Pseudo-allosteric regulation of the anion binding affinity of a macrocyclic coordination complex

Article abstract of DOI:10.1039/b905150c

The anion binding affinity of a macrocyclic Rh complex can be allosterically regulated by reaction with a small molecule (an isocyanide), which effects a change in macrocycle size and shape. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b905150c

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Pseudo-allosteric regulation of the anion binding affinity of a macrocyclic
coordination complexw
Junpei Kuwabara,a Hyo Jae Yoon,a Chad A. Mirkin,*a Antonio G. DiPasqualeb
and Arnold L. Rheingoldb
Received (in Cambridge, UK) 13th March 2009, Accepted 4th June 2009
First published as an Advance Article on the web 19th June 2009
DOI: 10.1039/b905150c
The anion binding affinity of a macrocyclic Rh complex can be
allosterically regulated by reaction with a small molecule
(an isocyanide), which effects a change in macrocycle size
and shape.
To synthesize macrocycle 1, the new phosphinothioether
hemilabile ligand 5 was first prepared (Scheme 2). Ligand 5
was made in 75% yield by the reaction of 2,6-pyridinedi-
carbonyl dichloride and 4-(2-(diphenylphosphino)ethylthio)-
phenylamine9 in the presence of NEt3 in CH2Cl2. The reaction
of 5 with [Rh(nbd)2][B(C6F5)4] (nbd = norbornadiene) in
CH2Cl2 resulted in the formation of a cyclic dinuclear
Rh(I) complex 6a in 96% yield. Complex 6a exhibits a single
31P{1H} NMR resonance at d 65.1 (d, JRh–P = 162 Hz), which
is highly diagnostic of k2-P,S ligand coordination to Rh(I).3
The 1H NMR spectrum shows a single resonance for the
amide proton at d 9.50 and aromatic resonances similar to
those of the metal-free ligand, indicating a symmetric structure
in the solution-state (Fig. 1a and b). Electrospray ionization
mass spectrometry (ESI-MS) of 6a exhibits a parent ion at
908 m/z corresponding to the [M-2B(C6F5)4]2+ ion. Elemental
analysis of the complex also supports the proposed structure
(see ESIw). The solid-state structure of 6a was confirmed by a
single-crystal X-ray diffraction study (Fig. 2).z The Rh(I)
centers exhibit distorted-square-planar geometries with cis-S
and cis-P coordination environments. Four N–H protons are
directed to the center of the macrocycle, suitable for anion
binding. Reaction of the PS ligand with [Rh(nbd)2][BF4] and
[RhCl(CO)2]2 gave related complexes but with different
Recent advances in coordination chemistry have led to the
development of efficient synthetic methods for the selective
formation of two- and three-dimensional supramolecular
structures that exhibit new properties and functions, which
sometimes exceed what is possible with small molecule
systems.1,2 Our group has been developing the weak-link
approach (WLA) for the synthesis of supramolecular
complexes.3 The complexes made by the WLA are comprised
of hemilabile ligands and metal nodes, and they can be
chemically interconverted between rigid condensed structures
and larger open macrocycles via ligand substitution reactions
that, in the case of the condensed structures, displace the more
weakly coordinating functionality of the hemilabile ligands.
Using this approach, we have developed a variety of allosteric
compounds, which use small molecules to regulate catalytic
reactions, the formation of pseudo-rotaxanes, and enantiomer
recognition.4 Indeed, these structures have led to the first
examples of allosteric enzyme mimics based upon coordina-
tion chemistry complexes,4a and new concepts for amplified
chemical detection, where small molecules induce conforma-
tional changes, which trigger
generates a signaling agent.4a–c,f,g
a catalytic reaction that
Biological systems that employ ion channels often use
allosteric regulatory events to control the recognition and
transport of ions across membranes,5 yet extension of this
concept to man-made coordination-based systems is limited.6
This prompted us to consider how one might design a
coordination complex with anion binding properties7 that
can be allosterically controlled,8 1–4 (Scheme 1). Herein, we
describe the synthesis and characterization of one such
complex based upon a Rh(I) macrocycle 1 synthesized via
the WLA.
a Department of Chemistry and the International Institute for
Nanotechnology, Northwestern University, 2145 Sheridan Road,
Evanston, IL 60208-3113, USA.
E-mail: chadnano@northwestern.edu; Fax: +1 847 467 5123;
Tel: +1 847 467 7302
b Department of Chemistry and Biochemistry, University of California,
San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA
w Electronic supplementary information (ESI) available: Experimental
procedures and spectral data for all new compounds 5–8. CCDC
719264 and 719265. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/b905150c
Scheme
1
Schematic representation describing the strategy for
allosterically controlling the anion binding affinity of a macrocycle.
Reaction of the macrocycle with a small molecule (tBuCN) at a metal-
based regulatory site increases the macrocycle size and changes its
flexibility, leading to an increased affinity for chloride ions.
ꢀc
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Scheme 2 Syntheses of macrocyclic complexes via the WLA.
Fig. 3 ORTEP drawing of complex 7 with thermal ellipsoids drawn
at the 50% probability. Solvent molecules and hydrogen atoms except
for amide protons have been omitted for clarity. Selected bond distances
(A) and angles (1): Rh(1)–P(1) = 2.240(2), Rh(1)–P(2) = 2.240(2),
Rh(1)–S(1) = 2.364(2), Rh(1)–S(2) = 2.356(2), Rh(2)–P(3) = 2.245(2),
Rh(2)–P(4)
=
2.247(2), Rh(2)–S(3)
=
2.362(2), Rh(2)–S(4)
=
2.3414(2), N(1)–Cl(2)
=
3.404(4), N(1)*–Cl(2)
=
3.265(4),
N(2)–Cl(2) = 3.277(6), N(2)*–Cl(2) = 3.292(2), P(1)–Rh(1)–P(2) =
96.40(6), P(1)–Rh(1)–S(1) = 85.77(6), P(1)–Rh(1)–S(2) = 176.78(5),
P(2)–Rh(1)–S(1)
S(1)–Rh(1)–S(2)
P(3)–Rh(2)–S(3)
P(4)–Rh(2)–S(3)
=
=
=
=
168.80(5), P(2)–Rh(1)–S(2)
92.77(5), P(3)–Rh(2)–P(4)
85.48(5), P(3)–Rh(2)–S(4)
175.67(5), P(4)–Rh(2)–S(4)
=
=
85.58(5),
97.94(5),
171.00(5),
85.36(5),
=
=
S(3)–Rh(2)–S(4) = 90.87(5).
acceptor than B(C6F5)4ꢁ, the resonance for the amide N–H in
6b exhibits a downfield shift compared to that of 6a
(Fig. 1b and c). Fig. 1d shows the N–H resonance of 7 at
d 11.40 indicating strong hydrogen bonding between the amide
groups and Clꢁ. The solid-state structure of 7 was confirmed
by a single-crystal X-ray diffraction study (Fig. 3).z Interest-
ingly, there are dramatic differences in the overall shape of
7 and 6a, although the Rh(I) centers of 7 exhibit distorted-
square-planar geometries similar to the Rh(I) centers in 6a.
Significantly, one of the Clꢁ ions of 7 is located in the cavity of
the macrocycle, and the other is outersphere with no evidence
of a bonding interaction with the macrocycle. For the
complexed Clꢁ in 7, the average distance between the Cl atom
and the N atoms in the amide groups is 3.31 A, consistent with
a strong hydrogen bonding interaction between them. This
complexation of Clꢁ through hydrogen bonding is likely
responsible for the severe structural differences between 6a
(cyclic) and 7 (saddle shape). Typically, Clꢁ prefers a
tetrahedral geometry with its four lone pairs interacting with
four hydrogen donor groups,10 but, in the solid-state, the
crystal structure of 7 shows a pyramidal geometry with the
Clꢁ assuming the top position of the pyramid. This could
be due to the rigidity of the condensed macrocycle due to the
k2-P,S coordination at the Rh centers, which prevents the
complexation of Clꢁ in a manner that allows for a tetrahedral
coordination geometry.
Fig. 1 The aromatic and amide regions of the 1H NMR spectra for
5, 6a,b and 7 in CD2Cl2 (300 MHz, 23 1C, 10 mM), respectively.
Fig. 2 ORTEP drawing of complex 6a with thermal ellipsoids drawn
at 50% probability. Solvent molecules, counter anions and hydrogen
atoms except for amide protons have been omitted for clarity. Selected
bond distances (A) and angles (1): Rh(1)–P(1)
Rh(1)–P(2) 2.2437(8), Rh(1)–S(1) 2.3385(8), Rh(1)–S(2)
2.3394(7), P(1)–Rh(1)–P(2)* = 97.34(3), P(1)–Rh(1)–S(1) = 85.78(3),
P(1)–Rh(1)–S(2)* 172.63(3), P(2)*–Rh(1)–S(1) 175.06(3),
= 2.2449(8),
=
=
=
=
=
P(2)*–Rh(1)–S(2)* = 85.34(3), S(1)–Rh(1)–S(2)* = 92.02(3).
Condensed macrocycle 6a can be opened quantitatively into
t
a structurally flexible macrocycle 8 by reacting it with BuNC
in CH2Cl2 (Scheme 3). Complex 8 exhibits a single 31P{1H}
counter anions (6b and 7, respectively) in near-quantitative
yields (Scheme 2). Since BF4ꢁ is a stronger hydrogen bonding
ꢀc
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collection 1.241 to 25.001, R1 = 0.0622, wR2 = 0.1734, GOF = 1.150
[I 4 2s(I)]. CCDC 719265.
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Scheme 3 Binding affinity of Clꢁ in closed and open states.
NMR resonance at d 18.2, indicating k1-P,S coordination.3
Complexes with two or three isocyanides on each Rh(I) center
are possible products, but based upon 1H NMR spectroscopic
t
studies and integration of resonances associated with the Bu
groups, the tris-isocyanide structure can be ruled out. The
conclusion that there are two rather than three isocycanides
per Rh(I) center is also supported by elemental analysis. The
trans configuration of 8 can be confirmed based upon a
comparison with known simpler model complexes.11
Most interestingly, the Clꢁ association constants (Ka)12 of
6a and 8, measured in CH2Cl2 at 23 1C (Fig. S1 and S2 in
ESIw), are significantly different. The open macrocycle 8 has a
Ka (2.5 ꢂ 106 Mꢁ1) approximately two orders of magnitude
larger than the condensed macrocycle 6a (4.2 ꢂ 104 Mꢁ1
)
because of the conformational flexibility of 8 as compared with
6a, which allows it to adopt a more optimal geometry for
Clꢁ binding.
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In summary, we have synthesized a macrocyclic complex 6a
that can react with small molecules to induce a ring expansion,
which significantly increases its affinity for chloride ion
(60-fold increase). The expansion leads to greater conforma-
tional flexibility of the amide groups responsible for Clꢁ
binding, as evidenced by solid-state structures and solution
spectroscopic data.
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We gratefully acknowledge the NSF, ARO, AFOSR and
DDRE for financial support of this research. C.A.M. is
grateful for a NSSEF Fellowship.
Notes and references
z Crystallographic
details
for
6aꢃ5CH2Cl2;
8 T. Nabeshima, T. Saiki, J. Iwabuchi and S. Akine, J. Am. Chem.
Soc., 2005, 127, 5507.
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C147H92B2Cl10F40N6O4P4Rh2S4, M = 3600.33, yellow block, Bruker
Smart 1000 CCD (Mo Ka radiation), T = 100(2) K, triclinic,
ꢀ
spacegroup P1, a = 11.7786(7) A, b = 15.5130(9) A, c = 22.633(2)
A, a = 71.650(4)1, b = 75.085(3)1, g = 71.629(3)1, V = 3667.3(4) A3,
Z = 1, Dcalc = 1.630 g cmꢁ3, absorption coefficient 5.397 mmꢁ1
,
33 224 measured reflections, 13 013 independent reflections
[Rint = 0.0362], y range for data collection 4.021 to 68.261, R1 = 0.0421,
wR2 = 0.1018, GOF = 1.045 [I 4 2s(I)]. CCDC 719264.
Crystallographic details for 7ꢃ4CH2Cl2; C98H94Cl10N6O4P4Rh2S4,
M = 2232.23, yellow block, Bruker Smart 1000 CCD (Mo Ka
radiation),
17.477(5) A,
b = 110.518(4)1, V = 9729(4) A3, Z = 4, Dcalc = 1.524 g cmꢁ3
absorption coefficient 0.821 mmꢁ1
70 319 measured reflections,
17 150 independent reflections [Rint = 0.0506], y range for data
T
=
100(2) K, monoclinic, spacegroup P2(1)/c,
a
=
b
=
37.81(1) A, 15.719(4) A,
c =
,
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New York, 1987; (b) P. Kuzmic, Anal. Biochem., 1996, 237, 260;
(c) L. Fielding, Tetrahedron, 2000, 56, 6151.
,
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 4557–4559 | 4559