An AAAA-DDDD quadruple hydrogen-bond array

Article abstract of DOI:10.1038/nchem.987

Secondary electrostatic interactions between adjacent hydrogen bonds can have a significant effect on the stability of a supramolecular complex. In theory, the binding strength should be maximized if all the hydrogen-bond donors (D) are on one component and all the hydrogen-bond acceptors (A) are on the other. Here, we describe a readily accessible AAAA-DDDD quadruple hydrogen-bonding array that exhibits exceptionally strong binding for a small-molecule hydrogen-bonded complex in a range of different solvents (K _a>3 × 10¹² M^-1 in CH ₂Cl₂, 1.5 × 10⁶ M^-1 in CH ₃CN and 3.4 × 10⁵ M^-1 in 10% v/v DMSO/CHCl₃). The association constant in CH₂Cl₂ corresponds to a binding free energy (ΔG) in excess of -71 kJ mol ^-1 (more than 20% of the thermodynamic stability of a carbon-carbon covalent bond), which is remarkable for a supramolecular complex held together by just four intercomponent hydrogen bonds.

Full text of DOI:10.1038/nchem.987

ARTICLES
PUBLISHED ONLINE: 21 FEBRUARY 2011 | DOI: 10.1038/NCHEM.987
An AAAA–DDDD quadruple hydrogen-bond array
1
2
1
1†
1
Barry A. Blight , Christopher A. Hunter , David A. Leigh , Hamish McNab and Patrick I. T. Thomson
*
Secondary electrostatic interactions between adjacent hydrogen bonds can have a significant effect on the stability of
a supramolecular complex. In theory, the binding strength should be maximized if all the hydrogen-bond donors (D)
are on one component and all the hydrogen-bond acceptors (A) are on the other. Here, we describe a readily
accessible AAAA–DDDD quadruple hydrogen-bonding array that exhibits exceptionally strong binding for a small-
1
2
–1
6
–1
molecule hydrogen-bonded complex in a range of different solvents (K > 3 3 10
M
CH CN and 3.4 3 10 M in 10% v/v DMSO/CHCl ). The association constant in CH Cl corresponds to a binding
in CH Cl , 1.5 3 10 M in
a
2 2
5
–1
3
3
2
2
–
1
free energy (DG) in excess of –71 kJ mol (more than 20% of the thermodynamic stability of a carbon–carbon
covalent bond), which is remarkable for a supramolecular complex held together by just four intercomponent
hydrogen bonds.
ultipoint hydrogen-bonding motifs are the cornerstone Results and discussion
of recognition processes in biology and are increasingly Synthesis of 12 and 13. The quadruple hydrogen-bond donor (12)
M
featuring in the design of multifunctional materials and and acceptor (13) units were each synthesized in three steps from
supramolecular polymers . In 1990, Jorgensen suggested that commercially available starting materials (Fig. 3). The DDDD
1
–5
þ
secondary electrostatic interactions play an important role in component 12 was assembled from 2-aminobenzimidazole 14 via
6
the stability of arrays of contiguous hydrogen bonds (Fig. 1) . formation of thiourea 15 (CS , pyridine, 130 8C, 18 h, 81%),
2
A corollary of this is that having all the hydrogen-bond donor
groups (D) in one partner and all the hydrogen-bond acceptor
ADA–DAD
C6H11
ADD–DAA
O
sites (A) in the other should be the arrangement that produces
the strongest binding, because all secondary electrostatic inter-
actions between neighbouring hydrogen-bond pairs are attrac-
tive. Although the significance of this effect has been
questioned based on the results of quantum-mechanical calcu-
Br
O
N
Br
1
2
3
O
N
H
N
H
N
N
H
N
H
N
4
H
N
H
N
N
O
7
lations on DNA base pairs , it accounts well for the general exper-
H
H
H
N
C6H5
imental trends found for triple hydrogen-bonded complexes
N
(
typical complex stability ADA–DAD , ADD–DAA , AAA–
N
Ph
8
–14
DDD)
and can be used quantitatively in empirical methods
Et
8
,15
Ka = 5.5 x 102 M–1
Ka = 2 x 104 M–1
(CDCl3, 1H NMR)10
for predicting complex stabilities
.
(
CHCl3, IR)9
The experimental trends are less clear cut for quadruple hydro-
.
.
AAA–DDD+
gen-bond complexes (see, for example, 9 9 and 10 11, Fig. 2).
However, there are far fewer examples of such arrays, and with a
small sample set it is difficult to separate the contribution of
the arrangement of the hydrogen-bond pairs from other factors
that contribute to complex stability, such as the hydrogen-bond
AAA–DDD
NO2
CF3
CF3
–
BArF–
B
=
EtO
O
OEt
O
H
4
...
acidity/basicity of the functional groups, additional CH O/N or
multipole interactions, entropy effects, solvation, tautomerism and
the strength of homodimerization of each partner. Indeed, of the
H
N
H
H
N
H
H
N
H
N
H
N
N
H
5
6
7
6
H
H
N
N
N
N
N
N
1
6–27
six possible quadruple hydrogen-bond permutations
, only
three have been definitively experimentally realized to date:
.
16
ADAD–DADA (for example, 8 8) , AADD–DDAA (for example,
.
17–21
.
22–24
9
9)
and ADDA–DAAD (for example, 10 11)
(Fig. 2). The
Ka = 2 x 107 M-1
(CH Cl , fluorescence)
Ka = 3 x 1010 M–1
AAAD–DDDA motif remains experimentally unexplored. Claims
for an ADAA–DADD (ref. 25) and a cationic AAAA–DDDD
1
3
14
þ
2 2
(CH Cl , fluorescence)
2
2
(
ref. 26) complex have been made, but both have anomalously low
Secondary electrostatic interactions:attractive
, repulsive
21
21
stability constants (K ¼ 590 M and 530 M in CDCl , respect-
a
3
ively) as a result of intramolecular hydrogen bonding that Figure 1 | Examples of triple hydrogen-bond arrays and their association
favours rotamers that do not correspond to the desired hydrogen- constants in various solvents. Different permutations of contiguous triple
.
.
bonding array (see Supplementary Information). Here we report hydrogen-bonded complexes ADA–DAD 1 2 (ref. 9), ADD–DAA 3 4
þ
þ
.
.
.
on a readily accessible AAAA–DDDD complex 12 13 that exhibits (ref. 10), AAA–DDD 5 6 (ref. 13) and cationic AAA–DDD 7 6 (ref. 14).
exceptional complex stability even in hydrogen-bond-disrupting Arrows indicate secondary electrostatic interactions (black, attractive; red,
solvent systems.
repulsive).
1
2
School of Chemistry, University of Edinburgh, The King’s Buildings, West Mains Road, Edinburgh EH9 3JJ, UK, Department of Chemistry, University of
†
Sheffield, Sheffield S3 7HF, UK; Deceased. *e-mail: david.leigh@ed.ac.uk
244
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NATURE CHEMISTRY DOI: 10.1038/NCHEM.987
ARTICLES
ADAD–DADA
R
AADD–DDAA
ADDA–DAAD
AAAA–DDDD+
BArF–
R'
N
N
H
4
C H
H
N
O
H
H
H
C4H9
O
9
N
N
N
N
N
N
N
O
N
N
N
N
H
C4H9
N
H
N
N
H
O
N
N
H
N
H
O
N
H
N
10
N
H
N
H
N
H
N
H
12
13
H
8
H
8
9 9
H
N
H
N
H
N
H
N
H
N
O
N
N
N
O
C4H9
N
N
C4H9
N
N
N
N
H
C4H9
11
O
N
O
O
C4H9
H
H
R
Ka = 1.9×104 M–1
CDCl3, 1H NMR)16
Ka = 6.0×107 M–1
Ka = 3.0×108 M–1
(CHCl3, fluorescence)23
tBu
tBu
17,18
Ka > 3×1012 M–1
(
(CH Cl , fluorescence)
2
2
Ka = 1.7 x 102 M–1
CDCl3/DMSO-d6 90:10, 1H NMR)20
(CH2Cl2, UV/vis competition expts)
Ka = 1.5×106 M–1(CH3CN, UV/vis)
Ka = 3.4×105 M–1
(
(
CDCl3/DMSO-d6 90:10, 1H NMR)
Figure 2 | Examples of quadruple hydrogen-bond arrays and their association constants in various solvents. Different permutations of contiguous
þ
.
.
.
quadruple hydrogen-bonded complexes: ADAD–DADA 8 8 (ref. 16), AADD–DDAA 9 9 (refs 17,18,20), ADDA–DAAD 10 11 (ref. 23) and AAAA–DDDD
.
1
2 13. Arrows indicate secondary electrostatic interactions (black, attractive; red, repulsive).
a
conversion to guanidine 16 (HgO, NH /MeOH, CHCl , 25 8C,
H
N
3
3
i
NH
S
HN
3
8
h, 50%), followed by protonation and ion-exchange (NaBArF,
NH2
M AcOH, 25 8C, 2 h, 40%) to the weakly coordinating
N
N
N
H
N
N
2
2
[B(3,5-(CF ) C H ) ] (BArF ) anion. The AAAA partner, 13, was
H
3
2 6 3 4
14
15
synthesized from 2,7-diamino-1,8-naphthyridine 17 via a double
bromination with N-bromosuccinimide (NBS) to afford 18 (NBS,
DMF (dimethylformamide), –10 to 25 8C, 3 h, 60%), followed by a
ii
one-pot
double
Suzuki
coupling–cyclization–aromatization
procedure1 with boronic acid 19.
3,14
H
H
N
N
N
þ
.
Characterization of complex 12 13. The DDDD component 12
has two intramolecular hydrogen bonds to help stabilize
tautomers that present three or four hydrogen-bond donors along
N
N
H
N
H
N
H
1
6
′
one edge of the molecule (12 and 12 , Fig. 3). The cationic charge
iii
should increase the donor strength of the hydrogen-bonding
groups compared to neutral systems1 . The AAAA unit 13 is a
hexacene system intended to improve its chemical stability
compared to underivatized linear arrays of pyridine rings linked
2,14
H
+ H
N
–
N
–
BArF
+
N
H
N
H
NH
NH
H
H
11,12
through their 2,3/4,5 edges . UV/vis titration of 13 with 12 in
N
N
N
2
5
N
CH Cl (ꢀ5 × 10 M) showed a decrease in the absorption
2
2
BArF
N
H
N
H
N
H
N
H
spectrum of 13 (l ¼ 426 nm) accompanied by the appearance
max
12'
of a new species bathochromically shifted by 11 nm (Fig. 4). The
complex was characterized by electrospray ionization mass
12
þ
.
spectrometry (ESI-MS) ([12 13] m/z ¼ 736.44; Supplementary
1
Fig. S7) and
H
NMR (nuclear magnetic resonance)
b
Br
Br
i
spectroscopy (Fig. 5). Particularly noteworthy are the large
downfield shifts (up to 10 ppm) of the NH protons of 12 upon
complex formation with 13, and the upfield shifts of the
benzimidazole CH protons as the NH bonds become more
polarized through hydrogen bonding. The broad NH signals in
free 12 may be a consequence of the interconversion of the
tautomers shown in Fig. 3 (ref. 28). In contrast, well-resolved
1
8
H2N
N
N
NH2
H2N
N
N
NH2
1
7
tBu
tBu
tBu
tBu
13
signals for three different types of NH protons (H ) are observed
ii
iii
abc
þ
.
in the spectrum of 12 13, as expected for the DDDD tautomer of
2. Rotating frame Overhauser effect spectroscopy (ROESY)
B(OH)2
1
N
N
N
N
experiments showed through-space interactions between the HC
20
19
O
O
protons of 13 and the H protons of 12 (Supplementary Fig. S4).
d
1
Figure 3 | Synthetic routes to DDDD 12 and AAAA 13. a,b, Synthesis of
1
þ
–
Spectroscopic evaluation of the stability of AAAA–DDDD
DDDD 12 (BArF salt) (a) and AAAA 13 (b). Reagents and conditions
.
complex 12 13 in dichloromethane. The binding constant of for a: (i) CS , pyridine, 130 8C, 18 h, 81%; (ii) HgO, NH /MeOH, CHCl
2 13 proved too strong to be measured directly by UV/vis or H 25 8C, 3 h, 50%; (iii) NaBArF, 8 M AcOH, 25 8C, 2 h, 40%. Reagents
2
3
3
1
.
1
NMR titrations (these methods are generally only useful for and conditions for b: (i) NBS, DMF, –10 to 25 8C, 3 h, 60%;
5
21 29
binding constants up to ꢀ1 × 10 M ) , and 13 proved (ii) NHCH (CH CH )N(CH ) , BuLi then B(OMe) , THF, –78 to 25 8C, 16 h,
3
2
2
3 2
3
photochemically unstable at the high light intensities required to 36%; (iii) Na CO , H O/DME (dimethoxyethane) 1:1, 80 8C, 1.5 h, 27%.
2
3
2
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NATURE CHEMISTRY DOI: 10.1038/NCHEM.987
ARTICLES
1
.
Complex stability of AAAA–DDD complex 12 13 in other
1
3
1
1
0
0
.6
.2
.8
.4
0
1
2·13
solvent systems. Solvent competition for hydrogen-bonding sites
can dramatically influence complex stability. If the thermodynamic
contributions of individual hydrogen bonds in a multiply hydrogen-
bonded complex are assumed to be additive in free energy, the
magnitude of the expected solvent effects can be estimated using
3
0
Hunter’s hydrogen bond parameters in conjunction with the
following equation:
ꢀ
0
−1
DG = −
(a − a )(b − b ) + 6 kJ mol
(1)
i
S
i
S
i
3
90
410
430
450
470
490
510
Wavelength (nm)
where a and b are the hydrogen-bond parameters of the solvent, a
i
S
S
1
and b are the hydrogen-bond parameters for the solute interaction
i
21
Figure 4 | UV/Vis titration of AAAA 13 with DDDD 12 in CH Cl . UV/vis
2
2
25
sites, the sum is over all solute–solute interactions, and 6 kJ mol
spectra of 13 (ꢀ5 × 10 M) on addition of 12 (0 ꢁ 5 equiv.), maintaining
is a constant representing the cost of forming a bimolecular
complex in solution.
If we assume that all the hydrogen-bond donor sites on 12 and 7
are similar and comparable to other ammonium and guanidinium
the concentration of 13 constant, in CH Cl at 298 K. Changes in
2
2
.
absorbance reflect changes in the amount of 13 and 12 13 present during the
titration experiment and differences in their UV/vis absorption spectra.
measure changes in fluorescence at low concentrations (ꢀ1 × cation hydrogen-bond donors that have been characterized exper-
2
10
10
M). Therefore competition experiments were performed in imentally (C.A. Hunter et al., unpublished results), it is possible
.
.
.
CH Cl to compare the association constant for 12 13 to that of to estimate stability constants for the 7 6 and 12 13 complexes in
2
2
þ
.
.
known complex AAA–DDD 7 6. Complex 7 6 was titrated with dichloromethane and in acetonitrile from equation (1) (see
1
1
1
2 (followed by changes in the UV/vis spectrum) to give K ¼ Supplementary Information). The calculated values in dichloro-
a
1
0
21
21
þ
9
21
13
21
× 10
M
(DG ¼ –57.1 kJ mol ) for AAA–DDDD complex methane, 4 × 10 M and 2 × 10
M
for three and four hydro-
10
21
.
.
2 6, slightly less than that of 7 6 (K ¼ 3 × 10
M ), probably gen bonds, respectively, are consistent with the experimental
a
þ
as a result of the guanidinium DDDD unit being less hydrogen- measurements. Changing the solvent to acetonitrile, a solvent in
bond acidic than the pyridinium DDD species. Density function which the strength of solute–solute interactions are significantly
calculations (B3LYP, 6-31G*, see Supplementary Information) reduced , lowers the stability constants estimated using equation
þ
3
0
3
21
4
21
carried out on 7 and 12 revealed that the pyridinium NH of 7 (1) to 2 × 10 M and 4 × 10 M , respectively.
2
carries the largest positive partial charge (þ667 kJ mol ),
1
þ
.
UV/vis titration of AAA–DDD complex 7 6 gave K ¼ 5.4 ×
a
3
21
21
whereas its amino-protons carry an electrostatic potential of 10 M (DG ¼ –21.3 kJ mol ) in CH CN, far less than the K of
3
a
2
1
10 21
þ605 kJ mol
.
In 12, the guanidinium protons have an 3.0 × 10
M
in CH Cl and in good agreement with the value
2 2
21
electrostatic potential of þ660 kJ mol
and the benzimidazole estimated from equation (1). During the titration of 13 with 12
21
NH protons þ565 kJ mol . (Note also that 12 may bind to the (Fig. 7a), in addition to the 1:1 complex a 2:1 binding mode was
þ
AAA system to a significant extent as the alternative DDD
also observed (confirmed by a Job plot; see Supplementary
′
.
.
.
tautomer 12 , shown in black in Fig. 3.)
Information). The complex stabilities of 12 13 and 13 (12 13) were
6
21
21
.
A UV/vis titration of 12 6 with 13 gave a lower limit for the K of determined to be K
¼ 1.5 × 10 M
(DG ¼ –35.2 kJ mol
)
a
12·13
1
1
21
.
.
1
2 13 of 1 × 10
M
(the experiment being complicated by 1:1 and (280× stronger than 7 6 and 50× stronger than the value estimated
.
2:1 complexes of 12 13 and the overlapping absorption spectra of 6 from equation (1)) and, for the second binding event, K
¼
1
3·(12·13)
5
21
21
.
.
and 13). The reverse UV/vis experiment was also performed (titrating 2.4 × 10 M (DG ¼ –30.6 kJ mol ). The formation of 13 (12 13)
þ
.
AAAA–DDDD 12 13 with a large excess of AAA 6 to liberate 13) to is probably due to favourable electrostatic interactions between 13
1
.
.
determine the stability of 12 13 at high concentrations of 6 (Fig. 6). and 12 13. A H NMR dilution experiment of 13 revealed a small
Free 13 began appearing above a threshold of 350 equiv. of 6, p-stacking component (Kdim , 100 M
21
;
see Supplementary
12
21
21
indicating a K of .3 × 10
M
(DG , –71 kJ mol ) for AAAA– Information), suggesting that there may be some reinforcing effect
a
þ
.
.
.
DDDD 12 13 in CH Cl .
that biases the formation of 13 (12 13) until equimolar
2
2
–
2
CD Cl2
d,g
CF3
h
h
e,f
i
B
i
abc
12
CF3
4
F
g
f
abc
H
H
e
N
N
N
h i
D E
d
B
N
N
H
N
H
N
H
C
B
1
1
2
3
A
H
abc
abc
abc
Complex 12·13
abc abc
d e f g
F
N
N
N
N
C
A
C
E D
8
E
13
A
B
D
tBu
tBu
16
15
14
13
12
11
10
9
7
6
5
4
3
2
F
Chemical shift (ppm)
1
.
Figure 5 | H NMR spectra (500 MHz, CD Cl , 298 K) of 12 (top), complex 12 13 (middle) and 13 (bottom). Dashed lines show the changes in chemical
2
2
.
shift of the resonances in 12 and 13 on formation of complex 12 13.
246
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NATURE CHEMISTRY DOI: 10.1038/NCHEM.987
ARTICLES
0.2
acceptor unit present in 13), so moderation of the stability of the
þ
AAAA–DDDD
complex is as expected. Dimethylsulfoxide
(
DMSO) is an even stronger hydrogen-bond acceptor than pyridine
Free 13
0
.15
9
3
0
40 equiv. of 6
50 equiv. of 6
equiv. of 6
and so might be anticipated to eliminate binding entirely. This
is the case in pure DMSO, but the AAAA–DDDD complex
proved remarkably stable in a solution of 10% DMSO in CHCl
þ
0.1
3
5
21
21
(K
¼ 3.4 × 10 M
(DG ¼ –31.6 kJ mol ); K
¼ 1.4 ×
1
2·13
13·(12·13)
5
21
21
1
0 M
(DG ¼ –29.4 kJ mol ); see Fig. 7b and Supplementary
0
.05
0
Figs S31–S35 for spectra and analysis), despite being held together
by only four intercomponent NH N hydrogen bonds. By way of com-
parison with other quadruple hydrogen-bonded systems, Meijer and
colleagues have reported studies on the tautomerization of 9 9 in
CDCl /DMSO-d mixtures . They determined the complex dimeriza-
...
.
4
00
425
450
475
500
525
2
0
Wavelength (nm)
3
6
.
tion constant (Kdim*) for 9 9 (equivalent to the product of the K of a
dim
Figure 6 | UV/vis competition experiment in which 13 is displaced from
2
7
single tautomer of 9 and the square of the tautomeric equilibrium
constant (K ) and slightly underestimates K ) to be ꢀ1.7 ×
.
.
1
2 13 by a large excess of 6. UV/vis spectra of 12 13 (ꢀ2 × 10 M)
taut
dim
following addition of 6 (0 ꢁ 950 equiv., 50 equiv. aliquots) in CH Cl at
2
21
21
2
2
1
0 M
(DG ¼ –12.8 kJ mol ) in 10% DMSO-d6 in CDCl
21
3
2
98 K. Spectra at 0 equiv. (blue), 350 equiv. (green) and 940 equiv.
21
31
(
3
ꢀ50 M in neat DMSO) . Zimmerman has reported a K of
a
(
orange) of added 6 are shown with thicker linewidths for clarity. For
3
21
.0 × 10 M
(DG ¼ –19.9 kJ mol
)
for an ADDA–DAAD
comparison, the spectrum of free 13 (black) is also shown.
complex in 5% DMSO-d in CDCl (ref. 22).
6
3
þ
.
The unexpected stability of the AAAA–DDDD complex 12 13
in very polar solvent systems such as DMSO/chloroform and, to a
lesser extent, acetonitrile, may be a result of poor solvation of the
uncomplexed components. In particular, the high density of inter-
action sites in 12, in either tautomer, may make it difficult to
a
6
–1
Component distribution
K12·13 =1.5×10 M
0
0
0
0
0
0
.6
.5
.4
.3
.2
.1
0
5
–1
K13·(12·13) =2.4×10 M
0.6
0.4
13
12
12·13
13
0
.2
13·(12·13)
þ
solvate the uncomplexed DDDD partner effectively. Closely
1
2·13
0
0
1
2
3
packed solvent heteroatoms around the hydrogen-bond donor sol-
vation sites would strongly repel each other. Such ineffective sol-
vation of free hosts or guests is reminiscent of the increase in
binding strength found using bulky solvents and in systems with
restricted space .
Equiv. of 12
3
2
3
3
390
410
430
450
470
490
510
Conclusions
Wavelength (nm)
þ
.
The AAAA–DDDD quadruple hydrogen-bond complex 12 13
exhibits exceptional complex stability for a small-molecule hydro-
b
12
21
5
–1
Component distribution
gen-bond array in a range of solvent systems (K . 3 × 10
M
K12·13 =3.4×10 M
a
6
21
5
21
0
0
0
0
0
0
.6
5
–1
in CH Cl , 1.5 × 10 M in CH CN and 3.4 × 10 M in 10%
K13·(12·13) =1.4×10 M
0.6
0.4
0.2
0
2
2
3
13
1
2
DMSO/CHCl ). Although the photostability of 13 may be a
3
.5
.4
.3
.2
.1
0
12·13
1
3
12·13
13·(12·13)
concern for applications with intense light sources, the strength of
binding and ease of synthesis of each partner of the AAAA–
12·13
þ
DDDD hydrogen-bond motif makes it a promising candidate
0
1
2
3
Equiv. of 12
for incorporation into supramolecular polymers and other
functional materials.
13
Methods
Synthesis, characterization and spectroscopic information for all compounds and
the details of the UV/vis titration experiments can be found in the Supplementary
Information.
3
90
410
430
450
470
490
510
Wavelength (nm)
Figure 7 | UV/vis titration experiments in which K12·13
and K
13·(12·13)
are
Description of UV/vis titration experiments. UV/vis experiments were performed
on a Varian Cary Bio-50 UV/vis spectrometer. Glass-distilled solvents were used
throughout. Absolute concentrations for each component of a titration experiment
were determined by standard calibration curves, and appropriate aliquots added
relative to the determined concentrations. All titration experiments with acceptor
measured by addition of 12 to 13 in CH CN or 10% DMSO in CHCl .
3
3
26
a, UV/vis spectra of 13 (ꢀ8 × 10 M) following addition of 12 (0 ꢁ
5
2
equiv.), while maintaining the concentration of 13 constant, in CH CN at
3
98 K. Component distribution over the course of the titration experiment is
(
A) as the host species were performed with a background concentration of acceptor
.
also illustrated (inset). Association constants for 12 13, modelled with a 2:1
in the guest solution so as to maintain a constant concentration of host species.
Aliquot injections were carried out with Hamilton microsyringes into a quartz
cuvette (cuvette size was dependent on concentrations used: 2 mm, 1 cm or 5 cm
cells) with a Teflon stopper. Spectrometer settings varied depending on the
absorbance and concentrations of the components and can be found for each
titration experiment in the Supplementary Information. Spectral analyses were
6
21
21
.
equilibrium, are K1 ¼ 1.5 × 10 M (DG ¼ –35.2 kJ mol ) for 12 13 and
2·13
5
21
21
K1
¼ 2.4 × 10 M (DG ¼ –30.6 kJ mol ) for the binding of a
3·(12·13)
. .
second AAAA unit to this complex to form 13 (12 13). b, UV/vis spectra of
25
1
3 (ꢀ1 × 10 M) following addition of 12 (0 ꢁ 4.5 equiv.), while
maintaining the concentration of 13 constant, in a solution of 10% DMSO
TM
performed using the ReactLab Equilibria spectral analyses suite (Jplus Consulting,
5
21
in CHCl at 298 K. Association constants are K
¼ 3.4 × 10 M
www.jplusconsulting.com). Repetitions of the binding experiments for each
complex gave association constants within 15% of the values shown, except for
3
12·13
21
5
21
21
(DG ¼ –31.6 kJ mol ) and K1
¼ 1.4 × 10 M (DG ¼ –29.4 kJ mol ).
3·(12·13)
.
the analysis of 12 13, which deviated by 18% (the error in data fitting for each
concentrations of the components are established during the course of experiment was ,5%).
the titration.
Acetonitrile is a stronger hydrogen-bond acceptor than dichloro- Received 27 August 2010; accepted 13 January 2011;
methane, but a weaker acceptor than a pyridine nitrogen (the basic published online 21 February 2011
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247
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2011 Macmillan Publishers Limited. All rights reserved.

NATURE CHEMISTRY DOI: 10.1038/NCHEM.987
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Author contributions
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Additional information
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The authors declare no competing financial interests. Supplementary information and
chemical compound information accompany this paper at www.nature.com/
naturechemistry. Reprints and permission information is available online at http://npg.nature.
com/reprintsandpermissions/. Correspondence and requests for materials should be
addressed to D.A.L.
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