Multi-responsive metal-organic lantern cages in solution

Article abstract of DOI:10.1039/c5cc00698h

Soluble copper-based M₄L₄ lantern-type metal-organic cages bearing internal amines were synthesized. The solution state integrity of the paramagnetic metal-organic cages was demonstrated using NMR, DLS, MS, and AFM spectroscopy. 1D s

Full text of DOI:10.1039/c5cc00698h

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Multi-responsive metal–organic lantern cages
in solution†
Cite this:DOI: 10.1039/c5cc00698h
Valentina Brega,a Matthias Zeller,b Yufan He,a H. Peter Lua and
Jeremy K. Klosterman*a
Received 24th January 2015,
Accepted 16th February 2015
DOI: 10.1039/c5cc00698h
www.rsc.org/chemcomm
22,23
24,25
Soluble copper-based M4L4 lantern-type metal–organic cages bearing
Lantern-type M2L4
or M4L4
cages assemble from four
internal amines were synthesized. The solution state integrity of the bent organic ligands and two metal ions or two square-paddlewheel
paramagnetic metal–organic cages was demonstrated using NMR, DLS, SBUs, respectively, to provide a simple host framework. Methoxy
MS, and AFM spectroscopy. 1D supramolecular pillars of pre-formed and decyloxy groups on the central phenyl ring of curved ligands L1
cages or covalent host–guest complexes selectively formed upon and L2 improve cage solubility (Fig. 1a) and, as hyperfine coupling
treatment with 4,40-bipyridine and acetic anhydride, respectively.
operates via delocalization of unpaired electron spin density through
the s and p framework and through-space dipolar coupling, we
Modern self-assembly synthetic protocols readily provide a plethora predicted that distant alkoxy groups would remain unaffected by
of capsule-like molecules in differing sizes and shapes,1–4 yet func- the paramagnetic SBUs and provide a spectroscopic tag for NMR
tional group incompatibilities can interfere with the assembly of analyses. Finally, internal amines serve as embedded nucleo-
pyridine and imine based coordination cages from ligands bearing philes for the covalent binding of guests.
Lewis basic groups5,6 and subsequent interactions with nucleophilic
Methoxy and decyloxy amino ligands L1 and L2 were synthe-
guests. The robust carboxylate-based secondary building units of sized in five steps from p-anisidine and 4-decyloxyaniline,
metal–organic frameworks (MOFs), and their capsule-like cousins, respectively. After dibromination, subsequent Sonogashira reac-
metal organic polyhedra (MOPs),7–9 however, readily tolerate tions were used to install ethynyl spacers and m-benzoic acid
embedded reactive groups10,11 and can be post-synthetically mod- groups. Ligand L1 was reacted with Cu(OAc)2ꢀH2O in DMSO at
ified (PSM) using standard organic reactions to covalently attach 85 1C for 16 hours to afford green crystals suitable for structure
functional groups not present in the initial ligands.12,13
determination (Fig. 1a). Single crystal X-ray diffraction analysis
The majority of MOP reports focus on solid state structure14–16 confirmed the M4L4 lantern-type cage structure containing two
and much about MOP formation and solution state behavior copper paddlewheel SBUs (Fig. 1b).‡ Cage 1 is an oblate spheroid
remains unexplored.17–20 First, nearly all MOPs utilize the paramag- where the major axis is B2.5 nm, i.e. distance between oxygen
netic copper(II) paddlewheel SBU that unfortunately renders NMR atoms in opposing exotopic methoxy groups, and the minor
analyses, which offer powerful insight into the solution integrity and axis B1.5 nm, i.e. the distance between the outer copper atoms.
host–guest behavior of artificial molecular capsules, obtuse due to The internal amino groups define a smaller spheroid with a
the hyperfine shift.21 Second, carboxylate based MOPs are neutral
and often poorly soluble. Here we report (i) the preparation of two
multi-responsive, soluble lantern-type M4L4 metal–organic cages, (ii)
their crystallographic and 1H NMR analyses and post-assembly
transformations to give (iii) extended 1D supramolecular coordina-
tion polymers and (iv) a covalently bound guest complex (Scheme 1)
in response to reactive guest substrates.
a Center for Photochemical Sciences, Department of Chemistry, Bowling Green State
University, Bowling Green, OH 43403, USA. E-mail: jkloster@bgsu.edu
b STaRBURSTT CyberInstrumentation Consortium, Youngstown State University,
Youngstown, OH 44555-3663, USA
† Electronic supplementary information (ESI) available. CCDC 1038504–1038507.
Scheme 1 Cartoon representation of M4L4 lantern cages and guest respon-
sive post-assembly supramolecular assembly and internal bond formation.
For ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/c5cc00698h
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Fig. 2 Structural analysis of cage
1
in solution. 1H NMR spectrum
(500 MHz, 300 K) of DMF-d7 solution of (a) L1 and (b) 1H NMR and
(c) DOSY spectrum from a DMF-d7 solution of redissolved crystals of
cage 1. (d) Particle size and distribution from dynamic light scattering
measurements of cage 1 in DMF (observed diameter = 2.4 nm), (e) AFM
image from a DMF solution of cage 1 on mica slide showing (f) single
particles with ca. 2.2 nm in height.
Fig. 1 (a) Assembly of lantern shaped cages 1 and 2 from multi-functional
ligands L1 and L2 and (b) single crystal X-ray (SXRD) structures of methoxy amino
cage 1 and decyloxy amino cage 2. Apical and included solvent molecules and
ligand disorder removed for the sake of clarity. See ESI† for details.
volume of 680 Å3, a major axis of 1.2 nm (distance between
opposing nitrogen atoms), and a minor axis of 0.9 nm (distance from enhanced nuclear relaxation (T1 & T2) from dipolar coupling
between inner copper atoms). In spite of the open cage frame- with the unpaired copper electrons, termed paramagnetic relaxa-
work, p-stacking interactions between cages render a dense tion enhancement.27 Cage 2 exhibits a similar augmentation in
structure without continuous solvate channels (Fig. S28, ESI†). observed diffusion rate (Fig. S23, ESI†).
Single crystals of cage 2 were obtained from slow vapor diffusion
Dynamic light scattering (DLS) measurements support the
of MeOH into a DMA solution of ligand L2 and Cu(OAc)2ꢀH2O over solution integrity of cage 1 with the observation of small particles
one week (Fig. 1a). X-ray diffraction analysis confirmed the isostruc- of 2.4 nm in diameter (Fig. 2d). AFM analysis of a DMF solution of
tural lantern-type cage 2 with decyloxy chains (Fig. 1b).‡ The core cage 1 cast on a mica surface after drying provided clean images
framework of cage 2 is identical to that of cage 1 with similar of spherical particles of ca. 2.2 nm in height (Fig. 2e and f).
distances and volumes. Opposing decyloxy chains are either both Finally, LTQ Linear Ion-Trap and Fourier Transform Ion Cyclo-
fully extended or bent in an anti-fashion to facilitate an interwoven, tron Resonance Mass Spectrometry (LTQ-FTMS) unambiguously
tightly packed structure (Fig. S31, ESI†). Conveniently, alkoxy tetra- confirmed the solution state M4L4 composition with prominent
mino cages 1 and 2 both proved sufficiently soluble (B1 mM) signals at m/z = 977.83, 965.33 and 411.33 which were assigned
in polar solvents, i.e. DMF, DEF, DMA and DMSO, and, given to [1ꢀCu]2+, [1ꢀCa]2+ and [L1]+ based on FTICR isotope patterns
the efficient synthesis of cage 1, we used 1 for solution studies. (Fig. S39, ESI†).28
1H NMR analyses of crystals of cage 1 dissolved in DMF-d7
Although crystallization is slow, cage 1 quickly assembles in
revealed a single set of peaks broadened due to strong magnetic solution at room temperature. Using the methoxy signals A as a
coupling with the paramagnetic metal centers (Fig. 2). The spectroscopic handle, the quantitative formation of a single
methoxy alkyl protons A and aromatic aniline protons B, however, complex could be observed by 1H NMR upon titration of a
are sufficiently distanced from the metal centers such that DMSO-d6 solution of ligand L1 with copper acetate at room
the corresponding signals remain well resolved at d = 6.85 temperature (Fig. S18, ESI†). Cage formation can also be followed by
and 3.64 ppm (Dd B ꢁ0.25 ppm). Signals from internal amino fluorescence spectroscopy as ligand emission is severely quenched
hydrogens appeared at d B 6.6 ppm but are quite broad due to upon metal coordination (Fig. S25, ESI†). No intermediate species
through space dipolar coupling with the copper centers. A single were observed using either method. Variable temperature 1H NMR
band was observed in the diffusion ordered spectroscopy (DOSY) spectroscopy revealed that once formed, cage 1 is stable throughout
NMR spectrum at log D = ꢁ8.91 (D = 10.5 ꢂ 10ꢁ10 m2 sꢁ1) from the range of the spectrometer, i.e. 223 K to 323 K (Fig. S19, ESI†).
cage protons A and B which substantiates the existence of a
Cage 1 possesses two potential reactive sites, the Lewis acidic
single complex in solution (Fig. 2c).26 It should be noted that apical positions of the copper atoms and the Lewis basic internal
the observed diffusion coefficient of cage 1 is faster than that amines. Initially solvent ligands occupy the apical positions but
of the free ligand L1, log D = ꢁ9.08 (D = 8.32 ꢂ 10ꢁ10 m2 sꢁ1). are labile and undergo exchange upon dissolution. Crystals of
The apparent discrepancy in observed diffusion rates arises as-synthesized cage 1 were dissolved in DMF and diffusion of
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Fig. 4 Post-assembly covalent modification of cage 1: (a) reaction
scheme showing amide bond formation with cage 1 and (b) 1H NMR
spectra (500 MHz, 300 K, DMSO-d6) of digested cage 4 showing 3 : 1
mixture of free amine L1 and amide ligand L10.
Fig. 3 Reaction scheme and SXRD crystal structure showing the post-
assembly modification of pre-assembled cage 1, in solution, to give the 1D
supramolecular chain of cages 3. Apical and included solvent molecules
and ligand disorder removed for the sake of clarity. See ESI† for details.
In summary, we designed, prepared and characterized two highly
soluble M4L4 metal organic cages with four internal amino groups.
Pendant alkoxy groups serve to increase solubility and function as
spectroscopic tags for NMR analyses. DOSY and VT NMR spectro-
scopy was used for the first time to demonstrate the solution
integrity of carboxylate based cages. Once assembled, the metal–
organic cages serve as supramolecular building blocks37,38 for the
construction of 1D supramolecular coordination polymers. The
amines enabled the successful covalent tethering of molecular
guests within a metal–organic cage using post-synthetic protocols.
Ongoing work is focused on the inclusion of functional guests
within soluble metal–organic cages and for the controlled assembly
of functional supramolecular architectures.
Et2O gave X-ray quality single crystals of cage 10 where the apical
DMSO molecules were replaced with DMF (Fig. S32, ESI†).‡
Supramolecular 1D coordination polymers of metal–organic
cages 3 formed in the presence of bridging bipyridine ligands.
The pillars of linked cages assembled from a DMF solution of pre-
assembled cage 1 and 4,40-bipyridine upon diffusion of diethyl
ether at room temperature over one week (Fig. 3). X-ray analysis of
the green crystals elucidated well-ordered polymeric columns of
cages connected by 4,40-bipyridines bridging the copper SBUs.‡
One molecule of methanol is bound to each of the internal coppers
as 4,40-bipyridine is too large to fit within the cage. The pillars of
cages align along a single axis with neighboring cages snugly
packed (Fig. S34, ESI†). Bridging bipyridines and disordered DMF
solvent molecules occupy the interstitial voids. We emphasize that
attempts to crystallize the pillars from the primary building blocks
failed. The supramolecular 1D columns only assemble from solu-
tions of the pre-formed cage 1.
This work was supported by Bowling Green State University, the
BGSU Building Strength program and in part by an allocation of
computing time from the Ohio Supercomputer Center. The diffracto-
meters were funded by NSF Grants 0087210 and 1337296, Ohio Board
of Regents Grant CAP-491, and by Youngstown State University.
Reaction of the internal amines provided a covalent host–
guest complex upon treating a DMF solution of cage 1 with
acetic anhydride. After 4 d, the solvent was removed in vacuo
Notes and references
‡ Crystal data for cage 1:39 C108H84Cu4N4O24S4ꢀ0.56(O), Mr = 2213.95,
%
and the recovered solid washed with copious MeOH, dissolved green block: 0.32 ꢂ 0.14 ꢂ 0.12 mm, triclinic, P1, a, b, c = 14.935(5),
16.106(6), 16.995(6) Å, a, b, g = 105.989(4)1, 109.453(4)1, 104.285(5)1, V =
in DMF and precipitated with diethyl ether. The green solid was
3438(2) Å3, Z = 1, r = 1.069 g cmꢁ3, Mo Ka, F(000) = 1136.5, m =
digested with HCl and extracted. 1H NMR analysis of the
0.73 mmꢁ1, T = 100 K, 2ymax = 31.398, 19 952 unique reflections used,
released ligands in DMSO-d6 revealed the presence of a second set 11 327 with Io 4 2s(Io), Rint = 0.048, 812 parameters, 490 restraints,
GoF = 1.047, R = 0.0735 [Io 42s(Io)], wR2 = 0.2218 (all reflections),
of signals (Fig. 4, in red) which include a new signal at d 2.1 ppm,
corresponding to the acetamide methyl, and an amide N–H proton
1.43 o Dr o ꢁ1.20 e Å3. Crystal data for cage 2: C137.18H142.36Cu4N4O24
ꢀ
1.82(C4H9NO) 6.07(CH4O)ꢀ2.14(H2O), Mr = 2877.26, green block, 0.21 ꢂ
signal at d 9.8 ppm. Integration indicates a B25% conversion or 0.19 ꢂ 0.15 mm, monoclinic, P21/c, a, b, c = 18.2648(11), 27.0741(17),
16.6959(9) Å, b = 110.078(2)1, V = 7754.4(8) Å3, Z = 2, r = 1.232 g cmꢁ3
,
approximately one acetamide guest per host. Molecular modeling
indicates the inclusion of a second substrate is disfavored due to
Cu Ka, F(000) = 3039.3, m = 1.21 mmꢁ1, T = 100 K, ymax = 66.882, 13 282
unique reflections used, 11 546 with Io 4 2s(Io), Rint = 0.022, 1267
steric interactions (Fig. S45, ESI†). Post-assembly synthetic modifica- parameters, 971 restraints, GoF = 1.046, R = 0.051 [Io 4 2s(Io)], wR2
tion occurs only in solution. Soaking crystals of the as-synthesized
=
0.146 (all reflections), 0.70 o Dr o ꢁ0.46 e Å3. Crystal data for cage
10:39 C136.45H149.05Cu4N16.15O34.15, Mr = 2815.82, green block, 0.18 ꢂ
0.14 ꢂ 0.12 mm, monoclinic, C2/c, a, b, c = 22.7256(6), 27.9980(6),
cage 1 in acetic anhydride yielded only the starting ligand L1 after
digestion. Presumably this is due to poor guest diffusion through 23.4326(5) Å, b = 91.8800(10)1, V = 14901.5(6) Å3, Z = 4, r = 1.255 g cmꢁ3
,
Cu Ka, F(000) = 5880, m = 1.273 mmꢁ1, T = 100 K, ymax = 66.9111, 13 021
unique reflections used, 12 202 with Io 4 2s(Io), Rint = 0.0225, 1323
parameters, 2459 restraints, GoF = 1.066, R = 0.0584 [Io 4 2s(Io)],
wR2 = 0.1574 (all reflections), 0.952 o Dr o ꢁ0.439 e Å3. Crystal data for
narrow channels in the crystal lattice. Unlike previous reports on
the PSM of cages, which focus on external modifications,29–33 the
internal covalent binding of guest molecules remains rare.34–36
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