Rigid rod and tetrahedral hybrid compounds featuring nucleobase and nucleoside End-capped structures

Article abstract of DOI:10.1039/b904889h

Being aimed at a new type of porous solids, a moduled design strategy of molecular tectons, making use of the conjugation between a shape defined artificial backbone and the bioinspired molecular fragments of nucleobases or nucleobase derivatives as functional end-caps, has been developed. This led to the formation of the new hybrid compounds 1-13 of linear and tetrahedral geometry, containing uracil, adenine, adenosine, guanosine and its acylated analogs as the sticky end-cap sites. The compounds were synthesized from a halogen or ethynyl substituted nucleobase component and the corresponding ethynylated spacer unit following a metal assisted coupling process as the key reaction step. X-Ray crystal structure analysis demonstrates that the parent compound 1 is a solvent complex with DMSO (1:2), showing the DMSO molecules incorporated in a hydrogen bonded layer structure. Specific dependencies of the fluorescence properties of the new compounds in solution on the structure of the molecules are reported. A selection of solid compounds has been studied in respect of their ability to adsorb organic vapours. They revealed significant differences both in the sorption capacity and the selectivity towards particular solvent vapours.

Full text of DOI:10.1039/b904889h

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Rigid rod and tetrahedral hybrid compounds featuring nucleobase and
nucleoside end-capped structures†
Diana Schindler, Frank Eißmann and Edwin Weber*
Received 10th March 2009, Accepted 1st June 2009
First published as an Advance Article on the web 9th July 2009
DOI: 10.1039/b904889h
Being aimed at a new type of porous solids, a moduled design strategy of molecular tectons, making use
of the conjugation between a shape defined artificial backbone and the bioinspired molecular fragments
of nucleobases or nucleobase derivatives as functional end-caps, has been developed. This led to the
formation of the new hybrid compounds 1–13 of linear and tetrahedral geometry, containing uracil,
adenine, adenosine, guanosine and its acylated analogs as the sticky end-cap sites. The compounds were
synthesized from a halogen or ethynyl substituted nucleobase component and the corresponding
ethynylated spacer unit following a metal assisted coupling process as the key reaction step. X-Ray
crystal structure analysis demonstrates that the parent compound 1 is a solvent complex with DMSO
(1:2), showing the DMSO molecules incorporated in a hydrogen bonded layer structure. Specific
dependencies of the fluorescence properties of the new compounds in solution on the structure of the
molecules are reported. A selection of solid compounds has been studied in respect of their ability to
adsorb organic vapours. They revealed significant differences both in the sorption capacity and the
selectivity towards particular solvent vapours.
based on hydrogen bonding. However, while these interactions
Introduction
were investigated in detail mostly in solution, their use in the
The conjugation of moduled synthetic building blocks to introduce
formation of new solid materials following the concepts of crystal
engineering15 in order to create porous hydrogen bonds16 or
metal coordination (MOF)17 crystalline network structures has
only scarcely been exploited.14 This is a noteworthy fact since
nucleobases make possible the creation of a quasi model type of
supramolecular synthons18 due to their complementary multiple
hydrogen bonding donor and acceptor sites.13,14 Moreover, nu-
cleobases possessing suitable shapes and systems of p-electrons
are also inclined to supramolecular stacking motifs.19 Both these
properties give rise to highly controlled molecular recognition
between two matching nucleobases, which would be a special
merit of an intended crystalline tecton20 for a particular solid state
construction, similar to the oligotopic 2-pyridinones designed by
Wuest21 or the melamine and barbituric acid complexes of the
Whitesides group.22 A conceptual outline of the intended new type
of porous solid structure is illustrated in Fig. 1.
This has stimulated the synthesis of a series of linear and tetra-
hedral hybrid compounds composed of artificial shape controlling
central units and bioinspired sticky terminal groups consisting of a
nucleobase or a derivative of it. We report the preparation of these
compounds, discuss the crystal structure of a solvated prototype
compound, give information on the fluorescence in solution, and
describe the sorption behaviour of selected solid materials of this
type towards vapours of organic solvents in view of a potential
sensor aspect.
parameters of a specific shape or functionality with components to
interface efficiently with biological systems is a highly challenging
topic.1 Hybrid compounds emerging from this are promising
targets in many significant fields including molecular diagnostics,2
tissue engineering,3 manipulation of cell adhesion4 and other tools
for chemical biology.5 Moreover, they are also expected to be useful
in the development of chemical sensors6 and adsorbents7 or poten-
tially for the construction of future electronic and optical devices.8
Important examples of structural units of high biological
relevance are nucleobases,9 which possess a crucial factor for the
stability of nucleic acid duplexes and logically are a vital point in
the very essential fields of genetic coding, biological information
storage and protein biosynthesis.10 Therefore, nucleobase deriva-
tives are widely used for medicinal or genetic applications.11 On the
other hand, considering their general importance, the potential of
nucleobases as tools in supramolecular chemistry has not yet been
fully exhausted,12 although they have been rather broadly studied
and currently reviewed in this respect by the groups of Sessler13
and Rowan.14 They show the number of different ways that the
nucleobases have already been used, including various dimeric
and polymeric assemblies, cage construction, metal coordination
and other kinds of host–guest or energy transfer systems, mainly
Institut fu¨r Organische Chemie, Technische Universita¨t Bergakademie
Freiberg, Leipziger Str. 29, D-09596, Freiberg/Sachsen, Germany. E-mail:
edwin.weber@chemie.tu-freiberg.de; Fax: (+49)3731-393170
† Electronic supplementary information (ESI) available: A. Experimental
details of compounds 2, 3, and 5–14; B. Spectroscopic data; C. 1H NMR
spectra of selected key compounds corresponding to the different struc-
tural types; D. Data of non-covalent interactions from the crystal structure
analysis. CCDC reference number 722856. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/b904889h
Results and discussion
Design strategy of compound structures
In order to obtain compounds featuring the desired property of
crystal tectones20 that will make use of the particular hydrogen
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Fig. 1 Conceptual diagram illustrating the intended new porous solid state structures based on a nucleobase pairing of molecular tectons.
Two-dimensional sketch by means of an uracil end-capped spacer molecule.
bond and heteroaromatic stacking behaviour of the biologi-
cal nucleobases, and thus create porous solids (cf. Fig. 1),13,14
terminal attachment of the respective nucleobases to a shape
defined backbone unit should be a promising working plan, as
sketched out with the linear and tetrahedral basic structures in
Fig. 2. The shape-persistency of the core units (S) is ensured
Fig. 3 Constitutional structure of the linear prototype compound 1.
by the use of particularly rigid and strictly geometrical defined
aromatic and ethynylene spacer moieties23 as well as a tetrakis(4-
species (9–13). The compound 8 represents a special case in
ethynylphenyl)methane building block24 in the one- and three-
that the molecular structure is asymmetric, because it contains
dimensional case, given by the linear (I) and tetrahedral (II)
a different nucleobase and nucleoside residue at both ends of
structural elements, respectively. The effective distance of the
the linear spacer unit. The nucleoside and substituted nucleoside
spacer moieties depends on the number of the linear connec-
structures, being present in several of the compounds (3, 5–8 and
tor units being inserted into the backbone structure. Selected
10–13), not only serve the purpose of avoiding low solubility of
nucleobases or nucleobase derivatives (Nu) applying to Fig. 2
the pure nucleobases and make their synthesis easier,13,25 but may
are uracil, adenine, adenosine, and guanosine as well as acetyl
also promote the polar interactions.
and isobutanoyl substituted analogs of the guanosine, respectively.
This gives rise to a modular construction principle as shown with
the formulas in Fig. 3–5.
Synthesis
The synthesis of the target compounds was performed by
metal assisted couplings including Eglinton26 and Sonogashira–
Hagihara27 procedures as the key reaction steps. These couplings
Table 1 Specification of the linear (arylene-ethynylene spacer type)
compounds in this study
Compound
S
Nu
R (R1-R3)
R¢
2a
2b
2c
3a
3b
3c
4
5a
5b
5c
6a
6b
6c
7a
7b
7c
8
A
B
C
A
B
C
A
A
B
C
A
B
C
A
B
C
A
2 X
2 X
2 X
2 Y
2 Y
2 Y
2 Y
2 Z
2 Z
2 Z
2 Z
2 Z
2 Z
2 Z
2 Z
2 Z
X, Y
—
—
—
R1
R1
R1
H
—
—
—
—
—
—
—
H
H
H
H
H
R1
R1
R1
R2
R2
R2
R3
R3
R3
R1
Fig. 2 Structural design concept of the linear (I) and tetrahedral (II)
target compounds with S referring to the rigid spacer units and Nu to the
nucleobase and nucleobase derivative terminal components.
H
i-butanoyl
i-butanoyl
i-butanoyl
—
Considering the specification listed in Table 1, a subdivision
of the compounds 1–13 can be made according to the following
scheme: prototype molecule (1), linear (2–8) and tetrahedral
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Fig. 4 Linear spacer (A–C), nucleobase and nucleobase derivative (X–Z) constructional components relating to the compound structures of
2–8 (Table 1).
involve reactions between halogen and ethynyl substituted
nucleobases or derivatives of nucleobases and ethynylated
spacer units. The halogenated nucleobases or nucleobase
derivatives that were used for couplings are 5-iodouracil,28
8-bromoadenosine,29 8-bromoguanosine,30 8-bromo-2¢3¢5¢-tri-O-
acetylguanosine31 and 8-bromo-2-i-butyramido-9-(2¢3¢5¢-tri-O-i-
butyryl-b-D-ribofuranosyl)-1H-purine-6-one.32 These particular
compounds were obtained by halogenation reactions of the
corresponding nucleobase or nucleobase derivatives according to
literature methods (see Experimental). 5-Ethynyluracil, which is
the coupling component for the synthesis of 1, was prepared from
5-iodouracil and monoprotected trimethylsilylacetylene (TMSA)
using the standard Sonogashira–Hagihara conditions, followed by
the cleavage of the protecting group, as described.28
The linear diethynyl spacer compounds, serving as build-
ing blocks for 2–8, were synthesized from the respective di-
bromoarene and 2-methyl-3-butyn-2-ol (MEBYNOL)33 via the
Sonogashira–Hagihara method27 and subsequent deprotection of
the ethynyl groups34 (Fig. 6). Tetrakis(4-ethynylphenyl)methane,
from which the compounds 9–13 derive, was analogously pre-
pared from tetrakis(4-bromophenyl)methane35 and MEBYNOL
followed by deprotection. It is worth mentioning here that two of
these compounds, namely 4,4¢-diethynylbiphenyl36 and tetrakis(4-
ethynylphenyl)methane,37 have previously been synthesized ap-
plying the TMSA route which, however, is much more costly
compared to the presently used MEBYNOL method. Thus
following the latter procedure is the better way to make these
compounds accessible.
Examples of synthesis for 1 and 2a as representatives of the
rod-shaped type of compounds (1–3 and 5–7), including both
the Eglinton26 and Sonogashira–Hagihara27 approach of coupling
reaction, are illustrated in Fig. 7 and 8, respectively. An analo-
gous coupling under Sonogashira–Hagihara conditions between
tetrakis(4-ethynylphenyl)methane and the respective brominated
nucleobase derivative was used for the preparation of the tetrahe-
dral compounds 9–13.
Courses different from those taken above are required for the
synthesis of compounds 4 and 8. While the diadenine 4 was
obtained by acid hydrolysis of the nucleoside 3a, the compound
8 being endowed with different nucleobase derivatives at both
ends of the molecule, i.e. uracil and adenosine, involves the
asymmetrically TMS protected 1,4-diethynylbenzene as one of the
starting compounds. This was reacted with 5-iodouracil to yield
the monoprotected spacer substituted uracil 14. Cleavage of the
blocking group to give 15 and coupling with 8-bromoadenosine
completes the sequence of reactions (Fig. 9).
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Fig. 7 Synthesis of compound 1 via Eglinton coupling.
7a–c and 13 could be carried out with catalyst I in toluene at
moderate temperature (50 ◦C). While in the synthesis of the
target compound 1 the Eglinton coupling step gave rise to only
a moderate yield of 26%, the coupling reactions according to
the Sonogashira–Hagihara method led to much higher yields.
Excepting the asymmetrical target compound 8 (final coupling
step of 27%), these yields range from about 50% in one case to more
than 90% both for the linear (2–7, including 14) and tetrahedral
species (9–13). All the final product compounds were obtained
as powdery solids that show high melting points (>300 ◦C) or
decompose before melting, except the acylated guanosines. They
possess lower melting points, decreasing in degrees from acetyl to
isobutanoyl groups. Most of the compounds are of low solubility in
common organic solvents, making purification processes difficult,
excepting the i-butanoyl modified guanosines (7a–c) which offer
the advantage of purification by column chromatography.
In the IR (KBr) spectra, the compounds containing an asym-
metrically substituted acetylenic group are typical of an intensive
absorption band between 2100–2250 cm-1, as contrasted with the
symmetrical ethynes showing only a very weak absorption. A
special structural feature is indicative of the pyrimidine ring in
compound 15, being in the tautomeric form of a 2-hydroxy-4-
oxopyrimidine structure instead of the commonly observed double
Fig. 5 Basic structure and specification of the tetrahedral compounds
(formula assignments in Fig. 3).
All Pd-catalyzed couplings were carried out under argon
in DMF or toluene under different conditions of temperature
and reaction time, and use of [Pd(PPh3)4]/CuI/Et3N (I)38 or
[Pd(PPh3)2]Cl2/CuI/Et3N (II)39 as catalytic systems, depending
on the individual case. For instance, the couplings involving
5-iodouracil (2a–c, 9 and 14) were performed in DMF at
room temperature with catalyst I, while most of the adenosine
containing compounds 3a–c and 10 were prepared at a higher
temperature (110 ◦C) due to the reduced reactivity of the bromo
derivative of adenosine40 and with the use of catalyst II, except
1
lactame structure. This is proven by H NMR (in DMSO-d6),
showing separate signals for the NH (d = 9.56 ppm) and OH
(d = 4.23 ppm) groups, and is also in correspondence with
literature data.41 Coupling of the halogenated nucleobases with
the ethynylated spacer units, making up the key reaction step, led
to distinct low field shifts in the 13C NMR spectra with reference
to the signals for the C5-pyrimidine and C8-purine carbon atoms,
ranging from 25 to 30 ppm for the uracil, and from 5 to 10 ppm
for the adenosine and guanosine derivatives. The difference in
the strength of the shift between the pyrimidines and the purines
is likely to be caused by both the different heterocyles and the
different halogens, that is iodine and bromine, which have been
◦
8 (50 C, catalyst I, 11 h). The guanosine type compounds 5a–c
and 11 as well as 6a–c and 12 were coupled in DMF at 70 ◦C with
catalyst I. On the other hand, owing to the increased solubility
caused by the i-butanoyl groups, the couplings to the compounds
Fig. 6 Synthesis of the linear diethynyl spacer compounds (schematic representation).
Fig. 8 Synthesis of 2a via Sonogashira–Hagihara coupling.
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Fig. 9 Synthesis of the asymmetrically end-capped compound 8 (R = R1, Fig. 4).
used for the halogenated pyrimidines and purines, respectively.
However, these shifts may serve as a convenient indication to
follow the course of the coupling reactions.
Crystal structure analysis
Due to the low solubility of the nucleobase end-capped com-
pounds in common low or moderate polar organic solvents, the
achievement of crystals that can be used for structural analysis
is hampered. Obviously, these solvents cannot compete with the
strong hydrogen bonds between the end-cap units. Hence, owing
to their high effectiveness as hydrogen bond acceptors, DMF
and DMSO are expected to be more promising solvents in this
respect.42 However, even when making use of these solvents,
only the linear prototype compound 1 was successful in the
formation of crystals suitable for an X-ray structural analysis.†
They were obtained by slow evaporation of a solution of 1 in
DMSO and crystallized in the monoclinic space group P21/c.
The asymmetric unit contains one molecule of 1 and two solvent
molecules (Fig. 10), thus being a solvated 1:2 complex of 1 with
DMSO.
Fig. 10 Molecular structure of 1·DMSO (1:2), including numbering of
non-hydrogen atoms.
Due to the planar geometry of compound 1, the crystal structure
is characterized by a sheet-like alignment of molecules which is
illustrated in Fig. 11. The packing shows an ABAB-sequence
of molecular layers, which are in parallel orientation to the
[101]-plane. Within one crystallographic layer, 1 and the solvent
molecules form a network stabilized by inverse bifurcated
N–H ◊ ◊ ◊ O hydrogen bonds involving two pyrimidine moieties
Fluorescence properties
Excepting the non-aromatic parent compound 1, all synthesized
nucleobase derivatives containing an aromatic spacer unit are
highly fluorescent in solution. Hence, detailed fluorescence mea-
surements were carried out in order to find a potential correlation
between molecular constitution and the particular fluorescence
maximum. As illustrated with Fig. 12(a–e), the following findings
are obvious.
Considering a distinction of the rigid core unit, no clear
tendency with reference to the emission maximum or intensity is
observed, apart from the fact that tetraphenylmethane derivatives,
due to the interrupted electronic conjugation by the central
carbon atom, show lower emission maxima than corresponding
benzene, biphenyl and tolane species. A comparison of compounds
having an identical spacer unit (e.g. benzene) but differ in the
˚
and a DMSO molecule [d(N1 ◊ ◊ ◊ O5) = 2.808 A, d(N2 ◊ ◊ ◊ O5) =
˚
˚
˚
2.871 A and d(N3 ◊ ◊ ◊ O6) = 2.768 A, d(N4 ◊ ◊ ◊ O6) = 2.843 A].
Even though the ratio of hydrogen donor (N–H) and acceptor sites
=
(C O) seems to be balanced for the molecule 1, no conventional
intramolecular hydrogen bonds between two pyrimidine moieties
are present; only weak C–H ◊ ◊ ◊ O and C–H ◊ ◊ ◊ p-interactions43,44
can be observed (ESI D†). Hence, the strong hydrogen bond
capacity of the nucleobase end-caps is eliminated by the interaction
with the solvent molecules.
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Fig. 11 Packing illustration of 1·DMSO (1:2), showing the supramolecular layer structure with hydrogen bond interactions given as broken lines
(top view). Consecutive layers are specified in bold and light drawing.
Fig. 12 Fluorescence spectra (0.1 mM solutions of 2, 3, 5, 6, 8–12 in DMSO and 7, 13 in CHCl3); intensity (ordinate) against wavelength in nm (abscissa).
The individual diagrams relate to derivatives of (a) uracil, (b) adenosine, (c) uracil and adenosine, (d) guanosine, (e) acetyl-protected guanosine, and
(f) i-butanoyl-protected guanosine.
nucleobase end-caps demonstrates a further noteworthy result.
The emission maxima of uracil derivatives are always lower than
the maxima of adenosine and guanosine derivatives, with the
latter showing the highest values for emission, on principle. On
the other side, the unprotected and acetyl-protected guanosine
derivatives do not differ significantly in the location of their
emission maxima, whereas the i-butanoyl-protected derivatives
show emission maxima at lower wavelengths and with higher
intensities. In conformity with the above observation, the emission
maximum of compound 8, featuring an aromatic spacer unit
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with attached uracil and adenosine moieties, lies in between the
corresponding values of the maxima of compounds 2a (uracil)
and 3a (adenosine). In the last analysis, nucleobase moieties as
the end-caps connected to a rigid aromatic core unit give rise to
a new structural type of luminescent molecules with fluorescent
property controllable by the used building blocks.
the high stability of the packing structure, whereas the crystalline
frameworks formed of the bulkily substituted guanosine and
adenosine molecules are more open to the vapour attack. Basically,
for the studied solids, it would seem that the property of organic
vapour sorption shows some correlation between the polarity of
the solid and the vaporous compounds.
The receptor and fluorescence properties that meet in the
present compounds are rather promising for practical fields
of application such as biomarkers in the chemical biology of
nucleic acids or a particular segment of DNA.2,45 Hence, in
a first simple test, complementary nucleobases and nucleobase
derivatives (adenine, uracil, acetyl-protected cytidin) were added
to solutions of the selected compounds 2, 3 and 6, respectively.
Unfortunately, as yet, in no case of this preliminary study was
a usable change of the emission maximum or the intensity
detected.
Conclusions
Being aimed at a new type of porous solids (Fig. 1), a moduled
design strategy of new tectonic compound structures has been
developed, making use of the conjugation between a shape
defined artificial backbone and the particular binding behaviour
of bioinspired molecular fragments to act as a specific type of
functional end cap. The shape persistency of the synthetic core unit
is considered by using particular rigid and geometrically defined
linear and tetrahedral aromatic, ethynylene and aliphatic building
blocks and spacers, while the molecular fragments derived from
biological molecules refer to nucleobases and their derivatives
(Fig. 2). Following this approach, the hybrid compounds 1–13
(Fig. 3–5 and Table 1), differing in the overall molecular geometry
and the connected nucleobase or nucleobase derivative such as
uracil, adenine, adenosine, guanosine and acetyl or isobutanoyl
substituted analogs, have been synthesized. The nucleosides in-
cluding the acetyl as well as the isobutanoyl derivatives were used
since they are easier to handle in solution compared to the pure
nucleobases.
Except the linear prototype compound 1, which was obtained
via Eglinton coupling from 5-ethynyluracil (Fig. 7), all the
other compounds 2–13 involve a Sonogashira–Hagihara coupling
process between the corresponding ethynyl containing spacer
elements and halogenated nucleobase derivatives as the key
reaction step (cf. Fig. 8). Selected conditions with reference to the
catalytic system, i.e. catalyst, solvent, temperature and reaction
time, have been tested in view of optimal conversion. In one
case, compound 4, the pure adenine end groups were liberated
by acid hydrolysis of the corresponding adenosine. Moreover,
the asymmetrically substituted compound 8, featuring different
nucleobases at both ends of the rigid rod, requires a stepwise
assembly with the use of a blocking group. All these compounds
were obtained as powdery solids that show high melting points
(>300 ◦C) or decompose before melting, except the acylated
guanosines which posses lower melting points.
The compounds are rather difficult to dissolve in common
organic solvents and resist crystallization to single crystals suitable
for an X-ray structural study, except the parent compound 1
which crystallized from DMSO in an adequate manner. The
corresponding crystals turned out to be a solvate with DMSO
featuring the solvent molecules incorporated in a hydrogen bonded
layer structure.
Fluorescence measurements performed of the different com-
pounds in solution show dependencies of the emission maxima
and intensities on the nature of the central spacer unit and the
capping nucleobase derivative, giving rise to a new structural type
of luminescent molecules with fluorescent property controllable
by the used building blocks. However, at present, the addition
of a complementary nucleobase or a nucleobase derivative, as
a possible analyte, to the solutions of the selected compounds
Organic vapour sorption
Although from the BET surface areas46 that have been taken for
random samples of solid compounds 2a, 2c, 3c, 6a–6c, 9, 10 and
12, sorption properties of this new type of molecular solids for
organic vapours are not very promising, the successful isolation
of a crystalline inclusion compound of 1 with DMSO may open
potential prospects. These possible expectations are also supported
by previous findings mentioned in the literature showing that
permanent porosity is not an absolute requirement for the sorptive
capability of a molecular solid.47 Hence a selection of solids of the
present new type of compounds was investigated with reference to
their potential property of organic vapour sorption. They involve
the compounds 2a, 3a, 7a, 10 and 13 being cases in point of linear
and tetrahedral compound structures or nucleoside and acylated
nucleoside species. The organic vapours that have been selected for
the sorption study include compounds such as ethanol, acetone,
dichloromethane, tetrahydrofuran and n-hexane, being exemplary
solvents of high and low polarity as well as of a protic and aprotic
nature. A quartz micro balance device48 was used to determine the
sorptive property of the particular solids towards the respective
solvent vapours. The results obtained are as follows (Fig. 13).
From among the solvent vapours, dichloromethane is adsorbed
the most intensively by all the solids while the adsorption of
n-hexane is of no significance. Regarding the different solid
compounds, the guanosine derivatives 7a and 13 are the most
effective ones both in the capacity and selectivity of sorption fea-
turing a distinct selectivity towards dichloromethane, compared
to the adenosine and uracil compounds. On the other hand,
these latter compounds show ratios of the adsorbed vapours that
are roughly in the same order of magnitude. A comparison of
the compounds containing linear and tetrahedral spacer units
reveals no significant differences in the guanosine cases (7a and
13), unlike the corresponding adenosines (3a and 10) which are
rather different in the sorption of THF, with the tetrahedral
derivative 10 being superior. Another remarkable finding is shown
by the adenosine compounds 3a and 10 providing a rather
strongly developed sorption of ethanol, in contrast to the acylated
guanosines, suggesting the potential ability of the adenosine
hydroxy groups to contact to the ethanol molecule via hydrogen
bonding. The linear uracil derivative 2a behaves as the less efficient
adsorbent in the series of the molecular solids, possibly indicating
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Fig. 13 Comparison of the responses of a QMB device coated with (a) guanosine derivatives 7a and 13a, and (b) adenosine derivatives 3a and 10 for
vapours of various solvents: (1) ethanol, (2) acetone, (3) dichloromethane, (4) tetrahydrofuran, (5) n-hexane.
resulted in no change of the fluorescence spectra suitable for a
practical use in chemical sensing.
Although the new compounds proved difficult to crystallize in
three dimensional bulk habitus, they are more promising for a
potential bottom-up layer type immobilization on surfaces.49 In
particular, the linear molecules are expected to act as correspond-
ing self-assembly building blocks due to the sticky nucleobase
end groups.50 In this context, ordered assemblies of this type
should result in appealing nanostructured aggregates because of
their potential applications in the realm of nanotechnology.51
It is also possible that molecules of this and related structures
are used as designed connecting pieces giving rise to electric
conductivity between biological systems.52 Another interesting
aspect relates to a potential topochemical solid state reactivity of
the uracil spacer molecules initiated by light to yield cyclobutane
dimerization products,53 possibly as a new type of polymeric
material.
Experiments to test the sorption property of a selection of solids
of the present compounds with reference to a variety of organic
vapours, investigated by quartz micro balance, demonstrated an
obvious selectivity in the sorptive behaviour with dichloromethane
adsorbing the best and n-hexane the worst. This behaviour
was most pronounced in the case of the studied guanosine
derivatives 7a and 13, while the linear and tetrahedral adenosine
derivatives 3a and 10 provide a rather strong developed sorption
of ethanol but show a distinct difference in the sorption of
THF. All this behaviour is likely to be connected with both
the stability of the solid packing structure and the polarity
interrelation between the adsorbed compound and the solid
adsorbent.
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General procedure (Pd(0) catalyzed coupling reaction) for the
synthesis of compounds 2, 3, and 5–14
Experimental section
General
The respective halogenated nucleobase or nucleoside deriv-
ative and the corresponding terminal ethynyl compound were
dissolved in a degassed mixture of triethylamine (TEA) and
N,N-dimethylformamide (DMF) or toluene. To this solution,
the catalyst, being composed of tetrakis(triphenylphosphane)-
palladium(0) (TTPd) or bis(triphenylphosphane)palladium(II)
chloride (BTPdCl) and copper(I) iodide (CuI), was added and
the mixture was stirred at room temperature under argon for 5 h.
The precipitate was filtered off and washed with hot water, ethyl
acetate and diethyl ether, in this sequence, unless otherwise stated.
Basic specifications are given below; for details see ESI A–C.†
The nucleobases, nucleosides and the catalytic species were
purchased from ABCR (uracil, [Pd(PPh3)2]Cl2) and ACROS
ORGANICS (adenosine, guanosine, Pd(OAc)2, [Pd(PPh)4]), and
were used without further purification. THF was freshly distilled
over sodium/benzophenone. Solvents for Sonogashira–Hagihara
coupling reactions were deoxygenated prior to use by ultrasound
(20 min) while bubbling argon through the solution. All reactions
were carried out under an argon atmosphere. TLC was performed
on aluminium plates coated with SiO2–60F254 (MERCK). For
column chromatography MERCK silica gel 60 (0.040–0.063 mm)
was used. Evaporation refers to removal of solvent under reduced
pressure using a rotary evaporator. Melting points were obtained
on a hot stage microscope PHMK (Rapido, Dresden) and are
uncorrected. IR spectra were recorded as KBr pellets on a Nicolet
510 FT-IR spectrometer. NMR spectra were obtained using a
Bruker DPX-400 spectrometer at 400.1 MHz (1H) or 100.6 MHz
(13C) and a Bruker DPX-500 spectrometer at 500.1 MHz (1H) or
125.8 MHz (13C); measurements were carried out at 25 ◦C with
TMS as an internal standard. Coupling constants are given in Hz
and resonance multiplicities are described as s (singlet); br s (broad
singlet); d (doublet); br d (broad doublet); dd (double doublet);
t (triplet); m (multiplet). The assignment of ribose protons is
recorded according to IUPAC nomenclature of sugar moieties.
Because of low solubility, solution 13C-NMR spectra could not be
obtained for compounds 8 and 9. Mass spectra were recorded
using the following instruments: Hewlett Packard 5890 Series
II/MS 5971 A (9, 16, 17), Varian/Ion Spec QFT FT-ICR (2a–2c,
3a, 3b, 5a, 7a), Finnigan MAT 8200 (3c, 4, 8), Bruker Daltonics
Ultraflex-II TOF-TOF (9, 10, 12), Bruker Daltonics MALDI-MS
Biflex III (5b, 5c, 6a-6c, 7b, 7c, 13), Bruker Daltonics Esquire-
LC (18) and Agilent Technologies (USA) 6890N/5973N MSD
(19). The fluorescence measurements were accomplished on a Spex
FluoroMax-3 spectrofluorometer.
5,5¢-[Benzene-1,4-diyl-di(ethyne-2,1-diyl)]diuracil (2a). 5-Iodo-
uracil, 1,4-diethynylbenzene, TTPd and DMF were used; yellow
powder (77%); mp > 300 ◦C (dec.) from DMF.
5,5¢-[Biphenyl-4,4¢-diyl-di(ethyne-2,1-diyl)]diuracil (2b). 5-Iodo-
uracil, compound 17, TTPd and and DMF were used; yellow
powder (62%); mp > 300 ◦C (dec.) from DMF.
5,5¢-[Ethyne-1,2-diyl-bis(benzene-4,1-diyl-ethyne-2,1-diyl)]di-
uracil (2c). 5-Iodouracil, 4,4¢-diethynyltolane, TTPd and DMF
were used; yellow powder (91%); mp > 300 ◦C (dec.) from DMF.
8,8¢-[Benzene-1,4-diyl-di(ethyne-2,1-diyl)]diadenosine (3a). 8-
Bromoadenosine, 1,4-diethynylbenzene, BTPdCl and DMF were
used. In modification of the general procedure, the reaction
mixture was stirred at 110 ◦C for 7 h and allowed to cool down to
room temperature Toluene was added and the precipitate washed
as described. The crude product was redissolved in hot DMF,
precipitated with toluene, collected and washed as before to yield
a brown powder (73%); mp > 300 ◦C (dec.).
8,8¢-[Biphenyl-4,4¢-diyl-di(ethyne-2,1-diyl)]diadenosine (3b). 8-
Bromoadenosine, compound 17, BTPdCl and DMF were used;
brown powder (64%); mp > 300 ◦C (dec.).
The following compounds were prepared according to litera-
ture protocols: 1,4-diethynylbenzene,34 and 4,4¢-diethynyltolane54
(from MEBYNOL and the corresponding aryl bromides followed
by deprotection), 4-ethynyl-1-(trimethylsilylethynyl)benzene55
(from 1,4-diethynylbenzene with n-BuLi and trimethylchlorosi-
lane), 5-iodouracil28 (from uracil and iodine monochlo-
ride), 8-bromoadenosine,29 8-bromoguanosine,30 8-bromo-2¢,3¢,5¢-
tri-O-acetylguanosine31 (by acetylation of guanosine fol-
lowed by bromination), 8-bromo-2-i-butyramido-9-(2¢3¢5¢-tri-O-
i-butyryl-b-D-ribofuranosyl)-1H-purine-6-one32 (by reaction of
8-bromoguanosine with i-butanoyl chloride) and 5-ethynyluracil28
(from 5-iodouracil and trimethylsilylacetylene followed by depro-
tection).
8,8¢-[Ethyne-1,2-diyl-bis(benzene-4,1-diyl-ethyne-2,1-diyl)]di-
adenosine (3c). 8-Bromoadenosine, 4,4¢-diethynyltolane, BT-
PdCl and DMF were used; brown powder (89%); mp > 300 C
◦
(dec.).
8,8¢-[Benzene-1,4-diyl-di(ethyne-2,1-diyl)]diguanosine (5a). 8-
Bromoguanosine, 1,4-diethynylbenzene, TTPd and DMF were
used. In variation of the general procedure, the reaction mixture
was stirred for 16 h at 70 ◦C and allowed to cool down to
room temperature. Dichloromethane was added, the precipitate
filtered off, stirred in boiling water, separated, washed with water,
stirred in ethyl acetate, separated and washed with ethyl acetate,
dichloromethane and in this sequence diethyl ether to yield an
orange-yellow powder (97%); mp > 300 ◦C.
5,5¢-(1,3-Butadiyne-1,4-diyl)diuracil
(1). 5-Ethynyluracil
(0.50 g, 4.0 mmol) was added to a suspension of copper(II)
acetate (0.38 g, 2.0 mmol) in pyridine/methanol (1:1, 10 cm3).
The mixture was heated to reflux for 4 h, then allowed to cool
down to room temperature and poured into sulfuric acid (9 N).
The precipitate was filtered off and washed with hot water and
diethyl ether. Recrystallization from DMF afforded a light cream
8,8¢-[Biphenyl-4,4¢-diyl-di(ethyne-2,1-diyl)]diguanosine (5b). 8-
Bromoguanosine, compound 17, TTPd and DMF were used;
orange-yellow powder (92%); mp > 300 ◦C.
8,8¢-[Ethyne-1,2-diyl-bis(benzene-4,1-diyl-ethyne-2,1-diyl)]-
diguanosine (5c). 8-Bromo-guanosine, 4,4¢-diethynyltolane,
TTPd and DMF were used; orange-brown powder (97%); mp >
300 ◦C.
◦
coloured powder (0.26 g, 26%); mp > 300 C (dec.) (lit.56 mp >
240 ◦C).
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8,8¢-[Benzene-1,4-diyl-di(ethyne-2,1-diyl)]bis(2¢,3¢,5¢-tri-O-ace-
tylguanosine) (6a). 8-Bromo-2¢,3¢,5¢-tri-O-acetylguanosine, 1,4-
diethynylbenzene, TTPd and DMF were used. In variatio◦n of the
general procedure, the mixture was stirred for 8 h at 50 C. The
solvent was evaporated and the residue stirred in boiling water.
The collected solid was washed with water, stirred in ethyl acetate,
separated and washed with ethyl acetate and diethyl ether to afford
an orange powder (85%); mp 270 ◦C (dec.).
8,8¢,8¢¢,8¢¢¢-[Methanetetrayl-tetrakis(benzene-4,1-diyl-ethyne-2,
1-diyl)]tetraguanosine (11). 8-Bromoguanosine, compound 19,
TTPd and DMF were used; orange powder (95%); mp > 300 ◦C.
8,8¢,8¢¢,8¢¢¢-[Methanetetrayl-tetrakis(benzene-4,1-diyl-ethyne-2,
1-diyl)]tetrakis(2¢,3¢,5¢-tri-O-acetylguanosine)
(12). 8-Bromo-
2¢,3¢,5¢-tri-O-acetylguanosine, compound 19, TTPd and DMF
were used; orange-brown powder (97%); mp 266 ◦C (dec.).
Tetrakis{4-[(2-i-butyramido-6-oxo-9-(2¢,3¢,5¢-tri-O-i-butyryl-
b -D-ribofuranosyl)-1H -purine-8-yl)ethynyl]phenyl }methane
(13). 8-Bromo-2-i-butyramido-9-(2¢3¢5¢-tri-O-i-butyryl-b-
D-ribofuranosyl)-1H-purine-6-one, compound 19, TTPd and
DMF were used. In modification of the general procedure, the
8,8¢-[Biphenyl-4,4¢-diyl-di(ethyne-2,1-diyl)]bis(2¢,3¢,5¢-tri-O-
acetylguanosine) (6b). 8-Bromo-2¢,3¢,5¢-tri-O-acetylguanosine,
compound 17, TTPd and DMF were used; orange powder (72%);
mp 220 ◦C (dec.).
◦
mixture was stirred for 20 h at 50 C. The solvent was removed
8,8¢-[Ethyne-1,2-diyl-bis(benzene-4,1-diyl-ethyne-2,1-diyl)]bis-
and the residue extracted with chloroform. Evaporation of the
(2¢,3¢,5¢-tri-O-acetylguanosine)
(6c). 8-Bromo-2¢,3¢,5¢-tri-O-
solvent yielded a light green powder (96%); mp 106–111 ◦C.
acetylguanosine, 4,4¢-diethynyltolane, TTPd and DMF were
used; orange powder (87%); mp 240 ◦C (dec.).
4-(2,4-Dioxo-1H,3H-pyrimidine-5-yl)-1-[(trimethylsilyl)ethy-
nyl ] benzene (14). 5-Iodouracil, 4-ethynyl-1-(trimethylsilylethy-
nyl)benzene, TTPd and DMF were used. In modification of
the general procedure, the reaction time was extended to 21 h.
From the collected precipitate which had formed, the symmetrical
coupling product of the used ethynyl starting compound was
isolated (0.36 g; mp 228–232 ◦C). Partial evaporation of the mother
liquor and use of the purification steps described for 2a yielded 14
as a yellow powder (50%); mp 292–300 ◦C (dec.).
1,4-Bis{[2-i-butyramido-6-oxo-9-(2¢,3¢,5¢-tri-O-i-butyryl-b-D-
ribofuranosyl)-1H-purine-8-yl]ethynyl}benzene (7a). 8-Bromo-
2-i-butyramido-9-(2¢3¢5¢-tri-O-i-butyryl-b-D-ribofuranosyl)-1H-
purine-6-one, 1,4-diethynylbenzene, TTPd and toluene were
used. In modification of the general procedure, the mixture
was stirred for 5 h at 50 ◦C. The solvent was evaporated and
the residue stirred in boiling water, then collected, washed with
water and dried. Purification by column chromatography (SiO2,
eluent: diethyl ether, then CH2CH2/MeOH, 9:1) yielded an
orange-brown powder (90%); mp 215 ◦C (dec.).
8,8¢-[Benzene-1,4-diyl-di(ethyne-2,1-diyl)]diadenine (4). A sus-
pension of 3a (0.40 g, 0.61 mmol) in hydrochloric acid (1M, 24 ml)
was heated to 100 ◦C for 4.5 h. The mixture was neutralized with
aqueous sodium hydrogencarbonate and cooled for several hours
to approx. 0 ◦C. The precipitate which formed was collected and
dried to yield a light brown solid (0.20 g, 83%); mp > 300 ◦C (dec.).
4,4¢-Bis{[2-i-butyramido-6-oxo-9-(2¢,3¢,5¢-tri-O-i-butyryl-b-D-
ribofuranosyl)-1H-purine-8-yl]ethynyl}biphenyl (7b). 8-Bromo-
2-i-butyramido-9-(2¢3¢5¢-tri-O-i-butyryl-b-D-ribofuranosyl)-1H-
purine-6-one and compound 17, TTPd and toluene were used.
Column chromatography with diethyl ether/MeOH (gradient
98:2–25:75) as eluent yielded a yellow-orange powder (63%); mp
145–150 ◦C.
4-(2-Hydroxy-4-oxo-pyrimidine-5-yl)-1-ethynylbenzene
(15).
To a solution prepared from finely powdered KOH (11.46 g,
204.0 mmol) in MeOH/THF (1:1, 50 cm3), compound 14 (0.60 g,
1.95 mmol) was added. The suspension was stirred for 7 h at
room temperature. After partial evaporation of the solvent, the
precipitate was collected and washed with small portions of
MeOH and diethyl ether to yield a yellow powder (0.21 g, 47%);
mp > 300 ◦C (dec.).
4,4¢-Bis{[2-i-butyramido-6-oxo-9-(2¢,3¢,5¢-tri-O-i-butyryl-b-D-
ribofuranosyl)-1H-purine-8-yl]ethynyl}tolane
(7c). 8-Bromo-
2-i-butyramido-9-(2¢3¢5¢-tri-O-i-butyryl-b-D-ribofuranosyl)-1H-
purine-6-one, and 4,4¢-diethynyltolane, TTPd and toluene were
used. Column chromatography with n-hexane/ethyl acetate (1:2)
yielded a yellow powder (51%); mp 145–148 ◦C.
4,4¢-Bis(3-hydroxy-3-methyl-1-butyne-1-yl)biphenyl (16). To a
degassed mixture of 4,4¢-dibromobiphenyl (8.30 g, 26.6 mmol),
2-methyl-3-butyn-2-ol (MEBYNOL) (6.30 cm3, 64.3 mmol), TEA
(50 cm3) and toluene (50 cm3) were added palladium(II) ac-
etate (80.0 mg, 0.356 mmol), triphenylphosphane (186.7 mg,
0.712mmol) andCuI (33.3 mg, 0.175 mmol). The resulting mixture
was heated to reflux for 8 h. After cooling to room temperature
the precipitate was filtered off. The filtrate was evaporated and the
residue recrystallized from toluene/2-propanol to obtain a white
crystalline powder (5.61 g, 88%); mp 233 ◦C.
1-[(6-Amino-9-b-D-ribofuranosyl-purine-8-yl)ethynyl]-4-[(2,4-
dioxo-1H,3H-pyrimidine-5-yl)ethynyl]benzene
(8). 8-Bromo-
adenosine, compound 15, TTPd and DMF were used. In
modification ◦of the general procedure, the reaction mixture was
stirred at 50 C for 11 h to yield a brown powder (27%); mp >
300 ◦C (dec.).
8,8¢,8¢¢,8¢¢¢-[Methanetetrayl-tetrakis(benzene-4,1-diyl-ethyne-2,
1-diyl)]tetrauracil (9). 5-Iodouracil, compound 19, TTPd and
DMF were used; yellow powder (79%); mp > 300 ◦C (dec.).
4,4¢-Diethynylbiphenyl (17). Compound 16 (5.25 g, 16.5 mmol)
was added to a solution prepared from sodium (0.16 g, 7.0 mmol)
in 2-propanol (104 cm3). The resulting mixture was heated to
reflux for 3 h. During this time a slight stream of argon was
passed through the mixture to remove liberated acetone. After
cooling to room temperature, the mixture was diluted with diethyl
ether (100 cm3) and washed with water (5 ¥ 50 cm3). The organic
8,8¢,8¢¢,8¢¢¢-[Methanetetrayl-tetrakis(benzene-4,1-diyl-ethyne-2,
1-diyl)]tetraadenosine (10). 8-Bromoadenosine, compound 19,
BTPdCl and DMF were used. In modification of the general
procedure, the mixture was stirred at 110 ◦C for 19 h to yield
a brown powder (83%); mp > 300 ◦C (dec.).
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layer was dried over Na2SO4 and the solvent evaporated. The
light yellow residue was recrystallized from 2-propanol to yield
based on F2 for all reflections.59 The hydrogen atoms were included
in the models in calculated positions, with the exception of the
amino hydrogens H1N to H4N, and were refined as constrained
to bonding atoms.
◦
a yellow-white cry◦stalline powder (2.18 g, 65%); mp 167–168 C
(lit.56 mp 167–169 C).
Tetrakis[4-(3-hydroxy-3-methyl-1-butyne-1-yl)phenyl]methane
(18). To
a suspension of tetrakis(4-bromophenyl)methane
Acknowledgements
(5.53 g, 8.7 mmol) and 2-methyl-3-butyn-2-ol (MEBYNOL)
(13.60 cm3, 139.2 mmol) in TEA (140 cm3) were added palla-
dium(II) acetate (156.3 mg, 0.696 mmol), triphenylphosphane
(365.1 mg, 1.392 mmol) and CuI (132.6 mg, 0.696 mmol). The
resulting mixture was heated to reflux for 11 h. After cooling to
room temperature, the precipitate was filtered off and washed with
diethyl ether (3 ¥ 50 cm3). The combined filtrates were evaporated
to yield an oily residue which was recrystallized from toluene/2-
propanol to obtain a light yellow powder (4.03 g, 72%); mp >
300 ◦C (dec.).
We thank Dr Sperling (IPF Dresden) and M. Jobst (TU
Bergakademie Freiberg, Institut fu¨r Physikalische Chemie) for
help with the fluorescence and sorption measurements, respec-
tively.
References
1 (a) H. A. Currie, S. V. Patwardhan, C. Perry, and P. Roach, in Hybrid
Materials, ed. G. Kickelbick, Wiley VCH, Weinheim, 2007, p. 225;
(b) H.-J. Schneider, in Intelligent Materials, eds. M. Shahinpoor, and
H.-J. Schneider, Royal Society of Chemistry, Cambridge, UK, 2008,
p. 506.
2 (a) A. Fegan, P. S. Shirude and S. Balasubramanian, Chem. Commun.,
2008, 2004; (b) Y. J. Seo and B. H. Kim, Chem. Commun., 2006, 150;
(c) Y. J. Seo, J. R. Ryu and B. H. Kim, Org. Lett., 2005, 7, 4931.
3 (a) P. Tomlins, in Degradation Rate of Bioresorbable Materials, ed.
F. J. Buchanan, Woodhead, Abington, 2008; (b) N. Kamazoe, G. Chen
and T. Tateishi, Hyomen, 2007, 45, 73.
4 P. Roach, D. Eglin, K. Rohde and C. Perry, J. Mater. Sci., 2007, 18,
1263.
5 K. Tsuru, S. Hayakawa, and A. Osaka, in Hybrid Materials, ed.
G. Kickelbick, Wiley VCH, Weinheim, 2007, p. 301.
6 (a) L. Baltzer, in Creative Chemical Sensor Systems (Topics in Current
Chemistry, vol. 277), ed. T. Schrader, Springer, Berlin-Heidelberg, 2007,
p. 89; (b) Fluorescence Sensors and Biosensors, ed. R. B. Thompson,
Marcel Dekker, New York, 2005.
Tetrakis(4-ethynylphenyl)methane (19). Compound 18 (4.41 g,
6.8 mmol) was added to a solution prepared from sodium (4.41 g,
191.8 mmol) in 2-propanol (270 cm3). The mixture was heated
to reflux for 6 h. During this time a slight stream of argon was
passed through the mixture to remove liberated acetone. After
cooling to room temperature, the mixture was diluted with water
(200 cm3) and extracted with diethyl ether (5 ¥ 50 cm3). The
combined organic extracts were washed with 5% HCl solution
(4 ¥ 50 cm3) and water (2 ¥ 50 cm3). The solvent was evaporated
and the resulting residue was purified by column chromatography
(SiO2, eluent: CHCl3) to yield a light yellow powder (2.10 g, 74%);
mp > 300 ◦C (dec.).
7 N. Hu¨sing, in Hybrid Materials, ed. G. Kickelbick, Wiley VCH,
Vapour sorption experiments
Weinheim, 2007, p. 175.
8 Functional Hybrid Materials, eds. P. G. Romero, and C. Sanchez, Wiley
VCH, 2003, p. 122 and 347.
The experimental setup of the quartz crystal microbalance consists
of two 10 MHz standard electronic quartzes with gold electrodes
(FOQ Piezo Technik, Germany). One of them is uncoated and
used as a reference; the other one is coated with the receptor. Both
quartzes are located in a thermostated metal block (controlled to
25 ◦C by a water thermostat). The measurements are carried out
with a constant flow of synthetic air. The resonance frequencies of
the quartzes are measured by a multichannel frequency counter
(HKR sensor systems Munich, Germany) with a resolution of
1 Hz. The frequency data can be read by the computer via a
serial interface. The coating of the quarzes was performed by
dipping the quartz into a saturated solution of the compound
in dichloromethane (7a, 13) or DMF (2a, 3a, 10). According
to the Sauerbrey equation,57 the measured frequency change is
proportional to the increase of mass caused by the adsorbed
solvent, which is given as a percentage of the coating. Therefore
the adsorption relates to the thickness of the coating and the data
meet the requirement for a reasonable comparison.
9 G. M. Blackburn, M. J. Gait, and D. Loakes, Nucleic Acids in Chemistry
and Biology, 3rd ed., Royal Society of Chemistry, Cambridge, UK, 2006.
10 (a) V. A. Bloomfield, D. M. Crothers, and J. Tinoco, Nucleic Acids–
Structures, Properties and Functions, University Science Books, Sausal-
ito, 2000; (b) D. Voet, and J. G. Voet, Biochemistry, 3rd ed., Wiley, New
York, 2004.
11 Modified Nucleosides, ed. P. Herdewijn, Wiley VCH, Weinheim, 2008.
12 (a) K. Ariga, and T. Kunitake, Supramolecular Chemistry–
Fundamentals and Applications, Springer, Berlin-Heidelberg, 2006;
(b) J. W. Steed, D. R. Turner, and K. J. Wallace, Core Concepts in
Supramolecular Chemistry and Nanochemistry, Wiley, Chichester, 2007.
13 J. L. Sessler, C. M. Lawrence and J. Jayawickramarajah, Chem. Soc.
Rev., 2007, 36, 314.
14 S. Sivakova and S. J. Rowan, Chem. Soc. Rev., 2005, 34, 9.
15 (a) Frontiers in Crystal Engineering, ed. E. R. T. Tiekink, and J. Vittal,
Wiley, Hoboken, 2006; (b) Design of Organic Solids (Topics in Current
Chemistry, vol. 198), ed. E. Weber, Springer, Berlin-Heidelberg, 1998;
(c) G. R. Desiraju, Crystal Engineering–The Design of Organic Solids,
Elsevier, Amsterdam, 1989.
16 T. Hertzsch, J. Hulliger, E. Weber, and P. Sozzani, in Encyclopedia of
Supramolecular Chemistry, ed. J. L. Atwood, and J. W. Steed, Marcel
Dekker, New York, 2004, p. 996.
17 (a) G. Fe´rey, Chem. Soc. Rev., 2008, 37, 191; (b) P. A. Wright, Microp-
orous Framework Solids, Royal Society of Chemistry, Cambridge, UK,
2008.
X-Ray diffraction†
18 (a) G. R. Desiraju, Angew. Chem., 1995, 117, 2541(Angew. Chem. Int.
Ed., 1995, 34, 2311); (b) A. Nangia, and G. R. Desiraju, in Design of
Organic Solids (Topics in Current Chemistry, vol. 198), ed. E. Weber,
Springer, Berlin-Heidelberg, 1998, p. 57.
19 I. Dance, in Encyclopedia of Supramolecular Chemistry, ed. J. L. At-
wood, and J. W. Steed, Marcel Dekker, New York, 2004, p. 1076.
20 P. Metrangolo, and G. Resnati, in Encyclopedia of Supramolecular
Chemistry, ed. J. L. Atwood, and J. W. Steed, Marcel Dekker, New
York, 2004, p. 1484.
Crystals of 1 suitable for structure analysis were obtained by slow
evaporation of a solution of 1 in DMSO. The intensity data
were collected on a Bruker APEX II diffractometer with Mo-
˚
Ka radiation (l = 0.71073 A) using w- and j-scans. Reflections
were corrected for background, Lorentz and polarisation effects.
Preliminary structure models were derived by application of direct
methods58 and were refined by full-matrix least squares calculation
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Org. Biomol. Chem., 2009, 7, 3549–3560 | 3559
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View Article Online
21 (a) O. Saied, T. Maris and J. D. Wuest, J. Am. Chem. Soc., 2003, 125,
14956; (b) M. Gallant, M. T. P. Viet and J. D. Wuest, J. Org. Chem.,
1991, 56, 2284.
22 (a) J. C. MacDonald and G. M. Whitesides, Chem. Rev., 1994, 94, 2383;
(b) J. A. Zerkowski, C. T. Seto and G. M. Whitesides, J. Am. Chem.
Soc., 1992, 114, 5473.
43 G. R. Desiraju, and T. Steiner, The Weak Hydrogen Bond (IUCR
Monographs on Crystallography), Oxford University Press, Oxford,
UK, 1999.
44 M. Nishio, CrystEngComm, 2004, 6, 130.
45 Y. J. Seo, G. T. Hwang and B. H. Kim, Nucleic Acids Symp. Ser., 2005,
49, 135.
23 T. Mu¨ller, W. Seichter and E. Weber, New. J. Chem., 2006, 30, 751.
24 (a) D. Laliberte, T. Maris and J. D. Wuest, Can. J. Chem., 2004, 82, 386;
(b) E. Galoppini and R. Gilardi, Chem. Commun., 1999, 173.
25 A. Harriman, D. J. Magda and J. L. Sessler, J. Phys. Chem., 1991, 95,
1530.
26 G. Eglinton and A. R. Galbraith, J. Chem. Soc., 1959, 889.
27 (a) S. Takahashi, Y. Kuroyama, K. Sonogashira and N. Hagihara,
Synthesis, 1980, 627; (b) K. Sonogashira, Y. Tohda and N. Hagihara,
Tetrahedron Lett., 1975, 4467.
28 Z. Janeba, J. Balzarini, G. Andrei, R. Snoek, E. De Clercq and M. J.
Robins, Can. J. Chem., 2006, 84, 580.
29 K. Meszarosova, A. Holy and M. Masojidkova, Collect. Czech. Chem.
Commun., 2000, 65, 1109.
46 G. Brezesinski, and H.-J. Mo¨gel, Grenzfla¨chen und Kolloide, Spektrum
Akademischer Verlag, Heidelberg, 1993, p. 42.
47 (a) S. K. Ghosh, W. Kaneko, D. Kiriya, M. Ohba and S. Kitagawa,
Angew. Chem., 2008, 120, 8975 (Angew. Chem. Int. Ed., 2008, 47, 8843);
(b) S. R. Halper, L. Do, J. R. Stork and S. M. Cohen, J. Am. Chem.
Soc., 2006, 128, 15255; (c) M.-H. Zeng, X.-L. Feng and X.-M. Chen,
J. Chem. Soc. Dalton Trans., 2004, 2217.
48 (a) A. Janshoff, H.-J. Galla and C. Steinem, Angew. Chem., 2000, 112,
4164 (Angew. Chem. Int. Ed., 2000, 39, 4004); (b) K. Matsuura, K.
Ariga, K. Endo, Y. Aoyama and Y. Okahata, Chem. Eur. J., 2000, 6,
1750; (c) U. Schramm, C. E. O. Roesky, S. Winter, T. Rechenbach,
P. Boeker, P. Schulze Lammers, E. Weber and J. Bargon, Sensors and
Actuators B, 1999, 57, 233.
30 J. C. Niles, J. S. Wishnok and S. R. Tannenbaum, Chem. Res. Toxicol.,
2000, 13, 390.
49 (a) J. V. Barth, G. Constantini and K. Kern, Nature, 2005, 437, 671;
(b) A. Dimitriev, H. Spillmann, N. Lin, J. V. Barth and K. Kern, Angew.
Chem., 2003, 115, 2774 (Angew. Chem. Int. Ed., 2003, 42, 2670); (c) S.
De Feyter and F. C. De Schryver, Chem. Soc. Rev., 2003, 32, 139.
50 L. M. A. Perdiga˜o, A. Saywell, G. N. Fontes, P. A. Staniec, G. Goretzki,
A. G. Phillips, N. R. Champness and P. H. Beton, Chem. Eur. J., 2008,
14, 7600.
51 D. M. Vriezema, M. C. Aragones, J. A. A. W. Elemans, J. Cornelissen,
A. E. Rowan and R. J. M. Nolte, Chem. Rev., 2005, 105, 1445.
52 D. Porath, G. Cuniberti and R. Di Felice, Top. Curr. Chem., 2004, 237,
183.
31 J. F. Gerster, B. C. Hinshaw, R. K. Robins and L. B. Townsend, J. Org.
Chem., 1968, 33, 1070.
32 J. L. Sessler, B. Wang and A. Harriman, J. Am. Chem. Soc., 1995, 117,
704.
33 P. V. S. N. Vani, A. S. Chida, R. Srinivasan, M. Chandrasekharam and
A. K. Singh, Synth. Commun., 2001, 31, 219.
34 J. A. H. MacBride and K. Wade, Synth. Commun., 1996, 26, 2309.
35 R. Rathore, C. L. Burns and I. A. Guzei, J. Org. Chem., 2004, 69,
1524.
36 L. Liu, Z. Liu, W. Xu, H. Xu, D. Zhang and D. Zhu, Tetrahedron, 2005,
53 S. S. Chawada and S. Jain, Asian J. Chem., 2001, 13, 1231.
54 E. S. Alekseyeva, M. A. Fox, J. A. K. Howard, J. A. H. MacBride and
K. Wade, Appl. Organomet. Chem., 2003, 17, 499.
55 G. Lowe, A. S. Droz, T. Vilaivan, G. W. Weaver, J. J. Park, J. M. Pratt,
L. Tweedale and L. R. Kelland, J. Med. Chem., 1999, 42, 3167.
56 N. G. Kundu, M. Pal and C. Chowdhury, J. Chem. Res. Synop., 1993,
432.
61, 3813.
37 K.-Y. Kim and K. S. Schanze, Proc. SPIE-Int. Soc. Opt. Eng., 2006,
6331, 63310C/1.
38 R. H. E. Hudson, G. Li and J. Tse, Tetrahedron Lett., 2002, 43,
1381.
39 A. G. Firth, I. J. S. Fairlamb, K. Darley and C. G. Baumann,
Tetrahedron Lett., 2006, 47, 3529.
57 G. Sauerbrey, Z. Phys., 1959, 155, 206.
40 M. Ikehara and M. Kaneko, Tetrahedron, 1970, 26, 4251.
41 (a) I. Gould and I. H. Hillier, J. Chem. Soc. Perkin Trans. 2, 1990, 329;
(b) D. Shugov and J. J. Fox, Biochim. Biophys. Acta, 1952, 9, 199.
42 E. Weber, J. Mol. Graphics, 1989, 7, 12.
58 G. M. Sheldrick, SHELXS-97, Program for solution of crystal struc-
tures, University of Go¨ttingen, Germany, 1997.
59 G. M. Sheldrick, SHELXL-97, Program for refinement of crystal
structures, University of Go¨ttingen, Germany, 1997.
3560 | Org. Biomol. Chem., 2009, 7, 3549–3560
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