Synergistic catalysis of dimetilan hydrolysis by metal ions and organic ligands

Article abstract of DOI:10.1021/es0009673

Hydrolysis of the insecticide dimetilan, which possesses a N,N-dimethylcarbamate moiety and a N,N-disubstituted urea moiety, has been used to explore metal ion-organic ligand synergistic effects on the degradation of agrochemicals. Dimetilan hydrolysis is strongly catalyzed by +II transition metal ions exhibiting strong affinities for nitrogen- and oxygen-donor ligands (Ni(II), Cu(II), and Zn(II)) but not Pb(II), which exhibits only a weak affinity. Comparisons among these four metal ions strongly suggest that metal ion coordination of dimetilan is necessary for catalysis to occur. A combined mechanism of metal ion coordination of dimetilan and the generation of a MeOH⁺ nucleophile is most plausible for the metal-catalyzed hydrolysis. In the absence of metal ions, citric acid (CIT), ethylenediamine (EN), and N-(2-hydroxyethyl)ethylenediamine (HEEN) ligands alone do not affect dimetilan hydrolysis. However, addition of these ligands significantly changes the catalytic effect of metal ions. CIT and EN reduce the capability of free metal ions to catalyze agrochemical hydrolysis. In contrast, HEEN enhances the catalytic effect of metal ions on dimetilan hydrolysis. The hydroxyl group of HEEN is believed to facilitate metal ion catalysis by acting as an intramolecular nucleophile or general base catalyst within the dimetilanmetal ion-HEEN ternary complex. This study provides a few examples of many possible synergistic/cooperative effects of metal ions and organic ligands in the environment often demonstrated in biological systems such as extracellular enzymes.Hydrolysis of the insecticide dimetilan, which possesses a N,N-dimethylcarbamate moiety and a N,N-disubstituted urea moiety, has been used to explore metal ion-organic ligand synergistic effects on the degradation of agrochemicals. Dimetilan hydrolysis is strongly catalyzed by +II transition metal ions exhibiting strong affinities for nitrogen- and oxygen-donor ligands (Ni^II Cu^II, and Zn^II) but not Pb^II, which exhibits only a weak affinity. Comparisons among these four metal ions strongly suggest that metal ion coordination of dimetilan is necessary for catalysis to occur. A combined mechanism of metal ion coordination of dimetilan and the generation of a MeOH⁺ nucleophile is most plausible for the metal-catalyzed hydrolysis. In the absence of metal ions, citric acid (CIT), ethylenediamine (EN), and N-(2-hydroxyethyl)ethylenediamine (HEEN) ligands alone do not affect dimetilan hydrolysis. However, addition of these ligands significantly changes the catalytic effect of metal ions. CIT and EN reduce the capability of free metal ions to catalyze agrochemical hydrolysis. In contrast, HEEN enhances the catalytic effect of metal ions on dimetilan hydrolysis. The hydroxyl group of HEEN is believed to facilitate-metal ion catalysis by acting as an intramolecular nucleophile or general base catalyst within the dimetilan-metal ion-HEEN ternary complex. This study provides a few examples of many possible synergistic/cooperative effects of metal ions and organic ligands in the environment often demonstrated in biological systems such as extracellular enzymes.

Full text of DOI:10.1021/es0009673

Environ. Sci. Technol. 2000, 34, 4117-4122
Synergistic Catalysis of Dimetilan
Hydrolysis by Metal Ions and
Organic Ligands
C H I N G - H U A H U A N G * A N D
A L A N T . S T O N E
Department of Geography and Environmental Engineering,
The Johns Hopkins University, Baltimore, Maryland 21218
Hydrolysis of the insecticide dimetilan, which possesses a
N,N-dimethylcarbamate moiety and a N,N-disubstituted
urea moiety, has been used to explore metal ion-organic
ligand synergistic effects on the degradation of agrochemicals.
Dimetilan hydrolysis is strongly catalyzed by +II transition
metal ions exhibiting strong affinities for nitrogen- and
FIGURE 1. The hydrolysis pathways of dimetilan.
II
II
II
II
oxygen-donor ligands (Ni , Cu , and Zn ) but not Pb , which
exhibits only a weak affinity. Comparisons among these
four metal ions strongly suggest that metal ion coordination
of dimetilan is necessary for catalysis to occur. A combined
mechanism of metal ion coordination of dimetilan and
O or OH-).
2
chemical or with the attacking nucleophile (e.g., H
In other situations, dissolved metal ions and metal oxides
decrease the hydrolysis rates of agrochemicals (8, 9).
Synergistic effects, which have received little attention in
the past, can be addressed using dual-amendment experi-
ments. Simultaneous addition of a metal ion and an organic
ligand results in the formation of metal-ligand complexes
which may react in ways quite distinct from the free metal
ion or free ligand. The importance of such synergistic effects
depends on the concentrations of metal-ligand complexes
in environmental media and their inherent reactivity.
Dissolved metal ions in aqueous environmental media
have been discussed recently (1, 8). As far as organic ligands
are concerned, appreciable concentrations of low-molecular
weight organic acids (e.g., oxalic acid and citric acid (10)),
monosaccharides (e.g., glucose and fructose (11)) and sugar
acids have been detected in soil waters and surface waters.
Hydroxamate siderophores (12) and aminocarboxylate sid-
erophores (e.g., mugineic acid (13) and rhizoferrin (14, 15))
are produced by organisms as diverse as bacteria, fungi, and
plants to coordinate iron(III). Other organism-derived organic
ligands and metal-organic ligand complexes, including
porphyrins and hydrolytic enzymes, have also been identified
in soils and waters (16-18). The identified extracellular
hydrolytic enzymes include protease, esterase, phosphatase,
and urease.
+
the generation of a MeOH nucleophile is most plausible
for the metal-catalyzed hydrolysis. In the absence of
metal ions, citric acid (CIT), ethylenediamine (EN), and N-(2-
hydroxyethyl)ethylenediamine (HEEN) ligands alone do
not affect dimetilan hydrolysis. However, addition of these
ligands significantly changes the catalytic effect of
metal ions. CIT and EN reduce the capability of free
metal ions to catalyze agrochemical hydrolysis. In contrast,
HEEN enhances the catalytic effect of metal ions on
dimetilan hydrolysis. The hydroxyl group of HEEN is believed
to facilitate metal ion catalysis by acting as an intramolecular
nucleophile or general base catalyst within the dimetilan-
metal ion-HEEN ternary complex. This study provides a few
examples of many possible synergistic/cooperative
effects of metal ions and organic ligands in the environment
often demonstrated in biological systems such as
extracellular enzymes.
Natural chemical and biological processes continually
rework the organic carbon pool, generating new organic
chemicals with distinctive properties. The higher molecular
weight, polyelectrolyte fraction is referred to as humic
substances. Hydrolysis in the presence of humic substances
has been studied in the absence of added metal ions (19);
the effects were found slight.
Introduction
Hydrolysis is believed to be the predominant degradation
pathway for a number of important agrochemicals under
field conditions. Hydrolysis rates measured in the laboratory,
however, often differ significantly from rates measured in
field test plots. This finding leads to the hypothesis that simple
aqueous media commonly employed in the laboratory (e.g.,
distilled water plus the agrochemical with a pH buffer) lack
chemical or biological constituents that catalyze or inhibit
hydrolysis under field conditions. As far as chemical con-
stituents are concerned, single-amendment experiments have
shown that dissolved metal ions (1), simple hydrous metal
oxides (2-5), and clays (6, 7) can increase hydrolysis rates
of agrochemicals dramatically. Catalysis may arise from
reaction of the added chemical constituent with the agro-
In this work, hydrolysis of the insecticide dimetilan (Figure
1
) is used to explore metal ion-organic ligand synergistic
effects. In common with early carbamate insecticides such
as pirimicarb, dimetilan possesses a N,N-dimethylcarbamate
moiety that inhibits cholinesterase enzymes (20). Hydrolysis
can occur via nucleophilic attack at this carbamate group or
at the substituted urea group (Figure 1). Four divalent metal
II
II
II
II
ions, Ni , Cu , Zn , and Pb , are included in this study.
Although these metal ions are probably not found at high
concentrations in most environments except in certain local
situations, the four metal ions possess distinctive chemical
properties that provide insight regarding mechanisms of
catalysis. Note that copper ranks third in fungicide use in the
*
Corresponding author phone: (404)894-7694; fax: (404)894-8266;
e-mail: ching-hua.huang@ce.gatech.edu. Present address: School
of Civil and Environmental Engineering, Georgia Institute of Tech-
nology, Atlanta, GA 30332.
1
0.1021/es0009673 CCC: $19.00

2000 Am erican Chem ical Society
VOL. 34, NO. 19, 2000 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
9
4 1 1 7
Published on Web 08/25/2000

Coordination of the central metal ion by an organic ligand
can alter the tendency of any remaining coordinated water
molecules to undergo deprotonation. Macrocyclic polyamines,
for example, have been observed to influence catalysis via
Mecha nism 2 by raising or lowering the log*K
1
associated
with the Me2 + H
+
O ) MeOH + H reaction (29, 30).
+
+
2
Hydroxyl groups acting in concert with metal ions have
been shown to participate in synergistic effects on hydrolysis
(31, 32) and transesterification (33, 34) reactions. The hydroxyl
group (analogous to serine within metalloenzymes) under-
goes metal ion-assisted deprotonation and subsequently
serves as an intramolecular nucleophile within a metal ion-
ligand-substrate ternary complex. As the reaction occurs,
the central metal ion holds the substrate and nucleophile
together and hence serves as a template. The organic ligand
N-(2-hydroxyethyl)ethylenediamine (HEEN) was designed
with this mechanism in mind; two amine groups anchor the
ligand onto the central metal ion, and the pendant hydroxyl
group is close enough to serve as an intramolecular nu-
cleophile. Using p-nitrophenyl picolinate as the hydrolyzable
FIGURE 2. Structure of citric acid (CIT), ethylenediamine (EN), and
N-(2-hydroxyethyl)ethylenediamine (HEEN) ligands.
U.S. (21), and zinc is moderately abundant in the environment
and in biological systems. Citrate (CIT) (Figure 2) serves as
a representative carboxylate-based naturally occurring or-
ganic ligand. Experiments with the synthetic organic ligands
ethylenediamine (EN) and N-(2-hydroxyethyl)ethylenedi-
amine (HEEN) (Figure 2) highlight the interrelationships
between coordination chemistry and catalysis.
Mechanistic Foundations. As discussed in a number of
recent publications (1, 8), metal ions catalyze hydrolysis via
one or a combination of the following three generalized
mechanisms: Mecha nism 1: The metal ion coordinates the
substrate in a manner that raises its susceptibility toward
nucleophilic attack. Mechanism 2: The metal ion coordinates
the nucleophile in a manner that raises its reactivity toward
electrophilic sites. Mecha nism 3: The metal ion coordinates
the leaving group, facilitating its exit from the higher-
coordinate intermediate. It should be noted that Mecha nism
II
substrate and Zn as the central metal ion, a dramatic
synergistic effect can be observed (33). As far as other
functional groups are concerned, pendant carboxylate groups
have been observed to facilitate metal ion-catalyzed amide
hydrolysis (35), and pendant amine groups have been
reported to participate in other reactions as general acid
catalysts (36).
2
has been strongly tied to the ability of metal ions to induce
Materials and Methods
Chem ical Reagents. Reagent grade water (18 MΩ-cm
resistivity) was prepared using a glass distillation apparatus
and a Milli-Q reagent-grade water system (Millipore, Bedford,
the deprotonation of coordinated water through reactions
such as Me + H
2
+
+
+
+
+
2
O ) MeOH + H , *K
1
) [MeOH ][H ]/
2
+
2+
2+
[
-
Me ]. Cu and Pb (possessing log*K values of -7.5 and
1
7.6, respectively) are far better at inducing water depro-
2
+
2+
MA). The inorganic reagents CuCl ‚2H O, NiCl ‚6H O, Pb-
tonation than Ni and Zn (log*K
1
values of -9.9 and -9.0)
2
2
2
2
(
(
NO
3 2 2
) , ZnCl , and NaCl were purchased from Aldrich
(
22).
Milwaukee, WI) at the highest possible purity. Acetic acid,
Organic ligand catalysis on hydrolysis is believed to occur
NaOH (from J. T. Baker, Phillipsburg, NJ), and MOPS (4-
morpholinepropanesulfonic acid, from Aldrich) were em-
ployed as pH buffers. Dimetilan (1-dimethylcarbamoyl-5-
methylpyrazol-3-yl-dimethylcarbamate) at greater than 98%
purity was obtained from the EPA Pesticides Repository and
used without further purification. Citric acid (CIT), ethyl-
enediamine (EN) (from Aldrich), and N-(2-hydroxyethyl-
ethylenediamine (HEEN) (from Lancaster, Windham, NH)
at greater than 99% of purity were used without further
purification.
through one or a combination of two different mechanisms:
Mecha nism 4: General acid-base catalysis, in which the
organic ligand donates a proton to the substrate or accepts
a proton from the attacking nucleophile in a manner that
accelerates the reaction. Mecha nism 5: Nucleophilic ca-
talysis, in which the organic ligand serves as a nucleophile,
forming an adduct which rapidly hydrolyzes into the expected
hydrolysis products.
Organic ligands cannot coordinate the substrate or
nucleophile, except through very weak hydrogen-bondings.
Hence, synergistic effects necessarily involve the formation
of metal-ligand complexes and arise from their effects on
Mecha nisms 1-5. The predominant coordination number
of the divalent metal ions included in this study is either five
Hydrolysis Experim ents. All glassware was soaked in 6
N HNO and rinsed several times with reagent-grade water
3
prior to use. The brown glass amber vials were autoclaved
prior to use, and reaction solutions were filter-sterilized to
inhibit biotic reactions. At 5-20 mM concentrations, acetic
acid with NaOH buffer was used for pH 4.0 to 5.7, and MOPS
with NaOH buffer was used for pH 5.9 to 8.0. Reaction
solutions were initially prepared with buffer, metal salt, and
organic ligands. Solution pH was adjusted by adding very
small amount of strong acid (HCl) or base (NaOH). After 3
to 4 h of stirring, an appropriate amount of freshly prepared
dimetilan stock solution was added to initiate hydrolysis.
Reaction solutions were continuously stirred in a 25 °C water
bath, and aliquots of solution were periodically collected for
analysis.
II
II
II
II
(
for Cu ) or six (for Ni , Zn , and Pb ). Whether or not the
central metal ion can simultaneously coordinate two entities
e.g., organic ligand plus substrate; organic ligand plus
(
nucleophile) has important mechanistic consequences.
If simultaneous coordination is not possible, metal-ligand
complex formation prevents either the metal ion or the
organic ligand from participating in the hydrolysis reaction.
As a consequence, catalysis by any of the five mechanisms
is impeded. A number of studies, for example, have shown
that metal ions lose their catalytic properties when coordi-
nated to carboxylate-containing ligands (23, 24) and to
bipyridine (25).
Decreases in the concentration of dimetilan were moni-
tored using a reversed-phase HPLC with a µ-Bondapac-C18
column and a UV detector set at 230 nm (Waters, Milford,
MA). The employed eluent consisted of 30% acetonitrile and
70% 1.0 mM phosphate (pH 7.0) buffer solution. Plots of the
log of dimetilan concentration versus time were linear,
indicating pseudo-first-order kinetics. Hydrolysis rate con-
When simultaneous coordination is possible, reactivity
within the ternary complexes that result must be considered.
Positive synergistic effects of this kind are believed to be
responsible for the high catalytic activity of metalloenzymes
(
26). Chemists have sought simpler, biomimetic complexes
-
1
built from hydroxyl-, carboxylate-, amino-, and thiol-
containing ligands in order to explore these effects (e.g., refs
stants kobs (in hours ) reported in this work correspond to
the slopes of these plots obtained by least squares linear
regression (r2 between 0.980 and 0.999). If the hydrolysis
2
7 and 28).
4
1 1 8
9
ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 34, NO. 19, 2000

the presence of metal ions, loss of dimetilan followed pseudo-
first-order kinetics.
As shown in Figure 3, in the presence of 1.0 mM CuII,
measurable values of log kobs can be obtained at pH 4.2. As
the pH is increased to 5.95, log kobs increases linearly with
slope equal to 0.80. Above this pH, kobs decreases dramatically
and approaches minimum measurable values at pH 7.6. In
II
this pH region, solutions became cloudy as Cu precipitated.
II
In the presence of 1.0 mM of Ni , the pH must be 1.6 log
II
units higher than observed with Cu in order to obtain
measurable values of log kobs. Again, log kobs increases linearly
as the pH is increased (Figure 3). The slope is equal to 0.67,
II
II
slightly less than the slope observed with Cu . Ni -containing
solutions remained clear throughout the pH range examined,
and no drop off in kobs at high pH was observed. For this
FIGURE 3. Effect of pH on metal ion-catalyzed hydrolysis of dimetilan.
-
5
Reaction conditions: 5.98 × 10 M dimetilan, 1.0 mM CuCl
or ZnCl , 6.67 mM acetate (up to pH 5.7) or MOPS (pH 5.9 and higher)
buffer, 25 °C.
2 2
, NiCl ,
2
II
reason, kobs is actually higher than observed with Cu when
the pH is greater than 7.18.
II
II
1
.0 mM Zn is a much less effective catalyst than Cu and
II
TABLE 1. Stability Constants for Metal Ion-Ligand Complexes
Ni , and measurable kobs values could only be obtained at
above pH 6.18. For the first three data points, log kobs increased
with increasing pH, yielding a slope equal to 0.25, much
a
(
22)
log K of Cu-Ln
log K of Zn-Ln
II
II
lower than observed with Cu and Ni . At pH 7.96, kobs
decreased, and the solution became cloudy as Zn precipi-
II
EN
pKa1: 6.85
pKa2: 10.93
pKa1: 6.34
pKa2: 9.56
pKa1: 3.13
pKa2: 4.76
pKa3: 6.40
10.50
(CuL)
(CuL2)
(CuL)
(CuL2)
(CuHL)
(Cu2L2)
5.66
10.60
5.28
10.07
4.79
(ZnL)
(ZnL2)
(ZnL)
(ZnL2)
(ZnL)
(ZnHL)
0
(L )
19.60
10.02
17.45
3.19
tated.
HEEN
.0 mM PbII did not yield measurable values of kobs
1
0
(
L )
throughout the pH range examined (4.0 <pH <7.4). Solutions
CIT
II
became cloudy at above pH 6.0 as Pb precipitated.
3
-)
(
L
14.80
2.78
1.30
II
II
II
II
The speciation of 1.0 mM of Ni , Cu , Zn , and Pb as a
function of pH under the conditions employed in these
experiments was calculated by the equilibrium computer
program HYDRAQL (39) using equilibrium constants from
the CRITICAL database (22). The four divalent metal ions
begin to precipitate as Me(OH)2(s) solids as the pH is increased
(ZnH2L)
a
For the reactions: Me2+ + xH+ + yLn- ) MeH (2+x-ny)+.
x y
L
reaction was too slow, decreases in the concentration of
dimetilan could not be distinguished from the experimental
error of the HPLC techniques. For this reason, kobs values
II
II
II
in the following order: Pb (pH 5.8) < Cu (pH 6.2) < Zn
-
4
-1
(pH 7.3) < NiII (pH 8.2). Therefore, PbII has the lowest and
Ni has the highest solubility. The appearance of turbidity,
below 1.0 × 10 hours cannot be measured.
II
Results and Discussion
which we interpret as precipitation, is consistent with these
trends in solubility. Dramatic decreases in kobs that correlate
with the occurrence of precipitation indicate that dissolved
metal ions are much more reactive catalysts than metal
Metal Ion-Free Solutions. Dimetilan hydrolysis experiments
in the absence of metal catalysts were performed at 25 °C in
solutions buffered between pH 4.0 and 8.0 (Figure 3). No loss
of dimetilan was detected after 14 days of reaction. In a
separate set of experiments, 0.1 µM to 0.1 M of EN, HEEN,
and CIT ligands were added at pH 5 and 7. No loss of dimetilan
was detected even when 0.1 M concentrations of ligands
(
hydr)oxide surfaces.
Solution pH affects the speciation of metal ions, thereby
affecting their interaction and reactivity toward substrates.
The reported kobs represents the overall rate for the metal-
catalyzed hydrolysis of dimetilan and can be expressed as a
function of different metal species in the solution
-4
-1
were added. Hence, kobs values were below 1.0 × 10 hours
in metal ion-free solutions and cannot be quantified.
The lack of observable dimetilan hydrolysis in metal ion-
free and organic ligand-free solutions is quite reasonable.
The N,N-dimethylcarbamate moiety is expected to be more
susceptible toward hydrolytic attack than the N,N-disub-
stituted urea moiety; oxygen is more electronegative than
nitrogen and less able to participate in resonance stabilization
with the carbonyl group. Uncatalyzed hydrolysis of the N,N-
dimethylcarbamate moiety has been estimated to occur on
time scales of hundreds of years (37).
kobs ) kMe [Me2+] + kMeOH [MeOH ] +
2
+
+
+
+
+
0
0
kMeAc [MeAc ] + k
[Me(Ac) ] +
Me(Ac)2
2
+
+
kMeCl [MeCl ] + ... etc. (1)
where Ac is the acetic acid buffer and k
for the metal species i. Under the experimental conditions,
i
is the rate constant
Me2 , MeOH , MeAc , Me(Ac)
+
+
+
0
, and MeCl species are
+
2
Mecha nisms 4-5 postulated for organic ligand catalysis
present at concentrations considerably higher than other
0
-
2-
4
are apparently not operative here. The pK
a
of the hydroxyl
species such as MeCl
2
, Me(OH)2(aq), Me(OH)
3
, Me(OH)
,
group of HEEN has been reported to be near 12 (33),
comparable to the reported pK (11.6) of the hydroxyl group
of CIT (38). Although the corresponding alcoholate ions are
undoubtedly strong nucleophiles, they are too strongly
protonated to have any significant effect on hydrolysis. The
etc. Determination of the rate constant for each metal species
is rather difficult; however, the relative importance of each
metal species to the overall rate can be discerned through
careful experiments. For instance, varying acetate and
chloride concentrations had negligible effects on the rate of
metal-catalyzed hydrolysis of dimetilan (data not shown),
indicating that the acetate- and chloride-coordinated metal
species are unlikely to play a major role in determining the
rates of dimetilan hydrolysis.
Metal-to-metal comparisons can be used to obtain
information regarding mechanism. For N,N-dialkylcarbam-
ates and N,N-disubstituted ureas, nucleophilic attack is
usually the rate-limiting step, rather than breakdown of a
a
a
pK (Table 1) values for the carboxylate groups of CIT (3.13,
4
.76, 6.40) and for the amine groups of EN (6.85, 10.93) and
HEEN (6.34, 9.56) are close enough to solution pHs that
general acid-base catalysis should be possible, if an ap-
propriate mechanism was available.
Metal Ion Catalysis. Experiments with divalent metal ions
employed the same temperature, pH range, and duration as
the experiments performed in metal ion-free solutions. In
VOL. 34, NO. 19, 2000 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
9
4 1 1 9

FIGURE 4. Metal ions can coordinate dimetilan through either a
five- or a six-membered chelate ring.
higher-coordinate intermediate. Hence, Mecha nism 3 can
1
be excluded. As noted in an earlier section, log*K compari-
II
II
sons indicate that Cu and Pb possess nearly the same ability
II
to induce the deprotonation of coordinated water, while Ni
and Zn have much less ability. The observation that Pb
II
II
does not yield significant catalysis strongly suggests that
deprotonation of coordinated water, and hence Mecha nism
2
, is not the sole mechanism. It is possible, however, for
Mecha nism 2 to be operative in concert with Mecha nism 1.
Such a “push-pull” mechanism has often been suggested
II
FIGURE 5. (a) Effect of EN and HEEN on Cu -catalyzed dimetilan
(
40-43). The fact that, within the solubility limits of metal
-
5
hydrolysis at pH 5.0, 25 °C. Reaction conditions: 5.98 × 10
M
ions, kobs increases with increasing pH also suggests that
species such as MeOH is important for the metal-catalyzed
II
+
dimetilan, 1.0 mM CuCl , and 6.67 mM acetate buffer. (b) and (c) Cu
2
+
speciation calculated using HYDRAQL.
hydrolysis of dimetilan since MeOH concentration increases
with increasing pH.
As far as Mecha nism 1 is concerned, the carbonyl oxygen
has been reported to be the preferred site of metal ion
coordination for both uncharged amides (44, 45) and
substituted ureas (46). However, monodentate coordination
of a carbonyl oxygen is generally weak, so other Lewis Base
groups capable of enhancing complex formation via chelation
should be sought. The nitrogen atom within the pyrazole
ring (marked * in Figure 4) suits this purpose; a five-
membered chelate ring is possible with the carbonyl oxygen
of the substituted urea, while a six-membered chelate ring
is possible with the carbonyl oxygen of the carbamate. Both
rings are sterically stable, and it is possible for the two rings
to form simultaneously.
Although complex formation constants involving dime-
tilan would be desirable, none are available. To observe trends
among metal ions, another neutral ligand can be used as an
analogy; a similar approach has been used previously (1, 8).
The magnitudes of the complex formation constants (log K)
for coordinating ammonia, for example, follow the order
FIGURE 6. (a) Effect of EN and HEEN on ZnII-catalyzed dimetilan
-
5
hydrolysis at pH 7.0, 25 °C. Reaction conditions: 5.98 × 10
M
II
II
II
II
II
Cu (4.2) . Ni (2.9) ∼ Zn (2.4) . Pb (1.5) (22). Thus, we can
dimetilan, 1.0 mM ZnCl , and 6.67 mM MOPS buffer. (b) and (c) Zn
2
II
II
predict that complex formation by Cu to be strongest, Ni
speciation calculated using HYDRAQL.
II
II
and Zn somewhat less but comparable, and Pb to be least.
This trend is borne out in the observed trends in hydrolysis
rate constants (Figure 3) if one compares either (i) the
minimum pH required for measurable hydrolysis to occur
or (ii) comparisons at fixed pH, as long as all four metal ions
are within their solubility limits.
As shown in Figure 6a, kobs values in the absence of organic
II
ligands is approximately 3.7 times lower for Zn than for
II
Cu . The ligand EN is again able to diminish kobs, although
higher concentrations are needed to obtain the same effect.
HEEN yields a significant increase in kobs. A maximum in kobs
-
3
is observed at HEEN concentration near 3.0 × 10 M and
corresponds to a nearly 4.8-fold increase in kobs in comparison
to HEEN-free solutions.
Metal Ion Plus EN or HEEN. Experiments investigating
the effects of EN and HEEN additions on metal ion catalysis
of dimetilan hydrolysis were conducted at pH 5.0 for 1.0 mM
II
II
To assist in interpreting the results of the organic ligand
Cu and at pH 7.0 for 1.0 mM Zn . In the presence of metal
ion catalysts, dimetilan loss followed pseudo-first-order
kinetics, regardless of whether EN or HEEN were present.
As shown in Figure 5a, low concentrations of EN had no
II
II
addition experiments, Cu and Zn speciation has been
calculated as a function of organic ligand concentration using
CRITICAL (22) and HYDRAQL (39). For these experiments,
metal species in solution include the species listed in eq 1
plus metal-organic ligand complexes. As a result, the kobs
can be expressed using the following equation
II
effect on kobs for the Cu -catalyzed hydrolysis. Once con-
II
centrations surpass the total dissolved Cu concentration,
however, kobs diminished dramatically. In the presence of
-
2
1
.0 × 10 M and 0.10 M EN, kobs values approached the
2
+
[Me2+] + k
+
+
kobs ) k
[MeOH ] +
Me
MeOH
minimum quantifiable limit.
+
+
0
0
+
+
-
4
HEEN concentrations below 1.0 × 10 M had a similar,
kMeAc [MeAc ] + k
[Me(Ac) ] + k
[MeCl ] +
Me(Ac)2
2
MeCl
II
negligible effect on kobs for Cu -catalyzed hydrolysis. HEEN
kMeL [Me-L2+] + kMeL2 [Me-L2 ] + kMeL3 [Me-L3 ] +
2+
2+
2
+
2+
2+
-
4
-3
concentrations between 3.0 × 10 M and 3.0 × 10 M, in
contrast, resulted in kobs values that were measurably higher
than observed in HEEN-free solution. Higher HEEN con-
centrations caused kobs values to drop in the same manner
observed with EN. Stated differently, within an intermediate
+
+
kMe(OH)L [Me(OH)L ] + ... etc. (2)
where L represents either HEEN or EN ligand. Note that
II
experiments with Zn were conducted at pH 7.0, and thus
II
range of HEEN concentrations, Cu catalysis was enhanced.
MOPS instead of acetate buffer was used.
4
1 2 0
9
ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 34, NO. 19, 2000

-
3
At the point where 1 × 10 M HEEN has been added, its
2
+
II
complexes (i.e., Cu-HEEN ) dominate Cu speciation
-
2
(
Figure 5b). For EN, a higher concentration of 1 × 10 M is
II
required to complex most of the Cu ions (Figure 5c).
II
Although the stability constants of Cu are higher for EN
than for HEEN, EN has higher basicity than HEEN (Table 1).
a
At pHs below the pK s of the two ligands, proton competition
II
with Cu for available ligand is more pronounced for EN
than for HEEN. Thus, HEEN is a better ligand at these pHs
II
for coordinating Cu . As indicated in Table 1, stability
II
constants for Cu are orders-of-magnitude higher than for
II
II
Zn . In order for HEEN to have the same effect on Zn , a 6.3
-3
times higher concentration (6.31 ×10 M) is required (Figure
6
b). Similarly, a higher concentration (0.1 M) is required for
II
EN to complex most of the Zn ions (Figure 6c).
Comparisons between the dimetilan hydrolysis experi-
ments and the HYDRAQL calculations indicate that 1:1 and
1
:2 metal ion-EN complexes are substantially less reactive
3
-
II
II
II
II
FIGURE 7. (a) Effect of citric acid (CIT ) L ) on Cu - and Zn -
5
catalysts than the Cu and Zn complexes they replace (e.g.,
Me (aq), MeAc , Me(Ac)
quite different. The 1:1 metal ion-HEEN are apparently more
-
catalyzed dimetilan hydrolysis. Reaction conditions: 6.96 × 10
M dimetilan, 1.0 mM CuCl or ZnCl , 0.02 M acetate (pH 5.0) or MOPS
pH7.0) buffer, 25 °C. (b) and (c) Cu and Zn speciation calculated
using HYDRAQL.
2
+
+
0
2
, etc.). With HEEN, the situation is
2
2
II
II
(
II
II
reactive catalysts than the Cu and Zn complexes they
replace, while 1:2 complexes are substantially less reactive.
Stating this differently, the pronounced enhancement effect
arising from HEEN addition can be attributed to the 1:1
complex, while the 1:2 complex inhibits metal ion-catalyzed
hydrolysis.
Since EN and HEEN have very similar log K values for
metal ion complexation, differences in their effect on metal
ion-catalyzed hydrolysis must arise from the hydroxyl group.
The fact that HEEN does not influence dimetilan hydrolysis
in the absence of metal ions indicates that HEEN can only
exert a catalytic effect on dimetilan hydrolysis cooperatively
with metal ions (i.e., a synergistic effect of metal ion and
HEEN). Coordination of the additional hydroxyl group of
HEEN to the central metal ion is possible since the hydroxyl
group is suitably placed for five-membered chelate ring
formation to occur.
There are three possibilities which can explain the effect
of HEEN: (A) metal ion complexation activates HEEN, making
it a reactive nucleophile or a general base catalyst; (B) metal
ion complexation activates dimetilan, making it susceptible
toward nucleophilic attack by HEEN; or (C) the metal ion
complexes both HEEN and dimetilan; in the ternary complex,
the hydroxyl group of HEEN facilitates dimetilan hydrolysis
as an intramolecular nucleophile or general base catalyst.
Of the above possibilities, (B) is least likely based upon
It is interesting that HEEN exerts a much greater en-
II
II
hancement effect on Zn catalysis than Cu catalysis.
However, this difference could arise from the different pHs
that the experiments were conducted or from the property
differences between Cu and Zn . The experiments with Cu
were not conducted at pH 7 due to concern of the solubility
II
II
II
II
II
limit of Cu . To fully understand differences between Cu -
HEEN systems and Zn -HEEN systems, experiments such as
II
the ones shown in Figures 5 and 6 should be conducted at
several pHs and using several dissolved metal ions concen-
trations.
Metal Ion Plus CIT. The effect of CIT additions on metal
ion catalysis of dimetilan hydrolysis was examined at pH 5.0
for 1.0 mM Cu and at pH 7.0 for 1.0 mM Zn . In the presence
of metal ion catalysts, dimetilan loss followed pseudo-first-
order kinetics, regardless of whether CIT was present.
II
II
-4
As shown in Figure 7a, 1.0 × 10 M CIT slightly decreased
II
II
k
obs for both the Cu - and Zn -catalyzed hydrolysis. When
-3
CIT concentrations reached 1.0 × 10 M and above, kobs
-2
values diminished dramatically. In the presence of 1.0 × 10
M and 0.10 M CIT, kobs values approached the minimum
quantifiable limit.
II
II
Cu and Zn speciation has been calculated as a function
of CIT concentration using CRITICAL (22) and HYDRAQL
-
3
two reasons. First, the pK
high that it is an improbable nucleophile or general base
catalyst under the experimental conditions used. Second,
a
of the HEEN hydroxyl group is so
(39). At the point where 1 × 10 M CIT has been added, CIT
II
complexes dominate Cu speciation (Figure 7b). At a
-3
concentration slightly higher than 1 × 10 M, CIT complexes
II
II
II
HEEN is very likely to be complexed with Cu and Zn , since
the log K values for both metal ions are quite large and
enhancement in catalysis is observed even when the HEEN
concentration is less than the metal ion concentration.
Option (C) is considered to be more likely than (A), since
the experimental results with the four divalent metal ions
strongly indicate that coordination of dimetilan with metal
ions is crucial for metal ion catalysis to occur. Furthermore,
the combined (“push-pull”) mechanism in which the metal
ion simultaneously coordinates the substrate and the nu-
cleophile occurs frequently (40-43). Therefore, (C) is the
most plausible explanation.
Compared to HEEN, EN lacks the hydroxyl functional
group that can act as an auxiliary nucleophile within the
metal ion-EN-dimetilan ternary complex. Therefore, EN
addition decreases metal catalysis. For both EN and HEEN,
the 1:2 complexes of metal and ligands are substantially less
reactive catalysts because excess ligands occupy most
coordination sites of metal ions, preventing the formation
of metal ion-organic ligand-dimetilan ternary complexes.
dominate Zn speciation (Figure 7c).
Comparisons between the dimetilan hydrolysis experi-
ments and the HYDRAQL calculations indicate that 1:1 and
1:2 metal ion-CIT complexes are substantially less reactive
II
II
toward dimetilan than the Cu and Zn complexes they
replace (e.g., Me2
+
+
0
(
aq)
2
, MeAc , Me(Ac) , etc.). The carboxylate
groups of CIT allow it to occupy three coordination sites of
metal ions, which may effectively prevent ternary complex
formation. Alternatively, it is possible that ternary complexes
form but possess no unusual reactivity; CIT coordination
may interfere with the ability of the metal ion to activate
dimetilan toward hydrolytic attack (Mecha nism 1) or may
interfere with the ability of the metal ion to generate a reactive
nucleophile through the induced deprotonation of water
(Mecha nism 2). Although induced deprotonation of the
hydroxyl group of CIT was observed with Fe (15), Cu and
Zn , which are less Lewis acidic than the trivalent metal ions,
are not believed to have the same ability. Thus, generation
of a reactive intramolecular nucleophile, possible with HEEN,
is not possible with CIT.
III
II
II
VOL. 34, NO. 19, 2000 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
9
4 1 2 1

To the author’s knowledge, this is the first study of metal
ion-organic ligand synergistic effects on the hydrolysis of
agrochemicals. Out of a long list of possible synergistic effects,
our experiments provide examples of only a few. EN and
CIT, both capable of coordinating +II metal ions but lacking
possible intramolecular nucleophilic groups, inhibit metal
ion-catalyzed dimetilan hydrolysis. Simple carboxylate ligands
similar to CIT (e.g., oxalic acid) are expected to lower the
catalytic effects of metal ions toward dimetilan hydrolysis.
It is possible, however, that other organic ligands exist which
lack intramolecular nucleophilic groups but nevertheless
facilitate catalysis (i.e., by encouraging ternary complex
formation with substrate or by facilitating shifts in electron
density that activate the substrate toward hydrolysis).
HEEN, capable of coordinating +II metal ions and
possessing a hydroxyl group that can serve as an intramo-
lecular nucleophile, significantly facilitates m etal ion-
catalyzed dimetilan hydrolysis. Moderately- and highly basic
functional groups (e.g., amines, phenols, thiols and hydroxyls)
near metal ion-binding moieties are found in many natural
products and can be postulated to occur within humic
substances. As mentioned earlier, extracellular enzymes are
already known to take advantage of metal ion-organic ligand
synergistic effects. It is quite possible that partially degraded
enzymes and other compounds released by cell lysis would
exhibit similar properties. As we learned more about the
identity and concentrations of metal ions and ligands in
pertinent microenvironments (e.g., the rhizosphere sur-
rounding roots and other soil interstitial solutions), we will
be in a better position to evaluate synergistic or inhibitory
effects on the degradation of agrochemicals. Hence, future
studies of metal ion-organic ligand synergistic effects on the
hydrolysis of agrochemicals are likely to be fruitful.
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Acknowledgments
Support by the USEPA National Center for Environmental
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Received for review February 4, 2000. Revised manuscript
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