Synthesis, characterization and X-ray crystal structures of cyclam derivatives. Part IV. 1,4,8,11-Tetraazacyclotetradecane-5,12-dione and its diprotonated forms

Article abstract of DOI:10.1039/b005052k

The synthesis, spectroscopic characterization (NMR, IR, MS) and protonation constants of a dioxocyclam derivative, 1,4,8,11-tetraazacyclotetradecane-5,12-dione (1), are described. The crystal structures of the free-base macrocycle and two diprotonated forms, with bromide and perchlorate as counter ions, have been determined by X-ray diffraction studies in order to evaluate the influence of both the secondary amine's protonation state and of the intermolecular hydrogen-bonding interactions on the macrocycle conformation. The spectroscopic, potentiometric and structural data indicate that both secondary amines behave independently from each other, their protonation inducing only limited conformational changes of the macrocyclic framework. In the crystal, the diprotonated species adopt two different [3,4,3,4] diamond-lattice-type conformations as a consequence of intermolecular hydrogen bonds involving the oxo groups and the surrounding anions.

Full text of DOI:10.1039/b005052k

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Synthesis, characterization and X-ray crystal structures of cyclam
derivatives. Part IV. 1,4,8,11-Tetraazacyclotetradecane-5,12-dione
and its diprotonated forms¤

Laurent Fremond,a Enrique Espinosa,a Michel Meyer,a Franck Denat,a Roger Guilard,*a
Volker Huchb and Michael Veithb
a L aboratoire dÏInge
CNRS UMR 5633), Faculte
1100 Dijon, France. E-mail: Roger.Guilard=u-bourgogne.fr; Fax: ]33 3 80 39 61 18;
Phone: ]33 3 80 39 61 11
b Anorganische Chemie, Universita

nierie Mole

culaire pour la Se

paration et les Applications des Gaz (L IMSAG,

des Sciences, Universite

de Bourgogne, 6 boulevard Gabriel,
2
Ž
t des Saarlandes, 66041 Saarbrucken, Germany
Ž
Received (in Strasbourg, France) 23rd June 2000, Accepted 11th September 2000
First published as an Advance Article on the web 15th November 2000
The synthesis, spectroscopic characterization (NMR, IR, MS) and protonation constants of a dioxocyclam
derivative, 1,4,8,11-tetraazacyclotetradecane-5,12-dione (1), are described. The crystal structures of the free-base
macrocycle and two diprotonated forms, with bromide and perchlorate as counter ions, have been determined by
X-ray di†raction studies in order to evaluate the inÑuence of both the secondary amineÏs protonation state and of
the intermolecular hydrogen-bonding interactions on the macrocycle conformation. The spectroscopic,
potentiometric and structural data indicate that both secondary amines behave independently from each other,
their protonation inducing only limited conformational changes of the macrocyclic framework. In the crystal, the
diprotonated species adopt two di†erent [3,4,3,4] diamond-lattice-type conformations as a consequence of
intermolecular hydrogen bonds involving the oxo groups and the surrounding anions.
The replacement of amine by amide groups in polyazacyclo-
alkanes yields a series of ligands that are structural inter-
mediates between the corresponding saturated macrocyclic
polyamines and oligopeptides. 1,4,8,11-Tetraazacyclotetra-
decane-5,7-dione (2), also called cis-dioxocyclam (Scheme 1),
and its N- or C-substituted derivatives have been among the
most extensively studied macrocyclic oxopolyamines.2 Ori-
ginally, this compound was synthesized by Tabushi et al.;3 the
Ðrst complexes were studied two years later by Kodama and
co-workers.4,5 The main characteristic of this series of ligands
is their ability to form neutral complexes with certain tran-
sition metal cations (i.e. Ni2`, Cu2`, Co2` and Pd2`) by dis-
placing the amide proton.6 In general, these dioxotetraamines
are more selective towards metal ions and their complexes
show faster dissociation kinetics when compared to the analo-
gous cyclic tetraamines.2 Their ligand Ðelds are stronger and
consequently these oxoamines may stabilize the less-common
]3 oxidation state of copper or nickel, similarly to oligo-
peptides.7 Appending additional chelating arms to the
dioxotetraamine causes considerable changes in the coordi-
nation properties of the ligands.8h11
Applications of cis-dioxocyclam and its derivatives are
multiple. From a synthetic point of view, it is, thus far, the
most convenient route towards C-substituted cyclam deriv-
atives and 1,11-di-N-functionalized cyclam-based macrocycles
can easily be obtained after reduction of the amide groups.
They might be used, for instance, for selective extraction of
platinum from aqueous metal ion mixtures12 or as side-
rophore analogs.13 Cobalt(II) and nickel(II) complexes of some
dioxocyclams have shown interesting dioxygen uptake proper-
ties.11,14 Nickel(II) complexes also catalyze the oxidation of
alkenes.15 The 1,4,8,11-tetraazacyclotetradecane-2,9-dione (3)
isomer has been obtained using the crab-like cyclization reac-
tion and its copper(II) complex has been studied.16,17 Another
isomer with two vicinal carbonyl groups, 1,4,8,11-
tetraazacyclotetradecane-2,3-dione (4),18 and its tetra-
methylated analog,19 have been recently described.
In 2, 3 and 4, both amide functions are contiguous. A few
dioxocyclam derivatives with trans amide groups have already
been described in the literature, like the tricyclic lactam
obtained by rearrangement of 1,8-bis(carboxymethyl)-1,4,8,11-
tetraazacyclotetradecane. This compound, which can be con-
sidered as a reinforced 2,9-dioxocyclam, has been crystallo-
graphically characterized.20,21
A
functionalized 5,12-
dioxocyclam has been obtained by dimerization, followed by
reduction of a suitable azapenam.22
Scheme 1
1
,4,8,11-Tetraazacyclotetradecane-5,12-dione (1), also called
5,12-dioxocyclam or trans-dioxocyclam, has been isolated
¤
For part III, see ref. 1.
from the reaction of ethylenediamine and methylacrylate23
DOI: 10.1039/b005052k
New J. Chem., 2000, 24, 959È966
959
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2000

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while the condensation of ethylenediamine and methyl meth-
acrylate yielded the corresponding dimethylated derivative.24
In contrast to the cis isomers, 5,12-dioxocyclam has yet only
been used for synthetic purposes, as a synthon for the pre-
paration of 1,8-disubstituted cyclams.25,26 This compound
constitutes an interesting starting material for the synthesis of
new cryptands27h29 and macrotricycles,30,31 because it can be
viewed as a trans ““autodiprotectedÏÏ cyclam. More recently,
we were also able to obtain trans N-arylated derivatives of
splitting of the transition into a doublet (1656 and 1640
cm~1), is observed when perchloric acid is used instead of
hydrobromic acid. The ClÈO stretching band appears as a
broad triplet between 1145 and 1089 cm~1, which is an indi-
cation of hydrogen-bonded perchlorate anions.33
Protonation constants
The protonation constants, deÐned by eqn. (1), of the diprotic
base 5,12-dioxocyclam were determined by means of poten-
1.32
tiometric titrations carried out in aqueous 0.1 M KNO solu-
As part of our general interest in the coordination chem-
3
tions maintained at 25.0(1) ¡C.
istry of tetraazamacrocycles, we are currently investigating the
metal-binding ability of this ligand. As a biomimetic model of
oligopeptides, its complexes should present interesting chemi-
cal and biological properties that may Ðnd applications in
Ðelds such as enzyme mimicry, stabilization of unusual oxida-
tion states, ion separation or catalysis. Herein, we report the
synthesis and characterization in solution of the free-base 1
together with a detailed conformational analysis of 1 in the
crystalline state and of two corresponding diprotonated forms
with two di†erent counter anions, bromide and perchlorate.
The protonation properties of 1 are discussed in light of those
reported for various 13- and 14-membered analogs.
LH(n~1)` ] H` ¢ LHn`
n~1
n
[
LHn`]
K
\
n
(1)
0
1n [LH(n~1)`][H`]
n~1
b
\ K
K
012
011 012
The mean values from three replicate determinations are log
K
\ 7.60(1) and log K \ 7.44(3) (Table 1), which give an
0
11
012
average protonation constant (log K ) of 7.52(3). Thus, each
av
secondary amine of 5,12-dioxocyclam is about two orders of
magnitude more acidic than the primary amine of b-
alaninamide [log K \ 9.20(1), I \ 0.1, T \ 25 ¡C].34 Com-
0
11
pared to cyclam, the presence of two electron-attracting
endocyclic amide groups decreases the basicity of the two
remaining amines by more than six orders of magnitude (log
Results and discussion
Synthesis and spectroscopic characterization
b
\ 15.04 and 21.734 for 1 and cyclam, respectively).
0
12
The Ðrst protonation constant found for 1 is in good agree-
The free-base 1,4,8,11-tetraazacyclotetradecane-5,12-dione was
synthesized according to the procedure described by Tomalia
and Wilson,23 which relies on a [2 ] 2] Michael condensation
of methyl acrylate in neat ethylenediamine at temperatures
close to 0 ¡C. The linear [1 ] 1] addition product readily
undergoes subsequent intermolecular and intramolecular ami-
dation reactions to form Ðrst the linear dimer and then the
cyclic diamide. Due to its lower solubility when compared to
the open chain adducts, the cyclization reaction is carried out
in aqueous solution. After 3 days, the reaction mixture is
diluted with water and allowed to stand for an additional
week at room temperature until the crude dioxocyclam pre-
cipitate is removed by Ðltration. Analytically pure compound
was obtained in 2% yield after recrystallization in water.
ment with the second protonation constant of the monoamide
compound 5, 1,4,8,11-tetraazacyclotetradecane-5-one [log
K
\ 7.32(2)].35 The value of log K
also compares well
with the corresponding value reported for isomer 3 [log
0
12
011
\ 7.81(1)] and for two related 13-membered analogs of
K
3
0
11
, namely 1,4,7,10-tetraazacyclotridecane-2,9-dione (6) [log
K
(
\ 7.21(2)] and 1,4,7,10-tetraazacyclotridecane-3,8-dione
0
11
7) [log K \ 7.69(1)].17 Among the three dioxocyclam
0
11
isomers for which thermodynamic parameters have been
determined, 2 is the most basic since the Ðrst protonation
occurs at much higher pH [log K \ 9.54(9)].34 The
0
11
enhancement of the basic character of 2 is a direct conse-
quence of the larger distance between the protonation sites
and the positively polarized carbon atoms belonging to the
carbonyl groups.
The 1H NMR spectrum in CDCl shows a single set of six
3
resonances. Four of them appear in the aliphatic CH region,
2
suggesting a C symmetric structure on the NMR time scale.
i
The relative magnitude of the second protonation constant
(K
) reÑects the free-energy cost of protonating an amine
Relying on the splitting pattern, the low-Ðeld doublet of tri-
0
12
located close to a quaternary ammonium center. Several con-
tributing factors might be listed, such as (i) the electrostatic
repulsion between two positive charges, (ii) the breakup of a
favorably chelated single proton shared between two amino
nitrogen atoms and/or of hydrogen bonds, (iii) a conforma-
tional rearrangement of the ring structure, (iv) the solvation
energy. Accordingly, 6 exhibits the most acidic amine [log
plets centered at 3.38 ppm is readily assigned to the methylene
groups adjacent to the amide nitrogen atoms, whereas the
most high-Ðeld-shifted triplet (2.39 ppm) is attributed to the
protons located in the positions a to the carbonyl groups. A
homodecoupling experiment enabled the assignment of the
two remaining triplets appearing at 2.80 and 2.92 ppm to the
methylene groups of the ethylenediamine and b-alaninamide
moieties, respectively. As expected, the amide protons give rise
to a broad singlet at 9.10 ppm. The integral and the chemical
shift suggest that the second broad signal at 1.48 ppm arises
from the four protons of the two cocrystallized water mo-
lecules, also evidenced by elemental analysis. Thus, both
protons belonging to the secondary amines most probably
give rise to a low-intensity signal that may overlap with the
water peak.
K
\ 3.02(2)] and thus the largest separation between log
0
12
Table 1 Protonation constants of cyclam and various mono and
dioxo derivatives
Ligand
log K
log K
log K [ log K
0
11
012
011
012
1a
2b
3
5
7.60(1)
9.54(9)
7.81(1)
10.87(2)
7.44(3)
5.80(5)
5.68(2)
7.32(2)
0.16
3.74
2.13
3.55
3.95f
1.1
c
d
The infrared spectrum of the free base exhibits the typical
NÈH and C2O stretching, and CÈNÈH bending modes of sec-
ondary amides at 3304, 1635 and 1556 cm~1, respectively.
Protonation of the amine nitrogen atoms gives rise to new
absorption bands between 2700 and 2850 cm~1, which are
3
.37(3)e
Cyclamb
6
7c
11.4(1)
7.21(2)
7.69(1)
10.3(1)
3.02(2)
5.90(1)
c
4.19
1.79
characteristic of the HR NÈH` oscillator, while the amide
2
a I \ 0.1 (KNO ), T \ 25 ¡C. b I \ 0.1, T \ 25 ¡C.34 c I \ 0.1 (KCl),
CÈNÈH bending vibration is split into a doublet at 1570 and
3
T \ 25 ¡C.17 d I \ 0.5 (KNO ), T \ 25 ¡C.35 e log K . f log K
3
013
012
1
531 cm~1. For [H (1)]Br , the carbonyl stretch shifts to
[
log K
.
2
2
013
higher energy by 21 cm~1. The same trend, together with a
960
New J. Chem., 2000, 24, 959È966

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K
and log K
11 012
(4.19 log units) since both protonation
nitrate anions present in large excess in the bulk solution.40
Considering the relative lipophilicity of the neutral free base,
the net charge increase upon protonation enhances the water
solubility of 1 and could result in a favorable hydration free-
energy change. Accordingly, the observed cooperativity would
be expected to be of entropic origin.42,43
0
sites belong to the same ethylenediamine moiety. The Ðrst
proton is most probably shared between both contiguous
ethylenediamine nitrogen atoms in [H(6)]`, which severely
hinders the second protonation. For the remaining com-
pounds, the log K
values increase in the following order: 3
012
[
5.68(2)], 2 [5.80(5)], 7 [5.90(1)] and 1 [7.44(3)]. The wider
However, one should also bear in mind that the separation
of both protonation constants of 1 is close to the resolution
limit of two overlapping equilibria and might therefore also be
due, at least in part, to a mathematical artifact. Indeed, the
distance between the pair of quaternary ammonium sites in
the propylenediamine fragments of [H (2)]2`, [H (3)]2` and
2
2
[H (7)]2` weakens the coulombic repulsion interaction.
2
Owing to the fact that both protonations occur in the same
pH range for 1, it may be inferred that the electrostatic repul-
sion between both trans-located amino groups is negligible.
This observation also suggests that the macrocyclic frame-
work undergoes only very limited structural changes upon
each protonation step in solution, giving rise to a small
entropy variation.
absolute values of log K
sidered with some caution since they were found to be highly
and log K
should be con-
0
11
012
correlated (r ^ 0.8). Thus, their sum [log b \ 15.04(2)] is
012
known with more accuracy than their individual values.44
X-Ray structures
For two noninteracting sites having identical microscopic
protonation constants, the di†erence between the successive
X-Ray quality crystals of 5,12-dioxocyclam and of two dipro-
tonated forms, [H (1)]Br and [H (1)](ClO ) , were obtained
2
2
2
4 2
macroscopic constants for both steps (log K
[ log K
012)
as colorless rectangular blocks by slow evaporation of each
compound from an aqueous solution. The nonprotonated
bisamide and the dihydrobromic derivative crystallize in the
011
would be equal to log 4 (\0.60) based on statistical consider-
ations.36 In the case of macrocycle 1, this di†erence is signiÐ-
cantly lower than the statistical factor. A limited number of
systems giving rise to protonation cooperativity, in which
protonation of the Ðrst site enhances the basicity of the second
one, have been reported over the past decade.34,37,38
6
centrosymmetric space group P1 (Table 2) with a half molecu-
lar unit belonging to the asymmetric unit. Two water mo-
lecules were also found in the molecular unit of compound 1,
conÐrming the results of the elemental analysis. The dihydro-
perchlorate form [H (1)](ClO ) crystallizes in the centro-
The acido-basic properties of the bridgehead tertiary
amines belonging to a small bicyclic tris-urea cryptand
provide such an example.39 A conformational reorganization
of the carbonyl groups, which rotate into the cavity and form
hydrogen bonds with the Ðrst incoming proton, was invoked
to explain the unusually high basicity of the second amine
located on the opposite site. Assuming that the macrocycle 1
retains approximately its solid-state structure (vide infra) in
solution as inferred from molecular dynamic simulations
carried out on large-size protonated polyazacycloalkanes,40
preorganization or hydrogen-bonding e†ects induced by
structural rearrangements upon protonation might not
account for the relative magnitude of the successive proto-
nation constants.
2
4 2
symmetric space group P2 /a, revealing the presence of two
1
independent half-molecules in the asymmetric unit. ORTEP45
views of the macrocycle found in 1 É 2H O and [H (1)](ClO )
2
2
4 2
are shown in Fig. 1, while relevant bond distances and bond
angles are summarized in Table 3.
In order to facilitate the conformational analysis of the
macrocycles, the sign and magnitude of the torsion angles are
graphically displayed vs. the bond number in Fig. 2. Compari-
son of the resulting polar maps enables one to locate the
corner positions by recognizing their characteristic torsion
angle sequences and further allows a facile identiÐcation of the
macrocyclic conformation. Following the original deÐnition
by Dale,46 a corner is deÐned as the central atom of an anti-
gauche-gauche-anti (agBgBa) bond sequence where both suc-
cessive gauche angles (ideally ^60¡) are of the same sign.
Alternatively, a pseudocorner may arise when both gauche
bonds of the same anti-gauche-gauche-anti arrangement have
opposite signs. A positive value of a torsion angle is assigned
to a gauche bond if the rear bond is rotated clockwise with
respect to the front bond when looking along the central bond
axis.47 According to DaleÏs nomenclature, each conformation
is designated by a series of numbers in square brackets, each
digit corresponding to the number of chemical bonds found
The observed cooperativity in the protonation of 1 is remi-
niscent of the acido-basic behavior of some large polyazacy-
cloalkanes belonging to the [3k]aneN or [4k]aneN series.41
k
k
Indeed, the values of the Ðrst and second protonation con-
stants become closer as the ring size and thus the Ñexibility
increase. Obviously, neither electrostatic nor conformational
arguments can explain this trend, which is characteristic of
these families of compounds. Rather, the smaller than
expected log K [ log K
11 012
in terms of solvation and interactions with the surrounding
di†erence might be rationalized
0
Table 2 Crystal data for 1 and its two diprotonated forms [H (1)]Br and [H (1)](ClO )
2
2
2
4 2
N O Br
Formula
C
264.33
Triclinic
P1
7.559(2)
4.997(2)
10.293(2)
116.96(3)
91.55(3)
100.31(3)
338.4(2)
1
H
N O É 2H O
C
H
C
429.22
Monoclinic
P2 /a
10.2700(2)
16.1690(4)
10.8995(2)
90
106.900(1)
90
1731.76(6)
4
112(2)
0.436
H
N O
10Cl
1
0
20
4
2
2
10 22
4
2
2
10 22
4
2
M
390.14
w
Crystal system
Triclinic
P1
6
6
Space group
1
a/A
b/A
c/A
Ž
5.2851(2)
8.0718(4)
9.5424(5)
109.126(3)
104.189(4)
97.989(3)
362.03(3)
1
Ž
Ž
a/¡
b/¡
c/¡
U/A
Ž
3
Z
T /K
293(2)
0.100
1163
1163
112(2)
5.600
k(Mo-Ka)/mm~1
No of collected reÑns
No of unique reÑns
R , R [I [ 2p(I)]a
2142 [R(int) \ 0.033]
7487 [R(int) \ 0.022]
1619
0.0255, 0.0670
4881
0.0328, 0.0924
0.0316, 0.0812
1
2
a R \ & p F o [ o F p /& o F o, R \ M&[w(F2 [ F2)2]/&[wF4]N1@2.
1
0
c
0
2
0
c
0
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Fig. 2 Polar maps displaying the torsion angle sequence of mo-
lecules 1 É 2H O (ÈÈ), [H (1)]Br (È È) and [H (1)](ClO ) (É É É). q is
2
2
2
2
4 2
1
deÐned as the N1ÈC2ÈC3ÈN2 torsion angle, the following angles
being obtained by a clockwise circular permutation around the
macrocyclic ring of 5,12-dioxocyclam.
location of the nitrogen atoms with respect to the corners was
designated by adding a capital letter.
Following this new classiÐcation, the bisamide rings in 1 É 2
H O and [H (1)]Br display a quadrangular [3,4,3,4]-B con-
2
2
2
formation in which the nitrogen atoms are endocyclic. As evi-
denced by the polar map shown in Fig. 2, these are positioned
one bond away from a corner position occupied by the C2,
C4, C2@ or C4@ methylenic carbon atoms. Despite their striking
similarity, superposition of the protonated and nonprotonated
molecules shows some conformational di†erences (Fig. 3). A
least-squares Ðtting of the 16 non-hydrogen atoms belonging
to the macrocycles gives a root mean square deviation (rmsd)
Fig. 1 ORTEP views of the macrocycle found in 1 É 2H O (top) and
2
[
H (1)](ClO ) (bottom), showing thermal ellipsoids at 50% probabil-
2
4 2
ity level and the numbering scheme for one-half of the molecule only
the symmetry related atoms are labeled according to the same
(
scheme and primed).
of 0.413 AŽ . As seen in Fig. 3, the major deviations occur in the
tilting of the carbonyl groups, giving rise to a set of C5ÈC1È
N1ÈC2 torsion angles of similar magnitude but opposite sign
between consecutive corner atoms.48h50 Although well
adapted to describe the conformation adopted by cyclic poly-
alkanes, this description becomes ambiguous for macrocycles
containing heteroatoms.51 A detailed stereochemical analysis
of such structures requires that the position of the hetero-
atoms within the cycle be taken into account, in order to dis-
tinguish the di†erent conformers possessing the same torsion
angle sequences. In a recent review, each of these stereoiso-
mers has been di†erentiated for the Ðrst time.52 Maintaining
the informative nomenclature introduced by Dale, the exact
(
q
and q in Fig. 2). The internal angle between the mean
6
13
plane deÐned by the C5ÈC1ÈO1ÈN1 atoms Mrmsd of 0.0002
and 0.0005 AŽ for 1 É 2H O and [H (1)]Br , respectivelyN and
2
2
2
the plane passing through the four corner positions C2ÈC4È
C2@ÈC4@ is wider open for 1 É 2H O [105.4(1)¡] than for
2
[
H (1)]Br [89.1(1)¡], where the carbonyl bonds point in a
2
2
perpendicular direction with respect to the macrocyclic skele-
ton.
As revealed by the crystallographic study of [H (1)]
2
(
ClO ) , protonated 5,12-dioxocyclam is able to adopt
4
2
Table 3 Selected bond lengths (A
Ž
) and angles (¡) for 1 and its two
a variety of stable conformations, depending on the counter
anion. The two independent macrocycles found in the struc-
ture exhibit essentially identical conformations, their overlay
diprotonated forms [H (1)]Br and [H (1)](ClO ) a
2
2
2
4 2
1
É 2H O [H (1)]Br
[H (1)](ClO ) a
2
2
2
2
4 2
producing a rmsd of 0.071 AŽ (Fig. 3). The main di†erence
appears again in the carbonyl group orientation. The cycles
show a quadrangular [3,4,3,4]-C arrangement where the exo-
cyclic amide nitrogen atom N1 is located two bonds away
from the adjacent corner atoms C3 and C5, while the amine
nitrogen atom N2 is located one bond away from the cor-
O1ÈC1
N1ÈC1
N1ÈC2
N2ÈC3
N2ÈC4
C1ÈC5
C2ÈC3
C4ÈC5@
1.264(2)
1.342(2)
1.453(2)
1.500(2)
1.462(2)
1.513(2)
1.509(2)
1.233(3)
1.342(3)
1.458(3)
1.490(3)
1.501(3)
1.511(3)
1.521(3)
1.242(2)
1.341(2)
1.454(2)
1.494(2)
1.498(2)
1.514(2)
1.516(2)
1.520(2)(iii)
121.8(1)
116.2(1)
122.1(1)
120.5(1)
117.4(1)
113.3(1)
113.2(1)
110.6(1)(iii)
113.2(1)(iii)
1.243(2)
1.338(2)
1.459(2)
1.497(2)
1.499(2)
1.517(2)
1.525(2)
1.528(2)(iv)
122.7(1)
115.2(1)
122.5(1)
120.3(1)
117.3(1)
113.23(9)
112.35(9)
111.6(1)(iv)
112.5(1)(iv)
1.527(2)(i) 1.522(3)(ii)
C1ÈN1ÈC2 121.4(2)
C3ÈN2ÈC4 113.6(1)
O1ÈC1ÈN1 122.9(1)
O1ÈC1ÈC5 122.0(1)
N1ÈC1ÈC5 115.1(1)
N1ÈC2ÈC3 112.1(1)
N2ÈC3ÈC2 111.3(1)
120.5(2)
115.5(2)
122.3(2)
120.7(2)
117.0(2)
113.0(2)
111.3(2)
N2ÈC4ÈC5@ 116.4(1)(i) 113.0(2)(ii)
C1ÈC5ÈC4@ 110.8(1)(i) 112.3(2)(ii)
a Symmetry transformations used to generate equivalent atoms: (i)
[ x, 1 [ y, [z; (ii) [x, [y ] 1, [z; (iii) [x ] 1, [y, [z ] 2; (iv)
x ] 1, [y, [z ] 1. b [H (1)](ClO ) crystallizes with two
2
Fig. 3 CHEM3D overlay of the bisamide rings in 1 É 2H O and
2
[
[H (1)]Br (left) and of both nonsymmetry related molecules of
2
4 2
2
2
nonsymmetry-related half-molecules in the asymmetric unit.
[H (1)](ClO ) (right). The rms deviation in 16 atom positions is 0.413
2
4 2
Ž , respectively (hydrogen atoms are omitted).
and 0.071 A
962
New J. Chem., 2000, 24, 959È966

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responding corner atom C3 and two bonds away from C5@. The
present study highlights the strong e†ect on the overall ring
conformation of the relative orientation of both carbonyl moi-
eties with respect to the macrocyclic cavity. As found for
by the fact that the N2ÈC3 and N2ÈC4 distances are sta-
tistically equal and average to 1.497(4) A
carbonÈamino nitrogen bond lengths di†er signiÐcantly in the
structure of 1, with C3ÈN2 \ 1.500(2) and C4È
N2 \ 1.462(2) A. While this di†erence in bond lengths is
Ž . In contrast, the two
A
Ž
1
É 2H O and [H (1)]Br , the amide groups take the most
Ž
2
2
2
stable Z arrangement. However, in the case of [H (1)](ClO )
4 2
the carbonyl bonds point towards the cavity, the mean amide
somewhat surprising, the value of the C4ÈN2 distance is
typical of nonprotonated amines in cyclam derivatives.52 The
same discrepancy is also observed for both angles involving
the secondary amine nitrogen atom, namely the N2ÈC3ÈC2
[111.3(3)¡] and N2ÈC4ÈC5@ [116.4(1)¡] angles. A possible
explanation could rely on the formation of two intermolecular
hydrogen bonds (Table 4): one between N2 and one cocrystal-
2
plane (rmsd of 0.0023 A) being rotated by 39.5(5)¡ and 44.7(5)¡
Ž
away from the C3ÈC5ÈC3@ÈC5@ plane for the two independent
molecules present in the asymmetric unit. The origin of this
displacement may be found in the di†erent environments
observed for the nonsymmetry related macrocycles in the unit
cell, which give rise to distinct hydrogen bond interactions
around the carbonyl oxygen atoms O1A and O1B (vide infra).
Likewise, three of the four possible [3,4,3,4] conformers have
been structurally characterized in the case of tetraprotonated
cyclam salt.52
lized water molecule [O3É É ÉN2 \ 2.865(2)
H6É É ÉN2 \ 164(3)¡] and the second between N1ÈH1 and the
carbonyl oxygen atom O1 [N1É É ÉO1 \ 2.933(2) A, N1È
A
Ž
,
O3È
Ž
H1É É ÉO1 \ 165(2)¡] belonging to an adjacent molecule gener-
ated by the symmetry transformation (x, 1 ] y, z). These
hydrogen bonds could displace the amino nitrogen atom N2
from its usual equidistant position between carbon atoms C3
and C4, giving rise to a lengthening of the C3ÈN2 bond and a
concomitant opening of the N2ÈC4ÈC5@ angle.
The directionality of each NÈR bond (i.e. R \ H in the
present case) is unique when the nitrogen atom is not occupy-
ing a vertex position, while a substituent attached to a nitro-
gen atom located at a corner or a pseudo-corner can point in
two possible directions (above or below the mean plane
encompassing the four nitrogen atoms). Thus, the conÐgu-
ration of the four nitrogen atoms is imposed by the three-
dimensional macrocyclic layout when the adopted
conformation is either [3,4,3,4]-B or [3,4,3,4]-C. Obviously,
there is a direct, and yet unrecognized, relationship between
DaleÏs description of macrocyclic conformations and the
stereochemical classiÐcation of 1,4,8,11-tetraazacyclotetra-
decane introduced by Bosnich et al.53 in the mid sixties. Most
intriguingly, this widely employed denomination relies solely
on the relative orientation (i.e. chirality) of the four NÈR
In all cases, the crystalline cohesion is mainly driven by a
network of hydrogen bonds. The crystal packing of both the
nonprotonated bisamide 1 and the dihydrobromic derivative
[H (1)]Br is almost equivalent. Macrocycles stack along
2
2
the shorter unit-cell axis (b \ 4.997 and a \ 5.2851 AŽ ,
respectively) by means of C2OÉ É ÉHÈN hydrogen bonds
forming molecular channels. The water molecules or bromine
anions are located between the parallel running chains of
macrocycles (Fig. 5), giving rise to a tridimensional network of
hydrogen bonds between neighboring stacks and the inter-
calated water molecules or anions.
bonds with respect to the N mean plane without considering
the topography of the macrocyclic chain. It can be easily re-
cognized from Fig. 4 that 14-membered cycloalkanes dis-
playing a [3,4,3,4]-B or [3,4,3,4]-C conformation can only
adopt a type IV geometry according to BosnichÏs formalism
Compared to 1 and [H (1)]Br , the crystal packing of
4
2
2
[H (1)](ClO ) (Fig. 6) shows basically the same features. The
2
4 2
main di†erence is related to the unit-cell axis along which the
stacking of macrocycles takes place: the presence of two inde-
pendent molecules in the crystal structure of [H (1)](ClO )
2
4 2
(i.e. both pairs of adjacent NÈH bonds belonging to ethyl-
induces a doubling of the cell parameter in the c axis direction
(c \ 10.8995 AŽ ).
enediamine moieties point in opposite directions).
For the three structures, the average C(sp3)ÈC(sp3) [1.518(7)
The relevant hydrogen bonding contacts found in the
crystal structures are reported in Table 4. Among them, the
strongest interaction systematically involves the carbonyl
AŽ ], C(sp3)ÈN [1.456(3) AŽ ] and carbonyl C(sp2)ÈN [1.341(3)
AŽ ] distances are typical of acyclic secondary amides.54 The
high quality di†raction data enabled us to localize at reason-
able bonding distances all the hydrogen atoms in the Fourier
di†erence maps at the end of the reÐnement process and con-
sequently to ascertain the protonation of the N2 atoms in
oxygen atom O1 as acceptor. In [H (1)]Br
and
2
2
Table 4 Intermolecular hydrogen bond distances (A
Ž ) and angles (¡)
for 1 and its two diprotonated forms [H (1)]Br and [H (1)](ClO ) a
2
2
2
4 2
[
H (1)]Br and [H (1)](ClO ) . The presence of quaternary
2
2
2
4 2
ammonium sites in these compounds is further corroborated
DÈHÉ É ÉA
d(DÈH) d(HÉ É ÉA) d(DÉ É ÉA) n(DHA)
1
É 2H O
2
N1ÈH1É É ÉO1(i)
N2ÈH2É É ÉO1(i)
O3ÈH6É É ÉN2
0.85(3)
0.91(2)
0.65(2)
2.10(3)
2.59(2)
2.23(2)
2.933(2)
3.435(2)
2.865(2)
165(2)
156(1)
164(3)
[
H (1)]Br
2
2
N1ÈHN1É É ÉBr1(ii)
N2ÈHN2É É ÉO1(ii)
N2ÈHN2É É ÉO1(iii)
N2ÈHN3É É ÉBr1(iv)
0.87(3)
0.85(3)
0.85(3)
0.89(3)
2.67(3)
2.04(3)
2.46(3)
2.39(3)
3.466(2)
2.825(3)
2.990(3)
3.251(2)
153(3)
153(3)
121(3)
162(3)
[
H (1)](ClO )
2
4 2
N1AÈHN1AÉ É ÉO2(v)
N1BÈHN1BÉ É ÉO6(vi)
N2BÈHN2BÉ É ÉO9(vi)
0.87(2)
0.80(2)
0.89(2)
2.18(2)
2.35(2)
2.36(2)
1.94(2)
1.98(2)
2.03(2)
2.14(2)
2.41(2)
3.052(2)
3.083(2)
2.991(2)
2.715(2)
2.856(2)
2.752(1)
2.934(1)
3.216(2)
174(2)
153(2)
128(1)
142(2)
169(2)
137(2)
147(2)
149(1)
N2AÈHN2AÉ É ÉO1A(vii) 0.90(2)
N2AÈNH3AÉ É ÉO9(viii)
N2BÈHN2BÉ É ÉO1B(ix)
N2BÈHN3BÉ É ÉO4(ix)
N2BÈHN3BÉ É ÉO5(ix)
0.89(2)
0.89(2)
0.90(2)
0.90(2)
a Symmetry transformations used to generate equivalent atoms: (i) x,
y ] 1, z; (ii) x [ 1, y, z; (iii) [x, [y ] 1, [z; (iv) [x, [y, [z; (v)
x ] 1/2, [y ] 1/2, z ] 1; (vi) x ] 1/2, [y ] 1/2, z; (vii) [x ] 1, [y,
[z ] 2; (viii) [x ] 1/2, y [ 1/2, [z ] 2; (ix) [x ] 1, [y, [z ] 1.
Fig. 4 Idealized wedge-type drawings of the quadrangular [3,4,3,4]-
B and [3,4,3,4]-C conformations showing the unique relationship with
BosnichÏs stereochemical representation of a type IV cyclam deriv-
ative.
New J. Chem., 2000, 24, 959È966
963

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tances were recalculated by placing the hydrogen atoms at the
mean bonded distance observed from neutron di†raction
experiments (N`ÈH \ 1.033 A
HN2AÉ É ÉO1A and N2BÈHN2BÉ É ÉO1B hydrogen bonding
distances change from 1.94 and 2.03 A to the more precise
values 1.84 and 1.93 A, respectively. Based on a previous study
Ž ).54 In this way, the N2AÈ
Ž
Ž
that established the relationship between the dissociation
energy D (in kJ mol~1) and the HÉ É ÉO interaction distance
E
r
(in A
Ž
) of XÈHÉ É ÉO hydrogen bonds (X \ C, N or O),
HÕ Õ ÕO
E
D \ 25 000 exp([3.6 r
both hydrogen bond interactions is close to 9.2 kJ mol~1.
This signiÐcant di†erence correlates with the presence of two
carbonyl stretching bands in the infrared spectrum of
),55 the energy di†erence between
HÕ Õ ÕO
[
H (2)](ClO ) separated by 16 cm~1.
4 2
In conclusion, the spectroscopic and crystallographic inves-
2
Fig. 5 Projection down the crystallographic b axis of the [H (1)]Br
tigations undertaken in the present work have shown that the
structural features of 5,12-dioxocyclam and its protonated
forms are mainly controlled by the crystal packing forces. As
evidenced by the potentiometric data, protonation of the se-
condary amines induces only limited conformational changes
in agreement with their optimized separation (N2É É ÉN2@ \
2
2
structure showing the crystal packing and the outline of one unit cell.
[
H (1)](ClO ) , O1 is hydrogen bonded to the protonated N2
4 2
nitrogen atom. The C1ÈO1 distances are signiÐcantly shorter
2
in the protonated structures (ranging from 1.233 to 1.243 A
Ž )
when compared to the nonprotonated molecule (1.264 A).
Ž
5
.32È5.57 AŽ ) in any of the quadrangular [3,4,3,4] conforma-
This indicates both a higher electron density in the C1ÈO1
bonds and a more important charge associated with the O1
atoms for the former compounds. Thus, the stronger inter-
action between the carbonyl oxygen and the surrounding
atoms in the protonated structures is reÑected by shorter
HÉ É ÉO hydrogen bonding distances compared to the non-
protonated compound and should lead to signiÐcant shifts
towards higher frequencies of the carbonyl stretching vibra-
tion.
tions. The major factor to be considered to explain the subtle
structural variations observed for the three compounds is the
intermolecular hydrogen bond network that involves the oxo
groups, the amine sites of adjacent molecules, and the sur-
rounding anions in the crystal lattice. Finally, the reported
results also a†ord new guidelines for understanding the pecu-
liar reactivity of this ““autodiprotectedÏÏ cyclam derivative
towards electrophilic reactants, allowing the synthesis of
numerous cross-bridged macrocycles and barrel-shaped
macrotricycles.
As expected, the shortest C2O distance M1.233 A for
Ž
[
H (1)]Br N correlates well with the infrared data recorded for
2
2
that compound, since the corresponding l band shifts to
CO
higher energy by 21 cm~1. In the case of [H (1)](ClO ) , both
Experimental
2
4 2
crystallographically independent molecules present in the cell
exhibit slightly longer and statistically equivalent C2O bond
lengths [1.242(2) and 1.243(2) AŽ ]. The shift to higher wave-
General
Unless otherwise noted, all reagents of analytical grade were
obtained from commercial suppliers and used without further
puriÐcation. 1H and 13CM1HN NMR spectra were recorded on
a Bruker AC 200 superconducting Fourier transform spectro-
meter operating at 200.13 and 50.03 MHz, respectively, at the
 
Centre de Spectroscopie Moleculaire de lÏUniversite de Bour-
gogne. All chemical shifts were referenced to the solvent peak.
Infrared spectra were measured as KBr pellets from 4000 to
numbers of the C2O band upon protonation of the ligand
with perchloric acid is therefore expected to be less important.
Moreover, splitting of the band into a doublet (1656 and 1640
cm~1) is experimentally observed, which might be related to
the di†erent environments surrounding the O1 atoms in both
independent molecules, namely their respective hydrogen
bonding patterns (Table 4).
In order to discuss this point further, the position of the
hydrogen atoms involved in the hydrogen bonds must be
accurately known. Although all the protons could be localized
in the di†erence Fourier maps, their exact position with
respect to the heavy atom cannot be determined by X-ray dif-
fraction experiments. As a Ðrst approximation, the N`ÈH dis-
400 cm~1 on a Bruker IFS 66v Fourier transform spectro-
meter. MALDI-TOF mass spectra were obtained on a Bruker
ProFLEX III spectrometer using dithranol as the matrix.
Microanalyses were performed on a Fisons EA 1108 CHNS
instrument or by the Service Central dÏAnalyse du Centre
National de la Recherche ScientiÐque, Vernaison, France.
Synthesis
1
,4,8,11-Tetraazacyclotetradecane-5,12-dione (1). To 5.6 L
(
83.57 mol) ethylenediamine maintained at 0 ¡C, 7.5 L (83.57
mol) methyl acrylate are added drop-wise over a period of 8 h.
The reaction mixture is then allowed to reach room tem-
perature and is stirred for 3 additional days. The cyclization
reaction is carried out in aqueous solution by dropping in 3.5
L of distilled water. After 6 more days of stirring, the white
precipitate is recovered by Ðltration, recrystallized in water
and dried (172 g, 1.8%). Anal. Found: C, 44.94; H, 9.15; N,
2
9
1.75; O, 24.22. C
H
N O É 2H O requires C, 45.44; H,
1
0 20 4 2
.15; N, 21.20; O, 24.21%. l
max
2
8
/cm~1: 3304 (br, l ), 2975
NH
(
l
), 2948 (l ), 2925 (l ), 2868 (l ), 1635 (l ) and 1556
CH2
CH2
CH2
3
CH2
CO
2
(d
); d (200 MHz, CDCl ): 1.48 (br s; 4H; H O), 2.39 (t,
Fig. 6 Projection down the crystallographic
c
axis of the
CNH
H
[
H (1)](ClO )
4 2 structure showing the crystal packing and the outline
3J \ 5.6 Hz; 4H; COCH ), 2.80 (t, 3J \ 5.2 Hz; 4H;
2
2
of one unit cell.
CONHCH CH ), 2.92 (t, 3J \ 5.6 Hz; 4H; COCH CH ) and
2
2
2
2
964
New J. Chem., 2000, 24, 959È966

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3
3
.38 (dt, 3J \ 5.2 Hz; 4H; CONHCH ); d (50 MHz, CDCl ):
square residuals on the observed emf readings (E ) is mini-
2
C
3
mes
5.5, 38.6, 45.8, 48.5 and 172.7; MALDI-TOF MS m/z: 229
mized according to the modiÐed Nernst equation: E
\
mes
[M ] H]`, 251 [M ] Na]`.
E0 ] S log[H`] ] J [H`] ] J K [H`]~1. In addition, the
a
b w
base-concentration factor (c) was also allowed to reÐne,
1,4,8,11-Tetraazacyclotetradecane-5,12-dione
dihydrobro-
whereas the ionic product of water was Ðxed (pK \ 13.78 in
w
0.1 M KNO at 25 ¡C).34 Calibration data were rejected when
3
mide, [H (1)]Br . Dioxocyclam (200 mg, 0.757 mmol) is dis-
2
2
solved in 50 mL hot methanol. After dissolution, addition of 1
mL of a concentrated HBr solution leads to the formation of a
white precipitate that is Ðltered o†, washed with cold meth-
anol and dried under vacuum (280 mg, 95%). X-Ray quality
crystals were obtained by slow evaporation of a saturated
aqueous solution. Anal. Found: C, 31.24; H, 5.88; N, 14.03.
the standard deviation of the residuals exceeded 0.12 mV. The
emf readings recorded for the subsequent titration were con-
verted with the help of an Microsoft Excel 5.0 spreadsheet
into p[H] values by iterative solving of the equation: p[H] \
(E0 [ E ] J [H`] ] J K [H`]~1)/S. The protonation
mes
a
b w
constants were reÐned by the weighted nonlinear least-squares
program Hyperquad 2000 for Windows NT.56 In the Ðnal
reÐnement step, the total amounts of titrated ligand and ini-
tially added acid were also allowed to vary. All presented
results are the average of at least three independent titrations.
The standard deviations of the stepwise protonation constants
(log KÏs) were derived from the full variance/covariance matrix
of the reÐned global constants (log bÏs).44
C
H
N O É 2HBr requires C, 30.79; H, 5.68; N, 14.36%.
1
0 20 4 2
l
8
/cm~1: 3257 (br, l ), 3139 (br, l ), 2939 (l ), 2849
max
NH
), 2757 (br, l `), 1656 (l ), 1570 (d ) and 1531 (d
NH CO CNH
NH
CH2
(
l
CNH).
CH2
1,4,8,11-Tetraazacyclotetradecane-5,12-dione
dihydroper-
chlorate, [H (1)](ClO ) . After dissolution of 200 mg (0.757
mmol) of dioxocyclam in 50 mL water, 1 mL of a concen-
trated HClO solution is added. Colorless, prismatic crystals
of diprotonated dioxocyclam suitable for X-ray di†raction
studies were obtained by slow evaporation of the reaction
mixture. Anal. Found: C, 28.63; H, 5.52; N, 12.88.
C
2
4 2
4
Crystal structure solution and reÐnement
High-quality, colorless single-crystal specimens of prismatic
shape M0.30 ] 0.22 ] 0.14 mm for 1, 0.14 ] 0.10 ] 0.10 mm
for [H (1)]Br , and 0.25 ] 0.12 ] 0.12 mm for [H (1)]
H N O É 2HClO requires C, 27.98; H, 5.17; N, 13.05%.
10 20 4 2
4
l
8
/cm~1: 3192 (br, l ), 3067 (br, l ), 2941 (l ), 2849
2
2
2
max
NH
NH
CH2
CNH
(
ClO ) N were selected for the X-ray di†raction experiments.
(
l
), 2778 (br, l `), 1656 (l ), 1640 (l ), 1570 (d ), 1533
4
2
CH2
NH
), 1115 (l
ClO4~
CO
CO
The X-ray source was graphite monochromatized Mo-Ka
radiation (j \ 0.710 73 A) from a sealed tube. Measurements
were collected at room temperature on a Stoe AED-2 (1) or at
12(2) K on a Nonius Kappa CCD di†ractometer equipped
(
d
), 1145 (l
) and 1089 (l
).
ClO4~
~
CNH
ClO4
Ž
Potentiometric titrations
1
with a nitrogen cryostream cooler from Oxford Cryosystems
All solutions were prepared with deionized water further puri-
Ðed by passage through an Elgastat UHQII (Elga) ion-
exchange cartridge system (resistivity 18 M) cm) and then
boiled for 2 h while being purged with argon. Titrant solu-
tions were stored under an atmosphere of puriÐed argon using
Ascarite II (Acros, 20È30 mesh) scrubbers in order to prevent
absorption of carbon dioxide. Carbonate-free 0.1 M KOH
was prepared from Merck concentrate (Titrisol}) and was
standardized by titrating against oven-dried (120 ¡C for 2 h)
potassium hydrogen phthalate (Aldrich, 99.99%) using a com-
bined Ag/AgCl glass semi-microelectrode (Mettler-Toledo)
Ðlled with a solution saturated with KCl and AgCl. Equiva-
lent points were calculated by the second-derivative method.
M[H (1)]Br and [H (1)](ClO ) N. Intensity data were record-
2
2
2
4 2
ed as u [ h scan proÐles (1), or r and u scans with i o†sets
M[H (1)]Br and [H (1)](ClO ) N up to a resolution of (sin h)/
2
2
2
4 2
j \ 0.59, 0.65 and 0.70 AŽ ~1, respectively. No signiÐcant inten-
sity decay was observed during the data collections. No
di†ractometer or temperature problems occurred during the
experiments. No signiÐcant absorption e†ects were observed
in any case, in particular for the quite small and roughly iso-
tropic [H (1)]Br crystal, in spite of its high linear absorption
2
2
coefficient [k(Mo-Ka) \ 5.6 mm~1]. Data reduction was done
using the commercial software X-RED release 1.1957 (1) or
DENZO58 M[H (1)]Br and [H (1)](ClO ) N.
2
2
2
4 2
The three structures were solved by direct methods using
the SHELXS97 program,59 the best phase set gave all the
positions for the non-H atoms in the diprotonated forms.
ReÐnements were carried out by full-matrix least squares on
F2 using the SHELXL97 program,60 and the complete set of
reÑections. Anisotropic thermal parameters were used for
non-H atoms. In all cases, the hydrogen atoms were located
by Fourier synthesis except for one belonging to a water mo-
lecule. In the case of the free-base form of 1, all hydrogen
atoms were reÐned with independent isotropic thermal factors.
For both protonated structures, the NÈH hydrogen atoms
were reÐned with isotropic thermal factors constrained to 1.2
times the equivalent isotropic thermal factor of their respec-
tive bonded atom, while the CÈH hydrogen atoms were
reÐned with a riding model and a global isotropic temperature
factor.
Solutions of 0.1 M HNO were similarly prepared and were
3
standardized by titrating against oven-dried (120 ¡C for 2 h)
TRIS bu†er (Aldrich, 99.9%). All titrations were performed
using a calibrated T110 (Schott) piston burette equipped with
a TA10 interchangeable unit of 10 mL and a TR250 (Schott)
data acquisition unit, both instruments being controlled by
TR600 software (release 5.2) running on an IBM-compatible
PC computer. Solutions were maintained under argon atmo-
sphere at constant ionic strength (I \ 0.1 KNO ) and tem-
3
perature [25.0(1) ¡C] by using a jacketed titration vessel Ðtted
to a Lauda RE 106 water bath.
Protonation constants were determined by pH-metric mea-
surements by using a XG100 (RadiometerÈTacussel) glass
electrode and a XR110 (RadiometerÈTacussel) KCl-saturated
calomel electrode. The reference electrode was separated from
the bulk of the solution by a sintered-glass bridge Ðlled with a
CCDC reference number 440/217. See http://www.rsc.org/
suppdata/nj/b0/b005052k/ for crystallographic Ðles in .cif
format.
0
.1 M KNO3
solution. Before each titration, the electrode
system was calibrated in hydrogen ion concentration units
(
p[H] \ [log[H`]) by titrating 4.00 mL of standardized
HNO diluted in 25 mL of 0.100 M KNO with standardized
3
3
KOH. The titration data comprised between p[H] 1.86 to
.65 and 10.97 to 11.89 were processed by nonlinear least-
squares minimization procedures available in Microsoft Excel
Acknowledgements
Dr Peter Gans (University of Leeds) is thanked for helpful
advice and stimulating discussions on potentiometric data
reÐnements. This work was supported by the Centre National
2
5
.0 in order to calculate the standard cell potential (E0), the
Nernst slope (S), together with the correction terms account-
ing for the changes in liquid junction potential in strongly
acid (J ) and alkaline (J ) media. The sum of the unweighted
de la Recherche ScientiÐque (CNRS) and the Conseil Re
de Bourgogne. L. F. thanks the Ministere de lÏEducation

gional
`
a
b
New J. Chem., 2000, 24, 959È966
965

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National, de la Recherche et de la Technologie for a Ph.D.
scholarship and E. E. gratefully acknowledges the CNRS for a
research grant (poste rouge).
28 H. Plenio and C. Aberle, Chem. Commun., 1998, 2697.
2
9
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