Billion-fold acceleration of the methanolysis of paraoxon promoted by La(OTf)3 in methanol

Article abstract of DOI:10.1021/ja034979a

The methanolysis of the insecticide paraoxon (2) was investigated in methanol solution containing varying [La(OTf)₃] (OTf = ^-OS(O)₂CF₃) as a function of _s^sPH at 25 °C. Plots of the pseudo-first-order rate constants (k₂obs) for methanolysis as a function of [La(OTf)₃]_total were obtained under buffered conditions from _s^sph 5.15 to 10.97, and the slopes of the linear parts of these were used to determine the second-order rate constants (k₂^obs) for the La³⁺-catalyzed methanolysis of 2. Detailed analysis of the potentiometric titration data of La(OTf)₃ in methanol through fits to a multicomponent equilibrium mixture of dimers of general stoichiometry La³⁺₂(-OCH₃)_n, where n assumes values of 1-5, gives the equilibrium distribution of each as a function of _s^spH. These data, when fit to a second expression describing k₂^obs in terms of a linear combination of individual rate constants k₂^2:1, k₂^2:2.....k₂^2:n for the dimers, allow one to describe the overall catalytic profile in terms of the individual contributions. The most catalytically important species are the three dimers La³⁺₂(^-OCH₃)₁, La³⁺₂(^-OCH₃)₂, and La³⁺₂(^-OCH₃)₃. The catalysis of the methanolysis of 2 is spectacular: a 2 × 10^-3 M solution of [La³⁺]_total, at neutral _s^sPH, affords a 10⁹-fold acceleration relative to the base reaction (t_1/2 ≈ 20 s at _s^sPH 8.2) with excellent turnover. A mechanism of the catalyzed reaction involving the La³⁺₂(^-OCH₃)₂ species is proposed.

Full text of DOI:10.1021/ja034979a

Published on Web 05/28/2003
Billion-fold Acceleration of the Methanolysis of Paraoxon
3
Promoted by La(OTf) in Methanol
Josephine S. Tsang, Alexei A. Neverov, and R. S. Brown*
Contribution from the Department of Chemistry, Queen’s UniVersity, Kingston,
Ontario, Canada K7L 3N6
Received March 4, 2003; E-mail: rsbrown@chem.queensu.ca
Abstract: The methanolysis of the insecticide paraoxon (2) was investigated in methanol solution containing
] (OTf ) -OS(O)
) as a function of pH at 25 °C. Plots of the pseudo-first-order rate
s
s
varying [La(OTf)
3
2
CF
3
3
constants (kobs) for methanolysis as a function of [La(OTf) ]total were obtained under buffered conditions
s
from pH 5.15 to 10.97, and the slopes of the linear parts of these were used to determine the second-
s
obs
3+
order rate constants (k
titration data of La(OTf)
general stoichiometry La
each as a function of pH. These data, when fit to a second expression describing k
combination of individual rate constants k
2
) for the La -catalyzed methanolysis of 2. Detailed analysis of the potentiometric
3
in methanol through fits to a multicomponent equilibrium mixture of dimers of
3+
-
2
( OCH
3
)
n
, where n assumes values of 1-5, gives the equilibrium distribution of
s
s
obs
2
in terms of a linear
2:1
2:2
2:n
2
, k
2
.....k
2
for the dimers, allow one to describe the overall
catalytic profile in terms of the individual contributions. The most catalytically important species are the
3
+
-
3+
-
3+
-
three dimers La
2
( OCH
3 1
) , La
2
( OCH
3
)
2
, and La
2
( OCH
3
)
3
. The catalysis of the methanolysis of 2 is
spectacular: a 2 × 10 M solution of [La3+]total, at neutral pH, affords a 10 -fold acceleration relative to
-
3
s
9
s
s
s
the base reaction (t1/2 ≈ 20 s at pH 8.2) with excellent turnover. A mechanism of the catalyzed reaction
3
+
-
involving the La
2 3 2
( OCH ) species is proposed.
Introduction
fective methods for destruction of organophosphorus materials
are available, none is applicable to all situations or classes of
compounds thus spurring research into alternative methods for
their destruction.
Activated organophosphate, phosphinate, and phosphonate
esters of the general form 1 are potent acetylcholinesterase
1
inhibitors. As such, these have important uses as animal and
2
crop protectants and, more regrettably, as chemical warfare
3
agents. This family includes the insecticides parathion (ROd
ZdOEt; XdS; YdOC6H4NO2) and paraoxon (ROdZdOEt;
XdO; YdOC6H4NO2), as well as the alkylphosphonofluoridate
nerve G-agents, for example, Soman (ROd(CH3)3CCH(CH3)O;
ZdCH3; XdO; YdF) and Sarin (ROd(CH3)2CHO; ZdCH3;
XdO; YdF) and finally the V-agents such as VX (ZdEt; XdO;
YdSCH2CH2N(CH(CH3)2)2). Due to their toxicity and the
attention drawn to them by the 1992 Chemical Weapons
In this report, we focus on a new method for controlled
decomposition of the pesticide paraoxon (2, often used as a
simulant for the G-agents), namely its catalytic methanolysis
3+
3+
-
promoted by La in a methanol medium. The La (OCH3 )
system is one that we have previously reported to promote the
4
Convention Treaty, requiring total destruction of chemical
weapons stockpiles by the signatories, considerable effort has
been directed toward methods of facilitating the controlled
decomposition of organophosphorus materials, particularly
through hydrolysis and oxidation.3 Although some very ef-
6
methanolysis of esters and activated amides such as acetyl
III
7
imidazole and its pentamino-Co derivative. Transition metal
ions and lanthanides have been shown to catalyze the hydrolysis
,5
8
of neutral phosphate and/or phosphonate esters, and Pt and Pd
metallocycles were recently shown to be efficacious for thio-
phosphate pesticide hydrolysis; but, as far as we are aware,
(
1) (a) Main, R. A.; Iverson, F. Biochem. J. 1966, 100, 525. (b) Emsley, J.;
Hall, D. The Chemistry of Phosphorus; Wiley: New York, 1976; p 494.
2) (a) Toy, A.; Walsh, E. N. Phosphorus Chemistry in EVeryday LiVing, 2nd
ed.; American Chemical Society: Washington, DC, 1987; Chapters 18-
9
(
little attention has been directed to the metal ion promoted
10
2
0. (b) Quin, L. D. A Guide to Organophosphorus Chemistry; Wiley: New
alcoholysis of phosphate triesters. Alcoholysis of organophos-
phates such as paraoxon should lead to relatively nontoxic
York, 2000. (c) Gallo, M. A.; Lawryk, N. J. Organic Phosphorus Pesticides.
The Handbook of Pesticide Toxicology; Academic Press: San Diego, CA,
1
991.
(3) (a) Yang, Y.-C.; Baker, J. A.; Ward, J. R. Chem. ReV. 1992, 92, 1729. (b)
(5) Morales-Rojas, H.; Moss, R. A. Chem ReV. 2002, 102, 2497 and references
Yang, Y.-C. Acc. Chem. Res. 1999, 32, 109. (c) Yang, Y.-C. Chem. Ind.
therein.
(London) 1995, 334.
(6) Neverov, A. A.; McDonald, T.; Gibson, G.; Brown, R. S. Can. J. Chem.
2001, 79, 1704.
(
4) Conference on Disarmament. The Convention of the Development, Produc-
tion, Stockpiling and Use of Chemical Weapons and on Their Destruction.
CD/1170. Geneva, August, 1992 (see http://www.dfait-maeci.gc.ca/nndi-
agency/cwc_1-en.asp).
(7) (a) Neverov, A. A.; Brown, R. S. Can. J. Chem. 2000, 78, 1247. (b)
Neverov, A. A.; Montoya-Pelaez, P.; Brown, R. S. J. Am. Chem. Soc. 2001,
123, 210.
7602
9
J. AM. CHEM. SOC. 2003, 125, 7602-7607
10.1021/ja034979a CCC: $25.00 © 2003 American Chemical Society

Acceleration of the Methanolysis of Paraoxon
A R T I C L E S
products,11 and the greater hydrophobicity of the alcoholic
medium may also be advantageous to improve decontamination
methods because of the enhanced solubility of the organophos-
complexing ligands, its demonstrated efficacy in promoting
transesterifications of unactivated carboxylic esters that do not
contain a metal binding site, and the fact that the core of the
PTA enzyme can be substituted with other metal ions such as
3a
phorus substrates. In certain cases, alcoholysis may proceed
with a different selectivity than hydrolysis as is known to be
the case for the uncatalyzed methanolysis of the V-agents, where
2
+
2+
2+
2+
17
Cd , Ni , Co , and Mn without loss of catalytic activity
3
+ -
suggested to us that La 2( OCH3)2 might be able to promote
the methanolysis of neutral phosphate and phosphonate esters.
Herein, we report our preliminary findings that this goal is
-
the reaction with alkoxide proceeds largely to displace the SR
group leading to phosphonate oxyesters.3,12,13
-
3
realized in the case of paraoxon (2) where as little as 10
M
In our previous studies, we proposed that the active form of
9
3+
of 3 can, at 25 °C, promote the methanolysis reaction by ∼10 -
the catalyst was a dimer, La 2(OCH3)2, having the dimethoxy
s
s
bridged structure 3.6 Interestingly, a very recent X-ray structure
of a phosphotriesterase (PTA) isolated from the soil dwelling
bacterium Pseudomonas diminuta shows the active site as
,7
fold relative to the background reaction at a neutral pH of
∼8.5.
Experimental Section
2+
having two Zn ions. These are bridged by a water or hydroxide
and a carboxylated lysine, the metal ions being further ligated
to the protein by four histidine imidazoles and an aspartate
A. Materials. Methanol (99.8% anhydrous), sodium methoxide (0.5
M solution in methanol), La(CF SO ) , and paraoxon were purchased
3 3 3
from Aldrich and used without any further purification. HClO (70%
4
-
14
COO . The dinuclear enzyme core, a feature seen in other
aqueous solution) was purchased from BDH.
15
enzymes that mediate the hydrolysis of phosphate diesters and
1
B. Methods. H NMR spectra were determined at 500 MHz and
16
monoesters, embues on the organism a catalytic efficiency for
referenced to the CD
2
H peak of D
4
methanol appearing at δ 3.31.
the hydrolysis of 2, its preferred substrate, for which the kcat/
+
The CH
3
OH
2
concentration was determined using a Radiometer
8
-1 -1 17
KM value is ∼10 M s .
Vit 90 Autotitrator equipped with a Radiometer GK2322 combination
(glass/calomel) electrode calibrated with Fisher Certified Standard
aqueous buffers (pH ) 4.00 and 10.00) as described in our recent
The putative dinuclear La3 species, 3,6,7 cannot be claimed
to be a “biomimetic” for the active site of the previously
mentioned PTA. However, its dinuclearity, which is spontane-
ously adopted in methanol without the need for sophisticated
+
papers.6
,7,18
Values of
s
s
pH were calculated by adding a correction
19
constant of 2.24 to the experimental meter reading as reported by Bosch
et al.20 The pK values of buffers used for the present kinetic studies
s
s
a
20
were obtained from the literature or measured at half neutralization
of the bases with 70% HClO in MeOH.
(
8) (a) Gellman, S. H.; Petter, R.; Breslow, R. J. Am. Chem. Soc. 1986, 108,
388. (b) Brown, R. S.; Zamkanei, M. Inorg. Chim. Acta. 1985, 108, 201.
c) Kenley, R. S.; Flemming, R. H.; Laine, R. M.; Tse, D. S.; Winterle, J.
2
(
4
C. Kinetics. UV kinetics of methanolysis were monitored at 25 °C
by observing the rate of loss of 2 at 268 nm or by the rate of appearance
S. Inorg. Chem. 1984, 23, 1870. (d) Cooperman, B. S. Met. Ions Biol.
Syst. 1976, 5, 79 and references therein. (e) Menger, F. M.; Gan, L. H.;
Johnson, E.; Durst, H. D. J. Am. Chem. Soc. 1987, 109, 2800. (f) Menger,
F. M.; Tsuno, T. J. Am. Chem. Soc. 1989, 111, 4903. (g) Scrimin, P.; Tecilla,
P.; Tonellato, U. J. Org. Chem. 1991, 56, 161 and references therein. (h)
Tafesse, F. Inorg. Chim. Acta. 1998, 269, 287. (i) Scrimmin, P.; Ghinlanda,
G.; Tecilla, P.; Moss, R. A. Langmuir 1996, 12, 6235. (j) Bunton, C. A.;
Scrimmin, P.; Tecilla, P. J. Chem. Soc., Perkin Trans. 2 1996, 419. (k)
Fujii, Y.; Itoh, T.; Onodera, K. Chem. Lett. Japan 1995, 305. (l) Oh, S. J.;
Yoon, C. W.; Park, J. W. J. Chem. Soc., Perkin Trans. 2 1996, 329. (m)
Berg, T.; Simeonov, A.; Janda, K. J. Comb. Chem. 1999, 1, 96. (n) Morrow,
J. R.; Trogler, W. C. Inorg. Chem. 1989, 28, 2330. (o) Hay, R. W.; Govan,
N. J. Chem. Soc., Chem. Commun. 1990, 714. (p) Bruice, T. C.; Tsubouchi,
A.; Dempcy, R. O.; Olson, L. P. J. Am. Chem. Soc. 1996, 118, 9867. (q)
Ketelar, J. A. A.; Gersmann, H. R.; Beck, M. M. Nature 1956, 177, 392.
9) (a) Kazankov, G. M.; Sergeeva, V. S.; Efremenko. L. A.; Varfolomeev, S.
D.; Ryabov, A. D. Angew. Chem., Int. Ed. 2000, 39, 3117. (b) Kazankov,
G. M.; Sergeva, V. S.; Borisenko, A. A.; Zatsman, A. I.; Ryabov, A. D.
Russ. Chem. Bull. 2001, 50, 1844.
-
5
of p-nitrophenol at 313 or 328 nm at [2] ) 2.04 × 10 M using an
OLIS-modified Cary 17 UV-vis spectrophotometer. The [La(OTf)
3
]
-
6
-3
was varied from 8 × 10 M to 4.8 × 10 M. All reactions were
followed to at least three half-times and found to exhibit good pseudo-
first-order rate behavior. The pseudo-first-order rate constants (kobs) were
evaluated by fitting the absorbance versus time traces to a standard
exponential model.
The kinetics were determined under buffered conditions. Buffers
s
s
were prepared from N,N-dimethylaniline ( pK ) 5.00), 2,6-lutidine
a
s
s
s
(
( pK ) 6.70), N-methylimidazole ( pK ) 7.60), N-ethylmorpholine
s
s
s
a
a
s
(
pK ) 8.60), and triethylamine ( pK ) 10.78). Due to the fact that
a
s
a
3+
added counterions can ion pair with La ions and affect its speciation
in solution,21 ionic strength was controlled through neutralization of
(
10) (a) Wadsworth, W. S. J. Org. Chem. 1981, 46, 4080. (b) Wadsworth, W.
C.; Wadsworth, W. S. J. Am. Chem. Soc. 1983, 105, 1631.
-3
the buffer. The total [buffer] varied between 7 × 10 M and 3 ×
(
11) (a) According to the Sigma-Aldrich Material Safety Data Sheet (P11238509,
-
2
0
9/02/2002), the oral LD50 toxicity of trimethyl phosphate is species
10 M, and the buffers were partially neutralized with 70% HClO
4
dependent and varies between 750 mg/kg and 1676 mg/kg for quail,
mouse, rat, and guinea pig. (b) http://physchem.ox.ac.uk/MSDS/TR/
triethyl_phosphate.html indicates that triethyl phosphate is an irritant with
a lowest published lethal dose of toxicity of 1600 mg/kg for guinea pigs
and rats.
-
-3
to keep the [ClO
4
] at a low but constant value of 5 × 10 M,
which leads to a reasonably constant ionic strength in solution. With
[La3 ] > 5 × 10 M at pH > 7.0, the metal ion was partially
+
-4
s
s
neutralized by adding an appropriate amount of NaOMe to help control
(
12) 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 and references
therein.
(
18) (a) Neverov, A. A.; Brown, R. S. Inorg. Chem. 2001, 40, 3588. (b) Brown,
R. S.; Neverov, A. A. J. Chem. Soc., Perkin Trans. 2 2002, 1039. (c) Tsang,
J.; Neverov, A. A.; Brown, R. S. J. Am. Chem. Soc. 2003, 125, 1559.
19) For the designation of pH in nonaqueous solvents, we use the forms
(
13) Three organophosphonothioates were shown to react with methoxide to
give 93-96% P-S cleavage, while, under similar hydroxide concentrations
1
2
in water, P-S cleavage proceeds to the extent of 74-88%. In the case
(
-
of hydrolysis, the reaction products from P-S cleavage (RP(dO)O (SR′))
20
described by Bosch and co-workers based on the recommendations of
are toxic in their own right and relatively resistant to further reaction, while
the IUPAC, Compendium of Analytical Nomenclature. DefinitiVe Rules
3
P-S cleavage in the methanolysis reactions yields RP(dO)OCH (SR′)
1
997, 3rd ed.; Blackwell: Oxford, U.K., 1998. If one calibrates the
which undergoes further reaction to give RP(dO)(OCH
14) Benning, M. M.; Shim, H.; Raushel, F. M.; Holden, H. M. Biochemistry
001, 40, 2712.
3 2
) .
measuring electrode with aqueous buffers and then measures the pH of an
(
(
w
w
aqueous buffer solution, the term pH is used; if the electrode is
calibrated in water and the “pH” of the neat buffered methanol solution is
then measured, the term s pH is used; and if the latter reading is made and
the correction factor of 2.24 (in the case of methanol) is added, then the
2
15) (a) Lipscomb, W.; Str a¨ ter, N. Chem. ReV. 1996, 96, 2375. (b) Coleman, J.
w
E. Curr. Opin. Chem. Biol. 1998, 2, 222. (c) Cowan, J. A. Chem. ReV.
1
998, 98, 1067. (d) Davies, J. F.; Hostomska, Z.; Hostomsky, Z.; Jordan,
s
S. R.; Mathews, D. A. Science 1991, 252, 88. (e) Beese, L. S.; Steitz, T.
A. EMBO J. 1991, 10, 25. (f) Lahm, A.; Volbeda, S.; Suck, D. J. Mol.
Biol. 1990, 215, 207.
term spH is used.
(20) (a) Bosch, E.; Rived, F.; Ros e´ s, M.; Sales, J. J. Chem. Soc., Perkin Trans.
2 1999, 1953. (b) Rived, F.; Ros e´ s, M.; Bosch, E. Anal. Chim. Acta 1998,
374, 309. (c) Bosch, E.; Bou, P.; Allemann, H.; Ros e´ s, M. Anal. Chem.
1996, 3651.
(
16) Gani, D.; Wilke, J. Chem. Soc. ReV. 1995, 24, 55.
(
17) Omburo, G. A.; Kuo, J. M.; Mullens, L. S.; Raushel, F. M. J. Biol. Chem.
1
992, 267, 13278.
(21) Gibson, G.; Neverov, A. A.; Brown, R. S. Can. J. Chem. In press.
J. AM. CHEM. SOC.
9
VOL. 125, NO. 25, 2003 7603

A R T I C L E S
Tsang et al.
Table 1. Observed Second-Order Rate Constants for the
La3 -Catalyzed Methanolysis of 2 at Various pH Values,
+
s
s
T ) 25 °C
s
s
obs,a M-1 s-1
pH
k
2
5
5
5
6
7
7
7
8
8
.15
.58
.82
.69
.10
.30
.72
.23
.96
0.065 ( 0.002
0.11 ( 0.01
0.28 ( 0.02
1.07 ( 0.04
2.4 ( 0.1
5.6 ( 0.1
11.3 ( 0.5
17.5 ( 0.5
23.2 ( 0.9
11.4 ( 0.8
5.4 ( 0.4
1
1
0.34
0.97
a
k2obs determined from slope of the kobs vs [La3+]total plots at higher
+
s
[
La3 ] at each pH.
s
3
+
Figure 1. Plot of kobs vs [La(OTf)3] for the La -catalyzed methanolysis
-
5
s
s
s
s
of paraoxon (2.04 × 10 M) at 25 °C, pH 8.96, (9); pH 8.23, (O); and
s
s
pH 7.72 (b).
s
s
s
the spH at the desired value. pH measurements were performed
before and after each experiment, and in all cases, the values were
consistent to within 0.1 units.
D. 31P NMR Experiment to Ascertain Turnover. To 2 mL of dry
methanol at ambient temperature was added N-ethylmorpholine (25.5
µL or 23 mg), half neutralized with 11.4 M HClO
4
(8.6µL) so that the
final total buffer concentration was 0.1 M. To this was added 16.0 mg
31
of paraoxon. The P NMR spectrum showed a single signal at δ -6.35
ppm. To the resulting mixture was added 12.9 mg of La(O SCF and
0 µL of 0.5 M NaOCH in methanol solution. At this point, the
concentration of paraoxon was 0.057 M and that of La(O SCF was
.011 M, and the measured pH of the methanol solution is 8.75,
3
3 3
)
4
3
3
3 3
)
s
0
s
essentially neutrality. The solution was allowed to stand for 10 min,
3
1
after which time the P NMR spectrum indicated the complete
disappearance of the paraoxon signal and the appearance of a new signal
at δ 0.733 ppm. The H NMR spectrum of the same solution also
Figure 2. Plot of the log k2obs vs pH for the La3+-catalyzed methanolysis
s
s
1
of 2 at 25 °C. Dashed line through the data was computed on the basis of
indicated the complete disappearance of the starting material and full
speciation and rate constants derived for various active species; see text.
release of free p-nitrophenol.
that the final concentration of lanthanum ion was 0.011 M and
Results
s
the measured pH was 8.75, essentially neutrality.
s
A. Kinetics. Shown in Figure 1 are three representative plots
of the pseudo-first-order rate constants (kobs) for the methanolysis
of 2 as a function of added [La(OTf)3] at pH 7.72, 8.23, and
31
After 10 min, the P NMR spectrum indicated the complete
disappearance of the paraoxon signal and the appearance of a
s
s
new signal at δ 0.733 ppm, attributed to diethyl methyl
3
+
1
8
.96. As was observed in our earlier studies of the La -
phosphate, and the H NMR spectrum indicated the full release
6
7
catalyzed methanolysis of esters and acetyl imidazole, these
plots exhibit two domains, a nonlinear one at low [La ]
suggestive of a second-order behavior in La , followed by a
linear domain at higher [La ]. Following the approach we have
of free p-nitrophenol.
3
+
The previously mentioned experiment shows that 10 turnovers
of 2 occurred relative to the La dimers formed in situ, thus
indicating the true catalytic nature of those species.
3+
3+
6
,7
3+
used before, we used the linear portion of these plots to
C. Speciation of La in Methanol. Recently, we presented
obs
calculate the observed second-order rate constants (k2 ) for
a study of the potentiometric titration of nine lanthanide metal
3+
s
s
2+
2+
2+
2+
4+
the La -catalyzed methanolysis of 2 at the various pH
ions as well as Zn , Cu , Co , Ni , and Ti in methanol
2
1
3+
values. These are tabulated in Table 1 and graphically presented
in Figure 2 as a log k2 versus pH plot, which is seen to have
solution. In the case of La , the titration data were obtained
obs
s
s
-3
under various conditions from 1 × 10 M e [La(OTf) ] e
3
s
s
-
3
a skewed bell-shape, maximizing at pH ≈ 9. (For original kobs
3 × 10 M, which is within the concentration range where
3+
3+
vs [La ] kinetic data, see Tables S1-S11, Supporting Informa-
tion).
the kinetic plots of kobs versus [La ] in this study are linear.
The potentiometric titration data were successfully analyzed with
B. 31P and H NMR Turnover Experiments. A 2 mL
aliquot of methanol NMR solution containing 0.1 M N-
ethylmorpholine buffer and 0.057 M paraoxon was formulated
as described in the Experimental Section. The 3 P NMR
spectrum of this showed a single signal at δ -6.35 ppm. To
the resulting mixture was added La(O3SCF3)3 and NaOCH3, so
1
the computer program Hyperquad through fits to the dimer
22
model presented in eq 1 where n assumes values of 1-5, to
s
s
give the various stability constants ( K ) that are defined in
n
1
(
22) The potentiometric data are fit using the computer program Hyperquad
000 (version 2.1 NT). Gans, P.; Sabatini, A.; Vacca, A. Talanta 1996 43,
1739.
2
7604 J. AM. CHEM. SOC.
9
VOL. 125, NO. 25, 2003

Acceleration of the Methanolysis of Paraoxon
A R T I C L E S
Table 2. Computed Second-Order Rate Constants for Various
3+
-
Dimeric Forms, La 2( OCH3)n, Catalyzing the Methanolysis of 2
obs
as Determined from Fits of k2 Data in Table 1 to Equation 3,
-
3
[
La(OTf)3]total ) 2 × 10 M, T ) 25 °C
2:1 2:2 2:3
2:4
k
2
k
2
k
2
k
2
(M- s-1
1
)
(M-1 s-1
)
(M-1 s-1
)
(M-1 s-1
)
R2
fit no.
1a
15.9 ( 3.2 49.8 ( 2.2
67.2 ( 36.0 8.8 ( 11.2 0.9976
b
2
18.4 ( 5.4 47.2 ( 2.4 110.4 ( 11.8
51.4 ( 2.8 103.4 ( 17
0.9861
0.9664
c
3
a
3+
-
3+ -
Including all dimeric forms except La 2( OCH3)0 and La 2( OCH3)6.
2:5
-1 -1 b
Computed value of k2 ) -3.4 ( 10.8 M
s
.
Computed without the
2
:4
2:5 c
involvement of k2 and k2
. Computed without the involvement of
2
:1
2:4
2:5
k2 , k2 , and k2
.
3
+
the presence of [La ] with an observed second-order rate
obs
-1 -1
s
s
constant, k2 , of ∼17.5 M
s
at the near neutral pH of
8
.23 (see Table 1). When it is assumed that the methoxide
reaction persists at pH 8.23, the acceleration afforded to the
s
s
s
s
-3
methanolysis of paraoxon at that pH by a 2 × 10 M solution
Figure 3. Speciation diagram for the distribution of La3 2( OCH3)n forms,
+
-
9
24
of La(OTf)3 is an impressive 1.1 × 10 -fold having a t1/2 of
s
s
22
n ) 1-5, as a function of pH. Speciation calculated for [La(OTf)3] )
2
0 s.
In the absence of additional information, the previous data
do not explicitly point to the nature of the catalytic species other
-
3
2
× 10 M. Data represented as (b) correspond to second-order rate
obs 3+
constants (k2 ) for the La -catalyzed methanolysis of 2 presented in
Table 1.
3
+
than its requiring La . As shown in Figure 2, the reactivity of
2
1
s
s
eq 2. On the basis of the five computed stability constants,
the catalytic species increases with pH up to ∼9.0 indicating
s
s
log K
) 11.66 ( 0.04, 20.86 ( 0.07, 27.52 ( 0.09,
1-5
the involvement of at least one methoxide, although the general
shape of the plot suggests the catalytic involvement of more
3
4.56 ( 0.20, and 39.32 ( 0.26, we constructed the speciation
diagram shown in Figure 3 which presents the distribution of
obs
than one species, vide infra. Since the second-order k2 values
3
+
-
s
s
s
s
the various La 2( OCH3)n forms as a function of pH at
[
3+
for the La -catalyzed reactions in the neutral pH region are
La(OTf)3]total ) 2 × 10-3 M.
OCH3
some 1000- to 2300-fold larger than the methoxide k2
, the
s
role of the metal ion is not to simply decrease the pK of any
s
a
3
+
-
3+
-
La ( OCH ) h 2La + nOCH3
(1)
(2)
bound CH3OH molecules that act as nucleophiles. This points
to a dual role for the metal, such as acting as a Lewis acid and
source of the nucleophile, as was suggested in our earlier
2
3 n
s
s
3+
-
3+ 2
- n
3
K ) [La ( OCH ) ]/[La ] [OCH ]
n
2
3 n
6
,7
work.
obs
Also included in Figure 3 as (b) are the k2 data for the
La -catalyzed methanolysis of 2 which predominantly coincide
with the pH distribution of La 2( OCH3)2 but with an
indication that higher order species such as La 2( OCH3)3 and/
or La 2( OCH3)4 have some activity. To determine the
activities for the various La 2( OCH3)n, we analyze the k2
Detailed mechanistic evaluation of our kinetic data requires
additional information such as the stoichiometries and concen-
3+
s
s
3+ -
3
+
trations of various La -containing species that are formed as
3+
-
s
3+
a function of both pH and [La ]. Recent reports from Jurek,
s
3
+
-
25
26
Jurek, and Martell and G o´ mez-Tagle and Yatsimirski deal
with the pH-dependent speciation in multicomponent equilibria
involving metal ions as well as the catalytic viability of the
species. In that work, as well as in the work reported here,
3+
-
obs
data as a linear combination of individual rate constants (eq 3)
where k22 , k2 ......k2 are the second-order rate constants for
:1
2:2
2:n
2
1,22
the methanolysis of 2
computer fitting of potentiometric titration data
to various
models allows one to determine the concentration of metal-
k2 ) (k2 [La3+ ( OCH ) ] + k [La3+ ( OCH ) ] + ...
obs
2:1
-
2:2
2
-
x+
containing species as a function of both pH and [M ]. We have
2
3 1
2
3 2
2
1
3+
chosen to analyze the titration data for a [La ]total of 2 ×
M, which is in the general concentration range where the
kinetic behavior of the methanolysis of 2 is linearly dependent
(3)
-
3
1
0
k2 [La3+ ( OCH ) ])/[La(OTf) ]
2
:n
-
2
3 n
3 t
3
+
on [La ] and, thus, largely controlled by dimeric species. The
titration data are satisfactorily fit to the series of equilibria shown
in eq 1 where there are five proposed dimers of general form
promoted by the various dimeric forms. Given in Table 2 are
the best-fit rate constants produced by fitting under various
assumptions.
3
+
-
21
La ( OCH ) , n ) 1-5. According to this model, which
2
3 n
generates the speciation diagram shown in Figure 3, the two
Discussion
dominant species have even numbers of attached methoxides;
3+
s
s
In the absence of La , the methoxide promoted reaction of
3+ -
La 2( OCH3)2 between pH 8 and 10 (maximum concentra-
OCH
s
s
2
M
1
proceeds with the second-order rate constant, k2
3
, of 0.011
3+ -
tion of ∼80% at pH 8.9), and La 2( OCH3)4 between pH 10
s
s
-1
-1
-2
s
determined from 1 × 10 M e [NaOCH3] e 4 ×
0- M. The methanolysis of 2 is markedly accelerated in
2
23
(24) Neutral pH in methanol is ∼8.4, and the accelerations at lower and higher
s
s
s
s
9
s
s
pH values are also impressive, being 2.3 × 10 -fold at pH 7.72 and
8
s
s
(
23) The pseudo-first-order rate constants for the reaction of 2 with 1.00, 2.00,
2.7 × 10 -fold at pH 8.96.
-2
-5
-4
and 4.00 × 10 M NaOCH
3
are 9.65 × 10 , 2.09 × 10 , and 4.50 ×
(25) Jurek, P. E.; Jurek, A. M.; Martell, A. E. Inorg. Chem. 2000, 39, 1016.
-4
-1
1
0
s
at 25 °C.
(26) G o´ mez-Tagle, P.; Yatsimirsky, A. K. Inorg. Chem. 2001, 40, 3786.
J. AM. CHEM. SOC.
9
VOL. 125, NO. 25, 2003 7605

A R T I C L E S
Tsang et al.
Scheme 1 a
a
Methanols of solvation omitted for clarity.
A. Proposed Mechanism. We have shown above that La3
+
in methanol is a remarkably effective catalyst for the decom-
position of paraoxon and that there are three dimeric species
s
s
s
Figure 4. Plot of the predicted k2obs vs. pH rate profile for the
which have maximal activities at different pH values. Of
s
3+
3+ -
La -catalyzed methanolysis of 2 (s s s) based on the kinetic contributions
these, the highest activity is attributed to La 2( OCH3)2
operating most effectively in the neutral pH region between
.7 and 9.2 (neutral pH in methanol is 8.4). Given in Scheme
1 is a proposed mechanism by which La 2( OCH3)2, as a bis-
3
+
-
3+
-
3+ -
of La 2( OCH3)1 (- - -); La 2( OCH3)2 (ss); and La 2( OCH3)3
s
s
‚ - ‚ - ‚ -) computed from the k22:1, k2 , and k2 rate constants (Table 2)
2:2
2:3
(
s
s
7
and their speciation (Figure 3). Square data points (9) are experimental
obs
3+ -
k2 rate constants from Table 2.
methoxy bridged dimer, promotes the methanolysis of 2.
Although none of our kobs versus [La ] kinetics profiles show
s
3
+
and 12 (maximum concentration of ∼80% at pH 11). La
s
3+
-
dimers with odd numbers of methoxides, La 2( OCH3)1 and
saturation behavior indicative of formation of a strong complex
3
+
-
3+
La 2( OCH3)3, are also present to a lesser extent, and their
maximum concentration of ∼25% each is reached at respective
between 2 and La , given the well-known coordinating ability
27
of trialkyl phosphates to lanthanides and actinides, the first
s
s
3+ -
pH values of 7.5 and 10.
2 3 2
step probably involves transient formation of a 2:La ( OCH )
Having established the species distribution as a function of
complex (4).
It is unlikely that a methoxy group bridged between two La3
ions, as in 4, is sufficiently nucleophilic to attack the coordinated
s
s
obs
+
pH, we analyzed the kinetic data by fitting the k2 for the
3+
La -catalyzed methanolysis of 2 (Table 1) to eq 3 to determine
best fit rate constants (k22 ) for each of the La 2( OCH3)n
:n
3+
-
28
3+
-
3+
phosphate, so we propose that one of the La - OCH -La
3
3+
-
species. In Table 2 are presented the best-fit constants along
bridges opens to reveal a singly coordinated La - OCH
3
2
with the R values for three fits of varying restriction. Fit #1
adjacent to a Lewis acid-coordinated phosphate (5) which then
undergoes intramolecular nucleophilic addition (6) followed by
ejection of the p-nitrophenoxy leaving group to give 7.
includes all species and has the best correlation coefficient but
generates values for k22:5 and k2 which are, respectively,
negative and with excessive error, such that one can reasonably
2:4
3
+ -
La ( OCH ) is regenerated from 7 by a simple deprotonation
2
3 2
exclude La3 2( OCH3)5 and La 2( OCH3)4 as being catalyti-
+
-
3+ -
of one of the methanols of solvation and dissociation of the
phosphate product, (EtO) P(O)OCH .
cally important. Fit #2 omits those terms generating three kinetic
2
3
3
+
-
3+
-
3+
constants for the La 2( OCH3)1, La 2( OCH3)2, and La 2-
There are well-accepted stereochemical requirements for
phosphoryl transfer that generally involve an apical attack of
the nucleophile, a pseudorotation within the five-coordinate
-
3+ -
(
OCH3)3, while Fit # 3 considers only the La 2( OCH3)2 and
3
+
-
2:1
La 2( OCH3)3 terms, omitting k2 as a trial because of its
relatively large uncertainty from Fit #2. Fits #2 and #3 become
progressively worse than Fit #1, at least on the basis of the
2
9
intermediate, and an apical departure of the leaving group.
3+
These requirements may place constraints on the La -catalyzed
2
decreasing R value, but each agrees that the two kinetically
3
+
-
3+ -
dominant forms are La 2( OCH3)2 and La 2( OCH3)3.
In Figure 4 are presented kinetic plots for all three species
(27) (a) Petrova, J.; Momchilova, S.; Haupt, E. T. K.; Kopf, J.; Eggers, G.
Phosphorus, Sulfur Silicon and Relat. Elem. 2002, 177, 1337. (b) Peterman,
D. R.; Fox, R. V.; Rollins, H. W. Abstract of Papers, 223rd ACS National
Meeting, Orlando, FL, April 7-11, 2002; American Chemical Society:
Washington, DC, 2002; NUCL-131. (c) Ferraro, J. R.; Herlinger, A. W.;
Chiarizia, R. Sol. Extract and Ion Exch. 1998, 16, 775. (d) Du Preez, R.;
Preston, J. S. S. Afric. J. Chem. 1986, 39, 137. (e) Peppard, D. F.; Mason,
G. W.; Driscoll, W. J.; McCarty, S. J. Inorg. Nuclear Chem. 1959, 12,
141. (f) Lebedeva, E. N.; Zaitseva, M. G.; Galaktionova, O. V.; Bystrov,
L. V.; Korovin, S. S. Koordinatesionnaya Khimiya 1981, 7, 870. CAN
95:87058. (g) Galaktionova, O. V.; Lebedeva, E. N.; Yastrebov, V. V.;
Korovin, S. S. Zhurnal Neorganicheskoi Khimii 1980, 25, 2660. CAN 93:
La3+2( OCH3)1, La 2( OCH3)2, and La 2( OCH3)3) based
-
3+
-
3+ -
(
on their second-order rate constants for the catalyzed metha-
s
nolysis of 2 and their concentrations as a function of pH.
s
s
Their combined reactivities as a function of pH give the
s
obs
s
s
predicted log k2 versus pH profile shown as the dashed line
in Figure 4. The computed line is also presented on the log
s
s
2
26562. (h) Pyartman, A. K.; Kopyrin, A. A.; Puzikov, E. A.; Bogatov, K.
obs
k2 versus pH plot in Figure 2. Included in Figure 4 as 9
B. Zhurnal Neorganicheskoi Khimii 1996, 41, 347. CAN 125:124905. (i)
Pyartman, A. K.; Kopyrin, A. A.; Puzikov, E. A.; Bogatov, K. B. Zhurnal
Neorganicheskoi Khimii 1996, 41, 686. CAN 126:11927. (j) Pyartman, A.
K.; Keskinov, V. A.; Kovalev, S. V.; Kopyrin, A. A Radiochemistry
symbols are the actual experimentally determined values which
fit on the computed profile with remarkable fidelity, strongly
indicating that these three species are responsible for the
(
Moscow) (Translation of Radiokhimiya) 1997, 39, 142 CAN 127:210889
AN 1997:471873.
s
s
3+ -
observed activity. At pH values below 9, the La 2( OCH3)2
(28) (a) Williams, N. H.; Cheung, W.; Chin, J. J. Am. Chem. Soc. 1998, 120,
8079. (b) Wahnon, D.; Lebuis, A.-M.; Chin, J. Angew. Chem., Int. Ed.
Engl. 1995, 34, 2412.
(29) Thatcher, G. R. J.; Kluger, R. AdV. Phys. Org. Chem. 1989, 25, 99-265.
s
complex accounts for essentially all the activity, while, at pH
0 and above, the dominantly active form is La3 2( OCH3)3.
s
+
-
1
7606 J. AM. CHEM. SOC.
9
VOL. 125, NO. 25, 2003

Acceleration of the Methanolysis of Paraoxon
A R T I C L E S
methanolysis of phosphate esters which are not specifically
addressed in Scheme 1 at this time. Some light on this question
neutrality, can be used to promote the methanolysis of paraoxon
9
s
with a 10 -fold acceleration over the base reaction at that pH.
s
3+
may be shed by comparison of the La -catalyzed methanolysis
of carboxylic esters and phosphate triesters. It is particularly
As far as we know, this system provides the largest reported
acceleration for any man-made catalyst capable of promoting
the solvolysis of a phosphate triester. Through the joint
interesting to us that La3 2( OCH3)2 can catalyze the metha-
nolysis of carboxylic esters with both good and poor leaving
groups, as exemplified by its k2 value for the methanolysis of
+ -
3
+
consideration of the kobs versus [La ] kinetics and a detailed
3+
analysis of the potentiometric titration data for La in methanol,
we have determined that the dominant species in solution are
-
1
-1
-1
p-nitrophenyl acetate (72 M s ) and ethyl acetate (0.14 M
-1
6
3+
3+ -
s ). However, La catalysis of the methanolysis of phosphate
triesters shows a great discrimination between good and poor
leaving groups. This is exemplified by the fact that the k2 value
dimers of the general formula La ( OCH ) where n ) 1-5,
2
3 n
3+ -
3+
-
and three of these dimers, La ( OCH ) , La ( OCH ) , and
2
3 1
2
3 2
3
+ -
La ( OCH ) , account for all the catalytic activity with
La ( OCH ) being the most important at pH < 9. Interest-
2
3 3
-1
-1
3+
-
s
s
for paraoxon is 50 M s , comparable to that for p-nitrophenyl
2
3 2
6
acetate, but the k2 value for trimethyl phosphate is 5 × 10 fold
ingly, one cannot come to this conclusion considering only the
-
6
-1 -1 30
3+
s
lower at 9.7 × 10
M
s . In the case of the methanolysis
kobs versus [La ] kinetic data. The pH profile of the second-
s
obs
3+
of carboxylic and phosphate triesters, good leaving groups can
depart from the intermediates without additional assistance by
the metal ion as a Lewis acid aiding departure. However, by
order observed catalytic rate constant (k2 ) for the La -
promoted methanolysis of 2 has a slope close to unity in the
s
s
low pH domain, as shown in Figure 2. Cursory consideration
3+
microscopic reversibility, a La -catalyzed delivery of meth-
of those data leads to the erroneous conclusion that the activated
3+
oxide via a putative La -OCH3 requires that the expulsion of
a poor leaving group (ethoxide or methoxide) be catalyzed
through coordination to La3 which seems to be the case for
carboxylic esters. Apparently, for the less sterically demanding
-
complex of the catalyst and phosphate contains a single OCH3,
s
s
with a bell-shaped activity profile. In reality, the pH depen-
+
dence of the metal ion is such that several complexes are present
with their individual concentrations maximized at different
3
+
s
s
intermediates involved in the transacylation of esters, the La
dimer can accommodate the tetrahedral geometries imposed.
However, in the transesterification of phosphates, the La
pH values. It is only through complementary analyses of the
kinetic and potentiometric titration data that one can satisfac-
torily explain the kinetic behavior of complex mixtures having
several pH-dependent forms.
3
+
dimer, although capable of delivering the nucleophile, may not
be geometrically suitable to assist in the departure of a poor
leaving group from the apical position of the more extended
trigonal-bipyramidal intermediate.
Acknowledgment. The authors gratefully acknowledge the
financial support of the Natural Sciences and Engineering
Research Council of Canada and Queen’s University.
Conclusions
Supporting Information Available: Tables S1-S11. Ob-
In the above, we have demonstrated that a methanol solution
3+
served pseudo-first-order rate constants for the La -catalyzed
containing 2 × 10-3 M La(OTf)3, at pH values around
s
s
s
methanolysis of 2 under various conditions of pH and varying
s
3
+
[
La ], (6 pages, print/PDF). This material is available free of
(
30) Determined by 1H NMR analysis of the reaction of d
-methanol solvent
4
2
-
-2
containing 1.3 × 10 M NaOCH
3
and La(OTf)
3
and 8.18 × 10
M
charge via the Internet at http://pubs.acs.org.
s
s
trimethyl phosphate, pH ≈ 8.5, ambient temperature, which generates 2%
3
of CH OH product over the course of 90 h.
JA034979A
J. AM. CHEM. SOC.
9
VOL. 125, NO. 25, 2003 7607