Synthesis and electrochemical evaluation of conjugates between 2′-deoxyadenosine and modified anthraquinone: Probes for hole-transfer studies in DNA

Article abstract of DOI:10.1021/jo900306g

(Chemical Equation Presented) Photoexcitation of anthraquinones (AQ) in association with DNA results in DNA damage mainly at guanine residues, with products from thymine oxidation also observed. Studies of adenine oxidation will be aided by systems with an increased driving force for charge transfer, achieved by adding electron-withdrawing groups to the AQ ring. Attaching AQ derivatives to adenine via a bridge with two carbon atoms should enable the intended regiocontrol within the DNA duplex structure. Herein we report the synthesis of conjugates between AQ and adenine in which the AQ moieties have been modified with a formyl, a trifluoroacetyl, and two methyl ester groups. These have been synthesized by palladium coupling of tert-butyldiphenylsilyl 5′-protected 8-ethynyl-2′-deoxyadenosine with the corresponding bromoanthraquinone intermediates. Bromo intermediates bearing formyl or trifluoroacetyl were prepared by monolithiation of 2,6-dibromoanthraquinone, a step that required protection of the anthraquinone carbonyls. A bromo intermediate bearing two methyl ester groups was obtained from 1,2,4-trimethylbenzene by Friedel-Crafts acylation with 4-bromobenzoyl chloride followed by oxidation to the tricarboxylic acid, cyclization to form the anthraquinone ring, and finally esterification. Hydrogenation of the ethynyl linker gave the ethanyl linker. Cyclic voltammetry showed that the conjugate with the two ester groups and ethynyl linker was the most easily reduced of the derivatives synthesized. These derivatives, with reduction potentials favorable for electron transfer, can be used in studies of adenine oxidation in DNA.

Full text of DOI:10.1021/jo900306g

Synthesis and Electrochemical Evaluation of Conjugates between
2′-Deoxyadenosine and Modified Anthraquinone: Probes for
Hole-Transfer Studies in DNA
Reham A. I. Abou-Elkhair, Dabney W. Dixon,* and Thomas L. Netzel†
Department of Chemistry, Georgia State UniVersity, P.O. Box 4098, Atlanta, Georgia 30302-4098
ddixon@gsu.edu
ReceiVed February 11, 2009
Photoexcitation of anthraquinones (AQ) in association with DNA results in DNA damage mainly at
guanine residues, with products from thymine oxidation also observed. Studies of adenine oxidation will
be aided by systems with an increased driving force for charge transfer, achieved by adding electron-
withdrawing groups to the AQ ring. Attaching AQ derivatives to adenine via a bridge with two carbon
atoms should enable the intended regiocontrol within the DNA duplex structure. Herein we report the
synthesis of conjugates between AQ and adenine in which the AQ moieties have been modified with a
formyl, a trifluoroacetyl, and two methyl ester groups. These have been synthesized by palladium coupling
of tert-butyldiphenylsilyl 5′-protected 8-ethynyl-2′-deoxyadenosine with the corresponding bromoan-
thraquinone intermediates. Bromo intermediates bearing formyl or trifluoroacetyl were prepared by
monolithiation of 2,6-dibromoanthraquinone, a step that required protection of the anthraquinone carbonyls.
A bromo intermediate bearing two methyl ester groups was obtained from 1,2,4-trimethylbenzene by
Friedel-Crafts acylation with 4-bromobenzoyl chloride followed by oxidation to the tricarboxylic acid,
cyclization to form the anthraquinone ring, and finally esterification. Hydrogenation of the ethynyl linker
gave the ethanyl linker. Cyclic voltammetry showed that the conjugate with the two ester groups and
ethynyl linker was the most easily reduced of the derivatives synthesized. These derivatives, with reduction
potentials favorable for electron transfer, can be used in studies of adenine oxidation in DNA.
Introduction
advantageous over other chromophores in that it can give an
initial triplet CT product. All things being equal, a triplet
CT product will live considerably longer than a singlet CT
product. This would facilitate a higher yield of secondary
hole transfer along DNA.7
Electron transfer through the DNA duplex continues to be
a field of intense study.1-6 In many instances, anthraquinone
(AQ) has been used as an electron acceptor chromophore to
initiate DNA oxidation upon photoexcitation with UV light.
In these systems, because the singlet excited state of AQ
lives for less than 1 ps,7 it is the triplet excited state of AQ
that gives the charge transfer (CT) product: a radical anion
on AQ and a hole on a DNA base. In this aspect, AQ is
Although adenine can serve as a hole carrier,8-14 oxidized
DNA in general gives final products due to reactions at a G
radical cation (G•+) site. Recent work on DNA linked to AQ in
which the DNA had only adenine (A) and thymine residues
(T) found that T formed oxidation products in preference to
A.15,16 Since A is easier to oxidize than T,17,18 this finding was
unexpected. These observations were attributed to the signifi-
† Deceased September 4, 2008. We remember him as a careful scholar,
dedicated mentor, caring teacher, and close friend.
4712 J. Org. Chem. 2009, 74, 4712–4719
10.1021/jo900306g CCC: $40.75  2009 American Chemical Society
Published on Web 06/09/2009

Probes for Hole-Transfer Studies in DNA
cantly higher reactivity of the T radical cation (T•+) compared
to that of the A radical cation (A•+). Upon photolysis, conjugates
with the anthraquinone covalently linked to DNA have also been
shown to give products arising from T radical cations.19
Our previous work showed that A•+ can be formed by
photolysis of a system containing both A and AQ.7 Whether or
not an AQ-A conjugate forms the AQ•-/A•+ CT photoproduct
depends on the details of the system studied. For example,
irradiation of the AQ-A conjugates AQYdA or AQEdA in
methanol20 or AQYdAP or AQEdAP21 in water22 did not give
the AQ•-/A•+ photoproduct. On the other hand, photoexcitation
of AQCOdA did give the AQ•-/A•+ in MeOH and DMSO.7 In
addition, photoexcitation of a bimolecular solution of 2′-
deoxyadenosine (dA) and anthraquinone-2-sulfonate in water
produced the AQ•-/A•+ CT product.20 One possibility for these
observations is that AQ•-/A•+ is formed only when the an-
thraquinone is substituted with an electron-withdrawing group,
which would be expected to result in a greater driving force
for the CT reaction.
the greatest potential for creation of a hole at a well-defined
position on the DNA duplex provided that the linker between
the base and AQ is very short. Long linkers permit a variety of
options for the position of AQ with respect to the DNA,
including intercalation between adjacent base pairs.30,34,35
Future studies in the area of A oxidation would be greatly
aided by access to a series of AQ-dA derivatives with short
linkers between the AQ and DNA and higher driving forces
for CT. Our work and literature studies indicate that these AQ
derivatives should have electron-withdrawing substituents on
the AQ ring.19,27,34,36-39 In such systems, the AQ can oxidize
its covalently attached A, giving a precise point of initial DNA
oxidation. This approach complements chemical production of
the A•+.8,9
Herein, we report the synthesis of AQ-dA conjugates (1-4)
bearing formyl, trifluoroacetyl, or methyl ester groups as
carbonyl-containing substituents. In view of the probable
importance of the linker in studies of AQ-A conjugates, the
diester has been prepared with both ethanyl and ethynyl linkers.
To place the anthraquinone in the major groove, we attached it
to the 8-position of the adenine. Literature studies indicate that
attachment of groups in this position may lead to slight
destabilization of the DNA duplex.28,40-44 Photolyses of DNA
(12) Bixon, M.; Jortner, J. Chem. Phys. 2006, 326, 252–258.
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Nucleotides Nucl. Acids 2006, 25, 601–612.
If the position of the initial radical on DNA is to be
pinpointed, it is necessary to have the AQ covalently bound to
specific positions along the DNA strand. This should minimize
side reactions such as oxidation of distant bases and charge
recombination during hole migration along the DNA duplex.
A variety of AQ derivatives linked to positions along the DNA
duplex have been reported in the literature. For example, AQ
has been linked to both the C-1′ and the C-2′ of a sugar.23-26
It has also replaced a base19,27 or been incorporated into the
backbone.27 AQ has also been covalently attached to both
adenine28 and uridine.29-33 This last class of derivatives has
(1) Giese, B. Annu. ReV. Biochem. 2002, 71, 51–70.
(2) Schuster, G. B.; Beratan, D. Long-range Charge Transfer in DNA I, II;
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Nucleotides Nucl. Acids 2007, 26, 921–925.
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126, 14732–14733.
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S. S. Nucleic Acids Res. 1996, 24, 890–897.
J. Org. Chem. Vol. 74, No. 13, 2009 4713

Abou-Elkhair et al.
SCHEME 1
duplexes with donors conjugated to the bases through an alkyne
group have been shown to give charge transfer products.45
Electrochemical potentials of these conjugates were measured
in acetonitrile.
and the chromatographic similarity of the protected bromo-dA
starting material and AQ-dA products.
Therefore, in our present work, we switched the order of the
alkynylation steps. 8-Bromo-2′-deoxyadenosine 521 was first
coupled with TMSA using Pd-based chemistry as illustrated in
Scheme 1 to give the protected alkyne 6. The yield of this step
was greatly affected by the interval between the addition of the
reagents. For example, when TMSA was added 2 min after
triethylamine (TEA) addition, the yield was 57%. On the other
hand, immediate addition of TMSA after TEA improved the
yield to 85%. The silyl group on the ethynyl of 6 was removed
quantitatively by using K2CO3 as an oxide46 leaving the silyl
protection on 5′-O intact to yield the free alkyne 7. This in turn
was Pd-coupled with bromoanthraquinone derivatives bearing
a formyl, a trifluoroacetyl, or two methyl ester groups.
Modification of AQ Moiety with a Formyl Group. We
chose to introduce the formyl group via lithiation of a bromide
on AQ using butyllithium. Because the AQ carbonyls are
susceptible to addition of such a strongly nucleophilic reagent,
protection of the AQ quinone function was necessary. A second
bromide on AQ was needed to couple AQ with the terminal
alkyne on 7 using Pd-based coupling. Thus, our synthetic
strategy started with 2,6-dibromoanthraquinone. Other strategies
based on electrophilic aromatic substitutions47,48 or Diels-Alder
reactions49 were avoided in order to circumvent obtaining
regioisomers. The feasibility of monolithiation of 2,6-dihaloan-
thraquinone was key in this synthesis.
As illustrated in Scheme 2, the initial step was transformation
of 2,6-diaminoanthraquinone (8) to the dibromo derivative 9
as described in the literature41 with minor modifications in the
procedure. In general, protection of the quinone functionality
is most commonly done by reductive methylation to form the
dimethoxyanthracene derivatives.50-53 However, a number of
different modifications of this reaction all gave mixtures with
low solubility including a substantial amount of unreacted 9,
which made chromatographic purification troublesome. To solve
this problem, use of a larger alkyl group was necessary.
Although the literature53 has reported good yields of reductive
propylation of 9 using n-propyl bromide, only trace amounts
of the propylated product were obtained in our hands. However,
use of butyl triflate as a more reactive alkylating agent in the
one pot reductive alkylation employing Na2S2O4 in phase-
Results and Discussion
Our choice of the substituents to modify AQ was based not
only on the feasibility of their preparations, but also on the
compatibility of such substituents toward a variety of conditions
used in the conventional DNA synthesis protocols. The final
target conjugates also required protection of at least one
hydroxyl on dA to improve solubility in acetonitrile to the
necessary concentrations for electrochemical measurements.
Hence, dA 5′-protected with a tert-butyldiphenylsilyl (TBDPS)
group was used as the starting material. This protection was
also important to increase the solubility of the synthetic
intermediates.
Synthesis of Deoxyadenosine Substrate. In our previous
work,21 we joined AQ to dA via an alkyne linker by first
allowing 2-iodoanthraquinone to react with trimethylsilylacety-
lene (TMSA) using Pd-catalyzed cross-coupling chemistry.
Deprotection of the trimethylsilyl group on the resulting
2-ethynylanthraquinone permitted a second Pd coupling with
5′-protected 8-bromo-dA to form the desired AQ-dA conju-
gates. However, working with the ethynylanthraquinone imposed
synthetic constraints due to its poor solubility, photoinstability,
(46) Li, Q.; Rukavishnikov, A. V.; Petukhov, P. A.; Zaikova, T. O.; Keana,
J. F. W. Org. Lett. 2002, 4, 3631–9634.
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544.
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Bioorg. Med. Chem. Lett. 2000, 10, 2005–2009.
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406.
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Y.; Saito, I.; Okamoto, A. J. Am. Chem. Soc. 2007, 129, 4776–4784.
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T. L. J. Phys. Chem. A 2005, 109, 10832–10845.
(49) Cormier, R. A.; Connolly, J. S.; Pelter, L. S. Synth. Commun. 1992, 22,
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Chem. 1986, 51, 3456–3462.
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Biehl, E. Synthesis 1995, 827–830.
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Org. Lett. 2005, 7, 323–326.
4714 J. Org. Chem. Vol. 74, No. 13, 2009

Probes for Hole-Transfer Studies in DNA
SCHEME 2
transfer catalysis gave the dibutylanthracene derivative 10 in
88% yield. Strict anaerobic conditions were essential to obtain
the product in good yield. A solution of the protected 10 in
tetrahydrofuran (THF) was successfully monolithiated with 1.05
equiv of n-BuLi at -72 °C; subsequent quenching with DMF
afforded the desired bromo intermediate 11. The optimal yield
was obtained when 15 mg/mL as a concentration of 10 in THF
was used; higher concentrations led to precipitation of 10 when
the solution was cooled to -72 °C, resulting in reduced yields
of monosubstitution with the formyl group.
Oxidative dealkylation of 11 to the anthraquinone aldehyde
13 was effected using AgO/HNO3 in dioxane54 for 5 min or
PhI(OCOCF3)2 in water55 and THF for 7 h. The former reagent
was preferred because filtration and water workup removed all
side products and chromatography was not required. The
AQ-dA conjugate 1 was obtained in moderate yield via Pd-
catalyzed coupling between 13 and 7, with 13 used in a higher
molar ratio than 7 to ease purification. Hydrogenation of 1 using
10% Pd/C in methanol resulted in the reduction of the alkyne
linker, with the product isolated as the corresponding dimethyl
acetal 15 in 86% yield.
nucleoside directly without protection,59 indicating that this
group can survive DNA synthesis conditions.
Modification of the AQ Moiety with a Trifluoroacetyl
Group. The bromo trifluoroacetate 12 was synthesized as
described above for 11, except that ethyl trifluoroacetate was
used instead of DMF as the quenching electrophile after
lithiation. Oxidative dealkylation of 12 with AgO/HNO3 gave
the desired product 14, and was preferable to PhI(OCOCF3)2,
which gave substantial amounts of a side product. Compound
14 was obtained as a mixture of the ketone and its water adduct,
the geminal diol, in a ratio of 2:1. This was judged by 1H NMR
resonances for H-5 at both 8.92 (ketone) and 8.56 (gem-diol)
ppm, and 19F NMR resonances at both -72.34 (ketone) and
-83.90 (gem-diol) ppm. COCF3 moieties are known to
hydrate.60-63 Following a protocol in the literature,64 shaking
of 14 in ethyl acetate with a solution of NaHCO3 in water,
followed by removal of the ethyl acetate, gave the ketone
exclusively as shown by NMR.
Conjugate 2 was synthesized by Pd coupling of anthraquinone
14 to 7 as described above. The product was isolated via silica
gel purification using a MeOH/EtOAc/hexane solvent mixture.
19F NMR in CDCl3/CD3OD showed a single resonance at
-83.57 ppm. The mass spectrum indicated that the majority of
the product was the geminal diol (rather than the hemiketal65
or ketal). Treatment of the diol form of 2 with NaHCO3 as
described for 14 did not result in reversion to the ketone form.
Literature studies indicate that the formyl group can be
incorporated into DNA. For instance, the formyl group has been
protected before incorporation into DNA, with later acidic
hydrolysis to afford an unprotected formyl moiety.56 The formyl
group has also been formed by postsynthetic oxidation of DNA
containing 1,2-dihydroxyethyl group with sodium periodate.57,58
In a third strategy, the formyl group has been introduced into
DNA using the phosphorimidite of 3-formylindole 2′-deoxy-
(59) Okamoto, A.; Tainaka, K.; Saito, I. Tetrahedron Lett. 2002, 43, 4581–
4583.
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Moshkin, V. S. Russ. Chem. Bull. 2005, 54, 2846–2850.
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(54) Tietze, L. F.; Gericke, K. M.; Singidi, R. R. Angew. Chem., Int. Ed.
2006, 45, 6990–6993.
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Tetrahedron Lett. 2001, 42, 6899–6902.
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Bull. 1994, 42, 2231–2237.
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I. Tetrahedron Lett. 1996, 37, 9067–9070.
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V. A. HelV. Chim. Acta 2005, 88, 1913–1921.
(62) Mitchell, L. H.; Samas, B. Synth. Commun. 2005, 35, 955–959.
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235–239.
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D. PCT/US 1998/006462, 1998, WO/1998/045278, 53-54.
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84, 3818–3821.
J. Org. Chem. Vol. 74, No. 13, 2009 4715

Abou-Elkhair et al.
SCHEME 3
TABLE 1. Reduction Potentials of AQ and AQdA Cconjugates in
CH3CN
However, when conjugate 2 was dissolved in a saturated solution
of K2CO3 in methanol and stirred overnight, treated with water,
and extracted with chloroform, the ketone form was obtained.
This was confirmed by the 19F NMR peak at -72.54 ppm and
1H NMR (CDCl3) peaks at 9.02, 8.53, and 8.49 ppm corre-
sponding to the three protons (H-5, H-8, and H-7, respectively)
of the AQ ring bearing the COCF3.
compd
linker with dA
substituent
E1/2 (SCE)
AQ
none
none
none
none
amide
CHO
di(CO2Me)
di(CO2Me)
-0.939
-0.782
-0.935
-0.734
-0.626
-0.574
-0.700
AQYdA-5′-O-TBDPS
Ct
C
AQEdA-5′-O-TBDPS
CH2CH2
amide
AQCOdA-3′,5′-di-O-Ac
1
3
4
Ct
Ct
C
C
Modification of the AQ Moiety with Two Methyl Ester
Groups. 6-Bromoanthraquinone-2,3-dicarboxylic acid (18) was
the key intermediate for making AQ-dA conjugates modified
with two methyl ester groups. As shown in Scheme 3, 18 was
prepared analogously to the literature procedure for anthraquinone-
2,3-dicarboxylic acid.66,67 Friedel-Crafts acylation of 1,2,4-
trimethylbenzene with 4-bromobenzoyl chloride afforded ben-
zophenone derivative 16. Following the original procedure, the
desired 16 was often contaminated with significant amounts of
a byproduct that was difficult to remove by either fractional
distillation or chromatography. This byproduct was isolated by
crystallization from ethyl acetate and identified by NMR as a
methyl homologue of 16 (methyl homologues result from a side
reaction common under Friedel-Crafts conditions68,69). To
increase the yield of 16, we minimized this side reaction by
preliminary mixing of AlCl3 and 4-bromobenzoyl chloride and
dropwise addition of 1,2,4-trimethylbenzene at -20 °C. Frac-
tional crystallization of the crude product from ethyl acetate/
methanol allowed separation of pure 16.
CH2CH2
of 17 was effected by concd H2SO4 to give the bromoan-
thraquinone 18. Removal of all H2SO4 from the product 18 by
washing with water was difficult due to its solubility in water.
Hence, the crude mixture of 18 was esterified in refluxing
methanol using the H2SO4 present in this crude material as the
catalyst to give the dimethyl ester 19. Compound 19 in turn
was coupled to 7 using Pd-catalyzed chemistry to give conjugate
3 and then hydrogenated in a manner similar to that described
above to give conjugate 4. The conjugates studied are stable to
ambient light, air, and water.
Solid-phase DNA synthesis generally employs ammonia in
the final deprotection step. Ammonia can react with methyl
esters to form amides71 which can further hydrolyze under basic
conditions to the corresponding carboxylic acids.72 The ammonia
step can be replaced by treatment with 0.05 M K2CO3 in
methanol; the AQ dimethyl ester was stable to these milder
conditions.
Electrochemical Results. Our first goal was to examine the
effect of electron-withdrawing groups on the reduction potential
of the AQ in the conjugate. Diester substitution (4) gave a
reduction potential of -0.700 V; this disubstitution makes the
conjugate easier to reduce than AQEdA-5′-O-TBDPS by 235
mV (both compounds with ethanyl linkers, Table 1). Formyl
conjugate 1 was more difficult to reduce than the diester
The tricarboxylic acid 17 was obtained by refluxing 16 in
20% aqueous HNO3 to give an alkali-soluble mixture of
monocarboxylic acids70 that was further oxidized with KMnO4
in 4% NaOH. To prevent any possible displacement of the
bromide on the product by hydroxide, the crude product mixture
was taken to pH ≈ 9 before concentration. Cyclodehydration
(66) Hallman, J. L.; Bartsch, R. A. J. Org. Chem. 1991, 56, 6243–6245.
(67) Lohier, J. F.; Wright, K.; Peggion, C.; Formaggio, F.; Toniolo, C.;
Wakselman, M.; Mazaleyrat, J. P. Tetrahedron 2006, 62, 6203–6213.
(68) Rae, I. D.; Woolcock, M. L. Aust. J. Chem. 1987, 40, 1023–1029.
(69) Vogel, A. I.; Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell,
A. R. Vogel’s Textbook of Practical Organic Chemistry, 5th ed.; Prentice Hall:
Upper Saddle River, NJ, 1996; p 1006.
(71) Sun, A.; Prussia, A.; Zhan, W.; Murray, E. E.; Doyle, J.; Cheng, L. T.;
Yoon, J. J.; Radchenko, E. V.; Palyulin, V. A.; Compans, R. W.; Liotta, D. C.;
Plemper, R. K.; Snyder, J. P. J. Med. Chem. 2006, 49, 5080–5092.
(72) March, J. AdVanced Organic Chemistry: Reactions, Mechanisms, and
Structure, 4th ed.; Wiley: New York, 1992; p 887.
(70) Clar, E. Chem. Ber. 1948, 81, 63–68.
4716 J. Org. Chem. Vol. 74, No. 13, 2009

Probes for Hole-Transfer Studies in DNA
conjugate 3 by approximately 50 mV (both compounds with
ethynyl linkers). Although the formyl group has been reported
to be stable on DNA in aqueous solution,56,57,59,73,74 formyl
conjugate 1 showed some degradation on repeated cycles of
reduction and reoxidation, indicating that photophysical studies
of this derivative might be problematic. Efforts to obtain
reproducible reduction potential values for the conjugate 2 with
the C(OH)2CF3 substituent were thwarted by the ease with which
this compound converted between the ketone and geminal diol
forms under the conditions of the electrochemistry experiments.
This has literature precedence in the electrochemistry of
trifluoroacetylbenzophenone75,76 and makes its use in DNA
conjugates problematic.
groups have been achieved. In these conjugates, AQ was linked
to adenine via ethanyl or ethynyl groups. Electrochemical
measurements of these conjugates revealed that the diester
modification facilitates the reduction of AQ by 235 mV
compared with the corresponding unmodified conjugates. In
addition, the ethynyl linkers further enhance the reduction
potential of the AQ by 125 -150 mV relative to ethanyl linkers.
Conjugates of AQ-dA with an ethynyl linker and diester
substituents on AQ would satisfy two advances required for
achieving better yields for hole transfer in DNA. The first is
favorable oxidation of A by virtue of the electron withdrawing
nature of the substituent groups. The second is regiocontrol of
the DNA secondary structure by the short and rigid linker
between AQ and A.
Our second goal was to understand the effect of the linker
on the reduction potential of the AQ. The reduction potential
of the AQEdA-5′-O-TBDPS conjugate, with an ethanyl linker,
was -0.935 V, which was the same as that of AQ itself at
-0.939 V. Thus, the ethanyl linker seems to isolate the AQ
group effectively from the rest of the molecule. Comparison of
the ethanyl and the ethynyl linkers showed that the conjugates
with the ethynyl linker were more easily reduced. Thus,
AQYdA-5′-O-TBDPS was easier to reduce than AQEdA-5′-O-
TBDPS by approximately 150 mV, and 3 was easier to reduce
than 4 by approximately 125 mV. The comparative ease of
reduction of AQ in the conjugates with the ethynyl linker is
consistent with the electron-withdrawing nature of the ethynyl
group as well as the extended conjugation in these systems.
The extended conjugation is seen spectroscopically in the
significantly larger extinction coefficient, and the red shift of
the absorbance, for the ethynyl derivative 3 in comparison with
the ethanyl derivative 4. This is also observed for AQYdA in
comparison with AQEdA (Supporting Information). Overall, the
molecule of choice for future photophysical studies is an-
thraquinone diester 3, both because it has the most favorable
reduction potential of the molecules studied and because it can
undergo cycles of reduction and reoxidation without degradation.
The redox potentials of both the adenine and anthraquinone
may alter when studied in DNA in aqueous solution. The
reduction potentials of anthraquinones in water are pH depend-
ent, with more negative potentials as the pH increases.77
Oxidation of adenine is significantly affected not only by pH
and medium effects, but also by base pairing and base
stacking.78-81 Thus, the driving force for electron transfer in
aqueous solution of these conjugates incorporated into duplex
DNA is expected to depend on a variety of factors, including
the base sequence studied.
Experimental Section
5′-O-tert-Butyldiphenylsilyl-8-[(trimethylsilyl)ethynyl]-2′-deoxy-
adenosine, 6. Compound 521 (2.5 g, 3.4 mmol), Pd(PPh3)2Cl2 (154
mg, 0.220 mmol, 0.0500 equiv), and CuI (84 mg, 0.44 mmol, 0.10
equiv) were combined and stirred in dry THF (25 mL) in a
glovebox. Triethylamine (TEA) (1.23 mL, 8.80 mmol, 2.00 equiv)
was added followed immediately by trimethylsilylacetylene (TMSA)
(1.50 mL, 13.2 mmol, 3.00 equiv). The dark brown mixture was
removed from the glovebox and stirred under a nitrogen atmosphere
at 60 °C in an oil bath for 30 min. The solvent was removed under
reduced pressure, and the black foam residue was dried in vacuo
at 45 °C for 2 h. The dry crude material was purified two times
with silica gel column chromatography. The first column was eluted
with MeOH/CH2Cl2 (0:100-3:97), and the second was eluted with
EtOAc/CH2Cl2 (1:9-1:1). Evaporation of the eluting solvent
1
afforded 6 as a light brown foam (2.20 g, 85% yield). H NMR
(300 MHz, CDCl3): δ (ppm) 0.03 (9H, s), 1.05 (9H, s), 2.27 (1H,
d, J ) 3.3 Hz), 2.41 (1H, ddd, J ) 4.5, 7.5, and 13.5 Hz), 3.35-3.44
(1H, m), 3.89 (1H, dd, J ) 4.8 and 9.6 Hz), 3.99-4.10 (2H, m),
4.97-5.14 (1H, m), 5.66 (2H, br s), 6.52 (1H, dd, J ) 3.3, 4.5
Hz), 7.26-7.45 (6H, m), 7.61-7.64 (4H, m), and 8.14 (1H, s).
13C NMR (125 MHz, CDCl3): δ (ppm) -0.6, 19.2, 26.9, 37.3, 64.4,
73.4, 84.8, 86.7, 92.5, 103.7, 120.0, 127.7, 129.8, 133.2, 134.3,
135.6, 149.2, 153.6, and 155.1. HRMS (ESI): calcd for
C31H40N5O3Si2 [M + H]+ 586.2670, found 586.2646.
5′-O-tert-Butyldiphenylsilyl-8-ethynyl-2′-deoxyadenosine, 7.
To a solution of 6 (0.29 g, 0.50 mmol) in CH2Cl2/MeOH (1:5 v/v,
6 mL) was added K2CO3 (89 mg, 0.64 mmol, 1.5 equiv). The
mixture was stirred at rt for 30 min. Water and more CH2Cl2 were
added, and the mixture was transferred to a separatory funnel. The
organic layer was separated, dried with anhyd MgSO4, and
evaporated to dryness. The residue was purified by silica gel column
eluted with MeOH/CH2Cl2 (0:100-4:96). Evaporation of the eluting
solvent afforded 7 as a white foam (252 mg). 1H NMR (400 MHz,
CDCl3): δ (ppm) 0.93 (9H, s), 2.29 (1H, ddd, J ) 4, 7.2, and 13.6
Hz), 3.29 (1H, s), 3.34-3.42 (1H, m), 3.53 (1H, br s), 3.79 (1H,
dd, J ) 5.2 and 10.4 Hz), 3.93 (1H, dd, J ) 7.6 and 10.4 Hz),
4.03-4.09 (1H, m), 4.86-4.89 (1H, m), 6.29 (2H, br s), 6.49 (1H,
t, J ) 7.2 Hz), 7.18-7.34 (6H, m), 7.51-7.57 (4H, m), and 8.07
(1H, s). 13C NMR (100 MHz, CDCl3): δ (ppm) 19.4, 27.0, 37.1,
64.2, 72.8, 72.9, 84.7, 85.2, 87.3, 127.8, 127.9, 129.9, 129.9, 133.2,
133.5, 133.8, 135.7, 135.7, 149.3, 153.9, and 155.6. HRMS (ESI):
calcd for C28H32N5O3Si [M + H]+ 514.2274, found 514.2271.
2,6-Dibromo-9,10-di-n-butoxyanthracene, 10. A suspension of
9 (3.0 g, 8.1 mmol) and n-Bu4NBr (2.37 g, 7.30 mmol, 0.900 equiv)
in CH2Cl2 (90 mL) was placed in a Synthware Glass 250-mL round-
bottom Schlenk flask with a side arm inlet controlled with a glass
stopcock. This Schlenk flask was equipped with a stirring bar and
connected to the vacuum line through an adapter with a valve. The
contents of the flask were degassed by freezing the suspension and
applying vacuum through the adapter until the pressure in the flask
Conclusions
The syntheses of AQ-dA conjugates with the AQ bearing
electron-withdrawing formyl, trifluoroacetyl and dimethyl ester
(73) Yan, H.; Tram, K. Glycoconjugate J. 2007, 24, 107–123.
(74) Karino, N.; Ueno, Y.; Matsuda, A. Nucleic Acids Res. 2001, 29, 2456–
2463.
(75) Scott, W. J.; Zuman, P. Anal. Chim. Acta 1981, 126, 71–93.
(76) Guthrie, J. P. J. Am. Chem. Soc. 2000, 122, 5529–5538.
(77) Quan, M.; Sanchez, D.; Wasylkiw, M. F.; Smith, D. K. J. Am. Chem.
Soc. 2007, 129, 12847–12856.
(78) Caruso, T.; Capobianco, A.; Peluso, A. J. Am. Chem. Soc. 2007, 129,
15347–15353.
(79) Crespo-Herna´ndez, C. E.; Close, D. M.; Gorb, L.; Leszczynski, J. J.
Phys. Chem. B 2007, 111, 5386–5395.
(80) Adhikary, A.; Kumar, A.; Khanduri, D.; Sevilla, M. D. J. Am. Chem.
Soc. 2008, 130, 10282–10292.
(81) Bose, A.; Sarkar, A. K.; Basu, S. Biophys. Chem. 2008, 136, 59–65.
J. Org. Chem. Vol. 74, No. 13, 2009 4717

Abou-Elkhair et al.
was e5 mTorr. The vacuum was then disconnected, and the mixture
was allowed to thaw. The freeze-vacuum-thaw cycle was repeated
until the pressure remained constant in the flask when the mixture
was frozen. The vacuum adapter was closed and the space in the
flask was filled with nitrogen gas through the side arm. Sodium
dithionite (4.92 g, 24.3 mmol, 3.00 equiv) was added to frozen
degassed water (23 mL) in a separate flask, and then the
water-dithionite mixture was degassed again. The resulting solution
was added to the suspension of 9 under nitrogen gas via a cannula.
After the mixture was stirred for 1 min, a dark green color
developed; the mixture was stirred for 5 min at rt. A degassed
solution of NaOH (1.65 g, 40.5 mmol, 5.00 equiv) in water (15
mL) was added under nitrogen gas via a cannula. After being stirred
for 15 min at rt, the dark red mixture was cooled to 0 °C using an
ice-water bath, and n-butyl triflate (13.2 mL, 81.0 mmol, 10.0
equiv) was added gradually (over 10 min). The ice bath was
removed, and the mixture was stirred at rt for 2 h to give two clear
layers with a yellow fluorescent organic layer. Saturated aqueous
NaHCO3 was added until the mixture became basic. The organic
layer was separated, and the aqueous layer was extracted two times
with CH2Cl2. The combined organic layers were dried with anhyd
MgSO4 and evaporated to dryness. The crude product was dissolved
in a minimal amount of hot chloroform, loaded on silica gel and
purified using silica gel chromatography on four Biotage columns
(40+M cartridge) eluted with CH2Cl2/hexane (5:95 v/v). Evapora-
tion of the eluting solvent afforded 10 as bright yellow crystals
(3.43 g, 88% yield). Mp: 125-127 °C. 1H NMR (400 MHz, CDCl3):
δ (ppm) 1.06 (6H, t, J ) 7.2 Hz), 1.62-1.72 (4H, m), 1.94-2.02
(4H, m), 4.09 (4H, t, J ) 6.4 Hz), 7.49 (2H, dd, J ) 2 and 9.2
Hz), 8.09 (2H, d, J ) 9.2 Hz) and 8.36 (2H, d, J ) 2 Hz). 13C
NMR (100 MHz, CDCl3): δ (ppm) 14.0, 19.4, 32.6, 76.4, 120.3,
124.1, 124.7, 124.8, 126.1, 129.3, and 147.0. HRMS (ESI): calcd
for C22H24Br2O2 [M]+ 478.0143, found 478.0195.
2-Bromo-6-formyl-9,10-di-n-butoxyanthracene, 11. Compound
10 (0.12 g, 0.25 mmol) was dissolved in anhyd THF (8 mL) and
cooled to -72 °C (dry ice-ethanol bath). n-BuLi (160 µL, 0.27
mmol, 1.1 equiv) was added dropwise (over 5 min), and the
homogeneous brown reaction mixture was stirred for an additional
10 min at the same temperature. DMF (0.10 mL, 0.75 mmol, 1.5
equiv) was added, which led to the change of the brown color to
yellow. The reaction mixture was stirred for 30 min at -72 °C
and for 30 min at rt. A saturated aqueous solution of NH4Cl was
added; this was followed by addition of water and CH2Cl2. The
organic layer was separated, dried over anhyd MgSO4, and
evaporated to dryness. The crude product was applied to a silica
gel column and eluted with CH2Cl2/hexane (0:100-35:65). Evapo-
ration of the eluting solvent afforded 11 as a bright intense yellow
powder (65 mg, 70% yield). Mp: 116-118 °C. 1H NMR (400 MHz,
CDCl3): δ (ppm) 1.06 (3H, t, J ) 7.2 Hz), 1.07 (3H, t, J ) 7.2
Hz), 1.63-1.72 (4H, m), 1.95-2.05 (4H, m), 4.09 (2H, t, J ) 6.4
Hz), 4.15 (2H, t, J ) 6.4 Hz), 7.52 (1H, dd, J ) 2 and 9.2 Hz),
7.86 (1H, dd, J ) 1.6 and 9.2 Hz), 8.11 (1H, d, J ) 9.2 Hz), 8.24
(1H, d, J ) 9.2 Hz), 8.39 (1H, d, J ) 2 Hz), 8.67 (1H, d, J ) 1.6
Hz) and 10.15 (1H, s). 13C NMR (100 MHz, CDCl3): δ (ppm) 14.2,
19.6, 19.6, 32.8, 32.9, 76.4, 77.4, 121.5, 122.0, 124.3, 124.3, 124.5,
125.16, 125.18, 127.4, 128.5, 129.6, 132.1, 134.0, 147.0, 150.4,
and 192.1. HRMS (EI): calcd for C23H25BrO3 [M]+ 428.0987, found
428.0984.
the mixture was removed by filtration over a layer of Celite and
washed with hot EtOAc. The organic layer was separated, dried
with anhyd MgSO4, and evaporated. The residue was coevaporated
with toluene to afford 13 as a pale yellow powder (54 mg, 82%
yield). Mp: 276-278 °C dec. 1H NMR (400 MHz, CDCl3): δ (ppm)
7.95 (1H, dd, J ) 2 and 8 Hz), 8.21 (1H, d, J ) 8 Hz), 8.28 (1H,
dd, J ) 1.6 and 8 Hz), 8.46 (1H, d, J ) 2 Hz), 8.45 (1H, d, J )
8 Hz), 8.77 (1H, d, J ) 1.6 Hz) and 10.22 (1H, s). 13C NMR (100
MHz, DMSO-d6): δ (ppm) 127.50, 127.53, 128.8, 129.0, 128.6,
131.8, 133.4, 133.5, 136.1, 137.1, 139.8, 180.7, 181.0, and 192.0.
HRMS (EI): calcd for C15H7BrO3 [M]+ 313.9579, found 313.9603.
5′-O-tert-Butyldiphenylsilyl-8-[(6-formylanthraquinone-2-yl)-
ethynyl]-2′-deoxyadenosine, 1. To 13 (43 mg, 0.11 mmol) were
added Pd(PPh3)4 (8.0 mg, 0.01 mmol, 0.05 equiv), CuI (3 mg, 10
µmol, 0.1 equiv), and TEA (0.04 mL, 0.27 mmol, 2.0 equiv). A
solution of 7 (67 mg, 0.13 mmol, 0.95 equiv) in anhyd DMF (5
mL) was immediately added to the reaction mixture. The mixture
was stirred under a nitrogen atmosphere in the dark at 65 °C in an
oil bath for 3 h. DMF was removed under reduced pressure, and
the brown residue was purified on a silica gel column eluted with
MeOH/CH2Cl2 (0:100-3:97). Evaporation of the eluting solvent
afforded 1 as a bright yellow glass (55 mg, 57% yield). ε355 (THF):
11730 ( 100 L mol-1 cm-1. ε355 (acetonitrile): 7133 ( 100 L mol-1
1
cm-1. ε355 (MeOH): 6907 ( 100 L mol-1 cm-1. H NMR (400
MHz, CDCl3): δ (ppm) 1.01 (9H, s), 1.90 (1H, br s), 2.43-2.49
(1H, m), 3.47-3.54 (1H, m), 3.90 (1H, dd, J ) 5.2 and 10.4 Hz),
4.03 (1H, dd, J ) 8 and 10.4 Hz), 4.12-4.17 [1H, m), 4.99-5.02
(1H, m), 6.33 (2H, br s), 6.57 (1H, t, J ) 6.8 Hz), 7.27-7.39 (6H,
m), 7.59-7.64 (4H, m), 7.81 (1H, d, J ) 7.2 Hz), 8.03 (1H, s),
8.13 (1H, d, J ) 7.2 Hz), 8.17 (1H, d, J ) 8 Hz), 8.32 (1H, d, J
) 8 Hz), 8.46 (1H, s), 8.71 (1H, s) and 10.12 (1H, s). 13C NMR
(100 MHz, CDCl3): δ (ppm) 19.4, 27.1, 37.1, 64.5, 73.3, 82.0, 85.5,
87.4, 94.1, 119.9, 126.2, 127.4, 128.0, 128.2, 130.1, 131.2, 132.7,
133.0, 133.4, 133.4, 133.7, 134.0, 135.7, 136.2, 136.4, 139.8, 148.9,
155.4, 181.0, 181.6, and 190.6. HRMS (ESI): calcd for
C43H38N5O6Si [M + H]+ 748.2591, found 748.2627.
4′-Bromo-2,4,5-trimethylbenzophenone, 16. A mixture of
4-bromobenzoyl chloride (6.09 g, 27.7 mmol) and AlCl3 (3.88 g,
29.1 mmol, 1.05 equiv) were dried in vacuo for 1 h. The flask was
filled with nitrogen gas and placed in a -20 °C bath (ethanol-ice-
salt). Anhydrous CH2Cl2 (30 mL) was added, and the mixture was
stirred at the same temperature for 10 min. To the resulting
homogeneous mixture was added 1,2,4-trimethylbenzene (3.78 mL,
27.8 mmol, 1.00 equiv) dropwise (over a period of 30 min) via a
syringe. The ice bath was removed, and the obtained light brown
mixture was stirred overnight. The reaction mixture was then poured
into a mixture of ice (20 g) and concd HCl (9 mL), which led to
discharge of the dark color. CH2Cl2 and water were added, and the
mixture was transferred to a separatory funnel and shaken. The
organic layer was separated, washed with saturated aqueous
NaHCO3, dried with anhyd MgSO4, and evaporated to dryness. The
white foam obtained was purified by crystallization from EtOAc/
MeOH to afford 16 as white needle-like crystals (6.79 g, 81% yield).
1
Mp: 69-71 °C. H NMR (400 MHz, CDCl3): δ (ppm) 2.21 (3H,
s), 2.25 (3H, s), 2.27 (3H, s), 7.04 (1H, s), 7.05 (1H, s), 7.55-7.58
(2H, m) and 7.62-7.65 (2H, m). 13C NMR (100 MHz, CDCl3): δ
(ppm) 19.4, 19.8, 20.0, 128.2, 130.4, 131.8, 131.9, 132.8, 133.7,
134.8, 135.7, 137.3, 139.9, and 197.8. HRMS (ESI): calcd for
C16H16BrO [M + H]+ 303.0385, found 303.0374; for C16H15BrNaO
[M + Na]+ 325.0204, found 325.0157.
2-Bromo-6-formylanthraquinone, 13. Solid 11 (74 mg, 0.18
mmol) and AgO (34 mg, 0.27 mmol, 1.5 equiv) were combined
and dried in vacuo for 30 min. Anhydrous dioxane (4 mL) was
added under nitrogen gas, and the mixture was stirred until 11 was
completely soluble (AgO was in suspension). When viewed under
long wavelength UV light, the solution was fluorescent. HNO3 (6
N, 0.36 mL) was added via a syringe and the mixture was stirred
at rt for 5 min, by which time all AgO was soluble and the mixture
lost its fluorescence. A saturated aqueous solution of NaHCO3 (4
mL) was added and the mixture was stirred for 1 min. Hot EtOAc
(120 mL) and water (50 mL) were added, the insoluble material in
4′-Bromobenzophenone-2,4,5-tricarboxylic Acid, 17. To a two-
neck flask containing 16 (6.619 g, 21.83 mmol) was added 20%
HNO3 (44 mL), and then a condenser was attached. The contents
of the flask were heated to 120 °C using oil bath, and the mixture
was refluxed for 48 h, by which time a pale yellow semisolid was
formed on the bottom. The mixture was cooled to 0 °C for 1 h,
and the HNO3 solution was removed with a pipet. The remaining
semisolid was triturated with water (3 × 30 mL) that was also
removed with a pipet. Addition of 10% NaOH (50 mL) followed
4718 J. Org. Chem. Vol. 74, No. 13, 2009

Probes for Hole-Transfer Studies in DNA
by H2O (75 mL) dissolved the semisolid. The resulting dark colored
solution was then heated to reflux (110 °C oil bath), and solid
KMnO4 (13.8 g, 87.5 mmol, 4.00 equiv) was added in small portions
over 1 h (caution: frothing occurs with rapid addition). The reaction
mixture was refluxed for additional 3 h, and then the resulting brown
solid was removed by filtration while still hot. The collected solid
was mixed with water (50 mL) and refluxed overnight, then
removed once again by filtration and washed with hot water. The
filtrates were combined, treated with solid NaHCO3 (5 g), and
reduced in volume to 100 mL by evaporation under reduced pres-
sure. The resulting solution was heated (∼ 70 °C) and filtered once
more over a layer of Celite while still hot and then treated
immediately with conc. HCl until bubbling stopped and pH was
about 2 (pH paper). The resulting white precipitate was separated
by filtration using a Bu¨chner funnel, washed with water, air-dried,
and finally further dried in vacuo to afford 17 as a white solid (6.314
g, 74% yield). Mp: 224-227 °C. 1H NMR (400 MHz, DMSO-d6):
δ (ppm) 7.58 (2H, d, J ) 8.4 Hz), 7.70 (1H, s), 7.73 (2H, d, J )
8.4 Hz), and 8.27 (1H, s). 13C NMR (100 MHz, DMSO-d6): δ (ppm)
127.3, 127.7, 130.4, 130.9, 131.3, 132.0, 133.0, 135.4, 137.2, 143.2,
165.5, 167.0, 167.7, and 194.3. HRMS (ESI): calcd for C16H8BrO7
[M - H]- 390.9453, found 390.9468.
Dimethyl 6-Bromoanthraquinone-2,3-dicarboxylate, 19. To
dry 17 (0.800 g, 2.04 mmol) was added concd H2SO4 (3.5 mL)
under a nitrogen atmosphere. The resulting homogeneous brown
reaction mixture was stirred at 125 °C for 3 h, at which time a
precipitate formed in the mixture. After being cooled to rt, the
mixture was poured over ice (10 g), and the resulting beige
suspension was transferred to two 20-mL centrifuge tubes. Ad-
ditional water (3.5 mL) was used to transfer all of the crude material.
After centrifugation, the supernatant was removed with a pipette,
and the remaining paste was lyophilized to give 1882 as an oily
brown suspension. This suspension was transferred (with methanol)
to a 100-mL recovery flask. The methanol was removed under
reduced pressure and vacuum was applied overnight. The flask
containing crude 18 was flushed with nitrogen gas and a condenser
was attached.
NMR matched those in the literature.82 HRMS (ESI): calcd for
C18H12BrO6 [M + H]+ 402.9817, found 402.9802.
5′-O-tert-Butyldiphenylsilyl-8-[2-(2,3-dicarboxyanthraquinone-
6-yl)ethyl]-2′-deoxyadenosine Dimethyl Ester, 4. Compound 3
(54 mg, 0.06 mmol) was dissolved in EtOH (20 mL) by slight
heating while stirring. The resulting solution was transferred to a
hydrogenation vessel containing 10% Pd/C (25 mg) that had been
activated by stirring under H2 gas (45 psi) in EtOH (10 mL) for 30
min at rt. The vessel was next charged with H2 gas and then
degassed using an aspirator in a cycle that was repeated five to six
times. The vessel was finally charged with H2 gas at 40 psi and
stirred at rt for 24 h, by which time TLC (MeOH/CH2Cl2, 7:93
v/v) showed complete conversion of an initial spot to a more polar
spot. The Pd/C catalyst was then removed by filtration over Celite,
and the adsorbed nucleoside residue was extracted from the catalyst
by washing with boiling 10% MeOH in CHCl3. The crude product
was applied to a silica gel column and eluted with MeOH/CH2Cl2
(0:100-3:97). Evaporation of the eluting solvent afforded 4 as a
pale yellow glass (43 mg, 80% yield). ε355 (THF): 2553 ( 100 L
mol-1 cm-1. ε355 (acetonitrile): 2907 ( 100 L mol-1 cm-1. ε355
(MeOH): 2598 ( 100 L mol-1 cm-1. 1H NMR (400 MHz, CDCl3):
δ (ppm) 0.97 (9H, s), 2.30 (1H, ddd, J ) 2.4, 6.8, and 13.2 Hz),
3.23-3.38 (4H, m), 3.60-3.67 (1H, m), 3.80 (1H, dd, J ) 5.2 and
10.4 Hz), 3.92-3.97 (1H, m), 3.98 (6H, s), 4.08-4.12 (1H, m),
4.92-4.95 (1H, m), 5.91 (2H, br s), 6.26 (1H, t, J ) 6.8 Hz),
7.24-7.38 (6H, m), 7.55-7.65 (5H, m), 8.06 (1H, s), 8.13 (1H, d,
J ) 8 Hz), 8.19 (1H, d, J ) 1.2 Hz), 8.54 (1H, s) and 8.56 (1H, s).
13C NMR (100 MHz, CDCl3): δ (ppm) 19.9, 27.0, 29.2, 33.4, 37.0,
53.4, 64.1, 72.6, 84.4, 87.0, 118.9, 127.6, 127.8, 127.8, 128.1, 128.2,
129.9, 131.7, 133.3, 133.3, 133.4, 134.8, 133.9, 135.1, 135.6, 135.6,
136.5, 136.6, 148.4, 150.9, 152.0, 154.8, 166.7, 166.5, 181.3, and
181.7. HRMS (ESI): calcd for C46H46N5O9Si [M + H]+ 840.3065,
found 840.3062.
Acknowledgment. We thank Daniel Rabinowitz for the cyclic
voltammetry measurements. We thank Dr. Siming Wang of
Georgia State University and David Bostwick of Georgia
Institute of Technology for MS analyses. We also thank
the Chemistry Department of Georgia State University and the
donors of the Petroleum Research Fund, administered by the
ACS, for support of this research (T.L.N.).
The flask containing the crude mixture was flushed with nitrogen
gas, and a condenser was attached. Anhydrous methanol (25 mL)
was added under nitrogen gas, and the yellow suspension obtained
was refluxed (80 °C) for 24 h until TLC (CH2Cl2) showed no further
progress in the reaction. The mixture was cooled to rt and treated
with a saturated aqueous solution of NaHCO3 until the reaction
mixture became basic (pH paper); water (20 mL) was then added.
The precipitate in the reaction mixture was separated by filtration,
washed with water followed by cold methanol, and finally air-dried
to afford 19 as a fine yellow powder (487 mg, 60% yield from
Supporting Information Available: Experimental proce-
dures for the preparation of 2, 3, 9, 12, 14, and 15; copies of
1H, 13C, and 19F NMR spectra for compounds prepared by the
methods described; electrochemical measurement conditions and
cyclic voltammetry plots; and UV-vis spectra of conjugates 3,
4, AQYdA and AQEdA. This material is available free of charge
via the Internet at http://pubs.acs.org.
17). Mp: 174-175 °C (lit.82 mp 178-179 °C). The H and 13C
1
(82) Qiao, W.; Zheng, J.; Wang, Y.; Zheng, Y.; Song, N.; Wan, X.; Wang,
Z. Y. Org. Lett. 2008, 10, 641–644.
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