Alternative demetalation method for Cu(I)-phenanthroline-based catenanes and rotaxanes

Article abstract of DOI:10.1021/ol200304d

A new and less hazardous procedure for demetalation of Cu(I)- phenanthroline-based interlocked molecules, using aqueous NH₄OH rather than toxic KCN, has been developed. The conditions are compatible with materials containing nucleophile-sensiti

Full text of DOI:10.1021/ol200304d

ORGANIC
LETTERS
2011
Vol. 13, No. 7
1808–1811
Alternative Demetalation Method for
Cu(I)-Phenanthroline-Based Catenanes
and Rotaxanes
Jackson D. Megiatto Jr.* and David I. Schuster*
Chemistry Department, New York University, New York City, New York 10003,
United States
jackson.megiatto@asu.edu; david.schuster@nyu.edu
Received February 3, 2011
ABSTRACT
A new and less hazardous procedure for demetalation of Cu(I)-phenanthroline-based interlocked molecules, using aqueous NH4OH rather than
toxic KCN, has been developed. The conditions are compatible with materials containing nucleophile-sensitive appended groups such as C60, and
coordinating moieties such as zinc(II)-porphyrins.
Cu(I)-phenanthroline [Cu(phen)2]þ complexes have
been shown to be useful building blocks in strategies for
construction of supramolecular systems such as catenanes,
rotaxanes, and knots.1 While the main function of Cu(I) is
to hold the two phen-ligands tightly together in the per-
pendicular arrangement required for the preparation of
interlocked molecules, the corresponding MLCT states
also act as effective relays in energy transfer (EnT) and
electron transfer (ET) processes between photo- and
redox-activemoieties.2 Theseprocesses can be conveniently
monitored spectroscopically by following formation and
decay of MLCT excited states.3
It is known from the work of Sauvage and co-workers
that removal of Cu(I) from rotaxane and catenane
systems results in major conformational changes, which
strongly affect the photophysical properties of these
supramolecular systems.1b,i The traditional demetala-
tion protocol involves use of KCN in a mixed solvent
system (usually, CH3CN/H2O), which affords the Cu-
free ligands in very high yields.1b Although efficient, this
method is not general. For example, Sauvage and co-
workers reported that [Cu(phen)2]þ-[2]catenanes bearing
metaloporphyrins as appended groups could not be
demetalated using KCN, presumably due to the com-
plexation of the cyanide anions to the metaloporphyrin
moieties.1e Another example comes from our own work.
We have found that [Cu(phen)2]þ rotaxanes and cate-
nanes possessing an appended C60 moiety are also not
compatible with the KCN methodology. Although the
loss of copper from the complex can be deteced using by
mass-spectrometry,1b it is not possible to obtain the
original copper-free supramolecular system, presumably
due to the nucleophilic addition of cyanide anions to the
electron deficient fullerene core.4
(1) (a) Dietrich-Buchecker, C. O.; Sauvage, J.-P.; Kintzinger, J.-P.
Tetrahedron Lett. 1983, 24, 5095–5098. (b) Dietrich-Buchecker, C. O.;
Sauvage, J.-P.; Kern, J. M. J. Am. Chem. Soc. 1984, 106, 3043–3045. (c)
Dietrich-Buchecker, C. O.; Sauvage, J.-P. Tetrahedron 1990, 46, 503–
512. (d) Weck, M.; Mohr, B.; Sauvage, J.-P.; Grubbs, H. R. J. Org.
Chem. 1999, 64, 5463–5471. (e) Amabilino, D. B.; Sauvage, J.-P. New J.
Chem. 1998, 22, 395–409. (f) Dietrich-Buchecker, C. O.; Sauvage, J.-P.;
Geum, N.; Hori, A.; Fujita, M.; Sakamoto, S.; Yamaguchi, K. Chem.
Commun. 2001, 13, 1182–1183. (g) Kang, S.; Berkshire, B. M.; Xue, Z.;
Gupta, M.; Layode, C.; May, P. A.; Mayer, M. F. J. Am. Chem. Soc.
2008, 130, 15246–15247. (h) Sato, Y.; Yamasaki, R.; Saito, S. Angew.
Chem., Int. Ed. 2009, 48, 504–507. (i) Faiz, J. A.; Heitz, V.; Sauvage, J.-P.
Chem. Soc. Rev. 2009, 38, 422–442. (j) Durola, F.; Sauvage, J.-P.;
Wenger, O. S. Coord. Chem. Rev. 2010, 254, 1748–1759. (k) Share,
A. I.; Parimal, K.; Flood, A. H. J. Am. Chem. Soc. 2010, 132, 1665–1675.
(2) (a) Amaroli, N.; Diederich, F.; Dietrich-Buchecker, C. O.; Flamigni,
L.; Marconi, G.; Nierengarten, J.-F.; Sauvage, J.-P. Chem.;Eur. J. 1998,
4, 406–416. (b) Li, K.; Schuster, D. I.; Guldi, D. M.; Herranz, M. A.;
Echegoyen, L. J. Am. Chem. Soc. 2004, 126, 3388–3389.
(3) Scaltrito, D. V.; Thompson, D. W.; O’Callaghan, J. A.; Meyer,
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r
10.1021/ol200304d
Published on Web 03/08/2011
2011 American Chemical Society

As part of our continuing interest5 in exploring these
[Cu(phen)2]þ rotaxanes and catenanes as photosynthetic
model systems, we have explored alternative demetalation
strategies for preparation of copper-free fullereno-rotaxanes
and -catenanes to compare their photophysical properties
with those of the corresponding [Cu(phen)2]þ systems.
A potential demetalating agent was serendipitously discov-
ered during our attempts to develop a protocol for the
synthesis of [Cu(phen)2]þ-[2]catenanes using Huisgen-1,3-
dipolar-cycloaddition (CuAAC or “click” chemistry).5a In
order to remove residual copper catalyst that might bind to
coordinating sites in triazole-linked catenanes, we intro-
duced an extra step into the workup procedure. This consis-
ted of dissolving the crude product in dichloromethane
(DCM), followed by washing the organic solution with
aqueous ammonium hydroxide solution (NH4OH). To
our surprise, the final isolated material after this workup
procedure was the Cu-free [2]catenane.
Figure 2. Partial 1H NMR spectra of catenate 1 and the corre-
sponding catenand 2 (400 MHz, CD2Cl2, 298 K). For assign-
ments, see Figure 1.
rings relative to one another that occurs upon demeta-
lation.1a-c The phenyl protons (Ho and Hm, Figure 2)
attached to the phen moieties move downfield revealing
that the two chelates are no longer entwined around the
Cu(I) complex. The upfield shifts observed for prorons
Figure 1. [2]catenate 1 and the corresponding [2]catenand 2.
After demetalation, a reorientation of the constituent rings
results in a molecular conformation with the two phen ligands
located away from each other.
This unexpected result suggested that NH4OH might
be a generally applicable reagent for demetalation of
[Cu(phen)2]þ-based interlocked molecules. We therefore
decided to systematically investigate the effects of NH4OH
on [Cu(phen)2]þ-based catenanes and rotaxanes. The first
system studied was the prototypical [2]catenate 1 (Figure
1).5d,6 Treatment of an acetonitrile (ACN) solution of 1 with
a large excess of NH4OH resulted in demetalation of 1 after 1
h at room temperature to give 2 (for details, see Supporting
Information). Since the solution of 1 is dark red and the
solution of 2 is colorless, the demetalation process could be
easily monitored by eye. The crude product was extracted
with DCM, extensively washed with water and purified by
column chromatography to afford the Cu-free [2]catenand 2
as a waxy solid in very good yield (88%).
0
0
H4 , H5 , Hb, and Hd suggest that the triazole-linked phenyl
ring is engaged in π-π interactions with the nearby phen
moiety, revealing that catenand 2 roughly adopts the
configuration depicted in Figure 1. For comparison, cate-
nate 1 was also demetalated with KCN under classical
conditions,1a-c and the 1H NMR spectrum of the KCN-
demetalated system (Figure not shown) was identical to
that shown in Figure 2.
MALDI-TOF spectrometry confirmed the interlocked
structure of 2, showing the molecular ion at m/z 1389.06
(M þ H3O)þ (m/z 1370.58 calculated for C80H78N10O12)
and the characteristic fragmentation pattern of catenanes,1d
namely stepwise fragmentation of the constituent rings.
Inductively-coupled plasma mass spectrometry (ICP-MS)
analysis was used to attest the quality of the Cu-free
catenanes. ICP-MS revealed residual copper level of less
than 250 ppm for the NH4OH treated material and of less
than 240 ppm for the KCN analog. These data clearly
show that both methods are highly effective in removing
copper from the [Cu(phen)2]þ core of catenate 1.
To obtain further insight into the demetalation reaction
of 1 with NH4OH, the progress of the reaction was mon-
itored by UV-vis spectroscopy (Figure 3) at 440 nm, which
is the absorption maximum of the [Cu(phen)2]þ complex.3
For comparison, a control experiment using the classical
KCN demetalation procedure was performed with catenate
1 (Figure not shown). As can be seen, the absorption in the
1H NMR analysis (see Figure 2) of the isolated product
revealed the well-known reorientation of the interlocked
(5) (a) Megiatto, J. D., Jr.; Schuster, D. I. J. Am. Chem. Soc. 2008,
130, 12872–12873. (b) Megiatto, J. D., Jr.; Schuster, D. I. Chem.;Eur.
J. 2009, 15, 5444–5448. (c) Megiatto, J. D., Jr.; Spencer, R.; Schuster,
D. I. Org. Lett. 2009, 11, 4152–4155. (d) Megiatto, J. D., Jr.; Schuster,
D. I. New J. Chem. 2010, 34, 276–286. (d) Megiatto, J. D., Jr.; Schuster,
D. I.; Abwandner, S.; de Miguel, G.; Guldi, D. M. J. Am. Chem. Soc.
2010, 132, 3847–3861. (e) Megiatto, J. D., Jr.; Li, K.; Schuster, D. I.;
Palkar, A.; Herranz, M. A.; Echegoyen, L.; Abwandner, S.; de Miguel,
G.; Guldi., D. M. J. Phys. Chem. B 2010, 114, 14408–14419. (f)
Megiatto, J. D., Jr.; Spencer, R.; Schuster, D. I. J. Mat. Chem. 2011,
1544–1550.
(6) Sauvage proposed the names catenates for interlocked systems
bearing transition-metal-complex (also called metalocatenanes) and
catenand for the corresponding metal-free structure. See refs 1a-1c.
Org. Lett., Vol. 13, No. 7, 2011
1809

a much stronger nucleophile than NH3 and OH-, a faster
decomplexation reaction using KCN was expected than
with NH4OH.
Figure 3. UV-vis kinetic study of the demetalation of catenate 1
in acetonitrile (10-5 mol L-1) with NH4OH (3 ꢀ 10-4 mol L-1),
monitoring the absorbance at 440 nm. Total run time = 10 min,
cycle time = 30 s, 298 K (au = arbitrary units).
Figure 4. Chemical structure of Cu-containing interlocked mo-
lecules with appended ZnP or C60 groups and the corresponding
Cu-free materials.
Encouraged by these results, we turned our attention to
more elaborate interlocked structures (Figure 4) that
cannot be efficiently demetalated by the usual KCN
procedure,1e such as ZnP-[2]catenate 3. When compound
3 was treated withNH4OHunder the sameconditionsused
for 1 (see Supporting Information), the ZnP-[2]catenand 4
was isolated as a purple solid in 79% yield after the usual
workup and chromatographic purification.
visible region at 440 nm decreases with time after adding
an excess of NH4OH to an ACN solution of [2]catenate 1
(10-5 mol L-1), reaching a steady state after 10 min, indi-
cating successful removal of Cu from most or all of the phen
ligands.
The increased absorption in the near-infrared region of
the spectrum in Figure 3 indicates the formation of a new
Cu complex and confirms the successful demetalation of 1.
Absorptions in this region are charcteristic of d-d transi-
tions of Cu(II) complexes (d9).7 Since the original
[Cu(phen)2]þ complex (d10) has no d-d transitions, one
can conclude that treatment of 1 with NH4OH results in 2,
followed by oxidation of Cu(I) to Cu(II) by air8 and
formation of [Cu(L)x]2þcomplexes, with L = H2O, OH,
NH3 and/or ACN molecules and x = 4-6. The absorption
maxima at 960 and 1040 nm can be accounted for by the
existence of a single complex in which two well-separated
d-orbital transitions are possible, or by two absorbing
species, each exhibiting a single band, as expected for
copper(II) complexes with square pyramidal (850-1000 nm)
or flattened tetrahedral (1000-1700) geometries.7
From the kinetics experiments, it was found that the
reaction obeys a pseudo first order rate law and a rate
constant k = 1.6 ꢀ 10-3 mol-1 L s-1 was determined. This
value revealed that the demetalation reaction of 1 with
NH4OH was about 2 orders of magnitude slower than the
KCN reaction under similar conditions, which also obeyed
first order kinetics9 with k=0.21mol-1 Ls-1 . SinceCN- is
Figure 5. Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) of
catenate 4 and catenand 5.
(7) (a) Ray, G. H. Can. J. Chem. 1966, 44, 2165–2171. (b) Praliaud,
H. A.; Mikhailenko, S.; Chajar, Z.; Primet, M. Appl. Catal., B 1998, 16,
359–374. (c) Cooper, D.; Plane, R. A. Inorg. Chem. 1966, 5, 1677–1682.
(d) Elleb, M.; Meullemeestre, J.; Schwing-Weill, M.-J.; Vierling, F.
Inorg. Chem. 1982, 21, 1477–1483. (e) Amuli, C.; Meullemeestre, J.;
Schwing, M.-J.; Vierling, F. Inorg. Chem. 1983, 22, 3567–3570.
(8) Cu(I) ions are rapidly oxidized to Cu(II) species by air in the
presence of nitrogen base ligands. For details see ref 7c.
1H NMR analysis (Figure 5) revealed that NH4OH
treatment of 3 resulted in the Cu-free structure 4, as
revealedby the downfield shift oftheprotons on thephenyl
groups attached to the phen moieties.1a-e MALDI-TOF
(9) Albrecht-Gary, M.; Saad, Z.; Dietrich-Buchecker, C. O.; Sauvage,
J.-P. J. Am. Chem. Soc. 1985, 107, 3205–3209.
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Org. Lett., Vol. 13, No. 7, 2011

mass spectrometry revealed a peak at m/z 2306.5 corre-
sponding to 4 [M þ H]þ (m/z 2305.33, calculated for
C
142H148N14O12Zn) and the characteristic fragmentation
pattern for catenated species,1d revealing that no damage
to the interlocked structure of 4 occurred upon treatment
with NH4OH.
The [2]catenate 5, which possesses a C60 moiety
(Figure 4) and has proved to be totally incompatible with
the nucleophilic character of cyanide ion, constitutes an
excellent example to test the general applicability of
NH4OH as a demetalation agent. Another feature of
catenate 5 is an ester linkage which is susceptible to
hydrolysis under the alkaline conditions of the reaction.
Using the same protocol that was applied to decomplexa-
tion of 1, Cu-free [2]catenand 6 was isolated in 64% yield.
The other component of the reaction mixture was the
starting catenate 5. No byproducts resulting from ester
cleavage were observed.
Figure 6. Fluorescence spectra in CH2Cl2 of a ZnP reference,
Cu(I) rotaxane 7 and Cu-free rotaxane 8 with O.D. = 0.20,
excitation at 424 nm, 298 K (au = arbitrary units).
These findings suggest that the presence of C60 on the
backbone of catenate 5 prevents to some extent the disen-
gagement of the rings which is necessary for demetalation,
reducing the efficiency of the reaction, presumably due to
stericconstraintsimposedby thelarge carboncage. The 1H
NMR spectrum of 5 showed concentration and tempera-
ture dependence, suggesting significant π-π stacking,
which is known10 to protect the metal core against external
ligands, contributing to stabilization of the [Cu(phen)2]þ
complex. MALDI-TOF spectrometry revealed the mole-
cular ion for 6 at m/z 2219.47 [M þ H]þ (m/z 2218.30
calculated for C145H82N10O16) and m/z signals at 1415.87
and 806.01, assigned to the constituent rings of 6 arising
from stepwise fragmentation during the ionization process
(see Supporting Information).
Compound 7 (Figure 4) was chosen to verify if our
NH4OH demetalation procedure could be extended to
rotaxane structures. The demetalation of 7 could not be
accomplished under precisely the same conditions used for
[2]catenate 1 due to the low solubility of 7 in ACN. Instead,
7 was first dissolved in 3 mL of a solvent mixture composed
of DCM/ACN (3:7, v/v) to which aq NH4OH was added
following the same protocol as described for 1. After
workup, Cu-free rotaxane 8 was isolated as a purple solid
in 90% yield. For the rotaxane case, the ZnP fluorescence
was used as a reliable probe to monitor the demetalation
reaction since the Cu-free compound 8 is fluorescent while
the analogous metalated rotaxane 7 is not. As shown in
Figure 6, the fluorescence intensity of the ZnP moiety in 8
nearly reaches the level of the tetraphenyl-Zn(II)-porphyr-
in reference, while in 7 the ZnP excited state is strongly
quenched by singlet-singlet energy transfer to the nearby
[Cu(phen)2]þ complex.5d Compound 8 was also charac-
terized by MALDI-TOF spectrometry (see Supporting
Information) which left no doubt about its Cu-free rotax-
ane structure (m/z found 3485.12 [M þ H]þ, calculated,
3484.70 for C219H234N18O15Zn2).
In conclusion, NH4OH has been shown to be a convenient,
efficient and “green” demetalating agent for [Cu(phen)2]þ
catenanes and rotaxanes. Although the kinetics of demetala-
tion with NH4OH are slower than with KCN, the former
procedure was shown to be applicable to systems that cannot
be successfully demetalated using KCN due to its incompat-
ibility with sensitive subunits, specifically ZnP and C60. We
believe that the less hazardous and less toxic NH4OH proce-
dure will further enhance the usefulness of the metal-template
approach pioneered by Sauvage and co-workers for the
synthesis of complex supramolecular assemblies.1a-c The
easy access to Cu-free catenanes and rotaxanes containing
ZnP and C60 subunits opens up the possibility of making
switchable electron donor-acceptor systems, which allows
tuning of the electron transfer dynamics in these materials
using external stimuli.
Acknowledgment. We are deeply grateful to the
National Science Foundation (Grant CHE-0647334) for
financial support. This investigation was conducted in part
in an instrument facility constructed with support from
Research Facilities Improvement Grant Number C06 RR-
16572-01 from the National Center for Research Re-
sources, National Institutes of Health.
Supporting Information Available.
Experimental
details for the preparation and spectral characterization
of all products and their precursors. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
(10) Armaroli, N.; Accorsi, G.; Cardinali, F.; Listorti, A. Top. Curr.
Chem. 2007, 280, 69–115.
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