Scheme 2 Reagents and conditions: i. NaH, DMF:THF (2+1), 0 °C, 60%; ii. NH4OH, MeOH, 95%; iii. HCO2H, MeNO2, rt, 84% (12), 82% (14); iv. TBAF,
THF, rt, 91% (13), 85% (14); v. HCO2H, H2O (8:2), rt, 75%.
Table 1 Association constants and thermodynamic parameters for the
dimers 11–13 in CDCl3
5.75 (d, J = 1.0, H–C(1A/II)); 5.36 (s, H–C(5/II)); 5.34 (dd, J = 6.3, 3.8, H–
C(3A/I)); 5.27 (dd, J = 1.0, 6.3, H–C(2A/II)); 4.87 (dd, J = 6.3, 4.5, H–C(3A/
II)); 4.55, 4.41 (AB, J = 11.8, 2 H–C(10/I)); 4.44, 4.03 (AB, J = 13.3, 2
H–C(7/II)); 4.31 (ddd, J = 3.8, 5.3, 4.9, H–C(4A/I)); 4.15 (ddd, J = 4.4, 5.4,
7.1, H–C(4A/II)); 3.85 (dd, J = 10.5, 5.4, H–C(5Aa/II)); 3.83 (dd, J = 10.5,
7.1, H–C(5Ab/II)); 3.79 (s, MeO); 3.65 (dd, J = 10.5, 5.3, H–C(5Aa/I)); 3.63
(dd, J = 10.5, 4.9, H–C(5Ab/I)); 1.55, 1.55, 1.42, 1.41 (4s, Me2C); 1.01–0.96
(m, (Me2CH)3–Si). 13C-NMR (75 MHz, CDCl3): 164.07 (s, C(2/II)); 158.50
(s, C(8/I)); 155.61 (s, C(6/I)); 151.91 (d, C(2/I)); 150.74 (s, C(6/II)); 150.24
(s,C(4/II)); 150.10 (s, C(4/I)); 148.81 (s, arom. C); 144.00 (s, arom. C);
135.08 (s, arom. C); 130.02 (d, arom. C); 128.10 (d, arom. CH); 127.81 (d,
arom. CH); 126.90 (d, arom. CH); 118.45 (s, C(5/I));113.59 (s, C(Me)2/I);
113.26 (s, C(Me)2/II); 113.17 (d, arom. CH);103.71 (d, C(5/II)); 91.39 (d,
C(1A/II)); 90.00 (d, C(1A/I)); 89.65 (d, C(4A/II)); 87.50 (s, CAr3);86.74 (d,
C(4A/I)); 84.37 (d, C(2A/II)); 83.57 (d, C(2A/I)); 82.26 (d, C(3A/II)); 81.67 (d,
C(3A/I)); 69.80 (t, C(5A/I)); 68.08 (t, C(7/II)); 64.50 (t, C(5A/II)); 59.27 (t,
C(10/I); 55.23 (q, 2 3 MeO); 27.36, 27.36, 25.76, 25.76 (4q, Me2C); 17.95
(q, Me2CH)3Si); 11.99 (d, Me2CH)3Si). HR-MALDI-MS: 303 (100%,
[DMTr]+); 1114.492 (23%, [M + Na]+; calc. 1114.4936). IR (CHCl3):
3488w, 3185w, 2993m, 2943m, 2866m, 2840w, 1712s, 1636m, 1608m,
1509s, 1446m, 1383m, 1157m, 1068s, 1036m, 882m, 831m.
Ka (M21 a
)
2DH° (kcal mol21
)
2DS° (e.u.)b
11
12
13
966
277
3222
15.8
21.8
24.4
40.4
63.7
64.8
a Determined at 22 °C, uncertainty in Ka estimated at 15%. b e.u. = entropy
units (1 e.u. = 1 cal per (mol.K)).
§
NMR was performed at 295 K on a Varian Gemini300 spectrometer
(300 MHz) in CDCl3 passed through aluminium oxide immediately prior to
use. Experiments started at the highest concentration, with stepwise
replacement of 0.2 ml of the 0.7 ml solution with 0.2 ml pure CDCl3. The
data were analysed graphically and by nonlinear least-squares fitting.8
Thermodynamic parameters were determined by van’t Hoff analysis. The
uridyl dH–N(3) was monitored between 50 and 230 °C at a fixed
concentration (between 20–80% of saturation). Linear fits of data collected
below 0 °C were poor.
Fig. 3 Concentration dependence of d(H–N(3)) for dimers 11, 12 and 13 in
CDCl3 at 295 K.
detritylated 12 compares favourably with that determined for
3A,5A-di-O-acetyl-2A-deoxyuridine with a 2A-deoxyadenosine
derivative (70 M21).9 The high Ka value for 13, and the inability
to dissociate 14 appreciably in CDCl3 correlate with a
downfield shift of H–O(5A) as compared to 1 (Dd ≈ 1.0 ppm),
and are rationalised by the formation of a C(5A)O–H…ONC(2)
intramolecular hydrogen bond.
Watson–Crick type base pairing is suggested by a cross-peak
between the hydrogen bonded imino H–N(3) and the adenine
H–C(2) in a 2D-NOESY experiment on associated dimer 11.9
These results support the contention that a structural
differentiation of nucleobases and backbone is not required for
pairing. We are now investigating the details of base pairing,
stacking, and hydrogen bonding.
1 S. Eppacher, N. Solladié, B. Bernet and A. Vasella, Helv. Chim. Acta,
2000, 83, 1311.
2 H. Gunji and A. Vasella, Helv. Chim. Acta, 2000, 83, 1331; H. Gunji and
A. Vasella, Helv. Chim. Acta, 2000, 83, 2975; H. Gunji and A. Vasella,
Helv. Chim. Acta, 2000, 83, 3229.
3 P. K. Bhardwaj and A. Vasella, Helv. Chim. Acta, 2002, 85, 699.
4 W. Saenger, Principles of Nucleic Acid Structure, Springer Verlag,
Berlin, 1984, p. 21; T. Wada, N. Minamimoto, Y. Inaki and Y. Inoue, J.
Am. Chem. Soc., 2000, 122, 6900; S. M. Gryaznov, D. H. Lloyd, J. K.
Chen, R. G. Schultz, L. A. DeDionisio, L. Ratmeyer and W. D. Wilson,
Proc. Natl. Acad. Sci. USA, 1995, 92, 5798; O. Almarsson and T. C.
Bruice, Proc. Natl. Acad. Sci. USA, 1993, 90, 5542.
5 H. Hayakawa, K. Haraguchi, H. Tanaka and T. Miyasaka, Chem. Pharm.
Bull., 1987, 35, 72.
6 W. Czechtizky and A. Vasella, Helv. Chim. Acta, 2001, 84, 594; W.
Czechtizky and A. Vasella, Helv. Chim. Acta, 2001, 84, 1000; W.
Czechtizky, X. Daura, A. Vasella and W. van Gunsteren, Helv. Chim.
Acta, 2001, 84, 2132; W. Czechtizky, Dissertation ETH No. 14239, ETH-
Zürich, 2001.
We thank The Royal Society (A. J. M.), the Swiss National
Science Foundation and F. Hoffmann-La-Roche AG, Basel for
generous support.
7 D. Gani and A. W. Johnson, J. Chem. Soc., Perkin Trans. 1, 1982, 1197;
S. Nieble, M. R. Sanderson, A. Subbiah, J. B. Chattopadhyaya and C. B.
Reese, Biochim. Biophys. Acta, 1979, 565, 379; L. Dudycz, R. Stolarski,
R. Pless and D. Shugar, Z. Naturforsch., 1979, 34, 359.
8 K. A. Conners, Binding Constants, John Wiley & Sons, New York, 1987;
W. C. Luo and J. S. Chen, Z. Phys. Chem., 2001, 215, 447; Associate v.
1.6, B. R. Peterson, Ph.D Thesis, University of California at Los Angeles,
1994.
Notes and references
† For the sake of simplicity, we have designated these analogues as
‘oligonucleotide analogues with a nucleobase-including backbone’, while,
strictly speaking, these systems do not possess a ‘backbone’.
‡ All new compounds showed satisfactory NMR, IR, and MS data. 11: I =
adenosyl unit; II = uridyl unit. H-NMR (500 MHz, CDCl3): 13.09 (br s,
H–N(3/II)); 8.37 (s, H–C(2/I)); 8.37–7.49 (m, 2 arom. H); 7.47–7.38 (m, 4
arom. H); 7.32–7.21 (m, 3 arom. H); 6.90 (br s, 2 H–N(6/I)); 6.86–6.83 (m,
4 arom. H); 6.22 (d, J = 1.3, H–C(1A/I)); 5.88 (dd, J = 1.3, 6.3, H–C(2A/I));
1
9 A. Dunger, H-H. Limbach and K. Weisz, J. Am. Chem. Soc., 2000, 122,
10109; G. M. Nagel and S. Hanlon, Biochemistry, 1972, 11, 823.
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