Copper(II) and zn(II) coordination chemistry of tetraaza[n]cyclophanes

Article abstract of DOI:10.1039/b303470d

The acid-base behaviour and Zn²⁺ and Cu²⁺ metal coordination chemistry of the novel orthocyclophane ligands 2,5,8,11-tetraaza[12]orthocyclophane (L²) and 2,5,9,12-tetraaza[13]orthocyclophane (L³) and metacyclophane 2,5,8,11-tetraaza[12]metacylophane (L¹) are studied. Important differences in the chemistry of these compounds are found depending on the substitution of the aromatic ring. The ortho derivatives are much more basic in their first two protonation steps while the metacyclophane presents much larger constants in the third and fourth protonation stages. The crystal structure of the picrate salt of [H₂L³]²⁺ shows an alternate disposition of the protons in the molecule with formation of N-H⁺...N hydrogen bonds between the protonated and non-protonated amino groups. While formation of mononuclear Cu²⁺ complexes is observed for L² and L³, the metaderivative L¹ forms also binuclear Cu²⁺ species which predominate largely for molar ratios M:L 2:1. The crystal structure of the complex [CuL³Cl](ClO₄) shows a chain-like arrangement with the [CuL³]²⁺ units interconnected by chlorine atoms. The coordination geometry around the metal ion is a distorted octahedron with the nitrogen atoms of the macrocycle at the vertices of the equatorial plane and chloride anions asymmetrically disposed at the axial positions. The Zn²⁺ complexes of the ortho derivatives L² and L³ are also much more stable than the meta counterparts. The crystal structure of [ZnL³Cl]Cl·H₂O shows a square pyramidal geometry with the nitrogen atoms of the macrocycle at the vertices of the equatorial plane and one chloride anion occupying the axial position. In this case there are not chain arrangements. The involvement of all the nitrogen atoms in the coordination of Zn²⁺ by L³ in aqueous solution is proved by ¹H and ¹³C NMR.

Full text of DOI:10.1039/b303470d

View Article Online / Journal Homepage / Table of Contents for this issue
Copper(II) and Zn(II) coordination chemistry of
tetraaza[n]cyclophanes
a
Martin Chadim, Pilar Dıaz, Enrique Garcıa-Espana,* Jana Hodacova,* Peter C. Junk,
b
b
a
d
´
Julio Latorre, Jose M. Llinares, Conxa Soriano and Jiri Zavada
´
˜
b
c
c
a
´
a
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
Flemingovo nam. 2, 166 10 Prague 6, Czech Republic. E-mail: hodacova@uochb.cas.cz
b
c
d
´
Departamento de Quımica Inorganica, Instituto de Ciencia Molecular, Universidad de Valencia,
C/ Dr. Moliner 50, 46100 Burjassot (Valencia), Spain. E-mail: enrique.garcia-es@uv.es.
´
´
´
Departamento de Quımica Organica, Instituto de Ciencia Molecular, Universidad de Valencia,
´
´
Avda. Vicente Andres Estelles, s/n, 46100 Burjassot (Valencia), Spain
School of Chemistry, PO Box 23, Monash University, Victoria, 3800, Australia.
E-mail: peter.junk@sci.monash.edu.au.
Received (in in London, UK) 27th March 2003, Accepted 13th May 2003
First published as an Advance Article on the web 12th June 2003
The acid–base behaviour and Zn2+ and Cu2+ metal coordination chemistry of the novel orthocyclophane
ligands 2,5,8,11-tetraaza[12]orthocyclophane (L2) and 2,5,9,12-tetraaza[13]orthocyclophane (L3) and
metacyclophane 2,5,8,11-tetraaza[12]metacylophane (L1) are studied. Important differences in the chemistry of
these compounds are found depending on the substitution of the aromatic ring. The ortho derivatives
are much more basic in their first two protonation steps while the metacyclophane presents much larger
constants in the third and fourth protonation stages. The crystal structure of the picrate salt of [H2L3]2+ shows
an alternate disposition of the protons in the molecule with formation of N–H+ꢀ ꢀ ꢀN hydrogen bonds between
the protonated and non-protonated amino groups. While formation of mononuclear Cu2+ complexes is
observed for L2 and L3, the metaderivative L1 forms also binuclear Cu2+ species which predominate largely for
molar ratios M:L 2:1. The crystal structure of the complex [CuL3Cl](ClO4) shows a chain-like arrangement with
the [CuL3]2+ units interconnected by chlorine atoms. The coordination geometry around the metal ion is a
distorted octahedron with the nitrogen atoms of the macrocycle at the vertices of the equatorial plane and
chloride anions asymmetrically disposed at the axial positions. The Zn2+ complexes of the ortho derivatives L2
and L3 are also much more stable than the meta counterparts. The crystal structure of [ZnL3Cl]ClꢀH2O shows a
square pyramidal geometry with the nitrogen atoms of the macrocycle at the vertices of the equatorial plane
and one chloride anion occupying the axial position. In this case there are not chain arrangements. The
1
involvement of all the nitrogen atoms in the coordination of Zn2+ by L3 in aqueous solution is proved by H
and 13C NMR.
are linked in para position through benzylic groups to a
Introduction
benzene ring (L).3 In such a ligand, on the one hand the
presence of the para-substituted ring prevents the simulta-
neous coordination of both benzylic nitrogens to a single
metal ion, and on the other hand the size of the polyamine
makes the bridge rigid enough to divide it into two sepa-
rated coordination sites This situation was evidenced by
the crystal structure of the binuclear Cu2+ complex of L,3
[Cu2LCl2]Cl2 , in which the tetraamine chain behaves as two
independent ethylenediame subunits each one of them coordi-
nating a Cu2+ metal ion. Larger more flexible chains would
not offer this characteristic.4
A recurrent feature in the active site of many metalloenzymes
is that they offer to the metal ions coordinatively unsaturated
environments so that the metal can fix through its vacant posi-
tions a given substrate inducing its transformation. Addition-
ally, a number of these metalloenzymes present binuclear
sites in which the two metal ions cooperate in the recognition
and activation of a given substrate.1
This knowledge from the biological world has prompted
many researchers to synthesize molecules displaying such char-
acteristics and several approaches have been used. Some of
these molecules could be: i) mononuclear complexes intercon-
nected by bridging ligands, ii) ditopic ligands with well-
separated and identifiable binding sites, iii) macrocycles
containing a large number of donor groups in the cavity.2
A much more novel strategy consists of generating cyclic
compounds with a reduced number of donors, in which
the binucleating ability is the result of a correct balance
between electron and stereochemical requirements. One such
example is the macrocycle 2,5,8,11-tetraaza[12]paracyclo-
phane in which both ends of a triethylenetetramine chain
In order to complete this picture and understand the effects
of the different substitution of the benzene spacer, macrocycles
with orthophenylene and methaphenylene units needed to be
analyzed. In the present work we report on the synthesis of
the new metacyclophane 2,5,8,11-tetraaza[12]metacyclophane
(L1), which is analogous to L but with the benzene ring meta-
substituted. We report on its protonation behaviour and its
coordination capabilities towards Cu2+ and Zn2+. We present
the same studies for the recently prepared compounds 2,5,8,11-
tetraaza[12]orthocyclophane (L2), the ortho counterpart of L
1132
New J. Chem., 2003, 27, 1132–1139
DOI: 10.1039/b303470d
This journal is # The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2003

View Article Online
Scheme 1
Synthesis of L2 and L3
The ligands L2 and L3 were synthesized following the experi-
mental procedure reported in ref. 5 and depicted in Scheme
1. The compounds were isolated and handled as the hydro-
chloride salts L2ꢀ3HCl and L3ꢀ4HCl and gave satisfactory
spectroscopic and elemental analysis. Anal Calcd. for
C14H27N4Cl3(L2ꢀ3HCl) C, 47.0, H, 7.6, N, 15.7. Found: C,
46.2, H, 7.6, N, 15.3%. C15H30N4Cl4(L3ꢀ4HCl) C, 44.1, H,
7.4, N, 13.7. Found: C, 43.8, H, 7.3, N, 13.5%.
Chart 1
and L1, and 2,5,9,12-tetraaza[13]orthocyclophane (L3). Addi-
tionally, we describe the crystal structure of the complexes
[CuL3Cl](ClO4) and [ZnL3Cl]ClꢀH2O.
X-ray crystallography
Crystal data and details of the data collection for the picrate
salt [H2L3](pic)2ꢀ1/2C3H6O (1) (pic ¼ 2,4,6-trinitrophenolate)
and the complexes [CuL3Cl](ClO4)2 (2) and [ZnL3Cl]ClꢀH2O
(3) are given in Table 1y.
Experimental
For (1) the crystal data was collected with an Enraf-Nonius
Synthesis of L1 4HBr
.
˚
CAD-4 single crystal diffractometer (l ¼ 0.71073 A) , and for
(2) and (3) with a Nonius Kappa CCD equipment (l ¼
The procedure used was a modification of that previously
described for related para- and metacyclophane derivatives.5,6
˚
0.71073 A). The crystals were monitored for decay during data
collection and corrections for decay were made, if warranted.
Profile analysis was performed on all reflections.7 A semiempi-
rical absorption correction, C-scan based, was performed .8
Lorentz and polarisation corrections were applied and the data
L1 4Ts
.
The pertosylated tetraamine trien L1 (5.0 g, 6.6 mmol),6 and
K2CO3(4.4 g. 31.6 mmol) were suspended in refluxing DMF
(100 mL). To this mixture, a solution of 1,3-bis(bromomethyl)-
benzene (1.8 g, 6.8 mmol) in 100 mL of DMF was added drop-
wise over a period of 4 h. After the addition was completed,
the reaction was kept refluxing for 48 h. The solution was
vacuum evaporated to dryness to obtain the crude product
that was recrystalised in CH2Cl2/EtOH to give the final pro-
were reduced to F2 values. The structure was solved by the
o
Patterson method using the program SHELXS-86 running
on an IBM PENTIUM III 1000 computer.9 Isotropic least-
squares refinement was performed by means of the program
SHELXL-93.10 In the crystallographic analysis of 1, the pro-
tons on the nitrogen atoms in the macrocycle have been
located. The other hydrogen atoms of 1 and those of 2 and 3
were placed in calculated positions.
All the non-hydrogen atoms were refined anisotropically.
The hydrogen atoms were refined with a common thermal
parameter. Atomic scattering factors were taken from the
International Tables for X-Ray Crystallography.11 The
molecular plots were produced by the program ORTEP.12
1
duct (5.3 g, 93% yield): mp 228–230. H NMR, 2.44 (s, 6H),
2.46 (s, 6H), 2.67 (s, 4H), 2.90–2.99 (m, 8H), 4.12 (s, 4H),
7.28–7.38 (m, 12 H), (7.66–7.76 m, 8H). 13C NMR, 21,6,
47.9, 48.8, 49.8, 54.4, 127.4, 127.5, 128.9, 129.6, 129.9, 130.0,
134.4, 135.5, 136.6, 143.8, 144.0. MS m/z (FAB) 865
[M + H]+.
[H2L3](pic)2 1/2C3H6O (1)
.
L1 4HBr
.
Crystals of 1 suitable for X-ray analysis were obtained on crys-
tallisation of L dipicrate from an acetone–water mixture. Anal.
Calcd. for C28.5H35N10O14.5 : C, 45.7, H, 4.7, N, 18.7. Found :
C, 45.6, H, 4.8, N, 18.9%.
In a round bottom flask were introduced L1ꢀ4Ts (3.0 g, 3.5
mmol), PhOH (16.2 g, 165 mmol) and HBr/AcOH (33%,
166 mL). The solution was stirred under reflux for 18 h to
obtain a precipate. This precipitate was filtrated and washed
consecutively with CH2Cl2 (100 mL) and EtOH (100 mL) to
obtain L1ꢀ4HBr as a white solid product (1.5 g, 74% yield):
mp 234–238 ꢁC. 1H NMR, 2.94–2.96 (m, 8H), 3.17 (t, 4H, J ¼
8 Hz), 4.31 (s, 4H), 7.40 (s, 1H), 7.55 (s, 2H), 7.63 (s, 1H).
13C NMR, 42.1, 42.6, 43.8, 50.5, 131.7, 132.0, 132.9, 133.2.
Anal Calcd. For C14H28N4Br4 : C, 29.4, H, 4.9, N, 9.8. Found:
C, 29.1, H, 4.9, N, 9.5%.
3
Synthesis of [CuL Cl]ClO4 (2) and [ZnL Cl]Cl H2O (3)
3
.
Crystals of 2 and 3 suitable for X-ray analysis were obtained
respectively by slow evaporation at pH 8.0 or pH 9.0 of solu-
y CCDC reference numbers 209937–209939. See http://www.rsc.org/
suppdata/nj/b3/b303470d/ for crystallographic data in .cif or other
electronic format.
New J. Chem., 2003, 27, 1132–1139
1133

View Article Online
Table 1 Crystal data and structure refinement for [H2L3](pic)2ꢀ1/2C3H6O (1), [CuL3Cl](ClO4) (2) and [ZnL3Cl]ClꢀH2O (3)
1
2
3
Empirical formula
Formula weight
Temperature (K)
C
749.66
28.5H35N10O14.5
C15H26Cl2CuN4O4
460.84
293(2)
C15H28Cl2ZnN4O
416.70
293(2)
173(2)
0.71073
Triclinic
˚
Wavelength (A)
Crystal syst
0.71073
Orthorhombic
Pmnb
0.71073
Triclinic
¯
P1
¯
P1
Space Group
˚
a (A)
˚
8.188(1)
13.392(2)
9.4520(2)
11.0000(3)
19.3590(7)
7.1050(2)
11.2190(3)
b (A)
˚
c (A)
15.778(2)
92.796(3)
12.2640(4)
98.202(1)
a (deg)
b (deg)
g (deg)
92.386(3)
101.263(3)
1692.4(4)
95.208(1)
92.828(1)
961.66(5)
3
˚
Volume (A )
2012.8(1)
4
1.521
Z
2
1.471
2
1.439
Calculated density (g cmꢃ3
)
Abs coeff (mmꢃ1
F(000)
)
0.120
784
1.378
956
1.563
436
yq range (degrees)
Reflections collected/unique
1.96 to 23.31
7904/4854
2.10 to 27.50
4286/2413
2.88 to 27.49
6918/4363
[R(int) ¼ 0.0362]
1.051
[R(int) ¼ 0.0432]
1.008
[R(int) ¼ 0.0201]
0.877
Goodness-of-fit on F2
Final R indices [I > 2s(I)]
R indices (all data)
R1 ¼ 0.0714, wR2 ¼ 0.2123
R1 ¼ 0.0441, wR2 ¼ 0.1285
R1 ¼ 0.1044, wR2 ¼ 0.1758
R1 ¼ 0.0361, wR2 ¼ 0.1062
R1 ¼ 0.0480, wR2 ¼ 0.1169
R1 ¼ 0.0989, wR2 ¼ 0.2435
w ¼ 1/[s2(Fo2) + (0.2537 P)2 + 12.86 P] where P ¼ (Max (Fo2) + 2 Fc2)/3.
tions containing L2ꢀ4HCl and Cu(ClO4)2 or Zn(ClO4)2 in 1:1
molar ratio. Anal 2. Calcd for C15H26Cl2CuN4O4(1): C, 39.1,
H, 5.7, N, 12.2. Found: C, 39.0, H, 5.5, N, 12.3%. Calcd for
C15H28Cl2ZnN4O (2): C, 43.2, H, 6.8, N, 13.5. Found: C,
43.2, H, 6.5, N, 13.4%. (CAUTION. Picrate and perchlorate
salts can be explosive and have to be handled with care.)
Finally, the sets of data were merged together and treated
simultaneously to give the final stability constants.
NMR measurements
The 1H and 13C NMR spectra were recorded on Varian
UNITY 300 and UNITY 400 spectrometers, operating at
299.95 and 399.95 MHz for 1H and at 75.43 and 100.58
MHz for 13C. The spectra were obtained at room temperature
in D2O or CDCl3 solutions. For the 13C NMR spectra dioxane
was used as a reference standard (d ¼ 67.4 ppm) and for the
1H spectra the solvent signal. Adjustments to the desired pH
were made using drops of DCl or NaOD solutions. The pH
was calculated from the measured pD values using the correla-
tion, pH ¼ pD ꢃ 0.4.17
emf Measurements
The potentiometric titrations were carried out at 298.1 ꢂ 0.1 K
using NaClO4 0.15 mol dmꢃ3 as supporting electrolyte. The
experimental procedure (burette, potentiometer, cell, stirrer,
microcomputer, etc.) has been fully described elsewhere.13
The acquisition of the emf data was performed with the com-
puter program PASAT.14 The reference electrode was an Ag/
AgCl electrode in saturated KCl solution. The glass electrode
was calibrated as a hydrogen-ion concentration probe by titra-
tion of previously standardized amounts of HCl with CO2-free
NaOH solutions and determining the equivalent point by the
Gran’s method,15 which gives the standard potential, Eꢁ0,
and the ionic product of water (pKw ¼ 13.73(1)).
Results and discussion
Acid–base behaviour
Table 2 shows the stepwise protonation constants of the
metacyclophane L1 orthocyclophanes L2 and L3, and those
previously reported for the paracyclophane derivative L.3
Both orthocyclophanes present very large constants for the
first and second protonation steps while the values of the pro-
tonation constants for the third and fourth protonations are
very low. As a matter of fact, under our experimental condi-
tions it has not been even possible to determine the values of
the constant for the last protonation step that can be estimated
to be clearly below 2 logarithmic units.
The computer program HYPERQUAD was used to calcu-
late the protonation and stability constants.16 The pH range
investigated was 2.5–10.5 and the concentration of the metal
ions and of the ligands ranged from 1 ꢄ 10ꢃ3 to 5 ꢄ 10ꢃ3 mol
dmꢃ3 with M:L molar ratios varying from 2:1 to 1:2 The dif-
ferent titration curves for each system (at least two) were
treated either as a single set or as separated curves without
significant variations in the values of the stability constants.
Table 2 Stepwise protonation constants for the metacyclophane L1 and orthocyclophanes L2 and L3. The corresponding constants for L have also
been included by means of comparison
Reaction
L1
L2
10.38(1)
L3
11.01(3)
Lc
L4d
10.35
L5e
L6e
L7e
H + L ¼ HLa
9.53(1)b
8.74(1)
5.61(2)
2.77(3)
9.39(2)
8.45(2)
5.38(2)
2.51(1)
11.5
10.5
1.5
10.92
9.40
4.62
2.00
10.64
9.82
3.5
H + HL ¼ H2L
H + H2L ¼ H3L
H + H3L ¼ H4L
9.30(1)
2.96(2)
10.88(3)
2.20(7)
9.71
2.05
< 2
< 2
< 1
0.9
1.4
a
Charges omitted for clarity. b Values in parentheses are standard deviations in the last significant figure. c Taken from ref. 3. d Taken from ref.
19. Taken from ref. 18, I ¼ 0.1 mol dmꢃ3
.
e
1134
New J. Chem., 2003, 27, 1132–1139

View Article Online
Interestingly enough, the macrocycle presenting the larger
constants for the two first protonation stages and the lower
constants for the last two is L3, containing a symmetric set
of two ethylenic and one propylenic hydrocarbon chains
between the nitrogen atoms in the bridge (Chart 1). The beha-
viour of the metacyclophane L1 is very close to that reported
for the analogue paracyclophane L and quite different from
that of L2 and L3. L1 shows large values, although much
reduced than L2 and L3, for the first two protonation con-
stants, one intermediate value for the third constant and a
much smaller value for the fourth protonation which is how-
ever, comparable to the one found for the third protonation
step of L2 and L3. Indeed, the values of the protonation
constants of the orthocyclophanes are close to those of satu-
rated azacycloalkanes. The dramatic decrease in basicity
between the second and third protonation steps of L2 and L3
(D(logKH L/H L) ¼ 6.34 and 8.68, respectively) lies between
in b-position with respect to N1, shows an important upfield
shift (Dd ¼ 7.8 ppm) on going from pH 11.0 to 5.0 where
the triprotonated species predominate in solution.
Correspondingly, the chemical shift of H1 moves markedly
downfield in the same pH range (Dd ¼ 0.7 ppm) (Fig. 1). At
lower pH values, in correspondence with the last protonation,
the chemical shifts of these signals do not bear further changes
while the signals of C4 and H4 shift upfield and downfield
respectively. All these data suggest that two out of the three
first protonation steps involve the benzylic nitrogen atoms.
Similar results have been obtained for the paracyclophane
L.2,23 The desolvation produced by the hydrophobic spacer
seems to be an important clue for this behaviour.
However, as above noted, the behaviour of the orthocyclo-
phane derivatives is completely different. For example, clear
tendencies are not found for the variation of the chemical shift
of the CB1 resonance and upfield movements accompany all
the protonation steps of L. Similar tendencies are observed
for the other signals, which show that in the ortho derivatives
the protons do not follow any fixed sequence and are shared by
the different nitrogens along the protonation process.
2
3
those reported for the well-known macrocycles cyclen L4
(D(logKH L/H L) ¼ 7.66) and cyclam L5 (D(logKH L/H L) ¼
2
3
2
3
9.0) and those of the macrocycles L6 (D(log KH L/H L) ¼
2
3
4.78) and L7 (D(log KH L/H L) ¼ 6.32) (Table 2) with the same
2
3
number of atoms in the ring as L2 and L3 but with a butylene
chain instead of the aromatic spacer.18,19 Actually, molecular
modeling calculations as well as the crystal structure of
[H2L3](pic)2ꢀ1/2C3H6O denote that, due to the rigidity
afforded by the ring, L2 and L3 present closer sizes to those
of cyclen and cyclam, respectively, than to those of L6 and
L7. These results reflect the key influence of the size and
arrangement of the macrocyclic cavity on determining the dis-
tribution of positively charged atoms and thereby, on the basi-
city of these cyclic polyamines. Nevertheless, just the repulsion
between same sign charges is not enough for explaining all the
tendencies found and intramolecular hydrogen bonding should
also play an important contribution to the large first two pro-
tonation constants observed for L2 and L3. Indeed, the crystal
structure of the picrate salt of the diprotonated form of
[H2L3]2+ shows such a formation of a hydrogen bond network
between the protonated and non-protonated amino groups
(vide infra, see Fig. 2B). Analogously, the dramatic drop in
basicity between the second and third protonation steps can
be probably ascribed among other factors to the disruption
of the intramolecular hydrogen bonding formed in the
[H2L3]2+ species. A similar behaviour has been described for
cyclam.20,21
Crystal structure of [H2L3](pic)2 1/2C3H6O, 1
.
Figs. 2A and 2B show the most distinctive features of the crys-
tal structure, which regard the conformation of the macrocycle
and the formation of either intramolecular or intermolecular
hydrogen bonds. The intramolecular hydrogen bonds are esta-
blished between alternated protonated and non-protonated
amino groups connected by the propylenic chains (Fig. 2B)
˚
˚
with distances N1–Hꢀ ꢀ ꢀN4 1.946 A and N3–Hꢀ ꢀ ꢀN2 1.797 A
and angles of 166.0 and 166.8ꢁ, respectively. This type of intra-
molecular bonds resemble very much those reported for the
perchlorate salt of the diprotonated form of 1,4,8,11-tetraaza-
cycloalkane ((H2L5)2+, H2(cyclam)2+),20 although the dis-
tances are in the present case shorter. Intermolecular
hydrogen bonds occur between the amino groups of L and
the trinitrophenolate anions.
The bifurcated hydrogen bonds are observed between the
phenolate oxygen atoms and the amino groups of the macro-
˚
cycle with distances N1–Hꢀ ꢀ ꢀO1A 2.083 A, N3–Hꢀ ꢀ ꢀO1A
˚
˚
˚
2.166 A, N2–Hꢀ ꢀ ꢀO1B 2.155 A and N4–Hꢀ ꢀ ꢀO1B 2.336 A
and angles of 154, 140, 144, and 128ꢁ, respectively. They are
ensembled with two weak hydrogen bonds between the proto-
nated amino groups and the nitro groups of the one picrate
˚
In order to obtain further information about the protona-
tion pattern of polyamine compounds, 1H and 13C NMR spec-
tra often provide valuable information. It is well established,22
that upon protonation, the carbon atoms placed in b-position
and the hydrogen nuclei attached to the carbon atom in
a-position to the nitrogen undergoing protonation are those
exhibiting the largest changes in chemical shifts. For the
metacyclophane L1, a plot of the variation in chemical shift
of the quaternary aromatic carbon CB1 (Fig. 1), located only
anion with distances N1–Hꢀ ꢀ ꢀO2A 2.362 A and N3–Hꢀ ꢀ ꢀO7A
ꢁ
˚
2.355 A and angles of 133 and 149 , respectively. One of the
picrate anions is placed quite parallel to the benzene ring
affording stacking between the rings.
The overall conformation of the macrocycle is folded (Fig.
2) by the effect of the intramolecular hydrogen bonds giving
a sort of boat shape to the compound.
Metal coordination
Solution studies
The stepwise stability constants for the formation of Cu2+ and
Zn2+ complexes of the metacyclophane L1 and of the ortho-
cyclophanes L2 and L3 are shown in Tables 3 and 4 conjointly
with those for L,2 and relevant data for some saturated tetra-
azacycloalkanes.18,24
The first aspect that deserves comment for the Cu2+ com-
plexes is that, accordingly with the protonation behaviour,
completely different speciation models are found for the ortho-
and meta-derivatives. The model for the systems Cu-L2 and
Cu-L3 consists just of the mononuclear species [CuL2]2+
,
[CuL2(OH)]3+, [CuHL3]3+ and [CuL3]2+, while L1 forms the
mononuclear species [CuH2L1]4+
, , ,
[CuHL1]3+ [CuL1]2+
[CuL1(OH)]+ and the binuclear ones [Cu2L(OH)]3+ and
[Cu2L(OH)2]2+ (Fig. 3).
Fig. 1 Representation of the variation of chemical shifts of carbon
B1 and hydrogen H1 with the pH for the metacyclophane L1.
New J. Chem., 2003, 27, 1132–1139
1135

View Article Online
The model found for L1 keeps some parallelism with that
previously reported for the analogue paraazacyclophane L.
Interestingly enough, the larger meta-derivative 2,6,9,13-tetra-
aza[14]metacyclophane L8 with a set of two propylenic and
one middle ethylenic chain does not form binuclear complexes.4
A second point of interest regards the magnitude of the
stability constants of the [CuL]2+ and [ZnL]2+ complexes,
which are much higher for the ortho-derivatives than for the
meta-derivatives. In turn, the meta-derivative L1 presents
higher stability than the para-derivative L (Tables 3 and 4).
On the other hand, the complexes of any of the cyclophane
ligands are clearly less stable than those of cyclam and cyclen.
These data can be interpreted taking into account the char-
acteristics of the different ligands here considered. Firstly, at
difference with the meta- and para-derivatives, the orthocy-
clophanes present a suitable size to coordinate a single metal
ion involving all their nitrogen donors. Molecular modeling
on the free non-protonated L, L1 and L2 show the distances
˚
˚
between the benzylic nitrogens (N1) to be 3.57 A, 5.34 A and
˚
6.95 A, respectively (Chart 2). For L the distance between the
˚
benzylic nitrogens would be 4.42 A. The crystal structure of
[H2L3]2+ shows distances of 2.83 A between the benzylic
˚
nitrogens.
Therefore, para- and meta-substitution prevents both
benzylic nitrogens from participating simultaneously in
the binding of
a single metal ion. This evidence was
already provided by several crystal structures involving
para-azacyclophanes.3,4 In the ortho-derivatives, however,
the nitrogens can approach close enough to the metal ion
for making bonds as denoted by the crystal structures of the
complexes [CuL3Cl]ClO4 and [ZnL3Cl]ClꢀH2O (vide infra).
Therefore, all four nitrogens of the ortho-derivatives L2 and
L3 should be involved in the coordination of the metal ions.
For L1, the comparison of the stability constants with those
of L2 and L and with relevant data for related systems sug-
gests three as the possible number of co-ordinating nitrogens.
The NMR spectra of a D2O solution containing zinc triflate
and L3 in molar ratio 1:1 at pH 7 where [ZnL3]2+ is the only
species in solution also support the full-involvement of the
nitrogen atoms of L in the coordination to Zn2+. The 13C
NMR spectrum presents five resonances in the aliphatic region
at 21.5, 47.6, 48.8, 49.9 and 51.7 ppm and three signals in the
aromatic zone at 129.6 ppm, 132.3 and 136.4 ppm denoting a
two-fold symmetry for the complex. The 1H NMR spectrum at
the same pH shows the same symmetry but evidences the stif-
fening afforded by the metal ion to the molecule. The benzylic
protons appear as an AB spin system (dA ¼ 4.08 ppm, dB
¼
3.56 ppm, JAB ¼ 11.2 Hz). The ethylenic chain and the central
propylenic chain present ABCD spin patterns denoting the
stiffening that the coordination of the metal imparts to the
molecule.
Fig. 2 A) ORTEP plot of the cation [H2L3]2+. Counteranions are
omitted. Thermal ellipsoids are drawn at the 50% probability level.
B) Stick drawing showing inter- and intramolecular hydrogen bonds.
As mentioned above the [CuL]2+ complexes of L2 and L3
are less stable than the related complexes of cyclen and cyclam.
A plausible explanation for this may rest in the 7-membered
chelate ring formed at the side of the aromatic ring that
Table 3 Logarithms of the stepwise stability constants for the formation of Cu2+ complexes by L1, L2 and L3 determined in 0.15 mol dmꢃ3 at
298.1 K. The corresponding constants for the paracyclophane L3 have also been included by means of comparison
Reaction
L1
L2
L3
Lc
L4d
L5d
L6d
CuHL + H ¼ CuH2La
3.58(5)b
CuL + H ¼ CuHL
6.90(2)
13.52(4)
ꢃ8.82(5)
10.67(4)
3.60(5)
3.89(5)
17.73(3)
6.51
10.41
Cu + L ¼ CuL
19.58(5)
ꢃ11.42(7)
24.6
27.2
15.47
CuL + H2O ¼ CuL(OH) + H
2Cu + L + H2O ¼ Cu2L(OH) + H
2Cu + L + 2H2O ¼ Cu2L(OH)2 + 2H
ꢃ8.14
3.44
a
Charges omitted for clarity. b Values in parentheses are standard deviations in the last significant figure. c Taken from ref. 3. d Taken from ref.
18, I ¼ 0.1 mol dmꢃ3
.
1136
New J. Chem., 2003, 27, 1132–1139

View Article Online
Table 4 Logarithms of the stepwise stability constants for the formation of Zn2+ complexes by L, L2 and L3 determined in 0.15 mol dmꢃ3 at 298.1
K. The corresponding constants for the paracyclophane L3 have also been included by means of comparison
Reaction
L1
L2
L3
Lc
L4d
L5d
L6d
ZnHL + H ¼ ZnH2La
ZnL + H ¼ ZnHL
7.08(4)b
6.27(3)
ꢃ7.97(5)
6.51
4.55
ꢃ8.60
Zn + L ¼ ZnL
13.45(1)
ꢃ8.96(2)
13.77(1)b
ꢃ10.33(2)
16.2
ꢃ8.02
15.5
ꢃ9.77
12.90
ZnL + H2O ¼ ZnL(OH) + H
a
Charges omitted for clarity. b Values in parentheses are standard deviations in the last significant figure. c Taken from ref. 3. d Taken from ref.
18, I ¼ 0.1 mol dmꢃ3
.
would bear energetically expensive conformational rearrange-
ments for binding the metal. However, the comparison of the
stability constants for L2 and the aza-cycloalkane L6 with the
same number of atoms in the macrocyclic ring denotes in
this case an even more energetically demanding situation.18,25
Crystal structure of [CuL3Cl](ClO4) (2)
The crystal structure of [CuL3Cl](ClO4) is a chain-like struc-
ture in which [CuL3]2+ fragments are interconnected through
asymmetric chloride bridges (Figs. 4A and 4B).
The coordination geometry around the copper is a strongly
distorted octahedron. The vertices of the equatorial plane are
defined by the nitrogen atoms of the macrocycle with distances
˚
˚
Cu1–N4 2.051(4) A and Cu(1)–N4 2.039(4) A. The Cu(II) ion is
sited in the average plane defined by the four nitrogen atoms.
The chloride anions placed at the axial positions connect
asymmetrically two metal ion centers (Cu–Cl distances
˚
2.718(2) and 2.810(2) A). Table 5 collects the distances and
angles around the coordination site.
The Cu–N distances are longer than those found in the
cationic complex [Cu(cyclam)]2+ denoting the steric hindrance
provided by the 7-membered chelate ring at the side of the aro-
matic fragment.26 The conformation of the five-membered che-
late rings is gauche while the six membered-ring presents a
chair conformation. An analogous conformation is displayed
by the seven-membered ring at the side of the aromatic ring
that might be defined as a chair with a back defined by the
Fig. 3 Distribution diagram for the system Cu2+-L1. A)
[Cu2+] ¼ [L1] ¼ 10ꢃ3 M. B) [Cu2+] ¼ 2 ꢄ 10ꢃ3 M, [L1] ¼ 10ꢃ3 M.
Fig. 4 A) ORTEP drawing for the cation [CuL2Cl]+. Thermal ellip-
soids are drawn at the 50% probability level. B) Portion of one of the
chains formed in the crystal structure.
Chart 2
New J. Chem., 2003, 27, 1132–1139
1137

View Article Online
Table 5 Bond angles and distances for [CuL3Cl](ClO4) (2)
Table 6 Selected bond angles and distances for [ZnL3Cl]ClꢀH2O (3)
Cu(1)–N(2)
Cu(1)–N(1)
Cu(1)–Cl(1)
2.036(3)
2.054(3)
2.7178(13)
Zn(1)–N(3)
Zn(1)–N(2)
2.129(2)
2.140 (2)
2.144(2)
2.145(2)
2.3507(7)
87.13(8)
160.07(8)
82.75(8)
83.15(7)
161.65(8)
101.52(7)
100.72(6)
98.21(6)
97.70(6)
98.87(5)
Zn(1)–N(1)
Zn(1)–N(4)
Zn(1)–Cl(1)
N(2)#1–Cu(1)–N(2)
N(2)#1–Cu(1)–N(1)
N(2)–Cu(1)–N(1)
N(2)–Cu(1)–N(1)#1
N(1)–Cu(1)–N(1)#1
N(2)–Cu(1)–Cl(1)
N(1)–Cu(1)–Cl(1)
91.41(19)
175.80(12)
84.83(14)
175.80(12)
98.87(17)
94.46(10)
87.70(10)
N(3)–Zn(1)–N(2)
N(3)–Zn(1)–N(1)
N(2)–Zn(1)–N(1)
N(3)–Zn(1)–N(4)
N(2)–Zn(1)–N(4)
N(1)–Zn(1)–N(4)
N(3)–Zn(1)–Cl(1)
N(2)–Zn(1)–Cl(1)
N(1)–Zn(1)–Cl(1)
N(4)–Zn(1)–Cl(1)
Symmetry transformations used to generate equivalent atoms: #1 ꢃx
+ 1/2,y,z, #2 ꢃx + 3/2,y,z
aromatic carbon atoms (see Fig. 4A). The disposition of the
hydrogen atoms of the nitrogen donors is ++ꢃꢃ following
the notation that Bosnich et al have introduced for related che-
lates,27 and the folding of he ligand will define a trans IIII
RRSS isomer.28
the substitution of the aromatic spacer and on the length of
hydrocarbon chain between the nitrogen atoms. While the
ortho-derivatives just form mononuclear complexes, in the
case of the meta- and para-derivatives the right selection of
the hydrocarbon spacers in the tetraaminic chains may yield
the formation of coordinatively unsaturated binuclear com-
plexes.
These characteristics are currently being explored from the
point of view of recognition of different substrates as tertiary
ligands through formation of mixed complexes and from the
point of view of assisting different catalytic processes.
3
Crystal structure of [ZnL Cl]Cl H2O (3)
.
The crystal structure consists of [ZnL2Cl]+ cations and chlor-
ide counteranions. The coordination geometry around the
Zn2+ metal ion is a square pyramid with the nitrogen atoms
occupying the vertices of the square and one chloride anion
placed in apical position. The mean distance Zn–N is ca.
˚
˚
2.14 A and the distance Zn–Cl 2.3507(7) A (Fig. 5, Table 6). At
difference with the structure of the Cu2+ complex, in this case
the chloride anions do not interconnect different macrocyclic
units.
Acknowledgements
The conformations of the different chelate rings around the
Zn2+ metal ions are similar to those described for the Cu2+
complexes with gauche disposition for the five-membered
rings, and chair and chair-like conformation for the six- and
seven-membered chelate rings.
We would like to acknowledge Ministerio de Ciencia y
´
Tecnologıa BQU2000-1424 and Academy of Sciences (project
Z4055905) and Grant Agency of the Czech Republic (203/
98/0726, 203/01/0067) for financial support.
The folding of the macrocycle defines again a trans IIII,
RRSS conformational isomer. The angle formed between
the plane defined by the aromatic ring and the mean plane
passing through the nitrogen donors is of ca. 30ꢁ. Interest-
ingly enough this angles rises when passing to the meta and
para-derivatives. For this last one, the disposition would be
almost normal.
References
1
2
W. Kaim, B. Schwederski, Bioinorganic Chemistry: Inorganic
Elements in the Chemistry of Life, An Introduction and Guide,
J. Wiley & Sons, Chichester, 1995; E. Solomon, T. C. Brunold,
M. I. Davis, J. N. Kemsley, S.-K. Lee, N. Lehnert, F.
Neese, A. J. Skulan, Y.-S. Yang and J. Zhou, Chem. Rev., 2000,
100, 235.
D. E. Fenton, Chem. Soc. Rev., 1999, 28, 159; Y. Murakami, J.-I.
Kikuchi, Y. Hisaeda and O. Hayashida, Chem. Rev., 1996, 96,
721; R. Breslow and S. D. Dong, Chem. Rev., 1999, 98, 1997;
N. Kitajima and W. B. Tolman, Prog. Inorg. Chem., 1995, 43,
419; J. H. Hartley, T. D. James and C. J. Ward, J. Chem. Soc.,
Perkin Trans., 2000, 1, 3155; E. Kimura, T. Koike, M. Shionaya
and M. Shiro, Chem. Lett., 1992, 787; A. Bencini, E. Berni, A.
Bianchi, V. Fedi, C. Giorgi, P. Paoletti and B. Valtancoli, Inorg.
Chem., 1999, 38, 6323.
Conclusions
The results presented provide a general and conclusive view of
how topologically simple ligands containing a benzene ring
linked to the ends of tetraaminic chains through benzylic posi-
tions can achieve different coordination modes depending on
´ ´
A. Andres, C. Bazzicalupi, A. Bianchi, E. Garcıa-Espan˜a, S. V.
´
Luis, J. F. Miravet and J. A. Ramırez, J. Chem. Soc.,Dalton
Trans., 1994, 1995.
3
4
´
´
A. Andres, M. I. Burguete, E. Garcıa-Espan˜a, S. V. Luis, J. F.
Miravet and C. Soriano, J. Chem. Soc., Perkin Trans., 1993, 2,
´
749; A. Domenech, J. V. Folgado, E. Garcıa-Espan˜a, S. V. Luis,
J.-M. Llinares, J. F. Miravet and J. A. Ramırez, J. Chem. Soc.,
´
´
Dalton Trans., 1995, 541; E. Garc´ıa-Espan˜a, J. Latorre, S. V. Luis,
´
J. F. Miravet, P. Pozuelo, J. A. Ramırez and C. Soriano, Inorg.
Chem., 1996, 35, 4591; B. Altava, M. I. Burguete, S. V. Luis,
´
J. F. Miravet, E. Garcıa-Espan˜a, V. Marcelino and C. Soriano,
Tetrahedron, 1997, 53, 4751; D. K. Chand, H.-J. Schneider,
´
J. A. Aguilar, F. Escartı, E. Garcıa-Espan˜a and S. V. Luis, Inorg.
Chim. Acta, 2000, 316, 71.
´
5
6
M. Chadim, M. Budesinsky, J. Hodacova and J. Zavada, Collect.
Czech. Chem. Commun., 2000, 65, 99.
´
A. Bencini, M. I. Burguete, E. Garcıa-Espan˜a, S. V. Luis, J. F.
Miravet and C. Soriano, J. Org. Chem., 1993, 58, 4749.
Fig. 5 ORTEP drawing for the cation [ZnL3Cl]+. Thermal ellipsoids
are drawn at the 50% probability level.
1138
New J. Chem., 2003, 27, 1132–1139

View Article Online
7
(a) M. S. Lehman and F. K Larsen, Acta Crystallogr., 114, 11,
Sect.A 1978; (b) D. F. Grant and E. F. Gabe, J. Appl. Crystallogr.
Sect A, 1978, 11, 114.
18 A. E. Martell, R. M. Smith and R. J. Moteikaitis, NIST Critical
Stability Constants, of Metal Complexes Database NIST Standard
Reference Database, Version 4, 1997.
´
8
9
A. C. T Nort, D. C. Philips and F. S. Mathews, Acta Crystallogr.
Sect. A, 1968, 24, 351.
G. M. Sheldrick, C. Kruger, R. Goddard, ed., Crystallographic
Computing, Clarendon Press, Oxford, England, 1985, p. 175.
19 A. Bencini, A. Bianchi, E. Garcıa-Espan˜a, M. Micheloni and J. A.
Ram´ırez, Coord. Chem. Rev., 1999, 88, 97.
20 C. Nave and M. Truter, J. Chem. Soc., Dalton Trans, 1974, 2351.
21 M. Studer, A. Riesen and T. A. Kaden, Helv. Chim. Acta, 1989,
72, 1253.
22 J. E. Sarnesky, H. L. Surprenant, F. K. Molen and C. N. Reiley,
Anal. Chem., 1975, 47, 2116.
10 G. M. Sheldrick, SHELXL-93, Program for Crystal Structure
Refinement, University of Go¨ttingen, Germany, 1993.
11 International Tables for X-ray Crystallography, The Kynoch Press,
Birmingham, England, 1974, vol. IV.
23 A. Bianchi, B. Escuder, E. Garc´ıa-Espan˜a, S. V. Luis, V.
´
Marcelino, J. F. Miravet and J. A. Ramırez, J. Chem. Soc., Perkin
12 C. K. Johnson, ORTEP; Report ORNL- 3794; Oak Ridge
National Laboratory, Oak Ridge, TN, 1971.
Trans., 1994, 2, 1253.
24 R. M. Izatt, K. Pawlak and J. S. Bradshaw, Chem. Rev., 1991, 91,
1721.
25 A. Bianchi, L. Bologni, P. Dapporto, M. Micheloni and P.
Paoletti, Inorg. Chem., 1984, 23, 1201.
´
13 E. Garcıa-Espan˜a, M.-J. Ballester, F. Lloret, J.-M. Moratal,
J. Faus and A. Bianchi, J. Chem. Soc., Dalton Trans., 1988, 101.
14 M. Fontanelli and M. Micheloni, Proceedings of the I Spanish-
Italian Congress on Thermodynamics of Metal Complexes, Diputa-
´
´
´
cion de Castellon, Castellon, Spain, 1990 Program for the
automatic control of the microburette and the acquisition of the
electromotive force readings.
26 P. A. Tasker and L. Sklar, J. Cryst. Mol. Struct., 1975, 5, 329.
27 B. Bosnich, C. K. Poon and M. L. Tobe, Inorg. Chem., 1965, 4,
1102.
15 G. Gran, Analyst (London), 1952, 77, 881; F. J. Rossotti and
H. Rossotti, J. Chem. Educ., 1965, 42, 375.
16 P. Gans, A. Sabatini and A. Vacca, Talanta, 1996, 43, 1739.
17 A. K. Convington, M. Paabo, R. A. Robinson and R. G. Bates,
Anal. Chem., 1968, 40, 700.
28 E. K. Barefield, A. Bianchi, E. J. Billo, P. J. Connolly, P. Paoletti,
J. S. Summers and D. G. . Van der Derveer, Inorg. Chem., 1986,
25, 4197 and references therein.
New J. Chem., 2003, 27, 1132–1139
1139