Kinetics of phosphodiester cleavage by differently generated cerium(IV) hydroxo species in neutral solutions

Article abstract of DOI:10.1039/b506170a

Neutral aqueous solutions of cerium ammonium nitrate obtained by dilution of their acetonitrile stock solution with imidazole buffer show high catalytic activity in the hydrolysis of bis(p-nitrophenyl) phosphate (BNPP) and better reproducibility than othe

Full text of DOI:10.1039/b506170a

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A R T I C L E
Kinetics of phosphodiester cleavage by differently generated
cerium(IV) hydroxo species in neutral solutions†
Ana L. Maldonado and Anatoly K. Yatsimirsky*
Facultad de Qu ´ı mica, Universidad Nacional Aut o´ noma de M e´ xico, 04510, M e´ xico D.F.,
M e´ xico. E-mail: anatoli@servidor.unam.mx
Received 4th May 2005, Accepted 13th June 2005
First published as an Advance Article on the web 1st July 2005
Neutral aqueous solutions of cerium ammonium nitrate obtained by dilution of their acetonitrile stock solution with
imidazole buffer show high catalytic activity in the hydrolysis of bis(p-nitrophenyl) phosphate (BNPP) and better
reproducibility than other similar systems, but suffer from low stability. The kinetics of catalytic hydrolysis is
+
second-order in Ce(IV), independent of pH in the range 5–8 and tentatively involves the Ce
2
(OH)
7
species as the
active form. Attempts to stabilize the active species by different types of added ligands failed, but the use of Ce(IV)
complexes pre-synthesized in an organic solvent with potentially stabilizing ligands as precursors of active hydroxo
species appeared to be more successful. Three new Ce(IV) complexes, [Ce(Phen)
Ce(BTP) (NO
by reacting cerium ammonium nitrate with the respective ligands in acetonitrile and were characterized by analytical
and spectroscopic techniques. Aqueous solutions of these complexes undergo rapid hydrolysis producing nearly
2
O(NO
3
)
2
], [Ce(tris)O(NO )(OH)] and
3
[
2
3
)
4
]·2H O (BTP = bis-tris propane, 1,3-bis[tris(hydroxymethyl)methylamino]propane), were prepared
2
neutral polynuclear Ce(IV) oxo/hydroxo species with high catalytic activity in BNPP hydrolysis. Potentiometric
+
titrations of the solutions obtained from the complex with BTP revealed the formation of Ce
4
(OH)15 species at pH >
2
+
3+
7
, which are protonated affording Ce
4
(OH)14 and then Ce (OH)13 on a decrease in pH from 7 to 5. The catalytic
4
activity increases strongly on going to species with a higher positive charge. The reaction mechanism involves first-
and second-order in catalyst paths as well as intermediate complex formation with the substrate for higher charged
species.
Introduction
peptide complexes show similar catalytic activities in DNA
10
hydrolysis ).
The cerium(IV) cation is attracting increasing interest as a
possible catalyst for various hydrolytic reactions due to its
extremely strong Lewis acidity. The form of Ce(IV) used most
often is cerium ammonium nitrate which is commercially
available as a pure, readily water soluble compound. The
use of cerium ammonium nitrate has been reported in the
Speciation of Ce(IV) in solution has been established only in
11
highly acid media. In dilute 0.1 mM Ce(IV) perchlorate solu-
tions the principal species in the pH range 0–1 are mononuclear
3+
2+
hydroxocomplexes Ce(OH) and Ce(OH)
2
, but in 10 mM
5+ 4+
solutions binuclear complexes Ce
2
(OH)
3
, Ce
2
(OH)
4
and
12+
11
hexanuclear Ce (OH)12
6
become predominant. In less acid
1
2
3
hydrolysis of phosphate diesters, DNA, peptides, cyclic acetals
solutions the average number of metal bound OH anions
increased to 2.35 at the highest pH of 2, but the type of hydroxo
4–6
and ketals. However, the behavior of this and other Ce(IV)
salts in water is very complex due to their hydrolytic and
redox instability, posing serious restrictions on the use and
further development of new Ce(IV)-based, potentially very
active, catalysts. Even in an acid medium Ce(IV) slowly forms
11
species was not identified. At a pH > 4, Ce(IV) hydroxide starts
to precipitate.
The hydrolysis of cyclic nucleotides by cerium ammonium
nitrate proceeds with an inversion of configuration consistent
with in-line nucleophilic attack on the metal-bound phosphate
hydroxo polymers, which eventually precipitate as CeO . In
neutral buffered solutions cerium ammonium nitrate rapidly
2
12
ester group. On the basis of kinetic results for cAMP hydrolysis
3
forms a hydroxo gel, surprisingly still active in peptide and
in the presence of cerium ammonium nitrate at a pH of around
2
DNA hydrolysis, but the use of a heterogeneous system of
4+
2
, the dinuclear Ce
2
(OH)
4
cation was claimed to be the active
an uncontrolled composition is rather inconvenient both for
practical applications and for research.
Several compounds allowing one to maintain homogeneous
solutions of Ce(IV) salts in neutral media were proposed
however, the composition of active species in such systems
remains unidentified. Complex formation with strongly coor-
dinating EDTA-type ligands solves the problem of stability,
but although the Ce(IV)–EDTA system is active in the single-
stranded DNA hydrolysis, reported catalytic activities of such
complexes in the hydrolysis of synthetic activated phosphodi-
2c
species. It seems, however, highly improbable that such species
may still exist and be responsible for the catalytic activity in
neutral solutions.
1
,2
The first homogeneous system studied kinetically with bis(p-
nitrophenyl) phosphate as a substrate involved cerium am-
monium nitrate in the presence of a hydrophobic ligand, e.g.
palmitate in a neutral micellar solution of nonionic surfactant
7–9
1a–c
Brij-35. Very large observed rate constants were reported, see
7
4+
Table 1, and the binuclear Ce
2
(OH)
4
complex was considered
to be the active species. The kinetic results for BNPP hydrolysis
in this and other Ce(IV) based systems reported in the literature
are summarized in Table 1.
All kinetic studies with Ce(IV) reported so far are semi-
quantitative in nature. In preliminary experiments attempting
to reproduce published results with cerium ammonium nitrate
as a source of Ce(IV) we observed extremely poor reproducibility
of rate parameters and often it was virtually impossible to
handle the reaction system, e.g. to vary pH, temperature or
concentrations of reactants without causing precipitation or
8
,9
esters like bis(p-nitrophenyl) phosphate do not surpass those
observed with trivalent lanthanides and so the anticipated
advantage of Ce(IV) actually disappears (e.g., Ce(IV) and Eu(III)
1
†
Electronic supplementary information (ESI) available: H NMR
spectra of complexes 1–3 and their respective free ligands in DMSO-
. Logarithmic plots of first-order observed rate constants for BNPP
d
6
cleavage by complex 2. Biphasic kinetic curve for BNPP hydrolysis in
the presence of 2. See http://dx.doi.org/10.1039/b506170a
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 5 9 – 2 8 6 7
2 8 5 9

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Table 1 Observed first-order rate constants for BNPP hydrolysis in the presence of Ce(IV) compounds
◦
−1
Reaction system
T/ C
pH
kobs/s
Ref.
4
1
2
3
4
5
6
7
8
9
1 mM (NH
2 mM (NH
4
)
)
2
2
Ce(NO
Ce(NO
3
3
)
)
6
6
+ 1 mM palmitate in 5 mM Brij
+ 1 mM palmitate in 5 mM Brij
37
37
37
25
25
25
25
25
25
7.0
7.0
8.0
7.0
7.0
7.0
7.5
5.45
5.5
6.0 × 10−
1a
1a
8
9
−
2
4
2.6 × 10
−
5
0.1 mM Ce
0.275 mM Ce(L)
0.275 mM Ce(L-CD)
0.5 mM (NH Ce(NO
2
(HXTA)
1.0 × 10
−
−
6
4
1.18 × 10
6.17 × 10
0.020
9
4
)
2
3
)
6
in 10 mM imidazole
this work
this work
this work
this work
−
4
1 mM complex 2
1 mM complex 2
1 mM complex 3
6.9 × 10
0.055
0.023
Chart 1
an unexpected drop in activity. The purpose of this paper
is to test different ways of preparing neutral homogeneous
Ce(IV) solutions, such as the dilution of cerium ammonium
nitrate with aqueous buffers containing potentially stabilizing
ligands and the use of Ce(IV) complexes pre-synthesized in non-
aqueous media as precursors (see Chart 1 for the structures of
the substrate and ligands employed in this study), in order to
find suitable conditions for a detailed kinetic study aimed at
identifying the type of active Ce(IV) species in neutral solutions
and to provide a plausible reaction mechanism.
Results and discussion
Reactivity of cerium ammonium nitrate
In preliminary experiments we employed stock solutions of
(
NH
4
)
2
Ce(NO
3
)
6
in 3 M HNO and observed, in line with
3
reported results (see the Introduction), that 0.1–5 mM Ce(IV)
solutions obtained by dilution are homogeneous up to pH 4 and
show high catalytic activity in the phosphodiester cleavage. At a
pH of around 3.5, the first-order rate constants (kobs) observed
for the cleavage of BNPP with 0.2 mM cerium ammonium nitrate
◦
Fig. 1 Observed first-order rate constants for BNPP hydrolysis at 25 C
4 2 3 6 3
in the presence of 0.2 mM (NH ) Ce(NO ) from 3 M HNO stock
solution diluted with water (open squares) and from the acetonitrile
stock solution diluted with 10 mM imidazole buffer (solid squares) as a
function of pH.
13
◦
−1
in unbuffered solutions at 25 C were about 0.001 s , but in
less acid solutions the activity rapidly decreased, Fig. 1. No
activity at all was observed in heterogeneous conditions with
Ce(IV) hydroxide in form of a gel or precipitate. Surprisingly in
spite of high acidity and high nitrate concentration, the nitric
acid stock solutions underwent rather fast “aging” and after
one week lost about 90% of the initial activity. In addition, using
these solutions was rather inconvenient because of necessity of
neutralizing with large amount of acid. Therefore, we tested
other ways of preparing stock solutions and observed the best
results using 0.05–0.1 M cerium ammonium nitrate in dry
acetonitrile, which conserved full activity over several weeks and
did not contain added acid.
amounts of alkali remained homogeneous for at least 1 h up
to pH 9 and showed a significant, but poorly reproducible
catalytic activity in the hydrolysis of BNPP in unbuffered
solutions. About 20 different compounds (amino acids, amino
alcohols, nitrogen heterocycles, oximes, hydroxamic acids, and
Good’s buffers) were tested as potentially stabilizing ligands
in order to improve the stability and reproducibility of the
catalytic system. Some of these compounds (iminodiacetic acid
and its derivatives, hydroxamic acids) completely prevented the
precipitation of Ce(IV) in neutral and even basic solutions, but
also completely inhibited the catalytic activity. The majority
of compounds tested did not show any significant effect, but
two of them, bis-tris propane (BTP) and imidazole allowed us
Diluted 0.1–1.0 mM cerium ammonium nitrate obtained
from these stock solutions by adding water containing variable
2
8 6 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 5 9 – 2 8 6 7

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to obtain more reproducible kinetic results. Observed activity
was higher in imidazole, which also served as a buffer in the
pH range 6–8 and for these reasons further experiments were
performed in imidazole solutions. Kinetic measurements under
these conditions allowed us to obtain reproducible trends in
protons liberated per one Ce(IV) cation in the range of pH 6–
8 was estimated (Fig. 3 shows the results of one of the series
of such experiments obtained with 10 mM imidazole at initial
pH 7.5). This indicates the formation of nearly neutral hydroxo
+
species of an average composition Ce
2
(OH)
7
. When the same
k
obs such as the effect of pH or concentration, but the absolute
amounts of cerium ammonium nitrate were added to pure water,
the pH dropped to approximately three and calculated numbers
of liberated protons varied from 3.0 to 2.3 per one Ce(IV) cation
at the highest and lowest pH values (3.22 and 2.86) respectively
(Fig. 3).
values of the rate constants were still rather inaccurate (see the
Experimental section).
Fig. 1 compares kobs for BNPP hydrolysis in the presence
of 0.2 mM cerium ammonium nitrate from the acetonitrile
stock solution as a function of pH in 10 mM imidazole (solid
squares) and in the absence of imidazole from a nitric acid
stock solution (open squares). Apparently the use of imidazole
allows one to keep the observed activity below pH 3.5, up
to pH 8. The results in Fig. 1 show that the reaction rate is
independent of pH in the range 5–8. Increased amounts of
imidazole produce an inhibitory effect (Fig. 2) consistent with
−
1
the formation of a weak complex (K = 100 M ) between the
active catalyst and the imidazole molecule. Imidazole does not
form detectable complexes with trivalent lanthanide cations, but
its complexation with the much more electrophilic Ce(IV) cation
seems quite probable. In these experiments the variation in pH
was achieved by changing the initial pH of the imidazole buffer
before the addition of an aliquot of cerium ammonium nitrate
stock solution. Attempts to vary pH by adding base or acid to
solutions already containing Ce(IV) always resulted in a loss of
reproducibility of the kinetic measurements and often in a loss
of stability and led to precipitation. Apparently the system is
not at true equilibrium, the formation of active Ce(IV) species is
controlled by the kinetics rather than by the thermodynamics of
the cation hydrolysis, but fortunately it is quite reproducible.
Fig. 3 Number of protons released per one mol of Ce(IV) on addition
of (NH ) Ce(NO ) to water (open squares) and to 10 mM imidazole
4 2 3 6
buffer (solid squares) and on addition of complex 1 to 10% v/v aqueous
DMSO (solid triangles).
It seems, therefore, that the observed independence of kobs of
pH (Fig. 1) results from an approximately constant degree of
Ce(IV) hydrolysis above pH 3 and the role of imidazole is to
prevent fast precipitation of Ce(IV) hydroxide owing to a weak
complexation of active hydroxo species.
In reality hydroxo complexes of Ce(IV) may be of mixed
oxo/hydroxo type (it was proposed that the real structure of
1
2+
12+ 11
the Ce
6
(OH)12
species is Ce
6
(O)
4
(OH)
4
) and may have a
higher nuclearity because of the known tendency of oxo and
hydroxo ligands to serve as bridges between metal ions. Thus
+
possible structures of Ce
2
(OH)
(O)
instances monocationic binuclear hydroxo or alcoxo complexes
7
may be deduced by analogy
+
3+
e.g. Ce
2
(O)
3
(OH) or Ce
6
9
(OH)
3
. Interestingly, in several
+
14
+15
of trivalent lanthanides, i.e. La
2
(OH)
5
and La
2
(OMe)
5
were
identified as the reactive forms for the phosphodiester cleavage in
Fig. 2 The effect of imidazole buffer concentration on the reactivity of
+
◦
water and methanol respectively. Also the fragment Ln (OH)
0
1
.2 mM (NH
4
)
2
Ce(NO
3
)
6
at pH 7.0 and at 25 C. The value of kobs in
2
5
0 mM imidazole is two times higher than the respective point in Fig. 1
due to variations in absolute rates in different series described in the
Experimental section.
stabilized by the neutral bis-tris propane ligand was found to
be the reactive form in BNPP hydrolysis by several lanthanide
16
ions.
Fig. 4 shows the effect of Ce(IV) concentration on the reaction
rate: initially the observed rate constant increases quadratically
with increasing in metal concentration (the inset shows the
results below 0.4 mM Ce(IV) in logarithmic coordinates, which
follow a linear dependence with the slope 1.9 ± 0.2), but then
passes through a maximum at 0.5 mM and decreases to an
approximately constant level between 1 and 1.5 mM. Apparently
this behavior can be attributed to the formation of less reactive
aggregates of Ce(IV) hydroxo species at higher concentrations.
It is noteworthy that kobs at the optimum Ce(IV) concentration
reaches the highest reported value so far of about 0.02 s ,
observed previously at a higher temperature and Ce(IV) con-
centration in a micellar medium (see Table 1).
Higher than first-order kinetics are not uncommon for
lanthanide-catalyzed BNPP hydrolysis: second-order kinetics
The instability of the system towards additions of acids and
bases makes it impossible to determine the species composition
by potentiometric titrations. The following procedure was used
instead. To 3–10 mM imidazole buffer solutions adjusted to dif-
ferent pHs from 6–8, portions of the cerium ammonium nitrate
stock solution were added to get final Ce(IV) concentrations of
0
.1–0.6 mM . These additions induced decreases in pH and by
using the known value of pK
a
= 7.1 for imidazolium cation,
concentrations of protonated imidazole were calculated from
pH readings before and after Ce(IV) additions. The difference
between these concentrations is equal to the number of protons
liberated during the hydrolysis of Ce(IV) and, consequently to
the number of OH anions bound to the resulting Ce(IV) hydroxo
species. From these results the average number of 3.5 ± 0.2
−
1
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 5 9 – 2 8 6 7
2 8 6 1

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◦
Fig. 4 Observed first-order rate constants for BNPP hydrolysis at 25 C as a function of (NH
4
)
2
Ce(NO
3
)
6
concentration in 10 mM imidazole buffer
at pH 7. The inset shows the results at concentrations below 0.4 mM in logarithmic coordinates.
were observed for Y(III) dinuclear hydroxo complexes with tris-
Pre-synthesized cerium(IV) complexes with neutral ligands
17
type ligands, third-order kinetics were reported for dinuclear
Testing potentially stabilizing ligands in water showed us that
a suitable ligand should be a neutral amine or amino alcohol
molecule because more potent anionic ligands decreased the
catalytic activity of the Ce(IV) cation too strongly. Even if such a
molecule cannot prevent deep hydrolysis of Ce(IV), it may work
as a mediator making the cation hydrolysis a slower and more
selective process leading to the formation of hydroxo complexes
of a more definite composition, as has been demonstrated in
the successful realization of the so-called ligand-controlled self-
assembly of polynuclear oxo/hydroxo complexes of trivalent
1
8
19
complexes of La(III) with a macrocyclic ligand, and second-,
20
21
third-, and even fourth-order kinetics were observed for
lanthanide peroxide complexes of different nuclearities.
The major drawback of this system is its very low stability.
Although precipitation of the metal hydroxide from neutral
imidazole solutions was only observed after several hours, these
solutions had already lost ca. 20% of their initial activity
(
estimated by comparison of initial rates) after 20 min of
incubation, ca. 50% after 40 min, and after 1 h solutions
which were still transparent were practically inactive. This
inactivation is not associated with a deeper hydrolysis of Ce(IV)
because the pH of cerium ammonium nitrate solutions stabilizes
in just few minutes. The reason for inactivation is probably
aggregation of hydroxo species to still soluble, but inactive,
hydroxo polymers. This instability was manifested perhaps most
clearly in the temperature dependence of the observed rate
22
lanthanides. In this procedure a weakly coordinating ligand,
e.g. an amino acid, is present in a solution of lanthanide salt
adjusted to the pH of hydroxide precipitation and then di-,
tetra- and even pentadecanucelar oxo/hydroxo complexes can
be isolated in good yields depending on type of the cation
and the ligand. The hydrolysis of Ce(IV) proceeds much more
vigorously than that of trivalent lanthanides and when the
◦
constant: increasing the temperature above 25 C leads to a
“controlling” ligand is added to water it probably does not
decrease rather than an increase in the rate constant, Fig. 5,
apparently because of faster inactivation of the reactive species.
manage to participate in the process. One may expect, however,
that if such a ligand was bound beforehand to Ce(IV) in an
organic solvent, then when the complex underwent the reaction
with water it might act more successfully. Proceeding from
these considerations we have prepared three new complexes
by reacting cerium ammonium nitrate in acetonitrile with
neutral ligands of increasing basicity, namely phenanthroline,
tris and bis-tris propane. In complexes with first and second
ligands, Ce(IV) had already undergone a partial hydrolysis
to oxo/hydroxo forms during preparation, but with all three
complexes we indeed obtained catalytic systems which were
more stable and reproducible, allowing easier manipulation
of the catalyst solutions, in particular, in the performance of
potentiometric titrations, and still possessing the high catalytic
activity expected for Ce(IV) cations.
Cerium(IV)-phenanthroline complex. The complex of com-
position [Ce(Phen)
2
O(NO
3
)
2
] (1) was prepared by reacting
(
NH Ce(NO with two mol equivalents of phenanthroline in
4
)
2
3 6
)
acetonitrile. Evidently, Ce(IV) had already undergone a partial
hydrolysis during synthesis. Complex 1 is soluble in DMSO,
but insoluble in other common organic solvents and water. The
proton NMR spectrum of 1 in DMSO shows small up-field shifts
for the signals of all ligand protons by ca. 0.1 ppm as compared
to the free ligand and loss of the multiplicity of the most up-
field signal, which appears as a quartet in the spectrum of free
phenanthroline (see the electronic supplementary information
Fig. 5 Arrhenius plots for the rate constants for BNPP hydrolysis in the
4 2 3 6
presence of 0.4 mM (NH ) Ce(NO ) at pH 7.4 (solid triangles), 0.7 mM
2
at pH 7.5 (open squares) and 1.0 mM 3 at pH 7.6 (solid squares).
2
8 6 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 5 9 – 2 8 6 7

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(
ESI)†). These observations indicate a rather weak interaction
general procedure. The catalytic activity and kinetic behavior
was very similar for both complexes. The complex with the bis-
tris propane (BTP) ligand, which possessed a more definite and
simple composition, was studied in more detail.
of the metal ion with the ligand. In D O/DMSO-d solution
2
6
the spectrum of the ligand practically coincides with that of free
phenanthroline indicating a complete loss of the ligand in water.
The kinetics of BNPP cleavage was studied in aqueous
DMSO. The catalytic activity increased with decreasing DMSO
content and therefore all measurements were performed at a
minimum DMSO content of 10% v/v which was sufficient to
dissolve 1 at millimolar concentrations. Addition of 1 to water
produced a significant acidification of the solution indicative of
further hydrolysis of Ce(IV). Changes in pH were smaller than
in the case of cerium ammonium nitrate and estimation of the
number of protons liberated per one mol of 1 performed in the
The complex of composition [Ce(BTP)
2
(NO
3
)
4
]·2H
2
O (2) was
prepared in a similar way to 1. Also, like 1 it was soluble only
in DMSO, but was still sufficiently soluble in 5% v/v aqueous
DMSO to allow us to make measurements at a lower organic
23
co-solvent content. Comparison of the proton NMR spectra
of free BTP and 2 (see the ESI †) indicates a tighter binding of
this ligand to the metal ion than observed for phenanthroline.
Signals of central propane fragments of BTP and of those
adjacent to N methylene groups are shifted downfield by 0.54
and 0.47 ppm, respectively, and nearly lose their multiplicity. The
signal of NH protons undergoes a very strong downfield shift
by 4.87 ppm due to complexation with the Ce(IV) ion. Much
smaller downfield shifts, of 0.24 and 1.06 ppm, are also observed
same way as for (NH
4
)
2
Ce(NO
3
6
) (Fig. 3, solid triangles) gives
an average number of 1.57 ± 0.08 protons liberated per one
Ce(IV) cation. This means that further hydrolysis of 1 in water is
accompanied by the generation of approximately three hydroxo
ions per two Ce(IV) cations. Taking into account that 1 already
for the signals of methylene and OH protons of CH OH groups,
2
contains one oxo ligand per Ce(IV) cation, the final composition
respectively, indicating weaker coordination of hydroxyl groups.
The reported X-ray structure of the bis-tris complex of La(III)
shows that the tris fragment is tridentate (N and two of three OH
groups). Therefore, in principle two BTP ligands may occupy
12 coordination sites of Ce(IV); this is the maximum possible
coordination number for this cation. However, after dilution
+
24
of Ce(IV) species in solution should be close to Ce
2
(O)
2
(OH)
3
,
+
which is a doubly dehydrated form of Ce
2
(OH)
7
. Thus using 1
as a precursor of the active catalyst leads to similar species in
neutral solution, but as one can see from Fig. 3, the results with
1
are much less scattered than with cerium ammonium nitrate.
Also the kinetic measurements were more reproducible in this
case and the catalytic activity was much more stable during the
time of incubation.
of the DMSO solution of 2 with D O, the spectrum of BTP
becomes identical to that of the free ligand at the same pH
indicating complete dissociation of the complex in water.
2
The kinetics of BNPP cleavage was studied in the pH range
–9 in 10% DMSO. The reaction rate decreased slightly on
In contrast to all previously studied systems, the addition
of 2 to water does not change the pH. This is explicable
by complete neutralization of the acid liberated during the
hydrolysis of Ce(IV) by the BTP ligand, which is much more
basic then phenathroline. Neutral solutions of complex 2 are
stable over ca. 2 h and then precipitation of Ce(IV) hydroxide
begins. Remarkably, the stability of the Ce(IV) species in this case
was so high that it was possible to perform the potentiometric
titration of the solution over a wide pH range. Fig. 7 shows the
results of typical titration experiments. Titration with NaOH
was terminated at pH 9 because of a rapid precipitation of
Ce(IV) hydroxide in the more basic media. The titration curve
for NaOH (Fig. 7A) coincides exactly with that expected for
7
increase in pH, changing by a factor of two at extreme pH
values. The concentration dependence of kobs is shown in Fig. 6.
Evidently, 1 is significantly less active than cerium ammonium
nitrate (cf. Fig. 4 and Fig. 6), but does not suffer from a decrease
in the reaction rate at higher concentrations. Another difference
is that the kinetic order with respect to total Ce(IV) is even
higher in this case. The solid line in Fig. 6 is a fit to the third-
order concentration dependence, and on plotting in logarithmic
coordinates gives a reaction order of 3.26 ± 0.09. Thus, although
the Ce(IV) hydroxo species generated in solution from 1 have a
similar total charge to those generated from cerium ammonium
nitrate, they behave differently. This may be attributed to the
different structures of these species, probably different nuclearity
and/or a different balance of oxo and hydroxo ligands, which
are intertransformable by the addition/elimination of water
molecules.
16
the titration of protonated BTP (pKa1 = 6.81, pKa2 = 9.06)
with no additional titratable groups attributable to the Ce(IV)
species. From the results of titrations with NaOH we determined
that 94.0 ± 0.8% of the total amount of BTP is protonated
in the solution of 2 in water. This means that 3.76 ± 0.03
protons are liberated per one Ce(IV) cation during the hydrolysis
of 2, which corresponds to the formation of a nearly neutral
+
hydroxo complex of the composition Ce
4
(OH)15 , probably in
a partially dehydrated form. The absence of titratable protons
indicates that this species remains unchangeduntil pH9andthen
deprotonates affording a Ce(IV) hydroxide precipitate. Titration
with HCl, however, consumes more acid than is required for
the protonation of the remaining 6% of BTP base. The dashed
line in Fig. 7B is the expected titration profile for BTP alone.
Evidently, the experimental curve occurs at higher pH values
indicating additional consumption of added acid attributable
to protonation of the Ce(IV) hydroxo species. The results fit
satisfactorily to a model involving two consecutive protonation
steps represented by eqns. (1) and (2). The protonation constants
given below are the mean values from four titrations.
+
+
2+
Ce
Ce
(OH)15 + 2 H ↔ Ce
In other words, the complex Ce
4
(OH)15 + H ↔ Ce
4
(OH)14 , logb11 = 5.2 ± 0.1
(1)
(2)
+
+
3+
◦
4
4
(OH)13 , logb12 = 9.7 ± 0.3
Fig. 6 Observed first-order rate constants for BNPP hydrolysis at 25 C
as a function of concentration of complex 1 in 4 mM BTP buffer
2
+
4
(OH)14 behaves as an acid
3+
containing 10% v/v DMSO at pH 7.5.
with a pK = 5.2, and the complex Ce
pK
= 4.5. It is worth noting that stoichiometrically the complex
Ce (OH)14 is a dimeric form of Ce (OH) which is the major
a
4
(OH)13 as an acid with a
a
2
+
+
Cerium(IV)-tris and bis-tris propane complexes. Two other
complexes with tris type ligands were prepared via the same
4
2
7
hydrolysis product of cerium ammonium nitrate (see above).
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 5 9 – 2 8 6 7
2 8 6 3

View Article Online
Fig. 8 Observed first-order rate constants for the BNPP hydrolysis at
◦
2
5 C vs. pH and the species distribution diagram for 1.0 mM 2.
Rates vs. complex concentration profiles at two pH values,
+
7
.9 when the reactivity is due to Ce
4
(OH)15 species and 5.8
2
+
when the major contribution is from Ce
4
(OH)14 , are shown
in logarithmic coordinates in Fig. 9. The formal linear fit of
these profiles gives a fractional reaction order of 1.7 ± 0.1 in 2
at both pH values. This is a lower value than for all previously
described systems, but it still indicates a significant second-order
contribution.
Fig. 7 Titration curves for 1 mM 2 by NaOH (A) and HCl (B); a is
the number of mol equivalents of base or acid per one mol of 2. The
solid lines are the curve fits in accordance with equilibria (1) and (2) and
protonation of BTP. The dashed line is the titration profile expected if
BTP were the sole titrating component.
The kinetics of BNPP cleavage by 2 was studied in the pH
range 5–9 in 5% DMSO. Above pH 7, the reaction proceeded
with simultaneous liberation of both nitrophenyl groups of
BNPP via first-order kinetics, but in more acidic solutions
two distinct consecutive steps for the cleavage of the starting
diester and the intermediate monoester were observed. The first-
order rate constants observed for the phosphodiester cleavage
determined in the presence of 1 mM 2 are plotted vs. pH in Fig. 8.
The species distribution diagram calculated in accordance with
eqns. (1) and (2) is superimposed on the kinetic results in the
same figure.
Fig. 9 The logarithmic plots of observed first-order rate constants for
◦
the BNPP hydrolysis at 25 C vs. total concentration of 2 at pH 7.9 (open
squares) and pH 5.8 (solid squares) and 3 at pH 8.3 (solid triangles).
The fractional kinetic order is often observed as an approx-
imation to a rate law, which in fact corresponds to a variable
reaction order, changing from, for example, one to two on
variation in the total reactant concentration. Looking more
carefully at the concentration profiles at lower and higher pH
values one can see that at pH 5.8 the slope of the profile
tends to decrease at higher Ce(IV) concentrations, but at pH 7.9
the opposite tendency is observed (see the ESI; Fig. 8S shows
expanded plots together with lines drawn having slopes of one
and two so that these trends can be seen more clearly). The plots
of apparent second-order rate constants k2app = kobs/[2] shown
in Fig. 10 were used for the quantitative analysis of the kinetic
The results in Fig. 8 show that the catalytic activity in the
pH range 7.5–9 is independent of pH and may be attributed to
+
Ce
4
(OH)15 species, which in this pH range constitute 100% of
total Ce(IV). The average value of the observed rate constant in
−
4
−1
the presence of 1 mM 2 is (6.9 ± 0.8) × 10 s , representing
a reasonably high activity in comparison to other Ce(IV) based
systems (see Table 1). A decrease in pH to below this range causes
a very strong increase in kobs which correlates with the degree
results. At pH 7.9 the plot (open squares) is linear with a positive
2
+
3+
of formation of the complexes Ce
4
(OH)14 and Ce
4
(OH)13
−1 −1
intercept in accordance with eqn. (3) where k
1
= 0.17 M
s
possessing higher positive charges. The observed rate constants
−2 −1
and k
2
= 630 M
s
are the respective second- and third-order
−
1
reach values close to 0.1 s demonstrating a very large catalytic
+
rate constants for the cleavage of BNPP by Ce (OH)15 .
4
1
0
◦
effect of 10 (for the spontaneous BNPP hydrolysis at 25 C
k
−
11 −1 19,25
obs = 10 s ).
k
2app = kobs/[2] = k
1
+ k
2
[2]
(3)
2
8 6 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 5 9 – 2 8 6 7

View Article Online
Fig. 10 Apparent second-order rate constants for the BNPP hydrolysis
Fig. 11 Observed first-order rate constants for the BNPP hydrolysis at
◦
at 25 C vs. total concentration of 2 at pH 7.9 (open squares) and pH 5.8
◦
◦
2
5 C vs. pH in the presence of 1.0 mM 3 at 25 C in 10% DMSO. Crosses
(
solid squares).
show representative data points for 1.0 mM 2 (cf. Fig. 8).
It is worth noting that the systems obtained from precursor
complexes also show, in contrast to cerium ammonium nitrate,
the normal behavior with variation in temperature. Fig. 5 shows
the Arrhenius plots for complexes 2 and 3, which are linear as
At pH 5.8 the plot (solid squares) is of a “saturation” type.
This may be due to different factors. One possibility is that
this saturation results from the auto-association of the reactive
2
+
−1
species, Ce
4
(OH)14 in this case, affording a dimer, which reacts
expected, and give the activation energies 76.2 ± 3.9 kJ mol
−
1
with BNPP via first-order catalyst kinetics while the reaction
for 2 and 60.9 ± 4.9 kJ mol for 3 (the activation energy for the
2
+
−1 25
with Ce
4
(OH)14 is second-order with respect to the catalyst.
spontaneous hydrolysis of BNPP equals 106.2 kJ mol ).
However, it seems difficult to explain why a species with higher
A common feature of all the systems studied above, mentioned
already in connection with the cerium ammonium nitrate
system, is the observation of higher than first-order kinetics
with respect to the catalyst. This reflects the participation of
more than one metal complex in the transition state of the
catalytic reaction. The reasons for this are probably the same
as those proposed to explain well the documented superiority of
positive charge undergoes auto-association while, in the same
+
concentration range, the monocationic species Ce
4
(OH)15 does
not. Another possibility is that “saturation” reflects the complex
formation between BNPP and the catalyst. Such complexation
is often observed for trivalent lanthanides having binding
−
1 26
constants in the range 100–500 M . Of course, one may expect
BNPP complexation with the more electrophilic Ce(IV) to be
more efficient and, in addition, the binding to a dicationic species
should be stronger than to a monocationic one, explaining why
there is no “saturation” at pH 7.9. A possible reaction scheme
is presented in eqns. (4) and (5), where C is the reactive catalyst
species.
27,28
binuclear over mononuclear catalytic centers.
In contrast to what is typically observed with other metal
complex catalysts, in particular those with complexes of trivalent
26
lanthanides, the catalytic activity of 2 and 3 decreases rather
than increases on going to higher pH values when hydroxo
complexes, usually considered as catalytically active forms, are
generated. The most widely accepted mechanism for catalytic
phosphodiester hydrolysis involves nucleophilic attack of the
coordinated hydroxo anion on the metal bound substrate;
K
←
−−
BNPP + C −− −−− −→ C(BNPP)
(4)
(5)
1,2
this mechanism was also postulated for Ce(IV) compounds.
kC
C(BNPP) + C −−−→ reaction products
However, the hydroxo anion bound to highly electrophilic Ce(IV)
dramatically loses its basicity and may also lose its nucleophilic
reactivity to the level observed for neutral water molecules.
Since water is present at a much higher concentration, it may
be possible that in the presence of Ce(IV) the phosphodiester
undergoes nucleophilic attack by water molecules and bound
hydroxo anions only reduce the positive charge on metal ion and
The respective rate equation takes the form
k
2app = kobs/[2] = k
C
K[2]/(1 + K[2])
(6)
and the fitting of the results in Fig. 10 to this equation gives
−
1
−1
the values k
1
C
= 35 ± 4 M
s
and K = (1.03 ± 0.25) ×
3
−1
0 M . Since at pH 5.8 only 20% of the total Ce(IV) exists
29
consequently the degree of Lewis acid activation. In support
2
+
as Ce
4
(OH)14 in accordance with protonation constants given
of this, a significant solvent isotope effect, k
observed with 1 mM 2 in H O at pH 6 vs. D
positive solvent isotope effect, k /k
H
/k
D
= 3.1, is
above (eqns. (1) and (2)), the binding constant for this species
2
2
O at pD 6. A
must be five times larger, assuming that there is no complexation
H
D
= 2.4, was also reported
+
of BNPP with Ce
5
4
(OH)15 . So the corrected value of K equals
for cyclic nucleotide cleavage by cerium ammonium nitrate in
an acidic medium and was attributed to proton transfer to
3
−1
× 10 M . Thus, this model requires a binding constant for
Ce(IV) one order of magnitude higher than is typically observed
for trivalent lanthanides and this seems reasonable from general
considerations.
2c
the leaving group. In the case of a BNPP substrate, such an
explanation is implausible because the basicity of nitrophenyl
groups leaving this substrate is too low to require the protonation
in the transition state. On the other hand, the “water” reaction
often involves proton transfer from the attacking water molecule
to e.g. another water molecule or a buffer component in the
The kinetic results for the third pre-synthesized complex,
[
Ce(tris)O(NO )(OH)] (3), with the tris ligand were very similar
3
to those for 2. Fig. 11 shows the pH-profile for 3 which is
essentially the same, both in shape and absolute rate constant
values, as seen for 2 (cf. Fig. 8). The concentration dependence
of 3 obtained in the pH-independent region is shown in Fig. 9
transition state and proceeds more slowly in D
2
O than in H O
2
30
with isotope effects k
H
D
/k in the range from three to six.
(
solid triangles) and it also nearly coincides with that for 2. The
Conclusions
reaction order in this case is 1.8 ± 0.2. We believe, therefore,
that both precursor complexes generate similar reactive Ce(IV)
hydroxo species in water.
Representative rate constants for the cleavage of BNPP in the
systems described in this study are included in Table 1 (entries
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 5 9 – 2 8 6 7
2 8 6 5

View Article Online
1
six–nine) together with the literature values for other Ce(IV)
based catalysts. In terms of observed catalytic activity, these
new systems are close to that reported for a micellar medium
at a somewhat higher temperature and catalyst concentration
H, 5.73; N, 11.51. H-NMR (DMSO-d
6
, 300 MHz): d = 1.99
(m, 2H); 3.02 (t, 4H); 3.37 (s, 4H); 3.55 (s, 12H); 5.29 (s, 6H);
8.23 (s, 2H). After addition of 10% vol. of D O (99.9% D) the
2
signals at 8.23 and 5.29 ppm disappeared and the signal at 3.37
became more intense indicating that the two downfield signals
belong to exchangeable (NH and OH) protons and the signal at
3.37 belongs to water protons. IR (KBr, cm ): 3361 sb, 3082 sh,
2891 m, 2395 w, 1762 w, 1584 m, 1384 s, 1049 m, 825 w, 756 w,
573 wb.
(
Table 1, entry two). A possible contribution of micellar catalytic
31
effects to the reactivity of the latter system was not discussed,
butcanbeexpectedsincethemetalionisboundtoahydrophobic
ligand and BNPP also possesses hydrophobic fragments. An
approximately 100-fold positive effect of a similar nature is
observed in the presence of cyclodextrins attached to the cerium
bound ligand (compare entries four and five in Table 1). Taking
into account these supramolecular contributions, we suppose
that by their intrinsic reactivity described in this study these
systems surpass previously reported Ce(IV) systems by at least
one or two orders of magnitude.
−
1
[
Ce(tris)O(NO
dissolved in 4 ml of methanol and added to a solution of
NH Ce(NO (0.56 g, 1.03 mmol) in acetonitrile (10 ml).
3
)(OH)] (3). Tris (0.5 g, 4.13 mmol) was
(
4
)
2
)
3 6
The mixture was stirred for 1 h at room temperature. The
solid formed was filtered and washed with ice-cold acetonitrile,
methanol, and then with ether. Yield: 0.29 g (75.2%). Anal.
O Ce (374.28 g mol ): C, 13.49; H, 3.40 N,
.86. Found C, 13.52; H, 3.12; N, 7.86. H-NMR (DMSO-d
Of course, it is much more desirable to obtain a well
characterized highly active Ce(IV) complex, stable in water and
possessing a definite structure in solution, rather than just a set
of metal hydroxo species. The results of this study indicate that,
in principle, this should be possible because we observe very
high reactivity for species of low total charge. Therefore, the
use of strongly coordinating anionic ligands should not be too
harmful just because they reduce the positive charge on metal.
We see, on the other hand, that in all cases the catalytic reaction
is second-order or higher with respect to the catalyst, indicating
the importance of the polynuclearity of the active catalyst form.
From this point of view, the inhibitory effect of strong ligands
may be attributed to the fact that they prevent the formation of
the required polynuclear species stabilizing mononuclear forms
and the future direction of research in this area should be the
design of ligands capable of stabilizing polynuclear complexes.
−
1
calcd. for C
4
H
12
N
2
8
1
7
6
,
3
(
00 MHz): d = 7.43 (broad s, 2H); 5.14 (s, 3H); 3.47 (s, 6H). IR
−
1
KBr, cm ): 3382 sb, 2921 sh, 1614 m, 1458 w, 1383 s, 1352 s,
059 m, 834 w, 700 w.
1
Instrumentation
Ultraviolet–visible spectra were obtained with a Hewlett
Packard 8453 spectrophotometer.
H NMR spectra were recorded on 300 MHz Varian Unity
INOVA spectrometer.
IR spectra were obtained with a Perkin-Elmer 1320 spec-
trophotometer.
Measurements of pH were taken on an Orion Model 710-A
research digital pH meter.
1
Experimental
Methodology
Materials
Stock solutions of (NH
4
)
2
Ce(NO
3
6
) were prepared in acetoni-
trile, stock solutions of complexes 1–3 were freshly prepared in
dimethylsulfoxide, and stock solutions of BNPP were prepared
in water.
The compounds (NH
4
)
2
Ce(NO ) , BTP (1,3-bis[tris(hydro-
3
6
xymethyl)methylamino]propane), imidazole, and phenanthro-
line were purchased from Aldrich. Tris(tris[hydroxymethyl]-
aminomethane) was purchased from Sigma. The compound
studied as the substrate, BNPP (bis(p-nitrophenyl) phosphate)
In experiments with (NH
4
)
2
Ce(NO
3
6
) the final amount of
acetonitrile in the reaction mixture was between 0.1 and 1%
v/v (in the majority of experiments 0.4% v/v) and variation
in pH was achieved by adjusting the pH of the imidazole
buffer, typically 10 mM, before mixing with the other reaction
components. Reaction solutions for kinetic measurements with
complexes 1–3 were prepared by adding the required volumes
of stock solution of reactants to an aqueous buffer containing
DMSO in the amounts required to obtain 10% v/v DMSO for
complexes 1 and 3 or 5% v/v DMSO for complex 2 in the
final solution, and pH was adjusted by adding small volumes
of strong acid or base as necessary. Reactions were initiated
by adding an aliquot of the substrate solution. The solution
pH was measured before and after each run and experiments
where the pH variation was larger than 0.1 were excluded.
The following 10 mM buffers were employed: pH 5–6.5 MES,
pH 6.5–8 imidazole and pH 7–9 BTP.
(
Aldrich) was recrystallized from water. All solvents were
purchased from J. T. Baker.
All solutions for NMR studies were prepared in purified
(
d
Milli-Q Reagent Water System) water or in D
purchased from Aldrich.
2
O or DMSO-
6
Syntheses
Ce(Phen)
.16 mmol) was dissolved in 5 mL of acetonitrile and
added to a solution of (NH Ce(NO (0.29 g, 0.54 mmol) in
[
2
O(NO
3
)
2
]
(1). Phenanthroline
(0.43
g,
2
4
)
2
)
3 6
acetonitrile (5 mL). The mixture was stirred for 2 h at room
temperature. The solid formed was filtered off and washed twice
with acetonitrile and then with ether. Yield: 0.25 g (72.3%).
−
1
Anal. calcd. for C24
.52; N, 13.12. Found C, 45.02; H, 2.55; N, 13.21. H-NMR
DMSO-d
H
16
N
4
O
7
Ce (640.54 g mol ): C, 45.00; H,
1
In experiments with (NH ) Ce(NO ) measurements repeated
2
4
2
3 6
immediately produced rate constants reproducible within ± 10%,
however, measurements made on different days produced rate
constants which varied by a factor of two or three, e.g. with
(
2
1
6
, 300 MHz): d = 7.79 (q, 2H); 8.03 (s, 2H); 8.54 (q,
−1
H); 9.08 (s, 2H). IR (KBr, cm ): 3036 m, 1624 m, 1517 m,
460 m, 1383 s, 1363 sh, 842 m, 728 m.
0
.2 mM Ce(IV) in 10 mM imidazole at pH 7.5 the observed
−
3
[
Ce(BTP)
solved in water (4 ml) and then mixed with 16 ml of acetonitrile.
Then a solution of (NH Ce(NO (1.94 g, 3.54 mmol) in
acetonitrile (15 ml) was added and the mixture was stirred for
h at room temperature. The dense orange oil was separated
by decantation and treated with 50 ml of dry acetone. After
h stirring it was transformed into a yellow powder, which was
filtered off and washed twice with acetonitrile and then with
ether. Yield: 3.30 g (94.3%). Anal. calcd. for C22
2
(NO
3
)
4
]·2H
2
O (2). BTP (2 g, 7.08 mmol) was dis-
rate constants varied from (1.1 ± 0.1) × 10 to (2.7 ± 0.3) ×
−
3
−1
10 in different series of experiments. Therefore, to obtain
s
4
)
2
3
)
6
reliable trends in kobs, such as the effects of pH, concentrations
of reactants, or temperature, measurements were performed on
one day with the same cells, buffer and stock solutions.
The course of BNPP cleavage was monitored spectrophoto-
metrically by the appearance of the 4-nitrophenolate anion at
400 nm. Kinetic measurements used 20–30 lM BNPP at a pH >
6.5, and 40–100 lM BNPP at lower pH values. In the majority
of experiments two moles of p-nitrophenol per one mol of
2
1
H
56
8
N O26Ce
−
1
(
988.83 g mol ): C, 26.72; H, 5.71; N, 11.33. Found C, 26.72;
2
8 6 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 5 9 – 2 8 6 7

View Article Online
BNPP were liberated and the observed first-order rate constants
were calculated by the integral method from the kinetic curves
followed to 95% or higher conversion of the substrate. The
fast hydrolysis of the intermediate monoester was confirmed
7 (a) T. Igawa, J. Sumaoka and M. Komiyama, Chem. Lett., 2000,
356; (b) Y. Kitamura, J. Sumaoka and M. Komiyama, Tetrahedron,
2
003, 59, 10403; (c) M. Komiyama, H. Arishima, M. Yokoyama, Y.
Kitamura and Y. Yamamoto, ChemBioChem, 2005, 6, 192.
M. E. Branum, A. K. Tipton, S. Zhu and L. Que, Jr., J. Am. Chem.
Soc., 2001, 123, 1898.
J. Yan, M. Atsumi, D. Yuan and K. Fujita, Helv. Chim. Acta, 2002,
85, 1496.
8
9
in a separate experiment. In experiments with (NH
4
)
2
Ce(NO
3
) ,
6
−
1
rate constants lower than 0.002 s were estimated from the
initial rates in order to eliminate the effect of inactivation of
the catalyst (see the text). For BNPP hydrolysis by complex
10 (a) R. T. Kovacic, J. T. Welch and S. J. Franklin, J. Am. Chem. Soc.,
2
2
003, 125, 6656; (b) M. Sirish and S. J. Franklin, J. Inorg. Biochem.,
002, 91, 253.
2
at pH > 6, biphasic kinetic curves were observed with fast
liberation of first nitrophenol followed by slower liberation of
the second nitrophenol molecule. These results were fitted to the
respective two-exponential equation derived for the mechanism
involving two consecutive steps of hydrolysis of BNPP to
mono(p-nitrophenyl) phosphate and then of the monoester to
1
1
1 C. F. Baes, Jr. and R. E. Mesmer, The Hydrolysis of Cations, Wiley,
New York, 1976.
2 P. M. Cullis and E. Snip, J. Am. Chem. Soc., 1999, 121, 6125.
13 Measurements in acid solutions do not require a buffer since
hydrolysis of 0.02 mM BNPP does not practically affect pH, e.g.
an initial pH 4.0 decreases to only 3.9 after complete hydrolysis.
16
inorganic phosphate. A typical kinetic curve and the fitting
procedure are shown in the ESI †, Fig. 9S.
1
4 P. Hurst, B. K. Takasaki and J. Chin, J. Am. Chem. Soc., 1996, 118,
9
982.
Potentiometric titrations were performed and analyzed as
1
1
1
5 A. A. Neverov and R. S. Brown, Inorg. Chem., 2001, 40, 3588.
6 P. Gomez-Tagle and A. K. Yatsimirsky, Inorg. Chem., 2001, 40, 3786.
7 P. Gomez-Tagle and A. K. Yatsimirsky, J. Chem. Soc., Dalton Trans.,
16
described previously.
2
001, 2663.
18 (a) P. E. Jurek and A. E. Martell, Chem. Commun., 1999, 1609;
b) P. E. Jurek, A. M. Jurek and A. E. Martell, Inorg. Chem., 2000,
9, 1016.
Acknowledgements
(
3
We thank DGAPA-UNAM for financial support (project IN
2
08901). A. L. Maldonado thanks CONACyT for the doctoral
19 B. K. Takasaki and J. Chin, J. Am. Chem. Soc., 1995, 117, 8582.
20 J. Komitani, J. Sumaoka, H. Asanuma and M. Komiyama, J. Chem.
Soc., Perkin Trans. 2, 1998, 523.
fellowship.
2
1 Y. Mej ´ı a-Radillo and A. K. Yatsimirsky, Inorg. Chim. Acta, 2003,
51, 97.
3
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O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 5 9 – 2 8 6 7
2 8 6 7