The impact of metal coordination on the assembly of bis(indolyl)methane-naphthalene-diimide amphiphiles

Article abstract of DOI:10.1039/d0dt02732d

The self-assembly and coordination of amphiphiles comprised of naphthalenediimide (NDI) and bis(indolyl)methane (BIM) chromophores were investigated as a function of pH and metal. As observed by TEM, SEM and AFM imaging, the self-assembly of NDI-BIM 1 pro

Full text of DOI:10.1039/d0dt02732d

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PAPER
The impact of metal coordination on the assembly of
bis(indolyl)methane-naphthalene-diimide amphiphiles
Sinan Bayindir,a Kwang Soo-Lee,b Nurullah Saracoglu,*c and Jon R. Parquette*b
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
The self-assembly and coordination of amphiphiles comprised of naphthalenediimide (NDI) and
bis(indolyl)methane (BIM) chromophores were investigated as a function of pH and metal. As observed by
TEM, SEM and AFM imaging, the self-assembly of NDI-BIM 1 produced irregular nanostructures at neutral pH
in CH3CN-H2O (1:1); whereas, well-defined nanotubes were observed at pH 2. Conversely, Fmoc-protected,
NDI-BIM 2 formed nanotubes at neutral pH and nonspecific aggregates at pH 2. Upon coordination of Cu2+ ions
to the bis(indoyl)methane moiety, a reorganization from nanotubes to vesicular structures was observed.
Introduction
create metal-binding nanostructure precursors, monomers 1
and 2 were comprised of bis(indolyl)methane (BIM), as the
The development of reliable strategies to create metal recognition site; 1,4,5,8-naphthalenetetracarboxylic acid
multifunctional soft materials via the self-assembly of small diimide (NDI), to drive assembly by  interactions; and a
molecules has enabled a wide range of applications in charged L-lysine head group to impart amphiphilicity (Fig 1). We
optoelectronics,1,2 biomaterials3-5, sensing, and drug delivery,6 reasoned that the amphiphilicity created by the juxtaposition of
inter alia.7 The potential for these materials to display the NDI/BIM segments on one end with the polar lysine
adaptivity, self-healing, and other forms of “intelligent” headgroup on the other would efficiently drive the assembly
behavior would be enhanced by the capability to transition process in water.
between multiple states.8 Methods to dynamically modulate
their structural features via external triggers are currently of
tremendous interest.9,10 Molecules, termed “molecular
switches,”11,12
that
interconvert
between
multiple
configurational states upon irradiation13 have the potential to
induce changes in local monomer packing as a mechanism to
modulate long-range nanostructural order. Although metal
coordination has been exploited to drive the assembly of
discrete self-assembled architectures,14-16 and in the formation
of coordination polymers,17 there are fewer examples of
coordination induced transformations among discrete self-
assembled states.
Nanomaterials capable of coordinating metal ions in
solution also have the potential to serve as chemosensors for
Fig. 1. Self-assembly of NDI-BIMs 1 and 2. NDI-BIMs 1 and 2 assembled into nanotubes
at pH 2 (for 1) or pH 7 (for 2), when the lysine head group was positively or negatively
charged, respectively. Copper coordination to NDI-BIM 2 at pH 7 induced a transition
from nanotubes to vesicular aggregates.
metal
analytes.18-21
Additionally,
bis(indolyl)methane
compounds have found application as pharmaceuticals,22,23
light-harvesting
materials,24,25
and
as
selective
colorimetric/fluorimetric sensors for copper cations.26-28 To
Results and Discussion
The NDI-BIM amphiphiles, 1 and 2, were prepared via the
sequential monoimidation of NDA with (di(1H-indol-3-
yl)methyl)aniline, 3, followed by Nα-Boc-L-lysine or Nα-L-lysine
to form 1, after N-Boc deprotection, and 2, respectively
(Scheme 1). Alternatively, reversing the monoimidation
sequence provided similar coupling efficiencies (Scheme S1).
a
Department of Chemistry, Faculty of Sciences and Arts, Bingöl University, Bingöl,
12000, Turkey
b Department of Chemistry and Biochemistry, The Ohio State University, 100 W. 18th
Ave. Columbus, Ohio 43210, USA, E-mail: parquett@chemistry.ohio-state.edu
c Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum, 25240,
Turkey, , E-mail: nsarac@atauni.edu.tr
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
.
Bis(indolyl)methane 3 was obtained via the Bi(NO3)3 5H2O-
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DOI: 10.1039/D0DT02732D
Scheme 1. (a) 4-nitrobenzaldehyde, Bi(NO3)3•5H2O, CH2Cl2, 99%; (b) NiCl2•6H2O, NaBH4,
CH3OH, 98% or H2, Pd-C, THF, 93%; (c) 1,4,5,8-naphthalenetetracarboxylic dianhydride,
DMF, 100°C, 98%; (d) Nα-(t-butoxycarbonyl)-L-lysine; DMF, 100°C, 92%; (e) Nα-(9H-
fluoren-9-yl)methoxy)carbonyl)-L-lysine, DMF, 100°C, 82%; (f) Et3SiH, TFA, CH2Cl2, 85%.
catalyzed reaction of indole with 4-nitrobenzaldehyde,29
followed by reduction with Ni(OAc)2/NaBH4 or H2/Pd-C (Scheme
S1).
We initially explored the self-assembly and metal-binding
capability of NDI-BIM 1, which displayed an unprotected lysine
headgroup. Ultraviolet (UV-Vis) and circular dichroic (CD)
spectra provided preliminary evidence for the self-assembly of
1 in CH3CN-H2O (1:1). NDI-BIM 1 exhibited absorbance bands
corresponding to the NDI chromophore in the range of 240 nm
(Band II) and 358/378 nm (Band I) in CH3CN-H2O at pH 7 (Fig.
2a). In pure 2,2,2-trifluoroethanol (TFE), in which 1 remained in
the monomeric form, these bands occurred at 238 nm (Band II)
and 356/376 nm. The red-shifting of the peaks going from TFE
to CH3CN-H2O was consistent with the formation of a J-type
aggregate.30,31 Thus, intermolecular  interactions among the
NDI units provided an additional driving force for the nanotube
assembly process. Lowering the pH to 2 with trifluoroacetic acid
(TFA) in CH3CN-H2O induced further bathochromic shifts to
360/381 nm (Band I), indicative of stronger  interactions.
Similarly, whereas the CD spectrum of 1 in TFE was a flat line,
Cotton effects in the range of 300-400 nm and 400-500 nm
emerged in CH3CN-H2O (1:1, pH 2), corresponding to the NDI
and BIM chromophores, respectively (Fig. 2b). Additionally, a
strong positive excitonic couplet centered at ca. 240 nm, due to
an NDI (Band II) transition, was present. The couplet at 240 nm
emerged from transitions polarized along the short axis of the
NDI, indicating the presence of a P-type intermolecular helical
orientation (Figs. 1,2b).32 At pH 7, the intensity of the CD peaks
was significantly reduced, indicating a less efficient self-
assembly process.
Fig. 2. UV and CD spectra of NDI-BIM 1 (a-b) and 2 (c-d) in CH3CN-H2O in and in pure TFE;
and NDI-BIM 2-Cu in CH3CN-H2O at pH 7 (e-f)
H2O (1:1). All of these metal salts failed to induce the
appearance of absorption bands, expected in the range of ~500
nm, or any associated color changes, which would have been
indicative of coordination to the BIM subunit.26 The difficulty in
metal complexation of 1 likely emerged from concomitant
coordination of the free lysine headgroup in 1.33
Accordingly, metal-binding studies were focused on NDI-
BIM 2, in which the lysine headgroup was protected as an Nα-
Fmoc group. Although 2 was insoluble in pure water, the self-
assembly could be evaluated in aqueous solvent mixtures
Preliminary metal binding studies on NDI-BIM 1 with a wide
range of metal chloride salts (Cr2+, Co2+, Cd2+, Mg2+, Sn2+, Fe2+,
Cu2+, Hg2+, Mn2+, Zn2+) were performed by mixing a 1:1 ratio of
the the metal salts (10 mM) to NDI-BIM 1 (10 mM) in CH3CN-
2 | J. Name., 2012, 00, 1-3
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(CH3CN, TFE, TFE/H2O (1/1), CH3CN/H2O (1/1)). Similar to 1, indicated
Paper
a
different intermolecular monomVieewr ArtpiclaecOknilninge
DOI: 10.1039/D0DT02732D
amphiphile 2 exhibited red-shifting of the absorptions in the UV orientation of 2-Cu compared with uncomplexed 2.
spectra going from TFE to CH3CN; and from TFE to CH3CN-H2O
A 1:1 (2:Cu2+) binding stoichiometry was determined from a
(1/1, pH 7), indicative of J-type aggregation (Fig. S14). The plot of the absorption at 509 nm versus the 2/CuCl2 mole
comparatively greater red-shifting in CH3CN-H2O (1:1, pH 7) fraction (Job plot) (Figs. 3b, S4).36 The association constant (Ks)
confirmed that assembly was most efficient in this solvent for the formation of 2-Cu was determined to be 2.07 × 104 M-1
mixture. In contrast to 1, at pH 2, a transition emerged at 506 from the slope of a plot of 1/A-A0 versus 1/[Cu2+] using the
nm reflecting the partial protonation of the BIM chromophore Benesi-Hildebrand equation (Fig. 3a,3c).37 The limits of
under these conditions.26 The CD spectrum showed cotton detection and quantitation (LOD and LOQ) for Cu2+ ions were
effects in the 300-350 and 350-400 nm ranges in CH3CN-H2O 22.1 µM and 66.9 µM in CH3CN/H2O (v/v: 1/1) solution (Fig. S3),
(1:1) at pH 2 and 7 (Fig 2c). In contrast, significantly reduced CD suggesting that 2 might find utility as a selective sensor of
signals in pure CH3CN, and flat lines in TFE and TFE-H2O (1:1) copper ions. The Ks and LOD values of NDI-BIM 2 compared
38-43
were indicative of a less efficient assembly process in these favorably to other published copper sensors (Table 1).
solvents, consistent with the UV studies.The excitonic couplet
at ~240 nm, due to positive excitonic spitting of the NDI band II
Table 1. Comparison of some Cu2+ selective chemosensors.
Ref.
38
39
40
41
42
43
This work
Ks (M−1)
LOD
Sensing Ions
transition was apparent in the CD spectrum at pH 7, also
indicative of P-type intermolecular  packing helicity of the
NDI chromophores. Although the intensity of the couplet was
substantially reduced, the sign was reversed at pH 2 (Fig. 2d).
The lower overall intensity of the CD bands and the smaller
excitonic couplet at ~240 nm suggested that the assembly
process was inhibited at pH 2, producing partial aggregates with
opposite M-type NDI helicity. This behavior contrasts with that
of NDI-BIM 1, which assembled more efficiently at pH 2 than at
pH 7 (Fig. S5B) into assemblies with P-type NDI helicity. Given
the low basicity of the bis(indolyl)methane moiety present in 1
and 2, the degree of protonation at pH 2 would be expected to
be minimal.34 Thus, the pH-dependent aggregation of the NDI-
BIM monomers could be correlated with the charge state of the
lysine headgroup. At low pH, amphiphile 1 displayed a positively
charged headgroup, which enhanced the amphiphilicity of the
monomer, thereby promoting aggregation. The charge would
be much lower near the isoelectric pH at ~pH 7, thus impeding
aggregation. In contrast, notwithstanding the small degree of
BIM protonation, amphiphile 2 would remain neutral at pH 2
and negatively charged at pH 7, thereby facilitating aggregation
at higher pH.
4.80 × 106 M−1
1.21 × 104 M−1
3.26 × 104 M−1
2.08 × 104 M−1
3.10 × 106 M−1
3.80 × 106 M−1
2.07 × 104 M−1
10.1 × 10-6
2.31 × 10−6
14.5 × 10−6
10.0 × 10−6
29.6 × 10-6
1.62 × 10-9
22.1 × 10-6
M
M
M
M
M
M
M
Cu2+
Cu2+, Hg2+
Cu2+
Cu2+
Cu2+
Cu2+, S2-
Cu2+
The Cu 2p photoelectron and Cu LMM X-ray Auger electron
spectra were consistent with copper in the divalent oxidation
state (Fig. 3d).44 Significant changes in the spectra were
indicative of a change in the ligand environment around the
copper. For example, a reversal in the relative intensities of the
two peaks in the Cu 2p 3/2 and Cu 2P1/2 spectral regions of 2-Cu,
compared with CuCl2 were apparent.
The capability of 2 to bind metal chloride salts was explored
by mixing the metal salts (10 mM) and 2 (10 mM) in CH3CN-H2O
(1:1) at pH 7 because these conditions promoted self-assembly
and concomitantly minimized protonation of the BIM subunit.
A scan of the potential of 2 to bind metal chloride salts (Cr2+,
Co2+, Cd2+, Mg2+, Sn2+, Fe2+, Cu2+, Hg2+, Mn2+, Zn2+) revealed a
high selectivity for Cu2+ (Fig. S1).26-28,35 In contrast to the other
metal ions, the addition of CuCl2 induced a color change from
pale yellow to red, the appearance of absorption at 509 nm,26
and slight red-shifting in the UV-Vis spectra, compared with
uncomplexed 2, from 359/380ꢀnm to 360/381ꢀnm (Fig. 2e).
Similarly, the CD spectrum of NDI-BIM 2-Cu showed cotton
effects in the 300-400 nm range at pH 7 (Fig. 2f). However,
whereas the excitonic couplet at ~240 nm, due to positive
excitonic splitting of the NDI band II transition was present in
the CD spectrum of NDI-BIM 2 at pH 7, the shape of the
transitions in the 225-275 and 320-400 nm regions of the CD
spectra were comparatively different for NDI-BIM 2-Cu. In fact,
the excitonic couplet at 240 nm resembled negative chirality,
consistent with M-type NDI packing. These differences
Fig. 3. (a) UV-vis titration of NDI-BIM 2 (10 mM) with CuCl2 in CH3CN/H2O (1:1). (b) Job
plot showing a 1:1 stoichiometry of complex NDI-BIM 2-Cu. (c) Benesi-Hildebrand plot
based on a 1:1 association stoichiometry between the NDI-BIM 2 with CuCl2; (d) XPS Cu
2p1/2 and Cu2p3/2 spectrum of NDI-BIM 2 (black), NDI-BIM 2 +CuCl2 (blue) and CuCl2 (red).
The self-assembly of 1 and 2 was characterized by electron
and atomic force microscopy (AFM). Accordingly, NDI-BIM 1
was incubated in CH3CN-H2O (1/1, 10 mM, 12 h) at pH 2 and 7.
A sparse array of nanotubes, along with irregular aggregates,
could be observed in the transmission electron microscopy
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J. Name., 2013, 00, 1-3 | 3
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Fig. 4. (a) TEM image of NDI-BIM 1 at pH 7, (b) TEM image of NDI-BIM 1 at pH 2 (inset:
nanotube dimensions), (c) SEM image of NDI-BIM 1 at pH 2 and (d) AFM image of NDI-
BIM1 at pH 2.
Fig. 5. (a) TEM image of NDI-BIM 2 at pH 2, (b) TEM image of NDI-BIM 2 at pH 7 (inset:
nanotube dimensions), (c) SEM image of NDI-BIM 2 at pH 7 and (d) AFM image of NDI-
BIM 2 at pH 7
(TEM) images of samples prepared at pH 7. In contrast, a
homogeneous array of uniform nanotubes were observed at pH
2.0 (Figs. 4a, b, and S7), consistent with the higher CD intensity
at this pH. The nanotubes appeared as two white, parallel lines
separated by a dark center, consistent with the cross-sectional
view of a hollow, tubular structure. Similarly, imaging by
scanning electron microscopy (SEM) revealed a protruding
nanotube tip, confirming a tubular structure (Fig. 4c). The
nanotubes displayed outer and inner diameters of 21.2 and 4.8
nm, respectively, and wall thicknesses of 8.2 nm, as imaged by
TEM. Tapping-mode AFM imaging of the nanotubes on mica
produced comparable cross-sectional heights (~15.8 nm) (Figs.
4d and S6). Cross-sectional heights measured by AFM are
typically slightly smaller than diameters determined by TEM,
due to the compression of the nanotubes during imaging, often
exhibiting heights of twice that of the wall thickness.45
Contrasting with the self-assembly of 1, NDI-BIM 2
assembled into well-defined nanotubes after incubating at pH 7
(10 mM, 12 h) (Figs. 5a-d, and S8), but formed a sparse array of
vesicular aggregates at pH 2, consistent with the UV and CD
spectra under those conditions. Similar to the nanotubes
formed by 1, SEM imaging revealed a nanotube end projecting
out of the array, thereby confirming the nanotube morphology
(Figs. 5c). Although the nanotubes exhibited larger diameters
(58 nm), compared with those of 1 (pH 2), the wall thicknesses
were similar (8.6 nm).
evidenced by red-shifting the UV and the corresponding CD
signals, indicated that intermolecular NDI  contacts played
an important role in stabilizing the assembled nanotubes. The
curvature of the membrane bilayers on the surface of the
nanotubes likely emerges from the chirality and charge of the
amphiphile headgroups, which causes the molecules to pack in
tilted orientations.48 Considering the extended lengths of 1 (2.0
nm) and 2 (2.3 nm) (Figs. 1 and S13), the walls of the nanotubes
from 1 (pH 2) and 2 (pH 7) would likely be comprised of two
bilayers containing a total of four NDI-BIM molecules.
Following the addition of one equiv. of CuCl2 to 2 (10 mM,
CH3CN/H2O (1:1), pH 7), a structural transformation from a
nanotube to a vesicle morphology was apparent by TEM, SEM
and AFM imaging (Figs. 6a-c). The vesicles appeared as dark
spheres with diameters ranging from 88-250 nm (Fig. S8).
Dynamic light scattering (DLS) also indicated a transition from
large aggregates of 2000-8000 nm for 2 (10 mM, MeCN/H2O, pH
7) to smaller aggregates (500 – 1400 nm) upon the addition of
one equiv. CuCl2 (Fig. 6d).
The change in morphology from nanotubes to vesicles likely
emanated from an increase in the polarity of the BIM segment
upon copper coordination, which modified the amphiphilic
nature and structure of 2. Access of the hydrophilic copper ions
to the nonpolar interior wall segments of the nanotubes would
be expected to be difficult.6 However, self-assembled systems
exist in dynamic equilibrium with the monomeric state, which
often accounts for their stimuli responsivity and ability for self-
repair.49 Thus, the copper ions could be expected to bind NDI-
BIM 2 via the monomer form, which drives the assembly
process toward a vesicular morphology with M-type NDI
packing.
The large impact of headgroup charge on the efficacy of
nanotube formation from 1 and 2 was consistent with an
amphiphilic assembly process.45-47 Thus, self-assembly was
driven by sequestration of the hydrophobic NDI and BIM
segments within the interior of the tube walls, while projecting
the charged lysine headgroups on the inner and outer surfaces
of the nanotubes. Additionally, the presence of J-aggregates, as
4 | J. Name., 2012, 00, 1-3
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performed on silica gel 60 (230-400 mesh, 60 Å) using the
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indicated solvents. All reactions wereDOpIe: r10fo.1r0m39e/dD0DuTn0d2e7r32Da
nitrogen atmosphere.
4-(Di(1H-indol-3-yl)methyl)aniline (3). To a suspension of
3,3'-((4-nitrophenyl)methylene)bis(1H-indole) (500 mg, 1.36
.
mmol) and NiCl2 6H2O (324 mg, 1.36 mmol) in CH3OH (3.8 mL)
was added NaBH4 (257 mg, 6.80 mmol) at 0°C and the mixture
was stirred at 0°C for 30 min. The reaction mixture was
quenched by addition of sat. NH4Cl at 0°C and extracted with
DCM. The combined organic layers were washed with brine
(2×50 mL), and the organic phase was dried over anhydrous
Na2SO4. The crude product (455 mg) was purified by flash
chromatography with 10% EtOAc/Hexane to give the product 4-
(di(1H-indol-3-yl)methyl)aniline (3, 450.0 mg, 98%). 1H-NMR
(400 MHz, CDCl3):  7.78 (s, NH, 2H), 7.42-7.40 (m, =CH, AA′ part
of AA′BB′ system, 2H), 7.30 (d, J = 8.2 Hz, =CH, 2H), 7.16 (t, J =
7.7 Hz, =CH, 2H), 7.12-7.10 (m, =CH, BB′ part of AA′BB′ system,
2H), 7.01 (t, J = 7.7 Hz, =CH, 2H), 6.61-6.58 (m, =CH, 4H), 5.78 (s,
CH, 1H), 3.52 (bs, NH2, 2H); 13C-NMR (100 MHz, CDCl3):  144.3,
136.7, 134.4, 129.5, 127.1, 123.6, 121.8, 120.2, 120.1, 119.3,
115.2, 111.1, 39.3; IR (KBr, cm–1): 3456, 3423, 3051, 2980, 2394,
1593, 1510, 1458, 1337, 916; ESI-MS calc. for C23H19N3: [M+H]+:
338.1657, found: 338.1652; TLC: Rf = 0.61 (EtOAc/Hexane
(10%), 254 nm).
Fig. 6. (a) AFM, (b) TEM and (c) SEM images of NDI-BIM 2 (pH 7) after coordinating with
Cu2 +; (d) DLS spectra of NDI-BIM 2 (black) and NDI-BIM 2-Cu (red) in MeCN-H2O (1:1, 10
mM, pH 7).
3,3′-Bis(indolyl)methane-NDI monoimide (4). 1,4,5,8-
Naphthalenetetracarboxylic dianhydride (NDI, 397 mg, 1.48
mmol) was dissolved in DMF (15 mL) and solution of 4-(di(1H-
indol-3-yl)methyl)aniline (3, 500 mg, 1.48 mmol) in DMF (5 mL)
was added slowly via dropping funnel at 90°C. The reaction
mixture was degassed with a nitrogen stream and heated to
100°C. After 4 h, the solvent was removed by evaporation at
reduced pressure, and the residue was purified by flash
chromatography with 10% DCM/MeOH to give 3,3′-
bis(indolyl)methane-NDI monoimide (BIM-NDI, 857 mg, 98%,
In conclusion, we have designed and synthesized novel NDI-
based amphiphiles containing a metal-binding BIM unit. These
amphiphiles assembled into nanotubes most efficiently at pH 2
for 1 and pH 7 for 2, when the lysine headgroup was positively
or negatively charged, respectively. NDI-BIM 2 exhibited high
selectivity for binding Cu2+, as a 1:1 complex with an association
constant of 2.07 × 104 M-1. Copper coordination to 2 induced a
transition from nanotubes to vesicular aggregates. The
transition from nanotubes to vesicles likely emerged from a
change in the amphiphilic nature of 2 upon copper binding. Low
LOD and LOQ values indicated that 2 would be useful as a
selective copper ion sensor.
1
M.p.> 400oC (DCM)) as eluent affording a red solid. H-NMR
(400 MHz, DMSO-d6):  10.88 (s, NH, 2H), 8.73-8.71 (m, =CH,
AA’ part of AA′BB′ system, 2H), 8.67-8.65 (m, =CH, BB′ part of
AA′BB′ system, 2H),7.54-7.52 (m, =CH, AA′ part of AA′BB′
system, 2H), 7.38-7.31 (m, =CH, 6H), 7.06 (t, J = 7.9 Hz, =CH, 2H),
6.93 (d, J = 2.2 Hz, =CH, 2H), 6.89 (d, J = 7.9 Hz, =CH, 2H), 5.95
(s, CH, 1H); 13C-NMR (100 MHz, DMSO-d6):  162.9, 162.6,
159.8, 145.3, 136.6, 133.0, 131.8, 130.3, 128.6, 128.5, 127.7,
126.6, 126.5, 123.7, 123.6, 120.9, 119.1, 118.2, 117.8, 111.5,
35.7; IR (KBr, cm–1): 3360 3048, 3030, 3011, 2933, 2866, 2637,
2400, 2394, 1907, 1788, 1600, 1526, 1592, 1340, 1285, 1130,
827; ESI-MS calc. for C37H21N3O5: [M]+: 587.1461, found:
587.1441; TLC: Rf = 0.26 (DCM/MeOH (10%), 254 nm).
Nα-Boc-L-lysine-NDI-3,3′-bis(indolyl)methane. The 3,3′-
bis(indolyl)methane-NDI monoimide 4 (500 mg, 0.85 mmol) was
dissolved in DMF (10 mL). After a solution of Nα-(tert-
butoxycarbonyl)-L-lysine (209 mg, 0.85 mmol) was added in
DMF (5 mL), the reaction was degassed with a nitrogen stream
and heated to 100°C for 3 h. DMF was removed by evaporation
at reduced pressure, and the residue was purified by flash
chromatography with 10% DCM/MeOH to give Nα-Boc-L-lysine-
NDI-3,3′-bis(indolyl)methane (637 mg, 92%, M.p. > 400oC
(DCM)) as eluent affording red solid. 1H-NMR (400 MHz, DMSO-
Experimental
General details. Circular dichroic (CD) spectra were taken
with a JASCO CD spectrometer. Atomic force microscopy (AFM)
was conducted in tapping mode under a nitrogen atmosphere.
Transmission electron microscopy (TEM) was carried out with
the Technai G2 Spirit instrument operating at 80 kV. Scanning
Electron Microscopy (SEM) was carried out with the FEI Nova
NanoSEM 400 scanning electron microscope. DLS
measurements were performed using a Malvern Nano series
Zetasizer. 1H and 13C NMR spectrums were recorded at 400 MHz
on a Bruker Avance III instrument. ESI mass spectra were
recorded on a Bruker MicroTOF coupled with HPLC in The Ohio-
State University Chemical Instrument Center-Chemistry. All
UV/Vis spectra were recorded with a SHIMADZU UV-2450 at
25°C. All fluorescence spectroscopy was performed on a
Shimadzu RF-6000 instrument using a cuvette with 1 mm or 1
cm pass length at 25°C. Dimethylformamide (DMF) was dried by
distillation from MgSO4. Chromatographic separations were
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J. Name., 2013, 00, 1-3 | 5
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d6):  11.50 (bs, CO2H, 1H), 10.89 (bs, NH, 2H), 8.63-8.60 (m, 2H), 7.55 (d, J = 8.0 Hz, =CH, 2H), 7.45-7.40 (m, =CH, 8H), 7.05
View Article Online
DOI: 10.1039/D0DT02732D
=CH, AA’ part of AA′BB′ system, 2H), 8.59-8.57 (m, =CH, BB’ part (d, J = 8.0 Hz, =CH, 2H), 6.96-6.92 (m, =CH, 4H), 5.97 (bs, CH, 1H),
of AA′BB′ system, 2H), 7.56-7.54 (m, =CH, AA′ part of AA′BB′ 5.49 (bs, NH, 1H), 4.31-4.20 (m, CH, 1H), 4.08-3.93 (m, CH, CH2,
system, 2H), 7.39-7.33 (m, =CH, 6H), 7.06 (t, J = 8.1 Hz, =CH, 2H), 3H), 3.40 (dd, J = 16.5, 8.8 Hz, CH2, 2H), 1.82-1.56 (m, CH2, 4H),
6.95 (bs, =CH, 2H), 6.91 (t, J = 6.0 Hz, =CH, 2H), 5.97 (s, CH, 1H), 1.31-1.16 (m, CH2, 2H); 13C-NMR (100 MHz, DMSO-d6):  185.5,
5.25 (d, J = 4.0 Hz, NH, 1H), 4.03 (bs, CH2, 2H), 3.89-3.88 (m, CH2, 162.7, 162.4, 145.3, 137.3, 136.6, 133.0, 132.9, 130.3, 128.8,
1H), 1.68-1.65 (m, CH2, 4H), 1.42-1.39 (m, CH2, 2H), 1.36 (s, CH3, 128.6, 127.2, 127.1, 126.6, 126.0, 125.6, 124.7, 123.6, 122.4,
9H); 13C-NMR (100 MHz, DMSO-d6):  174.2, 162.7, 162.4, 121.7, 121.3, 120.9, 119.9, 119.1, 118.2, 117.9, 111.5, 109.6,
155.6, 145.3, 136.6, 130.4, 130.3, 128.7, 128.5, 126.7, 126.6, 56.6, 40.1, 36.9, 35.7, 30.7, 28.8, 23.6, 15.2; IR (cm-1): 3455,
126.3, 126.1, 126.0, 123.6, 120.9, 119.1, 118.2, 117.8, 111.5, 3366, 3165, 3059, 3048, 3011, 2945, 2859, 2637, 2400, 1890,
77.9, 53.3, 35.7, 30.7, 30.5, 28.2, 27.0, 23.2; IR (cm-1): 3366, 1526, 1907, 1591, 1542, 1441, 1285, 1130, 827; ESI-MS calc. for
3048, 3011, 2945, 2859, 2637, 2400, 1890, 1526, 1907, 1591, C58H43N5O8: [M+Na]+: 960.3009, found: 960.3032.
1542, 1441, 1285, 1130, 827; ESI-MS calc. for C48H41N5O8:[M]:
815.2955, found: 815.2947; TLC: Rf = 0.21 (DCM/MeOH (15%),
254 nm)
UV-Vis detection of cations. A solution of NDI-BIM 2 (1×10-
2
M) and cations (chloride of metal ions, 1×10-2 M) were
prepared in CH3CN/H2O (1:1/v:v). The solution (1×10-5 M) was
NH2-L-lysine-NDI-3,3′-bis(indolyl)methane (1). To the then placed in a quartz cell and the UV-Vis spectrum was
solution of Nα-Boc-L-lysine-NDI-3,3′-bisindole (500.0 mg, 0.62 recorded. After the introduction of the solution of cations (1
mmol) in TFA/DCM (1:1, 10 mL) was added 1 mL of equiv.), the changes in absorbance intensity were recorded at
triethylsilane. The mixture was stirred for 2 h at room room temperature each time (Figure S1).
temperature before the solvent was removed by evaporation at
UV-Vis titration of the ligand with CuCl2. The solution of
reduced pressure affording a dark red oil. The crude oil was NDI-BIM 2 (1×10-2 M) and CuCl2 (1×10-2 M) was prepared in
washed with cold diethyl ether (3×15 mL) and MeCN (1×15 mL) CH3CN/H2O (1:1/v:v) ap pH 7. The concentration of a solution of
resulting a dark red precipitate and crude product was dissolved ligand used in the experiments was 1×10-5 M. The UV-Vis
in H2O:MeCN (1:1, 40 mL). The crude product (390 mg) was titration spectra were recorded by adding a corresponding
purified by reversed phase HPLC on preparative Varian concentration of CuCl2 to the solution of a ligand in CH3CN/H2O
Dynamax C18 column eluting with a linear gradient of (v/v: 1:1). Each titration was repeated at least twice until
MeCN/H2O with 0.1% TFA (20/80 to 90/10 over 5h). As a result consistent values were obtained (Fig. S2).
of this purification, H2N-L-lysine-NDI-3,3′-bis(indolyl)methane
Job’s plot measurement. NDI-BIM 2 was dissolved in
was obtained (1, 372 mg, 85%, M.p.> 400 oC (DCM)) as a dark CH3CN/H2O (1:1/v:v) to achieve a concentration of 1×10-2 M.
1
red solid. H-NMR (400 MHz, DMSO-d6):  10.93 (s, =NH, 2H), 5.00, 4.75, 4.50, 4.25, 4.00, 3.75, 3.50, 3.25, 3.00, 2.75, 2.50,
8.65-8.63 (m, =CH, 4H), 7.47-7.45 (m, =CH, AA′ part of AA′BB′ 2.25, 2.00, 1.75, 1.50, 1.25, 1.00, 0.75, 0.50 and 0.25 mL aliquots
system, 2H), 7.36 (d, J = 8.2 Hz, =CH, 2H), 7.32 (d, J = 8.2 Hz, =CH, of the ligand solution were taken and transferred to vials. CuCl2
2H), 7.32-7.25 (m, =CH, 4H), 7.07 (t, J = 8.2 Hz, =CH, 2H), 7.05- was dissolved in CH3CN/H2O (1:1/v:v) to make solution
6.97 (m, =CH, 3H), 6.16 (s, CH, 1H), 4.07-4.05 (m, CH2, 2H), 3.93 concentrations of 1×10-2 M. 0.25, 0.50, 0.75, 1.00, 1.25, 1.50,
(bs, CH, 1H), 1.86-1.83 (m, CH2, 2H), 1.71-1.70 (m, CH2, 2H) 1.47 1.75, 2.00, 2.25, 2.50, 2.75, 3.00, 3.25, 3.50, 3.75, 4.00, 4.25,
(bs, NH2, 2H), 1.43-1.40 (m, CH2, 2H); 13C-NMR (100 MHz, 4.50, 4.75 and 5 mL aliquots of the copper solution were then
DMSO-d6):  171.0, 162.8, 162.6, 162.5, 142.3, 136.4, 133.0, added to each ligand solution. Each vial had a total volume of 5
130.4, 128.8, 127.0, 126.8, 126.4, 126.2, 123.3, 121.0, 118.7, mL. After shaking the vials for a few seconds, UV–vis spectra
118.5, 118.3, 113.4, 111.4, 100.9, 51.8, 37.7, 30.6, 29.7, 27.0, were taken at room temperature (Fig. S4).
21.9; IR (cm-1): 3360, 3050, 3015, 2940, 2859, 2400, 1907, 1597,
1546, 1445, 1285, 1238, 1198, 1130, 1051, 930, 827; ESI-MS Acknowledgments
calc. for C43H33N5O6: [M+H]+:716.2509, found: 716.2554.
Nα-Fmoc-L-lysine-NDI-bis(indolyl)methane (2). The 3,3′- This manuscript is based upon work supported by the National
bis(indolyl)methane-NDI-monoimide (4, 500 mg, 0.85 mmol) Science Foundation (CHE-1708390) and by the U.S. Army
was dissolved in DMF (10 mL). After a solution of Nα-Fmoc-L- Research Laboratory and the U.S. Army Research Office under
Lys-OH (314 mg, 0.85 mmol) in DMF (5 mL) was added, the grant number W911NF-14-1-0305. S. Bayindir is thankful for the
reaction was degassed with a nitrogen stream and heated to doctoral fellowship (2214/A) to the Scientific and Technological
100°C for 4h. DMF was removed by evaporation at reduced Research Council of Turkey (TÜBİTAK). N. Saracoglu is grateful
pressure. The crude product (720 mg) was purified by reversed for the supports to the Council of Higher Education (CoHE) of
phase HPLC on preparative Varian Dynamax C18 column eluting Turkey and Atatürk University. We acknowledge the technical
with a linear gradient of MeCN/H2O with 0.1% TFA (20/80 to assistance and usage of the Campus Microscopy & Imaging
90/10 over 7 h). As a result of this purification, Nα-Fmoc-L- Facility at OSU.
lysine-NDI-3,3′-bis(indolyl)methane (2, 655 mg, 82%, M.p. > 400
1
oC (DCM)) was obtained affording a red solid. H-NMR (400 Conflicts of interest
MHz, DMSO-d6):  10.92 (s, NH, 2H), 8.63-8.59 (m, =CH, 4H,
8.63-8.59 (m, =CH, 4H), 8.54-8.50 (m, =CH, AA′ part of AA′BB′ There are no conflicts of interest to declare.
system, 2H), 8.33 (d, J = 7.5 Hz, =CH, 2H), 8.02 (d, J = 7.5 Hz, =CH,
6 | J. Name., 2012, 00, 1-3
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35. R. M. N. Kalla, S. C. Hong and I. Kim, ACS Omega, 2018, 3, 2242-
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DOI: 10.1039/D0DT02732D
TOC Graphic
The impact of metal coordination on the assembly of bis(indolyl)methane-
naphthalene-diimide amphiphiles
Sinan Bayindir, Kwang Soo Lee, Nurullah Saracoglu,* and Jon R. Parquette*
In this work, we report the impact of pH and metal coordination on the self-assembly of amphiphiles comprised
of naphthalenediimide (NDI)-bis(indolyl)methane (BIM) chromophores with a charged L-lysine head group. The
self-assembly of NDI-BIM 1 produced irregular nanostructures at neutral pH in CH3CN-H2O (1:1); whereas, well-
defined nanotubes were observed at pH 2. Conversely, Fmoc-protected, NDI-BIM 2 formed nanotubes at neutral pH
and nonspecific aggregates at pH 2. Upon coordination of Cu2+ ions to the bis(indolyl)methane moiety, a
reorganization from nanotubes to vesicular structures was observed.