Control of helical chirality in supramolecular chromophore-DNA architectures

Article abstract of DOI:10.1039/c8cc08887j

Four different d- and l-configured chromophore-2′-deoxyuridine conjugates were applied to elucidate the helical chirality of their non-covalent assemblies along the d- and l-configured DNA templates by optical spectroscopy. There is no configuration-selective recognition between these nucleosides and the DNA templates. The helicity of the DNA assemblies is either controlled by the configuration of the DNA template or by the nucleoside configuration.

Full text of DOI:10.1039/c8cc08887j

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Control of helical chirality in supramolecular
chromophore–DNA architectures†
Cite this:DOI: 10.1039/c8cc08887j
Robert Hofsaß, Philipp Ensslen and Hans-Achim Wagenknecht
¨
*
Received 7th November 2018,
Accepted 7th January 2019
DOI: 10.1039/c8cc08887j
rsc.li/chemcomm
0
Four different D- and L-configured chromophore–2 -deoxyuridine templates to obtain supramolecular DNA–chromophore assemblies
21
conjugates were applied to elucidate the helical chirality of their as functional photoactive layers in solar cells. Most recently, we
non-covalent assemblies along the D- and L-configured DNA templates showed that ethynyl pyrene and ethynyl nile red can be assembled
by optical spectroscopy. There is no configuration-selective recognition in a sequence-programmable fashion controlled by the DNA
2
2
between these nucleosides and the DNA templates. The helicity of the template.
DNA assemblies is either controlled by the configuration of the DNA
template or by the nucleoside configuration.
The construction of p-functional supramolecular chromo-
phore assemblies faces the challenge that chromophores have
to be kept in close proximity but complete self-quenching has
The regular right-handed helical structure of DNA is spontaneously to be ruled out. Helical stacking is an important solution to this
formed by two complementary oligonucleotides and shows problem, and therefore, the helicity is the most important key
well-defined p–p stacking distances between the base pairs feature of double-stranded DNA for chromophore architectures,
2
3
and sequence-selective hydrogen bonding encoded by the as shown, for instance, with triphenylamines. The helical twist
canonical pairing rules. These two major interactions drive also controls the rate and efficiency of energy and electron transfer
the formation of the majority of known DNA nanoarchitectures, processes and reduces the complete self-quenching that is
1
,2
as pioneered by Seeman and Rothemund, in a programmable typically observed in non-helical aggregates. This principle
3–5
way. The covalent attachment of chromophores to the nucleotides guided us, for instance, to develop a white-light emitting
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8,24
21
as DNA building blocks adds promising light-harvesting or opto- DNA
and to use such DNA architectures in solar cells.
electronic properties to DNA by structurally designed photo- The key and basic question is how helical chirality is controlled
6–9
physics. In order to build new and defined chromophore–DNA in such supramolecular DNA–chromophore architectures. In
0
architectures supramolecular oligomerization of building blocks is principle, chirality may be governed by the 2 -desoxyribofuranoside
10
the straightforward bottom-up approach. It is synthetically less configuration of the DNA template, which is either D or L. It is
challenging because it avoids the ‘‘bottleneck’’ of solid-phase known that both unmodified DNA double helices possess the
oligonucleotide synthesis and purification for covalent connections same conformation and dynamic properties except for chirality.
11
between the building blocks. For this supramolecular approach, The higher order structures of double-stranded L-DNA are also
the Watson–Crick base pairing of single-stranded DNA templates the exact mirror images (left-handed helices) of that of natural
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5,26
together with chromophore-enhanced p–p stacking drives the D-DNA.
To our knowledge, however, L-configured chromo-
self-assembly of chromophores. By these means, Schenning phore–nucleoside conjugates were not studied before for supra-
1
2–14
15,16
et al.
and Balaz et al.
assembled naphthalenes, oligo- molecular assemblies. Herein, we follow this path and present a
p-phenylenevinylenes, or porphyrins non-covalently along new study to elucidate the origin of chirality in DNA-templated
single-stranded DNA templates. H ¨a ner et al. even prepared chromophore assemblies. We used a combination of two different
1
7,18
functional DNA-grafted polymers.
We evidenced the assembly D- and L-configured chromophor–nucleoside conjugates, 1D/1L and
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0
of ethnyl pyrenes and ethynyl nile reds as 2 -deoxyuridine 2D/2L, as building blocks which are non-covalently assembled along
conjugates specifically along oligo-2 -deoxyadenosines as DNA D- and L-configured DNA templates to study the chirality of supra-
0
molecular DNA architectures by means of optical spectroscopy.
The four chromophore–nucleosides differ by the attached
Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT),
chromophore, either ethynylpyrene (1D and 1L) or ethynyl nile red
Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany. E-mail: Wagenknecht@kit.edu
0
(
2D and 2L), and by the configuration of the 2 -deoxyribofuranosides,
†
Electronic supplementary information (ESI) available: Synthesis of 1L, 2L and
a
20, and additional optical spectroscopy. See DOI: 10.1039/c8cc08887j
either D or L (Fig. 1). The D-configured conjugates 1D and 2D
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chromophores could simply be removed from the sample by short
centrifugation (1 min at 16 000g, Fig. 1). A DNA-typical annealing
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procedure as previously described is not necessary to form DNA
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0
assemblies with nearly complete occupation of binding sites.
This indicates a thermodynamically driven assembly. After
centrifugation, the supernatants of the samples were studied
by means of optical spectroscopy.
Firstly, we checked if the nucleosides show selective binding
to the differently configured DNA templates. The DNA templates
0
A
20 and a20 are complementary to all four chromophore–2 -
deoxyuridine conjugates. Titration experiments were carried out
to determine how many binding sites at these DNA templates
are occupied. Each chromophore–nucleoside aliquot was equal
to the binding of one nucleoside to the template (see Fig. S22
and S23, ESI†). Expectedly, the absorption of the supernatant
indicated high occupancy rates for the assemblies with match-
ing configurations between nucleosides and DNA templates
(Table 1): 90% of binding sites on A20 are occupied by 1D and
80% of binding sites on a20 are occupied by 1L. 2D and 2L bind
even quantitatively to their configuration-matching templates
A20 and a , respectively, indicating a stronger p–p-stacking
20
interaction between ethynyl nile red chromophores compared
to ethynylpyrenes. Surprisingly, high occupancy rates were also
observed for those DNA assemblies in which the configurations
do not match between nucleoside and template: for instance,
1D binds to 85% binding sites available on a20, and even 100%
binding sites on A20 are occupied by 2L.
These results conclusively show that there is no (or at least
no significant) configuration-selective recognition between
these four nucleosides and their templates A20 and a20. The
DNA assemblies with 1D and 1L show only slightly reduced
occupancy rates if their configuration does not match with that
of the template. A closer look on the absorbance reveal also only
very minor alterations indicating also only slight differences for
stacking interactions. Based on the knowledge that the new
L-configured nucleoside conjugates 1L and 2L bind to both A20
Fig. 1 Structure of 1D, 2D, 1L and 2L, and preparation of chromophore
assemblies along single-stranded DNA templates A20 (with D-configuration)
and a20 (with L-configuration), and idealized schematic drawing of the
assemblies of 1D along A20 and of 2L along a20
.
1
9,20
were described previously;
the L-configured conjugates were and a20 the specific base pairing was additionally checked with
20, G20 and C20. In contrast to A20 (and a20), the three ‘‘wrong’’
synthesized accordingly (see ESI† and Fig. S2 and S3). Stock
T
solutions in DMSO were prepared for each of the four nucleo- DNA templates T20, G20 and C20 are not able to keep a
sides. The absorbance and fluorescence properties of the new significant amount of 1L or 2L in aqueous solution (see Fig.
L-configured nucleosides were nearly identical (within the experi- S20 and S21, ESI†). This shows that the binding of 1L and 2L to
mental error) to those of the D-configured ones (see Fig. S16–S19, the DNA templates follows the specific base pairing rules as
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0
ESI†). The DNA-templated self-assemblies were prepared according previously evidenced for 1D and 2D assembled along A .
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0
to the following procedure (Fig. 1). Small amounts of the nucleoside Similar to double-stranded DNA, these chromophore assemblies
stock solutions in DMSO were added to the aqueous solution show cooperativity with a melting temperature at approximately
containing the DNA templates, which are the D-configured A20 or 70 1C (see ESI,† for 2D with A20, Fig. S26).
the L-configured a20. Not more than 2% DMSO were added to the
final DNA samples in water. Notably, all four nucleoside conjugates
were nearly completely insoluble in water, and only those
Table 1 Occupancy fraction f 1D, 1L, 2D and 2L along the DNA templates
nucleosides that were bound by specific base pairing to the A20 (D-configuration) and a20 (L-configuration) and chirality c of the
given DNA template were kept in aqueous solution. We know assembled chromophore helices (‘‘+’’ = right-handed or ‘‘ꢀ’’ = left-
handed) after centrifugation in water (r.t., pH 7)
from previous studies that 1D and 2D specifically bind only to
0
oligo-2 -deoxyadenosines as correct templates and not to oligo-
1D
1D 1L
1L 2D
2D 2L
2L
c
2
0
thymidines as wrong templates. This represents an important Template f (%)
c
f (%)
c
f (%)
c
f (%)
advantage for the preparation of our supramolecular chromophore
assemblies along DNA templates, because excess, hence unbound
A
20
90 ꢁ 9
85 ꢁ 9
ꢀ
65 ꢁ 7
80 ꢁ 8
ꢀ
100 ꢁ 10
85 ꢁ 9
ꢀ
ꢀ
100 ꢁ 10
100 ꢁ 10
+
+
a
20
+
+
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1D shows eximer-like fluorescence in DNA-templated assemblies, left-handed helicity, although the configuration of the nucleoside
whereas the fluorescence of 2D is completely quenched in the and the DNA template do not match. In contrast, both assemblies
20
assemblies. Hence, we did not further investigate the fluorescence of 1D and 1L, each along a , show opposite CD effect and thus
2
0
properties of the other chiralities. More importantly, we probed right-handed helicity. The CD signal of 1L with A20 is weaker
the chromophore assemblies bound to the DNA templates (after probably than the others due to the lower occupation fraction of
centrifugation) by circular dichroism (CD) spectroscopy in order 65% in this assembly. This makes conclusively clear, that the
to gain more information on the helical chromophore chirality. chirality of the assembled supramolecular chromophore helix
All four applied chromophore–nucleoside monomers alone show is controlled by the configuration of the DNA template: The
no significant CD signal, which is typical for small molecules, D-configured template A20 yields left-handed helical ethynyl
0
although they bear the chiral 2 -deoxyribofuranosides. Moreover, pyrene assemblies whereas the L-configured a20 yields right-
unbound aggregates have been removed by centrifugation during handed helical assemblies.
the sample preparation. Taken together, CD spectroscopy selec-
For the assemblies with 2D and 2L exciton-coupled CD
tively probes the assemblies of chromophores along the DNA signals were observed in the ethynyl nile red-typical absorption
templates without overlaying signals from potentially present range, consisting of two Cotton effects at 517 nm and 566 nm,
excess, but unbound monomers. Unfortunately, the helicity of and an intervening axis intersection at 540 nm (Fig. 3). The
0
the DNA core consisting of the 2 -deoxyadenosines of the templates comparison of the CD of the 2D assembly along A20 with the
0
and the 2 -deoxyuridines of the chromophore conjugates 1D, 1L, 2D published CD of a DNA with five covalently attached 2D
2
9
and 2L in these supramolecular assemblies cannot be clearly building blocks, reveals again left-handed chirality. However,
determined, because the CD spectra in the absorption range of in contrast to 1D and 1L, the chirality of the DNA assemblies
the A-dU base pair core around 260–280 nm is overlaid by the with 2D and 2L is not at all controlled by the configuration of
ethynyl pyrene or ethynyl nile red chromophores that also absorb the DNA template. Instead, both assemblies of 2D along A20
0
light in this range. But the CD spectra of the ethynylpyrene-2 - (matching) and along a20 (non-matching configuration) show
deoxyuridine assemblies (Fig. 2) show clear exciton-coupled signals left-handed helicity, whereas both assemblies of 2L along
in the typical ethynylpyrene absorption range with two Cotton
A20 and a20 show right-handed helicity. Obviously, the stronger
effects at 370 nm and 413 nm and an intervening axis intersection p–p-stacking interactions between ethynyl nile red chromophores
at 385 nm. The assembly of 1D along A20 serves as first reference that gain not only higher occupancy fractions at the templates
and shows positive Cotton effect followed by a negative one. This is additionally control the chirality of the helical DNA assemblies. It
opposite to the published CD spectrum of a right-handed double- is known that 2D stacks in left-handed chiral aggregates even in
27
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stranded DNA with five covalently attached building blocks of 1D.
the absence of any template and thereby overrules the chirality
Accordingly, the non-covalent assembly of 1D along A20 can be control by the templates A20 and a20 that was observed for 1D and 1L.
assigned to a left-handed chromophore helicity. Interestingly, such This result tracks well with an important observation by Schenning
left-handed chirality was also found by others for binding et al., that, for larger p–p interactions between chromophores in
of Zn(II)-cyclen perylene/naphthalenebisimide conjugates to the assembly, the hydrogen bonding interaction to the template
the same template A20 indicating complexer mechanisms of diminishes, and the stacking has stronger influence on the
2
8
30,31
assembly. Moreover, the assembly of 1L along A20 shows also structure, here in particular chirality.
Fig. 2 Circular dichroism spectra of DNA assemblies with 1D and 1L along
20 and a20; [DNA template] = 1.25 mM, [nucleosides] = 25 mM in water +
% DMSO, supernatant after centrifugation; grey: double-stranded (ds)
DNA covalently modified with five units of 1D adjacent to each other
Fig. 3 Circular dichroism spectra of DNA assemblies with 2D and 2L along
A20 and a20 templates; [DNA template] = 1.25 mM, [nucleosides] = 25 mM in
water + 2% DMSO, supernatant after centrifugation; grey: double-stranded
A
2
(ds) DNA covalently modified with five units of 2D adjacent to each other
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(2.5 mM in 50 mM Na–P
i
buffer, 250 mM NaCl, pH 7.0, r.t.).
i
(1.0 mM in 50 mM Na–P buffer, 250 mM NaCl, pH 7.0, r.t.).
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In conclusion, we studied the way how chirality is controlled
in supramolecular DNA-templated chromophore assemblies. We
applied a combination of four different D- and L-configured
chromophor–nucleoside conjugates, 1D/1L and 2D/2L, to probe
their non-covalent assembly along the D- and L-configured
templates A20 and a20, respectively. There are several results:
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(
i) the chirality of these supramolecular chromophore–DNA
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the DNA template, which could have been expected based on the
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the chromophore–2 -deoxyuridine conjugates follow specific
base pairing rules, there is no configuration-selective recognition
1
1
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1
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1
L are controlled by the configuration of the DNA template.
1
Interestingly, the chirality of these non-covalent assemblies is
2
27
opposite to the published covalently connected DNA architectures.
iv) In contrast, the ethynyl nile red conjugates 2D and 2L form
chiral stacks (as previously evidenced also for non-DNA-templated
5
(
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2
2
2
2
2
2
2
2
2
2
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DNA template, presumably by their stronger p–p-stacking inter-
actions. Taken together, these are important and basic results
for the design of DNA-architectures, in particular with respect
to their application as emitters and sensors for circularily
polarized luminescence.
2
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