On/off regulation of catalysis by allosteric control of metal complex nuclearity

Article abstract of DOI:10.1039/b316225g

The nature of the allosteric metal ion M (Pd²⁺ or Pt ²⁺) in complexes ML of a polytopic ligand controls uptake of additional Cu²⁺ ions; while [Cu₂Pd(L-4H)]²⁺ is a highly active catalyst for phosphodie

Full text of DOI:10.1039/b316225g

On/off regulation of catalysis by allosteric control of metal complex
nuclearity†
Larisa Kovbasyuk,a Hans Pritzkow,a Roland Krämer*a and Igor O. Fritskyb
a Anorganisch-Chemisches-Institut, Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg,
Germany. E-mail: roland.kraemer@urz.uni-heidelberg.de
b Department of Chemistry, National Taras Shevchenko University, Volodimirska Str. 64, Kyiv 01033,
Ukraine
Received (in Cambridge, UK) 11th December 2003, Accepted 30th January 2004
First published as an Advance Article on the web 4th March 2004
The nature of the allosteric metal ion M (Pd2+ or Pt2+) in
complexes ML of a polytopic ligand controls uptake of
additional Cu2+ ions; while [Cu2Pd(L-4H)]2+ is a highly active
catalyst for phosphodiester cleavage, [CuPt(L-4H)] is inactive.
7. Surprisingly, the absorbance diagrams indicate that 1 incorpo-
rates two, but 2 only one, copper ion (Fig. 1). This behaviour is
confirmed by ESI mass spectra of [M(L-4H)]22–Cu(OAc)2 (M =
Pd, Pt) 1:2 mixtures in 3 : 1 DMSO–H2O media. In particular, in the
spectrum of the Pd complex signals of only dicopper complexes
[Cu2Pd(L-4H)(OH)] (m/z 649.0) and [Cu2Pd(L-4H)(OH)(OAc)]
(m/z 709.1) are observed, while in the spectrum of the Pt complex
a signal of only a monocopper complex [CuPt(L-4H)]+H+ (4) is
observed (m/z 657.3). In the EPR spectra of 1–Cu(OAc)2, both 1 :
1 and 1 : 2 mixtures in DMSO–H2O glass at 77 K, a rather broad
and featureless signal with g = 2.09 G is found. This indicates the
formation of the dinuclear complex with intramolecular coupling
interaction of the two Cu. In contrast, the EPR spectrum of
2–Cu(OAc)2 1 : 1 reveals well resolved peaks (g4 = 2.06, g∑ =
2.25, A∑ = 163 cm21), typical for mononuclear Cu2+ complexes
with in-plane coordination by four nitrogen donor atoms.6 We
suggest a tetradentate in-plane coordination of Cu2+ by two
pyrazole N and two pyridyl N, according to molecular models with
significant elongation of the Cu–Npy bonds and widening of the
Npy–Cu–Npy angle. On addition of a second equivalent Cu(OAc)2,
EPR signals of the 1 : 1 complex overlap with those of free Cu2+,
supporting the idea that this complex does not incorporate a second
Cu ion. Interestingly, a very similar behaviour is found for a
1–CuCl2 mixture (g4 = 2.06, g∑ = 2.25, A∑ = 150 cm21),
indicating that acetate stabilizes the dicopper complex and is
essential to its formation.
The formation of a dicopper complex [Cu2Pd(L-4H)(m-OH) (m-
OAc)] (3) has been confirmed by X-ray crystallography.7 The
complex (Fig. 2) is nearly planar with exception of the bridging OH
coligand that lies 1.14 Å above the best plane. The Pd atom is
coordinated by four nitrogen atoms in a square planar fashion, with
significant widening of the Npz–Pd–Npz angle (118.5 °). The two
Cu2+ ions occupy the bidentate sites of L and are bridged by OH
and acetate, with a Cu…Cu distance of 3.17 Å. Cu coordination is
highly distorted from square planar, apparently the cavity of [Pd(L-
4H)]22 is too small for incorporation of two Cu2+ ions in a regular
square planar coordination. Although the bonding parameters of
Pd(II) and Pt(II) in their tetraaza square planar complexes are very
similar,8 the Pt2+ complex of L coordinates only one Cu2+ ion,
possibly because Pt2+ as a third row transition metal is less tolerant
to distortions from regular square planar coordination (such as
widening of one angle to > 118°) than Pd2+.
Allosteric1 modulation of activity is a common feature of biological
receptors and enzymes. The use of allosteric interactions enables
chemists to control molecular function, an important aspect in the
development of functional supramolecular devices of increasing
complexity. Only recently the first abiotic allosteric catalysts have
been described.2,3 In one such catalyst2a–2c the allosteric metal ion
controls the conformation and reactivity of a dinuclear, catalytic
site.2 Depending on the nature of the allosteric metal ion, the
cleavage rate of a phosphate ester varies by a factor of up to 70.
We have now observed in a related polynuclear complex a
different type of activity control: the allosteric metal ion controls
the uptake of metal ion cofactors which are essential for catalysis.
Ligand L4 has an allosteric subunit that coordinates Pd2+ or Pt2+,
and a catalytic subunit for the binding of either one or two copper(II
)
ions (Scheme 1). The nuclearity of the complex, i.e. formation of
either a monocopper(II) or dicopper(II) complex, is dependent on
the nature of the allosteric metal ion, and only the dicopper complex
is an active catalyst for the cleavage of a phosphodiester.
Allosteric control of the binding of catalytic metal ion cofactors
has been reported for enzymatic systems e.g. in the case of
ribonucleotide reductase which consists of two protein subunits
with a diiron active site.5
Complexes Na2[(Pd(L-4H)]·3H2O and K2[(Pt(L-4H)]·5H2O
have been prepared from L and metal salts in the presence of base.
Spectroscopic and microanalytical data support a structure with
tetradentate Pd and Pt coordination by two deprotonated amide and
two deprotonated pyrazole nitrogen atoms in the complex dianion.
It is shown by electrospray MS that these complexes are inert
against metal exchange in the presence of even large excess
Cu2+.
We have followed the coordination of Cu2+ to [(Pd(L-4H)]22 (1)
and [(Pt(L-4H)]22 (2) by spectrophotometric titration of the
complexes with copper(II) acetate in 3 : 1 DMSO–H2O media at pH
Scheme 1
† Electronic supplementary information (ESI) available: EPR spectra. See
http://www.rsc.org/suppdata/cc/b3/b316225g/
Fig. 1 Decrease of 300 nm absorbance on photometric titration of 1 (1025
M) (0), and 2 (1025 M) (5) with copper(II) acetate solution.
880
C h e m . C o m m u n . , 2 0 0 4 , 8 8 0 – 8 8 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

titration of [Pd(L-4H)]22 with Cu(NO3)2 in the presence of the inert
phosphodiester dimethyl phosphate (5 3 1024 M) which is
apparently less effective in stabilizing [Cu2Pd(L-4H)]2+ than the
better donor acetate. Activity decreases at > 5 equiv Cu, possibly
due to competitive complexation of the substrate by free Cu2+.
Acetate (1 equiv) is a strong inhibitor of catalysis, presumably
since it competes with the phosphodiester substrate for coordina-
tion to the free Cu sites. We suggest double Lewis acid activation9
of HPNP by bridging coordination to both Cu(II) ions as an
important mechanistic contribution to the high reactivity of the
dicopper complex.
In conclusion, we describe a new type of allosteric catalyst in
which the metal ion coordinated to an allosteric site controls the
nuclearity (mono- or dicopper) of a catalytic site. This corresponds
to an on/off regulation of catalysis of phosphodiester cleavage since
only the dicopper species is catalytically active. Interestingly, this
is achieved with allosteric metal ions Pd2+ and Pt2+ which usually
have very similar bonding parameters in their square-planar
complexes. Possibly the higher tolerance of Pd2+ to distortions of a
regular coordination favours incorporation of two Cu2+ ions into
[(L-4H)M]2+.
Fig. 2 The molecular structure of [PdCu2(L-4H)(OH)(CH3COO)] with the
crystallographic numbering of atoms.
We have studied in situ prepared copper complexes of 1 and 2 as
catalysts for the cleavage of the activated phosphodiester, 2-hy-
droxypropyl-p-nitrophenyl phosphate (HPNP), an analogue of
RNA. Intermolecular cyclization of this phosphodiester (Scheme 2)
was followed photometrically by the 400 nm absorbance of
released nitrophenolate. Kinetic studies were performed at varying
Cu2+ concentrations in a buffered DMSO–water 1 : 1 mixture at pH
7.0, 1024 M complex concentration and 5 3 1024 M HPNP.
Cleavage rate of HPNP at 0–1 equiv Cu2+ is very low which is
explained by saturation of in-plane coordination sites of metal ions
in both the allosteric (Pd2+ or Pt2+) and catalytic site. Further
additions of Cu(NO3)2 do not increase activity of 2, but sub-
This work was funded by the Deutsche Forschungsgemeinschaft
(Gerhard Hess-Programm) and supported by the Fonds der
Chemischen Industrie
Notes and references
stantially that of 1, with maximum rate at about 3 equiv Cu2+ (kobs
≈
)
1 In enzyme catalysis allosteric regulation is the control of enzyme activity
by noncovalent modifiers (molecules of ions) which bind to the enzyme
at a site other than the active site but alter the conformation of the active
site.
2 (a) I. O. Fritsky, R. Ott and R. Kramer, Angew. Chem., 2000, 39(18),
3255; (b) I. O. Fritsky, R. Ott, H. Pritzkow and R. Kramer, Chem. Eur. J.,
2001, 7(6), 1221; (c) I. O. Fritsky, R. Ott, H. Pritzkow and R. Kramer,
Inorg. Chim. Acta, 2003, 346, 111; (d) L. Kovbasyuk, M. Hoppe, H.
Pritzkow and R. Krämer, Eur. J. Inorg. Chem., 2001, (5), 1353; (e) K. P.
Strotmeyer, I. O. Fritsky, R. Ott, H. Pritzkow and R. Kraemer, Supramol.
Chem, 2003, 15, 529.
8.0 3 1025 s21) (Fig. 3). As in our previous studies on dicopper(II
allosteric catalysts,2a this can be explained by incomplete complex
formation at 2 equiv Cu. This is confirmed by spectrophotometric
3 A. Scarso, S. U. Scheffer, M. Gobel, Q. B. Broxterman, B. Kaptein, F.
Formaggio, C. Toniolo and P. Scrimin, Proc. Natl. Acad. Sci. USA, 2002,
99, 5144; T. Tozawa, S. Tokita and Y. Kubo, Tetrahedron Lett., 2002,
43(19), 3455; N. C. Gianneschi, P. A. Bertin, S. B. T. Nguyen, C. A.
Mirkin, L. N. Zakharov and A. L. Rheingold, J. Am. Chem. Soc., 2003,
125, 10508.
Scheme 2 Intramolecular cleavage of the phosphodiester 2-hydroxypropyl-
p-nitrophenyl phosphate (HPNP).
4 R. Krämer, I. O. Fritsky, H. Pritzkow and L. A. Kovbasyuk, J. Chem.
Soc., Dalton Trans., 2002, 7, 1307.
5 B. S. Pierce, T. E. Elgren and M. P. Hendrich, J. Am. Chem. Soc., 2003,
125, 8748.
6 G. Wilkinson, R. D. Gillard and J. A. McCleverty, Comprehensive
Coordination Chemistry, Vol. 5, Late Transition Elements, Pergamon
Press, Oxford, 1987, p. 662.
7 The quality of the crystals available did not allow a satisfactory structure
determination, but the connectivity could be determined. Therefore we
are not publishing details of the structure.
8 E. C. Constable, S. M. Elder, M. J. Hannon, A. Martin, P. R. Raithby and
D. A. Tocher, J. Chem. Soc., Dalton Tran., 1996, 12, 2423; C. W. Chan,
C. M. Che, M. C. Cheng and Yu. Wang, Inorg. Chem., 1992, 31(23),
4874.
9 Jik. Chin and J. H. Kim, Angew. Chem., Int. Ed. Engl., 1990, 102(5), 580;
Jik. Chin, Acc. Chem. Res., 1991, 24(5), 145.
Fig. 3 kobs for cleavage of HPNP (5 3 1024 M) in solutions containing 1(8)
(1024 M) and 2 (2) (1024 M) and varying copper(II) nitrate concentrations.
Buffer 5 mM 3-(N-morpholino)propanesulfonic acid (MOPS), T = 20 °C.
Cleavage by free Cu2+ is negligible.
C h e m . C o m m u n . , 2 0 0 4 , 8 8 0 – 8 8 1
881