DNA-Decorated Two-Dimensional Crystalline Nanosheets

Article abstract of DOI:10.1021/jacs.7b09283

Design and synthesis of high aspect ratio 2D nanosheets with surface having ultradense array of information-rich molecule such as DNA is extremely challenging. Herein, we report a universal strategy based on amphiphilicity-driven self-assembly for the crafting of high aspect ratio, 2D sheets that are densely surface-decorated with DNA. Microscopy and X-ray analyses have shown that the sheets are crystalline. The most unique feature of the sheets is DNA-directed surface addressability, which is demonstrated through the decoration of either faces of the sheet with gold nanoparticles through sequence-specific DNA hybridization. Our results suggest that this design strategy can be applied as a general approach for the synthesis of DNA decorated high aspect ratio sheets, which may find potential applications in materials science, drug delivery, and nanoelectronics.

Full text of DOI:10.1021/jacs.7b09283

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Communication
DNA-Decorated Two-Dimensional Crystalline Nanosheets
Shine K. Albert, Irla Sivakumar, Murali Golla, Hari Veera Prasad Thelu,
Nithiyanandan Krishnan, Joseph Libin K. L., * Ashish, and Reji Varghese
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b09283 • Publication Date (Web): 13 Nov 2017
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DNA-Decorated Two-Dimensional Crystalline Nanosheets
Shine K. Albert,† Irla Sivakumar,† Murali Golla,† Hari Veera Prasad Thelu,† Nithiyanandan Krishnan,†
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Joseph Libin K. L.,† Ashish,‡ Reji Varghese*,†
†School of Chemistry, Indian Institute of Science Education and Research (IISER) Thiruvananthapuram, Trivandrum-
695551, Kerala, India
‡ Protein Science and Engineering Division, Institute of Microbial Technology, Sector 39-A, Chandigarh–160036, India
Supporting Information Placeholder
properties of hydrophobic domain, offers a unique op-
portunity for the crafting of functional 2D and 3D na-
nomaterials with surface having ultra-dense array of
DNA.4 Recently, we have reported a series of DNA-
amphiphiles and have shown their amphiphilicity-driven
self-assembly into nano-to-micro sized DNAsomes.5 We
envisioned that the replacement of hydrophobic segment
of DNAsome forming amphiphile with a strongly p-
stacking hydrophobic core such as hexa-peri-
benzocoronene (HBC) could direct the self-assembly
into DNA decorated 2D sheets. Pioneering works of Ai-
da et al.6 and Müllen et al.7 on the self-assembly of am-
phiphilic HBCs have shown the high propensity of HBC
to assemble through p-stacking. However, DNA based
amphiphilic systems of HBC have not yet been ex-
plored.
ABSTRACT: Design and synthesis of high aspect ratio
2D nanosheets with surface having ultra-dense array of
information-rich molecule such as DNA is extremely
challenging. Herein, we report a universal strategy based
on amphiphilicity-driven self-assembly for the crafting
of high aspect ratio, 2D sheets that are densely surface-
decorated with DNA. Microscopy and X-ray analyses
have shown that the sheets are crystalline. The most
unique feature of the sheets is DNA-directed surface
addressability, which is demonstrated through the deco-
ration of either faces of the sheet with gold nanoparticles
through sequence-specific DNA hybridization. Our re-
sults suggest that this design strategy can be applied as a
general approach for the synthesis of DNA decorated
high aspect ratio sheets, which may find potential appli-
cations in material science, drug delivery, and nanoelec-
tronics.
Herein we describe a simple, efficient, and general
strategy based on amphiphilicity-driven self-assembly of
DNA-amphiphile for the crafting of micrometer-sized,
crystalline, 2D sheets that are densely surface-decorated
with DNA. Sheet structure consists of DNA-based hy-
drophilic surface and a functional core that results from
the self-assembly of alkylated HBC segment through p-
stacking and van der Waals interactions. The unique fea-
ture of the nanosheet is the dense surface display of
DNA, which allows the reversible decoration of the
sheet surface with other functional molecules through
sequence specific DNA hybridization. As a representa-
tive example, DNA-directed surface addressability of
sheet is explored for the organization of Au-NPs on the
surfaces of the sheet.
Crafting of two-dimensional (2D) nanosheets with high
aspect ratio is extremely important due to their potential
applications in material science and nanotechnology.1
Even more beneficial would be the design of high aspect
ratio sheets with surface having ultra-dense array of
highly information-rich molecule like DNA. This is be-
cause DNA-directed surface addressability of such
sheets makes it an ideal 2D nanoplatform for the precise
organization of other functional molecules on their sur-
face through sequence-specific DNA hybridization.2
DNA nanotechnology has proven to be an ideal ap-
proach towards this goal as this strategy allows the self-
assembly of DNAs into well-defined 2D and 3D
nanostructures decorated with DNA.3 Though the de-
signing principles of DNA nanotechnology permit the
fabrication of 2D sheets, the integration of other func-
tional domains of interest into these systems is challeng-
ing. Hence, the development of a simple and general
strategy for the synthesis of functional 2D nanosheets
densely decorated with DNA is extremely important.
The covalent conjugation of alkyl chains (-C10H21)
tethered HBC segment to the hydrophilic DNA was
achieved using the standard phosphoramidite chemistry
(Scheme 1). The precursor alcohol 1 was synthesized
following a reported procedure (SI).8 The only structural
difference between DNA1 and DNA2 is the length of
the hydrophilic DNA segment, which is increased from
DNA1 (9-mer) to DNA2 (18-mer) keeping the hydro-
phobic HBC core same (Scheme 1). Self-assembly of
the amphiphile was achieved by annealing DNA1/2
Self-assembly of DNA-amphiphiles, which combines
the structural characteristics of DNA and the functional
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DNA surface
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e)
f)
HBC-based core
Scheme 1. Synthesis of DNA1 and DNA2: a) dichloro-
methane, diisopropylamine, 2-cyanoethyl N,N-diisopropyl-
chlorophosphoramidite, rt, 2h, 80 %. Schematic representa-
tion depicting the amphiphilicity-driven self-assembly of
DNA1/2 into DNA-decorated 2D sheets. The protruding
ssDNA on the sheet surface need not be rigid as shown.
500 nm
100 nm
(1 µM Tris-buffer, pH 7.3 or Milli-Q water) at 90 °C for
5 minutes followed by cooling to room temperature (rt).
Figure 1. (a) Absorption spectra, (b) DLS size distribution,
and (c) SAXS curves of DNA1 and DNA2. The insets of
(a) and (b) show the absorption and DLS graphs of DNA1
at 20 °C and 70 °C, respectively. (d) Fluorescence micro-
scopic, (e) SEM, and (f) TEM images of DNA1 sheet.
Figure 1a shows the electronic absorption spectra of
DNA1 and DNA2, which displays the characteristic ab-
sorptions of DNA at 260 nm (e260nm = 1.2 ´ 105 M-1cm-1
for DNA1; 2.2 ´ 105 M-1cm-1 for DNA2) and p-stacked
HBC at 358 nm (e358nm = 5.3 ´ 104 M-1cm-1).6a Interest-
ingly, no noticeable change is observed in the absorption
spectrum of DNA1 and DNA2 with the increase in tem-
perature from 20 °C to 70 °C (Figure 1a inset and Figure
S2a). Dynamic light scattering (DLS) analyses of DNA1
and DNA2 reveal the formation of aggregates in solution
with size ranging from 60 nm to 1.5 µm and 30 nm to
1.2 µm, respectively (Figure 1b). Furthermore, size dis-
tribution graphs for DNA1 and DNA2 remain un-
changed even at a high temperature of 70 °C (Figure 1b
inset and Figure S2b). These results imply that the
strong p-stacking of HBC and van der Waals interaction
of the alkyl chains in aqueous medium lead to the for-
mation of thermally stable (at least stable up to 70 °C)
nanostructures for DNA1 and DNA2. Surface decoration
of the aggregates with negatively charged DNA is evi-
dent from the zeta potential measurements of DNA1 and
DNA2 aggregates, which show values of –15.5 mV and
–17.4 mV, respectively (Figure S3). Small angle X-ray
scattering (SAXS) curves of DNA1 and DNA2 aggre-
gates respectively show slopes of –2 and –2.1 in the low
Q (modulus of the scattering vector) region, confirming
the formation of sheet-like nanostructures in solution
(Figure 1c).9 Sheet morphology of DNA1 and DNA2
aggregates is further established using fluorescence mi-
croscopy (Figure 1d and Figure S5), scanning electron
microscopy (Figure 1e and Figure S7), and transmission
electron microscopy (TEM) analyses (Figure 1f and
Figure S9). Interestingly, lateral dimensions of the sheets
are several micrometers, and in some cases, extended
even up to one millimeter (Figure S10), which is hard to
achieve.10 Sheet formation is also confirmed under dif-
ferent experimental conditions, demonstrating the ro-
bustness of the self-assembly (Figure S11).
Molecular level understanding of the sheet structure
was obtained through atomic force microscope (AFM),
high resolution–TEM (HR-TEM), and X-ray analyses.
AFM height images of DNA1 and DNA2 display the
formation of sheets on mica surface with heights of 120
nm and 200 nm, respectively (Figure 2a and b). Since
the observed heights of the sheets are several folds larg-
er than their calculated monolayer thicknesses (~12 nm
for DNA1 and ~19 nm for DNA2 when completely ex-
tended conformations were assumed for the molecular
units), they are multilayered in nature. HR-TEM images
show that the sheets consist of parallel stripes that are
straight over several hundred nanometers (Figure 2c–f).
These stripes can be attributed to the assembly of the
amphiphiles in one dimension in a lamellar fashion with
hydrophilic DNA exposed to the polar medium on either
side of the supramolecular polymer chain. Furthermore,
HR-TEM reveal the crystalline nature of DNA1 and
DNA2 sheets. The distance separating the individual
supramolecular polymer chain (distance between the
stripes) is ~3.4 Å (Figure 2d and 2f). This corresponds to
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Figure 3. (a) Schematic representation illustrating the NP
decoration on DNA1 sheet through DNA hybridization. (b)
and (c) TEM images of Au-NP decorated DNA1 sheet. (d)
Comparison of absorption spectra of Au-NPs alone and
after their assembly onto DNA1 sheet, and inset shows the
corresponding emission spectral changes. (e) TEM image
of a DNA1 sheet after the self-assembly with non-
complementary DNA modified NP.
Figure 2. AFM height images of (a) DNA1 and (b) DNA2
sheets and insets show the corresponding section analyses.
HR-TEM images (c) & (d) of DNA1 and (e) & (f) of
DNA2 sheets. The insets of (d) and (f) show the SAED
pattern of DNA1 and DNA2 sheets, respectively.
the p-p stacking distance of HBC core (plane-to-plane
distance of p-stacked HBC), which permits the assembly
of the individual supramolecular chain in the other di-
mension, leading to the formation of crystalline 2D
sheets. Selected area electron diffraction patterns of
DNA1 (Figure 2d inset) and DNA2 (Figure 2f inset)
reveal bright and narrow rings, further confirm the crys-
talline nature of the sheets. Furthermore, a broad peak at
2q = 18–33° is observed in the wide angle XRD patterns
of DNA1 and DNA2 sheets, which corresponds to a d-
spacing of 4.9–2.7 Å, respectively (Figure S14). This
can be assigned to the combination of p-stacking of
HBC and the assembly of the alkyl chains. Based on
these results, a plausible molecular model for the
nanosheet is schematically depicted in Scheme 1.
after hybridization of the protruding ssDNA on the sheet
surface with the corresponding complementary DNA
strands (Figure S15), which is extremely important for
application of the sheet as a template.
The most striking feature of the sheet is the DNA di-
rected surface addressability, which allows the defined
incorporation of other functional molecules onto the
sheet surface through DNA hybridization. As a proof of
concept, we demonstrate the decoration of either faces
of DNA1 sheet with ~20 nm gold nanoparticles (Au-
NPs) that are pre-modified with DNA (5'-
TGGGTGCGA-3').11 The DNA on the surface of the
NPs is complementary to the DNA on the surface of the
sheet. Self-assembly of 1:1 molar ratio of DNA1 sheet
and AuNP shows dense loading of NPs on the sheet sur-
face (Figure 3b and 3c). It is worth noting that NPs dec-
orates on both faces of the sheet as it is evident from the
difference in contrast for the NPs present on each face.
These results not only show the unique self-assembly
power of DNA but also provide direct evidence for the
proposed sheet structure (Scheme 1). Furthermore, in-
terparticle surface plasmon coupling is seen due to the
close packing of NPs. Accordingly, a red-shift of 6 nm is
observed in the plasmon absorption band of Au-NPs that
It is to be noted that though the hydrophilic content of
the amphiphile is increased from DNA1 to DNA2, the
morphology and molecular level packing of the sheets
remain the same. This suggests that the self-assembly of
the DNA amphiphiles is essentially dictated by hydro-
phobic interactions (π-stacking of HBC and van der
Waals interaction of the alkyl chains), and the hydro-
philic DNA has little influence on directing the self-
assembly. It is also worth noting that no change in the
sheet morphology of DNA1 and DNA2 is observed even
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are assembled on the sheet when compared with the cor- REFERENCES
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carried out with NP modified with non-complementary
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In summary, we have reported for the first time, an
amphiphilicity-driven self-assembly approach for the
design of DNA-based surface addressable, high aspect
ratio, crystalline, 2D sheets. Our results suggest that the
strong self-assembling property of the hydrophobic
segment of the amphiphiles essentially dictates the as-
sembly into sheets irrespective of the chain length and
rigidity of hydrophilic DNA. Hence, this approach can
be applied as a general design strategy for the synthesis
of DNA based micrometer-sized sheets by choosing
strongly p-stacking moiety as the hydrophobic segment.
Though nanosheets derived from the self-organization of
amphiphilic systems are known in the literature, the
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The present sheet consists of a functional core (HBC-
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ASSOCIATED CONTENT
The Supporting Information is available free of charge on
the ACS Publications website.
Experimental procedure and additional data (PDF)
AUTHOR INFORMATION
(11) Sharma, J.; Chhabra, R.; Andersen, C. S.; Gothelf, K. V.; Yan,
H.; Liu, Y. J. Am. Chem. Soc. 2008, 130, 7820.
Corresponding Author
*reji@iisertvm.ac.in
ACKNOWLEDGMENT
Financial supports from DBT (BT/PR7030/NNT/28/63/-
2012), CSIR, and UGC are gratefully acknowledged. We
thank MGU for mass analyses. We are grateful to Prof.
Takuzo Aida, University of Tokyo, Japan for his sugges-
tions on the synthesis of HBC derivatives.
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