Synthesis of Porphyrins Di- and Tetra-Functionalized with Nucleobases

Article abstract of DOI:10.1002/ejoc.202001406

A library composed of ten porphyrins bearing nucleobases is prepared, following two strategies: substitution or Sonogashira cross-coupling reactions. The former strategy led to the synthesis of four porphyrins (T₂?Po1, A₂?Po1, C

Full text of DOI:10.1002/ejoc.202001406

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Synthesis of Nucleobase di- and tetra-functionalized Porphyrins
Authors: Elsa Tufenkjian, Christophe Kahlfuss, Nathalie Kyritsakas, Mir
Wais Hosseini, and Véronique Bulach
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202001406
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0
1/2020

European Journal of Organic Chemistry
10.1002/ejoc.202001406
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Synthesis of Nucleobase di- and tetra-functionalized Porphyrins
[
a]
[a]
[a]
[a]
Elsa Tufenkjian, Christophe Kahlfuss, Nathalie Kyritsakas, Mir Wais Hosseini,* and
Véronique Bulach*[a]
[
a]
Dr. E. Tufenkjian, Dr. C. Kahlfuss, N. Kyritsakas, Pr. M. W. Hosseini, Pr. V. Bulach
Institution Department Chemistry of Complex Matter laboratory ,UMR 7140
University of Strasbourg, Institut Le Bel, 67000, Strasbourg, France
Supporting information for this article is given via a link at the end of the document.
Abstract: A library composed of ten porphyrins bearing nucleobases
is prepared, following two strategies: substitution or Sonogashira
cross coupling reactions. The former strategy led to the synthesis of
2 2 2 2
four porphyrins (T -Po1, A -Po1, C -Po1 and P -Po1) bearing
nucleobases (NBs) at two trans meso-positions. These 4 porphyrins
were obtained by reacting 5,15-di(4-(bromomethyl)phenyl)-10,20-
dimesitylporphyrin (Po1) with thymine (T), adenine (A), cytosine (C)
and 2-amino-6-chloropurine (P),
respectively in the presence of a suitable base. A fifth porphyrin, 5,15-
di(N9-methylphenylguanine)-10,20-dimesitylporphyrin (G -Po1) was
obtained by hydrolysis of P -Po1. A thymine tetra-functionalized
porphyrin was also synthesized following the same strategy starting
from and 5,10,15,20-tetrakis[4-(bromomethyl)phenyl]porphyrin
Po2). The second strategy based on Sonogashira cross coupling
reactions between 5,15-dibromo-10,20-dipentylporphyrin (Po3) and
ethynyl-substituted nucleobases resulted in four rigid porphyrins (U
Po3, C -ZnPo3, A -ZnPo3 and G -ZnPo3).
a precursor of guanine (G),
Figure 1. Nucleobases and their possible base paring
2
2
Both porphyrins and nucleobases (NBs) are naturally occurring
molecules, and when linked together they lead to entities with a
wide range of properties and applications. For example, Sessler
T
(
7
et al. described several dimeric assemblies based on porphyrin
bearing guanine and cytosine forming photo antennas for photo-
2
-
8,9
10
induced energy transfer or for photo-induced electron transfer .
In addition, Champness et. al. recently reported the synthesis and
the surface based assemblies of thymine and adenine bearing
2
2
2
porphyrins.1
1,12
Moreover, Balaz et. al.
13a-c
and Stulz et. al.
13d-e
described the synthesis, properties and applications of several
DNA-templated porphyrin assemblies.
Introduction
Porphyrins have been extensively studied due to their unique
structure, biological properties and their vital role in several
natural processes. Their distinctive chemical and physical
NB-Porphyrins were synthesized following different strategies,
such as Sonogashira cross coupling reaction1
0,13a
or by reacting
1
aldehydes bearing the corresponding nucleobases with
pyrrole11,12 or dipyrromethanes . Other synthetic approaches
were also used to introduce NBs to the porphyrin scaffold. For
instance, the uracil-functionalized porphyrins described by Drain
properties, in addition to their thermal stability and robustness,
make them candidates of choice for the construction of conductive
polymers, light-harvesting materials, chemical sensors, organic
8,9
2
devices and others. Furthermore, porphyrins are widely used in
14
15
et al. , the water-soluble NB-porphyrins reported by Maiya et al.
molecular tectonics due to the presence of their four meso and
eight -pyrrolic positions that can be functionalized by a variety of
coordinating and H-bonding sites. Moreover, the tetra-aza core
may bind various metal cations and self-assemble through π-π
interactions.3
and the NB-porphyrin hybrid compounds described by Schneider
et al.16 were synthesized by an Adler synthesis , an alkylation
reactions of NB’s active amine sites and by a condensation
reaction between corresponding NBs and porphyrin derivatives
respectively. Furthermore, the synthesis of porphyrins bearing
nucleobases via ethoxy and acetyl linkers18 or via amide linkers19
was also reported. Taking in consideration the previously followed
synthetic pathways, we developed two new simple approaches to
synthesize NB-porphyrins tectons. Herein, we describe the
synthesis of 10 new NB-functionalized porphyrins via substitution
reactions of porphyrin precursors bearing bromobenzyl groups by
nucleobases or through Sonogashira cross coupling reactions
17
H-bonded porphyrin assemblies have attracted a considerable
4
5
interest , especially in molecular tectonics . However, concerning
H-bonds as assembling nodes, the control and thus the prediction
of the final architecture is a challenge because of their high
reversibility and flexibility. Nature has provided nucleobases
(NBs) that are known for their complementary base pairing
properties in DNA and RNA as stable, reliable and predictable
hydrogen bonding patterns, indeed thymine (T) (in DNA) or uracil
between
a
trans meso-dibromoporphyrin and ethynyl-
(U) (in RNA) is complementary to adenine (A) whereas cytosine
nucleobases. These new tectons are well suited for the formation
of H-bonded porphyrin based networks either in the crystalline
(
C) is complementary to guanine (G) (in DNA and RNA) (Figure
). Therefore, several examples of nucleobase-functionalized
6
1
20
porphyrin were reported in the past decade.7-12
phase or on surface . We describe here the formation of such a
1
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European Journal of Organic Chemistry
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H-bonded network in the crystals for the tecton bearing two dipyrromethane is crucial to avoid the formation of porphyrins
cytosines in trans positions. Moreover, the complementarity of the
mixtures due to scrambling.23 Po1 was then reacted with
tectons open the possibility to generate H-bonded networks nucleobases in the presence of a suitable base (Scheme 1). The
based on complementary pairs such as T Po/A Po or C Po/G Po. reaction conditions are summarized in Table 1.
2 2 2 2
Such networks have been investigated either in the solid state or
on surface and will be reported elsewhere. Furthermore, the
possibility to introduce metallic cations in the porphyrin cavity
opens the way to molecular networks of higher dimensionality by
taking advantage of the possibility of introducing additional
ligands in the axial position of the metal cation present in the
tetraaza core of the porphyrin cavity.
2
Synthesis of T -Po1
Po1 was reacted with an excess of thymine in the presence of
o
K CO in dry DMF at 40 C to yield 72% of the targeted 5,15-di(N1-
2
3
methylphenylthymine)-10,20-dimesitylporphyrin
2
(T -Po1),
bearing thymine in the two trans meso-positions.
1
The H-NMR spectrum of T
2
-Po1 confirmed the presence of two
thymine moieties. Interestingly, it also showed that the peaks
corresponding to the CH protons are affected by the nature of the
deuterated solvent, which suggest that the two protons of the CH
site are diastereotopic. In CDCl , the signals of the methylene
protons appeared as two peaks each integrating for two protons
with a δ of 0.25 ppm. Upon addition of drops of deuterated
methanol, these peaks shifted closer to each other with a δ of
2
Results and Discussion
2
3
The targeted tectons are porphyrin molecules functionalized at
their meso-positions by NBs via phenyl or ethynyl groups leading
to flexible or rigid tectons respectively.
0
.07 ppm (Figure ESI 1). Moreover, in d
water) the signal corresponding to the CH appeared as a singlet
integrating for four protons. The presence of two singlets in a non-
protic solvent such as CDCl could indicate the formation of
intermolecular H-bonds between thymine that lead to two non-
equivalent signals for the CH protons.
6
-DMSO (containing
Synthesis of flexible NB-porphyrins tectons
2
Various examples in the literature proved that the substitution of
N1 site of pyrimidines and N9 site of purines with different alkyl
substituents can be easily achieved.21 Therefore, we aimed to
3
2
apply a similar procedure between nucleobases’ active amino
sites and porphyrins bearing either two (Scheme 1A) or four
(Scheme 2) 4-(bromomethyl) phenyl groups at meso positions.
Table 1. Reaction conditions and yields of NB
2
-Po1 synthesis from Po1
Di-functionalized NB-porphyrins
NB (nb eq)
Base (nb eq)
CO (3)
NaH (3)
Product (Yield)
The
5,15-bis[4-(bromomethyl)phenyl]-10,20-bis(mesityl)
T (5)
C (5)
A (5)
P (5)
K
2
3
T
2
-Po1 (72%)
porphyrin (Po1) was used as starting material. It was prepared
C
2
-Po1 (37%)
22
23
as described by Jones et al. , from mesityl-dipyrromethane and
-(bromomethyl)benzaldehyde. The use of a sterically hindered
4
K
2
2
CO
3
3
(3)
(3)
A
2
-Po1 (54%) + A-Po1-A’ (5%)
K
CO
P
2
-Po1 (80%) + P-Po1-P’ (8%)
Scheme 1. A) Synthetic route of NB
2
2
-Po1. B) Synthetic route of G -Po1. C) Chemical Structure of the nucleobases and their active amino site shown in red.
2
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2
Synthesis of C -Po1
2
Synthesis of A -Po1
The pKa value of cytosine (C) is higher than that of thymine,
therefore a stronger base was used to deprotonate its N1 site.6(b)
Po1 was reacted with an excess of C in the presence of NaH
The 5,15-di(N1-methylphenyladenine)-10,20-dimesityl porphyrin
(A -Po1) was synthesized following the same procedure, where
Po1 was reacted with an excess of adenine and K CO in dry
2
2
3
resulting in C
is due to the low solubility and high polarity of C
2
-Po1 with a 37% yield. The low yield of the reaction
DMF leading to the targeted porphyrin in 54% yield. In addition, a
minor by-product A-Po1-A’ was isolated in 5% yield.
2
-Po1, which affect
the purification process, decreasing the yield compared to the
The mass spectrum of this by-product A-Po1-A’ showed the
previous substitution reaction with thymine.
same mass as A
spectra of the isomers were found to be different. The H-NMR of
2
-Po1 however, the 1H-NMR and 13C-NMR
1
1
The H-NMR spectrum of C
2
-Po1 showed two broad peaks at
1
7.13 and 7.23 ppm integrating each for two protons (Figure ESI
A
2
-Po1 showed a C2 symmetry for the molecule, whereas the H-
4
). These signals are the fingerprint of the tautomeric form of
NMR of A-Po1-A’ in 1% of CD
peaks for the protons of the CH
3
OD in CDCl
3
showed two sets of
6, 24
cytosine displaying two NH sites (Figure 2).
2
linker the adenine protons at the
,
C8 position, the mesityl protons and the -pyrrolic hydrogens
indicating that the C2 symmetry is broken in A-Po1-A’ (Figure 3).
This could be explained by the connection of both adenine
2
molecules to the porphyrin via their N9 position in A -Po1,
whereas in A-Po1-A’ one adenine molecule is connected via its
N9 and the other via its N7, which is possible because of the
tautomeric forms of adenine (Figure 2). Moreover, A-Po1-A’ is
more soluble and less polar than A
be explained by less favored intermolecular H-bonds between
adenines in A-Po1-A’ compared to A -Po1.
2
-Po1, these differences could
2
Figure 2. The tautomeric forms of C, A and P
1
Figure 3. Portion of H-NMR spectra of A
2
3 3
-Po1 (500 M Hz) and A-Po1-A’ (300 MHz) in CDCl + CD OD
3
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Synthesis of G
2
-Po1
P
2
-Po1 was then hydrolyzed using an aqueous HCl solution
2
(Scheme 1B), and the target porphyrin G -Po1 was obtained in
The use of guanine to reach the targeted tecton 5,15-di(N9-
methylphenylguanine)-10,20-dimesityl porphyrin (G -Po1) was
98% yield by precipitation at neutral pH. The hydrolysis of P to G
was confirmed with the IR spectroscopy of G -Po1 by the
2
appearance of a peak at 1682 cm-1 which corresponds to the C=O
2
unsuccessful, due to its low solubility and high polarity, making its
purification unfeasible. Therefore, a two-step procedure was
followed. 2-amino-6-chloropurine (P) was used as a precursor of
guanine (G) given its higher solubility and its possible hydrolysis
into G under acidic conditions.25
stretching of G.
Tetra functionalized NB-porphyrin
The porphyrin bearing four NBs could lead to higher complexity
networks. To prepare such molecules, 5,10,15,20-tetrakis[4-
(bromomethyl)phenyl] porphyrin (Po2)26 was reacted with an
2 3
An excess of P was reacted with Po1 and K CO resulting in 80%
yield of P
2
-Po1 and 8% of a minor product P-Po1-P’. By
1
comparing the H-NMR spectrum of both products, the latter was
identified as an isomer bearing two non-equivalent tautomeric
forms of P connected in trans meso-positions of the porphyrin,
one via its N9 site and another via its N7 site (Figure 4).
excess of thymine in the presence of K
2 3
CO affording the targeted
T
4
-Po2 in 93% yield (Scheme 2). We tried to apply this strategy
with C, A and P. Unfortunately, it led to the formation of mixtures
of partially substituted porphyrins which were impossible to purify
due to their low solubility.
1
Figure 4. A portion of H-NMR spectra of P
2
-Po1 and P-Po1-P’ (CDCl
3
+ CD
3
OD, 500 MHz)
4
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4
Scheme 2. Synthesis of T -Po2
Synthesis of Rigid NB-porphyrins based tectons
Our second objective was to replace the flexible methylene linker
by a more rigid one, the ultimate goal of such tectons being to
favour and master their organization on surface. In order to
generate rigid frameworks based on porphyrins and NBs, we first
envisioned to introduce the NBs directly on the porphyrin scaffold
through a Suzuki cross coupling reaction between a porphyrin
boronic ester and halogenated NBs. Unfortunately, this strategy
led to insoluble mixtures whose purification and characterization
were difficult. We then focused on the introduction of NBs via rigid
ethynyl linkers.
coplanarity of the H-bonding sites and the porphyrin main plane.
In addition, pentyl side chains were introduced on the other two
remaining trans meso-positions to increase solubility of the final
tectons and further enhance their affinity for the surface. The first
strategy to synthesize the rigid tectons was to introduce the
ethynyl group on the porphyrin and then to perform a Sonogashira
cross coupling reaction between the porphyrin and halogenated
nucleobases. However, this strategy was not successful.
Therefore, we proceeded in synthesizing ethynyl-functionalized
nucleobases and then coupling them with brominated porphyrins
using a strategy that has proven to be successful for porphyrin
bearing ethynylpyridine groups at the meso positions.2
Our targeted tectons are porphyrin molecules bearing NBs on two
trans meso-positions connected via ethynyl linker, which will allow
0b
Scheme 3. Synthetic route to A) Ethynyl-G and B) Ethynyl-A.
5
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European Journal of Organic Chemistry
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step of the later was adapted from a procedure described by
In order to increase the solubility of the nucleobases bearing
ethynyl groups, a hexyl chain was introduced on the N1 position
of pyrimidine derivatives and on the N9 site of purine derivatives.
The targeted C5-ethynyl-functionalized pyrimidines, Ethynyl-U
and Ethynyl-C, have been prepared following a methodology
described by González-Rodríguez et al.27
29
Raptopoulou et al . The resulting 8-bromo-9-hexyladenine 3 was
then reacted in a standard Sonogashira cross coupling reaction
with TMS-acetylene yielding molecule 4, which was deprotected
in a final step using TBAF. Ethynyl-A was obtained with an
overall yield of 35% (Fehler! Verweisquelle konnte nicht gefunden
werden. 3B).
The synthesis of Ethynyl-G (Fehler! Verweisquelle konnte nicht
gefunden werden. 3A) was inspired by a five-step procedure
described by Wasielewski et al.25 for a N9-octyl substituted
guanine derivative using 2-amino-6-chloropurine (P) as starting
material. The alkylation of the N9 position of P was performed
Synthesis of NB -Po3
2
The ethynyl-funtionalized nucleobases (Ethynyl-C, Ethynyl-U,
Ethynyl-A and Ethynyl-G) were reacted with zinc 5,15-dibromo-
using 1-iodohexane and K
intermediate 2-amino-6-chloro-N9-hexylpurine
2
CO
3
in dry DMF. The resulting
was then
27
10,20-dipentylporphyrin ZnPo3 (Fehler! Verweisquelle konnte
hydrolyzed in aqueous hydrochloric acid yielding 79 % of N9-
hexylguanine. The C8 position of the latter was then brominated
with NBS in a water/acetonitrile mixture, giving rise to compound
nicht gefunden werden. 4) in a mixture of THF and triethylamine
or a mixture of THF, DMF and trimethylamine in the presence of
bis(triphenylphosphine)palladium dichloride and copper iodide as
catalysts.
1
with a yield of 82 %.
Compound 1 was subjected to a Sonogashira cross coupling
reaction using TIPS-acetylene in a DMF/triethylamine mixture
resulting in compound 2, which was followed by a final desilylation
step with TBAF resulting in the Ethynyl-G. The yields (26% and
Rigid porphyrin-nucleobases derivatives U
ZnPo3 and G -ZnPo3 were obtained. Unfortunately, only U
has been obtained as pure compound and has been fully
2
characterized. The low solubility of C -Po3, A -ZnPo3 and G -
2
-Po3, C
2
-Po3, A
2
-
2
2
-Po3
2
2
49%) corresponding to the two last steps described hereby are
ZnPo3 prevented efficient purifications. Nevertheless, the purity
of these three tectons is estimate to be higher than 90%. The
conditions used for the cross coupling reactions and their yields
are summarized in Table 2. The targeted bis-pyrimidine-
porphyrins U -Po3 and C -Po3 were found to be easier to purify
relatively low and is probably due to the low solubility of the final
molecule causing loss of product during the purification process
(Fehler! Verweisquelle konnte nicht gefunden werden.A).
The C8-ethynyl-functionalized adenine moiety Ethynyl-A was
prepared in four steps from the commercially available adenine.
The first step consists in an alkylation of the N9 position of the
2
2
when the porphyrin core was demetallated. Thus, TFA was added
to the crude material before the purification step. However, the
purine A using 1-bromohexane and K
2 3
CO in dry DMF, following
two bis-purine-porphyrin derivatives A
2 2
-ZnPo3 and G -ZnPo3
a modified procedure for the synthesis described by Verma et
al. , which resulted in 90 % of N9-hexyladenine. The bromination
have shown a lower solubility than U -ZnPo3 and C -ZnPo3, and
2
2
28
they were almost insoluble when demetallated. Therefore,
purification by multiple washings of the crude metallated product
with various solvents were followed and no demetallation step
was performed.
6
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European Journal of Organic Chemistry
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2 2
Scheme 4. Synthetic route to the NB -Po3 (NB = U and C) and NB -ZnPo3 (NB = U, C, A, G) tectons
Table 2. Reaction conditions and yields of NB
2
-Po3 and NB
2
-ZnPo3 synthesis
Ethynyl-NB (nb eq)
Ethynyl-U (3)
Ethynyl-C (3)
Ethynyl-A (3)
Ethynyl-G (3)
PdCl
2
(PPh
3
)
2
(mol%)
CuI (mol%)
THF/DMF/Et
3
N (ratio)
T (°C)
40
Product (Yd)
20
8
10
4
4:0:1
4:0:1
4:0:1
2:2:1
U
2
-Po3 (70%)[a]
-Po3 (<64%)[a][b]
-ZnPo3 (<23%) [b]
-ZnPo3 (<30%) [b]
40
C
2
10
10
10
4
40
A
2
50
G
2
[
a] The yield of Sonogashira coupling step and the demetallation step. [b] The yields were calculated assuming a 100% purity, and is thus overestimated.
2
Hydrogen bonded Molecular Network of C -ZnPo3
Moreover, water molecules are H-bonded to the carbonyl oxygen
atom and the amine group of two adjacent cytosines with
distances in the range of 2.70 – 2.77 Å (Figure 5B). In the 1D
staircase sequence, the porphyrins are parallel. The planes
formed by two successive macrocycles are separated by 2.87 Å,
while two porphyrins of two adjacent 1D sequences are  stacked
and their mean planes are separated by 3.22 Å. The distance
between two zinc ions is 20.18 Å within the 1D arrangement and
Dark green single crystals suitable for XRD have been obtained
for C -ZnPo3 by slow evaporation of a 10 mM solution in 9:1
DMSO/THF. The compound crystallized as [C -ZnPo3
DMSO) (H O)] in the triclinic space group (Figure 5). Two DMSO
molecules are coordinated in the axial positions of the zinc ion
present in the porphyrin cavity with a Zn-O distance of 2.57 Å
2
2
(
3
2
(Figure 5A). Cytosine of two adjacent porphyrins are H-bonded
thus leading to a 1D staircase H-bonded network (Figure 5B).
Hydrogen bonding between the cytosine moieties involves amine
and the N3 pyrimidyl nitrogen atom in a complementary fashion
9.14 Å between 2 layers. An additional interaction between a
water molecule and the carbonyl group of the cytosine in the
adjacent layer (dO-O = 2.84 Å) leads to the formation of a 2D
hydrogen bonded network (Figure 5B).
(dN-N = 3.00 Å).
Figure 5. A) Portion of the crystal structure of [C
2
-ZnPo3(DMSO)
(H
3 2
O)], B) Portion of the crystal structure showing the intermolecular H-bonding
interactions (DMSO molecules, hydrogen of the water molecules and alkyl side chains of cytosine molecules have been omitted for clarity),
C) Portion of the structure view along the a axis (DMSO molecules have been omitted for clarity).
7
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European Journal of Organic Chemistry
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5
0
,15-bis(4-(bromomethyl)phenyl)-10,20-dimesityl porphyrin (132 mg,
.1497 mmol, 1 eq) and thymine (94 mg, 0.748 mmol, 5 eq) were dissolved
2 3
in dry degassed DMF (8 mL). K CO (62 mg, 0.449 mmol, 3 eq) was added
to the suspension and stirred for 24 hours at 40 oC. The reaction was
followed by TLC and stopped when all starting porphyrin was consumed.
The solvent was evaporated and the resulting solid was washed with water
Conclusion
The synthesis of ten new porphyrins bearing nucleobases was
(10 mL) to remove the excess of thymine and salt. The crude product was
achieved following different synthetic strategies. Po1 (5,15-di(4-
purified by column chromatography (Silica gel, 5% methanol in DCM) to
(
bromomethyl)phenyl)-10,20-diphenylporphyrin) was used as a
give a purple solid (106 mg, 72 %).
1
H NMR (400 MHz, CDCl
J=7.8 Hz, 4H), 7.61-7.59 (d, JH,H=8.0 Hz, 4H), 7.30 (s, 2H), 7.22 (s, 4H),
3
+ MeOD): δ=8.70-8.64 (m, 8H), 8.18-8.16 (d,
starting material to introduce two NBs in trans meso-positions of
the porphyrin scaffold via a substitution reaction of the N1 site of
3
3
5
.25 (s, 2H), 5.18(s, 2H), 2.57 (s, 6H), 1.96 (s, 6H), 1.76 ppm (s, 12H); 13C
NMR (126 MHz, CDCl + MeOD): δ=164.9, 151.6, 142.1, 140.4, 139.4,
38.3, 137.9, 135.1, 135.0, 127.8, 126.1, 123.8, 118.5, 111.5, 53.5, 51.1,
1.6, 21.4, 12.4 ppm; IR: ν˜=419.3, 470.9, 558.2, 738.4, 756.5, 810.5,
30.2, 933.7, 981.9, 1027.6, 1201.1, 1243.2, 1380.4, 1423.7, 1445.3,
thymine and cytosine in the presence of K
respectively, and to the N9 site of adenine and 2-amino-6-
chloropurine using K CO . The substitution reaction between
guanine and Po1 was unsuccessful. However, the porphyrin
bearing guanines (G -Po1) was obtained by the hydrolysis of the
porphyrin bearing 2-amino-6-chloropurine (P -Po1). In addition, it
was possible to synthesize a porphyrin bearing four thymine
moieties at its four meso-positions by reacting 5,10,15,20-
tetrakis(4-(bromomethyl)phenyl)porphyrin (Po2) with thymine in
2 3
CO and NaH
3
1
2
8
2
3
-
1
3
2
1477.9, 1666.6, 1715.8, 2928.8, 3028.3 cm ; UV/Vis (DMF): λmax (εx10 )=
644 (2.38), 589 (2.99), 549 (3.85), 515 (9.69), 419 nm (227.97 mol .L.cm
-
1
-
2
1)
75.4322.
+
+
54 8 4
, HRMS (ESI): m/z calcd for C62H N O +H : 975.4323 [M+H] ; found:
9
2
C -Po1
2 3
the presence of K CO . The substitution reactions of the other
nucleobases with Po2 was not successful due to the low solubility
of the final products. Furthermore, four rigid tectons bearing two
NBs in trans positions (U -Po3, C -Po3, A -ZnPo3 and G -
2 2 2 2
ZnPo3) have been synthesized using the Sonogashira cross
coupling methodology with ZnPo3 and the corresponding NB-
5
0
,15-bis(4-(bromomethyl)phenyl)-10,20-dimesitylporphyrin
.156 mmol, 1 eq) and cytosine (86 mg, 0.779 mmol, 5 eq) were dissolved
(130
mg,
in dry degassed DMF (12 mL). NaH (11.20 mg, 0.467 mmol, 3 eq) was
added to the suspension and stirred for 24 hours at 40 oC. The reaction
was followed by TLC and stopped when all starting porphyrins were
consumed. The reaction was dried under vacuum, and then washed with
water to remove the excess of salt and cytosine. The crude was purified
by column chromatography (Silica gel, 5% Methanol in DCM) to give a
Ethynyl derivatives. Moreover,
2
C -ZnPo3 has been
characterized in the solid state by X-ray diffraction. The self-
complementarity of the cytosine leads to the formation of a
hydrogen bonded network. The next step is to use this library of
NB-porphyrin based tectons in order to generate H-bonded
networks based on complementary pairs and also to take
advantage of the porphyrin cavity as an additional coordinating
site to design more complex assemblies bearing hydrogen
bonding donor/acceptor groups as well as coordinating units.
purple solid (55 mg, 37 %).
1
): δ=8.78 (d, 3
H NMR (400 MHz, DMSO-d
6
J
H,H=4.7 Hz, 4H), 8.62 (d,
3JH,H=4.6 Hz, 4H), 8.21-8.20 (d, 3JH,H=7.9 Hz, 4H), 7.99-7.98 (d, JH,H=7.2
3
Hz, 2H), 7.68-7.66 (d, 3JH,H=7.9 Hz, 4H), 7.35(s, 4H), 7.23 (s, brd, 2H),
.13 (s, brd, 2H), 5.84-5.82 (d, 3JH,H=7.3 Hz, 2H), 5.21 (s, 4H), 2.58 (s, 6H),
.75 (s, 12H), -2.78 ppm (s, 2H); 13C NMR (126 MHz, DMSO-d
7
1
6
): δ=166.2.
156.2, 146.5, 139.9, 138.5, 137.8, 137.7, 134.4, 127.9, 126.0, 117.8, 94.0,
6
1
5.0, 51.5, 21.3, 21.1 ppm; IR: ν˜=410.7, 606.2, 726.3, 787.3, 1077.7,
-
1
3
264.7, 1384.9, 1489.3, 1644.5, 3320.8 cm ; UV/Vis (DMF): λmax (εx10 )=
-
1
-
6
47 (2.85), 591 (3.21), 548 (4.87), 514 (9.50), 418 nm (190.49 mol .L.cm
Experimental Section
1
+
)
; HRMS (ESI): m/z calcd for C60
52
H N
10
O
2
: 945.4347 [M+H] ; found:
9
45.4354.
Experimental Details. All the starting reagents were obtained from
commercial sources and used as received. The starting porphyrins: 5,15-
2
A -Po1
23
bis(4-(bromomethyl)phenyl)-10,20-dimesitylporphyrin (Po1), 5,10,15,20-
tetrakis[4-(bromomethyl)phenyl]porphyrin26 (Po2) and zinc 5,15-dibromo-
0,20-dipentylporphyrin27 (ZnPo3) were obtained following the described
5,15-bis(4-(bromomethyl)phenyl)-10,20-dimesitylporphyrin
.170 mmol, 1 eq) and adenine (114.5 mg, 0.848 mmol, 5 eq) were
dissolved in dry degassed DMF (10 mL). K CO (70.1 mg, 0.508 mmol, 3
(150
mg,
1
0
procedures. Brucker AC or AV-300, AV-400 or AV-500 spectrometer was
used to record NMR spectra at room temperature with the deuterated
solvent as the internal reference. NMR chemical shifts and J values are
given in parts per million (ppm) and in Hertz respectively. Mass
spectrometry was performed at the Common Analysis Service of the
University of Strasbourg. X-ray crystallography data were collected on a
Bruker SMART CCD diffractometer with Mo-Kα radiation at 173 K for all
compounds. The structures were solved using SHELXS-97 and refined by
2
3
eq) was added to the suspension and stirred for 24 hours at 40 oC. The
reaction was followed by TLC and stopped when all starting porphyrin was
consumed. The mixture was dried under vacuum, and then washed with
water (10 mL) to remove the excess of salt and adenine. The crude was
purified by column chromatography (Silica gel, 5% methanol in DCM) to
give A
2
-Po1 (90 mg, 54%) and A-Po1-A’ (8 mg, 5%) as purple solids.
-Po1: H NMR (500 MHz, CDCl
1
A
2
3
+ MeOD): δ=8.68-8.63 (m, 8H), 8.40 (s,
full matrix least-squares on F2 using SHELXL-2014 with anisotropic
thermal parameters for all non-hydrogen 0144830 Hydrogen atoms were
introduced at calculated positions and refined using the riding model.
2H), 8.17-8.16 (d, JH,H= 7.9 Hz, 4H), 8.07 (s, 2H), 7.62-7.60 (d, 3JH,H=7.9
3
Hz, 4H), 7.23 (s, 4H), 5.69 (s, 4H), 2.58 (s, 6H), 1.76 (s, 12H), -2.74 ppm
(
br s, 2H); 13C NMR (126MHz, CDCl
3
+ MeOD): δ=155.7, 153.3, 150.0,
CCDC 2026828 contains the supplementary crystallographic data for [C2-
1
1
7
1
42.3, 140.6, 139.4, 138.3, 137.9, 135.1, 134.9, 127.8, 126.1, 119.1, 118.6,
18.3, 47.4, 21.6, 21.5 ppm; IR: ν˜= 407.7, 544.1, 727.7, 745.1, 771.8,
91.6, 825.1, 967.5, 1021.5, 1076.1, 1076.1, 1245.9, 1308.8, 1332.1,
431.3, 1468.4, 1580.9, 1603.7, 1681.2, 2851.8, 2922.1, 3076.5 cm ;
ZnPo3 (DMSO)
3 2
(H O)]. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif.
-
1
2
T -Po1
3
UV/Vis (DMF): λmax (εx10 )= 648 (2.22). 591 (2.30), 551 (2.68), 516 (3.19),
8
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.202001406
FULL PAPER
-
1
-1
4
9
18 nm (283.28 mol .L.cm ); HRMS (ESI): m/z calcd for C62
H
52
N
14
:
4
T -Po2
+
93.4575 [M+H] ; found : 993.4516.
A-Po1-A’: H NMR (500 MHz, CDCl
1
3
+ MeOD): δ=8.73-8.66 (m, 8H), 8.52
5
,10,15,20-tetrakis(4-(bromomethyl)phenyl)porphyrin (200 mg, 0.203
mmol, 1 eq), thymine (255 mg, 2.03 mmol, 10 eq) and K CO (141 mg,
.02 mmol, 5 eq) were dissolved in 10 mL of degassed DMF. The mixture
(
s, 1H), 8.45 (s, 1H), 8.27 (s, 1H), 8.25- 8.23 (d, 3JH,H=7.9 Hz, 2H), 8.21-
2
3
8
7
2
.19 (d, 3 H,H=7.8 Hz, 2H), 8.09 (s, 1H), 7.78-7.76 (d, 3
J JH,H=7.9 Hz, 2H),
1
.65-7.63 (d, 3JH,H=7.9 Hz, 4H), 7.27 (s, 4H), 5.74 (s, 2H), 5.67 (s, 2H),
o
was stirred overnight at 40 C under argon. The reaction was followed by
TLC. After the disappearance of the starting porphyrin, the reaction was
dried under vacuum and then triturated with water (10 mL). The purple
precipitate was filtered over a frit and washed with water (20 mL), then
dried under vacuum to give a purple solid (220 mg, 93 %).
.62 (s, 6H), 1.81 (s, 12H), -2.66 ppm (s, 2H).
1H NMR (400 MHz, DMSO-d
): δ=11.50 (br s, 4H), 8.82-8.81 (s, 8H), 8.22-
.21 (d, 3JH,H= 7.7 Hz, 8H), 7.96 (s, 4H), 7.73-7.72 (d, 3JH,H=7.7 Hz, 8H),
.22 (s, 8H), 1.88 (s, 12H), -2.97 ppm (s, 2H); 13C NMR (126 MHz, DMF-
): δ=165.4, 164.8, 152.0, 141.8, 141.4, 138.1, 137.6, 135.2, 126.7, 120.2,
10.0, 108.3, 73.4, 50.7, 12.0, 11.7 ppm; IR ν˜=411.8, 477.6, 558.6, 798.8,
66.1, 982.2, 1212.8, 1349.1, 1382.2, 1661.0, 2925.5 cm ; UV/Vis
6
8
5
d
1
9
2
P -Po1
7
5
0
,15-bis(4-(bromomethyl)phenyl)-10,20-dimesitylporphyrin
.113 mmol, 1 eq) and 2-amino-6-chloropurine (95.81 mg, 0.565 mmol, 5
eq) were dissolved in dry degassed DMF (15 mL). K
mmol, 3 eq) was added to the suspension and stirred for 24 hours at 50 C.
The reaction was followed by TLC and stopped when all starting porphyrin
was consumed. The reaction was dried under vacuum then washed with
water (5 mL) to remove the excess of 4-chloro-1-aminopurine and salt. The
crude product was purified by Column Chromatography (Silica gel, 5%
(100
mg,
-1
3
(
DMF): λmax (εx10 )= 646 (4.08). 593 (4.42), 550 (6.69), 515(11.20), 419
2
CO
3
(46.85 mg, 0.339
-1
-1
nm (231.96 mol Lcm ); HRMS (ESI): m/z calcd for
68 54 12 8
C H N O :
o
+
1
167.4260[M+H] ; found: 1167.4257.
2
-amino-6-chloro-N9-hexylpurine
9
To a solution of 6-chloro-N -hexylpurine P (2.28 g, 13.4 mmol) in dry DMF
2
Methanol in DCM) to give P -Po1 (96 mg, 80%) and P-Po1-P’ (10 mg, 8%)
(50 mL) potassium carbonate (2.8 g, 20.2 mmol) was added. The mixture
as purple solids.
was heated at 40 °C for 30 min and 1-iodohexane (2 mL, 13.4 mmol) was
then added. The resulting mixture was allowed to stir at 40 °C for 18 h.
After completion of the reaction, the solvents were evaporated under
vacuum and the crude product was dissolved in dichloromethane and
washed with water. The organic layer was dried over anhydrous sodium
sulfate, filtered and evaporated to dryness. The crude material was
-Po1: 1H NMR (500 MHz, CDCl
): δ=8.73-8.72 (d, 3
JH,H=4.7 Hz, 4H),
P
2
3
.68 (d, 3
H
,
H
3
8
7
2
+
1
J
=
4
.
7
H
z
,
4
H
)
,
8
.
2
2
-
8
.
2
0
(
d
,
JH,H=8.0 Hz, 4H), 8.05 (s, 2H),
.65-7.63 (d, 3JH,H=7.9 Hz, 4H), 7.28 (s, 4H), 5.61 (s, 4H), 5.21 (s, 4H),
.63 (s, 6H), 1.81 (1s, 12H), -2.68 ppm (s, 2H); 3C NMR (126 MHz, CDCl
1
3
MeOD) δ=159.4, 154.2, 151.8, 142.5, 142.4, 139.5, 138.4, 137.9, 135.2,
34.8, 129.9, 127.9, 126.2, 125.5, 118.7, 118.4, 47.3, 21.8, 21.6 ppm; IR:
ν˜=437.9, 496.2, 528.4, 605.9, 638.8, 734.1, 755.9, 782.7, 819.2, 914.2,
91.9, 1119.3, 1165.8, 1210.9, 1348.0, 1391.8, 1407.6, 1469.1, 1518.0,
subjected to a chromatography column over silica gel using CH
97:3) as eluent to provide a pure product (2.77 g, 81%).
2 2
Cl /MeOH
(
1
H NMR (500 MHz, d
3JH,H=7.2 Hz, 2H), 1.75 (quint, 3JH,H=7.2 Hz, 2H), 1.28-1.17 (m, 6H), 0.82
ppm (t, 3JH,H=6.7 Hz, 3H); 13C NMR (125 MHz, d
-DMSO): δ=159.7, 154.1,
6
-DMSO): δ=8.14 (s, 1H), 6.90 (br s, 2H), 4.02 (t,
9
1
(
-
1
559.1, 1628.7, 1699.9, 3073.9, 33313.1, 3458.8 cm ; UV/Vis
3
6
DMF): λmax (εx10 )= 647 (4.43). 591 (5.07), 548 (7.33), 514 (16.15), 418
-
1
-1
149.3, 143.3, 123.3, 43.0, 30.7, 28.9, 25.7, 22.0, 13.9 ppm; HRMS (ESI):
nm (348.60 mol .L.cm ), HRMS (ESI): m/z calcd for
62 50 2
C H N14Cl :
+
+
m/z calcd for C11
N9-hexylguanine
A suspension of 2-amino-6-chloro-N
H
17
N
5
Cl: 254.1167 [M+H] ; found: 254.1173.
1
061.3793 [M+H] ; found: 1061.3782.
1
P-Po1-P’: H NMR (500 MHz, CDCl
m, 4H), 8.05 (s, 1H), 7.64-7.63 (d, 3
3
): δ=8.69 (m, 8H), 8.28 (s, 1H), 8.21
(
J
H,H=7.9 Hz, 2H), 7.52-7.50 (d,
3
J
H,H=7.9 Hz, 2H), 7.28 (s, 4H), 5.88 (s, 2H), 5.60 (s, 2H), 5.26 (s, 2H),
.21 (s, 2H), 2.63 (s, 6H), 1.82 (s, 12H), -2.67 ppm (s, 2H); 13C NMR (126
5
9
-hexylpurine (2.77 g, 10.9 mmol) in
MHz, CDCl
3
+ MeOD): δ=164.6, 159.7, 159.5, 154.2, 151.8, 149.0, 144.1,
aqueous hydrochloric acid (0.5 M, 200 mL) was stirred under reflux for 18
h. The resulting solution was neutralized with a concentrated aqueous
solution of sodium hydroxide and the resulting white precipitate was filtered,
washed with water and dried under vacuum to provide N9-hexylguanine
as a pure white solid (2.2 g, 79%).
1
1
42.5, 139.4, 138.3, 137.9, 135.2, 134.9-134.8, 127.9, 126.2, 125.5, 125.3,
18.7, 118.4, 118.2, 116.8, 50.7, 47.3, 21.8, 21.6 ppm; MS: m/z calcd for
+
62
C H
50
N
14Cl
2
: 1061.38 [M+H] ; found : 1061.38.
1H NMR (500 MHz, d
H), 3.91 (t, 3JH,H=7.1 Hz, 2H), 1.70 (quint, 3JH,H=7.1 Hz, 2H), 1.30 – 1.16
m, 6H), 0.83 ppm (t, 3 H,H=6.8 Hz, 3H); 13C NMR (125 MHz, d
-DMSO):
-DMSO): δ=10.52 (s, 1H), 7.67 (s, 1H), 6.42 (br s,
6
2
G -Po1
2
(
J
6
5
,15-bis(N
9
-methylphenyl-2-amino-6-chloropurine)-10,20-dimesityl
δ=156.9, 153.4, 151.2, 137.5, 116.6, 42.6, 30.7, 29.4, 25.7, 22.0, 13.9
porphyrin (60 mg, 0.0565 mmol, 1 eq) was dissolved in 20 mL of MeOH.
+
ppm; HRMS (ESI): m/z calcd for C11
H
18
N
5
O 236.1506, [M+H] ; found:
0
7
.1 M of HCl aqueous solution was added to the mixture (4 mL, 0.4 mmol,
eq). Upon addition of HCl, the color of the solution changed from purple
2
36.1515.
to green. The mixture was stirred overnight under reflux, and the reaction
was followed by TLC. When all starting material was consumed, 0.1 M
NaOH solution was added drop wise to neutralize the solution (ca. 3 mL).
The resulting purple precipitate was filtered, washed with water (10 mL)
and acetone (10 mL) and dried under reduced pressure to give the final
8
-bromo-N9-hexylguanine (1)
N-bromosuccinimide (753 mg, 4.2 mmol) was added in small portions to a
suspension of N -hexylguanine (664 mg, 2.8 mmol) in water (15 mL) and
9
product (56 mg, 98 %).
acetonitrile (30 mL). The mixture was allowed to stir at room temperature
for 1.5 h. Acetonitrile was evaporated under vacuum and the resulting
yellowish precipitate was filtered, washed with water and dried under
vacuum to provide 1 as a pure solid (726 mg, 82%).
1
): δ=10.87 (br s, 2H), 8.75-8.74 (d, 3JH,H=4.2
H,H=8.0 Hz, 4H),
.04 (s, 2H), 7.64-7.62 (d, 3JH,H=7.8 Hz, 4H), 7.34 (s, 4H), 6.77 (br s, 4H),
.55 (s, 4H), 2.58 (s, 6H), 1.74 (s, 12H), -2.80 ppm (s, 2H); IR: ν˜=477.9,
88.9, 757.1, 797.8, 1017.1, 1093.7, 1167.7, 1213.1, 1260.0, 1409.3,
H NMR (500 MHz, DMSO-d
6
Hz, 4H), 8.63-8.62 (d, 3JH,H=4.2 Hz, 4H), 8.22-8.21 (d, 3
J
8
5
6
1
1H NMR (500 MHz, d
3JH,H= 7.3 Hz, 2H), 1.66 (tt, 3JH,H=7.3 Hz and 6.7 Hz, 2H), 1.30 – 1.21 (m,
6H), 0.84 ppm (t, 3JH,H=6.5 Hz, 3H); 13C NMR (125 MHz, d
-DMSO):
6
-DMSO): δ=10.66 (s, 1H), 6.57 (br s, 2H), 3.90 (t,
-
1
480.3, 153.5, 1606.8, 1682.8, 2852.0, 2923.1, 3113.9 cm ; UV/Vis
6
3
(
DMF): λmax (εx10 )= 647 (1.34), 591 (1.44), 548 (2.09), 514 (4.00), 418
δ=155.6, 153.8, 152.4, 120.7, 116.8, 43.4, 30.7, 28.8, 25.6, 22.0, 13.8
-
1
-1
+
nm (76.94 mol .L.cm ); HRMS (ESI): m/z calcd for
C
62
H
52
N
14
O :
2
ppm; HRMS (ESI): m/z calcd for C11
H
17
N
5
OBr: 314.0611 [M+H] ; found:
+
5
13.2272 [M/2+H] ; found: 513.2272.
314.0611.
9
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.202001406
FULL PAPER
9
-hexyl-8-[2-(triisopropylsilyl)ethynyl]guanine (2)
150.7, 126.3, 119.0, 43.7, 30.7, 28.7, 25.6, 21.9, 13.8 ppm; HRMS (ESI):
+
m/z calcd for C11H N
17 5
Br: 298.0662 [M+H] ; found: 298.0666.
To a degassed solution of 8-bromo-N9-hexylguanine (1) (366 mg, 1.16
mmol) in DMF/Et (2:1, 30 mL) was added
3
N
9-hexyl-8-[2-(trimethylsilyl)ethynyl]-adenine (4)
tetrakis(triphenylphosphine)palladium (67 mg, 58 µmol), copper iodide (22
mg, 116 µmol) and (triisopropylsilyl)acetylene (1.0 mL, 4.7 mmol). The
resulting mixture was allowed to stir under an argon atmosphere at 50 °C
for 40 h. After completion of the reaction, the solvents were evaporated
and the crude material was subjected to a short chromatography column
To a degassed solution of 8-bromo-N
9
-hexyladenine (3) (389 mg, 1.30
10 mL) was added
mmol) in THF/Et (4:1,
3
N
tetrakis(triphenylphosphine)palladium (75 mg, 65 µmol), copper iodide (25
mg, 130 µmol) and ethynyltrimethylsilane (720 µL, 5.2 mmol). The
resulting mixture was allowed to stir under an argon atmosphere at 50 °C
for 18 h. After completion of the reaction, the solvents were evaporated
and the crude material was subjected to a chromatography column over
silica gel using ethyl acetate as eluent to provide 4 as a pure product (310
over silica gel using CH
product (125 mg, 26%).
2 2
Cl /MeOH (96:4) as eluent to provide 2 as a pure
1H NMR (500 MHz, d
-DMF): δ=10.75 (s, 1H), 6.80 (br s, 2H), 4.10 (t,
3JH,H=7.3 Hz, 2H), 1.82 (quint, 3
H,H=7.3 Hz, 2H), 1.37-1.26 (m, 6H), 0.86
ppm (t, 3JH,H=6.8 Hz, 3H); 13CNMR (125 MHz, d
-DMF): δ= 157.6, 155.9,
52.4, 131.1, 118.4, 97.8, 96.6, 44.2, 32.3, 27.3, 23.4, 19.3, 14.6, 12.1
7
J
7
mg, 75%).
1
1
6
H NMR (500 MHz, d -DMSO): δ=8.17 (s, 1H), 7.46 (br s, 2H), 4.16 (t,
+
ppm; HRMS (ESI): m/z calcd for C22
H
38
N
5
OSi: 416.2840 [M+H] ; found:
3JH,H=7.0 Hz, 2H), 1.78 (quint, 3
J
H,H=7.0 Hz, 2H), 1.29-1.20 (m, 6H), 0.83
-DMSO):
δ=155.9, 153.8, 149.0, 132.6, 118.6, 101.4, 93.8, 42.9, 30.5, 28.8, 25.5,
4
16.2843.
t, 3JH,H=6.8 Hz, 3H), 0.29 ppm (s, 9H); 13C NMR (125 MHz, d
(
6
8
-ethynyl-9-hexylguanine (Ethynyl-G)
21.9, 13.8, -0.7 ppm; HRMS (ESI): m/z calcd for C16
26
H N
5
Si: 316.1952
+
[
M+H] ; found: 316.1960.
Tetrabutylammonium fluoride (1 M in THF, 0.6 mL, 0.6 mmol) was added
to a solution of 9-hexyl-8-[2-(triisopropylsilyl)ethynyl]-guanine 2 (125 mg,
8-ethynyl-9-hexyladenine (Etynyl-A)
0
.30 mmol) in THF (6 mL) and methanol (0.3 mL) at 0 °C and the mixture
was allowed to stir at room temperature for 2 h. After completion of the
reaction, the solvents were evaporated and the crude material was
subjected to a short chromatography column over silica gel using
Tetrabutylammonium fluoride (1 M in THF, 2.4 mL, 2.4 mmol) was added
to a solution of 9-hexyl-8-[2-(trimethylsilyl)ethynyl]-adenine 4 (309 mg,
0
.98 mmol) in dry THF (25 mL). The mixture was allowed to stir at room
2 2
CH Cl /MeOH (94:6) as eluent to provide Ethynyl-G as a pure product (38
mg, 49%).
temperature for 1 h. After completion of the reaction, the solvents were
evaporated and the crude material was subjected to a chromatography
column over silica gel using ethyl acetate as eluent to provide Ethynyl-A
as a pure product (166 mg, 70%).
1
7
H-NMR (500 MHz, d -DMF): δ=10.77 (s, 1H), 6.80 (br s, 2H), 4.70 (s, 1H),
4
6
1
.08 (t, 3
J
H,H= 7.1 Hz, 2H), 1.80 (quint, 3
J
H,H=7.1 Hz, 2H), 1.33–1.25 (m,
-DMF): δ=157.6,
H), 0.86 ppm (t, JH,H=6.9 Hz, 3H); 13C NMR (125 MHz, d
3
7
1H NMR (500 MHz, d
-DMSO): δ= 8.18 (s, 1H), 7.47 (br s, 2H), 4.93 (s,
6
55.9, 152.5, 130.7, 118.3, 85.0, 75.1, 44.0, 32.2, 30.2, 27.0, 23.4, 14.6
H), 4.18 (t, 3JH,H=7.1 Hz, 2H), 1.78 (quint, 3JH,H=7.1 Hz, 2H), 1.32 – 1.18
1
+
ppm; HRMS (ESI): m/z calcd for C13
H
18
N
5
O: 260.1506 [M+H] ; found:
m, 6H), 0.82 PPM (t, 3 H,H=6.7 Hz, 3H);13C NMR (125 MHz, d
(
J -DMSO):
6
2
60.1510.
δ=155.9, 153.8, 149.2, 132.4, 118.4, 86.5, 73.2, 42.9, 30.6, 28.9, 25.6,
1.9, 13.8 ppm; HRMS (ESI): m/z calcd for C13
: 244.1557 [M+H]+,
found: 244.1562.
2
18 5
H N
N9-hexyladenine
Adenine A (100 mg, 0.74 mmol, 1 eq) and K
2
CO
3
(121 mg, 0.88 mmol, 1.2
2
U -Po3
eq) were dissolved in 20 mL of degassed DMF. 1-bromohexane (146 mg,
0
.12 mmol, 0.88 mmol, 1 eq) was added drop wise to the suspension. The
Bis(triphenylphosphine)palladium(II) dichloride (6 mg,
9
µmol) and
o
reaction was stirred for 12 hours at 40 C under argon. After completion of
the reaction, the mixture was evaporated to dryness, solubilized in DCM
copper(I) iodide (1 mg, 4.5 µmol) were added to a degassed solution of
zinc porphyrin ZnPo3 (30 mg, 45 µmol) and Ethynyl-U (29.5 mg, 1.3
mmol) in a 4:1 mixture of THF and triethylamine (4 mL) and the solution
was allowed to stir at 40 °C for 18 h. The solvents were evaporated and
the crude product was dissolved in chloroform (30 mL) and TFA (0.5 mL)
was added. The mixture was allowed to stir for 15 min at room temperature
and a saturated aqueous solution of sodium carbonate was added. The
organic phase was dried over anhydrous sodium sulfate, evaporated and
(50 mL) and washed with 20 mL of water and then with 20 mL of brine
solution. The organic phase was dried over MgSO , filtered and dried
4
under reduced pressure. The crude product was purified by column
chromatography (silica gel, 2% MeOH in DCM) to give N9-hexyladenine
as a white solid (250 mg, 90 %).
1H NMR (300 MHz, CDCl
): δ=8.36 (s, 1H), 7.78 (s, 1H), 5.58 (s, brd, 2H),
3
.18 (t, 3JH,H=7.3 Hz, 2H), 1.88 (tt, JH,H=7.5 Hz and 7.3 Hz, 2H), 1.30 (m,
3
4
6
1
subjected to a chromatography column using CH
9:1) as eluent to give U -Po3 as a pure green product (28 mg, 70%).
-DMSO: δ=11.96 (s, 2H), 9.83 (d, 3JH,H=4.5 Hz, 4H),
2 2
Cl /MeOH (99.5:0.5 to
H), 0.86 ppm (t, 3JH,H=7.0 Hz, 3H);13C NMR (126 MHz, CDCl
3
): δ=156.1,
9
2
53.2, 150.3, 140.6, 120.0, 44.2, 31.5, 30.3, 26.6, 22.7, 14.2 ppm.
1
H NMR (500 MHz, d
6
9
J
.66 (d, 3JH,H=4.5 Hz, 4H), 8.88 (s, 2H), 4.90 (t, 3JH,H=6.8 Hz, 4H), 3.90 (t,
3
H,H=7.0 Hz, 4H), 2.41-2.29 (m, 4H), 1.80 (quint, 3JH,H=6.7 Hz, 4H), 1.69
8
-bromo-N9-hexyladenine (3)
3
H,H=7.6 Hz, 4H), 1.51-1.32 (m, 14 H), 0.93 (t, 3
(quint,
J
J
H,H=6.9 Hz, 6H),
3
0
C
.89 (t, JH,H=7.3 Hz, 6H), -2.0 ppm (br s, 2H); HRMS (ESI): m/z calcd for
To a solution of N9-hexyladenine (1.17 g, 5.3 mmol) in glacial acetic acid
16 mL) was added sodium acetate (1.96 g, 23.9 mmol) and bromine (820
µL, 16 mmol). The resulting mixture was protected from light and stirred at
0 °C for 48 h. A saturated aqueous solution of sodium metabisulfite was
added and the mixture was extracted with ethyl acetate. The organic layer
was washed twice with saturated aqueous solution of sodium
+
54
H
63
N
8 4
O : 887.4967 [M+H] ; found: 887.4973.
(
5
C -Po3
2
a
Bis(triphenylphosphine)palladium(II) dichloride (3.6 mg, 5.1 µmol) and
copper(I) iodide (0.5 mg, 2.6 µmol) were added to a degassed solution of
zinc porphyrin ZnPo3 (43 mg, 64 µmol) and Ethynyl-C (42.1 mg, 0.19
mmol) in a 4:1 mixture of THF and triethylamine (6 mL) and the solution
was allowed to stir at 40 °C for 18 h. The solvents were evaporated and
the crude product was dissolved in CHCl (30 mL) and TFA (0.5 mL) was
3
added. The mixture was allowed to stir for 15 min at room temperature and
a saturated aqueous solution of sodium carbonate was added. The organic
bicarbonate, dried over anhydrous sodium sulfate, filtered and evaporated
under vacuum. The crude material was subjected to a chromatography
column over silica gel using ethyl acetate as eluent to provide 3 as a pure
product (1.18 g, 74%).
1H NMR (500 MHz, d
3JH,H=7.1 Hz, 2H), 1.73 (quint, 3
ppm (t, 3JH,H=6.8 Hz, 3H); 13C NMR (125 MHz, d
6
-DMSO): δ=8.13 (s, 1H), 7.38 (br s, 2H), 4.10 (t,
H,H=7.1 Hz, 2H), 1.28-1.21 (m, 6H), 0.82
-DMSO): δ=154.8, 152.8,
J
6
1
0
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European Journal of Organic Chemistry
10.1002/ejoc.202001406
FULL PAPER
phase was dried over anhydrous sodium sulfate, evaporated and
Keywords: Porphyrin • Nucleobases • H-bonds • Molecular
subjected to a chromatography column using CH
eluent. Eventually a size exclusion chromatography column over lipophilic
2
Sephadex gel was performed using CHCl /MeOH (65:35) providing C -
2 2
Cl /MeOH (94:6) as
tectonic
3
Po3 with an enhanced purity (36 mg, < 64%). Once dry, the solubility of
the target product was too low in common solvents to perform satisfying
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(ESI):
m/z calcd
for
:443.2680 [M+2H]2 ; found: 443.2678.
+
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C H N O
C
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2
3
/MeOH mixture (9:1) and a large excess
2
of zinc acetate (a saturated solution in MeOH) was added. The mixture
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prior to evaporation of the solvents providing C -ZnPo3 in quantitative
2
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2
1
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yields.
38.
1
-THF 9 :1): δ=9.67 (d, 3JH,H=4.5 Hz, 4H),
8
H NMR (500 MHz, d
6
-DMSO/d
H,H=4.5 Hz, 4H), 8.75 (s, 2H), 7.94 (br s, 2H), 7.14 (br s, 2H),
.94 (t, 3JH,H=6.9 Hz, 4H), 3.91 (t, 3JH,H=6.9 Hz, 4H), 2.42 (quint, 3JH,H=7.4
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1
9
2H), 0.96-0.88 ppm (m, 12H); HRMS (ESI) calcd for C54
47.4421 [M+H] ; found: 947.4415.
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63 10 2
Zn
+
2
013, 112, 515-521; (e) R. Paolesse, D. Monti, S. Nardis, C. Di
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A -ZnPo3
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copper(I) iodide (1.7 mg, 9 µmol) were added to a degassed solution of
zinc porphyrin ZnPo3 (59 mg, 90 µmol) and Ethynyl-A (64 mg, 0.26 mmol)
in a 4:1 mixture of THF and triethylamine (8 mL) and the solution was
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crude product was sonicated in methanol, filtered over a fritted funnel
,
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2 2 2
and washed with CH Cl , THF and warm pyridine to give A -ZnPo3 (20
mg, < 23%) as a pure green product with an enhanced purity.
+
HRMS (ESI) calcd for C56
H
63
N
14Zn: 995.4646 [M+H] ;found : 995.4649.
2
G -ZnPo3
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7
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2
/methanol (3:1) mixture, filtered
1
984,
over a fritted funnel and washed with warm pyridine to give G
mg, < 30%) as a pure green product with an enhanced purity.
2
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388-390.
6
8
-DMSO/d -THF 9 :1): δ=10.84 (s, 2H), 9.59-9.65 (m,
8
H), 6.74 (s, br, 4H), 4.92 (t, 3JH,H=7.4 Hz, 4H), 4.55 (t, 3JH,H=7.1 Hz, 4H),
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3
H,H=7.6 Hz, 4H), 1.60 (quint, 3JH,H=7.5 Hz, 4H), 1.51 (sext, JH,H=7.4 Hz,
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Entry for the Table of Contents
The synthesis of nucleobase-functionalized porphyrins was achieved via two strategies: substitution and Sonogashira cross coupling
reactions, which resulted in five porphyrins having two nucleobases (NBs) at trans meso-positions linked by flexible methylene linkers
and four porphyrins bearing two NBs at trans meso-positions linked by ridged ethynyl linkers respectively.
1
3
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