Macrocyclic ligand design. A large covalently-linked ring system incorporating four cyclam units and its interaction with nickel(II), copper(II), Zinc(II), and cadmium(II)

Article abstract of DOI:10.1071/CH09312

A cyclic, tetra-linked macrocyclic species incorporating four 1,4,8,11-tetraazacyclotetradecane (cyclam) subunits has been synthesized employing Boc amine-group protecting chemistry coupled with high dilution conditions for the cyclization step. A series

Full text of DOI:10.1071/CH09312

RESEARCH FRONT
Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2009, 62, 1207–1213
Macrocyclic Ligand Design. A Large Covalently-Linked Ring
System Incorporating Four Cyclam Units and its Interaction
with Nickel(II), Copper(II), Zinc(II), and Cadmium(II)∗
Ying DongA and Leonard F. LindoyA,B
ASchool of Chemistry, The University of Sydney, NSW 2006, Australia.
BCorresponding author. Email: lindoy@chem.usyd.edu.au
A cyclic, tetra-linked macrocyclic species incorporating four 1,4,8,11-tetraazacyclotetradecane (cyclam) subunits has been
synthesized employing Boc amine-group protecting chemistry coupled with high dilution conditions for the cyclization
step. A series of 4:1 (metal:ligand (M:L)) complexes with nickel(ii), copper(ii), zinc(ii), and cadmium(ii) has been
synthesized. Visible spectophotometric (including spectrophotometric titration), EPR, NMR, and electrochemical studies
are reported for individual complexes and are in general accord with similar 4:1 (M:L) coordination behaviour occurring
in both the solid state and in solution. The study makes available an example of a new category of large cyclic receptors
whose cavity can be tuned electronically through variation of the metal centres incorporated in the cavity walls.
Manuscript received: 2 June 2009.
Manuscript accepted: 19 June 2009.
Introduction
Over recent years there has been a trend towards the synthesis of
discrete nano-scale molecular entities that are multi-component
in nature, often incorporating multi-metal ion binding sites
that may act as centres of functionality. Because of their ten-
dency to yield both kinetically and thermodynamically stable
complexes[1] and hence retain their integrity under a variety of
conditions, macrocyclic rings have often been favoured compo-
nents for incorporation into such extended systems.[2,3] Linked
derivatives of cyclam (1,4,8,11-tetraazacyclotetradecane) have
received particular attention in studies so far; in part, reflect-
ing the well documented rich transition metal chemistry of this
14-membered tetraaza ring.[3]
NH
N
N
N
HN
N
NH
HN
N
HN
N
NH
N
N
NH
HN
Linked two-ring tetraaza macrocycles have been widely stud-
ied and interest in this ligand category has been heightened
by the finding that individual compounds (and selected metal-
ion derivatives), incorporating either alkyl or aromatic linking
groups between the rings, were shown to be effective in inhibit-
ing human immunodeficiency virus type 1 (HIV-1) and type 2
(HIV-2) with low levels of toxicity.[4,5]
In contrast to bis-ligand systems of the above type, only a lim-
ited number of studies involving related tris-tetraazamacrocyclic
ligand systems have been reported.[6]
As a continuation of our previous investigations in the
area,[7–12] we now report the synthesis of the unprecedented,
linked four-cyclam derivative 1 (Scheme 1) containing each of
its four cyclam units in identical environments. An initial study
of the interaction of this unique cyclic species with nickel(ii),
copper(ii), zinc(ii), and cadmium(ii) is also presented.
1
Scheme 1.
Results and Discussion
Ligand Synthesis
The cyclic tetra-linked cyclam derivative 1 was obtained using
the procedure outlined in Scheme 2 starting from the previously
reported trans-di-N-protected cyclam derivative 2.[13,14] The
procedure involved the application of sequential Boc and Troc
protection/deprotection chemistry based, in part, on that used for
our previously reported syntheses of both branched and linearly
linked tris-cyclam derivatives.[7]
∗Dedicated to the memory of the late Professor A. M. Sargeson FAA, FRS – a great chemist and a true friend for more than 35 years.
© CSIRO 2009 10.1071/CH09312 0004-9425/09/101207

RESEARCH FRONT
1208
Y. Dong and L. F. Lindoy
Boc
O
Boc
Boc
Troc
Boc
O
Troc
Boc
N
N
N
N
NH N
N HN
N
N
Cl3CCH2OCOCl
Et3N, DCM
Cl
Cl
N HN
Et3N, DCM
Boc
2
3
4
Cl
3
Boc
Boc
Boc
Troc
Boc
Troc
Boc
N
N
O
HN
N
NH
N
N
N
N
N
N
N
N
O
N
N
Zn/HOAc
N
Boc
Boc
Boc
O
6
5
2
CI
CI
CI
CI
Boc Boc
O
O
N
N
N
N
N
N
N
N
O
Boc
Boc
7
6
O
O
N
Boc
Boc
Boc
Boc
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
Boc
Boc
Boc Boc
Boc
ϩ
9
8
Boc
Boc
Boc
O
O
N
N
N
N
N
O
O
N
N
N
N
N
N
N
N
N
N
N
O
Boc
Boc
Boc
Boc
O
3 M HCl-MeOH
3 M HCl-MeOH
O
O
N HN
NH N
NH N
N HN
N HN
NH N
NH N
N HN
ϩ
10
11
O
O
BH3, Me2S
N HN
NH N
O
N HN
NH N
O
NH N
NH N
N HN
O
N HN
O
1
Scheme 2.
The initial attempt to introduce a singleTroc protection group
into 2 to yield 3 by reaction of a molar equivalent of 2 with
2,2,2-trichloroethyl chloroformate under conditions of moderate
dilution proved unsuccessful and resulted instead in the forma-
tion of ‘diTroc/diBoc-cyclam’ as the major product. In view
of this, the reaction was repeated under high dilution condi-
tions, with the Troc reagent (in a 0.8 molar equivalent ratio)
being added over 84 h with the aid of a motorized syringe
pump, resulting in a 56% yield of 3. Reaction of 3 with
4-(chloromethyl)benzoyl chloride yielded 4, which was then
condensed with one equivalent of 3 to give the bis(cyclam)
derivative 5.The partially deprotected species 6 was then reacted
with two molar equivalents of 4-(chloromethyl)benzoyl chlo-
ride resulting in the formation of 7. The condensation of molar

RESEARCH FRONT
A Large Covalently-Linked Ring System Incorporating Four Cyclam Units
1209
Two reduction processes were also observed for [Ni4(1)]8+
andareassignedtonickel(ii)/(i)couples;theseoccurat−0.817V
(reversibility limited or masked by absorption phenomena)
and −0.983V (ꢀE = 200 mV). The corresponding value for
[Ni(cyclam)]2 + [9] is −1.447V (ꢀE = 225 mV), in accordance
with reduction from Ni(ii) to Ni(i) being more facile in the case
0.6
0.5
0.4
0.3
0.2
0.1
0
of [Ni4(1)]8+
.
Copper(II) Studies
The room temperature magnetic moment (1.83 µB, per copper
atom) of the purple complex, [Cu4(1)](ClO4)8·2H2O, falls in
the normal range for a copper(ii) species with S = 1/2. The EPR
spectrum (X band) of the complex in a dimethylformamide glass
yielded a single broad signal with an apparent g value at ∼2.06;
because of the poorly resolved parallel component(s) as well as
the absence of hyperfine structure, no further interpretation of
this spectrum was attempted.
0
1
2
3
4
5
6
7
Metal:ligand
Fig. 1. Spectrophotometric titration for the addition of nickel(ii) nitrate
hexahydrate to 1 (2.455 × 10−3 mol dm−3) in dimethylsulfoxide.
equivalents of 6 and 7 was then undertaken under high dilution
conditions over 84 h (with the aid of a dual syringe pump) in the
presence of caesium carbonate to yield the ring-closed mixed
isomeric products 8 and 9 which were not separated; the NMR
spectra of the mixture indicated that both isomers were formed
in significant amounts. Deprotection and subsequent reduction
of this mixture with borane-methyl sulfide then gave the required
tetra-linked cyclam derivative 1.
The solid state and solution (acetonitrile) visible spectra
of the above complex each show a single broad absorp-
tion with maxima at 519 nm and 532 nm (ε = 905 M−1 cm−1),
respectively. Both spectra are consistent with the presence
of a Cu(ii)-N4 chromophore in an (essentially) square pla-
nar arrangement.[18,19] The corresponding maximum absorption
for [Cu(cyclam)](NO3)2 in the solid state is 508 nm and in
acetonitrile 511 nm (ε = 58 M−1 cm−1).
A UV-Vis spectrophotometric titration of 1 with copper(ii)
nitrate was also performed under similar conditions to those
employed for the corresponding nickel(ii) nitrate system; once
again a linear increase in the absorption (at 533 nm) was
observed up to a 4:1 ratio at which a clear endpoint was once
again observed.
Metal Complexes
Nickel(ii), copper(ii), zinc(ii), and cadmium(ii) complexes of
type [M4(1)]X8·(solvate)n (X = ClO4 or NO3), showing the
expected 4:1 (metal:ligand (M:L)) stoichiometries, were syn-
thesized by mixing hot solutions of the appropriate metal salt
and 1 in methanol. The solid state electronic spectrum of yellow
[Ni4(1)](ClO4)8·H2O shows a single band in the visible region
with a maximum absorption at 471 nm, which is characteris-
tic of nickel(ii) in a square planar (low spin) geometry. The
absorption maximum of this complex in acetonitrile also shows
a major peak at 471 nm (ε = 348 M−1 cm−1), consistent with
the solid state spectrum. However, in this case it also shows a
further very weak peak at ∼850 nm that likely reflects the pres-
ence of a small amount of ‘yellow-to-blue’ interconversion in
thissolvent.[15,16] Thepresenceofsuchyellow-to-bluebehaviour
was also observed for the nickel complexes reported in our pre-
vious studies involving N-benzylated[9] and tris-linked cyclam
derivatives[10,11] and has been well documented previously for
other open chain and macrocyclic tetra-amine complexes of
nickel(ii).[17]
The tetracopper(ii) complex displays irreversible to quasi-
reversible waves in its cyclic voltammogram, determined in
acetonitrile, that are assigned to copper(iii)/(ii) and copper(ii)/(i)
processescorrespondingtoan E1/2 valueof+1.664V, while E1/2
values at −0.590V and −0.912V were also observed (the corre-
sponding values for [Cu(cyclam)]2+ are +1.377V (irreversible)
and −0.853V (ꢀE = 85 mV), respectively). However, it needs
to be noted that for the present system the peak position, inten-
sity, and shape were found to vary somewhat with the number of
scans and with the state of the electrode, presumably reflecting
the presence of interfering adsorption phenomena.[20]
NMR Studies: Zinc(II) and Cadmium(II)
1
The H and 13C NMR spectra of the zinc(ii) and cadmium(ii)
A UV-Vis spectrophotometric titration of nickel(ii) 1 with
nitrate in acetonitrile was carried out (Fig. 1). The plot of
absorbance versus the nickel:1 ratio in dimethylsulfoxide shows
a 4:1 endpoint, confirming that the solid state stoichiometry
of the nickel derivative is maintained in solution. The steady
increase in the absorption at the wavelength employed (477 nm)
up to the endpoint is in accord with both high affinity and similar
ligand field environments existing for all four of the nickel(ii)
binding sites.
complexes of 1 were recorded in dimethylsulfoxide-d6. On com-
plexation, the chemical shifts for the free ligand are shifted
slightly downfield in the case of the 1H NMR spectra and upfield
in the case of the 13C NMR spectra. Both the 1H and 13C spectra
were considerably more complex than those for the respective
free ligands and show additional resonances and splitting (in the
case of the 1H NMR spectra) as well as a tendency for greater
peak overlap. For example, the signals for the methylene pro-
tons adjacent to the aromatic ring are split from singlets for the
free ligand to complex ‘multiplets’ and additional complexity
occurs elsewhere in the spectra, in accord with loss of flexibility
occurring on complexation (and also probably due to the pres-
ence of configurational isomers that reflect different chirality
patterns for the bound nitrogen donors).[21] Such behaviour has
been well documented by us and others for a range of cyclam
complex derivatives (including linked derivatives); indeed even
1:1 complexes of cyclam and its derivatives with several metal
The cyclic voltammogram of [Ni4(1)]8+ in acetonitrile dis-
plays two partially overlapping reversible oxidation waves that
are assigned to nickel(iii)/(ii) couples. The E1/2 values of
+1.327V (ꢀE = 59 mV) and +1.140V (ꢀE = 60 mV) (ver-
sus Ag/AgCl) are more positive than the values of +1.100V
(ꢀE = 75 mV) and +0.583V (ꢀE = 70 mV) obtained for
[Ni(cyclam)]2+ [9]
in keeping with the oxidation to nickel(iii)
,
being more difficult in the former case.

RESEARCH FRONT
1210
Y. Dong and L. F. Lindoy
ions, including normally labile ions, have been shown to give
rise to more complex spectra than cyclam itself.[5,22]
2H), 1.98 (m, BocNCH2CH2CH2NTroc, 2H), 2.61–2.64 (t,
BocCH2CH2CH2NH, 2H), 2.78–2.81 (t, BocNCH2CH2NH,
2H), 3.34–3.45 (m, BocNCH2, 12H), 4.74–4.77 (d,
Cl3CCH2OCO, 2H). 13C NMR (CDCl3): d 28.50, 29.57, 30.79,
44.25, 45.87, 46.70, 46.88, 47.51, 50.02, 50.58, 50.93, 74.88,
75.10, 79.55, 79.64, 95.73, 95.84, 154.38, 155.48, and 156.33.
Conclusion
A synthetic procedure for obtaining the first example of a new
category of macro-rings composed of cyclically linked cyclam
units is described and the ability of the present four-cyclam
species to form tetranuclear complexes with divalent nickel, cop-
per, zinc, and cadmium has been demonstrated. Investigations
of the inclusion properties of the macro-ring 1 as a receptor for
nano-sized guests as well as of the effect of tuning the electronic
environment of the central cavity (by variation of the complexed
metal ion type) on the properties of an included guest are clearly
of considerable interest. Studies of these types are planned for
the future.
Compound 4
Triethylamine (0.46 g, 4.60 mmol) and 4-(chloromethyl)
benzoyl chloride (0.79 g, 4.18 mmol) were added to a solution
of 3 (2.00 g, 3.48 mmol) in dry dichloromethane (100 cm3). The
reaction mixture was stirred at room temperature for 12 h and
was then ‘washed’ by shaking with water (2 × 50 cm3). The
organic layer was dried (anhydrous Na2SO4), evaporated under
reduced pressure, and the residue then purified by column chro-
matography on silica gel (eluting with CH2Cl2-MeOH, 50:1).
Compound 4 was isolated as a white powder (2.40 g, 95%).
(Found: (M + H)+, 729.2182 (FAB). C31H47Cl4N4O7 requires
(M + H)+, 729.2169.) 1H NMR (CDCl3): d 1.27–1.48 (m, tBu,
18H), 1.87 (m, NCH2CH2CH2, 4H), 3.25–3.61 (m, NCH2,
16H), 4.58 (s, PhCH2Cl, 2H), 4.75 (s, Cl3CCH2OCO, 2H), 7.42–
7.47 (m, ArH, 4H). 13C NMR (CDCl3): d 28.42, 45.40, ∼44–50
(broad overlapping signals), 75.25, 80.30, 95.48, 126.79, 128.41,
128.71, 130.90, 136.56, 138.68, 154.34, 155.49, and 171.35.
Experimental
Where available, all reagents and solvents were of analyt-
ical (or HPLC) grade. Acetonitrile was dried by shaking
analytical grade (AR) with Linde 4A molecular sieves, stir-
ring with calcium hydride until no further hydrogen was
evolved, and then fractionally distilling from fresh cal-
cium hydride. Dichloromethane (AR grade) was dried as
described elsewhere.[23] Dry tetrahydrofuran was prepared by
refluxing analytical grade over phosphorus pentoxide fol-
lowed by distillation, then repeating the process over sodium
wire and fractionally distilling. The synthesis of 1,8-bis(tert-
butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecane 2 has been
reported previously.[13,14] 1H and 13C NMR spectra were
recorded on a Bruker Avance DPX300 spectrometer. HRMS
spectra were obtained on a Kratos M25RFA spectrometer and
low resolution (ESI) spectra on a Finnigan LCQ-8 spectrometer.
The EPR spectra were obtained on DMF glasses at 77 K using
a Bruker EMX EPR spectrometer at 9.464 GHz (X-band). Solid
state UV-Vis spectra were measured on a CARY 1E spectropho-
tometer (samples spread on filter paper), solution UV-Vis spectra
were measured on a CARY 5E UV-VIS-NIR spectrophotometer.
Cyclic voltammetry experiments were performed using a BAS-
100B electrochemical system in conjunction with a glassy car-
bon working electrode in dry acetonitrile (supporting electrolyte
was 0.1 mol dm−3 tetrabutylammonium perchlorate); scans at
several scan rates were performed. The ferrocenium/ferrocene
reference couple had E1/2 at +0.52V (acetonitrile) under these
conditions.
Compound 5
Compound 3 (2.06 g, 3.58 mmol) in dry acetonitrile (25 cm3)
was added to a suspension of 4 (2.60 g, 3.58 mmol), caesium
carbonate (1.40 g, 4.30 mmol), and potassium iodide (0.07 g,
0.43 mmol) in dry acetonitrile (25 cm3). The reaction mixture
was refluxed for 5 h after which the suspension was filtered and
the residue was washed with hot chloroform (500 cm3). The
combined organic layers were dried (anhydrous Na2SO4) and
evaporated under reduced pressure. The resulting pale-yellow
viscous oil was purified by column chromatography on silica gel
(eluting with CH2Cl2-MeOH, 50:1). Compound 5 was isolated
as a white powder (3.85 g, 85%). (Found: (M + H)+, 1265.4545
(FAB). C54H87Cl6N8O13 requires (M + H)+, 1265.4524.) 1H
NMR (CDCl3): d 1.43 (br s, tBu, 36H), 1.69–1.99 (m,
NCH2CH2CH2, 8H), 2.41 (m, BocCH2CH2CH2NCH2Ph, 2H),
2.66 (m, BocNCH2CH2NCH2Ph, 2H), 3.27–3.48 (m, NCH2,
28H), 3.59 (s, PhCH2N, 2H), 4.75 (s, Cl3CCH2OCO, 2H), 4.77
(s, Cl3CCH2OCO, 2H), 7.28–7.33 (m, ArH, 4H). 13C NMR
(CDCl3): d 28.43, ∼44–50 (broad overlapping signals), 51.49,
52.97, 59.04, 75.03, 75.20, 79.68, 80.18, 95.48, 95.67, 126.43,
128.79, 135.32, 139.97, 154.39, 155.45, 155.62, 156.06, and
171.64.
Syntheses
Compound 3
Compound 6
2,2,2-Trichloroethyl chloroformate (1.69 g, 8 mmol) in dry
dichloromethane (50 cm3) was added with the aid of a syringe
pump to a solution of 1,8-bis(tert-butoxycarbonyl)cyclam 2
(4.00 g, 10 mmol) and triethylamine (1.01 g, 10 mmol) in dry
dichloromethane (1600 cm3) over a period of 84 h at room
temperature. The reaction mixture was stirred for a further
2 h at room temperature and then concentrated to 200 cm3
under reduced pressure. The organic layer was washed with
water (2 × 50 cm3), dried (anhydrous Na2SO4), and evaporated
under reduced pressure. Purification of this compound was
achieved by column chromatography on silica gel (eluting with
CH2Cl2-MeOH, 100:1). Compound 3 was isolated as a white
powder (2.57 g, 56%). (Found: (M + H)+, 575.2152 (FAB).
C23H42Cl3N4O6 requires (M + H)+, 575.2170.) 1H NMR
(CDCl3): d 1.47 (s, tBu, 18H), 1.73 (m, BocNCH2CH2CH2NH,
Compound 5 (1.90 g, 1.50 mmol) was dissolved in glacial
acetic acid (40 cm3) and stirred with activated zinc dust (8.83 g,
135 mmol) at room temperature for 2 h. The reaction mix-
ture was filtered through celite and the residue was then
washed with glacial acetic acid. The combined acetic acid solu-
tion was evaporated under reduced pressure and the residue
was then partitioned between 10% aqueous sodium hydrox-
ide (30 cm3) and dichloromethane (30 cm3) at 0◦C. The two
phases were separated and the aqueous layer was exacted with
dichloromethane (2 × 30 cm3). The combined organic phases
were dried (anhydrous Na2SO4) and evaporated under reduced
pressure. Compound 6 was isolated as a white powder (0.962 g,
70%) after purification by column chromatography on silica
gel (eluting with CH2Cl2-MeOH, 20:1). (Found: (M + H)+,

RESEARCH FRONT
A Large Covalently-Linked Ring System Incorporating Four Cyclam Units
1211
917.6428 (FAB). C48H85N8O9 requires (M + H)+, 917.6440.)
phases were combined, dried (anhydrous Na2SO4), and evap-
orated under reduced pressure. The pale-yellow oily residue
that remained was dissolved in absolute ethanol (5 cm3) and
HBr (47% in acetic acid, 5 cm3) was added. The resulting
white precipitate that resulted was filtered off, washed with
cold ethanol, and again added to a 10% aqueous sodium
hydroxide (20 cm3)/chloroform (40 cm3) mixture with shak-
ing and the procedure described above repeated. The com-
bined chloroform phases were dried (anhydrous Na2SO4)
then evaporated under reduced pressure. A mixture of 10
and 11 was obtained as a colourless viscous oil (0.192 g,
90%). (Found: (M + H)+, 1265.9056 (FAB). C72H113N16O4
requires (M + H)+, 1265.9130.) 1H NMR (CDCl3): d 1.68
(m, NCH2CH2CH2N, 8H), 1.85 (m, NCH2CH2CH2NCO, 8H),
2.53–2.73 (m, PhCH2NCH2, NHCH2, 48H), 3.52–3.65 (m,
CONCH2, 16H), 3.76 (s, PhCH2N, 8H), 7.33 (s, ArH, 16H).
13C NMR (CDCl3): d 25.71, 26.96, ∼28.0–29.5 (broad overlap-
ping signals), 29.64, ∼45–53 (broad overlapping signals), 53.78,
54.53, 57.73, 59.16, 126.62, 128.81, 129.36, 135.82, 138.76,
141.02, 141.14, and 172.10.
t
1H NMR (CDCl3): d 1.21–1.49 (m, Bu, 36H), 1.69–2.05 (m,
NCH2CH2CH2N, 8H), 2.52–2.66 (m, NHCH2, 8H), 2.80 (m,
PhCH2NCH2, 4H), 3.26–3.46 (m, BocNCH2, 20H), 3.62 (s,
PhCH2N, 2H), 7.32–7.40 (m, ArH, 4H). 13C NMR (CDCl3): d
28.44, ∼43–54 (broad overlapping signals), 53.47, 60.14, 78.91,
79.23, 79.48, 126.50, 128.46, 130.87, 135.27, 141.27, 155.00,
155.59, 156.04, 156.47, and 171.78.
Compound 7
Triethylamine (0.152 g, 1.505 mmol) and 4-(chloromethyl)
benzoyl chloride (0.259 g, 1.368 mmol) were added to a solution
of 6 (0.522 g, 0.570 mmol) in dry dichloromethane (20 cm3).
The reaction mixture was stirred at room temperature for
12 h and the solution was washed with water (2 × 10 cm3).
The organic layer was dried (anhydrous Na2SO4) and evapo-
rated under reduced pressure. Purification of the oily residue
was achieved by column chromatography on silica gel (elut-
ing with CH2Cl2-MeOH, 50:1) to give 7 as a colourless
viscous oil (0.626 g, 90%). (Found: (M + H)+, 1221.6502
(FAB). C64H95Cl2N8O11 requires (M + H)+, 1221.6497.) 1H
NMR (CDCl3): d 1.45 (br s, tBu, 36H), 1.69–2.14 (m,
NCH2CH2CH2N, 8H), 2.38 (m, PhCH2NCH2CH2CH2NBoc,
2H), 2.68 (m, PhCH2NCH2CH2NBoc, 2H), 3.26–3.37 (m,
BocNCH2, CONCH2, 28H), 3.60 (s, PhCH2N, 2H), 4.58 (s,
PhCH2Cl, 4H), 7.29–7.44 (m, ArH, 12H). 13C NMR (CDCl3): d
28.42, 45.50, ∼43–54 (broad overlapping signals), 58.84, 79.81,
80.26, 126.50, 126.81, 126.92, 128.73, 129.30, 135.37, 136.58,
138.72, 139.83, 155.79, 171.38, and 171.75.
Compound 1
Using a similar procedure to that described previously,[24]
a solution of borane-methyl sulfide complex (2.0 mol dm−3
;
4 cm3, 8.04 mmol) was added to a solution of the mixture of 10
and 11 (0.170 g, 0.134 mmol) in dry tetrahydrofuran (10 cm3).
The solution was refluxed overnight and excess borane was
destroyed by careful addition of methanol. The solvent was
removed under reduced pressure and the residual white pow-
der was then added to a MeOH-H2O-conc.HCl (20:5:2, 10 cm3)
mixture and heated at reflux temperature for 2 h. The solvent
was evaporated under reduced pressure and the residue was par-
titioned between 10% aqueous sodium hydroxide (10 cm3) and
chloroform (20 cm3) with shaking. The aqueous layer was sepa-
rated and extracted with chloroform (3 × 20 cm3), the combined
organic phases were dried (anhydrous Na2SO4) and evaporated
under reduced pressure. The crude oily product was purified as
described above for the mixed isomers 10 and 11 to yield 1
(0.146 g, 90%) as a colourless viscous oil. (Found: (M + H)+,
1209.9781 (FAB). C72H121N16 requires (M + H)+, 1209.9960.)
1H NMR (CDCl3): d 1.80 (m, NHCH2CH2, 16H), 2.48–2.54
(m, NHCH2, 32H), 2.68 (m, PhCH2NCH2, 32H), 3.34 (br m,
NH, 8H), 3.54–3.72 (m, PhCH2N, 16H), 7.22 (s, ArH, 16H).
13C NMR (CDCl3): d 25.68, 29.64, 47.50, 50.24, 51.40, 53.54,
53.85, 57.42, 63.76, 124.99, 129.06, 129.31, and 135.61.
Compounds [8]·1.25CH2Cl2 and [9]·1.25CH2Cl2
(Mixed Isomers)
Compound 6 (0.430 g, 0.469 mmol) in dry acetonitrile
(50 cm3) and 7 (0.572 g, 0.469 mmol) in dry acetonitrile
(50 cm3) were added simultaneously by means of a double drive
syringe pump into a suspension of caesium carbonate (0.764 g,
2.345 mmol) and potassium iodide (0.039 g, 0.235 mmol) in
dry acetonitrile (400 cm3) over a period of 84 h at reflux
temperature. The reaction mixture was refluxed for a further
48 h and then filtered through Celite. The filtrate was evap-
orated under reduced pressure to yield the crude product as
a pale-yellow viscous oil. A mixture of isomers 8 and 9 was
obtained as a white powder (0.408 g, 40%) after purification
of the crude product by column chromatography on silica gel
(eluting with CH2Cl2-MeOH-saturated NH3·H2O, 50:1:0.5).
(Found: C 62.64, H 8.47, N 10.18%. C113.25H178.5Cl2.5N16O20
requires C 62.60, H 8.28, N 10.31%.) 1H NMR (CDCl3):
d 1.41 (br s, tBu, 72H), 1.68–2.04 (m, NCH2CH2CH2N,
16H), 2.43 (m, PhCH2NCH2CH2CH2NBoc, 8H), 2.68 (m,
PhCH2NCH2CH2NBoc, 8H), 3.36 (m, NCH2, 48H), 3.58 (s,
PhCH2N, 8H), 7.34(s,ArH, 16H). 13CNMR(CDCl3):d∼26–30
(broad overlapping signals), 28.46, ∼43–55 (broad overlapping
signals), 53.44, 59.81, 79.35, 79.81, 80.20, 126.57, 128.59,
129.33, 135.20, 135.40, 140.37, 141.23, 155.74, and 171.80.
[Ni4(1)](ClO4)8·H2O
Nickel(ii) perchlorate hexahydrate (0.073 g, 0.200 mmol) in
methanol (5 cm3) was added to 1 (0.060 g, 0.050 mmol) in
methanol (5 cm3).The yellow solution was stirred and heated for
0.5 h and then left to stand at room temperature overnight. The
yellow product that formed was filtered off and recrystallized
from water (0.056 g, 50%). (Found: C 38.36, H 5.66, N 9.76%.
C72H122Cl8Ni4N16O33 requires C 38.30, H 5.45, N 9.92%.)
Compounds 10 and 11 (Mixed Isomers)
[Cu4(1)](ClO4)8·2H2O
The mixed tetraamide isomers 8 and 9 (0.35 g, 0.169 mmol)
were stirred in a solution of 3 mol dm−3 HCl-MeOH (15 cm3)
overnight at room temperature. The resulting white precipi-
tate was removed by filtration, washed with cold methanol
then shaken in a 10% sodium hydroxide (20 cm3) and chloro-
form (40 cm3) mixture. The aqueous phase was separated
and extracted with chloroform (3 × 40 cm3) and the organic
Using a similar procedure to that described for [Ni4(1)]
(ClO4)8·H2O, four molar equivalents of copper(ii) perchlorate
hexahydrate (0.074 g, 0.200 mmol) were reacted with 1 (0.060 g,
0.050 mmol) to yield the product as a purple powder (0.063 g,
55%) after recrystallization from water. (Found: C 37.80, H 5.32,
N 9.57%. C72H124Cl8Cu4N16O34 requires C 37.67, H 5.44, N
9.76%.)

RESEARCH FRONT
1212
Y. Dong and L. F. Lindoy
[Zn4(1)](NO3)8·8H2O
(f) S. El Ghachtouli, C. Cadiou, I. Dechamps-Olivier, F. Chuburu,
M. Aplincourt, T. Roisnel, V. Turcry, V. Patinec, M. Le Baccon,
H. Handel, Eur. J. Inorg. Chem. 2008, 4735. doi:10.1002/EJIC.
200800149
Using a similar procedure to that described for [Ni4(1)]
(ClO4)8·H2O, four molar equivalents of zinc(ii) nitrate tetrahy-
drate were reacted with 1 to yield the required product as a white
powder after recrystallization from methanol/acetonitrile (yield
35%). (Found: C 40.88, H 6.29, N 15.67%. C72H136N24O32Zn4
[5] X. Liang, M. Weishaüpl, J. A. Parkinson, S. Parsons,
P.A. McGregor, P.A. Sadler, Chem. Eur. J. 2003, 9, 4709. doi:10.1002/
CHEM.200304808
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297. doi:10.1016/0010-8545(90)80045-U
1
requires C 40.96, H 6.49, N 15.92%.) H NMR (DMSO-d6):
d 1.69 (m, NHCH2CH2, 14H), 2.34 (m, NHCH2CH2, 2H;
NHCH2CH2CH2N, 16H), 2.66–3.05 (m, NCH2, 48H), 3.75 (m,
PhCH2N, 6H), 3.95 (m, PhCH2N, 4H), 4.23–4.26 (m, PhCH2N,
6H), 4.53–5.25 (br m, NH, 8H), 7.35–7.38 (m, ArH, 16H).
13C NMR (DMSO-d6): d 22.87, 23.84, ∼44–56 (overlapping
signals), 60.15, 62.39, ∼130–133 (overlapping signals).
(b) E. Kimura, S. Aoki, T. Koike, M. Shiro, J. Am. Chem. Soc. 1997,
119, 3068. doi:10.1021/JA9640408
(c) S. Sun, J. Saltmarsh, S. Mallik, K. Thomasson, Chem. Commun.
1998, 519. doi:10.1039/A706711I
(d) P. V. Bernhardt, E. J. Hayes, J. Chem. Soc., Dalton Trans. 1998,
3539. doi:10.1039/A806586A
(e) E. Kimura, M. Kikuchi, H. Kitamura,T. Koike, Chem. Eur. J. 1999,
5, 3113. doi:10.1002/(SICI)1521-3765(19991105)5:11<3113::AID-
CHEM3113>3.0.CO;2-L
(f) S. Aoki, M. Shiro, T. Koike, E. Kimura, J. Am. Chem. Soc. 2000,
122, 576. doi:10.1021/JA993352I
(g) B. Korybut-Daszkiewicz, A. Wieckowska, R. Bilewicz,
˛
S. Domagala, K. Woz´niak, J. Am. Chem. Soc. 2001, 123, 9356.
doi:10.1021/JA0108537
(h) S. Aoki, M. Shiro, E. Kimura, Chem. Eur. J. 2002, 8, 929.
doi:10.1002/1521-3765(20020215)8:4<929::AID-CHEM929>3.0.
CO;2-Q
(i) S. Aoki, M. Zulkefeli, M. Shiro, E. Kimura, Proc. Natl. Acad. Sci.
USA 2002, 99, 4894. doi:10.1073/PNAS.072635899
(j) E. Kikuta, S. Aoki, E. Kimura, J. Am. Chem. Soc. 2001, 123, 7911.
doi:10.1021/JA0108335
[Cd4(1)](NO3)8·6MeOH·H2O
Using a similar procedure to that described for [Ni4(1)]
(ClO4)8·H2O, four molar equivalents of cadmium(ii) nitrate
tetrahydrate were reacted with 1 to yield the required product
as a white powder after recrystallization from methanol (yield
40%). (Found: C 39.75, H 6.14, N 14.17%. C78H146Cd4N24O31
1
requires C 39.60, H 6.22, N 14.21%.) H NMR (DMSO-d6):
d 1.73 (m, NHCH2CH2, 14H), 2.10–2.18 (m, NHCH2CH2,
2H), 2.43 (m, NHCH2CH2CH2N, 16H), 2.64–3.05 (m, NCH2,
48H), 3.82–3.93 (m, PhCH2N, 9H), 4.22–4.26 (m, PhCH2N,
7H), 7.35–7.39 (m, ArH, 16H). 13C NMR (DMSO-d6): d 24.12,
24.80, 44.73, 45.01, 49.13, 50.78, 52.41, 53.93, 55.57, 56.28,
62.42, 125.95, 128.69, 130.57, 131.22, 131.83, and 142.61.
CAUTION: perchlorate-containing complexes are poten-
tially explosive and appropriate precautions should be in place
for their preparation, handling and storage.
(k) E. Kikuta, S. Aoki, E. Kimura, J. Biol. Inorg. Chem. 2002, 7, 473.
doi:10.1007/S00775-001-0322-2
(l)L. Siegfried, C. N. McMahon,T.A. Kaden, C. Palivan, G. Gescheidt,
Dalton Trans. 2004, 2115. doi:10.1039/B402089H
(m) P. Comba, Y. D. Lampeka, A. Y. Nazarenko, A. I. Prikhod’ko,
H. Pritzkow, Eur. J. Inorg. Chem. 2002, 1464. doi:10.1002/1099-
0682(200206)2002:6<1464::AID-EJIC1464>3.0.CO;2-R
(n) M. Soibinet, D. Gusmeroli, L. Siegfried, T. A. Kaden, C. Palivan,
A. Schweiger, Dalton Trans. 2005, 2138. doi:10.1039/B503385N
(o) L. Fabbrizzi, F. Foti, A. Taglietti, Org. Lett. 2005, 7, 2603.
doi:10.1021/OL0507064
(p) P. Comba, Y. D. Lampeka, A. I. Pikhod’ko, G. Rajaraman, Inorg.
Chem. 2006, 45, 3632. doi:10.1021/IC052124O
(q) M. Atanasov, P. Comba, Y. D. Lampeka, G. Linti, T. Malcherek,
R. Miletichy, A. I. Prikhod’ko, H. Pritzkow, Chem. Eur. J. 2006, 12,
737. doi:10.1002/CHEM.200500365
Acknowledgement
We thank the Australian Research Council for support and Professor
G. A. Lawrance for assistance with the electrochemical determinations.
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