1,1′-homodisubstituted ferrocenes containing adenine and thymine nucleobases: Synthesis, electrochemistry, and formation of H-bonded arrays

Article abstract of DOI:10.1021/om200671b

Four organometallic nucleobases have been prepared and characterized, each consisting of a disubstituted ferrocene unit connected through either a conjugated or saturated linker group to adenine or thymine nucleobases. Their assembly behavior has been stu

Full text of DOI:10.1021/om200671b

ARTICLE
pubs.acs.org/Organometallics
1,10-Homodisubstituted Ferrocenes Containing Adenine and Thymine
Nucleobases: Synthesis, Electrochemistry, and Formation of
H-Bonded Arrays
Huy V. Nguyen, Antoine Sallustrau, Louise Male, Peter J. Thornton, and James H. R. Tucker*
School of Chemistry, University of Birmingham, Edgbaston, Birmingham, U.K., B15 2TT
S Supporting Information
b
ABSTRACT: Four organometallic nucleobases have been pre-
pared and characterized, each consisting of a disubstituted ferro-
cene unit connected through either a conjugated or saturated
linker group to adenine or thymine nucleobases. Their assembly
behavior has been studied in the solid state via X-ray crystal-
lography, revealing intermolecular H-bonded arrays. The elec-
trode potentials in DCM are strongly dependent upon the
nature of the linker group between the ferrocene unit and the
nucleobase.
’ INTRODUCTION
Bioorganometallic chemistry is a growing research area in
which classical organometallic chemistry is combined with
biology to achieve materials with unique and novel properties.1
Within this area, the tagging of ferrocene to nucleic acids2 is a
topical theme, mainly due to continued interest in the electro-
chemical sensing of various biomolecules and biological units.
Ferrocenes are commonly connected to nucleosides (i.e., base
plus sugar) via derivatization at a carbon atom on the base,3
which if required would allow incorporation into a nucleic acid
Figure 1. Known examples of thymine nucleobases bridged by a
ferrocene unit attached at the N1 position, where n = 1 and n = 4.
The n = 2 linker (compound 1) is reported in this study.
strand by standard automated chemical synthesis. Alternatively,
the idea of using metallocene-containing nucleobases4 (i.e., base
minus sugar) as bioorganometallic H-bonding motifs can be
conveniently explored by attaching groups at the nitrogen atom
where normally the sugar would be connected (i.e., N1 in
thymine and N9 in adenine). The N1 position of thymine has
received some attention in this respect, and recently bis-func-
tionalized ferrocene derivatives with alkyl linker lengths n = 14a
and 44b (Figure 1) have been reported. Adenine-containing
derivatives are generally less common than their thymine/uracil
counterparts, although a monofunctionalized ferrocene attached
at the N9 position with a linker length n = 1 is known.4c
Herein we report the synthesis, via a novel route, of bis-
functionalized ferrocenylalkyl conjugates to thymine 1 and
adenine 2, each with an ethyl linker, as well as their unsaturated
analogues 3 and 4 (Figure 2). Their solid-state and electroche-
mical behavior are also examined and compared through X-ray
crystallographic analysis and voltammetric analysis, respectively.
’ RESULTS AND DISCUSSION
Synthesis. The four target compounds were made starting from
readily accessible ferrocene-1,10-dicarboxaldehye 5,5 which was
reacted via a HornerꢀWadsworthꢀEmmons procedure with the
corresponding phosphonates 66 and 7 (Scheme 1), the latter which
was made by reacting 9-(diphenylphosphorylmethyl)adenine6 with
benzoyl chloride in pyridine.
Although trial reactions with the monocarboxaldehyde indi-
cated no significant difference in the yield of the coupling
reaction whether the N3 of thymine was protected or not, the
Received: July 23, 2011
Published: September 08, 2011
r
2011 American Chemical Society
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Figure 2. The four target compounds synthesized in this study.
Scheme 1. Synthetic Scheme for the Formation of the Four Target Compoundsa
a Reagents: (1) (a) Pd(OH)2/C, H2 balloon, (b) MeNH2; (2) MeNH2. Compounds 8 and 9 formed as a mixture of isomers (only the major Z isomer is
drawn).
yields of the bis-coupling reaction were greatly improved if
this atom was benzoylated first. Therefore the adenine system
was bis-benzoylated to preclude the occurrence of similar
problems. The products gave approximately a 4:1 ratio of Z
(shown as compounds 8 and 9 in Scheme 1) to (E + E/Z)
isomers in both the thymine and adenine systems, as deter-
mined by vicinal CHdCH coupling constant values on the
1H NMR spectra. This was further verified when the major
fractions in each case were debenzoylated with methylamine
solution to afford the target compounds 3 and 4, with the
X-ray crystal structure of 3 clearly indicating a Z geometry for
both alkenes (Figure 3).
Hydrogenation of the protected 8 and 9 with Pd(OH)2/C
(20%) and H2 (gas at 1 atm), followed by debenzoylation with
methylamine solution afforded the saturated targets 1 and 2 in
good yields.7 It is worth noting that hydrogenation of the un-
protected bis-thymine 3 via the above method was not successful,
even using an alternative hydrogenation method8 (Pd(OH)2/C
(20%), cyclohexene in ethanol). As with compound 3, com-
pound 1 was recrystallized by slow evaporation from a DCM/
MeOH mixture to afford crystals suitable for X-ray diffraction
(Figure 4). The X-ray structure of the adenine analogue, crystals
of which were also grown from a DCM/MeOH mixture, is
presented in Figure 5.
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Table 1. Selected Bond Lengths (Å), Angles (deg), and
Torsion Angles (deg) for 1 and 3a
1
3a
C11ꢀC12
1.519(2)
1.520(2)
1.217(2)
1.230(2)
1.224(2)
1.220(2)
1.371(2)
1.373(2)
1.361(2)
1.382(2)
112.8(1)
110.1(1)
109.0(1)
112.7(1)
122.2(1)
120.3(1)
126.9(1)
122.7(1)
119.9(1)
127.5(1)
ꢀ168.5(1)
ꢀ178.3(1)
1.317(4)
1.325(3)
1.224(3)
1.217(3)
1.207(3)
1.227(3)
1.362(3)
1.390(3)
1.368(3)
1.377(3)
129.7(2)
124.1(2)
129.5(2)
124.0(2)
122.4(2)
119.7(2)
127.4(2)
122.7(2)
119.9(2)
127.1(2)
0.8(4)
C18ꢀC19
O1ꢀC13
O2ꢀC14
O3ꢀC20
O4ꢀC21
N2ꢀC13
N2ꢀC14
N4ꢀC20
N4ꢀC21
Figure 3. Molecular structure of compound 3 showing the atom-
numbering scheme with the ellipsoids drawn at the 50% probability
level. The structure of 3 contains two crystallographically independent
molecules (see Figure 7 and also Supporting Information), with only
one shown here for clarity.
C1ꢀC11ꢀC12
C11ꢀC12ꢀN1
C6ꢀC18ꢀC19
C18ꢀC19ꢀN3
O1ꢀC13ꢀN2
O2ꢀC14ꢀN2
C13ꢀN2ꢀC14
O3ꢀC20ꢀN4
O4ꢀC21ꢀN4
C20ꢀN4ꢀC21
C1ꢀC11ꢀC12ꢀN1
C6ꢀC18ꢀC19ꢀN3
7.0(4)
a The structure of 3 includes two crystallographically independent
molecules. Parameters for one molecule only are given, with the
equivalents from the other molecule being virtually identical. Parameters
for both molecules are given in the Supporting Information.
Figure 4. Molecular structure of compound 1 showing the atom-
numbering scheme with the ellipsoids drawn at the 50% probabil-
ity level.
Figure 5. Molecular structure of compound 2 showing the atom-
numbering scheme with the ellipsoids drawn at the 50% probability
level. The iron atom is located on an inversion center such that only half
of the molecule is crystallographically unique. Selected bond lengths (Å)
and angles (deg): C6ꢀC7 = 1.536(9), N2ꢀC8 = 1.31(1), N2ꢀC9 =
1.415(9), N5ꢀC12 = 1.321(9), C1ꢀC6ꢀC7 = 115.1(6), C6ꢀC7ꢀN1
= 110.3(6), C8ꢀN2ꢀC9 = 103.6(6), N4ꢀC12ꢀN5 = 117.9(7),
C9ꢀC12ꢀN5 = 126.0(7).
Figure 6. Molecular structure of the H-bonded dimer formed by 1 in
the solid state.
feature of ferrocene-containing nucleobases in the solid state.4a,b
It is interesting to note that the three structures show remarkably
different packing arrangements as outlined below.
First, compound 1 forms an intermolecular H-bonded dimer
in the solid state, with each imide NH H-bonded to a carbonyl
oxygen (Figure 6). In each molecule, a carbonyl para to the alkyl-
substituted nitrogen on one thymine and a carbonyl ortho to the
substituent on the other partakes in H-bonding. Hydrogen bond
lengths and angles are presented in Table 2. The Cp rings are
virtually eclipsed (twist angle = 10.8(2)ꢀ), and to allow the
X-ray Crystallography. Selected bond lengths and angles for
the thymine derivatives 1 and 3 are presented in Table 1 to allow
a comparison between the two structures. The major difference is
the larger C11ꢀC12 and C18ꢀC19 bond lengths in 1 for the
saturated linkage, which are similar to the analogous bonds in 2.
However the particular arrangement of the arms and the Cp twist
angles in each system derive from their packing, which is
mediated by intermolecular H-bonding interactions, a common
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Table 2. Hydrogen Bonds (Å and deg) in 1, 2, and 3
Figure 9, and the electrode potentials for all four compounds are
presented in Table 3. The compounds gave satisfactory electro-
chemical reversibility (see Supporting Information for further
details).
DꢀH
A
d(DꢀH) d(H A) d(D A) —(DHA)
3 3 3
3 3 3
3 3 3
1: N2ꢀH2A O3a
0.88
0.88
0.88
0.88
0.88
0.88
0.88
0.88
1.97
1.89
2.28
2.02
1.96
1.90
1.92
1.99
2.839(2)
2.768(2)
3.159(8)
2.850(8)
2.830(2)
2.768(2)
2.797(3)
2.857(3)
171.8
172.0
175.3
156.8
170.3
170.5
175.0
166.9
3 3 3
1: N4ꢀH4A O2a
It is clear that the nature of the linker between the nucleobase and
the ferrocene unit has a significant effect on the electrode potential
values, with the double bonds in 3 and 4 making oxidation more
difficult with respect to compounds 1 and 2. Similar trends have
been observed previously in studies on related compounds contain-
ing either an ethyl spacer or a conjugated double bond between the
ferrocene unit and aromatic moieties.9 However in this case the
difference in potentials (greater than +0.2 V) is larger and in fact is
similar in magnitude to studies on adenine-based derivatives4d
containing either a triple bond or an ethyl group between the
ferrocene unit and the nucleobase. In all these studies, the saturated
linker lowers the ferrocene-centered redox couple, which is con-
sistent with the ferrocenium center being stabilized through a
positive inductive effect.
In conclusion four bis-substituted ferrocenes, containing either
thymine or adenine units, have been synthesized, which has widened
our understanding of the electrochemical behavior and the solid-
state aggregation behavior of organometallic nucleobases. Further
studies are now planned to examine connectivities to other nucleo-
bases and improve the solubility of this class of compound to
facilitate studies of aggregation behavior in solution.
3 3 3
2: N5ꢀH5A N2b
3 3 3
2: N5ꢀH5B N4c
3 3 3
3: N2ꢀH2A O102d
3 3 3
3: N4ꢀH4A O103
3 3 3
3: N102ꢀH10A O1e
3 3 3
3: N104ꢀH10B O4
3 3 3
a Symmetry transformations used to generate equivalent atoms: ꢀx+2,
ꢀy+1, ꢀz+2. b ꢀxꢀ2, yꢀ0.5, ꢀz+0.5. c ꢀxꢀ2, y+0.5, ꢀz+0.5. d x+1, y,
z. e xꢀ1 ,y, z.
formation of the dimer, the structure adopts a rather open
position, with the torsion angle between the two substituents
(C11ꢀC1ꢀC6ꢀC18) being ꢀ122.3(2)ꢀ. The use of polar
solvents to render compound 1 sufficiently soluble at NMR
concentrations prevented the observation of any similar inter-
molecular interactions in solution (as was also the case for
compounds 2, 3, and 4).
In contrast compound 3, the unsaturated analogue of 1, forms
an H-bonded chain (Figure 7) involving oligomers of the two
crystallographically independent molecules. In this ribbon-like
structure, the torsion angles between the subsitutuents on the
ferrocenes (C11ꢀC1ꢀC6ꢀC18 and C111ꢀC101ꢀC106ꢀC118)
are 67.4(2)ꢀ and 55.9(2)ꢀ, respectively, with Cp twist angles of
3.5(3)ꢀ and 17.0(4)ꢀ. However the arrangement of H-bonding
atoms within each molecule is in fact the same as in 1, with each
thymine forming a pair mediated by two H-bonds and the methyl
groups on each thymine being cisoid to one another across the T:T
pair. The H-bond lengths and angles in 1 and 3 are generally similar
(see Table 2).
’ EXPERIMENTAL SECTION
General Comments. Reagent grade reactants and solvents were
used as received from chemical suppliers. Anhydrous solvents were dried
by the usual procedures and were stored over 4 Å molecular sieves. All
reactions were carried out under an inert atmosphere of nitrogen or argon.
Column chromatography was performed on silica gel (Merck, grade 60).
N-Benzoyl-N-(9-((diphenylphosphoryl)methyl)-9H-purin-6-yl)ben-
zamide, 7. To a solution of 9-(diphenylphosphorylmethyl)adenine6
(100 mg; 0.286 mmol) in pyridine (4 mL) at 0 ꢀC was added 132 μL of
benzoyl chloride. The solution was stirred for 5 min. The mixture was
then warmed to room temperature overnight. The pyridine was
removed using high vacuum, and the residue was then dissolved in
dichloromethane, washed with 5% sodium bicarbonate, dried on sodium
sulfate, and evaporated. The crude product was purified on silica gel
using an initial 70/30 ethyl acetate/hexane mixture. A gradient of ethyl
acetate in hexane was then used from 70% to 100% followed by a
gradient of methanol in ethyl acetate from 2% to 10%. A white foam was
obtained (124 mg; 78%). 1H NMR δH (400 MHz, CDCl3): 8.51 (1 H,
s), 8.48 (1 H, s), 7.85ꢀ7.74 (9 H, m), 7.56 (2 H, td, J 7.4, 1.3),
7.52ꢀ7.43 (7 H, m), 7.34 (5 H, t, J 7.8), 5.10 (2 H, d, J 6.2). 13C NMR
(101 MHz, CDCl3): δ 172.14, 153.04, 151.88, 151.74, 145.06, 134.06,
133.02, 132.90, 131.14, 131.05, 129.41, 129.09, 128.97, 128.64, 128.21,
126.54, 43.80, 43.09. MS (ES) (m/z): calcd for C32H24N5O3P 580.1514,
found 580.1511 (M+ + Na). IR (cmꢀ1): 3059, 2975, 2924, 1696, 1597,
1577, 1234. Mp: 108ꢀ110 ꢀC.
There are some notable differences with previous examples of
ferrocenes disubstituted with linker units to thymine (Figure 1,
n = 14a and n = 44b). First these previous examples form
H-bonded arrays, whereas the direct analogue here (compound
1, n = 2) forms an intermolecular dimer. Second, in contrast to
the array formed by 3, these arrays exibit more secondary
supramolecular interactions (e.g., CꢀH O interactions) in
3 3 3
their packing and in fact adopt a transoid orientation of methyl
groups in T:T base pairings, with only the carbonyl ortho to the
alkyl substituent forming H-bonds.
Finally compound 2, the adenine analogue of 1, forms an array
best described as a sheet of H-bonded ribbons (Figure 8). Each
adenine forms four H-bonds, two involving separate nitrogen
heteroatoms on the purine ring as H-bond acceptors and two
involving the amine group as an H-bond donor. However the
symmetry of the molecule is such that there are only two different
H-bonds in the structure, as summarized in Table 2.
The iron atom in 2 is located on an inversion center such that
only half of the molecule is crystallographically unique and the
two Cp rings are identical. Thus the torsion angle between the
ferrocene substituents (C6ꢀC1ꢀC1ꢀC6) is exactly 180ꢀ by
symmetry with the Cp twist angle being exactly 36ꢀ.
Electrochemistry. The redox properties of all four com-
pounds were examined by cyclic voltammetry in DCM. The
general poor solubility of the compounds necessitated filtration
of the electrolyte solution before each experiment. Cyclic vol-
tammograms for the adenine compounds 2 and 4 are shown in
1,10-Bis[(Z)-2-(N3-benzoylthymin-1-yl)ethenyl]ferrocene, 8. In a 200 mL
Schlenk tube compound 6 (1.39 g; 3.13 mmol) was dissolved in dry
pyridine (10 mL) with gentle heating. The pyridine was evaporated, and the
mixture was redissolved with dry DMF (15 mL). NaH (119 mg, 4.69 mmol,
95%) was added, and the mixture was stirred under an inert atmosphere
at room temperature for 1 h before 1,10-dicarboxylaldehyde ferrocene5 (5,
215 mg, 0.89 mmol) dissolved in DMF (20 mL) was added. After 16 h the
reaction mixture was quenched with water (100 mL) and extracted with
EtOAc (30 mL ꢁ 3). The combined organic fractions were dried over
MgSO4, the solvent was removed, and the crude material was purified on
silica gel to give the product as an orange foam (358 mg, 58%, mixture of
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Figure 7. Molecular chain formed by T:T base pairs between pairs of crystallographically independent molecules of 3.
Figure 8. Molecular packing diagram of 2 showing the H-bonded sheet.
Table 3. Electrochemical Data at 500 mV/s in DCMa
1
2
3
4
0
E0
0.524
0.552
0.765
0.770
0
0
a Electrode potentials, E0 , where E0 = (Epa + Epc)/2, are referenced to
decamethylferrocene (ca. 1 mM), which was used as an internal
reference. The confidence limit is (5 mV. Pt working, Pt counter,
and Ag/AgCl reference electrodes were used with tetrabutylammonium
hexafluorophosphate (0.1 M) as supporting electrolyte.
m), 7.02 (2 H, d, J 1.2), 6.47 (2 H, d, J 8.4), 6.25 (2 H, d, J 8.5), 4.39 ꢀ 4.33
(4 H, m), 4.29ꢀ4.22 (4 H, m), 1.90 (6 H, d, J 1.2); 13C NMR (101 MHz,
CDCl3) δ 168.81, 163.10, 148.98, 140.40, 135.10, 131.71, 130.54, 129.17,
125.60, 121.61, 110.77, 77.46, 71.31, 70.94, 12.26; IR (cmꢀ1) 1646, 1743,
2926; MS (ES) (m/z) calcd for C38H30FeN4O6Na 717.1412, found
717.1422 (M+ + Na).
Figure 9. Cyclic voltammograms of 2 (dotted line) and 4 in the
presence of decamethylferrocene (dmfc, shown at ca. ꢀ0.04 V vs Ag/
AgCl) in DCM. Scan rate = 500 mV/s. For other experimental
conditions, see Table 3 and the Supporting Information.
1,10-Bis[(Z)-2-(N6-dibenzoyladenin-9-yl)ethenyl]ferrocene, 9.Compound
7 (800 mg; 1.43 mmol) was dissolved in 6 mL of pyridine. The solution was
evaporated using high vacuum. The residue was then redissolved in 6 mL of
DMF under argon. After 5 min of stirring, 36 mg of sodium hydride 95%
1
ca. 4:1 ratio of Z to (E + E/Z)). Z isomer data: H NMR (300 MHz,
CDCl3) δ 8.00 (4 H, dd, J 8.4, 1.3), 7.73ꢀ7.65 (2 H, m), 7.60ꢀ7.49 (4 H,
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Table 4. Crystal Data and Structure Refinement for 1, 2, and 3
1
2
3
formula
C
24H26FeN4O4
C24H24FeN10
508.38
C24H22FeN4O4
486.31
fw
490.34
space group (no.)
a; b; c (Å)
β (deg)
P21/c (14)
P21/c (14)
P21/c (14)
16.7580(8); 10.9624(6); 11.9973(6)
6.3611(6); 8.0936(11); 20.680(3)
20.6631(9); 11.7587(5); 19.2280(8)
98.978(3)
90.135(8)
112.103(3)
V (Å3)
2177.0(2)
1064.7(2)
4328.5(3)
Z
4
2
8
temperature (ꢀC)
λ (Å)
ꢀ123(2)
1.54184
ꢀ153(2)
0.71073
ꢀ153(2)
1.54184
Dcalcd (g cmꢀ3
μ (cmꢀ1
)
1.496
1.586
1.492
)
5.895
0.747
5.929
final R indices (I > 2σ(I))
final R indices (all data)
R1 = 0.0278, wR2 = 0.0757
R1 = 0.0298, wR2 = 0.0770
R1 = 0.0674, wR2 = 0.1285
R1 = 0.0932, wR2 = 0.1461
R1 = 0.0368, wR2 = 0.0902
R1 = 0.0476, wR2 = 0.950
(1.505 mmol) was added in one portion at room temperature. The mixture
was stirred at room temperature for 2 h. Then the bis-carboxaldehyde5 5
(116 mg; 0.478 mmol), previously dissolved in 5 mL of DMF, was added at
room temperature. After stirring overnight, the reaction was quenched with
water/ethyl acetate (1:1) (20 mL) at 0 ꢀC and extracted with ether. The
organic layers were combined, dried over sodium sulfate, and concentrated.
The crude material was purified on silica gel using an initial 6:4 ethyl
acetate/hexane mixture and then a gradient from 60% to 100% of ethyl
acetate. An orange foam was obtained (84 mg; 32%; mixture of ca. 4:1 ratio
of Z to (E + E/Z)). Z isomer data: 1H NMR (400 MHz, CDCl3) δ 8.75 (2
H, s), 8.09 (2 H, s), 7.89 (9 H, d, J 7.1), 7.50 (4 H, t, J 7.5), 7.37 (9 H, t, J
7.7), 6.84 (2 H, d, J 8.7), 6.39 (2 H, d, J 8.7), 4.20 ꢀ 4.17 (4 H, m), 3.85 (4
H, t, J1.8); 13C NMR (101 MHz, CDCl3) δ172.25, 152.99, 152.81, 152.00,
144.29, 134.16, 132.97, 129.46, 128.68, 127.06, 126.29, 116.15, 77.67, 71.44,
70.43; MS (ES) (m/z) calcd for C52H36FeN10O4Na 943.2168, found
943.2198 (M++ Na); IR (cmꢀ1) 3063, 2961, 2923, 2853, 1697, 1596, 1572,
1229; Mp 106ꢀ108 ꢀC (dec).
temperature for 16 h, after which time the mixture was filtered through a short
pad of Celite to yield a pale yellow solution. The solvent was then removed,
and the residue was stirred with MeNH2 (5 mL) for 10 min before being
evaporated under high vacuum (0.1 mmHg). Purification on silica gel gave
the product as a pale yellow solid (165 mg, 78%), which was recrystallized by
slow evaporation from a DCM/MeOH mixture to yield single pale yellow
crystals: 1H NMR (300 MHz, DMSO) δ 11.23 (2 H, s), 7.43 (2 H, s), 4.07
(8 H, d, J 6.4), 3.83ꢀ3.66 (4 H, m), 2.66ꢀ2.53 (4 H, m), 1.72 (6 H, s); 13C
NMR (101 MHz, DMSO) δ 164.26, 150.71, 141.50, 108.10, 84.33, 68.57,
68.04, 48.12, 28.15, 11.84; IR (cmꢀ1) 1648, 2998, 3155; MS (ES) (m/z)
calcd for C24H26FeN4O4Na 513.1201, found 513.1206 (M+ + Na); Mp
204ꢀ205 ꢀC (dec). Anal. Calcd for C24H26FeN4O4 1/3H2O: C, 58.08; H,
3
5.42; N, 11.29. Found: C, 57.89; H, 5.51; N, 11.66.
1,10-Bis[2-(adenin-9-yl)ethyl]ferrocene, 2. The same procedure as
described above for the preparation of compound 1 was applied using
compound 9 (92mg; 0.099 mmol). The crude was purified on silica gel
using a 45:5 DCM/methanol solvent mixture. A yellow solid was obtained
(33 mg, 66%): 1H NMR 1H NMR (300 MHz, DMSO) δ 8.15 (1 H, s),
8.02 (1 H, s), 7.17 (1 H, s), 4.28 (1 H, t, J7.4), 4.05 (1 H, d, J1.7), 4.01 (1 H,
d, J 1.6), 2.84 (1 H, t, J 7.4); 13C NMR (75 MHz, DMSO) δ 156.38, 152.81,
149.92, 141.22, 119.25, 84.99, 69.00, 68.55, 44.40, 29.67; MS (ES) (m/z)
1,10-Bis[(Z)-2-(thymin-1-yl)ethenyl]ferrocene, 3. In a 100 mL round-
bottom flask compound 8 (200 mg; 0.29 mmol) was stirred with MeNH2
(5 mL) for 10 min before being evaporated under high vacuum (0.1 mmHg).
Purification on silica gel gave the product as an orange solid (134 mg, 96%),
which was recrystallized by slow evaporation from a DCM/MeOH mixture to
yield single orange crystals: 1H NMR (300 MHz, DMSO) δ 11.45 (2 H, s),
7.20 (2 H, s), 6.37 (2 H, d, J 8.4), 6.24 (2 H, d, J 8.5), 4.27 (8 H, dd, J 20.8,
19.1), 1.74 (6 H, s); 13C NMR (101 MHz, DMSO) δ 164.17, 149.84,
calcd for C24H25N10Fe 508.1613, found 509.1638 (M+ + H); IR (cmꢀ1
)
3273, 3109, 2924, 2852, 1659, 1598, 1571, 1305; Mp 284ꢀ286 ꢀC (dec).
X-ray Crystallography. Suitable crystals were selected, and data sets
were measured on a Bruker SMART 6000 diffractometer for 1 and 3 and on
a Bruker APEXII CCD diffractometer at the window of a Bruker FR591
rotating anode for 2. The data collections were driven by SMART10 and
processed by SAINTPLUS11 for 1 and 3 and were driven by COLLECT12
and processed by DENZO13 for 2. Absorption corrections for all three
structures were applied using SADABS.14 The structures were all solved and
refined by a full-matrix least-squares procedure on F2 in SHELXTL.15 All
non-hydrogen atoms were refined with anisotropic displacement param-
eters. All hydrogen atoms were added at calculated positions and refined by
use of a riding model with isotropic displacement parameters based on the
equivalent isotropic displacement parameter (Ueq) of the parent atom.
Figures were produced using OLEX2,16 and structural analysis was carried
out in Mercury 2.4.17 The crystal of sample 2 was a merohedral twin with the
two domains related by the twin law (1 0 0 0 ꢀ1 0 0 0 ꢀ1). The refined
percentage ratio of the twin domains was 52:48. Crystal data and structure
refinement details are given in Table 4.
140.78, 124.70, 122.42, 109.01, 77.77, 70.75, 70.47, 11.79; IR (cmꢀ1
)
1651, 2965, 3172; MS (ES) (m/z) calcd for C24H22FeN4O4Na 509.0888,
found 509.0894 (M+ + Na); Mp 285ꢀ286 ꢀC (dec). Anal. Calcd for
C24H22FeN4O4: C, 59.28; H, 4.56; N, 11.52. Found: C, 59.26; H, 4.43;
N, 11.33.
1,10-Bis[(Z)-2-(adenin-9-yl)ethenyl]ferrocene, 4. Compound
9
(31mg; 0.034 mmol) was dissolved in 1 mL of methylamine. The mixture
was stirred at room temperature for half an hour under argon, and the
methylamine then evaporated. The crude material was purified on silica gel
with a 45:5 DCM/methanol mixture. An orange solid was obtained (13 mg;
77%): 1H NMR (300 MHz, DMSO) δ 8.16 (1 H, s), 8.00 (1 H, s), 7.33
(2 H, s), 6.78 (1 H, d, J 8.5), 6.50 (1 H, d, J 8.6), 4.21ꢀ4.09 (2 H, m),
3.86ꢀ3.69 (2 H, m); 13C NMR (75 MHz, DMSO) δ 156.51, 153.50,
150.00, 140.27, 127.74, 118.82, 117.63, 78.43, 71.16, 70.46; MS (ES) (m/z)
calcd for C24H20FeN10 527.1119, found 527.1138 (M+ + Na); IR (cmꢀ1
)
3303, 3122, 1670, 1645, 1595, 1572, 1302; Mp 256ꢀ258 ꢀC (dec).
1,10-Bis[2-(thymin-1-yl)ethyl]ferrocene, 1. To a 100 mL round-bottom
flask containing compound 8 (200 mg; 0.29 mmol), dissolved in EtOAc
(10 mL) was added Pd(OH)2 (20% wt on carbon, 465 mg, 1.05 mmol). The
reaction was stirred under a H2 (ballon pressure) atmosphere at room
’ ASSOCIATED CONTENT
S
Supporting Information. NMR spectra of selected com-
b
pounds, electrochemical data showing variable scan rate dependence,
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dx.doi.org/10.1021/om200671b |Organometallics 2011, 30, 5284–5290

Organometallics
ARTICLE
X-ray data including CIF file (CCDC deposition numbers 1:
831176, 2: 831177, and 3: 831178), and tables of bond lengths
and angles. This material is available free of charge via the Internet at
http://pubs.acs.org.
(12) Hooft, R. W. W. COLLECT Data Collection Software; Nonius B.
V.: Delft, The Netherlands, 1998.
(13) Otwinowski, Z.; Minor, W. In Methods in Enzymology; Carter,
C. W.; Sweet, R. M., Eds.; Academic Press: New York, 1997; Vol. 276, p
307.
(14) Sheldrick, G. M. SADABS, Version 2007/2; Bruker AXS Inc.:
Madison, WI, USA, 2007.
’ AUTHOR INFORMATION
(15) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112.
(16) Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.;
Puschmann, H. J. Appl. Crystallogr. 2009, 42, 339.
Corresponding Author
*E-mail: j.tucker@bham.ac.uk.
(17) Macrae, C. F.; Bruno, I. J.; Chisholm, J. A.; Edgington, P. R.;
McCabe, P.; Pidcock, E.; Rodriguez-Monge, L.; Taylor, R.; van de
Streek, J; Wood, P. A. J. Appl. Crystallogr. 2008, 41, 466–470.
’ ACKNOWLEDGMENT
Advantage West Midlands (AWM) is acknowledged for
equipment funding, and the EPSRC is thanked for the award of a
Leadership Fellowship to J.H.R.T. The UK National Crystallography
Service is also acknowledged for data collection on compound 2.
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