8
496
T. Gunnlaugsson et al. / Tetrahedron Letters 43 (2002) 8493–8497
3
1
carried out a preliminary P NMR titration in water.
5. (a) Gunnlaugsson, T.; Harte, A. J.; Leonard, J. P.;
Nieuwenhuyzen, M. Chem. Commun. 2002, 2134; (b)
Gunnlaugsson, T. Tetrahedron Lett. 2001, 42, 8901; (c)
Gunnlaugsson, T.; Mac D o´ naill, D. A.; Parker, D. J. Am.
Chem. Soc. 2001, 123, 12866; (d) Gunnlaugsson, T.; Mac
D o´ naill, D. A.; Parker, D. Chem. Commun. 2000, 93.
6. Gunnlaugsson, T.; Davies, R. J. H.; Nieuwenhuyzen, M.;
Stevenson, C. S.; Viguier, R.; Mulready, S. Chem. Com-
mun. 2002, 2136.
7. (a) Molenveld, P.; Engbersen, J. F.; Reinhoudt, D. M.
Chem. Soc. Rev. 2000, 29, 75; (b) Williams, N. H.;
Takasaki, B.; Wall, M.; Chin, J. Acc. Chem. Res. 1999,
32, 485; (c) Perreault, D. M.; Anslyn, E. V. Angew.
Chem., Int. Ed. 1997, 36, 432; (d) Chin, J. Acc. Chem.
Res. 1991, 24, 145.
−
Upon adding diethylphosphate [(CH CH O) PO )]
which lacks the 2% hydroxy group, and should thus be
less susceptible to hydrolysis) to 1La, a gradual shift
was observed for the phosphorus signal upon binding
to 1La. However it took over 13 equiv. for the signal to
achieve saturation. For 1Eu, only 3 equiv. were needed
3
2
2
2
(
31
to achieve saturation in the P signal. Hence the bind-
ing of the phosphate diester to the metal centre is much
weaker for 1La than 1Eu. We propose that similar
binding preferences would be expected for HPNP.
From the above results we can conclude that the com-
plexes are quite efficient in promoting hydrolysis of
HPNP and of mRNA. We deduce that even though the
above complexes may suffer from steric hindrance due
to the peptide walls, they give rise to the formation of
a cavity that is hydrophobic. This, in combination with
the metal bound water molecules, could give rise to
increased rates of hydrolysis of HPNP. We thus con-
clude that the lanthanide complexes of 1 can be used to
mimic the hydrophobic nature of the active site of
ribonucleases. In summary, we have developed new
types of lanthanide ion based complexes that mimic the
hydrophobic cavity of ribonucleases. We found that
when using La(III) the rate of hydrolysis was highly pH
dependent, showing dual pH behaviour, where within
the physiological pH range, the greatest efficiency was
achieved at pH 7.0. We are currently investigating these
features in greater detail.
8. (a) Blask o´ , A.; Bruice, T. C. Acc. Chem. Res. 1999, 32,
475; (b) Komiyama, M.; Sumaoka, J. Curr. Opin. Chem.
Biol. 1998, 2, 751; (c) Hannon, C. L.; Bell, D. A.;
Kelly-Rowley, A. M.; Cabell, L. A.; Anslyn, E. V. J.
Phys. Org. Chem. 1997, 10, 396.
9. Wilcox, D. E. Chem. Rev. 1996, 96, 2435.
10. (a) Chand, D. K.; Bharadwaj, P. K.; Schneider, H.-J.
Tetrahedron 2001, 57, 6727; (b) Roigh, A.; Schneider,
H.-J. Eur. J. Org. Chem. 2001, 205; (c) Liu, S.; Hamilton,
A. D. Tetrahedron Lett. 1997, 38, 1107; (d) Liu, S.; Lou,
Z.; Hamilton, A. D. Angew. Chem., Int. Ed. 1997, 36,
2678; (e) Kirby, A. J.; Marriott, R. E. J. Am. Chem. Soc.
1995, 117, 833; (f) Chapman, W. H., Jr.; Breslow, R. J.
Am. Chem. Soc. 1995, 117, 5462; (g) Barbier, B.; Brack,
A. J. Am. Chem. Soc. 1988, 110, 6880; (h) Baykal, U.;
Akkaya, E. U. Tetrahedron Lett. 1998, 39, 5861.
1
1. (a) H a¨ ner, R. Chimia 2001, 55, 286; (b) Leumann, C. J.
Chimia 2001, 55, 301; (c) Trawick, B. N.; Daniher, A. T.;
Bashkin, J. K. Chem. Rev. 1998, 98, 939.
Acknowledgements
1
2. Aime, S.; Barge, A.; Bruce, J. I.; Botta, M.; Howard, J.
A. K.; Moloney, J. M.; Parker, D.; de Sousa, A. S.;
Woods, M. J. Am. Chem. Soc. 1999, 121, 5762.
3. Caravan, P.; Ellison, J. J.; McMurry, T. J.; Lauffer, R. B.
Chem. Rev. 1999, 99, 2293.
We thank Kinerton Ltd., Enterprise Ireland (Basic
Research Grant), Dublin Corporation (postgraduate
scholarship to S.M.), and TCD for financial support
and Drs. Hazel M. Moncrieff and Julie Tierney for
their helpful discussion. We especially thank Professor
R. Jeremy H. Davies and Clarke S. Stevenson, Depart-
ment of Biology and Biochemistry, Queen’s University
of Belfast for their help and support.
1
1
4. Compound 1: calcd for C H N O : C, 51.60; H, 7.58;
32
56
8
12
N, 15.04. Found: C, 51.52; H, 7.28; N, 14.74. Expected
+
for C H N O : 745.4096 (MH ). Found: 745.4058.
32
56
8
12
Yield: 0.456 g (49%); lH (CDCl , 400 MHz): 7.9 (1H, d,
3
J=7.0 Hz, N-H), 4.6 (1H, m, J=7.0 and 7.5 Hz,
CHCH CO CH ), 3.7 (3H, s, CO CH ), 3.2 (2H, dd,
3
2
3
2
3
References
J=14 and 16 Hz, CH CO-), 2.88 (4H, dd, J=10 Hz,
2
cyc-CH s), 1.4 (3H, d, J=7.0 Hz, CHCH CO CH ); l
2
3
2
3
C
1
. (a) Kimura, E. Acc. Chem. Res. 2001, 34, 171; (b) Kamin-
skaia, N. V.; Spingler, B.; Lippard, S. J. J. Am. Chem.
Soc. 2001, 123, 6555; (c) Kaminskaia, N. V.; He, C.;
Lippard, S. J. Inorg. Chem. 2000, 93, 3365; (d)
Murakami, Y.; Kikuchi, J.-I.; Hisaeda, Y.; Hayashida, O.
Chem. Rev. 1996, 96, 721.
(CDCl , 100 MHz): 173, 170, 59, 52.5, 51.9, 47, 17, 14;
3
+
+
−1
m/z: 745 (M ), 768 (MNa ); IR w
(cm ): 3384, 3048,
max
2954, 2825, 1745, 1667, 1539, 1455, 1291, 1212, 1163,
1102, 1055, 1012, 951, 898, 850, 757, 605, 502. Com-
+
pound 1La: expected: 883.3081 (M ). Found: 883.3099.
Yield: 53%; mp 262–265°C; lH (acetone, 400 MHz): 9.2
2
. (a) Kirby, A. J. Angew. Chem., Int. Ed. 1996, 35, 707; (b)
Kimura, E. Prog. Inorg. Chem. 1994, 41, 443; (c) Kirby,
A. J. Angew. Chem., Int. Ed. 1994, 33, 551; (d)
Komiyama, M.; Sumaoka, J. Curr. Op. Chem. Biol. 1998,
(1H), 4.6 (1H), 4.0 (1H), 3.7 (3H), 2.9 (5H), 1.5 (4H), 0.01
+
+
+
(2H); m/z: 294 (M /3), 308 (MK /3), 321 (M2K /3), 335
+
+
+
(M3K /3), 515 (MTrif /2), 1180 (M2Trif ); IR w
max
−
1
(cm ): 3448, 2926, 2856, 1750, 1625, 1579, 1459, 1259,
2
, 751.
1162, 1029, 956, 640, 577, 518. Compound 1Eu: expected:
897.3230 (M ). Found: 897.3273. Yield: 18.5%; mp 270–
+
3
. Habicher, T.; Diederich, F.; Cramlich, V. Helv. Chim.
Acta 1999, 82, 1066.
273°C; lH (CD OD, 400 MHz): 24.4 (1H, s, cyc), 2.5
3
4
. (a) Feiters, M. C.; Rowan, A. E.; Nolte, R. J. Chem. Soc.
Rev. 2000, 29, 375; (b) H a¨ ner, R.; Hall, J.; Pf u¨ tzer, A.;
H u¨ sker, D. Pure. Appl. Chem. 1998, 70, 111.
(6H, s), 1.2 (3H, s), 0.5 (6H, s), −2.7 (2H, cyc-H), −4.3
(1H, cyc-H), −8.1 (2H, cyc-H), −8.9 (1H, cyc-H), −12.2
(1H, cyc-H); m/z: 299 (M /3); 448 (M /2); 523 (Mtrif /2);
+
+
+