Narcissistic self-sorting of hydrogen-bonded dimeric capsules formed through self-assembly of flexible tripodal receptors in polar solvents

Article abstract of DOI:10.1039/c2cc33645f

Purely hydrogen-bonded dimeric capsule formation through self-sorting of three different tripodal receptors, having similar size and bearing the same functionality, through dynamic self-assembly in polar solvents is reported.

Full text of DOI:10.1039/c2cc33645f

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Narcissistic self-sorting of hydrogen-bonded dimeric capsules formed
through self-assembly of flexible tripodal receptors in polar solvents
Ashutosh S. Singh and Shih-Sheng Sun*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
50
Purely hydrogen-bonded dimeric capsule formation through
self-sorting of three different tripodal receptors having
similar size and bearing the same functionality have been
reported through dynamic self-assembly in polar solvents.
55
10 Controlled formation of discrete compartments with different
domains in response to external stimuli by artificial receptors
is of paramount significance to mimic biological
phenomenon1 and also to develop system chemistry2. Weak
intermolecular interactions provide primary tools to achieve
15 the self-sorting process through dynamic self-assembly with
good feasibilty and high fidelity.3 Several elegent examples of
H-bonded compartmentalization by self-sorting process have
been reported in literature by Böhmer,4 Isaacs,3a Rebek,5
Schalley,4b Sijbesma,6 and others.7 However, formation of
20 purely hydrogen-bonded discrete compartments by the self-
sorting process in a polar solvent is highly demanded yet a
challenging task due to the unfavorable competition from
solvation interactions.
60
65
Both urea4,8 and amide5,9 moieties have been explored in
25 non-polar solvents for the formation of a hydrogen-bonded
discrete entity through self-sorting phenomenon. In polar
solvents, these two moieties have been explored either with
the formation of gel10 or recently with the formation of
micelles.6 To the best of our knowledge, simple amide
30 functionality based discerete compartmentalization (or capsule
formation) in a mixture of competitive components through
self-sorting process is not known.
70 Fig 1. A schematic representation of receptors employed for studies (top)
and the topographical representation of binding patterns (bottom) in their
corresponding self-assembled capsules.
To explore the effect of substituents on N-terminal aromatic
ring, receptors 2 and 3 have been synthesized in a similar way
75 as reported previously11 and their identities were confirmed
by high-resolution electrospray ionization mass spectrometry
(HRESIMS) and NMR spectra (see supporting information).
1
The H NMR titration spectra of receptor 3 in a DMSO-d6
Herein, we report the first example of hydrogen-bonded
discrete compartmentalization of three flexible acyclic
35 tripodal receptors having similar size and shape incorporating
simple amide moieties on each branch with different
substituents at para positions of the N-terminal aromatic rings
(Fig. 1) in polar solvents. Previously, we have shown solvent
polarity dependent molecular capsule formation by receptor 1
40 through dynamic self-assembly where the nitro group at ortho
position of N-terminal aromatic ring is mandatory for the self-
assembled molecular capsule formation.11
solution with gradual addition of CDCl3 showed a similar
80 pattern of peak shifting as observed previously11 with receptor
1, indicative of the formation of homo-dimeric capsule (3.3).
However, a different binding mode was observed for the
1
formation of homodimer (2.2). The H NMR titration spectra
of receptor 2 in a DMSO-d6 solution with gradual addition of
85 CDCl3 showed a downfield shift of the meta C-H protons of
N-terminal aromatic rings (proton
f of receptor 2, see
Supplementary Information Fig. S16-S18). In receptor 2, a
nitro group at ortho position of the N-terminal aromatic ring
makes the meta position (ortho position with respect to the
90 nitro group) electron deficient and thus protons f in receptor 2
participate in the intermolecular hydrogen bonds. However,
electron donating groups at para position for receptors 1 and 3
render the ortho positions with respect to the amide groups of
__________________________________________________
Institute of Chemistry, Academia Sinica, 115 Nankang, Taipei, Taiwan,
45 Republic of China Fax: +011-886-2-27831237; Tel: +011-886-2-
27898596; E-mail:sssun@chem.sinica.edu.tw
† Electronic Supplementary Information (ESI) available: experimental
procedure, characterization data and titration spectra. See
DOI: 10.1039/b000000x/
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red color, Fig. S34) alomost merged to the parent spectra,
the N-terminal aromatic ring the most electron deficient and
thus protons h of receptors 1 and 3 are most susceptible to the
indicative of reversibility of capsule formation. The similar
intermolecular hydrogen bonding interactions to form the self- 65 observation noted upon titration of equimolar mixture solution
assembled homodimeric capsules (1.1 and 3.3). The self-
assembled homodimeric capsules were also observed by
gradual addition of either acetone-d6 or CD3NO2 into DMSO-
d6 solutions of receptors 1, 2 and 3, as confirmed by their
of receptors 1 and 2 in DMSO-d6 with gradual increasing
amount of acetone-d6 (Fig. 2). After partial evaporation of
acetone-d6, peaks of the resulting spectrum merged to the
original one. Similar observations noted in titration spectra of
5
corresponding titration spectra and positive mode HRESI 70 other two-component systems (receptors
mass spectra (Fig. S14-S15, S17-S18, and S20-S21). No receptors 2 with 3, see Fig. S35-S38).
1 with 3 and
10 solvent molecules were identified encapsulated in these self-
assembled homodimeric capsules as evidenced by HRESI
mass spectra. Evaporation of the volatile solvent from
solution mixture brought the spectrum back to the original one
recorded in DMSO-d6, which demonstrates the reversibilty of
15 capsule formation. These experiments suggested individual
dimeric capsule formation in their respective polar solvents
although their binding patterns along the seam of capsule are
different, which depends upon the electronic nature of N-
75
80
85
90
terminal aromatic ring (see Fig. 1 and Fig. S30).
20
25
30
35
Fig. 3 Three-component self-sorting: 1H NMR (400 MHz, 30 ºC) titration
spectra of receptors 1, 2 and 3 (in a 1:1:1 ratio, 6.25 mM each) in a
DMSO-d6 solution upon addition of varying amount of acetone-d6. After
partial evaporation of acetone-d6, the resulting spectra (in red color)
95 merged to the original one recorded in DMSO-d6. The color marks are
defined the same as those shown in Fig. 2.
The present studies were further elaborated for the three-
component system. An equimolar mixture of all the three
receptors 1, 2, and 3 in DMSO-d6 also showed well resolved
100 peaks for amide N-H and aromatic protons (Fig. 3 and Fig.
S39). Upon titration of DMSO-d6 solution containing a
mixture of the three receptors 1, 2 and 3 with gradual
increasing amount of CDCl3, a similar pattern of peak shifting
for amide N-Hs as well as for aromatic protons without
105 appearance for any new peaks observed (Fig. 3, top). After
partial evaporation of CDCl3, the resulting spectrum
essentially superimposed to the original one, indicative of the
reversible conversion of respective capsules in the mixture
solution. The smililar observations were also noted for
110 titrations carried out in polar solvents like acetone-d6 (Fig. 2,
bottom).
1
Fig. 2 Two-component self-sorting: H NMR (400 MHz, 30 ºC) titration
spectra of receptors 1 and 2 in a 1:1 ratio (6.25 mM each) in a DMSO-d6
40 solution upon addition of varying amount of acetone-d6. After partial
evaporation of acetone-d6, the resulting spectra (in red color) merged to
the original one recorded in DMSO-d6. Star marks in green and red colors
in spectra represent peaks for DMSO-d6 solvent and from internal
reference in TMS, respectively. Circle marks in green and red colors
45 represent the residual water peaks from deuterated solvents.
Inspired from these results, we envisaged the possiblity of
co-existence of both types of capsules in the same mixture
1
solution with a self-sorting behavior. The H NMR spectra of
an equimolar mixture solution (6.25 mM) of receptors 1 and 2
50 as well as an equimolar mixture solution (6.25 mM) of
receptors 2 and 3 in DMSO-d6 displayed well resolved peaks
for amide N-Hs and aromatic protons (see Fig. 2 and Fig. S31-
S32). A similar observation was noted for an equimolar
mixture solution of receptors 1 and 3 (Fig. S33). Upon
55 titration of the DMSO-d6 mixture solution of receptors 1 and 2
with CDCl3 (Fig. S34), the peaks for amide N-H protons and
aromatic proton h of receptor 1 and proton f of receptor 2,
respectively, responsible for hydrogen bonding along the seam
of capsules 1.1 and 2.2, shifted downfield in a similar way to
60 their individual solutions (see Fig. S13 and S16) without
appearance of any new peak. After partial evaporation of
CDCl3, the corresponding peak of resulting spectra (shown in
The affinity for self-recognition (narcissistic self-
sorting)3b,12 between the individual receptor components is
remarkable. The titration spectra showed no appearance of
115 any new peak and the patterns of peak shifting were similar to
that of an equimolar mixture in both CDCl3 (Fig. 4 and S41)
and acetone-d6 (Fig. S40-S41) even with increasing one
component to five-fold excess. Furthermore, after partial
evaporation of CDCl3 or acetone-d6, the resulting spectra
120 merged to that of original ones, showing hydrogen-bonded
self-assembled capsule formation through narcissistic self-
sorting process with high fidelity in a polar solvent.
In conclusion, in contrast to the basic molecular recognition
codes (size and shape) generally reported for self-sorting
2
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process,3b we have disclosed unique examples of narcissistic
self-sorting by highly flexible acyclic tripods possessing
similar size and shape with the same functionality appended
on each branch. Both receptors 1 and 3 having electron
donating groups on N-terminal aromatic rings and the same
binding motifs for seaming along the curvature for self-
assembled capsule formation, The degree of electron donating
ability (intrinsic information coded in the molecule) of these
receptors that results in different binding modes of the
5
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capsule formation can be expressed with high fidelity in polar
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present approach and the related research is currently
15 underway for detail studies.
8
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Fig. 4 Three-component self-sorting: 1H NMR (400 MHz, 30 ºC) titration
spectra of receptors 1, (31.3 mM) 2 (6.25 mM) and 3 (6.25 mM) in a
35 DMSO-d6 solution upon addition of varying amount of CDCl3. After
partial evaporation of CDCl3, the resulting spectrum (in red color) merged
to that of original one recorded in DMSO-d6. The color marks are defined
the same as those shown in Fig. 2.
40
We are grateful to the National Council of Taiwan (Grant
No 100-2628-M-001-002-MY3) and Academia Sinica for
support of this research. A.S.S. thanks the postdoctoral
fellowship sponsored by the National Science Council of
Taiwan (Grant No 100-2811-M-001-090). Mass spectrometry
45 analyses were performed by Mass Spectrometry facility of the
Institute of Chemistry, Academia Sinica.
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