Exchange coupling mediated through-bonds and through-space in conformationally constrained polyradical scaffolds: Calix[4]arene nitroxide tetraradicals and diradical

Article abstract of DOI:10.1021/ja063567+

Calix[4]arenes constrained to the 1,3-alternate conformation and functionalized at the upper rim with four and two tert-butylnitroxides have been synthesized and characterized by X-ray crystallography, magnetic resonance (EPR and ¹H NMR) spectr

Full text of DOI:10.1021/ja063567+

Published on Web 09/23/2006
Exchange Coupling Mediated Through-Bonds and
Through-Space in Conformationally Constrained Polyradical
Scaffolds: Calix[4]arene Nitroxide Tetraradicals and Diradical
Andrzej Rajca,*,† Sumit Mukherjee, Maren Pink, and Suchada Rajca
†
‡
†
Contribution from the Department of Chemistry, UniVersity of Nebraska, Lincoln,
Nebraska 68588-0304, and IUMSC, Department of Chemistry, Indiana UniVersity, Bloomington,
Indiana 47405-7102
Received May 22, 2006; E-mail: arajca1@unl.edu
Abstract: Calix[4]arenes constrained to the 1,3-alternate conformation and functionalized at the upper rim
with four and two tert-butylnitroxides have been synthesized and characterized by X-ray crystallography,
1
magnetic resonance (EPR and H NMR) spectroscopy, and magnetic studies. The 1,3-alternate nitroxide
tetraradical and diradical provide unique polyradical scaffolds for dissection of the through-bond and through-
space intramolecular exchange couplings. In addition, detailed magnetic studies of the previously reported
calix[4]arene nitroxide tetraradical, which possesses cone conformation in solution, reveal conformational
dependence of exchange coupling. Through-bond coupling between the adjacent nitroxide radicals is
mediated by the nitroxide-m-phenylene-CH -m-phenylene-nitroxide coupling pathway, and through-
2
space coupling is found between the diagonal nitroxide radicals at the conformationally constrained N‚‚‚N
distance of 5-6 Å. Magnetic studies of the calix[4]arene polyradical scaffolds in frozen solutions show that
the through-bond exchange coupling in the 1,3-alternate calix[4]arene tetraradical is antiferromagnetic,
while that in cone calix[4]arene tetraradical is ferromagnetic. The through-space exchange couplings are
antiferromagnetic in both cone and 1,3-alternate calix[4]arene tetraradical, as well as in the 1,3-alternate
calix[4]arene diradical. The exchange coupling constants (|J/k|) are of the order of 1 K.
Introduction
likely to be exchange coupling, mediated through-bonds and/
or through-space. In general, the exchange coupling is mediated
1
The spin-spin interactions between unpaired electrons in
more effectively through-bonds, especially through cross-
organic diradicals and polyradicals are of critical importance
3
,6-10
in organic magnetism,1-3 molecular charge-transfer,4 and mul-
conjugated π-system, than through-space.
Such exchange
tiple spin labeling in structural biology.5 When unpaired
electrons are in close proximity, the dominant interaction is
coupling can be either ferromagnetic or antiferromagnetic,
depending upon the topology and conformation of the coupling
1
,8-12
pathway connecting the radicals.
†
University of Nebraska.
Indiana University.
Stable polyradical scaffolds with constrained conformations
may provide a new approach for controlling through-bond and
through-space exchange couplings. The fixed conformations of
‡
(
1) (a) Iwamura, H.; Koga, N. Acc. Chem. Res. 1993, 26, 346-351. (b) Rajca,
A. Chem. ReV. 1994, 94, 871-893. (c) Lahti, P. M., Ed. Magnetic
Properties of Organic Materials; Marcel Dekker: New York, 1999; pp
1
,3-alternate and cone calix[4]arenes, which are functionalized
1
-713. (d) Itoh, K., Kinoshita, M., Eds. Molecular Magnetism; Gordon
and Breach: Kodansha, 2000; pp 1-337. (e) Rajca, A. Chem.-Eur. J. 2002,
, 4834-4841. (f) Rajca, A. AdV. Phys. Org. Chem. 2005, 40, 153-199.
2) (a) Rajca, A.; Wongsriratanakul, J.; Rajca, S. Science 2001, 294, 1503-
505. (b) Rajca, S.; Rajca, A.; Wongsriratanakul, J.; Butler, P.; Choi, S. J.
8
(6) Spagnol, G.; Shiraishi, K.; Rajca, S.; Rajca, A. Chem. Commun. 2005,
5047-5049.
(
1
(7) Dougherty, D. A. Acc. Chem. Res. 1991, 24, 88-94.
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Am. Chem. Soc. 1993, 115, 1744-1753. (b) Jacobs, S. J.; Dougherty, D.
A. Angew. Chem., Int. Ed. Engl. 1994, 33, 1104-1106.
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Am. Chem. Soc. 2004, 126, 6972-6986. (c) Rajca, A.; Wongsriratanakul,
J.; Rajca, S. J. Am. Chem. Soc. 2004, 126, 6608-6626. (d) Rajca, A.;
Wongsriratanakul, J.; Rajca, S.; Cerny, R. L. Chem.-Eur. J. 2004, 10, 3144-
3
157. (e) Rajca, A.; Shiraishi, K.; Vale, M.; Han, H.; Rajca, S. J. Am.
Chem. Soc. 2005, 127, 9014-9020.
(
(
3) Fukuzaki, E.; Nishide, H. J. Am. Chem. Soc. 2006, 128, 996-1001.
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Wasielewski, M. R. J. Am. Chem. Soc. 2004, 126, 5577-5584. (b) Weiss,
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(12) For an effect of heteroatoms on through-bond exchange coupling: (a) West,
A. P., Jr.; Silvermann, S. K.; Dougherty, D. A. J. Am. Chem. Soc. 1997,
119, 1452-1463. (b) Matsuda, K.; Yamagata, T.; Seta, T.; Iwamura, H.;
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Chem. Res. 1997, 30, 238-244. (d) Shultz, D. A.; Bodnar, S. H.; Lee, H.;
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124, 10054-10061.
0
64504-1-8. (c) Weiss, E. A.; Tauber, M. J.; Kelley, R. F.; Ahrens, M.
J.; Ratner, M. A.; Wasielewski, M. R. J. Am. Chem. Soc. 2005, 127, 11842-
1850. (d) Chernick, E. T.; Mi, Q.; Kelley, R. F.; Weiss, E. A.; Jones, B.
A.; Marks, T. J.; Ratner, M. A.; Wasielewski, M. R. J. Am. Chem. Soc.
006, 128, 4356-4364.
1
2
(
5) (a) Hustedt, E. J.; Beth, A. H. Annu. ReV. Biophys. Biomol. Struct. 1999,
2
8, 129-153. (b) Eaton, S. S.; Eaton, G. R. Biol. Magn. Reson. 2000, 19,
-27. (c) Altenbach, C.; Oh, K.-J.; Trabanino, R.; Hideg, K.; Hubbell, W.
1
Biochemistry 2001, 40, 15471-15482. (d) Hanson, P.; Millhauser, G.;
Formaggio, F.; Crisma, M.; Toniolo, C. J. Am. Chem. Soc. 1996, 118,
7
618-7625.
10.1021/ja063567+ CCC: $33.50 © 2006 American Chemical Society
J. AM. CHEM. SOC. 2006, 128, 13497-13507
9
13497

A R T I C L E S
Rajca et al.
Scheme 1. Synthesis of Nitroxide Tetraradical 1 and Diradical 2a
Figure 1. 1,3-Alternate and cone calix[4]arene scaffolds, functionalized
on the upper rims with radicals.
a
Conditions: (i) t-BuLi (8 equiv), THF, -78 °C for 2 h, then -20 °C
for 15 min; (ii) [(CH3)3CNO]2 (2.1 equiv) in THF, -78 °C then slowly
warm to room temperature overnight; (iii) n-BuLi (2.2 equiv), THF; (iv)
[(CH3)3CNO]2 (1.2 equiv); (v) Ag2O, CHCl3 or CH2Cl2.
and studies of ambient stable nitroxide tetraradical 1 and
diradical 2 in the fixed 1,3-alternate calix[4]arene conformations
(Figure 2). Magnetic studies of 1 and 2, as well as magnetic
studies of 3 in solution, are described. Both through-bond and
through-space exchange couplings are determined, as well as
their conformational dependence.
Results and Discussion
Synthesis. The synthesis starts from tetrabromocalix[4]arene
4
, constrained in the 1,3-alternate conformation (Scheme 1 and
1
5
Supporting Information). The Li/Br exchange on 4 with an
excess amount of t-BuLi gives intermediate tetrakis(aryllithium),
which is reacted with 2-methyl-2-nitrosopropane dimer, to
provide tetrahydroxylamine 5. An analogous procedure, in which
the t-BuLi is replaced with n-BuLi (2 equiv), gives dihy-
droxylamine 6.
Figure 2. Nitroxide tetraradical 1 and diradical 2 with the constrained
conformations of 1,3-alternate calix[4]arene, and nitroxide tetraradical 3
with the constrained conformation of cone calix[4]arene.
1
6
The presence of the hydroxyl groups in 5 and 6 is confirmed
at the upper rim with stable aryl-delocalized radicals, may be
viewed as such scaffolds.13a,14 In these scaffolds, the through-
bond exchange coupling between the adjacent radicals is
mediated by the radical-m-phenylene-CH2-m-phenylene-
radical coupling pathway, with distinct conformations in the
-1
1
by IR (e.g., νO-H ≈ 3230-3240 cm ) and H NMR spectra
(
D2O-exchangeable 4-proton or 2-proton singlet at 9.1-9.3
1
ppm). In the H NMR spectra, only one sharp singlet for tert-
butyl group protons is observed for each compound. The other
H resonances are relatively broadened at ambient temperature,
due to the restricted rotations along the C(aromatic)-N bonds;
1
1
,3-alternate and cone calix[4]arenes (Figure 1). In addition,
the through-space exchange coupling at fixed radical-radical
distances of approximately 5-6 Å, as found for the diagonal
radicals, may be probed (Figure 1).
the coalescence temperatures for aromatic protons suggest that
-1
the barrier for rotation is on the order of 15 kcal mol (Table
S1, Supporting Information). In the high-temperature limit, 5
Recently, we reported the synthesis, crystallography, and
magnetic characterization of the cone calix[4]arene scaffold,
and 6 possess D2d (T > 325 K) and C2V (T > 306 K) point
1
groups, respectively, on the H NMR (400 MHz) time scale.
13
nitroxide tetraradical 3 (Figure 2). In the solid state, this
tetraradical adopts a pinched cone conformation, forming an
intramolecular dimer with strong antiferromagnetic coupling
Oxidation of 5 and 6 with freshly prepared silver oxide gives
the corresponding nitroxide tetraradical 1 and diradical 2
Scheme 1).
(
(
|J/k| ) 200-300 K) between the two diagonal nitroxides. In
Molecular Structure of 1 and 2. Nitroxide tetraradical 1
solution, 3 was found to possess a 4-fold symmetric cone
crystallizes with one molecule per asymmetric unit, without
inclusion of solvent. For diradical 2, two crystallographically
unique molecules are found, with one-quarter benzene molecule
per formula unit (one-half benzene molecule per asymmetric
unit). The X-ray structure determinations of nitroxide tetraradical
conformation, but exchange coupling could only be estimated
13
as 30 K > |J/k| >> 1.8 mK. Now, we report the synthesis
(
13) (a) Rajca, A.; Pink, M.; Rojsajjakul, T.; Lu, K.; Wang, H.; Rajca, S. J.
Am. Chem. Soc. 2003, 125, 8534-8538. (b) Because of technical difficulties
in measurements of magnetic susceptibility data for 3 in solution at low
temperatures, a wide range of values for the exchange coupling were
obtained (30 K > |J/k| >> 1.8 mK).
1
[
and diradical 2 confirm 1,3-alternate conformation of the calix-
4]arene macrocycle for both molecules (Figure 3, Table 1).
(
14) Nitroxides and nitronyl nitroxides on the upper and lower rim of calix[4]-
arene: (a) Ulrich, G.; Turek, P.; Ziessel, R. Tetrahedron Lett. 1996, 37,
8
1
755-8758. (b) Wang, Q.; Li, Y.; Wu, G. Chem. Commun. 2002, 1268-
(15) Verboom, W.; Datta, S.; Reinhoudt, D. N. J. Org. Chem. 1992, 57, 5394-
5398.
(16) Larsen, M.; Jørgensen, M. J. Org. Chem. 1996, 61, 6651-6655.
269. (c) Kr o¨ ck, L.; Shivanyuk, A.; Goodin, D. B.; Rebek, J., Jr. Chem.
Commun. 2004, 272-273.
13498 J. AM. CHEM. SOC.
9
VOL. 128, NO. 41, 2006

Exchange Coupling in Polyradical Scaffolds
A R T I C L E S
Figure 3. Molecular structure and conformation for nitroxide tetraradical 1 (left) and diradical 2 (right) with constrained conformations of 1,3-alternate
calix[4]arene. Carbon, nitrogen, and oxygens atoms are depicted with thermal ellipsoids set at the 50% probability level. Only one of the two unique
molecules of 2 and without the solvent of crystallization (benzene) is shown.
Table 1. Summary of the X-ray Crystallographic Data
each aryl nitroxide moiety. In the other molecule, the NO groups
property
1
2 (0.25
‚
C
6
6
H )
have parallel N-O bond axes (syn) and they form torsional
am n og il ee tsy o. f ∼40° with the benzene rings within each aryl nitroxide
molecular formula
formula weight
crystal/color
crystal system
space group
a, Å
b, Å
c, Å
R, deg
â, deg
C56H80N4O12
1001.24
red block
monoclinic
P21/c
14.920(4)
35.167(9)
10.593(3)
90
100.379(7)
90
5467(2)
4
C49.50H63.50Br2N2O10
1006.34
red block
triclinic
For 1 and 2, the C(ipso)-C(CH2)-C(ipso) angles within
calix[4]arene macrocycles are in the 110-113° range.17 The
dihedral angles between the planes defined by the C(ipso)-
C(CH2)-C(ipso) and the benzene rings are in the 59-73° range
P-1
14.698(5)
19.752(6)
20.370(7)
96.911(9)
110.227(9)
111.428(9)
4955(3)
(Table S2, Supporting Information). In this geometry of 1,3-
alternate conformation, the π-systems of the adjacent arylni-
troxides are pointing away from each other. However, in a cone
conformation, which is adopted by tetraradical 3 in solution,
the dihedral angles between the C(ipso)-C(CH2)-C(ipso) and
benzene ring planes are close to 90°, with the π-systems of the
adjacent arylnitroxides pointing toward each other. Therefore,
the through-space interactions between the adjacent arylnitroxide
moieties in the 1,3-alternate conformation of 1 should be
relatively small, as compared to those in the cone conformation
of 3.
ø, deg
volume, Å
3
Z
4
-
3
Dcalcd/g cm
1.216
82 665
1.349
66 102
reflns collected
unique reflns
data/restraints/parameters 12 675/0/665
R1 (I > 2σ(I))
wR2 (I > 2σ(I))
GOF
12 675 (Rint ) 0.0554) 22 927 (Rint ) 0.0627)
22 927/48/1206
0.0483
0.1082
0.0461
0.1141
1.019
1.014
In tetraradical 1, the molecular structure is consistent with
significant repulsion between the bulky tert-butyl nitroxide
moieties. The N-C(ipso)-C(para) angles of <180° (e.g., N1-
C3-C6 angle of 172°) and pyramidalized nitrogen atoms
indicate outward bending of the nitroxide groups, with relatively
long N1‚‚‚N3 (5.78 Å) and N2‚‚‚N4 (5.70 Å) distances between
the diagonal nitroxide groups. Dihedral angles between nitroxide
groups and benzene rings are significantly different for each of
the four aryl nitroxide units; for each pair of the diagonal tert-
butyl nitroxide moieties, the bulky tert-butyls occupy the
significant part of the space between the nitroxide groups (Figure
1
Structure of 1 and 2 in Solution. H NMR spectra of
tetraradical 1 and diradical 2 in chloroform-d at room temper-
ature show resonances for those protons that are expected to
possess relatively small spin densities, that is, all protons except
those of the aryl moieties of the arylnitroxides (Figure 5).1
b,13a,18,19
Four broad resonances are observed for tetraradical 1, as
expected for a structure with the D2d point group. The relatively
less broadened 12-proton and 16-proton singlets at 4.34 and
.84 ppm are assigned to the methyl (CH3) and dimethylene
CH2CH2) of the methoxyethyleneoxy (OCH2CH2OCH3) groups,
respectively. The two most upfield shifted broad singlets,
-proton at -0.8 ppm and 36-proton at -5.9 ppm, are assigned
3
(
4
).
In diradical 2, the structures for the two crystallographically
8
unique molecules show the two nitroxide groups in relatively
closer proximity, with N‚‚‚N distances of 5.07 and 5.37 Å and
nearly planar nitrogen atoms, as compared to 1. In one of the
unique molecules, the NO groups have antiparallel N-O bond
axes (anti) and they are coplanar with the benzene rings within
(
17) C(CH
2
) and C(ipso) refer to the CC-bonded carbon atoms of the methylene
group and benzene ring of the calix[4]arene scaffold. An example of the
2
C(ipso)-C(CH )-C(ipso) angle is the C5-C7-C8 angle of 112.6° in 1.
(
18) NMR of Paramagnetic Molecules; La Mar, G. N., Horrocks, W. DeW.,
Jr., Holm, R. H., Eds.; Academic Press: New York, 1973.
(19) Sharp, R. R. Nucl. Magn. Reson. 2005, 34, 553-596.
J. AM. CHEM. SOC.
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VOL. 128, NO. 41, 2006 13499

A R T I C L E S
Rajca et al.
Figure 4. Conformation of the tert-butyl nitroxide moieties (ball-and-stick) in crystalline nitroxide tetraradical 1 and diradical 2. For 2, two crystallographically
unique molecules are shown; in one of the molecules, disorder in the ethylenoxymethyl chain and the tert-butyl group is omitted for clarity.
assigned to the aromatic, OCH3, and OCH2CH2O protons of
the diamagnetic bromophenyl moieties of 2, respectively.
The significant upfield chemical shifts of several parts-per-
million for the protons of tert-butyl groups and of methylene
groups in tetraradical 1 and diradical 2, when compared to the
corresponding hydroxylamines 5 and 6, indicate substantial
negative spin densities at the hydrogen atoms in these groups.
The negative sign of the spin density for the hydrogen atoms
of the tert-butyl groups is consistent with the spin polarization
through σ-bonds of the positive spin density at the nitrogen atom
of the nitroxide, as found for N-tert-butylnitroxides.21 The
negative sign for the hydrogen atoms of the methylene groups
is compatible with both hyperconjugation and spin polarization
of the negative spin density from the meta-carbon (meta-position
with respect to the nitroxide) in the benzene ring.22 The near
coincidence of resonances for the methyl (CH3) and dimethylene
(CH2CH2) of the methoxyethyleneoxy (OCH2CH2OCH3) groups
in 1 and 2, and in diamagnetic 5 and 6, suggests negligible spin
densities at the hydrogen atoms of the OCH2 fragment. Similar
behavior was found in 3,5-dimethyl-4-methoxyphenyl-tert-
1
butylnitroxide, in which a very small value of H-hyperfine
splitting, aH ) +0.0006 mT, for the methoxy hydrogens was
ascribed to the twisting of the methoxy group out of conjugation
2
2,23
1
with the benzene ring and the nitroxide.
These H NMR
spectral assignments confirm the structures of 1 and 2 in solution
and are in agreement with the reported spectra for the fixed
1
3a
cone calix[4]arene nitroxide tetraradical 3.
EPR spectrum of 1 in toluene at 295 K shows a well-resolved
nonet (Figure 6). An excellent numerical spectrum fit to a single
component, that is, nitroxide tetraradical 1, is obtained, confirm-
ing high degree of radical purity (98+%) of 1.24 The
14
N
hyperfine coupling with peak-to-peak splitting ∆Hpp ≈ 0.319
mT ) aN/4, that is, aN ) 1.28 mT, is identical to the value
reported for 3,5-dimethyl-4-methoxyphenyl-tert-butylnitrox-
Figure 5. 1H NMR (500 MHz, chloroform-d, LB ) 1 Hz) spectra for
nitroxide tetraradical 1 (top) and diradical 2 (bottom). Inset plot: LB ) 10
Hz. The singlets at 7.26 ppm and ∼1.5 ppm correspond to the residual
nondeuterated chloroform and water peaks. The other sharp, relatively weak
peaks are assigned to diamagnetic impurities.
(20) Two types of protons (AB or AX spin system) are expected for the
methylene groups of the macrocycle in diradical 2. An AB spin system is
observed for the corresponding protons in dihydroxylamine 6 at T > 306
K.
to the methylene groups of the macrocycle and the tert-butyl
groups, respectively.
Four broad resonances with chemical shifts similar to those
in 1 may be identified for diradical 2; specifically, two of those
resonances appear in the -5 ppm region as a broad singlet with
a shoulder, which may be assigned to the two tert-butyl groups
and four methylene groups of the macrocycle.20 In addition,
relatively narrow singlets at 7.47, 4.30, and 3.69 ppm are
(
21) (a) Rassat, A.; Ray, P. Tetrahedron 1973, 29, 2845-2848. (b) Rajca, A.;
Lu, K.; Rajca, S.; Ross, C. R., II. Chem. Commun. 1999, 1249-1250.
22) Forrester, A. R.; Hepburn, S. P.; McConnachie, G. J. Chem. Soc., Perkin
Trans. 1 1974, 2213-2219.
(
(23) Hyperfine splitting of a ) +0.019 mT for the methoxy hydrogens in
H
4-methoxyphenyl-tert-butylnitroxide has been reported (ref 22).
(
24) The numerical fits with three components, tetraradical, triradical, and
diradical, indicate 98+% content of tetraradical. The three-component fit
and the one-component fit have coincident values of hyperfine splittings
for tetraradical and nearly identical sums of squared residuals (Figure S4,
Supporting Information).
13500 J. AM. CHEM. SOC.
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VOL. 128, NO. 41, 2006

Exchange Coupling in Polyradical Scaffolds
A R T I C L E S
Figure 7. EPR (X-band, 9.4424 GHz) spectrum of 0.6 mM nitroxide
diradical 2 in toluene/chloroform (4:1) at 140 K. The spectral simulation
of the |∆ms| ) 1 region is shown as red trace. The fitting parameters for
-
2
-1
the spectral simulation to the S ) 1 state are: |D/hc| ) 1.39 × 10 cm
-
1
(
2
|D/gµB| ) 14.9 mT), |E/hc| ) 0 cm , gx ) 2.0064, gy ) 2.0064, gz )
.0030, Gaussian line (Lx ) 12 G, Ly ) 20 G, Lz ) 40 G). The center lines
correspond to an S ) /2 (monoradical) impurity.
1
is rather low, especially as compared to those for tetraradical
28
14
1
; consequently, the N hyperfine coupling with peak-to-peak
splitting ∆Hpp ≈ 0.8 mT ) aN/2, that is, aN ) 1.6 mT for 2,
should be viewed as an approximate estimate. These results are
in agreement with significant exchange coupling between
nitroxide radicals (|J/gµB| . |aN|).
Figure 6. EPR (X-band) spectra of 1 in toluene at 295 and 135 K.
Numerical fit (red dashed line) to the experimental spectrum at 295 K
corresponds to a single nitroxide tetraradical species; correlation coefficient
is 0.999, and the values for the variable parameters are as follows:
Lorentzian line width of 0.156 mT, g-shift of -0.045 mT (g-value )
In rigid matrixes, the EPR spectra of 2 clearly show the
presence of significant zero-field splitting, as indicated by the
large spectral width of |∆ms| ) 1 region and relatively intense
1
4
1
2
.0059), N-splitting of 0.319 mT for 4 nuclei, H-splitting of 0.048 mT
for 8 nuclei.
|
∆ms| ) 2 transition. The |∆ms| ) 1 spectrum of 2 in toluene/
ide.22,25 This result indicates exchange-coupled nitroxides with
chloroform glass at 140 K consists of four symmetrically
disposed broad peaks, corresponding to the zero-field splitting
14
a coupling constant significantly greater than the N hyperfine
coupling, |J/gµB| . |aN|, that is, |J/k| >> 1.8 mK. At 135 K,
the EPR spectrum of 1 in toluene glass shows a single peak in
the |∆ms| ) 1 region, with a somewhat broader spectral
envelope, as compared to the solution-phase spectrum for the
same sample (Figure 6). Furthermore, the |∆ms| ) 2 transition
is barely detectable. These results suggest that tetraradical 1
possesses rather small zero-field splitting (|D/hc|) that is
compatible with relatively high average symmetry for the
disposition of nitroxide radicals.2
-
2
-1
-1
parameters |D/hc| ) 1.39 × 10 cm and |E/hc| ) 0 cm
(
Figure 7). Similar four-peak |∆ms| ) 1 spectra are obtained at
low temperatures in 2-methyltetrahydrofuran, dichloromethane/
methanol (4:1), and ethanol (Figures S10 and S11, Supporting
Information); for the first two matrixes, the two side peaks
consist of five symmetrically disposed shoulders (pentuplet-
14
like), corresponding to the N hyperfine coupling with spacings
-
1
of (|Azz|/2)/hc ≈ 0.0013 cm ((|Azz|/2)/gµB ≈ 1.4 mT). (The
pentuplet in the |∆ms| ) 2 region possesses similar 1.4-mT line
spacings.) It is usually assumed that the largest principal values
of the magnetic dipole tensor and nuclear hyperfine tensor
correspond to the direction of the z-axis connecting the nitroxide
radicals and the direction of the nitrogen 2pπ-orbital, respec-
tively. The observation of the relatively large value of |Azz|/2
in the |∆ms| ) 1 region suggests that these two directions are
approximately coinciding; this may correspond to the limiting
conformation of diradical 2, with the parallel N-O bond axes
and the planar phenylnitroxide moieties. Spectral widths of the
6,27
EPR spectra of diradical 2 in solution (toluene, toluene/
chloroform (4:1), acetonitrile, dichloromethane, and dichlo-
romethane/methanol (4:1)) at ambient temperature show an
intense broad peak, with a discernible pentuplet spectral pattern;
furthermore, additional sharp peaks, with relatively low intensity,
are superimposed on the broad peak (Figures S6-S9, Supporting
Information). The EPR spectra of 2 in dichloromethane/methanol
2
9
(4:1) show pronounced sharpening at higher temperatures, with
a clearly defined pentuplet at 320 K; upon decreasing the
temperature, this peak is progressively broadened. For a 1 mM
solution of 2 in toluene at 295 K, the numerical spectrum fits
are compatible with a mixture of diradical and monoradical
|
∆ms| ) 1 regions, |2D/gµB| ) 29-31 mT, are solvent
dependent. Based upon a simple point-dipole approximation,
2D/gµB| ) 29-31 mT corresponds to an effective distance of
|
(98:2). Because of the dynamic effects, the quality of these fits
(
25) The agreement for the 1H hyperfine, which is not resolved in the EPR
spectrum of 1, is less satisfactory: a
(28) Polimeno, A.; Zerbetto, M.; Franco, L.; Maggini, M.; Corvaja, C. J. Am.
Chem. Soc. 2006, 128, 4734-4741.
H
) 0.019 mT versus 0.024 mT in 1
and in 3,5-dimethyl-4-methoxyphenyl-tert-butylnitroxide, respectively.
26) Wertz, J. E.; Bolton, J. R. Electron Spin Resonance; Chapman and Hall:
New York, 1986; Chapter 10, pp 223-257.
(29) (a) Griffith, O. H.; Cornell, D. W.; McConnell, H. M. J Chem. Phys. 1965,
43, 2909-2910. (b) In particular, Azz ) 3.2 mT was measured in di-tert-
(
(
1
4
butylnitroxide radical. As the solution-phase N hyperfine splittings for
aryl-alkyl nitroxide radicals, compared to the more localized alkyl-alkyl
nitroxide radicals, are lowered by a typical factor of 0.8-0.9, the value of
|Azz| ≈ 2.6 mT measured for aryl-alkyl nitroxide diradical 2 is reasonable.
27) The small zero-field splitting in tetraradical 1 is in contrast to the spectral
width of about 20 mT in tetraradical 3 in the cone conformation in solution
(ref 13).
J. AM. CHEM. SOC.
9
VOL. 128, NO. 41, 2006 13501

A R T I C L E S
Rajca et al.
Figure 8. SQUID magnetometry for 5 mM 1 in THF with numerical fits
to the tetraradical model (Figure 10, eqs 1 and 2). For the øT versus T fits
Figure 9. SQUID magnetometry for 7 mM 2 in THF with numerical fits
to the diradical model (eq 4 with J1/k ) 0). For the øT versus T fits (top)
and the M/Msat versus H/T fits (bottom), the variable parameters (parameter
(
top) and the M/Msat versus H/T fits (bottom), the J2/k (diagonal coupling)
is set to -1.1 and -0.5 K, respectively. The variable parameters (parameter
2
dependence and R ) are as follows: at 30 000 Oe in the warming mode,
2
dependence and R ) are as follows: at 5000 Oe in the warming mode, J2/k
J1/k ) -1.4 K, w ) 1.11 (0.32, 0.998); at 5000 Oe in the warming mode,
)
-0.8 K, w ) 0.89 (0.25, 0.990); at 5000 Oe in the cooling mode, J2/k
J1/k ) -1.2 K, w ) 1.10 (0.30, 0.995); at 1.8 K, J1/k ) -0.6 K, Msat )
)
-0.8 K, w ) 0.88 (0.26, 0.982); at 1.8 K, J2/k ) -0.6 K, Msat ) 0.80
0
.76 µB (0.85, 0.999); at 3 K, J1/k ) -0.7 K, Msat ) 0.86 µB (0.97, 1.000).
µB (0.62, 1.000); at 3 K, J2/k ) -0.6 K, Msat ) 0.82 µB (0.91, 1.000).
about 5.6-5.8 Å between the two magnetic dipoles.30 For 1
mM 2 in toluene/chloroform (4:1) with |2D/gµB| ) 30 mT, the
relative intensities of the |∆ms| ) 1 and |∆ms| ) 2 transitions
with antiferromagnetic exchange coupling, corresponding to a
mean-field parameter, θ ≈ -2.3 K. The antiferromagnetic
exchange coupling is most likely intramolecular, as the curvature
and onset of the downward turn are not dependent on the
concentration of 1 (5 and 13 mM). The presence of antiferro-
magnetic exchange coupling is also indicated by the relatively
slow saturation behavior for the M versus H data; the M/Msat
versus H/T plots at T ) 1.8-5 K have significantly different
curvatures, which are much smaller than the curvature of the
-
4
are 5.06 × 10 at 9.4848 GHz, providing the interspin distance
estimate of 5.73 Å.31 These distance measurements, which are
comparable to the expected distance between the midpoints of
the N-O bonds of the diagonal nitroxides in the 1,3-alternate
conformation of 2, should be viewed as approximate estimates,
as the spin density in 2 is delocalized and factors other than
magnetic dipole-dipole interactions may contribute to the value
of |2D|.
1
Brillouin curve for four independent spins S ) /2.
Considering their structural similarity, magnetic studies of
diradical 2 may provide additional insight into the nature of
intramolecular antiferromagnetic exchange coupling in tetraradi-
cal 1. For 7 mM 2 in THF (Figure 9), the relatively small
curvature of the downward turn in the øT versus T plot at low
temperature and the slightly different curvatures of the M/Msat
versus H/T plots in the T ) 1.8-5 K range are readily corrected
with a small mean-field parameter θ ≈ -0.5 K, accounting for
weak antiferromagnetic exchange coupling between two spins
The EPR spectra support structural assignments for 1 and 2
and provide the lower bound estimate for |J|, similar to that
found for 3. Values of J are determined by magnetic studies of
1
-3.
Magnetic Studies of 1, 2, and 3 in Solution. Magnetization
(
1
3
M) is measured as a function of magnetic field (H ) (0-5) ×
4
0 Oe and T ) 1.8, 3, and 5 K) and temperature (T ) 1.8-
00 K at H ) 30 000, 5000, or 500 Oe). The M versus H and
1
M versus T data are plotted as the M/Msat versus H/T and the
øT versus T, respectively, where Msat is the magnetization at
saturation and ø is the paramagnetic susceptibility.
For tetraradical 1 in tetrahydrofuran (THF), the value of øT
is constant in the 40-150 K range (Figure 8). The downward
turn in the øT versus T plot at low temperature is consistent
S ) /2. A similar weak antiferromagnetic coupling (θ ≈
-0.5 K) is observed for more concentrated, 15 and 24 mM,
samples of 2 in THF (Figures S13 and S14, Supporting
Information).
Magnetic data for 5 mM 1 in 2-MeTHF and ∼5 mM 2 in
chloroform/methanol (1:1) suggest significantly weaker anti-
ferromagnetic exchange couplings, θ ) -1.5 K and θ ) -0.1
to -0.2 K, respectively; for 2, the magnetic data are approaching
the near perfect paramagnetic behavior of two independent spins
(
30) (a) The following equation applies to distance, r (in Å), between two point-
1/3
dipoles: r ) (55 600/|(2D/gµ
B
)|) , where |2D/gµ | and r are expressed
B
in gauss and angstroms, respectively. (b) For localized nitroxide diradical,
in which the intramolecular distances between the midpoints of the N-O
1
S ) /2 (Figure S16, Supporting Information).
bonds were approximately 6.2 Å, |2D/gµ | ≈ 25 mT was measured: Rohde,
B
O.; Van, S. P.; Kester, W. R.; Griffith, O. H. J. Am. Chem. Soc. 1974, 96,
311-5318.
31) Eaton, S. S.; More, K. M.; Sawant, B. M.; Eaton, G. R. J. Am. Chem. Soc.
983, 105, 6560-6567.
These results indicate that exchange coupling in diradical 2
in THF is intramolecular and it is significantly weaker, as
compared to that in tetraradical 1 in THF. This suggests that
5
(
1
13502 J. AM. CHEM. SOC.
9
VOL. 128, NO. 41, 2006

Exchange Coupling in Polyradical Scaffolds
A R T I C L E S
M ) (11 180N)M [2(F + F )/(G + G )]
(1)
(2)
(3)
(4)
sat
1
2
1
2
øT ) (1.118T/H)w[2(F + F )/(G + G )]
1
2
1
2
M ) (11 180N)M [(F + F )/(G + G )]
sat
1
2
1
2
øT ) (1.118T/H)w[(F + F )/(G + G )]
1
2
1
2
1
Figure 10. Cluster of spins S ) /2 with pairwise exchange couplings J1
(
through-bond) and J2 (through-space) as the tetraradical model for 1 and
F1 ) sinh(a) + 2 sinh(2a)
F ) [sinh(a)][(exp((-4J /k)/T)) +
1
3
. The diradical model for 2 corresponds to a dimer of spins S ) /2 with
pairwise exchange coupling J2.
2
1
2
(exp((-(2J + 2J )/k)/T))]
1 2
the stronger antiferromagnetic exchange coupling in tetraradical
1
is mediated through-bonds, with the coupling pathway
G ) 1 + 2 cosh(a) + 2 cosh(2a) +
1
consisting of nitroxide-m-phenylene-CH2-m-phenylene-ni-
troxide; in diradical 2, with the additional m-phenylene-CH2
unit in the coupling pathway, the through-bond exchange
coupling should be negligible.32 This would imply that the weak
antiferromagnetic exchange coupling for 2 in THF may be
associated with the through-space exchange coupling between
the diagonal nitroxides. Such through-space exchange coupling
is likely to be antiferromagnetic and strongly dependent on the
distance between the nitroxides (NO). Although the N‚‚‚N
distance in the 1,3-alternate conformation of 2 is fixed at
(
exp((-6J /k)/T)) + (exp((-(2J + 4J )/k)/T))
1 1 2
G ) [1 + 2 cosh(a)][(exp((-4J /k)/T)) +
2
1
2(exp((-(2J + 2J )/k)/T))]
1
2
a ) 1.345[H/(T - θ)]
The two-parameter numerical fits of the øT versus T and the
M/Msat versus H/T data for diradical 2 in THF, using the
diradical model (eqs 3 and 4, with J1/k set to zero), give J2/k ≈
5
-6 Å, rotation along the C(aryl)-N bonds may provide
-
0.7 K for the through-space exchange coupling between the
conformations with significantly different N‚‚‚O and O‚‚‚O
distances that may lead to modulation of the through-space
exchange coupling between the diagonal nitroxides. The evi-
dence for such conformations is obtained from X-ray crystal-
lography and EPR spectroscopy of 2. In particular, the nitroxide-
nitroxide distances, as measured by the values of |2D| for 2,
and the strength of the through-space antiferromagnetic ex-
change coupling are dependent on the solvent (matrix).
For tetraradical 1 and diradical 2, both temperature-
dependence (øT vs T) and field-dependence (M vs H) of the
experimental magnetic data are well fit by the tetraradical model
and the diradical model, respectively. In these models, based
diagonal nitroxides (Figure 9 and Figure S15, Supporting
Information).
34
The numerical fits of 1 to the tetraradical model (Figure 10)
would require three variable parameters: J1/k, J2/k, and w (or
Msat). Because such three-parameter fits are typically over-
parametrized, the fits with two variable parameters for the øT
versus T data are considered. The two-parameter fits for
tetraradical 1 in THF, which account only for the through-space
exchange coupling (J2/k) as in diradical 2, give J2/k ≈ -2 K
2
and an unsatisfactory coefficient of determination (R ) 0.96,
eq S2, Supporting Information). The quality of two-parameter
2
fits is improved (R ) 0.98) when the through-bond exchange
33
upon the Heisenberg Hamiltonian (2JSn‚Sn+1), tetraradical 1
may be viewed as a cluster of four S ) /2 spins located at the
vertexes of a square (Figure 10, eqs 1 and 2); analogously,
diradical 2 may be considered as a dimer of two diagonally
coupling parameter is optimized (J1/k ≈ -1.5 K), with J2/k set
1
2
to zero; however, R significantly improves, when J2/k is set to
a small negative value rather than zero. For the øT versus T
2
data, the best fits (R ) 0.998) give J1/k ≈ -1.3 K with J2/k
1
positioned S ) /2 spins (Figure 10, eqs 3 and 4). Each of the
set to about -1 K. Analogous fits are obtained for the M/Msat
four identical pairwise exchange couplings (J1/k), along the sides
of the square, corresponds primarily to the through-bond
exchange coupling between the adjacent nitroxides, mediated
by the nitroxide-m-phenylene-CH2-m-phenylene-nitroxide
coupling pathway in 1. Each of the two diagonal exchange
couplings (J2/k) in the square corresponds to the through-space
exchange coupling between the diagonal nitroxides in 1 and 2.
Another variable parameter is used to account for impurities
and inaccuracies in the mass balance, that is, “magnetization at
saturation”, Msat (eqs 1 and 3, expressed in units of Bohr
magnetons per nitroxide), and the mass factor, w (eqs 2 and 4).
versus H/T data, with the smaller values of |J1/k| and |J2/k|
35
(
Figure 8 and Figure S12, Supporting Information). Therefore,
it is concluded that the through-bond exchange couplings
2
(34) The singlet ground state for diradical 2 with J /k ) -0.7 K (the singlet-
triplet gap of about 1-2 K) is consistent with the observation of a thermally
populated triplet state at 140 K in the EPR spectra of 2, as well as with the
lower bound of exchange coupling, |J/gµ
B
| >> |a |, determined by the
N
EPR spectroscopy.
(
35) Another model, which may be viewed as corresponding to a structure of
tetraradical 1 with two distinct conformations of the diagonal pairs of
nitroxides, was considered. One pair of the diagonal nitroxides was treated
as a diradical with exchange coupling J
was treated as two independent spins S )
Information). For two-parameter numerical fits of the øT versus T data at
000 Oe in the warming mode for 5 mM 1 (sample identical to that in
2
(Figure 10), and the other pair
1
2
/ (eq S6a, Supporting
(
For selected fits, the mean-field parameter, θ, could be used
in place of J2/k.) N denotes number of moles of tetraradical
eqs 1 and 3). Equations 1-4 account for paramagnetic
saturation.
5
2
Figure 8), the variable parameters (parameter dependence and R ) are as
follows: J
2
/k ) -5.2 K, w ) 1.09 (0.38, 0.993). For analogous three-
(
parameter fits, in which exchange couplings for both pairs of the diagonal
nitroxides are optimized, similar results are obtained; that is, one relatively
large and one several times smaller value of |J/k| are found (eq S4a with
1 2
J * J , Supporting Information). For such distinct conformations of the
(
32) (a) The presence of parallel exchange coupling pathways in diradical 2
may partially offset the decrease of the through-bond exchange coupling
in 2, as compared to tetraradical 1. (b) Rajca, A.; Rajca, S.; Wongsrira-
tanakul, J. Chem. Commun. 2000, 1021-1022.
diagonal pairs of nitroxides, the structure of 1 would be significantly
distorted from the D2d point group. However, the EPR spectra for 5 mM 1
in THF (sample identical to that in Figure 8, after magnetic measurements)
show a single peak with the peak-to-peak width of 0.8 mT (8 G); thus,
symmetry lowering is not detectable by EPR spectroscopy.
(33) Belorizky, E.; Fries, P. H. J. Chim. Phys. (Paris) 1993, 90, 1077-1100.
J. AM. CHEM. SOC.
9
VOL. 128, NO. 41, 2006 13503

A R T I C L E S
Rajca et al.
Figure 12. SQUID magnetometry for solid nitroxide tetraradical 1 with
numerical fits to the tetraradical model, using J2/k ) 0 (Figure 10, eqs 1
2
and 2). The variable parameters (parameter dependence and R ) are as
follows: at 1.8 K, J1/k ) -0.6 K, Msat ) 0.94 µB (0.75, 1.000); at 3 K,
J1/k ) -0.5 K, Msat ) 0.95 µB (0.94, 1.000); at 5000 Oe in the warming
mode, J1/k ) -0.6 K, w ) 0.96 (0.23, 0.993).
Figure 11. SQUID magnetometry for 20 mM 3 in 2-MeTHF with
numerical fit to the tetraradical model (Figure 10, eq 2). For the øT versus
T plot (top), the variable parameters (parameter dependence) for the
numerical fits to the tetraradical model at 5000 Oe in the cooling mode are
as follows: J1/k ) 1.0 K (0.98), J2/k ) -0.7 K (0.98), w ) 0.85 (0.61); R2
diagonal nitroxides. In such a case, the magnetic data for 3 may
be modeled by the cluster of four S ) /2 spins positioned at
the vertexes of a square, as for tetraradical 1 (Figure 10).
1
The øT versus T data for 3 in 2-MeTHF (Figure 11) provide
an excellent three-parameter fit to the tetraradical model (eq
)
0.996. For the M/Msat versus H/T plot at T ) 2 K (bottom), theoretical
1
Brillouin curves for paramagnet with S ) /2 and S ) 1 are shown.
2
), to give J1/k ) +1.0 K (ferromagnetic) for the through-bond
exchange coupling between the adjacent nitroxides and J2/k )
0.7 K (antiferromagnetic) for the direct through-space coupling
between the adjacent nitroxides and the through-space exchange
couplings between the diagonal nitroxides in the 1,3-alternate
calix[4]arene conformation of tetraradical 1 in THF are both
antiferromagnetic, with J1/k ≈ J2/k ≈ -1 K. Similar through-
bond antiferromagnetic exchange couplings, J1/k ≈ -0.9 K, but
weaker through-space antiferromagnetic exchange couplings,
-
between the diagonal nitroxides. An alternative numerical fit
with J1/k ) +1.3 K is obtained, when the presence of the
antiferromagnetic exchange coupling is modeled with a mean-
field parameter θ ) -0.7 K (Figure S17, Supporting Informa-
tion). Similar numerical fits are obtained for 3 in THF, although
the values of |J2/k| are relatively greater (Figures S18 and S19,
3
6
J2/k ≈ -0.3 K, are obtained for 5 mM 1 in 2-MeTHF.
The results of magnetic studies for ∼20 mM tetraradical 3
in THF or 2-MeTHF (Figure 11 and Figures S18 and S19,
Supporting Information) are qualitatively different, as compared
to those for 1 in THF or 2-MeTHF. Notably, the øT versus T
plot for 3 shows an upward turn at T < 40 K, consistent with
the presence of ferromagnetic exchange coupling, most likely
intramolecular. The ferromagnetic exchange coupling is also
indicated by the relatively fast saturation behavior for the M
versus H data. The M/Msat versus H/T plots at T ) 1.8-5 K
are bracketed by the Brillouin curves corresponding to S ) 1
3
7,38
Supporting Information).
Magnetic Studies of 1 and 2 in the Solid State. The øT
versus T plots for solid tetraradical 1 (Figure 12) and diradical
2
(Figure S20, Supporting Information) are flat, except for a
downward turn at low temperatures.
In the flat sections of the plots (20-300 K), the values of øT
1.45 and øT ) 0.70 emu K mol are measured for solid 1
-
1
)
and 2, respectively. These values are in excellent agreement
1
with the theoretical, spin-only øT ) 1.50 and øT ) 0.75 emu
and S ) /2; that is, the curvatures of the experimental data are
-
1
K mol for tetraradicals and diradicals, with independent S )
significantly greater, as compared to the theoretically predicted
1
1
/ radicals. Similarly, quantitative values of øT ≈ 1.3-1.5 and
paramagnetic behavior for four independent spins S ) /2. In
2
-
1
øT ≈ 0.8 emu K mol are obtained for 1 and 2 in chloroform
addition to this ferromagnetic exchange coupling, a weaker
antiferromagnetic exchange coupling appears to be present; for
example, for 15 mM 3 in THF, an additional downward turn
may be observed in the øT versus T plot at T ≈ 2-3 K. The
strength of antiferromagnetic exchange coupling in 3 is similar
to that in diradical 2 and may be of a similar origin, that is, due
to the direct through-space exchange coupling between the
1
at room temperature (295-300 K), respectively, using the H
3
9
NMR-based Evans method. Within accuracy of the Evans
(
37) The M/Msat versus H/T data for 3 could not be fit to the tetraradical model
with ferromagnetic J /k > 0, due to overparametrization.
(38) The values of |J
1
1
/k| for through-bond ferromagnetic exchange coupling
between the adjacent nitroxides in tetraradical 3 may be somewhat
underestimated by the present model, due to the possible contribution from
antiferromagnetic exchange coupling between the adjacent nitroxides. Such
through-space contribution is possible, as the adjacent nitroxides are
relatively close in space in 3 with cone conformation. We thank the reviewer
for pointing out the possibility of significant antiferromagnetic through-
space interactions between the adjacent nitroxides in the cone conformation.
(
36) For 5 mM tetraradical 1 in 2-MeTHF, the three-parameter fit has still
acceptable values of parameter dependence of significantly less than one;
for example, values of parameter dependence are 0.87, 0.82, and 0.53 for
2
J
1
/k, J
2
/k, and w, respectively (R ) 0.998).
13504 J. AM. CHEM. SOC.
9
VOL. 128, NO. 41, 2006

Exchange Coupling in Polyradical Scaffolds
A R T I C L E S
However, in contrast to the samples of 1 in THF, the numerical
fits for solid 1 could not be improved by the additional weak
antiferromagnetic exchange couplings, such as J2/k < 0 or θ <
0
, reflecting the impact of crystal packing on magnetic data.
For diradical 2, the shortest intermolecular contacts are
associated with the rectangular dimers of nitroxides, which are
formed between the two crystallographically unique molecules;
the N2A‚‚‚O6B and N2B‚‚‚O6A distances of 4.96 and 4.98 Å
are found, respectively (Figure S3, Supporting Information).
Therefore, for one-half of the nitroxide radicals, pairwise
intermolecular antiferromagnetic exchange coupling in solid 2
is expected. This intermolecular exchange coupling may be
described by the “diradical plus two monoradicals” model. In
this model, one-half of the nitroxide radicals, forming dimers,
corresponds to exchange-coupled “diradicals”, and the other half
1
of the nitroxide radicals is treated as independent S ) /2
Figure 13. Crystal packing of nitroxide tetraradical 1. Hydrogen atoms
are omitted for clarity.
“monoradicals”. A comparable numerical fit for solid 2 is
obtained using the diradical model, describing intramolecular
exchange coupling only.
For 1 and 2, the magnetic data in the solid state, in
conjunction with the analysis of crystals packing, are consistent
with the magnetic data in solution. Nevertheless, the magnetic
data for 1 and 2 in frozen solutions, devoid of detectable
intermolecular exchange coupling, are far more informative.
Conformational Dependence of Exchange Coupling in
method, these values are in good agreement with the values of
øT for solid 1 and 2.
The downward turns of the øT versus T plots at low
temperature are consistent with overall antiferromagnetic ex-
change couplings between nitroxide radicals. The presence of
antiferromagnetic exchange coupling is also indicated by the
relatively slow saturation behavior for the M versus H data at
1
-3. The magnetic studies of 1, 2, and 3 in frozen THF (or
1
.8 K. In particular, the overall antiferromagnetic exchange
2
-MeTHF) indicated that the through-bond exchange coupling
coupling in 1 is significantly weaker in the solid state (θ ≈
between the adjacent nitroxides, mediated by the nitroxide-
m-phenylene-CH2-m-phenylene-nitroxide coupling pathway,
is antiferromagnetic in 1 (J1/k ≈ -1 K) and ferromagnetic in 3
-
0.7 K), as compared to that in THF solution (θ ≈ -2.3 K).
For a quantitative fit to the magnetic data for solid 1 and 2,
both intramolecular and intermolecular exchange coupling would
need to be considered. Such models may be suggested by the
analysis of the crystal packing.
(
J1/k ≈ +1 K). In addition, the through-space exchange coupling
between the diagonal nitroxides in 1, 2, and 3 is antiferromag-
netic (J2/k ≈ -1 K).
Crystal Packing of 1 and 2. Crystal packing of both 1 and
For cross-conjugated m-phenylene-based diradicals, exchange
coupling changes from ferromagnetic (J > 0) to antiferromag-
netic (J < 0) when the radical moieties are twisted out of the
plane of the m-phenylene with torsional angles of near 90°.4
For diradicals, in which radical moieties are cross-conjugated
through two m-phenylenes, that is, through 3,3′-biphenylyne,
antiferromagnetic exchange couplings are typically found;3
however, there is no clear-cut evidence for the change of sign
of J, upon severe twisting to the near 90° torsional angle along
2
may be described in terms of layers of calix[4]arene
macrocycles in the approximate bc- or (100)-plane (Figure 13,
Figures S1-S3, Supporting Information).
0-43
For tetraradical 1, dimers of nitroxides, in which the two N2-
O4 moieties form two short sides of parallelogram (N2-O4-
N2-O4 torsion of 180°), with intermolecular O4‚‚‚O4 distance
of 4.60 Å, are found. Another intermolecular distance is the
O1‚‚‚N1 distance of 4.75 Å, which is found in a uniform one-
dimensional zigzag chain of nitroxides along the c-axis (N1-
O1-N1-O1 torsion of 166°). In addition, short intermolecular
O‚‚‚C distances (O1‚‚‚C2 ) 3.97 Å and O4‚‚‚C11 ) 3.58 Å)
between the nitroxide groups and the corresponding ortho-
carbon atoms of the benzene rings are found. For each O‚‚‚C
distance, the N-O bond axis and the 2pπ(C)-orbital axis
2b,44,45
9,46
the C1-C1′ bond. For trimethylene diradicals (and the related
tetraradicals) with constrained CCC-angles, Dougherty and co-
workers developed the model explaining the preference for high-
spin ground states (ferromagnetic exchange coupling).7
,8,47-50
(
40) Dvolaitzky, M.; Chiarelli, R.; Rassat, A. Angew. Chem., Int. Ed. Engl. 1992,
31, 180-181.
(centered on carbon atom) are nearly orthogonal, with the N-O
(41) Fang, S.; Lee, M.-S.; Hrovat, D. A.; Borden, W. A. J. Am. Chem. Soc.
bond axis pointing approximately toward the nodal plane of
the 2pπ(C)-orbital. As these intermolecular interactions are
associated with relatively long distances and may contribute to
either ferromagnetic or antiferromagnetic exchange coupling,
their overall impact on magnetic data of solid 1 is probably
small but not negligible. The øT versus T and the M/Msat versus
H/T data for solid 1 may still be fit to the tetraradical model
1995, 117, 6727-6731.
(
42) Rajca, A.; Rajca, S. J. Chem. Soc., Perkin Trans. 2 1998, 1077-1082.
43) A “Karplus-Conroy-type” relationship for exchange coupling in trimeth-
ylenemethane-based bis(semiquinone) diradicals was proposed; see ref 11.
44) Rajca, A.; Rajca, S. J. Am. Chem. Soc. 1996, 118, 8121-8126.
45) Sakane, A.; Kumada, H.; Karasawa, S.; Koga, N.; Iwamura, H. Inorg. Chem.
2000, 39, 2891-2896.
(
(
(
(46) Rajca, A.; Utamapanya, S.; Smithhisler, D. J. J. Org. Chem. 1993, 5, 5650-
5652.
(47) Goldberg, A. H.; Dougherty, D. A. J. Am. Chem. Soc. 1983, 105, 284-
290.
(Figure 10, eqs 1 and 2), but the antiferromagnetic exchange
(48) (a) Hoffmann, R. Acc. Chem. Res. 1970, 4, 1-6. (b) Hay, P. J.; Thibeault,
coupling J1/k ≈ -0.6 K is much smaller as compared to that in
J. C.; Hoffmann, R. J. Am. Chem. Soc. 1975, 97, 4884-4899.
(49) (a) Buchwalter, S. L.; Closs, G. L. J. Am. Chem. Soc. 1975, 97, 3857-
the analogous fits of the solution data with J2/k set to zero.
3
4
858. (b) Buchwalter, S. L.; Closs, G. L. J. Am. Chem. Soc. 1979, 101,
688-4694.
(
39) (a) Evans, D. F. J. Chem. Soc. 1959, 2003-2005. (b) Live, D. H.; Chan,
(50) Sherrill, C. D.; Seidl, E. T.; Schaefer, H. F., III. J. Phys. Chem. 1992, 96,
3712-3716.
S. I. Anal. Chem. 1970, 42, 791-792.
J. AM. CHEM. SOC.
9
VOL. 128, NO. 41, 2006 13505

A R T I C L E S
Rajca et al.
1
,3-alternate analogue. Therefore, the cone and 1,3-alternate
calix[4]arene scaffolds favor through-bond ferromagnetic and
antiferromagnetic exchange coupling, respectively.
Conclusion
Through-bond and through-space exchange coupling in the
calix[4]arene scaffolds functionalized on the upper rim with
nitroxide radicals was studied. The through-bond exchange
coupling between the adjacent nitroxide radicals is controlled
by the conformation of the nitroxide-m-phenylene-CH2-m-
phenylene-nitroxide coupling pathway. In the 1,3-alternate
calix[4]arene scaffold (tetraradical 1), the exchange coupling
is antiferromagnetic (J1/k ≈ -1 K), and, in the cone calix[4]-
arene scaffold (tetraradical 3), the exchange coupling is ferro-
magnetic (J1/k ≈ +1 K). The through-space exchange coupling
between the diagonal nitroxides at the N‚‚‚N distance of 5-6
Å in the 1,3-alternate and cone calix[4]arene scaffolds (1, 2,
and 3) is antiferromagnetic (J2/k < 0), with the matrix-dependent
coupling strength (|J2/k| < -1 K).
Figure 14. Relative orientations of the 2pπ-orbitals at the ipso-positions
in the 1,3-alternate and cone calix[4]arene polyradical scaffolds, and the
corresponding trimethylene and 2,2′-bis(allyl)methane diradicals.
Highly symmetric (D2d point group) and electron-rich 1,3-
alternate calix[4]arene may serve as a scaffold for polyradicals
with negligible net magnetic dipole-dipole coupling and,
possibly, ionophoric properties. Control of both exchange
coupling and magnetic dipole-dipole coupling, as well as their
modulation by metal ions, is of importance for electronic
relaxation processes, especially for the development of organic
The antiferromagnetic and ferromagnetic through-bond ex-
change couplings in tetraradicals 1 and 3 indicate a profound
effect of torsions within the exchange pathway comprised of
two m-phenylene groups and one methylene group. Although
this magnetic behavior is not well understood, the relative
orientations of π-systems, especially those of 2pπ-orbitals of
the ipso-carbon atoms adjacent to the methylene group, are likely
to play an important role. Based upon the experimental EPR
spectra and the spin polarization mechanism within the π-sys-
tem, the two carbon atoms, which correspond to the nonbonding
MO nodal positions of the benzylic-like radicals, are expected
6
paramagnetic contrast agents.
Experimental Section
Tetrahydroxylamine 5. t-BuLi in pentane (1.70 M, 0.80 mL, 1.31
mmol) was added to a solution of tetrabromocalix[4]arene 4 (0.152 g,
0
.156 mmol) in THF (10 mL) at -78 °C. The resultant yellowish-
orange solution was stirred at -78 °C for 2 h, and then allowed to
attain -25 °C for 15 min. The color of the solution changed to a dark
orange. Subsequently, the reaction mixture was cooled to -78 °C, and
then a solution of 2-methyl-2-nitrosopropane dimer (65.4 mg, 0.375
mmol) in THF (3.5 mL) was added. The reaction mixture was allowed
to attain room temperature overnight. The usual aqueous workup with
1
,51
to possess a substantial negative π-spin density.
This
electronic structure may be compared to simple diradicals such
as 2,2′-bis(allyl)methane or trimethylene,52 although their
detailed analyses concerning correlations between the torsional
5
3,54
angles and the exchange coupling are not available.
We
4
ether, including drying over MgSO , was followed by column chro-
propose the following analysis. In the 1,3-alternate calix[4]arene
scaffold, the π-systems of the adjacent radicals are pointing
away from each other, and, in the cone, they are pointing toward
each other. The relative orientations of the 2pπ-orbitals at ipso-
positions in the 1,3-alternate and the cone calix[4]arene scaffolds
are analogous to the approximate (70,70)- and (90,90)-
conformations of bis(allyl)methane diradical (or trimethylene
diradical), derived by the conrotatory and disrotatory motion
from the (0,0)-conformation, respectively (Figure 14). We
suggest that the closer balance between the through-space and
through-bond interactions between the adjacent radicals is
attained in the cone calix[4]arene scaffold, as compared to its
matography (TLC grade silica, 14-20% ether in hexanes), to yield
tetrahydroxylamine 5 (75.8 mg, 48%) as a white powder. From two
other reactions done on 400-mg scale, 0.205 g (49%) and 0.248 g (60%)
of tetrahydroxylamine 5 was obtained from 0.402 and 0.401 g of
tetrabromocalix[4]arene 4, respectively. Mp 232-234 °C (under Ar,
1
dec). H NMR (400 MHz, CDCl
3
): 9.277 (s, 4H, exch D
2
O), 7.369
(bs, 4H, ArH), 6.677 (bs, 4H, ArH), 3.911 (bs, s, 12H), 3.75 (bs, 4H),
3.540 (s, 12H, OMe), 3.47, 3.36 (bs, 2H, bs, 8H), 1.152 (s, 36H, t-Bu).
1
3
C NMR (100 MHz, CDCl
124.6, 72.4, 72.2, 59.7, 59.0, 26.1. IR (ZnSe, cm ): 3225, 3090, 2931,
875, 1592, 1454, 1386, 1359, 1210, 1125, 1063, 1030, 878. LR/HR
3
): 152.6, 142.1, 132.5, 131.8, 126.2, 124.7,
-1
2
FABMS (3-NBA matrix): m/z (ion type, % RA for m/z 500-1300,
+
deviation for the formula) at 1005.6134 ([M + H] , 100, 3.0 ppm for
12
1
14 16
85
+
12
1
14 16
84 4
N O12).
(
51) Hyperfine splittings of a
ortho hydrogens in 4-methoxyphenyl-tert-butylnitroxide in carbon tetra-
chloride have been reported (ref 22). As the positive sign of a for the
meta hydrogen was determined by H NMR spectroscopy, this implies the
presence of negative π-spin density at the meta carbon.
52) We thank the reviewer for pointing out that bis(allyl)methane diradical
would be a better model, as compared to trimethylene diradical.
H
) 0.09 mT and a
H
) 0.18 mT for the meta and
C
56
H
N
4
O
12), 1004.6084 ([M] , 88, 0.2 ppm for
C
56
H
Dihydroxylamine 6. n-BuLi in hexane (2.14 M, 0.16 mL, 0.34
H
1
mmol) was added to a solution of tetrabromocalix[4]arene 4 (0.151 g,
0.155 mmol) in THF (10 mL) at -78 °C. The resultant bright orange
solution was stirred at -78 °C for 2 h, and then allowed to attain -30
°C for 15 min. Subsequently, a dark orange solution was cooled to
(
(
53) 2,2′-Bis(allyl)methane diradical was apparently generated as an intermediate
upon thermolysis of 1,3-dimethylenecyclopentane: (a) Gajewski, J. J.;
Salazar, J. D. C. J. Am. Chem. Soc. 1981, 103, 4145-4154. (b) Gajewski,
J. J.; Salazar, J. D. C. J. Am. Chem. Soc. 1981, 103, 4145-4154.
54) Calculations on trimethylene diradical: (a) Yamaguchi, Y.; Osamura, Y.;
Schaefer, H. F., III. J. Am. Chem. Soc. 1983, 105, 7506-7511. (b) Skancke,
A.; Hrovat, D. A.; Borden, W. T. J. Am. Chem. Soc. 1998, 120, 7079-
-
78 °C, and then a solution of 2-methyl-2-nitrosopropane dimer (32.4
mg, 0.186 mmol) in THF (3 mL) was added. The reaction mixture
was allowed to attain room temperature overnight. The green reaction
mixture was subjected to a usual aqueous workup with ether, including
(
7
084.
4
drying over MgSO , and then evaporated to dryness. Column chroma-
13506 J. AM. CHEM. SOC.
9
VOL. 128, NO. 41, 2006

Exchange Coupling in Polyradical Scaffolds
A R T I C L E S
tography (TLC grade silica, 14-17% ether in hexanes) gave dihy-
droxylamine 6 (57.6 mg, 37%) as a white powder. Mp 218-219 °C
Nitroxide Diradical 2. Freshly prepared silver oxide (0.530 g, 2.286
mmol) was added to a solution of dihydroxylamine 6 (56.5 mg, 0.057
mmol) in CH Cl (1.5 mL). After being stirred at room temperature in
2
(under N , dec). From another reaction on 400-mg scale, 0.183 g (44%)
2
2
of dihydroxylamine 6 was obtained from 0.406 g of tetrabromocalix-
darkness for 4 h, the reaction mixture was filtered, and then the red
filtrate was evaporated to dryness to obtain a reddish-orange oil. Column
purification with deactivated flash silica gel at 0 °C under nitrogen,
followed by recrystallization from an ether/heptane mixture, gave
diradical 2 (23.9 mg, 42%) as dark-red needles. From another reaction
on 150-mg scale (using 20 equiv of silver oxide), 70.5 mg (47%) of
diradical 2 was obtained from 0.150 g of dihydroxylamine 6. Yields
are corrected for the residual solvents (ether and heptane) remaining
after recrystallization. Magnetic and spectroscopic studies were carried
using another sample of 2 (orange-red solid), which was prepared from
1
[
7
3
3
4]arene 4. H NMR (400 MHz, CDCl
3
): 9.124 (s, 2H, exch D
.36 (bs, 2H), 7.260 (s, under the solvent peak, 4H), 6.79 (bs, 2H),
.90, 3.87 (bm, m, 12H), 3.81 (m, 4H), 3.644 (s, 6H), 3.530 (s, 6H),
2
O),
1
3
.33-3.48 (bm, 8H), 1.177 (s, 18H). C NMR (125 MHz, CDCl
3
):
1
54.4, 152.6, 142.3, 135.5, 134.6, 133.2, 131.9, 114.9, 72.5, 72.4, 72.3,
-
1
7
2
7
2.0, 59.9, 59.4, 59.3, 58.9, 34.1, 26.1. IR (ZnSe, cm ): 3235, 3070,
933, 2877, 1596, 1573, 1451, 1361, 1199, 1125, 1059, 1028, 850,
17. LR/HR FABMS (3-NBA matrix): m/z (ion type, % RA for m/z
+
700-1500, deviation for the formula) at 991.2975 ([M + 4] , 38, -7.0
1
2
1
14
16
81
+
ppm for
C
48
H
N
64 2 2
N O10 Br ), 988.2939 ([M + 2] , 53, -3.3 ppm
1
2
481H64
14
16
81
79
+
dihydroxylamine 6 and silver oxide in chloroform. Mp 151-153 °C
for
C
2
O
10 Br Br), 986.2918 ([M] , 25, 1.0 ppm for
1
12
481H6414
16O1079Br
+
(under Ar, dec). H NMR (500 MHz, CDCl
3
): 7.469 (s, 4H), 4.304,
C
N
2
2
), 970.3 ([M - 18] , 100).
4
.084, ∼3.9, 3.688 (s, bs, bs, s, 28-32H), -5.132 (v. bs(sh) 22-26H).
Nitroxide Tetraradical 1. Freshly prepared silver oxide (0.285 g,
.23 mmol) was added to a solution of tetrahydroxylamine 5 (0.124 g,
.0199 mmol) in CHCl (6 mL). After being stirred at room temperature
3
-1
IR (ZnSe, cm ): 3077, 2929, 2875, 1574, 1451, 1364, 1195, 1124,
054, 925, 858. Evans method (2 measurements, CDCl /CHCl , 298
1
0
1
3
3
-1
and 300 K), øT ≈ 0.80, 0.78 emu K mol (2.2, 2.1 unpaired electrons).
in darkness for 9 h, the reaction mixture was filtered, and then the red
filtrate was evaporated to dryness to obtain the nitroxide tetraradical 1
Acknowledgment. This research was supported by the
National Science Foundation (CHE-0107241 and CHE-0414936),
including the purchase of the Electron Paramagnetic Resonance
(
0.119 g, 96%) as a brick-red solid. A similar procedure, except for
the increased amount of silver oxide (40 vs 15 equiv), gave 0.193 g
96%) of 1 from 0.200 g of tetrahydroxylamine 5; this was the primary
(
sample for magnetic and spectroscopic studies. Two other reactions
were carried out with tetrahydroxylamine 5 (75.8 mg and 0.205 g) and
silver oxide (40 equiv) in dichloromethane; the crudes obtained after
filtration and drying were further recrystallized from methanol, to yield
3
(
EPR) spectrometer (DMR-0216788). Part of this research was
performed in facilities renovated with support from the NIH
RR16544-01). We thank Drs. Kouichi Shiraishi and Hongxian
(
1
Han, and Kausik Das, for help with the EPR spectroscopy and
preparation of samples for SQUID magnetometry.
9.6 mg (52%) and 0.109 g (53%) of 1, respectively. H NMR spectra
of the recrystallized samples showed a sharp singlet at ∼3.6 ppm (1.5H,
assigned to residual methanol) and a broad singlet at 7.1 ppm (0.14H).
1
Supporting Information Available: General procedures and
materials, additional experimental details (synthesis of 4, SQUID
magnetometry data, EPR spectra), and X-ray crystallographic
files in CIF format. This material is available free of charge
via the Internet at http://pubs.acs.org.
All yields are reported after correcting for the extraneous H NMR
resonances (solvent of crystallization, stopcock grease, etc.). Mp 169-
1
3
cm ): 3078, 2978, 2930, 2878, 1576, 1458, 1347, 1203, 1123, 1050,
8
)
1
71 °C (under Ar, dec). H NMR (500 MHz, CDCl
3
): 4.341 (bs, 12H),
.842 (bs, 16H), -0.753 (bs, 8H), -5.881 (v. bs, 36H). IR (ZnSe,
-
1
83. Evans method (4 measurements, CDCl
1.30-1.52 emu K mol (3.6, 4.1, 4.0, 3.5 unpaired electrons).
3
/CHCl
3
, 297-300 K), øT
-
1
JA063567+
J. AM. CHEM. SOC.
9
VOL. 128, NO. 41, 2006 13507