Effective concentration as a tool for quantitatively addressing preorganization in multicomponent assemblies: Application to the selective complexation of lanthanide cations

Article abstract of DOI:10.1021/ja0772290

The beneficial entropic effect, which may be expected from the connection of three tridentate binding units to a strain-free covalent tripod for complexing nine-coordinate cations (M^z+ = Ca²⁺, La ³⁺, Eu³⁺, Lu

Full text of DOI:10.1021/ja0772290

Published on Web 12/22/2007
Effective Concentration as a Tool for Quantitatively
Addressing Preorganization in Multicomponent Assemblies:
Application to the Selective Complexation of Lanthanide
Cations
Gabriel Canard,† Sylvain Koeller,† Ge´rald Bernardinelli,§ and Claude Piguet*,†
Department of Inorganic, Analytical and Applied Chemistry, UniVersity of GeneVa, 30 quai E.
Ansermet, CH-1211 GeneVa 4, Switzerland, and Laboratory of X-ray Crystallography,
UniVersity of GeneVa, 24 quai E. Ansermet, CH-1211 GeneVa 4, Switzerland
Received September 18, 2007; E-mail: Claude.Piguet@chiam.unige.ch
Abstract: The beneficial entropic effect, which may be expected from the connection of three tridentate
binding units to a strain-free covalent tripod for complexing nine-coordinate cations (Mz+ ) Ca2+, La3+
,
Eu3+, Lu3+), is quantitatively analyzed by using a simple thermodynamic additive model. The switch from
pure intermolecular binding processes, characterizing the formation of the triple-helical complexes [M(L2)3]z+
,
to a combination of inter- and intramolecular complexation events in [M(L8)]z+ shows that the ideal structural
fit observed in [M(L8)]z+ indeed masks large energetic constraints. This limitation is evidenced by the faint
effective concentrations, ceff, which control the intramolecular ring-closing reactions operating in [M(L8)]z+
.
This predominence of the thermodynamic approach over the usual structural analysis agrees with the
hierarchical relationships linking energetics and structures. Its simple estimation by using a single microscopic
parameter, ceff, opens novel perspectives for the molecular tuning of specific receptors for the recognition
of large cations, a crucial point for the programming of heterometallic f-f complexes under thermodynamic
control.
Introduction
ferent trivalent lanthanides, Ln(III), into organized metallosu-
pramolecular edifices remains an unsolved chemical challenge.4
Despite attractive applications in (i) the double-sensing of
protein domains and biological tissues,1 (ii) the development
of efficient homogeneous fluoroimmunoassays,2 (iii) the efficient
cleaveage of phosphodiester bonds,3 and (iv) the design of novel
materials for directional light-conversion,4 photonic amplifica-
tion,5 nonlinear optical up-conversion,6 and molecular four-level
lasers,7 the programmed thermodynamic incorporation of dif-
Currently, the only viable route for preparing pure heterometallic
4f-4f complexes relies on some stepwise metalation/demeta-
lation processes operating in kinetically inert complexes pos-
sessing negatively charged ligands, such as (i) porphyrins and
phthalocyanins,8 (ii) metallocryptands,9 (iii) podands, or (iv)
macrocycles grafted with peripheral carboxylate donors.10
However, recent contributions reporting on the quantitative
preparation of heterometallic 4f-4f complexes with unsym-
metrical compartmental Schiff bases11 or with terpyridine-
carboxylates12 suggest that thermodynamic recognition may
† Department of Inorganic Chemistry.
§ Laboratory of X-ray Crystallography.
(1) (a) Nitz, M.; Sherawat, M.; Franz, K. J.; Peisach, E.; Allen, K. N.; Imperiali,
B. Angew. Chem., Int. Ed. 2004, 43, 3682-3685. (b) Harte, A. J.; Jensen,
P.; Plush, S. E.; Kruger, P. E.; Gunnlaugsson, T. Inorg. Chem. 2006, 45,
9465-9474. (c) Martin, L. J.; Ha¨hnke, M. J.; Nitz, M.; Wo¨hnert, J.;
Silvaggi, N. R.; Allen, K. N.; Schwalbe, H.; Imperiali, B. J. Am. Chem.
Soc. 2007, 129, 7106-7113. (d) Silvaggi, N. R.; Martin, L. J.; Schwalbe,
H.; Imperiali, B.; Allen, K. N. J. Am. Chem. Soc. 2007, 129, 7114-7120.
(2) (a) Bu¨nzli, J.-C. G. In Metal Ions in Biological Systems; Sigel, A., Sigel,
H., Eds.; Marcel Dekker Inc.: Basel, New York, 2004; Vol 42, pp 39-75.
(b) Charbonnie`re, L. J.; Hildebrandt, N.; Ziessel, R. F.; Lo¨hmannsro¨ben,
H.-G. J. Am. Chem. Soc. 2006, 128, 12800-12809. (c) Lou, X.; Zhang,
G.; Herrera, I.; Kinach, R.; Ornatsky, O.; Baranov, V.; Nitz, M.; Winnik,
M. A. Angew. Chem., Int. Ed. 2007, 46, 6111-6114.
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Inorg. Chem. 2005, 2612-2618.
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35, 1219-1221. (b) Liu, C.; Wang, M.; Zhang, T.; Sun, H. Coord. Chem.
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9
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J. AM. CHEM. SOC. 2008, 130, 1025-1040
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A R T I C L E S
Canard et al.
Scheme 1. Structures of the Ligands L1-L7
result from a judicious combination of different binding sites
within the same semiflexible receptor. Following this reasoning,
Bu¨nzli and co-workers designed the neutral heterotopic bis-
tridentate ligand L3 (Scheme 1),13 which combined a N2O
binding unit of L1-type, favoring the complexation of small
lanthanides in [Ln(L1)3]3+ because of electrostatic driving
forces,14 and a more rigid N3 binding unit of L2-type, which is
known to stabilize [Ln(L2)3]3+ complexes with large lanthanides
because of the operation of unfavorable interligand interactions
with small cations.15 Upon reaction of L3 (3 equiv) with a
stoichiometric amount of two different lanthanides LnA (1 equiv)
and LnB (1 equiv), it was demonstrated that the thermodynamic
formation of the bimetallic triple-stranded helicate [LnALnB-
(L3)3]6+ systematically exceeded 50% of the ligand speciation,
the value predicted by the statistical binomial distribution
between two equivalent coordination sites.13 However the
mixture of C3-symmetrical head-to-head-to-head (HHH) and C1-
symmetrical head-to-head-to-tail (HHT) isomers resulting from
the relative orientation of the three Cs-symmetrical ligands in
[LnALnB(L3)3]6+ prevented further thermodynamic investiga-
tions of these remarkable observations.16 The recent thorough
analysis of the metal distribution occurring in the closely related
D3-symmetrical complexes [(LnA)x(LnB)3-x(L4)3]9+ (x ) 0-3)17
and [(LnA)x(LnB)4-x(L5)3]12+ (x ) 0-4),18 which also possess
adjacent N2O (L1-type) and N3 (L2-type) tridentate binding
units, but no possibility for isomerization, indicates that the
Ln
Ln
microscopic affinities f
and f of the different tridentate
N2O
N3
chelates for a given Ln(III) are indeed very similar. Conse-
quently, selective metallic recognition in these systems mainly
relies on the modulation of the free energy of intramolecular
LnA,LnB
1-2
intermetallic interaction, ∆E
, which is induced by subtle
changes in solvation processes.18 The rational programming of
LnA,LnB
∆E
is currently inaccessible for discrete molecular
1-2
objects, and this strategy has been exploited only for large
(polymeric) objects, in which numerous intermetallic interactions
operate.18
We therefore turn our attention to the exploration of the
alternative concept of preorganization, measured by the effective
concentration (ceff),19 for selectively coordinating Ln(III) in
discrete molecular objects. In simple words, the replacement
of some intermolecular connection processes with their intramo-
(12) Chen, X.-Y.; Bretonnie`re, Y.; Pe´caut, J.; Imbert, D.; Bu¨nzli, J.-C. G.;
Mazzanti, M. Inorg. Chem. 2007, 46, 625-637.
(13) (a) Andre´, N.; Scopelliti, R.; Hopfgartner, G.; Piguet, C.; Bu¨nzli, J.-C. G.
Chem. Commun. 2002, 214-215. (b) Andre´, N.; Jensen, T. B.; Scopelliti,
R.; Imbert, D.; Elhabiri, M.; Hopfgartner, G.; Piguet, C.; Bu¨nzli, J.-C. G.
Inorg. Chem. 2004, 43, 515-529.
(14) Le Borgne, T.; Altmann, P.; Andre´, N.; Bu¨nzli, J.-C. G.; Bernardinelli, G.;
Morgantini, P.-Y.; Weber, J.; Piguet, C. Dalton Trans. 2004, 723-733.
(15) (a) Piguet, C.; Bu¨nzli, J.-C. G.; Bernardinelli, G.; Williams, A. F. Inorg.
Chem. 1993, 32, 4139-4149. (b) Petoud, S.; Bu¨nzli, J.-C. G.; Renaud, F.;
Piguet, C.; Schenk, K. J.; Hopfgartner, G. Inorg. Chem. 1997, 36, 5750-
5760.
(16) Jensen, T. B.; Scopelliti, R.; Bu¨nzli, J.-C. G. Inorg. Chem. 2006, 45, 7806-
7814.
(17) Floquet, S.; Borkovec, M.; Bernardinelli, G.; Pinto, A.; Leuthold, L.-A.;
Hopfgartner, G.; Imbert, D.; Bu¨nzli, J.-C. G.; Piguet, C. Chem.sEur. J.
2004, 10, 1091-1105.
(18) Dalla-Favera, N.; Hamacek, J.; Borkovec, M.; Jeannerat, D.; Ercolani, G.;
Piguet, C. Inorg. Chem. 2007, 46, 9312-9322.
9
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Preorganization in Multicomponent Assemblies
A R T I C L E S
Figure 1. Successive complexation processes24 leading to (a) HHH-[Ln(L1)3]3+ and (b) [Ln(L6)]3+ with thermodynamic formation constants modeled with
eq 2.22 The statistical factors ωmch,inral ‚ ωLn,L are calculated in Figure S1 (Supporting Information),23,24 and the definition of the various microscopic parameters
m,n
are given in the text.22
lecular counterparts should improve the influence of molecular
design on the complexation process, a strategy previously
established for improving both stability and structural control
in standard coordination complexes with multidentate ligands
(i.e., the chelate effect). As a first step toward this goal, we
synthesized the podand ligand L6, in which three tridentate N2O
binding units of L1-type were connected to a strain-free covalent
helical tripod.20 The complexation reactions leading to [Ln-
(L1)3]3+ or to [Ln(L6)]3+ mainly differ in the successive
operation of three intermolecular Metal-Ligand connection
processes for [Ln(L1)3]3+ (Figure 1a), while the initial inter-
molecular binding event in [Ln(L6)]3+ is followed by two
intramolecular ring-closing reactions (Figure 1b).21 The ap-
plication of the simple additive thermodynamic site binding
model (eqs 1 and 2)22 to the complexation processes depicted
in Figure 1 predicts that the cumulative formation constants for
[Ln(L1)3]3+ (eq 3) and for [Ln(L6)]3+ (eq 4) are very similar
chiral
m,n
except for some slightly different statistical factors ω
‚
M,L
ω
) ∏i(σreactant ‚ σreactant )ni/∏j(σproduct ‚ σpsyromdmucettry,i)nj (Figure
m,n
chiral,j symmetry,i chiral,j
9
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A R T I C L E S
Canard et al.
S1, Supporting Information, σsymmetry is the geometrical sym-
metry number of each species, σchiral is the symmetry number
accounting for the entropy of mixing of enantiomers of each
species, ni is the stoichiometric coefficient of compound i in
prevent HHH T HHT isomerization processes, we considered
the podand L7 (Scheme 1), in which three C2V-symmetrical
tridentate binding units of L2-type are connected to the strain-
free tripod. However, we were unable to prepare the three ether
bridges in L7, despite considerable synthetic efforts. In this
contribution, the limiting ether connectors of L7 are replaced
with thioether bridges in L8, which can be easily prepared by
the reaction of nucleophilic deprotonated thiols with alkyl
chlorides (Scheme 2). After checking for the conservation of
the structural strain-free conditions imposed by the novel tripod
in [Ln(L8)]3+, a thorough thermodynamic investigation eventu-
ally provides reliable and quantitative estimates for ceff, which
can be used as a tool for programming preorganization for the
selective complexation of large cations.
the considered equilibrium)23,24 and for the introduction of
inter-∆Gintra)/RT
the effective concentration ceff ) e(∆G
in eq 4,
which corresponds to the free energy correction (-RT ln(ceff))
required when an intermolecular binding event (∆Ginter ) -RT
ln(f Mi ,L)) is replaced with its intramolecular counterpart (∆Gin
tra ) -RT ln(fMi ,L ‚ ceff)).19
-
M,L
m,n
m M + n L h [MmLn]
â
(1)
mn
M,L
M,L
m,n
m,n
â
) e-(∆G
/RT) ) ωchiral ‚ ωM,L
‚
‚
f M,L
‚
∏
m,n
m,n
i
i)1
Results and Discussion
mn-m-n+1
cei ff
uM,M
‚
uL,L (2)
Synthesis and Structural Characterization of the Podand
L8 and of Its Complexes [Ca(L8)](CF3SO3)2 and [Ln(L8)]-
(CF3SO3)3 (Ln ) La, Nd, Eu, Gd, Tb, Lu, Y). The ligand L8
is prepared in 25 synthetic steps from the commercially available
synthons 1, 3, 7, and 15 (Scheme 2). The tripod 18 is obtained
according to a published multistep procedure,20b and it is
eventually reacted with thionylchloride in pyridine to yield the
electrophilic trichloride intermediate 19.25 The associated low
yield (27%) results from competitive intra- and intermolecular
condensation reactions involving partially chlorinated hydroxy
tripods. The use of smooth basic conditions for hydrolyzing the
ester group of 5 affords excellent yields of an unprecedented
2-pyridinecarboxylic acid 6 bearing a reactive o-nitroarene
amide group. Its remarkable solubility in standard organic
solvent allows its efficient acylation, and its coupling with 8
eventually gives 9. Reductive cyclization followed by depro-
tection and activation steps yield 13, which can be hydrolyzed
under anaerobic acidic conditions to give 14 (in the presence
of oxygen in neutral or basic media, the bridged disulfur dimer
is rapidly formed). The ultimate coupling of deprotonated 14
with 19 under anaerobic conditions affords L8 in fair yield.
Its 1H NMR spectrum in CDCl3 displays nine signals for the
aromatic protons, five signals for enantiotopic methylene
protons, and four signals for methyl protons in agreement with
L8 adopting dynamically average C3V symmetry in solution
(Figure 2a and Table S1, Supporting Information). The lack of
nuclear Overhauser enhancement effect (NOE) detected within
the H10-H16 and H8-H14 pairs is compatible with the
standard trans-trans conformation adopted by each 2,6-bis-
(benzimidazol-2-yl)pyridine strand (numbering in Figure 2).
Reaction of L8 (1 equiv) with stoichiometric amounts of
diamagnetic Ca(CF3SO3)2‚0.5H2O (1 equiv, Figure 2b) or Ln-
(CF3SO3)3‚xH2O (1 equiv, Ln ) La, Lu, x ) 1-3, Figure 2c-
d, Table S1) in acetonitrile yields C3-symmetrical [Ca(L8)]2+
and [Ln(L8)]3+ complexes, whereby each pair of methylene
protons is diastereotopic because of the loss of the symmetry
planes consequent to the helical wrapping of the three tridentate
strands in the final podates. The observation of strong NOE
effects within the H8-H14 and H10-H16 pairs is diagnostic
for the trans-trans to cis-cis conformational change resulting
from the meridional tricoordination of each 2,6-bis(benzimida-
zol-2-yl)pyridine unit to the central metal. The considerable low-
∏
∏
∏
k<l
i,j
k,l
i)1
i<j
â
) 4 ‚ (f
)3 ‚ (uL,L 3
)
(3)
(4)
Ln,L1
1,3
Ln
N2O
)3 ‚ (uL,L)3 ‚ (ceff)2
Ln,L6
1,1
Ln
â
) 12 ‚ (f
N2O
Ln
N2O
In these equations, f
represents the intermolecular mi-
croscopic affinity characterizing the connection of the lanthanide
L,L/RT)
Ln to the N2O binding site and uL,L ) e-(∆E
is the
Boltzmann’s factor accounting for the interligand ∆EL,L free
energy of interaction operating in the final complexes. Assuming
that the enthalpic contributions of inter- and intramolecular
complexation processes are identical when using a strain-free
connector (∆Hinter ≈ ∆Hintra), the so-called effective concentra-
tion corresponds to a pure entropic term ceff ) e(∆S
intra-∆Sinter)/R
measuring the benefit (ceff > 1) or drawback (ceff < 1) of the
preorganization of the binding sites.
The term (f LNn2O)3 ‚ (ceff)2 in eq 4 thus indicates that, among
the three successive fixations of N2O binding units to Ln(III),
Ln
N2O
one is intermolecular (f
) and two are intramolecular
Ln
N2O
((f
‚ ceff)2). However, due to extra enthalpic terms origi-
nating from intramolecular interligand stacking interactions
favoring the formation of HHT-[Ln(L1)3]3+ 14
, we were unable
to obtain reliable values of ceff for [Ln(L6)]3+. In order to
(19) (a) Kuhn, W. Kolloid Z. 1934, 68, 2-15. (b) Jacobson, H.; Stockmayer,
W. H. J. Chem. Phys. 1950, 18, 1600-1606. (c) Flory, P. J.; Suter, U. W.;
Mutter, M. J. Am. Chem. Soc. 1976, 98, 5733-5739. (d) Jencks, W. P.
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Galli, C.; Mandolini, L. Eur. J. Org. Chem. 2000, 3117-3125. (j) Gargano,
J. M.; Ngo, T.; Kim, J. Y.; Acheson, D. W. K.; Lees, W. J. J. Am. Chem.
Soc. 2001, 123, 12909-12910. (k) Kitov, P. I.; Bundle, D. R. J. Am. Chem.
Soc. 2003, 125, 16271-16284. (l) Mulder, A.; Huskens, J.; Reinhoudt, D.
N. Org. Biomol. Chem. 2004, 2, 3409-3424.
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2003, 9, 1062-1074. (b) Koeller, S.; Bernardinelli, G.; Piguet, C. Dalton
Trans. 2003, 2395-2404.
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5226. (b) Hamacek, J.; Borkovec, M.; Piguet, C. Chem.sEur. J. 2005, 11,
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111, 12195-12203.
(24) For the sake of simplicity in calculating symmetry numbers, we consider
that Ln(III) exists in acetonitrile strictly as the tricapped trigonal prismatic
complex [Ln(CH3CN)9]3+, although it has been experimentally demonstrated
that the main species in equilibrium in lanthanide triflate solutions in
anhydrous acetonitrile are [Ln(CF3SO3)2(CH3CN)x]+ and [Ln(CF3SO3)3(CH3-
CN)y]; see: Di Bernardo, P.; Choppin, G. R.; Portanova, R.; Zanonato, P.
L. Inorg. Chim. Acta 1993, 207, 85-91.
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9
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Preorganization in Multicomponent Assemblies
A R T I C L E S
Scheme 2. Synthesis of the Ligand L8
Eu,para
H5
Eu,para
H13
Table S1) and in [Eu(L8)]3+ (δ
) 5.24 ppm, δ
)
field shift affecting H5 (1.19-1.46 ppm, Table S1) and H13
(0.83-1.22 ppm, Table S1) upon complexation to diamagnetic
metals in [Ca(L8)]2+ and [Ln(L8)]3+ (Ln ) La, Lu, Y) is
characteristic of the triple-helical wrapping of the strands, which
puts these protons in the shielding region of the benzimidazole
ring of an adjacent strand.15 The concomitant large paramagnetic
4.07 ppm, Table S1) further confirm their location close to the
paramagnetic lanthanide in the triple-helical complex because
-3
Ln-Hi
15
pseudo-contact shifts depend on r
. Diffusion of diethyl-
ether into a concentrated acetonitrile solution of [Ca(L8)]2+ and
[Ln(L8)]3+ yields 69-94% of pale yellow microcrystalline
powders whose elemental analyses correspond to [Ca(L8)](CF3-
SO3)2‚3H2O and [Ln(L8)](CF3SO3)3‚xH2O (Ln ) La, x ) 4;
Ln,para
Ln,exp
La,dia
shifts δ
) δ
- δ
calculated for H5 and H13 in
Hi
Hi
Hi
Nd,para
H5
Nd,para
[Nd(L8)]3+ (δ
) -4.42 ppm, δ
) -6.35 ppm,
H13
9
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A R T I C L E S
Canard et al.
Figure 2. 1H NMR spectra of (a) L8 in CDCl3 and (b) [Ca(L8)]2+, (c) [La(L8)]3+, and (d) [Lu(L8)]3+ in CD3CN (298 K).
Ln ) Nd, x ) 4; Ln ) Eu, x ) 4; Ln ) Gd, x ) 4; Ln ) Tb,
x ) 3; Ln ) Lu, x ) 4; Ln ) Y, x ) 2, Table S2, Supporting
Information).
X-ray quality plates of [Eu(L8)](ClO4)3‚2CH3CN‚C2H5OH‚
0.5H2O (20) were obtained by slow diffusion of tert-butylm-
ethylether into a concentrated solution of [Eu(L8)](CF3SO3)3‚
9
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Preorganization in Multicomponent Assemblies
A R T I C L E S
Figure 4. (a) Chemical structure of ligand L9. (b) Optimized superimposi-
tion of the three bound tridentate strands in [Eu(L9)3]3+ (red) and in [Eu-
(L8)]3+ (blue). The upper covalent tripod in [Eu(L8)]3+ (blue) has been
omitted for clarity.
Figure 3. Perspective views of [Eu(L8)]3+ perpendicular to the pseudo-
threefold axis in the crystal structure of 20. Ellipsoids are represented at
the 50% probability level (C ) gray, N ) blue, S ) yellow, H ) white,
Eu ) violet).
As inferred from 1H NMR data in solution, the isolated [Eu-
(L8)]3+ complex possesses a pseudo-threefold symmetry axis
passing through the metal and the apical C1 carbon atom. The
europium atom is nine-coordinate in a pseudo-tricapped trigonal
prismatic arrangement produced by the three wrapped tridentate
2,6-bis(benzimidazol-2-yl)pyridine strands. Eu(III) is located
close to the center of the trigonal prism and almost in the plane
defined by the three capping pyridine nitrogen atoms (deviation
from this plane 0.042(1) Å toward the terminal nitrogen tripod
N4a,N4b,N4c). The Eu-N distances (2.534-2.631 Å, Table
1) do not deviate from the average value 2.58(3) Å. Using
Shannon’s definition and r(N) ) 1.46 Å,26 we calculate RECuN)9
) 1.121(5) Å for the ionic radius of nine-coordinate Eu(III) in
Table 1. Selected Bond Distances (Å) and Angles (deg) for
[Eu(L8)](ClO4)3‚2CH3CN‚C2H5OH‚0.5H2O (20)
Bond Distances
Eu-N1a
Eu-N1b
Eu-N1c
2.571(6)
2.614(5)
2.534(6)
Eu-N3a
Eu-N3b
Eu-N3c
2.553(5)
2.583(6)
2.559(6)
Eu-N4a
Eu-N4b
Eu-N4c
2.597(6)
2.631(6)
2.591(6)
Bond Angles
N1a-Eu-N3a
N1a-Eu-N4a
N1a-Eu-N1b
N1a-Eu-N3b
N1a-Eu-N4b
N1a-Eu-N1c
N1a-Eu-N4c
N1a-Eu-N3c
N3a-Eu-N4a
N3a-Eu-N1b
N3a-Eu-N3b
N3a-Eu-N4b
N3a-Eu-N1c
N3a-Eu-N4c
N3a-Eu-N3c
N4a-Eu-N1b
N4a-Eu-N3b
N4a-Eu-N4b
63.4 (2)
126.9 (2)
80.0 (2)
75.8 (2)
75.8 (2)
87.0 (2)
144.0 (2)
138.6 (2)
63.7 (2)
134.4 (2)
127.1 (2)
73.5 (2)
74.2 (2)
134.2 (2)
126.9 (2)
139.4 (2)
145.5 (2)
93.8 (2)
N4a-Eu-N1c
N4a-Eu-N4c
N4a-Eu-N3c
N1b-Eu-N3b
N1b-Eu-N4b
N1b-Eu-N1c
N1b-Eu-N4c
N1b-Eu-N3c
N3b-Eu-N4b
N3b-Eu-N1c
N3b-Eu-N4c
N3b-Eu-N3c
N4b-Eu-N1c
N4b-Eu-N4c
N4b-Eu-N3c
N1c-Eu-N4c
N1c-Eu-N3c
N4c-Eu-N3c
74.6 (2)
81.3 (2)
74.8 (2)
61.4 (2)
124.6 (2)
77.8 (2)
91.4 (2)
66.4 (2)
64.6 (2)
137.6 (2)
69.4 (2)
106.0 (2)
147.5 (2)
80.9 (2)
143.4 (2)
125.5 (2)
63.5 (2)
63.2 (2)
[Eu(L8)]3+, a value identical to (i) the standard ionic radius
CN)9
R
) 1.120 Å expected for nine-coordinate Eu(III)26 and
Eu
CN)9
(ii) R
) 1.13 Å reported for [Eu(L9)3]3+, in which three
Eu
independent L2-type tridentate binding units are bound to Eu-
(III) (Figure 4).27 Except for some minor deviations of the six-
membered aromatic rings of the benzimidazole groups connected
to the sulfur tripod in [Eu(L8)]3+ (Figure 4b), the arrangements
of the three wrapped tridentate bound ligands are almost
superimposable in [Eu(L8)]3+ and [Eu(L9)3]3+ (Figure 4b),
which provides very similar Eu(III) coordination spheres in the
two complexes (Table S3, Supporting Information).
The aromatic rings are planar within experimental error (Table
S4, Supporting Information), and the helical torsion responsible
for the wrapping of the strands is limited to rotations about the
C-C bonds connecting the pyridine and benzimidazole rings,
which affords a close packing of the aromatic rings of the
different strands along the pseudo-threefold axis in both
complexes. We thus detect two significant intramolecular
interligand π-stacking interactions in [Eu(L8)]3+. The first one
involves two benzimidazole rings belonging to strands a and b
4H2O in acetonitrile/ethanol (99.9:0.1) containing (nBu)4NClO4
(3 equiv). The crystal structure of 20 contains nine-coordinate
[Eu(L8)]3+ cations, together with three noncoordinated per-
chlorate anions and interstitial solvent molecules. The analysis
of the crystal packing shows that the [Eu(L8)]3+ cations are
pairwise associated about a center of inversion, thus leading to
a π-stacking interaction between two benzimidazole rings
belonging to the different cations of the pair (interplane angle:
0°, interplanar distance 3.54(3) Å, Figure S2, Supporting
Information). Figure 3 shows a perspective view of the
molecular structure of [Eu(L8)]3+ in 20 (numbering scheme in
Figure S3, Supporting Information), and selected bond distances
and angles are collected in Table 1.
(26) Shannon, R. D. Acta Crystallogr. 1976, A32, 751-767.
(27) Piguet, C.; Bu¨nzli, J.-C. G.; Bernardinelli, G.; Bochet, C. G.; Froidevaux,
P. J. Chem. Soc., Dalton Trans. 1995, 83-97.
9
J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008 1031

A R T I C L E S
Canard et al.
Table 2. Helical Pitches Pij, Linear Distances dij, and Average
Twist Angle ωij along the Pseudo-C3 Axis in the Crystal Structures
20b
of [Eu(L6)](ClO4)3 and [Eu(L8)](ClO4)3
[Eu(L6)](ClO4)3
[Eu(L8)](ClO4)3
helical
portiona
dij/Å
ωij/deg
Pij/Å
dij/Å
ωij/deg
Pij/Å
F1-F2b
F2-F3
F3-F4
F4-F5
F5-F6
F6-F7
1.48
1.71
3.69
1.38
0.41
0.08
57.6
52.1
60.7
0.07
11.8
27.4
9.3
11.8
21.9
7452
12.5
1.1
1.68
1.65
3.16
1.56
0.54
1.68
53.9
53.3
64.1
9.5
13.2
53.9
11.2
11.2
17.7
58.9
14.7
11.2
a
Each helical portion Fi-Fj is characterized by (i) a linear extension
dij defined by the separation between the facial planes, (ii) an average twist
angle ωij defined by the angular rotation between the projections of Ni and
Nj belonging to the same ligand strand, and (iii) its pitch Pij defined as the
ratio of axial over angular progressions along the helical axis. Pij ) (dij/
ωij) ‚ 360 corresponds to the length of a cylinder containing a single turn
of the helix defined by the geometrical characteristics dij and ωij.20,27 b F1:
N4a, N4b, N4c; F2: N3a, N3b, N3c; F3: N1a, N1b, N1c; F4: C3a, C3b,
C3c; F5: S1a, S1b, S1c; F6: C2a, C2b, C2c; F7: C1a, C1b, C1c.
[Eu(L8)]3+ is more flexible than the analogous O-tripod in [Eu-
(L6)]3+, which affords a less regular wrapping of the alkyl arms
and an overall flattening of the capping tripod in [Eu(L8)]3+
.
However, these minor variations do not impose any serious
constraints on the wrapping of the tridentate 2,6-bis(benzimi-
dazol-2-yl)pyridine units bound to Eu(III), which adopt almost
Figure 5. (a) Optimized superimposition of the podates [Eu(L6)3]3+ (red)
and [Eu(L8)]3+ (blue). (b) Schematic representation of the seven facial
planes along the pseudo-threefold axis. (c) Optimized superimposition of
the coordination spheres in [Eu(L6)3]3+ (red) and in [Eu(L8)]3+ (blue). The
green atoms represent the terminal oxygen atoms in [Eu(L6)3]3+. (d) View
of the covalent tripods perpendicular to the C1-C2 directions in [Eu(L6)3]3+
(red) and in [Eu(L8)]3+ (blue) assuming the same helicity of the three bound
tridentate units about the metal in each complex.
identical arrangements in [Eu(L8)]3+ and in [Eu(L9)3]3+
.
Solution Behaviors and Thermodynamic Stabilities of the
Podates [Ca(L8)](CF3SO3)2 and [Ln(L8)](CF3SO3)3 (Ln )
La-Lu, Y except Pm). Electrospray-ionization mass spectro-
metric (ESI-MS) titrations of L8 (10-4 M in acetonitrile) with
Ca(CF3SO3)2‚0.5H2O or Ln(CF3SO3)3‚xH2O (Ln ) La-Lu, Y;
x ) 2-9) show the formation of [Ca(L8)(CF3SO3)n](2-n)+
(n ) 0, 1) and [Ln(L8)(CF3SO3)n](3-n)+ (n ) 0-2) as the
major species, together with traces of binuclear complexes
[Ca2(L8)(CF3SO3)n](4-n)+ (n ) 2, 3) and [Ln2(L8)(CF3SO3)n](6-n)+
(n ) 2-5, Figure 6 and Table S6, Supporting Information).
The systematic observation of a pronounced end point for
M:L8 ) 1.0 combined with the detection of an isosbestic point
at 347 nm for M:L8 e 1.0 during spectrophotometric titrations
of L8 (10-4 M in acetonitrile containing 10-2 M (nBu)4NClO4)
with Ca(CF3SO3)2‚0.5H2O or Ln(CF3SO3)3‚xH2O (Ln ) La-
Lu, Y; x ) 2-9) confirm the qualitative model established by
ESI-MS and the almost exclusive formation of the podates
[M(L8)]3+ in this stoichiometric range (Figure 7). The absence
of further evolution of the absorption spectra for M:L8 > 1.0
with the larger cations (M ) Ca, La-Dy; RCMN)9 g 1.079 Å,
Figure 7a) shows the conservation of the complex [M(L8)]3+
in an excess of metal in these conditions. On the contrary, the
smooth evolution of the absorbance observed for M:L8 > 1.0
with small cations (M ) Ho-Lu, Figure 7b) indicates the des-
truction of [M(L8)]3+ and the formation of detectable quantities
of the binuclear complexes [M2(L8)]6+ in an excess of metal.
The spectrophotometric data can be thus satisfyingly fitted
to equilibrium 5 for M ) Ca, La-Dy, Y and to equilibria 5
and 6 for M ) Ho-Lu by using nonlinear least-squares
techniques (Table 3).28
(bza1-bzb4, interplanar angle 13.0(2)°, average interplanar
distance 3.2(2) Å), and the second one operates between one
benzimidazole ring of strand c and the pyridine ring of strand
b (bzc4-pb3, interplanar angle 13.1(2)°, average interplanar
distance 3.3(3) Å, Table S4, Supporting Information).
Finally, the superimposition of the related nine-coordinate
podates [Eu(L6)]3+ and [Eu(L8)]3+ displays considerable dis-
crepancies (Figure 5a) arising from (i) the different terminal
donor groups (O-carboxamide in [Eu(L6)]3+ and N-benzimi-
dazole in [Eu(L8)]3+, Figure 5c) and (ii) the distorted wrapping
of the tripod in [Eu(L8)]3+, which significantly deviates from
C3 symmetry (Figure 5d). A detailed geometrical analysis of
the six successive helical portions in the podates [Eu(Li)]3+ (i
) 6, 8) delimited by the seven facial planes F1-F7 depicted in
Figure 5b (Table S5, Supporting Information) first shows the
expected stretching of the helical pitch about the metallic sites
in the F1-F2 domain when carboxamide groups in [Eu(L6]3+
are replaced with benzimidazole units in [Eu(L8]3+ (Table 2).
The helical wrapping induced by the coordination of the
tridentate binding units to Eu(III) in the F1-F4 domain stops
within the F4-F5 domain and then restarts with the same screw
direction for [Eu(L8)]3+, but with the opposite screw direction
for [Eu(L6)]3+ (F5-F7 domain, Figure 5a and 5d, Table 2).
This difference, combined with the small C3-S-C2 bond
angles (98.8°-102.5°) in [Eu(L8)]3+ (C3-O-C2 ) 115° in
[Eu(L6)]3+),20b produces a flattening of the sulfur-containing
tripod testified by the Eu‚‚‚C1 distance, which amounts to 7.012-
M,L8
1,1
z+ + L8 h [M(L8)]z+
2 Mz+ + L8 h [M2(L8)]2z+
â
(5)
(6)
(7) Å in [Eu(L8)]3+ and 7.57(2) Å in [Eu(L6)]3+
.
M
We conclude from this detailed analysis of the molecular
structures in the solid-state that the sulfur-containing tripod in
M,L8
2,1
â
9
1032 J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008

Preorganization in Multicomponent Assemblies
A R T I C L E S
Figure 6. ESI-MS spectrum of [Eu(L8)](CF3SO3)3 (10-4 M in acetonitrile, OTf- ) CF3SO3-).
Figure 7. Variation of the absorption spectra (left) and of the molar extinctions at five different wavelengths (right) observed during the spectrophotometric
titration of L8 with (a) La(CF3SO3)3‚3.3H2O and (b) Lu(CF3SO3)3‚1.6H2O (|L8|tot ) 10-4 M, acetonitrile + 10-2 M (nBu)4NClO4, 298 K).
) 1.18 Å)26 is identical to that of Pr(III) (RPCrN)9 ) 1.179 Å),26
we cannot invoke some improved matching between the ligand
We first note the surprising stability of the bivalent calcium
complex [Ca(L8)]2+ (log(â1C,a1,L8) ) 8.6(8)) with respect to that
of the trivalent lanthanide complexes [Ln(L8)]3+ (7.2 e
cavity and the metallic size. Moreover, Figure 8 shows that no
Ln,L8
1,1
log(â
) e 8.0, Table 3), despite the much larger electro-
size-discriminating effect can be evidenced within experimental
error along the lanthanide series for [Ln(L8)]3+, a behavior
which contrasts with the pronounced inverse electrostatic trend
reported for the formation of analogous [Ln(2,6-bis(1-methyl-
static contribution to the coordination bonds expected for the
latter metals (z2/RLCaN)9 ) 7.40 compared with z2/RCCNa )9
3.39).26 Since the ionic radius of nine-coordinate Ca(II) (RCCNa )9
)
9
J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008 1033

A R T I C L E S
Canard et al.
Table 3. Formation Constants of [Mm(L8)]mz+ (log(âmM,,1L8), m ) 1, 2, z ) 2, 3) and [M(L2)n]z+ (log(â1M,,nL2), n ) 1-3, z ) 2, 3) at 298 K
(Acetonitrile + 0.01 M (nBu)4NClO4)
M
)
Ca
M
)
La
M
)
Ce
M
)
Pr
M
)
Nd
M
)
Sm
M
)
Eu
M ) Gd
M,L8
1,1
8.6(8)
4.4(1)
7.6(2)
6.9(1)
7.2(2)
7.3(2)
7.6(2)
7.8(2)
7.2(1)
9.2(5)
7.5(2)
log(â
log(â
log(â
log(â
)
)
)
)
M,L2
1,1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
M,L2
1,2
M,L2
1,3
8.6(1)
13.0(1)
17.3(1)
16.9(8)
21.8(8)
11.8(3)
M
)
Tb
M
)
Dy
M
)
Ho
M
)
Er
M
)
Tm
M
)
Yb
M
)
Lu
M
) Y
M,L8
7.8(2)
7.4(2)
7.9(1)
11.7(3)
3.8(4)
-
-
-
7.4(1)
11.8(4)
4.4(5)
-
-
-
7.9(1)
11.6(1)
3.7(2)
-
-
-
7.4(1)
11.6(1)
4.2(2)
-
-
-
8.0(1)
12.7(1)
4.6(2)
7.3(2)
log(â
log(â
log(K
)
)
1,1
M,L8
2,1
-
-
-
M,L8
2,1
a
-
-
-
-
-
-
-
-
-
-
-
-
)
M,L2
1,1
9.9(3)
log(â
log(â
log(â
)
M,L2
1,2
17.7(5)
23.4(7)
)
)
M,L2
1,3
a Second successive stability constant log(KM2,1,L8) ) log(âM,L8) - log(âM,L8).
2,1
1,1
L,L/RT)
M,M/RT)
benzimidazol-2-yl)pyridine)3]3+ complexes.15 In this context, the
transformation of the podates [Ln(L8)]3+ into the binuclear
complexes [Ln2(L8)]6+ in an excess of metal can be safely
assigned to an extra stabilization of the binuclear complexes
with small cations. We also note that the replacement of the
three terminal carboxamide goups in [Ln(L6)]3+ with benzimi-
dazole units in [Ln(L8)]3+ has only a minor impact on the
stability constants measured in the same solvent (Figure 8),20
an observation which again contrasts with the inadequate29 but
commonly accepted rule that trivalent lanthanides should display
enthalpic preferences for O-donor ligands.
uL,L ) e-(∆E
and uM,M ) e-(∆E
are the Boltzmann’s
factors accounting for, respectively, the intramolecular interli-
gand ∆EL,L and intermetallic ∆EM,M free energies of interaction
operating in the final complexes; and ceff ) e(∆G
)/RT is
inter-∆Gintra
the effective concentration measuring the energetic effect of
preorganization on intramolecular connection processes. The
chiral
m,n
M,L
statistical factors ω
‚ ω
are calculated in Figure S4
m,n
(Supporting Information)23 by using the symmetry point groups
assigned to each complex in Figure 10.
z+ + L8 h [M(L8)]z+
â
â
â
â
â
â
(5)
(6)
M,L8
M
1,1
A parallel 1H NMR titration of L8 (10-2 M in CD3CN) with
Lu(CF3SO3)3‚1.6H2O shows the formation of the C3-sym-
metrical podate [Lu(L8)]3+ (Figure 9a), followed by its suc-
cessive transformation into [Lu2(L8)]6+ and [Lu3(L8)]9+, the
M,L8
2,1
2 Mz+ + L8 h [M2(L8)]2z+
3 Mz+ + L8 h [M3(L8)]3z+
M,L8
3,1
(7)
1
z+ + L2 h [M(L2)]z+
(8)
M,L2
1,1
two latter complexes being labile on the H NMR time scale
M
(Figure 9b and c). In an excess of metal (Lu:L8 ) 4.0), the
z+ + 2 L2 h [M(L2)2]z+
(9)
M,L2
1,2
quantity of [Lu2(L8)]6+ becomes negligible and the exchange
M
1
process does not affect the H NMR spectrum of [Lu3(L8)]9+
z+ + 3 L2 h [M(L2)3]z+
(10)
M,L2
1,3
(Figure 9d).30 The conservation of the threefold axis (a total of
18 1H NMR signals are detected), combined with the deshielding
of the protons H5 and H13 and the observation of enantiotopic
M
â
) 12 ‚ (f NM3)3 ‚ (uL,L)3 ‚ (ceff)2
) 108 ‚ (f NM3)3 ‚ uL,L ‚ ceff ‚ uM,M
(11)
(12)
(13)
(14)
(15)
(16)
M,L8
1,1
methylene protons H2, H3, H4, H14, and H16 in [Lu3(L8)]9+
,
M,L8
2,1
â
â
â
â
â
indicates the formation of a nonhelical dynamically averaged
C3V-symmetry for this trinuclear complex on the NMR time
scale. Interestingly, the speciation found by NMR suggests
M,L8
3,1
) 216 ‚ (f MN3)3 ‚ (uM,M 3
)
Lu,L8
2,1
Lu,L8
) much larger than those
3,1
M,L2
1,1
) 6 ‚ f MN3
values of log(â
) and log(â
estimated by spectrophotmetric titrations, a discrepancy which
can be attributed to the effect of the larger ionic strength
operating during the NMR experiment, which is known to favor
the formation of highly charged complexes.
) 12 ‚ (f MN3)2‚uL,L
M,L2
1,2
M,L2
1,3
) 16 ‚ (f MN3)3‚(uL,L 3
)
Thermodynamic Model and Rationalization of the Com-
plexation Process. The application of the site binding model
(eq 2)22 to equilibria 5-10 gives eqs 11-16, whereby fMN3
represents the microscopic affinity, including desolvation,
characterizing the intermolecular connection of the metal M to
the N3 binding site (assumed to be identical for L2 and L8);
If we focus on the four easily accessible thermodynamic
M,L8
1,1
M,L2
1,1
M,L2
1,2
M,L2
(eq
1,3
constants â
(eq 5), â
(eq 8), â
(eq 9), and â
10), we obtain a set of four equations (eqs 11, 14-16) containing
only three parameters fMN3, uL,L, and ceff to be fitted. We have
thus performed spectrophotometric titrations of L2 (10-4 M in
acetonitrile containing 10-2 M (nBu)4NClO4) with Ca(CF3SO3)2‚
0.5H2O or Ln(CF3SO3)3‚xH2O (Ln ) La, Eu and Lu; x ) 1-4),
which display the usual successive formation of the three
complexes [Ln(L2)n]3+ (n ) 1-3, Figure S5, Supporting
(28) (a) Gampp, H.; Maeder, M.; Meyer, C. J.; Zuberbu¨hler, A. Talanta 1985,
32, 1133-1139. (b) Gampp, H.; Maeder, M.; Meyer, C. J.; Zuberbu¨hler,
A. Talanta 1986, 33, 943-951.
(29) Senegas, J.-M.; Bernardinelli, G.; Imbert, D.; Bu¨nzli, J.-C. G.; Morgantini,
P.-Y.; Weber, J.; Piguet, C. Inorg. Chem. 2003, 42, 4680-4695.
(30) Pons, M.; Millet, O. Prog. Nucl. Magn. Reson. Spectrosc. 2001, 38, 267-
324.
Information).15 Nonlinear least-square fits of these spectropho-
M,L2
1,n
tometric data28 provides the formation constants â
col-
9
1034 J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008

Preorganization in Multicomponent Assemblies
A R T I C L E S
accompanying the fixation of the second and third tridentate
binding units to the metal in [Ln(L8)]3+ is more than balanced
by unfavorable constraints occurring in the covalent tripod
during the complexation process. This effect escapes detection
in the solid state because the criteria of the superimposable
strands observed in the crystal structures of [Ln(L8)]3+ and [Ln-
(L9)]3+ (Figure 4b) does not refer to the energy change
accompanying the formation of the complexes from the
separated ligands and metals. In contrast to the intermolecular
connection processes ∆GiLnnter, its intramolecular counterpart ∆
Ln
intra
G
is insensitive to the variation of the electrostatic effect
along the lanthanide series, a phenomenon which can be
assigned to increasing constraints operating in the tripod when
the three strands wrap about small metal ions (∆GLconrr increases
from 27 kJ/mol in [La(L8)]3+ to 43 kJ/mol in [Lu(L8)]3+, Table
4). The latter unfavorable contribution affecting the complex-
ation of small lanthanides in [Ln(L8)]3+ is responsible for the
unwrapping of the strands and the detection of competitive
polynuclear complexes [Ln2(L8)]6+ and [Ln3(L8)]9+, in which
the intramolecular connections are stepwise replaced with more
favorable intermolecular processes. In this context, the combina-
tion of eq 12 with the previous set of eqs 11, 14-16 for Lu-
(III) allows the estimation of the intermetallic interaction ∆ELu,Lu
Ln,L8
1,1
Ln,L6
Figure 8. Plot of log(â
) (2) and log(â
) (0)20b as a function of the
) .
1,1
CN)9
-1
inverse of the nine-coordinate ionic radii (R
Ln
lected in Table 3. For each cation Ca2+, La3+, Eu3+, and Lu3+
,
we can thus easily estimate fMN3, uL,L, and ceff by using
multilinear least-squares fits of eqs 11, 14-16 in their loga-
rithmic forms (Table 4). The quality of the fits is excellent
(agreement factors AFM ) 0.003-0.016, Table 4),31 and the
M,L8,calcd
1,1
M,L2,calcd
1,n
) 42(1) kJ/mol operating in [Lu2(L8)]6+. Introducing this
formation constants log(â
) and log(â
) com-
M,L8
3,1
puted by introducing the fitted microscopic parameters in eqs
11, 14-16 closely match the experimental data (Table S7,
Supporting Information).
strongly repulsive parameter in eq 13 affords log(â
) ) 7.6,
which explains the low stability of the complex [Lu3(L8)]9+
and its exclusive detection at high concentration and in an excess
of metal (1H NMR titration). However, this intermetallic
interaction parameter ∆ELu,Lu reflects a delicate balance between
considerable intramolecular intermetallic electrostatic repulsions
and huge changes in solvation accompanying the stepwise
The only favorable driving force accompanying the com-
plexation of the tridentate 2,6-bis(benzimidazol-2-yl)pyridine
units to Ca(II) or Ln(III) results from the intermolecular metal-
ligand connection process (-51 e ∆GMinter e -21 kJ/mol,
Table 4), which includes the change in solvation occurring in
transformation of [Lu(L8)]3+ into [Lu2(L8)]6+ and [Lu3(L8)]9+
.
the first coordination sphere of the metal.22 As expected,32
∆
Its detailed interpretation will be delayed until reliable solvation
energies will be available for these two complexes in solution.34
GMinter becomes more favorable (i.e., more negative, -35 g ∆
Ln
G
g -51 kJ/mol) with increasing electrostatic factors
inter
z2/RCMN)9 (M ) Ca: 3.39; M ) La: 7.40; M ) Eu: 8.04; M )
Experimental Section
Lu: 8.72 eu/Å-1). The value for Ln ) Eu, ∆GEinuter ) -49(2)
Chemicals were purchased from Fluka AG and Aldrich and used
without further purification unless otherwise stated. Ethyl-(4-methyl-
2-nitro-phenyl)amine (2),35 pyridine-2,6-dicarboxylic acid monomethyl
ester (4),36 ethyl-(4-methoxymethyl-2-nitro-phenyl)amine (8),37 1,5-
dihydroxy-3-(2-hydroxy-ethyl)-3-methylpentane (18),20b and 1,5-
dichloro-3-(2-chloro-ethyl)-3-methylpentane (19)25 were prepared ac-
cording to literature procedures. The trifluoromethanesulfonate salts
Ln(CF3SO3)3‚xH2O (Ln ) La-Lu, Y, x )1-9) were prepared from
the corresponding oxides (Aldrich, 99.99%).38 The Ln content of solid
salts was determined by complexometric titrations with Titriplex III
(Merck) in the presence of urotropine and xylene orange.39 Acetonitrile
and dichloromethane were distilled over calcium hydride. Thin layer
chromatography (TLC) used silicagel plates Merck 60 F254, and Fluka
silica gel 60 (0.04-0.063 mm) was used for preparative column
chromatography.
Eu
inter
kJ/mol is of the same order of magnitude as that for ∆G
)
-30 kJ/mol previously reported for the same tridentate N3 unit
connected to different spacers in self-assembled triple-stranded
helicates [Ln3(L4)3]9+ and [Ln4(L5)3]9+ in pure acetonitrile.22,33
The minor anticooperative interligand interactions 1 e ∆EL,L
e 10 kJ/mol (Table 4) result from the successive fixation of
electron-rich N3 binding units to hard cations, which stepwise
reduces the global charge of the metallic center by polarization.22
Obviously, this effect is more pronounced when the total charge
increases, for instance in going from Ca2+ to Ln3+, and it reaches
∆EL,L ) 10 kJ/mol for Ln ) Eu3+, a value which fairly matches
8(2) kJ/mol previously reported in triple-stranded helicates.22,33
However, the dramatic 60-80% decrease of the absolute affinity
of the N3 site for the metal, which is observed when the
intermolecular connection process is replaced with its intramo-
lecular counterpart (-12 e ∆GMintra ) (∆GiMnter + ∆GcMorr) e -8
kJ/mol, Table 4), represents the most striking feature of this
contribution. It implies that the favorable entropic chelate effect
Preparation of 6-[Ethyl-(4-methyl-2-nitro-phenyl)-carbamoyl]-
pyridine-2-carboxylic Acid Methyl Ester (5). Pyridine-2,6-dicar-
(34) Canard, G.; Piguet, C. Inorg. Chem. 2007, 46, 3511-3522.
(35) Senegas, J.-M.; Koeller, S.; Bernardinelli, G.; Piguet, C. Chem. Commun.
2005, 2235-2237.
(36) Johansen, J. E.; Christie, B. D.; Rapoport, H. J. Org. Chem. 1981, 46,
4914-4920.
(37) Nozary, H.; Piguet, C.; Tissot, P.; Bernardinelli, G.; Bu¨nzli, J.-C. G.;
Deschenaux, R.; Guillon, D. J. Am. Chem. Soc. 1998, 120, 12274-12288.
(38) Desreux, J. F. In Lanthanide Probes in Life, Chemical and Earth Sciences;
Bu¨nzli, J.-C.G., Choppin, G. R., Eds.; Elsevier Publishing Co.: Amsterdam,
1989; Chapter 2.
(39) Schwarzenbach, G. Complexometric Titrations; Chapman & Hall: London,
1957; p 8.
(31) Willcott, M. R.; Lenkinski, R. E.; Davis, R. E. J. Am. Chem. Soc. 1972,
94, 1742-1744.
(32) Choppin, G. R. In Lanthanide Probes in Life, Chemical and Earth Sciences;
Bu¨nzli, J.-C.G., Choppin, G. R., Eds.; Elsevier Publishing Co.: Amsterdam,
1989; Chapter 1.
(33) Zeckert, K.; Hamacek, J.; Senegas, J.-M.; Dalla-Favera, N.; Floquet, S.;
Bernardinelli, G.; Piguet, C. Angew. Chem., Int. Ed. 2005, 44, 7954-7958.
9
J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008 1035

A R T I C L E S
Canard et al.
Figure 9. 1H NMR spectra recorded during the titration of L8 with Lu(CF3SO3)3‚1.6H2O for (a) Lu:L8 ) 1.0, (b) Lu:L8 ) 2.0, (c) Lu:L8 ) 3.0 and (d)
Lu:L8 ) 4.0 (|L8|tot ) 10-2 M, CD3CN, 298 K).
boxylic acid monomethyl ester (4, 1.99 g, 11 mmol), CH2Cl2 (25 mL),
thionyl chloride (7.7 mL, 110 mmol, 10 equiv), and DMF (10 µL)
were refluxed for 1.5 h under nitrogen and evaporated to dryness.
The white residue was dried under vacuum for 1 h and dissolved in
CH2Cl2 (10 mL), and a solution of ethyl-(4-methyl-2-nitro-phenyl)-
amine (2, 1.8 g, 10 mmol) and triethylamine (1.5 mL, 11 mmol) in
CH2Cl2 (15 mL) was added dropwise. The resulting mixture was
strirred at room temperature for 30 min, refluxed for 1 h, successively
washed with aq. sat. NaHCO3 (2 × 20 mL) and aq. sat. NH4Cl (1 ×
20 mL), dried over MgSO4, and evaporated to yield a brown oil, which
was purified by column chromatography (silicagel, CH2Cl2/MeOH
100:0 f 97:3) to afford 5 as a brown-orange oil (3.3 g, 9.6 mmol,
Ar-H), 7.80 (s, 1H; Ar-H), 7.85-7.90 (m, 2H; Ar-H), 7.97 ppm
(d, 3J ) 7.2 Hz, 1H; Ar-H); ESI-MS (CH2Cl2/MeOH 9:1): 344.1
[M + H+].
Preparation of 6-[Ethyl-(4-methyl-2-nitro-phenyl)-carbamoyl]-
pyridine-2-carboxylic Acid (6). A solution of LiOH‚H2O (2.1 g, 50
mmol) in methanol (40 mL) and water (20 mL) was added dropwise
to a solution of 6-[ethyl-(4-methyl-2-nitro-phenyl)-carbamoyl]-pyridine-
2-carboxylic acid methyl ester (5, 3.43 g, 10 mmol) in methanol (20
mL) at 0 °C. The resulting mixture was stirred for 3 h at 0 °C, diluted
with water (400 mL), and washed with CH2Cl2 (3 × 25 mL). The pH
of the aqueous phase was adjusted to 2 with concentrated hydrochloric
acid (37%). The solution was extracted with CH2Cl2 (4 × 40 mL), and
the combined organic phases were dried over MgSO4 and evaporated
1
3
96%). H NMR ((CD3)2SO, 440 K): δ ) 1.80 (t, J ) 7.1 Hz, 3H;
CH3(Et)), 2.37 (s, 3H; Ar-CH3), 3.50-4.16 (m, 5H; CH2 (Et) and
to dryness to afford 6 as a yellow solid (3.23 g, 9.8 mmol, 98%).
1H
NMR (CDCl3): δ ) 1.28 (t, J ) 7.2 Hz, 3H; CH3(Et)), 2.44 (s, 3H;
3
3
3
OCH3), 7.34 (d, J ) 7.2 Hz, 1H; Ar-H), 7.47 (d, J ) 8.2 Hz, 1H;
9
1036 J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008

Preorganization in Multicomponent Assemblies
A R T I C L E S
Figure 10. Successive complexation reactions leading to (a) [Mm(L8)]zm+ (z ) 2, 3 and m ) 1-3) and (b) [M(L2)n]z+ (z ) 2, 3 and n ) 1-3) with
chiral
m,n
M,L
m,n
thermodynamic formation constants modeled with eq 2 (S ) CH3CN).22,24 The statistical factors ω
‚ ω
are calculated in Figure S4 (Supporting
Information).23
Ar-CH3), 3.82 (sext, 3J ) 7.2 Hz, 1H; CH (Et)), 4.18 (sext, 3J ) 7.2
8.00 (t, 3J ) 7.8 Hz, 1H; Ar-H), 8.12 (dd, 3J ) 7.8 Hz, 4J ) 1.0 Hz,
3
3
3
4
Hz, 1H; CH (Et)), 7.28 (d, J ) 8.1 Hz, 1H; Ar-H), 7.43 (dd, J )
1H; Ar-H), 8.20 ppm (dd, J ) 7.8 Hz, J ) 1.0 Hz, 1H; Ar-H);
4
4
8.1 Hz, J ) 1.4 Hz, 1H; Ar-H), 7.68 (d, J ) 1.4 Hz, 1H; Ar-H),
ESI-MS (CH2Cl2/MeOH 9:1): 330.5 [M + H+].
9
J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008 1037

A R T I C L E S
Canard et al.
Table 4. Fitted Microscopic Thermodynamic Parameters for [Mm(L8)]mz+ (m ) 1, 2, z ) 2, 3) and [M(L2)n]z+ (n ) 1-3, z ) 2, 3;
Simultaneous Linear Least-Squares Fits of Eqs 11, 14-16, Acetonitrile + 0.01 M (nBu)4NClO4, 298 K)a
microscopic parameters
Ca
La
Eu
Lu
Lub
log(fMN3)/∆GiMnter (kJ/mol)
log(fMN3 ‚ ceff)/∆GMintra (kJ/mol)
log(ceff)/∆GcMorr (kJ/mol)
log(uL.L)/∆EL,L (kJ/mol)
log(uM,M)/∆EM,M (kJ/mol)
AFc
3.8(2)/-21(1)
2.2(4)/-12(4)
-1.6(2)/9(1)
-0.2(2)/1(1)
-
6.3(2)/-35(1)
1.5(2)/-8(1)
-4.8(2)/27(1)
-0.9(2)/5(1)
-
8.7(3)/-49(2)
1.4(2)/-8(1)
-7.3(3)/39(2)
-1.8(3)/10(2)
-
9.15(8)/-51.3(5)
1.52(8)/-8.5(4)
-7.63(8)/42.8(4)
-1.74(9)/9.8(5)
-
9.15(8)/-51.3(5)
1.52(8)/-8.5(4)
-7.63(8)/42.8(4)
-1.74(9)/9.8(5)
-7.4(2)/42(1)
0.003
0.014
0.012
0.012
0.003
b
c
a The uncertainties correspond to those obtained during the multilinear least-square fit processes. Fitted with eqs 11, 12, 14-16; see text. Agreement
factor AF ) (∑ (log(âexp)-log(âci alcd))2)/(∑i(log(âei xp))2).
x
i
i
Preparation of Pyridine-2,6-dicarboxylic Acid 2-[Ethyl-(4-meth-
oxymethyl-2-nitro-phenyl)-amide] 6-[Ethyl-(4-methyl-2-nitro-phen-
yl)-amide] (9). A mixture of 6-[ethyl-(4-methyl-2-nitro-phenyl)-
carbamoyl]-pyridine-2-carboxylic acid (6, 0.68 g, 2.1 mmol), CH2Cl2
(5 mL), thionyl chloride (1.4 mL, 20 mmol, 10 equiv) and DMF (10
µL) was refluxed for 1.5 h under a nitrogen atmosphere and evaporated
to dryness. The yellow residue was dried under vacuum for 1 h and
then dissolved in CH2Cl2 (3 mL). A solution of ethyl-(4-methoxymethyl-
2-nitro-phenyl)amine (8, 0.42 g, 2.0 mmol) and triethylamine (0.3 mL,
2.0 mmol) in CH2Cl2 (3 mL) was then added dropwise. The mixture
was stirred at room temperature for 30 min, refluxed for 1 h washed
with aq. half-sat. NH4Cl (2 × 10 mL), dried over MgSO4, and
evaporated to yield a brown oil, which was purified by column
chromatography (silicagel, CH2Cl2/MeOH 100:0 f 97:3) to afford 9
as a beige solid (1.0 g, 1.9 mmol, 96%). 1H NMR ((CD3)2SO, 440 K):
δ ) 1.10 (m, 6H; CH3(Et)), 2.37 (s, 3H; Ar-CH3), 3.34 (m, 3H; OCH3),
3.70 (m, 4H; CH2(Et)), 4.48 (s, 2H; Ar-CH2O), 7.27 (m, 1H; Ar-H),
mmol) was stirred for 16 h at room temperature and poured into an
ice-cooled aq. 1 M KOH (400 mL). The aqueous layer was extracted
with CH2Cl2 (2 × 10 mL). The combined organic phases were washed
with deionized water until neutral, dried over Na2SO4, filtered, and
evaporated to dryness to afford the crude acetate, which was dissolved
in methanol (80 mL) and aq. 1 M KOH (50 mL) and stirred for 15 h
at room temperature. The methanol was distilled under vacuum, and
the resulting solution was poured into brine (150 mL) and extracted
with CH2Cl2 (4 × 30 mL). The combined organic phases were washed
with deionized water until neutral, dried over MgSO4, filtered, and
evaporated to dryness. The resulting crude compound was purified by
column chromatography (silicagel, CH2Cl2/MeOH 98:2 f 94:6) to
afford 11 as a white solid (0.57 g, 1.38 mmol, 99%). 1H NMR
3
3
(CDCl3): δ ) 1.37 (t, J ) 7.2 Hz, 3H; CH3 (Et)), 1.39 (t, J ) 7.2
3
Hz, 3H; CH3 (Et)), 2.55 (s, 3H; Ar-CH3), 4.79 (q, J ) 7.2 Hz, 2H;
CH2 (Et)), 4.81 (q, 3J ) 7.2 Hz, 2H; CH2 (Et)), 4.86 (s, 2H; Ar-
CH2O), 7.22 (dd, 3J ) 8.3 Hz, 4J ) 1.4 Hz, 1H; Ar-H), 7.39 (d, 3J )
3
3
4
7.38 (m, 1H; Ar-H), 7.46-7.48 (m, 3H; Ar-H), 7.62 (d, J ) 7.0
8.3 Hz, 1H; Ar-H), 7.43 (dd, J ) 8.3 Hz, J ) 1.4 Hz, 1H; Ar-H),
3
Hz, 1H; Ar-H), 7.75 (s, 1H; Ar-H), 7.81 (m, 1H; Ar-H), 7.87 ppm
(s, 1H; Ar-H); ESI-MS (CH2Cl2/MeOH 9:1): 522.5 [M + H+].
Preparation of 6-(1-Ethyl-5-methoxymethyl-1H-benzoimidazol-
2-yl)-2-(1-ethyl-5-methyl-1H-benzoimidazol-2-yl)-pyridine (10). To
a solution of pyridine-2,6-dicarboxylic acid 2-[ethyl-(4-methoxymethyl-
2-nitro-phenyl)-amide] 6-[ethyl-(4-methyl-2-nitro-phenyl)-amide] (9,
2.48 g, 4.75 mmol) in ethanol/water (315 mL/95 mL), activated iron
powder (4.25 g, 75.8 mmol) and concentrated hydrochloric acid (37%,
11.6 mL, 138.6 mmol) were added. The mixture was refluxed for 18
h under nitrogen, the excess of iron was filtered off, and ethanol was
distilled under vacuum. The resulting mixture was poured into CH2Cl2
(100 mL), Na2H2EDTA‚2H2O (51 g, 137 mmol) in water (250 mL)
was added, and the resulting stirred mixture was neutralized (pH 7.0)
with concentrated aqueous NH4OH solution. Concentrated H2O2
solution (30%, 2.7 mL, 27 mmol) was added under vigorous stirring,
and the pH was adjusted to 8.5 with aqueous NH4OH solution. After
15 min, the organic layer was separated and the aqueous phase was
extracted with CH2Cl2 (3 × 50 mL). The combined organic phases
were washed with water until neutral, dried over Na2SO4, and
evaporated to dryness. The crude residue was purified by column
chromatography (silicagel, CH2Cl2/MeOH 100:0 f 97:3) to afford 10
7.48 (d, J ) 8.3 Hz, 1H; Ar-H), 7.69 (s, 1H; Ar-H), 7.82 (s, 1H;
3
3
Ar-H), 8.01 (t, J ) 7.9 Hz, 1H; Ar-H), 8.31 ppm (d, J ) 7.9 Hz,
2H; Ar-H); ESI-MS (CH2Cl2/MeOH 9:1): 412.5 [M + H+].
Preparation of 6-(5-Chloromethyl-1-ethyl-1H-benzoimidazol-2-
yl)-2-(1-ethyl-5-methyl-1H-benzoimidazol-2-yl)-pyridine (12). A mix-
ture of {1-ethyl-2-[6-(1-ethyl-5-methyl-1H-benzoimidazol-2-yl)-pyridin-
2-yl]-1H-benzoimidazol-5-yl}-methanol (11, 1.02 g, 2.48 mmol),
CH2Cl2 (40 mL) and thionyl chloride (1.8 mL, 25 mmol) was stirred
for 16 h at room temperature; it was then poured into aq. sat. NaHCO3
(400 mL). The aqueous layer was extracted with CH2Cl2 (3 × 20 mL),
and the combined organic phases were washed with deionized water
until neutral, dried over MgSO4, filtered, and evaporated to dryness.
The resulting crude compound was purified by column chromatography
(silicagel, CH2Cl2/MeOH 100:0 f 98:2) to afford 12 as a white solid
1
3
(0.89 g, 2.07 mmol, 83%). H NMR (CDCl3): δ ) 1.38 (t, J ) 7.2
3
Hz, 3H; CH3 (Et)), 1.39 (t, J ) 7.2 Hz, 3H; CH3 (Et)), 2.55 (s, 3H;
Ar-CH3), 4.80 (m, 4H; CH2 (Et)), 4.82 (s, 2H; Ar-CH2Cl), 7.23 (dd,
4
3
3J ) 8.4 Hz, J ) 1.1 Hz, 1H; Ar-H), 7.39 (d, J ) 8.4 Hz, 1H;
Ar-H), 7.45 (dd, 3J ) 8.4 Hz, 4J ) 1.6 Hz, 1H; Ar-H), 7.50 (d, 3J )
8.4 Hz, 1H; Ar-H), 7.69 (s, 1H; Ar-H), 7.89 (s, 1H; Ar-H), 8.08 (t,
3J ) 7.9 Hz, 1H; Ar-H), 8.34 (dd, J ) 7.9 Hz, J ) 1.0 Hz, 1H;
Ar-H), 8.38 ppm (d, 3J ) 7.9 Hz, 1H; Ar-H); ESI-MS (CH2Cl2/MeOH
9:1): 430.4 [M + H+].
3
4
1
as a white solid (1.93 g, 4.53 mmol, 95%). H NMR (CDCl3): δ )
3
3
1.37 (t, J ) 7.2 Hz, 3H; CH3 (Et)), 1.38 (t, J ) 7.2 Hz, 3H; CH3
(Et)), 2.55 (s, 3H; Ar-CH3), 3.44 (s, 3H; OCH3), 4.65 (s, 2H; Ar-
Preparation of Thioacetic Acid S-{1-Ethyl-2-[6-(1-ethyl-5-methyl-
1H-benzoimidazol-2-yl)-pyridin-2-yl]-1H-benzoimidazol-5-ylmeth-
yl} Ester (13). 6-(5-Chloromethyl-1-ethyl-1H-benzoimidazol-2-yl)-2-
(1-ethyl-5-methyl-1H-benzoimidazol-2-yl)-pyridine (12, 500 mg, 1.16
mmol) was dissolved in a suspension of potassium thioacetate (797
mg, 6.97 mmol, 6 equiv) in acetone (15 mL) and dichloromethane (15
mL). The mixture was stirred and heated at 55 °C for 16 h and then
evaporated to dryness. The resulting solid was dissolved in ethyl acetate
(20 mL) and water (20 mL). The aqueous phase was separated and
extracted with ethyl acetate (2 × 30 mL). The combined organic phases
were washed with brine, dried over Na2SO4, and evaporated to yield a
3
4
CH2O), 4.81 (m, 4H; CH2 (Et)), 7.22 (dd, J ) 8.3 Hz, J ) 1.4 Hz,
1H; Ar-H), 7.40 (m, 2H; Ar-H), 7.49 (d, J ) 8.3 Hz, 1H; Ar-H),
7.68 (s, 1H; Ar-H), 7.84 (s, 1H; Ar-H), 8.07 (t, J ) 7.9 Hz, 1H;
3
3
Ar-H), 8.36 ppm (m, 2H; Ar-H); ESI-MS (CH2Cl2/MeOH 9:1): 426.0
[M + H+].
Preparation of {1-Ethyl-2-[6-(1-ethyl-5-methyl-1H-benzoimida-
zol-2-yl)-pyridin-2-yl]-1H-benzoimidazol-5-yl}-methanol (11). A
mixture of 6-(1-ethyl-5-methoxymethyl-1H-benzoimidazol-2-yl)-2-(1-
ethyl-5-methyl-1H-benzoimidazol-2-yl)-pyridine (10, 0.6 g, 1.4 mmol)
in acetic anhydride/CH2Cl2 (10 mL/10 mL) and BF3‚Et2O (0.9 mL, 7
9
1038 J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008

Preorganization in Multicomponent Assemblies
A R T I C L E S
Table 5. Summary of Crystal Data, Intensity Measurement, and
Structure Refinement for [Eu(L8)](ClO4)3‚2CH3CN‚C2H5OH‚0.5H2O
(20)
pale yellow viscous oil, which was purified by column chromatography
(silicagel, CH2Cl2/MeOH 98:2) to afford 13 as a white solid (523 mg,
1
3
1.14 mmol, 96%). H NMR (CDCl3): δ ) 1.34 (t, J ) 7.2 Hz, 6H;
CH3(Et)), 2.36 (s, 3H; Ar-CH3), 2.52 (s, 3H; CH3CO), 4.31 (s, 2H;
formula
fw
C89H100Cl3EuN17O13.5S3
1978.6
3
Ar-CH2), 4.73-4.80 (m, 4H; CH2(Et)), 7.19 (d, J ) 8.3 Hz, 1H;
CH), 7.30 (dd, J ) 8.4 Hz, J ) 1.0 Hz, 1H; CH), 7.36 (d, J ) 8.3
Hz, 1H; CH), 7.40 (d, J ) 8.4 Hz, 1H; CH), 7.65 (s, 1H; CH), 7.78
(s, 1H; CH), 8.04 (t, J ) 7.9 Hz, 1H; CH), 8.30 (dd, J ) 7.9 Hz, J
crystal system
space group
a (Å)
b (Å)
c (Å)
R (deg)
â (deg)
γ (deg)
V (Å3)
monoclinic
P21/c
14.4595 (6)
15.5595 (5)
43.521 (1)
90
96.035 (5)
90
9737.2 (7)
4
3
4
3
3
3
3
4
3
) 1.0 Hz, 1H; CH), 8.33 ppm (d, J ) 7.9 Hz, 1H; CH); ESI-MS
(CH2Cl2/MeOH 9:1): 470.9 [M + H+].
Preparation of {1-Ethyl-2-[6-(1-ethyl-5-methyl-1H-benzoimida-
zol-2-yl)-pyridin-2-yl]-1H-benzoimidazol-5-yl}-methanethiol (14).
Thioacetic acid S-{1-ethyl-2-[6-(1-ethyl-5-methyl-1H-benzoimidazol-
2-yl)-pyridin-2-yl]-1H-benzoimidazol-5-ylmethyl} ester (13, 310 mg,
0.66 mmol) was dissolved in methanol (46 mL) and concentrated HCl
(37%, 4 mL). The mixture was stirred and heated at 45 °C for 16 h.
The methanol was then evaporated, and ethyl acetate (20 mL), water
(20 mL), and aq. sat. NaHCO3 (20 mL) were added to the resulting
solution. The aqueous phase was separated and extracted with ethyl
acetate (2 × 30 mL). The combined organic phases were washed with
brine, dried over Na2SO4, and evaporated to yield a pale yellow viscous
oil, which was purified by column chromatography (silicagel, CH2Cl2/
MeOH 98:2) to afford 14 as a white solid (278 mg, 0.65 mmol, 99%).
Z
crystal size (mm3)
0.048 × 0.21 × 0.26
d
calcd (g‚cm-3
)
1.350
µ(Mo KR) (mm-1
min, Tmax
2θ max (deg)
)
0.858
0.8561, 0.9594
51.8
78259
19010
T
no. of reflns collected
no. of independent reflns
criterion (q) for obsd reflnsa,b
no. of obsda (usedb) reflns
no. of variables
4
8832 (9465)
1188
0.0002
1.60, -1.86
1.37(1)
weighting scheme pc
max and min ∆F (e Å-3
GOF d (all data)
Re, ωRf
)
3
1H NMR (CDCl3): δ ) 1.35 (m, 6H; CH3(Et)), 1.82 (t, J ) 7.4 Hz,
1H; SH), 2.52 (s, 3H; Ar-CH3), 3.92 (d, 3J ) 7.4 Hz, 2H; Ar-CH2),
0.050, 0.049
3
3
4.76 (m, 4H; CH2(Et)), 7.19 (d, J ) 8.3 Hz, 1H; CH), 7.35 (d, J )
a
|Fo| > q σ(Fo). bUsed in the refinements (including reflns with |Fo| e
3
8.3 Hz, 2H; CH), 7.42 (d, J ) 8.3 Hz, 1H; CH), 7.65 (s, 1H; CH),
q σ(Fo) if |Fc| > |Fo|). cω ) 1/[σ2(Fo) + p(Fo)2]. dS ) [∑{((Fo - Fc)/
3
3
7.78 (s, 1H; CH), 8.03 (t, J ) 7.90 Hz, 1H; CH), 8.32 ppm (t, J )
σ(Fo))2}/(Nref - Nvar)]1/2
.
eR ) ∑||Fo| - |Fc|/∑|Fo|. ωR ) [∑(ω|Fo| -
f
7.90 Hz, 2H; CH); ESI-MS (CH2Cl2/MeOH 9:1): 428.5 [M + H+].
|Fc|/∑ω|Fo| ]1/2
.
2
Preparation of L8. {1-Ethyl-2-[6-(1-ethyl-5-methyl-1H-benzoimi-
dazol-2-yl)-pyridin-2-yl]-1H-benzoimidazol-5-yl}-methanethiol (14, 1.67
g, 3.91 mmol, 4 equiv) and 1,5-dichloro-3-(2-chloro-ethyl)-3-methyl-
pentane (19, 213 mg, 0.98 mmol, 1 equiv) were dissolved in a
suspension of dry cesium carbonate (1.27 g, 3.91 mmol, 4 equiv) in
freshly distilled DMF (50 mL) under a nitrogen atmosphere. The
mixture was stirred, heated at 60 °C for 16 h, filtered, and evaporated
to dryness. The resulting solid was dissolved in dichloromethane (100
mL) and brine (50 mL). The organic phase was washed with water (50
mL) and brine (50 mL), dried over Na2SO4, and evaporated to dryness
to yield a solid, which was purified by column chromatography
(silicagel, CH2Cl2/MeOH 98:2 f 96:4) to afford L8 as a white solid
were obtained by slow diffusion of tert-butylmethylether into a
concentrated solution of [Eu(L8)](CF3SO3)3‚4H2O in acetonitrile/ethanol
(99.9:0.1) containing (nBu)4NClO4 (3 equiv).
Single-Crystal Structure Determination. Summary of crystal data,
intensity measurements, and structure refinements for [Eu(L8)]-
(ClO4)3‚2CH3CN‚C2H5OH‚0.5H2O (20) were collected in Table 5. The
crystal was mounted on a quartz fiber with protection oil. Cell
dimensions and intensities were measured at 150 K on a Stoe IPDS
diffractometer with graphite-monochromated Mo KR radiation (λ )
0.710 73 Å). Data were corrected for Lorentz and polarization effects
and for absorption. The structure was solved by direct methods
(SIR97),40 and all other calculation were performed with the XTAL41
system and ORTEP42 programs. CCDC-658414 contains the supple-
mentary crystallographic data for 20. The perchlorates e and f were
disordered and refined with restraints on bond distances and bond
angles. Two oxygen atoms of the perchlorate were refined on two sites
with population parameters of 0.65/0.35 and 0.6/0.4, respectively. Both
molecules of ethanol and the water molecule were refined with
population parameters of 0.5, 0.5, and 0.25, respectively, and the atomic
positions of the hydrogen atoms of these molecules were not calculated.
For all the other atoms, the atomic positions of the hydrogen atoms
were calculated. The cif files can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ,
UK; fax: (+44) 1223-336-033; or deposit@ccdc.cam.ac.uk).
1
(1.05 g, 0.75 mmol, 77%). H NMR (CDCl3): δ ) 0.77 (s, 3H; H1),
1.30-1.35 (m, 18H; H15,17), 1.41-1.45 (m, 6H; H2), 2.27-2.31 (m,
6H; H3), 2.52 (s, 9H; H18), 3.81 (s, 6H; H4), 4.73 (q, 3J ) 7.0 Hz, 12H;
3
4
3
H14,16), 7.18 (dd, J ) 8.3 Hz, J ) 1.0 Hz, 3H; H12), 7.30 (dd, J )
8.4 Hz, 4J ) 1.3 Hz, 3H; H6), 7.33 (d, 3J ) 8.3 Hz, 3H; H11), 7.37 (d,
3J ) 8.4 Hz, 3H; H7), 7.64 (s, 3H; H13), 7.74 (s, 3H; H5), 7.99 (t, 3J )
7.8 Hz, 3H; H9), 8.33-8.39 ppm (m, 6H; H8,10); ESI-MS (CH2Cl2/
MeOH 9:1): 1391.3 [M + H+], 696.3 [M + 2H+]. C83H87N15S3‚0.5H2O
(1399.9) calcd: C, 71.21, H, 6.34; N, 15.00. found: C, 71.02; H, 6.33;
N, 14.90.
Preparation of the Complexes [Ca(L8)](CF3SO3)2‚3H2O and [Ln-
(L8)](CF3SO3)3‚xH2O (Ln ) La, x ) 4; Ln ) Nd, x ) 4; Ln ) Eu,
x ) 4; Ln ) Gd, x ) 4; Ln ) Tb, x ) 3; Ln ) Lu, x ) 4; Ln )
Y, x ) 2). A solution of Ca(CF3SO3)2‚0.5H2O or Ln(CF3SO3)3‚xH2O
(Ln ) La, Nd, Eu, Gd, Tb, Lu, Y; 21 µmol) in acetonitrile (4 mL) was
added to a solution of L8‚0.5H2O (30 mg, 21 µmol) in dichloromethane
(4 mL). The resulting pale yellow mixture was evaporated to dryness.
The residue was dissolved in acetonitrile, and diethyl ether was added
to precipitate the complex. The resulting pale yellow powders were
collected by filtration and dried to give [Ca(L8)](CF3SO3)2‚3H2O and
[Ln(L8)](CF3SO3)3‚xH2O (Ln ) La, x ) 4; Ln ) Nd, x ) 4; Ln ) Eu,
x ) 4; Ln ) Gd, x ) 4; Ln ) Tb, x ) 3; Ln ) Lu, x ) 4; Ln ) Y,
x ) 2) in 69-94% yield. All the complexes gave satisfying elemental
analyses (Table S2, Supporting Information), ESI-MS and NMR spectra.
X-ray quality plates of [Eu(L8)](ClO4)3‚2CH3CN‚C2H5OH‚0.5H2O (20)
Spectroscopic and Analytical Measurements. Electronic spectra
in the UV-vis were recorded at 20 °C from solutions in CH3CN with
a Perkin-Elmer Lambda 900 spectrometer using quartz cells of 0.1 or
1 mm path length. Spectrophotometric titrations were performed with
a J&M diode array spectrometer (Tidas series) connected to an external
(40) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G.; Giacovazzo, C.;
Guagliardi, A.; Moliterni, G.; Polidori, G.; Spagna, R. J. Appl. Crystallogr.
1999, 32, 115-119.
(41) XTAL 3.2 User’s Manual; Hall, S. R., Flack, H. D., Stewart, J. M., Eds.;
Universities of Western Australia and Maryland, 1989.
(42) Johnson, C. K. ORTEP II; Report ORNL-5138; Oak Ridge National
Laboratory: Oak Ridge, Tennessee, 1976.
9
J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008 1039

A R T I C L E S
Canard et al.
computer. In a typical experiment, 25 mL of L8 (10-4 M) in CH3CN
+ 10-2 M (nBu)4NClO4 were titrated at 20 °C with a solution of Ca-
(CF3SO3)2‚0.5H2O or Ln(CF3SO3)3‚xH2O (10-3 M) in the same solvent
under an inert atmosphere. After each addition of 0.10 mL, the
absorbance was recorded using Hellma optrodes (optical path length
0.1 cm) immersed in the thermostated titration vessel and connected
to the spectrometer. Mathematical treatment of the spectrophotometric
data was performed with factor analysis43 and with the SPECFIT
program.28 1H and 13C NMR spectra were recorded at 25 °C on a Bruker
Avance 400 MHz spectrometer. Chemical shifts are given in ppm with
respect to TMS. Pneumatically assisted electrospray (ESI-MS) mass
spectra were recorded from 10-4 M solutions on a Finnigan SSQ7000
instrument. Elemental analyses were performed by Dr. H. Eder from
the microchemical Laboratory of the University of Geneva. Linear least-
square fits were performed with Excel.
going from Ln3+ to Ca2+ is responsible for the unexpected large
formation constant observed for [Ca(L8)]2+, despite the limited
electrostatic contribution brought by this bivalent cation. We
thus suspect that the complexation of Ca(II) in the cavity of
the podate [Ca(L8)]2+, while conserving C3-symmetry, is
significantly different from that evidenced with Ln(III). We were
however unable to obtain crystal structures with [Ca(L8)]2+
.
Based on this reasoning, we conclude that ceff is a crucial factor
for quantitatively estimating (i) the preorganization of the
receptor (either covalent or self-assembled) and (ii) its capicity
to selectively complex a specific cation. Its drastic decrease
related in the order Ca . La > Eu ≈ Lu indicates that the
receptor L8 has a preference for large cations, with a special
emphasis for Ca(II). On the other hand, its tighter wrapping
about Eu(III) or Lu(III) disfavors the intramolecular processes
to such an extent that competitive pathways, which minimize
intramolecular events, can be detected with the formation of
the polynuclear complexes [Ln2(L8)]6+ and [Ln3(L8)]9+. Since
our thermodynamic analysis is quite general in its essence, the
effective concentration ceff can be considered as an efficient tool
for estimating preorganization in any multicomponent assembly
process. The correlation between molecular design and ceff relies
on intuitions derived from previous work on flexible polymers,19
but no reliable concept can be currently proposed for its
programming in assembly processes involving semirigid com-
ponents. We however note that the use of flexible tripods
compatible with the structural “strain-free” wrapping of the
strands about the metal is misleading because the small entropic
gain is overcome by considerable enthalpic constraints, which
cannot be addressed in the analysis of the solid-state structures.
Thermodynamic investigations of related systems with shorter
and/or more rigid tripods are required to establish further trends
and to improve a rational chemical programming of preorga-
nization.
Conclusion
According to a structural point of view, the 25 synthetic steps
required for connecting three tridentate N3 binding units to a
“strain-free” flexible covalent tripod are fully justified by the
superimposable arrangements of the coordinated strands ob-
served in [Eu(L8)]3+ and [Eu(L9)3]3+. However, the latter
concept turned to be a disaster for the complexation of nine-
coordinate cations because of the very low effective concentra-
tions (10-7.6 e ceff e 10-4.8 for Ln ) La-Lu, Table 4), which
prevent efficient intramolecular coordination processes. These
values can be compared with ceff ) 10-0.8 reported for the
closely related but labile noncovalent tripod, promoting the
formation of the polynuclear Eu(III) triple-stranded helicates
[Eu3(L4)3]9+ and [Eu4(L5)3]12+ 22,33
Taking the preorganization
.
of the labile tripods in [Eu3(L4)3]9+ and [Eu4(L5)3]12+ as
reference, and assuming that both types of tripod (i.e., covalent
in L8 and noncovalent in the triple-stranded helicates) are flex-
ible enough to use a d-3/2 dependence of ceff on the distance,19
we predict on a pure entropic basis that ceff ) (10-0.8) ‚ (21/
18)-3/2 ) 10-0.9 for the intramolecular ring-closing reaction
operating in [Eu(L8)]3+ because the separation between two
N3 binding site connected by the labile tripod amounts to 2 ×
9 ) 18 Å in the triple-stranded helicates22,24 and to ca. 21 Å in
L8. The experimental value ceff e 10-7.3 is more than 6 orders
of magnitude smaller, which unambigously indicates that,
beyond obvious differences in the rigidity of the two types of
tripods, some severe enthalpic constraints prevent the efficient
complexation of Ln(III) in the final podate [Eu(L8)]3+. Interest-
ingly, the effective concentration observed in [Ca(L8)]2+ (ceff
) 10-1.6) fairly matches that predicted when the noncovalent
tripod of triple-standed helicate is used as a reference for
preorganization (ceff ) 10-0.9). This drastic increase of ceff in
Acknowledgment. We thank P. Ryan for graphical repre-
sentations of the complexes and P. Perrottet for carefully
recording ESI-MS spectra. Financial support from the Swiss
National Science Foundation is gratefully acknowledged.
Supporting Information Available: Data for structural and
spectroscopic analyses (Tables S1-S6 and Figures S2, S3, and
S5), for thermodynamic calculations (Table S7), and for
statistical factors (Figures S1 and S4). Crystallographic data for
the compound 20 in CIF format. This material is available free
of charge via the Internet at http://pubs.acs.org.
(43) Malinowski, E. R.; Howery, D. G. Factor Analysis in Chemistry; Wiley:
New York, Chichester, 1980.
JA0772290
9
1040 J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008