Rapid luminescent detection of phosphate esters in solution and the gas phase using (dppe)Pt{S2C2(2-pyridyl)(CH2CH2OH)} [5]

Full text of DOI:10.1021/ja982365d

J. Am. Chem. Soc. 1998, 120, 12359-12360
12359
Complex, 1, was prepared by the literature procedure (eq 1).26a,d
Rapid Luminescent Detection of Phosphate Esters in
Solution and the Gas Phase Using
(dppe)Pt{S2C2(2-pyridyl)(CH2CH2OH)}
Kelly A. Van Houten, Danica C. Heath, and Robert S. Pilato*
UniVersity of Maryland
Department of Chemistry and Biochemistry
College Park, Maryland 20742
The chemical conversion of 1 to [(dppe)Pt{S2C2(CH2CH2-N-2-
pyridinium)}]+, 2, by activated phosphate esters (eq 2) can be
ReceiVed July 6, 1998
Organophosphate inhibitors of acetylcholine esterase (in-
cluding phosphinates and phosphonates) are used as pesticides
and as chemical warfare agents.1-7 As such, their detection over
a range of concentrations and conditions is required and has
attracted considerable attention.8-22 Several detection methods
rely on an immobilized acetylcholine esterase detector coupled
to a transducer (i.e., pH electrodes,5,9,11-13,15,16,22 fiber optics,10,21
and piezoelectric crystals14). Although the immobilized enzymes
are sensitive and detect a broad spectrum of acetylcholine esterase
inhibitors, they lack selectivity and are prone to false positives
when exposed to choline mimics.15,23,24
The rapid detection of volatile fluoro and cyano phosphates is
of particular interest since these are major constituents in the
chemical warfare arsenal. Reported is a new selective method
for the rapid detection of these esters. The method uses a new
platinum 1,2-enedithiolate complex with an appended alcohol that
upon exposure to selected phosphate esters is converted to a room-
temperature lumiphore.25
monitored by the emissions from 2 which have been assigned to
a thiolate to heterocycle π* intraligand charger-transfer singlet,
1ILCT*, and triplet, 3ILCT*. While 1, and 1H+, are nonemissive
(φ < 0.00001), 2 is emissive in room-temperature solution (1φ )
3
0.002, φ ) 0.01, DMSO) and when immobilized in cellulose
3
acetate/triethylcitrate films (1φ ≈ 0.01, φ ≈ 0.2).26
(1) Somani, S. M. Chemical Warfare Agents; Academic Press: San Diego,
1992.
Neutral pyridine-substituted complexes such as (dppe)Pt{S2C2-
(2-pyridyl)(R)} R ) H, and CH2CH2OH, are not emissive due to
a lowest lying d to d transition which leads to rapid nonradiative
decay of emissive excited states.26 However, the emissive
properties of 2 are similar to those of [(dppe)Pt{S2C2(2-pyridini-
um)(H)}]+ suggesting that either the steric bulk or solution
dynamics of the [(dppe)Pt{S2C2(2-pyridinium)(CH2CH2OH)}]+
side-chain increases the nonradiative decay rate. The gross
differences in the photophysical properties of 2 and [(dppe)Pt-
{S2C2(2-pyridinium)(H)}]+ from those of 1H+ could arise from
the necessity for the 1,2-enedithiolate and heterocycle to be
coplanar for emission from the ILCT excited states.26d Whereas
in 2 the 1,2-enedithiolate and heterocycle are held coplanar in
the ground state,26d the ability of the 1,2-enedithiolate and het-
erocycle to be coplanar in the [(dppe)Pt{S2C2(2-pyridinium)(R)}]+
complexes depends on the bulk of the R group, and this could
account for the emission from R ) H and not R ) CH2CH2OH.
Given the chemical reactivity of 1 and combined photophysical
properties of 1 and 2, activated phosphate esters serve to turn on
the emission in this family of complexes. The reaction of 1 with
phosphate, thiophosphate, and phosphinate esters (10-1-10-6 M)
leads to the generation of 2 (eq 2). These reactions can be
followed by exciting a deaerated CH2Cl2 solution at 450 nm and
monitoring the 605 and 710 nm emissions.
(2) Skladal, P. Food Technol. Biotechnol. 1996, 34, 43-9.
(3) Gunderson, C. H.; Lehmann, C. R.; Sidell, F. R.; Jabbari, B. Neurology
1992, 42, 946-50.
(4) Khan, S. U. Pesticides in the Soil EnVironment; Elsevier: Amsterdam,
The Netherlands, 1980.
(5) Hendji, A. M. N.; Jaffrezic-Renault, N.; Martelet, C.; Clechet, P. Anal.
Chim. Acta 1993, 281, 3-11.
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of the Cholinesterase Family; Plenum Press: New York, 1995.
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(9) Tran-Minh, C.; Pandey, P. C.; Kumaran, S. Biosens. Bioelectron. 1990,
5, 461-71.
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M. Fundam. Appl. Toxicol. 1991, 16, 810-20.
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511-6.
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B 1992, 7, 513-7.
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1995, 308, 129-36.
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Am. Chem. Soc. 1986, 108, 5444-7.
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Lett. 1991, 24, 191-8.
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(17) Lenz, D. E.; Brimfield, A. A.; Cook, L. A. In DeVelopment of
Immunoassays for Detection of Chemical Warfare Agents; Lenz, D. E.,
Brimfield, A. A., Cook, L. A., Eds.; American Chemical Society: Washington,
DC, 1997; Vol. 657, pp 77-86.
Sulfonyl chlorides and anhydrides convert 1 to 2 while car-
boxylic acid chlorides and anhydrides convert 1 to the corre-
sponding nonemissive esters. As such, these reagents interfere
with phosphate detection. However, amines and pyridines (com-
mon acetylcholine esterase inhibitors) have essentially no effect
upon this phosphate detection.
(18) Ewing, K. J.; Dagenais, D. M.; Bucholtz, F.; Aggarwal, I. D. Appl.
Spectrosc. 1996, 50, 614-8.
(19) Taranenko, N.; Alarie, J. P.; Stokes, D. L.; VoDinh, T. J. Raman.
Spectrosc. 1996, 27, 379-84.
(20) Polhujis, M.; Langenberg, J. P.; Benschop, H. P. Toxicol. Appl.
Pharmacol. 1997, 146, 156-161.
(21) Anis, N. A.; Wright, J.; Rogers, K. R.; Thompson, R. C.; Valdes, J.
J.; Eldefrawi, M. E. Anal. Lett. 1992, 25, 627-35.
(22) Marty, J. L.; Sode, K.; Karube, I. Electroanalysis 1992, 4, 249-52.
(23) Taylor, P. The Pharmacological Basis of Therapeutics, 7th ed.;
MacMillan Co.: New York, 1985.
(26) (a) Kaiwar, S. P.; Hsu, J. K.; Liable-Sands, L. M.; Rheingold, A. L.;
Pilato, R. S. Inorg. Chem. 1997, 36, 4234-40. (b) Kaiwar, S. P.; Vodacek,
A.; Blough, N. B.; Pilato, R. S. J. Am. Chem. Soc. 1997, 119, 9211-4. (c)
Kaiwar, S. P.; Vodacek, A.; Blough, N. V.; Pilato, R. S. J. Am. Chem. Soc.
1997, 119, 3311-6. (d) Van Houten, K. A.; Heath, D. C.; Barringer, C. A.;
Rheingold, A. L.; Pilato, R. S. Inorg. Chem. 1998, 37, 4647-53.
(24) O’Brien, R. D. Insecticides: Actions and Metabolism; Academic
Press: New York, 1967.
(25) Van Houten, K. A.; Heath, D. C.; Pilato, R. S., patent pending.
10.1021/ja982365d CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/13/1998

12360 J. Am. Chem. Soc., Vol. 120, No. 47, 1998
Communications to the Editor
Table 1. Rates of Conversion of 1 to 2 Relative to the Rate of
(O)P(OEt)2Cl
phosphate ester
(O)P(OEt)2X
rates relative (O)P(OEt)2Cla
X ) F
∼1.1b
1.0
0.71
X ) Cl
X ) CN
(S)P(OEt)2Cl
0.24
(O)P(Me)2Cl
1.1
1.0
0.069
<0.0003
<0.0003
(O)P(OPh)2Cl
(O)P(OPh)(OC6H4p-NO2)2
(O)P(OPh)2(OC6H4p-NO2)
(S)P(OEt)2SPh
a Rates are relative to those required for the conversion of 1 (10-4
M) to 2 in the presence triazole (10-2 M) and 10-3 M (O)P(OEt)2Cl at
20 °C in CH2Cl2. All phosphate ester concentrations are 10-3 M. The
maximum conversions of 1 to 2 are 70-90%. Under the pseudo-first-
order conditions listed, 2 is generated with (O)P(OEt)2Cl at a rate of
1.2 × 10-5 M s-1
.
b Generated from (O)P(OEt)2Cl and benzoyl fluoride
and used without purification.
The relative conversion rates of 1 to 2 by various phosphate
esters (10-3 M) with 1 (10-4 M) and triazole (10-2 M) in CH2Cl2
are shown in Table 1. Triazole, a common reagent used in
phosphorylation strategies,27 serves both to activate the phosphate
and as a base in these reactions. The rates of reaction are
dependent upon the leaving group attached to the phosphate ester.
The relative rates are consistent with a rate-determining step that
involves activation of the phosphate by triazole or addition of
the phosphate to the alcohol. These results are inconsistent with
a rate determining step that involves nucleophilic attack by the
pyridine and loss of a phosphate monoanion. Support for this
assertion is seen in the relative rates (O)P(OPh)2Cl > (O)P(OPh)-
(OC6H4p-NO2)2 . (O)P(OPh)2(OC6H4p-NO2). This is the ex-
pected sequence if initial addition of the phosphate is rate
determining. If phosphate loss were rate determining, the relative
rates should have been (O)P(OPh)(OC6H4p-NO2)2 . (O)P(OPh)2-
(OC6H4p-NO2) ≈ (O)P(OPh)2Cl. Additional support for this
assertion is the rapid conversion of 1 to 2 with (O)P(OEt)2X X
) F,28 Cl and CN. These rates reflect the initial loss of X rather
than the subsequent loss of (O)P(OEt)2O- which is among the
poorest phosphate leaving group in this study. Steric bulk is not
a major factor since the rates for (O)P(OR)2Cl R ) Et are
essentially identical to those of R ) Ph.
Complex 1 was immobilized in cellulose acetate/triethylcitrate
(CA/TEC), RTV-108, and RTV-118 (∼0.5-mm thick films) and
its ability to serve as a gas-phase detector screened (Figure 1).
The polymer/plasticizer ratios of the cellulose acetate/triethylci-
trate films were varied and the P(OEt)2(O)X, X ) Cl, F,28 and
CN detection times monitored (Table 2).25 For the CA/TEC films,
the time required for both minimum detection of the phosphate
as well as for complete conversion of 1 to 2 drops with increasing
plasticizer (TEC) content. The addition of plasticizers to polymers
such as CA are well-known to increase permeability and mobility
of polar analytes.29-34 Detection of the esters was not possible
when the TEC content was below 20% of the CA weight. Using
CA/50% TEC films and monitoring the emission spectra (fol-
lowing 470 nm excitation), the generation of 2 was found to be
linear with phosphate exposure time.
Figure 1. The luminescence spectra of 1 (0.3%/wt) immobilized in a
cellulose acetate/150% triethylcitrate film (0.5 mm thick): (- ‚ ‚ -)
Control film. (- - -) Film exposed to 0.9 g/m3 OP(OEt)2Cl in N2 for 2
min at 50 mL/s. (s) Film exposed to HCl.
Table 2. Exposure Times for the Conversion of 1 to 2 in Various
Polymer/Pasticizer Combinations
minimum
exposure
time (s)e
complete
exposure
time (s)f
polymer/plasticizera phosphate ester
CA
(O)P(OEt)2Clb
(O)P(OEt)2Clb
(O)P(OEt)2Clb
(O)P(OEt)2Clb
(O)P(OEt)2Clb
(O)P(OEt)2Clb
(O)P(OEt)2Clb
(O)P(OEt)2Fc
not observed not observed
CA/25% TEC
CA/50% TEC
CA/100% TEC
CA/150% TEC
GE-RTV108
GE-RTV118
CA/150% TEC
CA/150% TEC
>600
not observed
600
40
15
<15
<15
<15
<30
<15
30
15
180
(O)P(OEt)2CNd <15
a Cellulose acetate (CA), triethylcitrate (TEC). Percentages listed are
for TEC wt % of CA. Loading of 1 is 0.3%/wt. Silicone films were
impregnated in CH2Cl2 solution containing 0.1% NEt3. b (O)P(OEt)2Cl
at 0.093 Torr (0.90 g/m3) in an N2 flow of 50 mL/s. c (O)P(OEt)2F at
0.130 Torr (1.2 g/m3) in an N2 flow 50 mL/s. d (O)P(OEt)2CN at 0.054
Torr (0.88 g/m3) in an N2 flow of 50 mL/s. e Minimum exposure
required for luminescence detection of a deareated sample, 470 nm
excitation, 570 and 675 nm emission. f Minimum exposure required
for maximum absorbance from the film at 470 nm.
platinum 1,2-enedithiolate with an appended alcohol as the sensor
molecule. The volatile fluoro and cyano esters were chosen for
this study since they are suitable mimics for SARIN, SOMAN,
and TABUN,17 three chemical agents in the current arsenal. Our
plans include preparing new molecules with reactive functional
groups similar to those found in 1 and varying the immobilizing
polymer in an attempt to optimize the conditions for fluoro and
cyano phosphonate and phosphate ester detection.
These results demonstrate a new method for detecting volatile
phosphate esters using an immobilized heterocyclic-substituted
Acknowledgment. We thank Professor Neil V. Blough of the
University of Maryland for helpful discussions.
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Supporting Information Available: The preparation and character-
ization of 1 and 2 and the details of phosphate ester detection are available
(3 pages, print/PDF. See any current masthead page for ordering
information and Web access instructions.
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