Job/Unit: I50161
/KAP1
Date: 07-04-15 12:39:45
Pages: 11
www.eurjic.org
FULL PAPER
ZrIV ions, which offer multiple coordination possibilities. The reaction mixtures were kept at 60 °C, and the H NMR spectra
1
were recorded after mixing and after different time increments. The
hydrolysis products were identified by comparison of the H NMR
chemical shifts with those of pure compounds at the same pD
value.
Furthermore, it is plausible that, similarly to 1, this POM
1
exists in a monomer/dimer equilibrium that is too fast to
observe on the NMR time scale.[18] This equilibrium would
IV
result in a monomeric complex bearing two Zr centers
Supporting Information (see footnote on the first page of this arti-
with several aqua ligands that could be readily substituted
by oligopeptide substrates. We are currently performing
theoretical calculations on the possible equilibria of 3 to
shed more light on this issue.
1
13
31
cle): H, C, and P NMR spectra; kinetic profiles for hydrolysis
reactions; UV/Vis absorbance spectra of 2 in the absence and pres-
ence of 3G.
For the oligopeptides, the extension of the chain length
from 2G to 3G and 4G still resulted in complete hydrolysis; Acknowledgments
therefore, POMs 1–3 can fully hydrolyze longer peptide
chains. On the basis of the preferential binding of 1 at the H. G. T. L. thanks the Vietnamese Government for support. KU
Leuven is thanked for doctoral fellowships to H. G. T. L. and
N-terminal Gly residues in 3G and the fact that no 2G is
T. N. P. V. (START1/09/028). G. A. thanks the Fonds voor Weten-
observed during the initial stages of 4G hydrolysis, in the
schappelijk Onderzoek – Vlaanderen (FWO) for the postdoctoral
absence of any specific secondary interactions, 1 likely starts
fellowship.
to hydrolyze Gly oligopeptides at their N-terminus, and the
hydrolysis then progresses further downstream until com-
[
1] a) A. Proust, R. Thouvenot, P. Gouzerh, Chem. Commun.
008, 1837–1852; b) D. L. Long, R. Tsunashima, L. Cronin,
Angew. Chem. Int. Ed. 2010, 49, 1736–1758; Angew. Chem.
010, 122, 1780.
plete hydrolysis is achieved. The rate of oligopeptide hydrol-
ysis in the presence of 1 was fastest for the tripeptide GSF,
in which the Gly-Ser bond was preferentially hydrolyzed.
2
2
This further demonstrates the beneficial role that Ser resi- [2] a) K. Nomiya, Y. Sakai, S. Matsunaga, Eur. J. Inorg. Chem.
2
011, 179–196; b) B. Keita, L. Nadjo, J. Mol. Catal. A 2007,
dues play as internal nucleophiles in peptide hydrolysis.
However, the presence of bulky neighboring residues such
as Phe impedes the active role that Ser plays in GSF hydrol-
ysis.
2
62, 190–215.
[3] a) M. T. Pope, A. Muller, Angew. Chem. Int. Ed. Engl. 1991,
30, 34–48; Angew. Chem. 1991, 103, 56; b) H. Stephan, M.
Kubeil, F. Emmerling, C. E. Müller, Eur. J. Inorg. Chem. 2013,
1585–1594; c) M. Ammam, J. Mater. Chem. A 2013, 1, 6291–
6312; d) Y. F. Song, R. Tsunashima, Chem. Soc. Rev. 2012, 41,
The demonstrated trend in selectivity can be best com-
[
12]
pared to that observed for oxidized insulin chain B. The
selectivity of hydrolysis was also driven by coordination
7
384–7402; e) A. Ogata, S. Mitsui, H. Yanagie, H. Kasano, T.
Hisa, T. Yamase, M. Eriguchi, Biomed. Pharmacother. 2005,
9, 240–244; f) T. Yamase, J. Mater. Chem. 2005, 15, 4773–
IV
chemistry between the Zr ion in the POM and the poly-
5
peptide, whereas no evidence of specific electrostatic inter-
actions, as is the case for protein hydrolysis, was observed.
This can be explained by the lack of any tertiary structure
in the substrates under study. The results obtained in this
study are of importance for the design of artificial peptidase
agents for biotechnology applications in which frequently [5] a) N. Mizuno, K. Kamata, K. Yamaguchi, Top. Catal. 2010,
denatured or polypeptide chains need to be selectively
hydrolyzed.
4782; g) H. Stephan, M. Kubeil, F. Emmerling, C. E. Muller,
Eur. J. Inorg. Chem. 2013, 1585–1594; h) S. Mitsui, A. Ogata,
H. Yanagie, H. Kasano, T. Hisa, T. Yamase, M. Eriguchi,
Biomed. Pharmacother. 2006, 60, 353–358.
[
4] J. T. Rhule, C. L. Hill, D. A. Judd, R. F. Schinazi, Chem. Rev.
1998, 98, 327–358.
5
3, 876–893; b) N. Mizuno, K. Yamaguchi, K. Kamata, Coord.
Chem. Rev. 2005, 249, 1944–1956; c) O. A. Kholdeeva, Eur. J.
Inorg. Chem. 2013, 1595–1605.
[
6] a) Z. Huang, Z. Luo, Y. V. Geletii, J. W. Vickers, Q. Yin, D.
Wu, Y. Hou, Y. Ding, J. Song, D. G. Musaev, C. L. Hill, T.
Lian, J. Am. Chem. Soc. 2011, 133, 2068–2071; b) Y. V. Geletii,
B. Botar, P. Kögerler, D. A. Hillesheim, D. G. Musaev, C. L.
Hill, Angew. Chem. Int. Ed. 2008, 47, 3896–3899; Angew. Chem.
2008, 120, 3960; c) M. Orlandi, R. Argazzi, A. Sartorel, M.
Carraro, G. Scorrano, M. Bonchio, F. Scandola, Chem. Com-
mun. 2010, 46, 3152–3154; d) D. Lieb, A. Zahl, E. F. Wilson,
C. Streb, L. C. Nye, K. Meyer, I. Ivanovic-Burmazovic, Inorg.
Chem. 2011, 50, 9053–9058.
Experimental Section
Chemicals: Complexes 1, 2, and 3 were synthesized according to
the procedures reported previously.[
8d,19]
Gly-Gly-Gly (3G), Gly-
Gly-Gly-Gly (4G), Gly-Ser-Phe (GSF), Gly-Gly-His (GGH), D
2
O,
DCl, and NaOD were purchased from Sigma–Aldrich.
1
Measurements: The H NMR spectra were recorded with a Bruker
[
7] a) C. Boglio, G. Lemière, B. Hasenknopf, S. Thorimbert, E.
4
Advance 400 spectrometer, and [D ]sodium 3-(trimethylsilyl)-
]TMSP) was used as an internal reference. The 13
Lacôte, M. Malacria, Angew. Chem. Int. Ed. 2006, 45, 3324–
propionate ([D
4
C
3327; Angew. Chem. 2006, 118, 3402–3405; b) H. El Moll, B.
NMR spectra were recorded with a Bruker Advance 400 spectrom-
eter. As a reference, tetramethylsilane (TMS) in an internal refer-
ence tube was used. The 31P NMR spectra were recorded with a
Nohra, P. Mialane, J. Marrot, N. Dupré, B. Riflade, M. Malac-
ria, S. Thorimbert, B. Hasenknopf, E. Lacôte, P. A. Aparicio,
X. López, J. M. Poblet, A. Dolbecq, Chem. Eur. J. 2011, 17,
Bruker Advance 400 spectrometer, and 25% H
internal reference tube was used as a reference.
3 4 2
PO in H O in an
14129–14138; c) C. Boglio, K. Micoine, P. Remy, B. Hasenk-
nopf, S. Thorimbert, E. Lacote, M. Malacria, C. Afonso, J. C.
Tabet, Chem. Eur. J. 2007, 13, 5426–5432; d) N. Dupré, P.
Rémy, K. Micoine, C. Boglio, S. Thorimbert, E. Lacôte, B.
Hasenknopf, M. Malacria, Chem. Eur. J. 2010, 16, 7256–7264.
8] a) S. Vanhaecht, G. Absillis, T. N. Parac-Vogt, Dalton Trans.
2012, 41, 10028–10034; b) S. Vanhaecht, G. Absillis, T. N. Pa-
rac-Vogt, Dalton Trans. 2013, 42, 15437–15446; c) H. G. T. Ly,
Hydrolysis Studies: The hydrolysis reaction mixtures typically con-
tained oligopeptide (1.0 mm), 1–3 (2.0 mm), and [2,2,3,3-D ]TMSP
in D O. The pD of the reaction mixtures was adjusted to 5.4 or
.4 with minor amounts of DCl (1.0 m) or NaOD (1.0 m). The pH
4
2
[
7
[20]
meter reading was corrected by the equation: pD = pH + 0.41.
Eur. J. Inorg. Chem. 0000, 0–0
9
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim