5 (d, JPC = 6.9 Hz, OCH2CH3), 128.9 (d, JPC = 14.75 Hz, meta), 131.6 (d, JPC = 10.6 Hz, ortho), 132.9 (d, JPC = 3.1 Hz, para), 132.3 (d, JPC = 150 Hz, ipso). 31 P NMR (CDCl3): δ 44.65. HRMS: calcd for C10H15O2SP 230.053 04 (EI+); found 230.053 64. The identical procedure was used to make the other phosphonothioates, except the dicyclohexylammonium salt 5 was added to iodomethane without toluene to form 7. 1H NMR (CDCl3): δ 2.8 (s, 3H), 7.5 (m, 3H, meta and para), 7.9 (d, 2H, ortho). 13C NMR (CDCl3): δ 12.4 (d, JPC = 3.1 Hz, SCH3), 16.8 (d, JPC = 6.9 Hz, OCH2CH3), 62.5 (d, JPC = 7.0 Hz, OCH2CH3), 128.9 (d, JPC = 14.75 Hz, meta), 131.6 (d, JPC = 10.6 Hz, ortho), 132.9 (d, JPC = 3.1 Hz, para), 132.3 (d, JPC = 150 Hz, ipso). 31P NMR (CDCl3): δ 44.65. HRMS: calcd for C9H13O2PS 216.037 39 (EI+); found 216.038 06. DEPP Hydrolysis. In a typical DEPP hydrolysis reaction, 0.75 mL of degassed MOPS (300 mM in D2O) was added to a small Schlenk tube containing Cp2MoCl2 (3−10 mg) outside the glovebox. Upon complete dissolution under N2, another 0.75 mL of the degassed Ag NP solution was added to the aqueous Cp2MoCl2. This solution was transferred to a screw-cap NMR tube that had been purged with Ar for ∼5 min. The monitoring of the hydrolysis reaction by NMR began after syringing in the DEPP (3−15 μL). For reactions involving compound 1, a screw-cap NMR tube with 0.70 mL of MOPS was saturated with 1. Since 1 was only sparingly soluble in water, excess 1 (∼10 mg) was added such that crystals were still visible. An additional 15 μL of DEPP followed by 0.70 mL of the silver nanoparticles was added to the NMR tube. It is important that the NPs be added last, as their presence causes the decomposition of air-sensitive Cp2MoCl2(aq). X-ray Structure Analysis of Compound 3. Crystals were grown by slow cooling of a boiling aqueous solution of 3. An orange crystal of dimension 0.16 mm × 0.06 mm × 0.04 mm was used for X-ray crystallographic analysis on a Bruker Apex CCD diffractometer at 173 K using Mo Kα radiation (λ = 0.710 73 Å). The space group P21/n was determined on the basis of systematic absences, and absorption corrections were applied by SADABS. Structures were solved by direct methods and Fourier techniques and refined on F2 using full-matrix least-squares procedures to R1 = 2.51%. All non-H atoms were refined with anisotropic thermal parameters, and the hydrogen atoms were refined in the calculated positions with a rigid group model. All calculations were performed with the Bruker SHELXTL (v. 6.10) package. Further crystallographic data and details of the X-ray diffraction of Cp2Mo(SCH3)2 are given in the Supporting Information.

Figure 1. 31P NMR spectra of a solution of Cp2MoCl2, DEPP, and AgNPs in 300 mM pH 7 MOPS buffer at 40 °C. The 44 ppm DEPP signal at time 0 is the phosphonothioate in a separate nonaqueous phase that is often seen when excess DEPP is used.

nanoparticles (Figure S3 in the Supporting Information). An NMR tube containing just DEPP in pH 7 MOPS (55 °C) with a flame-sealed capillary insert standard (benzenephosphonic acid in the same buffer solution) showed that the phosphonothioate did not evaporate through the screw-cap NMR tubes during a 1 week period (Figure S4 in the Supporting Information). Sodium borohydride (2.0 mM) was used as another negative control for DEPP hydrolysis to ensure that the AgNPs’ borohydride capping agent did not effect the same chemistry seen in Figure 1 (Figure S5 in the Supporting Information). A byproduct of the DEPP synthesis was dicyclohexylammonium iodide, which was removed through repeated hexane extraction of the phosphonothioate. To examine the effect of any residual iodide, a reaction of sodium iodide and DEPP under the same aqueous conditions was carried out and yielded no O-EPP product after eight days (Figure S6 in the Supporting Information). Ag+ Ions + DEPP. Silver ions have previously been employed by DeBruin and co-workers43,45 to synthesize phosphonates from phosphonothioates through exclusive alkanethiolate abstraction; therefore, it was important to investigate the possibility that DEPP was being directly hydrolyzed by silver ions dissolving from the AgNPs. Recent reports, prompted by questions of Ag+ toxicity, have shown that silver nanoparticles readily release Ag+ ions at rates of dissolution dependent on temperature, dissolved oxygen, NP capping ligand, and pH.46−48 Most of the Ag+ dissolution occurred within the first 2 days of AgNP incubation, and in some cases the nanoparticles released up to 90% of their weight. We found P−S scission of DEPP by Ag+(aq) ions occurred at a relatively high 10 mM AgNO3 concentration. The AgNPs used in this study, however, were prepared from mixing 10 mL 1 mM AgNO3 with 30 mL of NaBH4, which gives an upper limit of 0.25 mM of Ag+(aq), assuming all the silver was present as Ag+ (i.e., no AgNPs were formed). Control experiments showed no DEPP hydrolysis at this lower 0.25 mM Ag+(aq) concentration (i.e., 0.25 mM AgNO3 and DEPP alone at 55 °C for 3 daysFigure S7A in the Supporting Information). The

■

RESULTS AgNPs Added to Cp2MoCl2 and DEPP Yield Modest Turnover. 31P NMR was used to evaluate the extent of the DEPP hydrolysis reaction in the presence of borohydridecapped silver nanoparticles (AgNPs). A 6/1 DEPP/Cp2MoCl2 ratio in 300 mM pH 7 MOPS buffer was confirmed using 1H NMR spectroscopy through integration of the phenyl versus cyclopentadienyl signals (Figure S2 in the Supporting Information). This 6/1 ratio is a lower limit, as it assumes all the cyclopentadienyl signals are due to the molybdocene in its dimeric form.44 After 1 day at 40 °C, the O-EPP signal at 15 ppm was observed (Figure 1), indicating that the reaction proceeded exclusively via P−S scission. The reaction proceeded to 50% completion, showing nonstoichiometric DEPP hydrolysis with modest turnover. Control Experiments. A series of control experiments were conducted to rule out alternative explanations for the turnover observed in the presence of AgNPs. Incubation of AgNPs with DEPP alone at 55 °C showed that DEPP was unaffected by the 5296

dx.doi.org/10.1021/om300251w | Organometallics 2012, 31, 5294−5301

Organometallics

Article

Figure 2. HSQC (13C−1H) of Cp2Mo(SEt)2 (1) in CDCl3 with 0.1% TMS (0.0 ppm). Triplet signals at 77 ppm (13C) are from CDCl3, and asterisks represent water and grease impurities.

Figure 3. 13C NMR of DEPP + Cp2MoCl2 under stoichiometric conditions (pH 7 MOPS buffer, 55 °C). No NPs were present. Doublets for signals a−c (2JPC = 7 Hz) are the β-methyl carbons. Upfield signals at 31.5 and 19.0 ppm are from compound 1, formed as shown in eq 3. Not shown is the 96.7 ppm 13C singlet (Cp).

thioate in comparison to the reaction of just Cp2MoCl2(aq) and DEPP (Figure 1). Direct Synthesis of Bis(ethanethiolate)molybdocene (1) and Characterization via 13C and 1H NMR. In a prior report, the reaction of Cp2MoCl2(aq) with DEPP (eq 2) yielded the bis(ethanethiolate)molybdocene compound (1) that was crystallographically characterized.27 In order to characterize the DEPP hydrolysis reaction products from the reactions described here, 1 was synthesized directly through the addition of sodium ethanethiolate (2 equiv) to Cp2MoCl2 under oxygen-free aqueous conditions. A red-brown precipitate formed overnight, which was unambiguously identified as 1 using 13C and 1H NMR (Figure 2). Although 1 is sparingly soluble in water, the addition of THF helps in its dissolution. 13 C NMR in CDCl3 showed that 1 had the characteristic cyclopentadienyl singlet at 96.9 ppm and the CH2 and CH3 singlets at 31.5 and 19.0 ppm, respectively (Figure 2). This was the same compound that was previously characterized by X-ray crystallography.27 Products of Cp2MoCl2 + DEPP Reaction Monitored via 13 C NMR. 13C NMR spectroscopy was employed to track possible species formed in the hydrolytic process, and stoichiometric conditions were chosen to increase the rate of the reaction. The 13C NMR spectrum of an aqueous reaction of

absence of DEPP reactivity was also observed at 0.50 mM Ag+(aq). Furthermore, when DEPP hydrolysis by Cp2MoCl2(aq) (5/1 DEPP/Cp2MoCl2(aq) ratio) was carried out in the presence of AgNO3 (0.25 mM), no enhancement of turnover was observed (Figure S7B in the Supporting Information). Use of KI To Sequester Ag+. As an additional measure to ensure no silver ions were present and interacting with the molybdocene complex, iodide ion was used to precipitate trace amounts of Ag + from the reaction of DEPP with Cp2MoCl2(aq). In two parallel DEPP hydrolysis reactions, AgNPs were incubated with Cp2MoCl2 and a ∼5-fold excess of DEPP at pH 7 and 55 °C, and the reactions were monitored using 31P NMR. One reaction had only these reactants (Figure S7C in the Supporting Information), while 1 mL of 10 mM KI was added to the other reaction (Figure S7D in the Supporting Information) to precipitate any residual Ag+ ions in solution as AgI (Ksp ≈ 10−17). In both reactions DEPP hydrolysis proceeded to the same degree. To investigate the activity of Cp2MoCl2(aq) in DEPP hydrolysis in the presence of AgI(s), a reaction containing AgNO3(aq) (not AgNPs as in Figure S7C,D) and KI was run (Figure S7E in the Supporting Information). There was no difference in the stoichiometric hydrolysis of the phosphono5297

dx.doi.org/10.1021/om300251w | Organometallics 2012, 31, 5294−5301

Organometallics

Article

DEPP (5 μL) with 4 mg of Cp2MoCl2 (3/1 DEPP/Cp2MoCl2) in pH 7 MOPS (no AgNPs) (Figure 3) showed the distinct singlets of compound 1 appearing at 96.7, 31.5, and 19.0 ppm after only 1 day (55 °C). Authentic addition studies shown in Figure S8 in the Supporting Information further demonstrate that these singlets are from compound 1. The O-EPP product signals at 61.5 ppm (doublet, 2JPC = 7 Hz) and 16.1 ppm (doublet, 2JPC = 7 Hz) appeared over time with concomitant disappearance of the starting DEPP aliphatic 13 C signals. After 3 days there was no evidence of the DEPP by 13 C NMR. Direct Synthesis of Ethanethiolatemolybdocene (2) and Characterization via 13C and 1H NMR. For use in comparison to the DEPP + Cp2MoCl2 + AgNPs reaction products, the monothiolated molybdocene complex Cp2Mo(SEt)(H2O)+ (2) was directly synthesized (eq 5) by adding

compound 2, which was made in situ during the reaction in the presence of AgNPs.

Figure 4. 13C NMR of the DEPP + Cp2MoCl2 reaction in the presence of AgNPs: (A) initial spectrum; (B) after 7 days at 40 °C. The disappearance of the singlets at 96.7, 30.5, and 19.0 ppm indicates the degradation of compound 1. In their place is the Cp signal at 99 ppm that results from formation of 2.

Investigation of the Role of AgNPs in the Reaction of 1 + DEPP. Direct NMR observation of the reaction of 1 with Ag+ ions was not possible, due to the poor solubility of 1 in water; therefore, an indirect method was used to track the fate of 1. As mentioned earlier, AgNPs alone did not affect DEPP (eq 6a, Figure S3 in the Supporting Information) and the

Cp2MoCl2 (50 mg, 0.16 mmol) to 1.1 equiv of NaSEt (16 mg, 0.18 mmol) in 2 mL of D2O. Unfortunately, we were unable to isolate this compound for complete analysis. The reaction products were characterized by HSQC, 1H−1H COSY, and 2-D NOESY. In this aqueous reaction several different products were formed, including 1, which was mostly removed with CDCl3 extraction. An HSQC of the D2O layer showed that compound 2 was the most prominent aqueous species, with a 13 C 99 ppm signal that correlated with the 1H singlet at 5.71 ppm (Figure S9 in the Supporting Information). The aliphatic 13 C 15 and 37 ppm singlets were also prominent, correlating with the 1H signals at 0.49 ppm (triplet) and 1.83 ppm (quartet), respectively. 2D-NOESY (Figure S10 in the Supporting Information) showed the 5.71 ppm cyclopentadienyl signal (10H) correlated to the 1.83 ppm quartet (2H) that was coupled (Figure S11 in the Supporting Information) to the triplet at 0.49 ppm (3H). The 1H integrals were found in Figure S12 in the Supporting Information. A more detailed analysis of 2 was unsuccessful, as attempts to isolate this compound through precipitation or solvent extraction did not yield a pure solid. However, it is worth noting that, when the resulting products of the Cp2MoCl2 + NaSEt (1.1 equiv) reaction (eq 5) that include 2 are added to DEPP, there is clear evidence of phosphonothioate hydrolysis (Figure S13 in the Supporting Information). There is no DEPP hydrolysis in the presence of 1 alone (vide infra). 13 C NMR Analysis of DEPP + Cp2MoCl2 + AgNPs Reaction Products. In an effort to understand the role of AgNPs in providing reaction turnover, 13C NMR was used to track speciation during the stoichiometric reaction of DEPP with Cp2MoCl2 in the presence of AgNPs. Under these conditions, the 19.0 and 31.5 ppm 13C NMR signals of 1 disappeared upon prolonged heating (7 days). No crystals of 1 were apparent, and so the disappearance of these singlets was not due to precipitation of 1. In place of the cyclopentadienyl singlet for 1 at 96.7 ppm, 13C singlets in the 99.0−105 ppm range appeared (Figure 4). These peaks correspond to

AgNPs + DEPP → no reaction

(6a)

absence of reactivity (3 days, 55 °C) also occurred when 1 was incubated with DEPP alone (eq 6b) even when THF was 1 + DEPP → no reaction

(6b)

added to promote the solubility of 1. However, when DEPP was added to an aqueous mixture of 1 and the AgNPs at 55 °C, a phosphonate signal consistent with O-EPP (15 ppm) appeared after just 3 days in air (eq 6c, Figure S14 in the AgNPs + DEPP + 1 → O‐EPP (∼ 15% after 3 days, 55 °C)

(6c)

Supporting Information). The results summarized in eq 6c show that the silver nanoparticles played an integral role in the turnover hydrolysis of DEPP by Cp2MoCl2(aq) that will be elaborated further in the Discussion. While the aforementioned spectral behavior (i.e., the appearance of 1 followed by its complete disappearance in the presence of nanoparticles) occurred under stoichiometric conditions, turnover reactions (6/1 DEPP/Cp2MoCl2) in AgNPs yielded the same outcome. Investigation of the Role of Ag+(aq) in the Reaction of 1 + DEPP. To evaluate the extent to which the regenerative property of the AgNPs resulted from the interaction of 1 with Ag+(aq) leached from the NPs, an experiment was run using AgNO3 as a source of Ag+(aq). Earlier it was shown that the addition of 0.25 and 0.50 mM AgNO3(aq) to solutions of DEPP had no effect on DEPP (Figure 7A in the Supporting Information). In the presence of compound 1, a 0.25 mM 5298

dx.doi.org/10.1021/om300251w | Organometallics 2012, 31, 5294−5301

Organometallics

■

AgNO3 solution shows small but very detectable hydrolysis (P−S scission) of DEPP (Figure 5) that was not present when the phosphonothioate was incubated with 1 (eq 6b) or AgNO3 (0.25 mM) alone.

Article

DISCUSSION

In reactions between DEPP and Cp2MoCl2 both with and without AgNPs, only the O-EPP signal at 15 ppm was produced (Figure 1), indicating that both types of reactions proceeded exclusively through P−S scission and no phosphonothioate (P−O scission) was made in these reactions. The presence of AgNPs led to a modest turnover, but further incubation at higher temperatures and longer times did not generate greater turnover. The control experiments showed that DEPP was inert toward AgNPs, BH4−, and I− ions and that it was unable to leak out of the NMR tube. The control reactions were carried out at a higher temperature (55 °C vs 40 °C) to ensure they could not account for the disappearance of excess DEPP (Figure 1). Therefore, the disappearance of the excess DEPP was due to hydrolysis through exclusive P−S scission to O-EPP. Attempts were made to study the effect of varying the alkyl leaving group on phosphonothioate hydrolysis. The compound O-ethyl-Smethyl phenylphosphonothioate (MEPP, 7) was made, but its hydrolysis by Cp2MoCl2(aq) in pH 7 MOPS clearly showed the appearance of a second 31P NMR signal at 33 ppm consistent with the undesirable P−O scission, resulting in a phosphonothioate. There is the possibility that P−S scission of DEPP was due to residual Ag+(aq) ions, since the borohydride-capped AgNPs were made from AgNO3 (1 mM), and AgNPs are known to dissolve over time.46,47 Ag+(aq) ions alone were found to have no effect on DEPP at dilute levels (i.e., 0.25 and 0.50 mM). The absence of P−S scission when Ag+(aq) was added to reactions of DEPP and Cp2MoCl2 at the maximum concentration likely to be found in the AgNP solution indicated that dissolution of Ag+(aq) from the AgNPs does not likely play a significant role in the observed turnover enhancement. However, one cannot totally discount the possibility that Ag+(aq) leached from the AgNPs would react with DEPP in the presence of Cp2MoCl2(aq) at pH 7. Therefore, an attempt was made to sequester any free Ag+(aq) ions leached from AgNPs to determine if even a trace amount of thiophilic metal ion has an effect on DEPP degradation in the presence of Cp2MoCl2(aq) at pH 7. Not only did AgNO3 added at the 0.25 mM concentration have no effect on the reaction between Cp2MoCl2(aq) and DEPP but also the addition of a source of iodide ions to sequester any residual Ag+(aq) in the reaction containing AgNPs showed the turnover was undiminished. Because the absence of Ag+(aq) (i.e., tied up as AgI(s)) did not preclude DEPP hydrolysis, the AgNP surface likely plays a role in DEPP hydrolysis in the presence of Cp2MoCl2(aq). The direct synthesis of compound 1 allowed its identification as a primary product of the reaction between Cp2MoCl2(aq) and DEPP, an expected result on the basis of the formation of the ethanethiol product and the known thiophilicity of Cp2Mo2+.49 Additionally, the results summarized in eq 6c showed that the silver nanoparticles played an integral part in the turnover hydrolysis of DEPP by Cp2MoCl2(aq). The products of the reaction in the presence of AgNPs showed a disappearance of the bis-thiolate compound 1 over time and the appearance of the monothiolate compound 2. The disappearance of 1 was most likely due to its reaction (or interaction) with the AgNPs or side product(s) such as free Ag+(aq). Such a process regenerated Cp2Mo2+(aq) or 2 that hydrolyzed another 1 equiv of DEPP.

Figure 5. 31P NMR of DEPP (10 μL, 35 mM) in a 0.25 mM solution of AgNO3 containing a suspension of compound 1 (∼2 mg, 5.7 × 10−6 mol) after 7 days at 40 °C. The total aqueous volume (33% D2O) was 1.0 mL with no MOPS buffer added.

Synthesis of Molybdocene Bis(methanethiolate) (3) and Its Reaction with DEPP + AgNPs. To investigate the generality of the activation of the bis-alkanethioate complexes of molybdocenes by silver NPs, the interaction of DEPP and AgNPs with molybdocene bis(methanethiolate) (3) was studied. Compound 3 was synthesized directly by combining Cp2MoCl2 and 2 equiv of sodium methanethiolate. Crystallographic analysis of 3 showed the discrete clamshell structure characteristic of bent metallocenes (Figure 6). More importantly, when 3 was incubated with AgNPs in the presence of DEPP (55 °C), the product phosphonate signal at 15 ppm (P−S scission) appeared after 3 days.

Figure 6. X-ray crystal structure of compound 3 (R1 = 2.52%) made from Cp2MoCl2(aq) and NaSCH3. Relevant metrical parameters: Mo−S = 2.4749 Å (average) and S−Mo−S = 75.990(19)°. 5299

dx.doi.org/10.1021/om300251w | Organometallics 2012, 31, 5294−5301

Organometallics One of the reasons for the slow turnover rate is the poor water solubility of 1, which ultimately is the source of the aquated Cp2Mo2+(aq) and/or 2. A combination of 1 and AgNPs (no DEPP), which is the reverse of the reaction shown in eq 3, would test the hypothesis that the nanoparticles regenerate Cp2Mo2+(aq) and/or 2 from 1. Unfortunately, it is impossible to track this process with 13C NMR due to the poor solubility of 1 in water in which the AgNPs are suspended. Instead, the disappearance of 1 was investigated further by incubating 1, DEPP, and AgNO3. As in the direct reactions between Cp2MoCl2(aq) and DEPP, AgNO3 was used as a source of Ag+ to investigate the role of free Ag+(aq) ions. Compound 1 and AgNO3 (0.25 mM) do not affect DEPP individually, but when both are incubated with DEPP, the P−S scission product is observed. This indirect method for interrogating the hydrolysis of 1 with Ag+(aq) suggested that the free Ag+(aq) leached from AgNPs may regenerate an active form of the molybdocene from 1. A hypothetical route toward the activation of Cp2Mo(SEt)2 (compound 1) by the AgNPs is the removal of an ethanethiolate to form 2. In Figure 4, the 99 ppm 13C signal that appeared in the presence of AgNPs clearly showed the formation of a Cp2Mo(SEt)(aq) species identifiable as 2. The reaction of compound 3 with DEPP was identical with the prior 1 + DEPP and AgNPs + DEPP reactions (eqs 6b and 6c) that yielded the phosphonate product. These observations with the molydocene thiolate compounds indicate that the silver nanoparticles serve to activate the Cp2Mo(SR)2 species to hydrolyze DEPP with specific P−S scission.

■

REFERENCES

(1) Larson, R. A.; Weber, E. J. Reaction Mechanisms in Environmental Organic Chemistry; Lewis: Boca Raton, LA, 1994. (2) Somani, M., Chemical Warfare Agents; Academic Press: San Diego, CA, 1992. (3) Gordon, J. J.; Leadbeater, L. Toxicol. Appl. Pharmacol. 1977, 40, 109−114. (4) Enison, M. K.; Sadler, B. A.; Montgomery, C. J.; Sarofim, A. F.; Bockelie, M. J. Prog. Comput. Fluid Dyn. 2007, 7, 51−57. (5) In Review and Evaluation of Alternative Chemical Disposal Technologies; National Research Council, Washington, DC, National Academy Press: Washington, DC, 1996. (6) Kennedy, R. J.; Stock, A. M. J. Org. Chem. 1960, 25, 1901−1906. (7) Zhu, W.; Ford, W. T. J. Org. Chem. 1991, 56, 7022−7026. (8) Webb, K. S. Tetrahedron Lett. 1994, 35, 3457−3460. (9) Bunton, C. A.; Foroudian, H. J.; Kumar, A. J. Chem. Soc., Perkin Trans. 1 1995, 2, 33−39. (10) Yang, Y.-C.; Berg, F. J.; Szafraniec, L. L.; Beaudry, W. T.; Bunton, C. A.; Kumar, A. J. Chem. Soc., Perkin Trans. 2 1997, 607−613. (11) Yang, Y.-C.; Szafraniec, L. L.; Beaudry, W. T. J. Org. Chem. 1993, 58, 25. (12) Yang, Y.-C.; Szafraniec, L. L.; Beaudry, W. T.; Rohrbaugh, D. K.; Procell, L. R.; Samuel, J. B. J. Org. Chem. 1996, 61, 8407−8413. (13) Tsang, J. S.; Neverov, A. A.; Brown, R. S. J. Am. Chem. Soc. 2003, 125, 7602−7607. (14) Liu, T.; Neverov, A. A.; Tsang, J. S.; Brown, R. S. Org. Biomol. Chem. 2005, 3, 1525−1533. (15) Melnychuk, S. A.; Neverov, A. A.; Brown, R. S. Angew. Chem., Int. Ed. 2006, 45, 1767−1770. (16) Desloges, W.; Neverov, A. A.; Brown, R. S. Inorg. Chem. 2004, 43, 6752−6761. (17) Beaudry, W. T.; Wagner, G. W.; Ward, J. R. J. Mol. Catal. 1992, 73, 77−90. (18) Beaudry, W. T.; Wagner, G. W.; Ward, J. R. J. Mol. Catal. 1993, 83, 183−195. (19) Beaudry, W. T.; Wagner, G. W.; Ward, J. R. J. Mol. Catal. 1994, 93, 221−231. (20) Yang, Y. C.; Baker, J. A.; Ward, J. R. Chem. Rev. 1992, 92, 1729− 1743. (21) Yang, Y. C. Acc. Chem. Res. 1999, 32, 109−115. (22) El-Sebae, A. H.; Soliman, S. A.; Ahmed, N. S. J. Environ. Sci. Health., Part B 1979, 14, 247−263. (23) Fisher, S. W.; Lydy, M. J.; Barger, J.; Landrum, P. F. Environ. Toxicol. Chem. 1993, 12, 1307−1318. (24) Mosha, R. D.; Gyrd-Hansen, N. Vet. Hum. Toxicol. 1990, 32. (25) Blasko, A.; Bunton, C. A.; Kumar, A. J. Phys. Org. Chem. 1997, 10, 427−434. (26) Berg, F. J.; Moss, R. A.; Yang, Y. C.; Zhang, H. Langmuir 1995, 11, 411−413. (27) Kuo, L. Y.; Adint, T. T.; Akagi, A. E.; Zakharov, L. Organometallics 2008, 27, 2560−2564. (28) Cooper, R. L.; Green, M. L. H. J. Chem. Soc. 1967, 1155−1160. (29) Morales-Rojas, H.; Moss, R. A. Chem. Rev. 2002, 102, 2497− 2521. (30) Kuo, L. Y.; Barnes, L. A. Inorg. Chem. 1999, 38, 814−817. (31) Daniel, M.-C.; Astruc, D. Chem. Rev. 2004, 104, 293−346. (32) Giljohann, D. A.; Seferos, D. S.; Daniel, W. L.; Massich, M. D.; Patel, P. C.; Mirkin, C. A. Angew. Chem., Int. Ed. 2010, 49, 3280−3294.

CONCLUSION This proof-of-concept experiment is the first example of the application of silver nanoparticles to enhance an organometallic-mediated hydrolysis process. The degree of turnover promoted by the nanoparticles is modest, but it nevertheless converts a strictly stoichiometric reaction (eqs 2 and 3) into one that regenerates a monothiolated molybdocene, compound 2, that hydrolyzes a third equivalent of the DEPP phosphonothioate. The cause of the formation of compound 2 from 1 in the presence of the silver NPs may be a combination of nanoparticle surface chemistry (Figure S7 in the Supporting Information) as well as Ag+(aq) ions leached from the AgNPs that react with 1. Nevertheless, the burden of turnover is shifted from the Cp2MoCl2 onto the Ag NPs. The inability of the silver nanoparticle suspension to regenerate a fully aquated molybdocene may be a key factor for the modest turnover. As such, future studies are directed toward methodologies that enhance the degree of turnover as well as understand the fate of the NPs. ASSOCIATED CONTENT

S Supporting Information *

Figures giving TEM image and particle size analysis of Ag NPs and detailed NMR spectra of control experiments and tables and a CIF file giving crystallographic data for 3. This material is available free of charge via the Internet at http://pubs.acs.org.

■

ACKNOWLEDGMENTS

This work was funded by NSF-RUI award CHE-0956740. A.K.B. and Y.A.S. thank the W. M. Keck Foundation and the Beckman Foundation, respectively, for financial support. We thank Lev Zacharov at the University of Oregon for solving the structure of 3. Electron microscopy was carried out at Portland State University’s Center for Electron Microscopy & Nanofabrication.

■

■

■

Article

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest. 5300

dx.doi.org/10.1021/om300251w | Organometallics 2012, 31, 5294−5301

Organometallics

Article

(33) Evanoff, D. D.; Chumanov, G. ChemPhysChem 2005, 6, 1221− 1231. (34) Wiley, B. J.; Chen, Y.; McLellan, J. M.; Xiong, Y.; Li, Z.-Y.; Ginger, D.; Xia, Y. Nano Lett. 2007, 7, 1032−1036. (35) Weisbecker, C. S.; Merritt, M. V.; Whitesides, G. M. Langmuir 1996, 12, 3763−3772. (36) Aslan, K.; Perez-Luna, V. H. Langmuir 2002, 18, 6059−6065. (37) Lin, S.-Y.; Tsai, Y.-T.; Chen, C.-C.; Lin, C.-M.; Chen, C.-H. J. Phys. Chem. B 2004, 108, 2134−2139. (38) Woehrle, G. H.; Brown, L. O.; Hutchison, J. E. J. Am. Chem. Soc. 2004, 127, 2172−2183. (39) Zhang, S.; Leem, G.; Srisombat, L.-o.; Lee, T. R. J. Am. Chem. Soc. 2008, 130, 113−120. (40) Ivanov, M. R.; Bednar, H. R.; Haes, A. J. ACS Nano 2009, 3, 386−394. (41) Tripathy, S. K.; Yu, Y.-T. Spectrochim. Acta, Part A 2009, 72, 841−844. (42) Solomon, S. D.; Bahadory, M.; Jeyarajasingam, A. V.; Rutkosky, S. A.; Boritz, C. J. Chem. Educ. 2007, 84, 5871−5879. (43) DeBruin, K. E.; Tang, C.-l. W.; Johnson, D. M.; Wilde, R. L. J. Am. Chem. Soc. 1989, 111, 5871−5879. (44) Balzarek, C.; Weakley, T.; Kuo, L. Y.; Tyler, D. R. Organometallics 2000, 19, 2927−2931. (45) Cooper, D. B.; Hall, C. R.; Harrison, J. M.; Inch, T. D. J. Chem. Soc., Perkin Trans. 1 1977, 1969−1980. (46) Liu, J.; Hurt, R. H. Environ. Sci. Technol. 2010, 44, 2169−2175. (47) Kittler, S.; Greulich, C.; Diendorf, J.; Koller, M.; Epple, M. Chem. Mater. 2010, 22, 4548−4554. (48) Glover, R. D.; Miller, J.; Hutchison, J. E. ACS Nano 2011, 5, 8950−8957. (49) Calhorda, M. J.; de C. T. Carrondo, M. A. A. F.; Dias, A. R.; Domingos, A. M. T. S.; Martinho Simoes, J. A.; Teixeira, C. Organometallics 1986, 5, 660−667.

5301

dx.doi.org/10.1021/om300251w | Organometallics 2012, 31, 5294−5301