Architectural spiroligomers designed for binuclear metal complex templating

Article abstract of DOI:10.1021/ic4003498

The first structurally, spectroscopically, and electronically characterized metal-spiroligomer complexes are reported. The binuclear [M₂L ₂]⁴⁺ ions (M = Mn, Zn) are macrocyclic "squares" and are characterized by X-ray diff

Full text of DOI:10.1021/ic4003498

Article
pubs.acs.org/IC
Architectural Spiroligomers Designed for Binuclear Metal Complex
Templating
Shivaiah Vaddypally, Chongsong Xu, Senzhi Zhao, Yanfeng Fan, Christian E. Schafmeister,*
and Michael J. Zdilla*
Department of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, Pennsylvania, United States
S
* Supporting Information
ABSTRACT: The first structurally, spectroscopically, and electroni-
cally characterized metal-spiroligomer complexes are reported. The
binuclear [M2L2]4+ ions (M = Mn, Zn) are macrocyclic “squares” and
1
are characterized by X-ray diffraction, H and 13C NMR, electronic
absorption, emission, and mass spectroscopies. The manganese
complex contains two spin-independent MnII ions and is additionally
characterized using EPR and CD spectroscopies and CV.
and functional group display.7 The three-dimensional structure
INTRODUCTION
■
of spiroligomers is controlled by the stereochemistry of the
The development of rationally designed transition metal
monomers, structure of the monomer rings, and regiochemistry
complexes depends upon strict control of the coordination
of the functional groups that they display. The control that they
geometry about the metal. As a result of this requirement,
permit over their three-dimensional structure suggest that
ligand design has become a major thrust in the development of
spiroligomers could serve as excellent scaffolds for the display
inorganic materials.1 In particular, development of chiral
of chiral multi-metal active sites to explore sophisticated multi-
coordination environments2 and multi-metal3 geometries has
functional catalysis and other metal-based applications.
become increasingly important. Despite the clear benefits of
While spiroligomers have demonstrated their utility in the
ligand design, a major drawback is that each new desired
rational design of functional molecules, they have only begun to
coordination environment demands a reinvention of the ligand
be applied to the construction of controlled transition metal
synthesis, involving new starting materials, catalysts, coupling
ligation environments.8 Inherently chiral and enantiomerically
agents, and purification techniques. For instance, the
pure, spiroligomers offer an excellent opportunity for controlled
preparation of an achiral hangman porphyrin designed to
geometric metal complex templating and for imparting chiral
model the sophisticated cytochrome C oxidase active sites
character onto metal centers. We report here the first fully
requires a 13 step synthesis from commercially available
characterized metal−spiroligomer complexes: binuclear dimers
of manganese and zinc using a simple spiroligomer with
terpyridine side chains. We also demonstrate the first X-ray
crystal structures of spiroligomers with or without bound
metals and the formation of the first metal-templated
supramolecular complex of two spiroligomers.
starting materials.4 A geometrically and functionally versatile
ligand synthesis template for rapid generation of new
coordination geometries is thus an important goal for
increasing throughput in the field of ligand design.
The Schafmeister group has developed a new class of
spiroligomer macromolecules ideally suited for this purpose.
Spiroligomers are shape-programmable ladder-oligomers that
display a large variety of functional groups with control over
their relative three-dimensional presentation. We have
developed spiroligomers that bind and stabilize the protein
HDM2 in cell culture5 and another that mimics the active site
of serine esterases and catalyzes a trans-esterification reaction.6
The preparation of these materials is achieved by solution-
phase or solid-phase synthesis via the modular assembly of
stereochemically pure protected bis-amino acids (from an ever-
growing library of ca. 24 monomers) through pairs of amide
bonds to create ladder oligomers with programmable shapes
RESULTS AND DISCUSSION
■
The spiroligomer L possesses two terpyridyl side chains on a
four-“S” stereocenter nucleus designed so that the side chains
are oriented on the same side of the 5−6−5 fused ring system
(Figure 1, top). Synthesis of the S,S configured bis-amino acid
1a (Scheme 1) has been previously reported.7 The terpyridyl
group was then attached to the primary amine by utilizing the
Received: February 11, 2013
Published: May 13, 2013
© 2013 American Chemical Society
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Scheme 1. Synthesis and Structure of S,S,S,S
Bis(terpyridyl)spiroligomer Ligand L
triethylamine to form phenyl hydantoin, which was treated
with 33% HBr in acetic acid to remove carboxybenzyl and tert-
butyl protecting groups to yield amino acid 5a. Finally, HATU
and DIPEA were applied with 5a to produce our desired
symmetric bifunctionalized spiroligomer L with a diketopiper-
azine structure and S,S,S,S stereochemistry shown in Figure 1.
For comparison, the S,S,S,R diastereoisomer is shown alongside
L, illustrating that by selection of precursor stereochemistry the
display of functional groups is controlled in the resulting
spiroligomers. L′ was prepared via an identical procedure to
that of L except that for the last step an asymmetrical coupling
method was used.
The manganese−ligand complex may be prepared by two
methods (identical but for the presence or absence of acetic
acid), resulting in two crystalline polymorphs of the product.
Both methods involve the addition of spiroligomer ligand to a
solution of manganese(II) in dichoromethane:acetonitrile
(1:1). Filtration and concentration of the reaction mixture
results in small colorless crystals of 1. The zinc complex is
prepared in 1:1 dichloromethane:acetonitrile by addition of
Zn(ClO4)2 to the ligand. The dried mixture is extracted into
hot DMF, and cooling gives colorless crystals of 2.
Table 1. Selected Distances (Å) and Angles (deg) with
Standard Deviations for Dimeric Complexes 1 and 2
1 (M = Mn)
2 (M = Zn)
N(11)−M(1)
N(21)−M(1)
N(31)−M(1)
M(1)···M(1′)
N(11)−M(1)−N(11A)
N(21)−M(1)−N(31)
N(11)−M(1)−N(21/31)
N(11)−M(1)−N(21/31)
2.104(3)
2.258(3)
2.214(5)
10.463(2)
163.2(2)
142.74(19)
73.07(17)
70.51(17)
2.091(4)
2.115(5)
2.194(4)
9.0058(8)
176.99(18)
152.21(15)
77.63(17)
74.58(16)
Figure 1. X-ray crystallographic structures of unmetalated ligand L
(S,S,S,S, top left, 50% probability ellipsoids), diastereoisomer L′
(S,S,S,R, top right, 50% probability ellipsoids), dimeric manganese−
spiroligomer complex cation 14+ (middle, 30% probability ellipsoids),
and dimeric zinc−spiroligomer complex cation 24+ (bottom, 50%
probability ellipsoids). Carbon atoms displayed as open ellipses, and
aryl-hydrogen atoms are omitted for clarity. Anions in 1 and 2 are not
shown.
Single crystal X-ray analysis reveals the structures as dimeric
complexes with the formula [M2L2]4+ (Table 1). A metal atom
is ligated to a terpyridine group of a spiroligomer, and the
remaining metal coordination sites are filled by the terpyridine
of a second spiroligomer ligand resulting in a linkage “square”
topologically related to a number of previously reported
complexes.10 In the manganese complex (1), the manganese
atoms are bowed outward, with the central bpy pyridine−
pyridine axial bond angle compressed to 163°, resulting in a
reductive alkylation method between 1a and aldehyde 2a (4′-
formyl-2,2′:6′2″-terpyridine).9 The resulting functionalized bis-
amino acid was combined with phenyl isocyanate and
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significant cavity of ca. 136 Å3 at the center of the molecule that
contains disordered solvent or anions.11 This cavity is smaller in
2 due to the analogous axial ligands on zinc being nearly linear
at 177° (Figure 1) and a π-stacking interaction (3.7 Å) between
pyridyl groups through the central cavity.12
The crystal structure of complex 2 exhibits four clearly
resolved perchlorate counterions, consistent with the assign-
ment of a dizinc(II) complex. In the structure of 1, the
manganese charge is balanced by perchlorate and possibly
acetate ions, though the protonation state of the latter cannot
be determined, and solvent flattening (SQUEEZE)11 may have
corrected for additional electron density from disordered
perchlorate or acetate ions. Thus, the oxidation state of Mn
is not assigned based on charge counting in the structure but
upon electronic structure analysis by spectroscopic techniques.
Figure 2. Top: EPR spectrum of 1. MW Freq: 9.476 GHz. MW
Power: 2.0 mW. Mod Freq: 100 kHz. Mod Amp: 10 G. Bottom:
Simulation of EPR spectrum of 1 with hyperfine from a single I = 5/2
Mn nucleus. gx = gy= gz = 2.03, ax = ay = az = 90 G, D = 470 G, E = 190
G.
Figure 3. Electronic absorption (top) and circular dichroism (bottom)
spectra of L (red) and 1 (black) taken in acetonitrile solvent. CD
spectra collected on 2 × 10−5 M and 1.32 × 10−4 M samples of L and
1, respectively.
The X-band EPR spectrum of 1 is given and simulated in
Figure 2. The signature is characteristic of a high-spin S = 5/2
Mn(II) system, with the anisotropy attributed to second-order
zero-field splitting.13 The similarity of the spectrum in Figure 2
to reported spectra of Mn-terpyridine ions suggests that the d5
high-spin Mn atoms are not only uncoupled from one another
but that the signal symmetry is not significantly distorted by the
nearby (∼10 Å) second magnetic ion. The isotropic g values
obtained from simulation are similar to those previously
reported.13
The electronic absorption spectrum of 1 (Figure 3, top)
exhibits similarities to that of the unmetalated ligand (L) but
with the appearance of two charge transfer bands appearing in
the region of 280−290 and 320−350 nm. No d−d transitions
are observed, consistent with the assignment of S = 5/2 Mn(II).
These are also highly analogous to the spectra of bis-
(terpyridyl)manganese(II) ions.14
The charge transfer features are exaggerated in the CD
spectrum (Figure 3, bottom). The CD signal at 290 nm is a
strong positive peak, while that at 340 nm is a moderate
negative peak. The CD results imply that despite the distance
between the metal ions and the stereocenters the chiral
backbone of the ligand is able to impart chiral character to the
metal-tpy coordination environment, as evidenced by the
observable Cotton effect in the charge transfer bands of the CD
spectrum.
Figure 4. Cyclic voltammagram of complex 1 vs SCE. Potential sweep
from +0.38 V to +2.0 V to −1.5 V and back to +0.38 V.
Cyclic voltammetry on the complex 1 (Figure 4) shows an
oxidation wave at a potential of 1.2 V vs SCE similar to that
reported for the parent MnII(tpy)2 ion,14 except that in the
2+
case of the spiroligomer, this oxidation is irreversible. In Mn-
terpyridine chemistry, oxidation of a Mn2+ terpyridine mixture
results in the formation of a mixed-valent Mn(III/IV)-oxo
dimer,15 though we have not isolated the spiroligomer analogue
of this product, and the methylene bridges to the terpyridine
ligands may not provide flexibility enough for the Mn atoms to
become sufficiently close for intramolecular oxo-dimer
formation. On the reduction end, the CV of 1 exhibits an
irreversible wave corresponding to reduction of the terpyridine
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(PPh3)4) was obtained from Aldrich. Anhydrous tetrahydrofuran
(THF) was obtained from EMD. O-(7-azabenzotriazol-1-yl)-
N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) and
HOAt were obtained from Genscript. Ammonium hydroxide
(NH4OH) was obtained from Fisher Chemicals. All other reagents
such as NMR solvent were obtained from Sigma-Aldrich and used
without further purification. The starting material, the pro4 amino
acids (compound 1a, 1b), was synthesized according to a published
procedure,7 as well as the synthesis of 4′-formyl-2,2′:6′2″-terpyridine
2a.9
ligand at −1.2 V vs SCE. Thus, ligand reduction triggers
complex decomposition as evidenced by the irreversibility of
the reduction wave.
In summary, we have reported the first structurally and
electronically characterized metal−spiroligomer complexes.
This is also the first crystallographic characterization of any
spiroligomer, and the three-dimensional structures of the metal
free and metal bound spiroligomers are consistent with the
designed stereochemistry and the predicted structures from
molecular mechanics calculations and nuclear magnetic
resonance determined solution structures that we have
determined in the past. The complex demonstrates that
spiroligomers are well suited for accessing stereochemical
control, multi-metal binding, and imposition of chiral character
to the metal center, and most importantly, versatility of design
and ease of preparation of the ligand itself. The next stage is to
design spiroligomer-based scaffolds that bring the metal centers
in close proximity with each other to encourage electronic
communication and cooperative catalysis.
Compound 3a: (3S,5S)-1-[(Benzyloxy)carbonyl]-3-({[2,6-bis-
(pyridin-2-yl)pyridin-4-yl]methyl}amino)-5-[(tert-butoxy)-
carbonyl]pyrrolidine-3-carboxylic Acid. 1a (2.09g, 5.74 mmol)
and 2a (1.50g, 5.74 mmol) were dissolved in 60 mL MeOH, and the
reaction mixture was stirred at room temperature for 1 h. A solution of
NaBH3CN (433 mg, 6.89 mmol) in 5 mL MeOH was added, and the
solution was stirred overnight. The reaction mixture was concentrated
and purified by flash chromatography (Al2O3, EtOAc/MeCN/MeOH/
NH4OH: 7/1/0.5/0.5 to 6/1/1/1) to afford 3a as a pale yellow solid
(1.80g, 2.95 mmol, 51.5%). 1H NMR (500 MHz, 350 K, DMSO-d6): δ
(ppm) 8.73 (2H, d, J = 4.0 Hz), 8.61 (2H, d, J = 7.9 Hz), 8.50 (2H, s),
8.02 (2H, t, J = 7.7 Hz), 7.50 (2H, t, J = 5.9 Hz), 7.38−7.28 (5H, m),
5.10 (2H, s), 4.32 (1H, t, J = 7.6), 4.19−4.06 (3H, m), 3.61 (1H, d, J =
11.2 Hz), 2.87 (1H, dd, J = 12.7, 8.8 Hz), 2.25 (1H, dd, J = 13.1, 7.2
Hz), 1.35 (9H, s). 13C NMR (125 MHz, 350 K, DMSO-d6): δ (ppm)
172.13, 169.84, 154.72, 154.64, 153.25, 148.64, 137.05, 136.22, 127.86,
127.34, 126.90, 123.92, 120.60, 120.32, 120.03, 80.72, 66.01, 58.54,
EXPERIMENTAL SECTION
■
Instrumentation. HPLC-MS analysis was performed on an
Agilent Technologies Series 1200 with a Waters Xterra MS C18
column (3.5 mm packing, 4.6 mm × 150 mm) with a solvent system of
H2O/acetonitrile with 0.1% formic acid at a flow rate of 0.8 mL/min.
NMR experiments were performed on a Bruker Advance 500 MHz
NMR. NMR chemical shifts (δ) are reported relative to DMSO-d6,
benzene-d6, or CDCl3 residual solvent peaks. When possible, rotamers
were resolved by performing the analysis at 350 K. Crystal diffraction
data for all compounds were collected using a Bruker APEX II DUO
diffractometer using Mo Kα radiation (λ = 0.71073) from a fine-
focused sealed tube. Data was collected at 173 K, and structures were
solved using direct methods and refined by full-matrix least-squares
refinement.
20
53.40, 47.54, 41.48, 37.18, 27.18. [α]D = −13.2°(MeOH). HPLC
analysis (30 min, 5−95% MeCN/H2O with 0.1% formic acid): Tr =
16.9 min. ESI HR-MS [M+H]+ Calculated: 610.2666. Found:
610.2660.
Compound 3b: (3R,5S)-1-[(Benzyloxy)carbonyl]-3-({[2,6-bis-
(pyridin-2-yl)pyridin-4-yl]methyl}amino)-5-[(tert-butoxy)-
carbonyl]pyrrolidine-3-carboxylic Acid. 1b (2.09g, 5.74 mmol)
and 2a (1.50g, 5.74 mmol) were dissolved in 60 mL MeOH, and the
reaction mixture was stirred at room temperature for 1 h. A solution of
NaBH3CN (433 mg, 6.89 mmol) in 5 mL MeOH was added, and the
solution was stirred overnight. The reaction mixture was concentrated
and purified by flash chromatography (Al2O3, EtOAc/MeCN/MeOH/
NH4OH: 7/1/0.5/0.5 to 6/1/1/1) to afford 3b as a pale yellow solid
(1.53g, 2.51 mmol, 43.7%). 1H NMR (500 MHz, 350 K, DMSO-d6): δ
(ppm) 8.75 (2H, d, J = 4.0 Hz), 8.64 (2H, d, J = 8.0 Hz), 8.60 (2H, s),
8.06 (2H, dt, J = 7.8 Hz), 7.55 (2H, m), 7.32 (5H, m), 5.08 (2H,
broad), 4.56 (1H, broad), 4.37 (2H, dd, J = 30.2, 13.6 Hz), 4.12 (1H,
d, J = 12.4 Hz), 3.88 (1H, d, J = 12.5 Hz), 2.94 (1H, m), 2.59 (1H, m),
1.38 (9H, J = 12.5 Hz). 13C NMR (125 MHz, 350 K, DMSO-d6): δ
(ppm) 173.1, 171.2, 155.3, 155.1, 154.6, 148.8, 136.7, 136.6, 127.7,
127.0, 126.6, 123.7, 123.5, 120.4, 119.6, 118.9, 85.8, 79.6, 68.8, 66.0,
59.3, 55.3, 47.9, 27.0. [α]D20 = −71.8°(sodium salt in MeOH). HPLC
analysis (30 min, 5−95% MeCN/H2O with 0.1% formic acid): Tr =
15.8 min. ESI HR-MS [M+H]+ Calculated: 610.2666. Found:
610.2896.
Optical rotation was determined on a PERKIN ELMER Polarimeter
341 (20 °C, 589 nm). Circular dichroism spectra were obtained on a
JASCO instruments model J-815 CD spectrometer.
Mass spectra were performed on an Agilent G6520 Q-TOF by Dr.
Cliff Soll at HunterCollege, CUNY, a Waters/micromass LC-TOF
mass spectrometer, LCT-Premier-XE at Boston College, MA, or a
6520 Accurate Mass Q-TOF-LC/MS at Temple University. UV−
visible spectra were recorded on a Shimadzu UV-1800 UV
spectrophotometer in the range of 200−900 nm. Fluorescence spectra
were obtained on a PTI Photon Technology International
Fluorometer with slit width set to 3.0 nm. All reported fluorescence
intensities are reported as relative values with relative intensities
consistent across all samples (L, 1, and 2). EPR spectra were acquired
on a Bruker EMX EPR spectrometer equipped with a liquid He
cryostat.
Cyclic voltammagrams were obtained using a CHI-630D electro-
chemical analyzer/workstation with PIcoamp booster. Electrochemical
studies were performed under anaerobic conditions using a standard
three-electrode assembly; glassy Pt working, Pt wire auxiliary, and Ag/
AgNO3 (10 mM Ag+) reference were employed. Cyclic voltammogram
of compound 1 (1 mM) was acquired in acetonitrile (1 mM TBAP)
with a scan rate of 50 mV/s at room temperature. The open circuit
potential was determined at around 0.38 V, and positive and negative
sweeps were examined. Ferrocene was used as a standard (0.16 V vs
SCE), and potentials were corrected to SCE.
General Methods for Spiroligomer Synthesis. Anhydrous
dichloromethane (DCM), hexanes, ethyl acetate (EtOAc), anhydrous
dimethylformamide (DMF), acetonitrile (MeCN), HBr (33% in
glacial AcOH), phenyl isocyanate, triethylamine, and redistilled
diisopropylethylamine(DIPEA) were obtained from Sigma-Aldrich
and used without purification. Sodium cyanoborohydride
(NaBH3CN), allyl chloroformate, borane dimethyl amine complex
(HNMe2·BH3), and tetrakis(triphenylphosphine) palladium(0) (Pd-
Compound 4a: 7-Benzyl 8-Tert-butyl (5S,8S)-1-{[2,6-bis-
(pyridin-2-yl)pyridin-4-yl]methyl}-2,4-dioxo-3-phenyl-1,3,7-
triazaspiro[4.4]nonane-7,8-dicarboxylate. To the solution of 3a
(1.80g, 2.95 mmol) in 90 mL THF was added Et3N (1.03 mL, 7.39
mmol), and then phenyl isocyanate (805 μL, 7.39 mmol) was added.
The resulted reaction mixture was stirred overnight at room
temperature. The reaction mixture was concentrated and purified by
flash chromatography (SiO2, EtOAc/hexanes: 3/7 to 1/1) to afford 4a
1
as a white solid (1.60g, 2.25 mmol, 76.4%). H NMR (500 MHz, 350
K, DMSO-d6): δ (ppm) 8.72 (2H, d, J = 4.2 Hz), 8.59 (2H, d, J = 8.0
Hz), 8.48 (2H, s), 8.00 (2H, dt, J = 7.7, 1.8 Hz), 7.54−7.40 (7H, m),
7.36−7.25 (5H, m), 5.06 (2H, s), 4.92 (2H, d, J = 7.7 Hz), 4.40 (1H, t,
J = 8.4 Hz), 4.07 (1H, d, J = 11.7 Hz), 3.75 (1H, d, J = 11.8 Hz), 2.81
(1H, dd, J = 13.6, 8.6 Hz), 2.31 (1H, dd, J = 13.7, 8.3 Hz), 1.26 (9H,
s). 13C NMR (125 MHz, 350K, DMSO-d6): δ (ppm) 172.6, 169.5,
155.2, 154.7, 154.4, 153.3, 148.8, 148.7, 136.8, 136.0, 131.5, 128.2,
127.8, 127.6, 127.3, 126.9, 126.2, 123.8, 120.5, 119.0, 80.9, 66.1, 57.9,
20
49.5, 42.1, 35.0, 27.0. [α]D = −16.5°(CHCl3). HPLC analysis (30
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Scheme 2. Full Synthetic Scheme for Preparation of Spiroligomer Ligand L
min, 5−95% MeCN/H2O with 0.1% formic acid): Tr = 23.8 min. ESI
HR-MS [M+H]+ Calculated: 711.2926. Found: 711.2924.
(505 mg, 1.33 mmol) were dissolved in 24 mL DMF and 8 mL DCM
followed by addition of DIPEA (575 μL). The solution was stirred
overnight at room temperature. An amount of 20 mL of water and
saturated NH4Cl (aq) was added to the reaction mixture followed by
the extraction of EtOAc (60 mL) three times, and the combined
organic layer was washed with 40 mL brine/water: 1/1 and then 40
mL brine and dried over Na2SO4. Then the organic layer was
concentrated and purified by flash chromatography (SiO2, toluene/
EtOAc: 1/1 to toluene/EtOAc/water: 1/4/0.04) to afford L (104 mg,
Compound 4b: 7-Benzyl 8-Tert-butyl (5R,8S)-1-{[2,6-bis-
(pyridin-2-yl)pyridin-4-yl]methyl}-2,4-dioxo-3-phenyl-1,3,7-
triazaspiro[4.4]nonane-7,8-dicarboxylate. To the solution of 3b
(1.53 g, 2.51 mmol) in 80 mL THF was added Et3N (0.88 mL, 6.28
mmol), and then phenyl isocyante (700 μL, 6.28 mmol) was added.
The resulted reaction mixture was stirred overnight at room
temperature. The reaction mixture was concentrated and purified by
flash chromatography (SiO2, EtOAc/hexanes: 3/7 to 1/1) to afford 4b
as a white solid (1.28 g, 1.80 mmol, 71.8%). 1H NMR (500 MHz, 350
K, DMSO-d6): δ (ppm) 8.69 (2H, broad), 8.58 (2H, d, J = 7.4 Hz),
8.45 (2H, s), 7.97 (2H, dt, J = 7.7, 1.8 Hz), 7.48 (7H, m), 7.21 (3H,
broad), 7.05 (2H, broad), 5.00 (1H, broad), 4.76 (2H, broad), 4.48
(2H, broad), 3.84 (1H, d, J = 11.8 Hz), 3.62 (1H, d, J = 12.0 Hz), 2.95
(1H, m), 2.44 (1H, m), 1.30 (9H, broad). 13C NMR (125 MHz, 350K,
DMSO-d6): δ (ppm) 170.9, 169.6, 155.1, 154.9, 154.5, 152.4, 148.8,
148.3, 136.8, 135.6, 131.6, 128.2, 127.6, 127.5, 127.2, 126.7, 126.2,
1
0.10 mmol, 31.0%) (Scheme 2). H NMR (500 MHz, rt, CDCl3): δ
(ppm) 8.65 (4H, d, J = 4.2 Hz), 8.60 (4H, d, J = 8.1 Hz), 8.36 (4H, s),
7.84 (4H, dt, J = 7.7, 1.7 Hz), 7.56−7.47 (8H, m), 7.44−7.39 (2H, m),
7.32 (4H, ddd, J = 8.65, 4.8, 1.2 Hz), 4.91 (2H, dd, J = 10.1, 7.1 Hz),
4.77 (4H, dd, J = 33.0, 17.0 Hz), 3.93 (2H, d, J = 12.9 Hz), 3.73 (2H,
d, J = 12.9 Hz), 2.66−2.53 (4H, m). 13C NMR (125 MHz, rt, CDCl3):
δ (ppm) 173.4, 165.1, 156.4, 155.6, 155.0, 149.3, 147.3, 137.0, 131.1,
129.4, 128.7, 126.1, 124.2, 121.6, 118.5, 66.5, 58.8, 48.7, 42.8, 34.1.
[α]D20 = −11.4°(CHCl3). HPLC analysis (30 min, 5−95% MeCN/
H2O with 0.1% formic acid): Tr = 19.3 min. UV−vis (acetonitrile) λ (ε
× 10−3): 236 (4.68), 252 (3.43), 278 (3.85), 302 (2.23), 314 (1.24).
Emission (λexcit = 278 nm). λ (relative intensity): 326 (25.9), 342
(3.57), 357 (3.24), 652 (0.252), 667 (0.265). ESI HR-MS [M+H]+
Calculated: 1005.3580. Found: 1005.3571.
Compound 6a: (5S,8S)-1-{[2,6-Bis(pyridin-2-yl)pyridin-4-yl]-
methyl}-2,4-dioxo-3-phenyl-7-[(prop-2-en-1-yloxy)carbonyl]-
1,3,7-triazaspiro[4.4]nonane-8-carboxylic acid. Compound 5a
(600 mg, 1.00 mmol) was suspended in 30 mL DCM and allyl
chloroformate (116 μL, 1.10 mmol) was added, followed by addition
of DIPEA (517 μL, 2.99 mmol). The resultant mixture was stirred
overnight at room temperature. To work up the reaction, another 30
mL of DCM was added, and the mixture was then washed with 20 mL
20
123.8, 120.5, 118.8, 81.1, 78.4, 68.5, 66.1, 58.2, 54.3, 42.8, 27.2. [α]D
= −38.1°(CHCl3). HPLC analysis (30 min, 5−95% MeCN/H2O with
0.1% formic acid): Tr = 22.6 min. ESI HR-MS [M+H]+ Calculated:
711.2926. Found: 711.3322.
Spiroligomer Ligand L (SSSS): 7-Benzyl 8-Tert-butyl (5R,8S)-
1-{[2,6-bis(pyridin-2-yl)pyridin-4-yl]methyl}-2,4-dioxo-3-phe-
nyl-1,3,7-triazaspiro[4.4]nonane-7,8-dicarboxylate. An amount
of 4.5 mL of 33% HBr/AcOH was added to the solution of 4a (1.60g,
2.25 mmol) in 80 mL DCM. Then the solution was stirred at room
temperature for 3 h. The reaction mixture was then concentrated and
transferred with DCM to a falcon tube and centrifuged to afford 5a as
a yellow solid (1.30 g, 2.16 mmol, 96.1%). Then it was used without
further purification. Compund 5a (400 mg, 0.665 mmol) and HATU
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Article
brine/water: 1/1, 20 mL saturated NH4Cl (aq), and 20 mL brine. The
organic layer was dried over Na2SO4 and then concentrated to afford
6a (422 mg, 0.70 mmol, 70%) as a white solid. 1H NMR (500 MHz, rt,
DMSO-d6): δ (ppm) 8.74 (2H, d, J = 4.2 Hz), 8.63 (2H, d, J = 8.0
Hz), 8.46 (2H, s), 8.02 (2H, dt, J = 7.8, 1.6 Hz), 7.52 (6H, m), 7.4
(1H, m), 5.82 (1H, m), 5.23 (1H, t, J = 17.0 Hz), 5.11 (1H, d, J = 10.5
Hz), 4.93 (2H, dd, J = 33.2, 17.0 Hz), 4.44 (3H, m), 4.04 (1H, t, J =
13.1 Hz), 3.63 (1H, dd, J = 46.0, 14.4 Hz), 2.81 (1H, m), 2.39 (1H,
m). 13C NMR (125 MHz, 350 K, DMSO-d6): δ (ppm) 172.8, 171.7,
155.2, 154.9, 153.2, 148.9, 148.7, 136.8, 132.5, 131.5, 128.3, 127.6,
126.2, 123.8, 120.6, 118.7, 116.3, 66.3, 65.0, 57.5, 49.8, 42.1, 35.2.
[ClO4]4·1.5 (C7H8), 98% based on L. UV−Vis (acetonitrile) λ(ε ×
10−3): 215 (16.5), 235 (11.8), 269 (58.1), 278 (6.06), 286 (64.3)325
(6.16). Emission (λexcit = 333 nm). λ(relative intensity): 357 (6.31),
408 (3.24), 432 (2.66), 682 (0.471), 708 (0.417). ESI MS [m/z] (m/z
theory): [Mn2(tt-Terpy-SSSS)2·2ClO4]2+ 1159.7 (1159.4), [Mn2(tt-
Terpy-SSSS)2·ClO4]3+ 739.9 (739.5).
Synthesis of [Zn2L2]·(ClO4)4 (2). Zinc perchlorate, Zn-
(ClO4)2·6H2O (0.00784 g, 0.02 mmol) was added to a slurry of
S,S,S,S bis(terpyridyl)spiroligomer ligand (L) (0.01g, 0.01 mmol) in 10
mL 1:1 acetonitrile:dichloromethane. The resultant mixture was then
stirred at room temperature for 24 h. The reaction mixture was
filtered, and the filtrate was dried under vacuum. The dried residue was
extracted with dimethylformamide and the solution heated to 80−90
°C for 5 min. Next, the solution was filtered, and the filtrate kept at
room temperature, while crystals grew by slow evaporation. White
rectangular crystals were obtained after two weeks. Yield 0.01 g of
20
[α]D = +9.44°(MeOH). HPLC analysis (30 min, 5−95% MeCN/
H2O with 0.1% formic acid): Tr = 15.5 min. ESI HR-MS [M+H]+
Calculated: 605.2143. Found: 605.2447.
Spiroligomer Ligand L′ (SSSR): (3′S,4R,9′S,11′S)-3,3″-Bis-
({[2,6-bis(pyridin-2-yl)pyridin-4-yl]methyl})-1,1″-diphenyl-
dispiro[imidazolidine-4,5′-[1,7]diazatricyclo[7.3.0.03,7]-
dodecane-11′,4″-imidazolidine]-2,2′,2″,5,5″,8′-hexone. Com-
pound 6a (273 mg, 0.45 mmol) and HOAt (369.1 mg, 2.71 mmol)
were dissolved in 12 mL DCM and 6 mL DMF, and then DIC (77.8
μL, 0.50 mmol) was added. The resultant mixture was stirred at room
temperature for 2 h, 5b (218 mg, 0.362 mmol). Compound 5b is
prepared by the same method as the preparation for 5a, except that the
precursor is the R stereoisomer. Compound 4b was dissolved in 6 mL
DMF, followed by addition of DIPEA (125 μL, 0.72 mmol). Then the
prementioned mixture of 6a was added dropwise to the mixture of 5b.
The resultant was stirred overnight. HNMe2·BH3 (159.8 mg, 2.71
mmol) and Pd(PPh3)4 (52.23 mg, 0.05 mmol) were dissolved in 3 mL
DCM and added to the reaction mixture. The resultant mixture was
stirred at room temperature overnight. An amount of 20 mL water and
saturated NH4Cl (aq) was added to the reaction mixture followed by
the extraction of EtOAc (60 mL) three times, and the combined
organic layer was washed with 40 mL brine/water: 1/1 and then 40
mL brine and dried over Na2SO4. Then the organic layer was
concentrated and purified by flash chromatography (SiO2, toluene/
EtOAc: 1/1 to toluene/EtOAc/water: 1/4/0.04) to afford L′ (163 mg,
1
[2][ClO4]4, 79% based on L. H NMR (500 MHz, rt, DMSO-d6): δ
(ppm) 8.83 (8H, s), 8.66 (8H, d, J = 7.3 Hz), 7.89 (8H, broad), 7.68
(8H, broad), 7.62 (8H, d, J = 7.7 Hz), 7.56 (8H, t, J = 7.8 Hz), 7.47−
7.43 (4H, m), 7.88 (8H, broad), 5.32 (4H, d, J = 17.6 Hz), 4.92 (8H, t,
J = 8.4 Hz), 4.15 (4H, d, J = 11.6), 3.91 (4H, broad), 2.95−2.91 (4H,
m), 2.68−2.64 (4H, m). 13C NMR (125 MHz, rt, DMSO-d6): δ
(ppm) 173.0, 164.4, 157.0, 155.0, 148.7, 147.6, 147.2, 141.0, 131.7,
128.7, 127.7, 126.5, 123.0, 121.1, 66.8, 58.3, 48.8, 42.9, 33.2. Emission
(λexcit = 333 nm. λ(relative intensity): 354 (100), 378 (61.6), 403
(33.0), 688 (7.51), 713 (5.50), 797 (0.580). LC-MS [m/z] (m/z
theory): [Zn2(tt-Terpy-SSSS)2]4+535.14, (535.14).
ASSOCIATED CONTENT
* Supporting Information
Crystallographic tables, NMR, fluorescence, and MS figures,
and crystallographic data in cif format. This material is available
free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail: schafmeister@temple.edu (C.E.S.); mzdilla@temple.
edu (M.J.Z.).
■
1
0.16 mmol, 44.7%). H NMR (500 MHz, rt, CDCl3): δ (ppm) 8.68
(2H, d, J = 3.8 Hz), 8.59 (6H, m), 8.44 (2H, s), 8.33 (2H, s), 7.81
(4H, m), 7.52 (6H, m), 7.41 (3H, m), 7.32 (3H, m), 7.24 (2H, m),
4.97 (1H, d, J = 16.3 Hz), 4.76 (4H, m), 4.51 (1H, t, J = 7.4 Hz), 4.20
(1H, d, J = 12.7 Hz), 3.88 (2H, m), 3.38 (1H, d, J = 12.7 Hz), 3.03
(1H, dd, J = 14.0, 6.2 Hz), 2.63 (1H, m), 2.55 (2H, dd, J = 12.8, 8.4
Hz). 13C NMR (125 MHz, rt, CDCl3): δ (ppm) 172.2, 171.2, 163.9,
163.6, 155.6, 155.1, 154.8, 154.5, 154.2, 153.9, 148.4, 148.2, 146.5,
146.5, 136.1, 135.9, 130.4, 130.4, 128.3, 128.2, 127.6, 127.6, 125.2,
125.1, 123.3, 123.1, 120.6, 120.5, 118.4, 118.0, 65.9, 65.3, 58.1, 57.6,
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the Defense Threat Reduction
Agency (DOD-DTRA) (HDTRA1-09-1-0009) and Temple
University for financial support of this work. This research was
supported by an allocation of advanced computing resources
provided by the National Science Foundation (TG-
CHE100059). The computations were performed on Kraken
at the National Institute for Computational Sciences (http://
www.nics.tennessee.edu/). Thank you to Prof. David Goldberg,
Catharine Prokop, and Alison McQuilken (Johns Hopkins
University) for assistance with EPR measurements, Sandeep
Kondaveeti for assistance with cyclic voltammetry, Marek
Domin for assistance with mass spectrometry, Mohit Patel for
assistance with fluorescence spectroscopy, and Larry Henling
for assistance with an X-ray crystallographic problem.
20
49.8, 49.4, 42.5, 41.8, 33.4, 33.4. [α]D = −12.33°(CHCl3). HPLC
analysis (30 min, 5−95% MeCN/H2O with 0.1% formic acid): Tr =
18.3 min. ESI HR-MS [M+H]+ Calculated: 1005.3580. Found:
1005.3907.
General Methods for Metal Complex Preparation. All
reagents were purchased from commercial sources (Aldrich, Strem
Chemicals). Anhydrous solvents such as benzene, dichloromethane,
and toulene were purified using an Innovative Technology, Inc. Pure
Solv. system. Diethyl ether was distilled from sodium benzophenone-
ketyl under a nitrogen atmosphere. Mn(ClO4)2·H2O and Zn-
(ClO4)2·6H2O were purchased from Strem Chemicals or Aldrich.
Anhydrous solvents were used throughout all experiments.
Synthesis of [Mn2L2]·(ClO4)4 (1). Manganese perchlorate, Mn-
(ClO4)2·H2O (0.005 g, 0.02 mmol) was added to a slurry of S,S,S,S
bis(terpyridyl)spiroligomer ligand L (tt-Terpy-SSSS) (0.01g, 0.01
mmol) in 10 mL 1:1 acetonitrile:dichloromethane. The resultant
yellow mixture was then stirred at room temperature for 24 h. The
reaction mixture was filtered, and the filtrate dried under vacuum. The
dried residue was extracted with acetonitrile, resulting in a yellow
solution, onto which was layered toluene in a 0.5 mm diameter vial.
Light yellow crystals of 1 were obtained at room temperature after
three weeks of diffusion in the closed vial. X-ray quality crystals were
grown by addition of 1 mL glacial acetic acid in the reaction mixture
and slow evaporation at room temperature. Yield 0.013 g of [1]
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