Highly fluorescent donor-acceptor purines

Article abstract of DOI:10.1039/b618171f

Donor-acceptor purines have been prepared that show near unity fluorescence quantum yields in organic solution, a step toward using simple biorelevant heterocycles in optoelectronic and photonic applications. The Royal Society of Chemistry 2007.

Full text of DOI:10.1039/b618171f

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www.rsc.org/materials | Journal of Materials Chemistry
Highly fluorescent donor–acceptor purines{{
Roslyn S. Butler, Andrea K. Myers, Prabhu Bellarmine, Khalil A. Abboud and Ronald K. Castellano*
Received 13th December 2006, Accepted 12th February 2007
First published as an Advance Article on the web 26th February 2007
DOI: 10.1039/b618171f
Donor–acceptor purines have been prepared that show near
Table 1 Synthesis of donor–acceptor purines
unity fluorescence quantum yields in organic solution, a step
toward using simple biorelevant heterocycles in optoelectronic
and photonic applications.
Modified nucleobases that display enhanced optical properties are
highly sought as probes of biological structure, dynamics, and
interactions.1–3 Among these, 2-aminopurine (2AP) derivatives4
are widely used due to their structural simplicity and synthetic
accessibility, despite the complex mechanistic photochemistry of
the parent 2AP chromophore.5 The development of nucleobases
(and related biorelevant heterocycles) as highly fluorescent building
blocks suitable for materials applications has received compara-
tively little attention. This is surprising since the built-in molecular
Yield (%)a
recognition functionality of the molecules could, in principle, be
Derivative
R1
R2
4
1
2
used to uniquely control molecular/supramolecular structure and
modulate optoelectronic properties.6 Toward this goal, reported
here are the syntheses of donor–acceptor (D–A) chromophores7
based on 2AP and 2-dimethylaminopurine (2DMAP), featuring
electron-accepting substituents in the C(8) position of the purine
heterocycle (see Table 1 for numbering). Investigation of their
optical properties, initially in organic solution, reveals fluorescence
quantum yields approaching unity (the highest values reported for
simple purines). Given that the ring substitutions only modestly
alter the purine core, the design also holds promise for the
construction of new bioprobes8 and sensors.9
a
b
c
d
a
NH2
NH2
N(CH3)2
NH2
b
H
24
78
68
71
60
86
75
82
80
91
77
42
N(CH3)2
NH2
OBnb
Isolated yields shown. Bn = benzyl
substrates. The nitriles are quintessential donor–acceptor chromo-
phores, although their photophysical properties are studied for the
first time here. Final treatment of the C(8) carbonitriles with
methanolic ammonia and then acid17 provides the corresponding
methyl esters 2a–d.
Synthesis of the D–A purines is shown in Table 1. Family 1
bears a cyano acceptor at C(8); family 2, a methyl ester. All
compounds feature a benzyl substituent in the N(9) position of the
heterocycle to impart moderate to good solubility in common
organic solvents and amino donor substituents, either NH2 or
N(CH3)2, on C(2). The same donors are varied in the C(6)
position, including also the O-benzyl group that can later be
deprotected to access guanine derivatives. Parent 8-H purines 3a–d
are available in excellent yields (in one step for 3a,10 3b, and 3d,11
and three steps for 3c) from readily prepared 2-amino-9-benzyl-6-
chloropurine.12 Bromination at C(8) is performed with Br2 and
provides purines 4a–d13 that bear a chemical handle for further
functionalization at this position.14,15 Conversion of the bromides
to the nitriles 1a–d is accomplished using a palladium(0)-mediated
cyanation,16 exhaustively optimized for these strongly coordinating
The absorption and emission data for the D–A purines (in
CH2Cl2) are summarized in Table 2. Optical densities were first
found to vary linearly with concentration in the range used for the
measurements (5–60 mM), important given potential aggregation
of the molecules by hydrogen bonding,18 and more significantly,
Table 2 Representative photophysical data for donor–acceptor
purines 1 and 2a
lmax,
abs/nm
log e/
M21 cm21
lmax,
em/nmb
c
WF
Purine
tF/ns
1a
1b
1c
1d
2a
2b
2c
2d
a
326
334
336
311
328
322
338
315
3.2
4.2
4.1
4.3
4.1
4.2
4.1
4.3
371
375
387
355
379
393
409
371
0.5 ¡ 0.2
1.6 ¡ 0.3
3.2 ¡ 0.3
3.1 ¡ 0.2
1.8 ¡ 0.2
3.1 ¡ 0.3
3.3 ¡ 0.1
2.5 ¡ 0.1
0.19
0.30
.0.95
0.81
0.41
.0.95
.0.95
.0.95
b
Department of Chemistry, P.O. Box 117200, University of Florida,
Gainesville, FL, 32611-7200, USA. E-mail: castellano@chem.ufl.edu;
Fax: +01 352 846 0296; Tel: +01 352 392 2752
{ This paper is part of a Journal of Materials Chemistry issue highlighting
the work of emerging investigators in materials chemistry.
{ Electronic supplementary information (ESI) available: synthetic details
and characterization data for all new compounds (including copies of 1H
and 13C NMR spectra), additional photophysical data, and sample
calculations. See DOI: 10.1039/b618171f
All measurements performed in CH2Cl2 at room temperature. All
experiments were performed using samples with optical densities
c
¡ 0.1 at the excitation wavelength (lex = 320 nm). Fluorescence
quantum yields are the average of five independent measurements
relative to the quantum yield of quinine sulfate in 0.05 M H2SO4
(WF = 0.546). Data using other standards are provided in the ESI.
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increase for 2a accompanies its methyl ester substitution at C(8).25
When compared to a range of recently reported fluorescent
nucleobase derivatives (or surrogates) that have been characterized
in organic solution,9,26–28 the D–A purines described here have
among the highest extinction coefficient maxima and quantum
yields.
The fluorescence lifetime data follow the trends in quantum
yield, where the best emitters have tF values of y3 ns. All decays
could be fit cleanly to a single exponential, and are consistent with
fluorescence emission from the low-lying S1 state. Finally,
preliminary photophysical studies in solvents of different polarity
(not shown) reveal the expected trends.29 The absorption spectra
appear weakly solvent dependent, while the emission maxima
show significant bathochromic shifts upon increases in polarity
(e.g. em lmax for 2c: 436 nm (CH3OH); 409 nm (CH2Cl2)). Also
pointing to the significant polar (charge-transfer) character of the
emitting excited state are increased Stokes shifts upon moving to
more polar solvents (e.g. Dlem for 2c: 91 nm (CH3OH); 71 nm
(CH2Cl2)).30 Of note, 2 appears to retain its high quantum yields in
polar, protic solvents.
Fig. 1 Normalized emission spectra (based on quantum yield) for 2a–d
in CH2Cl2 (concentration = 5 6 1026 M; lex = 320 nm).
dipolar p-stacking (vide infra).19,20 The lowest energy absorption
band, corresponding to the 1(pp* La) transition by analogy to
parent 2AP,5 is red-shifted (by y20 nm) upon introduction of the
C(8) acceptors (versus structurally related but unsubstituted (8-H)
2AP derivatives studied in organic solution4,21–23). Of particular
note, the extinction coefficient maxima (log e) are uniformly high24
and the absorption maxima are comparable between the nitriles 1
and esters 2.
Studies of isomeric nitriles 1b and 1c in the solid state by X-ray
crystallography§ identify the expected interactions between the
molecules (Fig. 2). Strong dipolar interactions are reflected by the
near-perfect antiparallel alignment of neighboring purines and
˚
˚
short p-stacking distances of 3.32(1) A (for 1b) and 3.38(1) A (for
1c; measured as the distance between the least-squares planes
defined by the purine nuclei). Purines 1b further show donor–
acceptor hydrogen bonding interactions via their N(3) face
31
(N(3) N(119) = 3.11(1) A). Derivative 1c shows similar
Changes in the emission spectra (Fig. 1) and corresponding
quantum yields (Table 2) are more significant between the two
classes and dramatic when compared to conventional purines. The
unstructured emission bands are red-shifted upon conversion of
the nitrile to the methyl ester (i.e. 1 versus 2), and the introduction
of multiple strong donors to the pyrimidine ring (e.g. 1,2a versus
1,2b). Comparison of 1,2b and 1,2c reveals that introduction of the
strongest donor, N(CH3)2, to C(2) has the most significant effect
on the emission maximum. This result is consistent with the
transition dipole moment lying along the long (longitudinal) axis
of the purine, such that C(2) substituents (that are oriented 30u
from this axis) significantly affect the energy of the emitting state.
Conversely, C(6) substituents, that are transversely oriented with
respect to the purine core, have a smaller effect (although they
significantly alter the non-emitting and higher energy 1(pp*
Lb) transition that occurs at y240–280 nm). The Stokes shifts,
40–70 nm, are largest for the methyl ester derivatives, suggesting a
greater degree of structural reorganization in the excited state for
these compounds.
…
˚
…
H-bonding but from its Hoogsteen edge (N(7) N(109) =
˚
3.00(1) A). Despite these intermolecular interactions, the
Fluorescence quantum yields were determined for the eight
D–A purines using three standards (anthracene in ethanol, 9,10-
diphenylanthracene in cyclohexane, and quinine sulfate in 0.05 M
H2SO4) with excellent agreement (¡5%); only the data obtained
using quinine sulfate are shown. The quantum yields are uniformly
high and near unity for the 2,6-disubstituted methyl esters; these
are unprecedented results for such simple nucleobases. While
donor introduction to C(6) significantly enhances the emission
of the purines, even 1a and 2a bearing a hydrogen in this position
(8-H) outperform the parent 2AP. By comparison, the fluorescence
quantum yields of 8-H 2AP derivatives4,21 and 3,4a–d (data not
shown) in organic solution are generally less than 0.15; a y4-fold
Fig. 2 X-Ray crystal data for structural isomers 1b (a) and 1c (b).
Disorder of the N(CH3)2 substituent of 1b is not shown, and some
hydrogens have been omitted for clarity.
1864 | J. Mater. Chem., 2007, 17, 1863–1865
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5 L. Serrano-Andre´s, M. Mercha´n and A. C. Borin, Proc. Natl. Acad. Sci.
U. S. A., 2006, 103, 8691–8696.
6 F. J. M. Hoeben, P. Jonkheijm, E. W. Meijer and A. Schenning, Chem.
Rev., 2005, 105, 1491–1546.
derivatives maintain fluorescence in the solid state and as thin
(drop-cast) films; measurement of the solid-state fluorescence and
testing of the materials in devices is under way.
7 H. Meier, Angew. Chem., Int. Ed., 2005, 44, 2482–2506.
8 A. A. Mart´ı, S. Jockusch, Z. Li, J. Ju and N. J. Turro, Nucleic Acids
Res., 2006, 34, e50.
9 S. J. Kim and E. T. Kool, J. Am. Chem. Soc., 2006, 128, 6164–6171;
K. M. Sum, C. K. McLaughlin, D. R. Lantero and R. A. Manderville,
J. Am. Chem. Soc., 2007, 129, 1894–1895.
10 F. Liu, B. Dalhus, L.-L. Gundersen and F. Rise, Acta Chem. Scand.,
1999, 53, 269–279.
11 J. A. Linn, E. W. McLean and J. L. Kelley, J. Chem. Soc., Chem.
Commun., 1994, 913–914.
12 A. Holy´, J. Gu¨nter, H. Dvora´kova´, M. Masoj´ıdkova´, G. Andrei,
R. Snoeck, J. Balzarini and E. De Clercq, J. Med. Chem., 1999, 42,
2064–2086.
13 K. Hirota, K. Kazaoka and S. Hironao, Bioorg. Med. Chem., 2003, 11,
2715–2722.
14 A. Kurimoto, T. Ogino, S. Ichii, Y. Isobe, M. Tobe, H. Ogita,
H. Takaku, H. Sajiki, K. Hirota and H. Kawakami, Bioorg. Med.
Chem., 2003, 11, 5501–5508.
15 Attempts to convert 3a–d or 4a–d directly to the acid or ester derivatives
using various lithiation strategies were met with complications.
16 L. L. Gundersen, Acta Chem. Scand., 1996, 50, 58–63.
17 T. Kato, E. Arakawa, S. Ogawa and Y. Suzumura, Chem. Pharm. Bull.,
1986, 34, 3635–3643.
In summary, straightforward modification of the purine core by
introduction of electron accepting groups to C(8) has significantly
improved the optical properties of the heterocycles. The advantage
that biorelevant heterocycles have over conventional chromo-
phores is their built-in molecular recognition functionality that
should provide additional, systematic ways to control super-
structure and solid-state organization.32 Near-term studies will
consider both materials and biosensing applications. For the
former, applications that parallel conventional D–A chromo-
phores (OLEDs, nonlinear optics, multi-photon absorbance,
resonance energy transfer, etc.) will be explored. For the latter,
water-soluble nucleoside derivatives will be prepared and studied
under various environmental conditions. Encouraging is that the
8-position substituents (–CN and –CO2CH3) appear not much
larger than groups known to be tolerated by the DNA duplex,33
where 2-aminopurine derivatives are capable of base pairing with
cytosine and thymine.34–37
We are grateful to the University of Florida and the Donors of
the American Chemical Society Petroleum Research Fund (PRF #
42229-G4) for financial support. RSB is a University of Florida
Alumni Graduate Fellow and AKM has been funded through the
NSF REU program (CHE-0139505). We thank Miss Priya
Vijapura, funded through the UF Student Science Training
Program, for initial spectroscopic studies of 4a–d. KAA thanks
the National Science Foundation and University of Florida for
funding the X-ray crystallography equipment. We especially thank
Profs Kirk Schanze and Linda Bloom and their respective research
groups for critical guidance and instrument access.
18 Y. Kyogoku, R. C. Lord and A. Rich, Proc. Natl. Acad. Sci. U. S. A.,
1967, 57, 250–257.
19 N. N. P. Moonen, R. Gist, C. Boudon, J.-P. Gisselbrecht, P. Seiler,
T. Kawai, A. Kishioka, M. Gross, M. Irie and F. Diederich,
Org. Biomol. Chem., 2003, 1, 2032–2034.
20 F. Wu¨rthner, S. Yao, T. Debaerdemaeker and R. Wortmann, J. Am.
Chem. Soc., 2002, 124, 9431–9447.
21 J. Smagowicz and K. L. Wierzchowski, J. Lumin., 1974, 8, 210–232.
22 N. Balu, M. P. Gamcsik, M. E. Colvin, O. M. Colvin, M. E. Dolan and
S. M. Ludeman, Chem. Res. Toxicol., 2002, 15, 380–387.
23 The nature of the N(9) substituent has limited effect on the optical
properties. See ref. 4.
24 Calculated from absorbance versus concentration plots for five
concentrations. See the ESI{ for details.
25 Unsubstituted (8-H) 2-dimethylaminopurines do show uniformly high
quantum yields in organic solution (0.65–0.75); see ref. 21.
26 L. M. Wilhelmsson, P. Sandin, A. Holme´n, B. Albinsson, P. Lincoln
and B. Norde´n, J. Phys. Chem. B, 2003, 107, 9094–9101.
27 E. Sharon, S. A. Le´vesque, M. N. Munkonda, J. Se´vigny, D. Ecke,
G. Reiser and B. Fischer, ChemBioChem, 2006, 7, 1361–1374.
28 W. Lin, H. Li, X. Ming and F. Seela, Org. Biomol. Chem., 2005, 3,
1714–1718.
Notes and references
¯
§ Crystal data for 1b: C15H15N7 (M = 293.34), triclinic, space group P1,
˚
radiation type = MoKa, l = 0.71073 A, a = 8.5576(6), b = 9.1964(7), c =
˚
10.2811(7) A, a = 79.739(2)u, b = 74.878(2)u, c = 65.164(2)u, V =
3
706.68(9) A , Z = 2, m = 0.090 mm21, Dc = 1.379 g cm23, F(000) = 308,
˚
T = 173(2) K, 3099 independent relections (Rint = 0.0258), final R indices
(208 parameters) [I . 2s(I)] are R1 = 0.0383, wR2 = 0.1027 (using 2624
reflections), GOF = 1.032. Refinement was done using F2. Crystal data for
1c: C15H15N7 (M = 293.34), monoclinic, space group P21/n, radiation
29 P. Suppan and N. Ghoneim, Solvatochromism, Royal Society of
Chemistry, Cambridge, 1997.
30 Preliminary studies do not show dual fluorescence (due to TICT
emission) for any of the dimethylamino-functionalized derivatives in
CH2Cl2. See B. Albinsson, J. Am. Chem. Soc., 1997, 119, 6369–6375.
31 R. K. Castellano, V. Gramlich and F. Diederich, Chem.–Eur. J., 2002, 8,
118–129.
32 A. M. Martin, R. S. Butler, I. Ghiviriga, R. E. Giessert, K. A. Abboud
and R. K. Castellano, Chem. Commun., 2006, 4413–4415.
33 N. B. Gaied, N. Glasser, N. Ramalanjaona, H. Beltz, P. Wolff,
R. Marquet, A. Burger and Y. Me´ly, Nucleic Acids Res., 2005, 33,
1031–1039.
˚
type = MoKa, l = 0.71073 A, a = 10.0863(8), b = 8.6914(7), c =
3
˚
˚
16.9812(14) A, a = c = 90u, b = 98.137(2)u, V = 1473.7(2) A , Z = 4, m =
0.087 mm21, Dc = 1.322 g cm23, F(000) = 616, T = 173(2) K, 3304
independent reflections (Rint = 0.0615), final R indices (207 parameters)
[I . 2s(I)] are R1 = 0.0475, wR2 = 0.1200 (using 2770 reflections), GOF =
1.048. Refinement was done using F2. CCDC reference numbers 630370
(1b) and 630371 (1c). For crystallographic data in CIF or other electronic
format see DOI: 10.1039/b618171f
1 M. J. Rist and J. P. Marino, Curr. Org. Chem., 2002, 6, 775–793.
2 U. Asseline, Curr. Org. Chem., 2006, 10, 491–518.
3 J. N. Wilson and E. T. Kool, Org. Biomol. Chem., 2006, 4, 4265–4274.
4 D. C. Ward, E. Reich and L. Stryer, J. Biol. Chem., 1969, 244,
1228–1237.
34 E. Freese, J. Mol. Biol., 1959, 1, 87–105.
35 B. L. Gaffney, L. A. Marky and R. A. Jones, Tetrahedron, 1984, 40,
3–13.
36 A. Chollet and E. Kawashima, Nucleic Acids Res., 1988, 16, 305–317.
37 S. Gryaznov and R. G. Schultz, Tetrahedron Lett., 1994, 35, 2489–2492.
This journal is ß The Royal Society of Chemistry 2007
J. Mater. Chem., 2007, 17, 1863–1865 | 1865