From Calcium Interaction to Calcium Electrochemical Detection by [(C 5H5)Fe(C5H4COCH=CHC 6H4NEt2)] and Its Two Novel Structurally Characterized Derivatives

Article abstract of DOI:10.1021/ic0345828

[(C₅H₅)Fe(C₅H₄COCH=CHC ₆H₄NEt₂)] (1) has been electrochemically evaluated toward different cations in solution. Calcium sensing by this compound and its two new derivatives [(C₅H₅)Fe(C ₅H₄CO(CH=CH)₂C₆H₄NMe ₂)] (2) and [(C₅H₅)Fe(C₅H ₄CH=CHCOCH=CHC₆H₄NEt₂)] (3) that exhibit a conjugated link between the ferrocene unit and the nitrogen atom has been thoroughly examined. Compounds 2 and 3 have been structurally characterized by single-crystal X-ray diffraction studies. The three related protonated species [1H][BF₄] (4), [2H][BF₄] (5), and [3H][BF₄] (6) have been isolated in a good yield. NMR experiments clearly established that calcium interaction occurs in the vicinity of the carbonyl group, and mass spectrometry studies confirmed that this interaction, which involves several ligand-Ca²⁺ adducts, is complex. A combination of electrochemical and NMR experiments highlighted an original salt influence on the electrochemical calcium sensing result.

Full text of DOI:10.1021/ic0345828

Inorg. Chem. 2004, 43, 2064−2077
From Calcium Interaction to Calcium Electrochemical Detection by
[(C H )Fe(C H COCHdCHC H NEt2)] and Its Two Novel Structurally
5 5
5 4
6 4
Characterized Derivatives
,†
Je´roˆme Maynadie´,† Be´atrice Delavaux-Nicot,* Dominique Lavabre,‡ Bruno Donnadieu,†
Jean-Claude Daran,† and Alix Sournia-Saquet†
Laboratoire de Chimie de Coordination du CNRS, UPR 8241, 205, route de Narbonne, F-31077,
Toulouse Cedex 04, France, and Laboratoire des Interactions Mole´culaires et Re´actiVite´ Chimique
et Photochimique, UMR 5623 du CNRS, UniVersite´ Paul Sabatier, 118 route de Narbonne,
F-31062, Toulouse Cedex, France
Received May 28, 2003
[(C H )Fe(C H COCHdCHC H NEt2)] (1) has been electrochemically evaluated toward different cations in solution.
5
5
5
4
6 4
Calcium sensing by this compound and its two new derivatives [(C H )Fe(C H CO(CHdCH)2C H NMe2)] (2) and
5
5
5
4
6 4
[(C H )Fe(C H CHdCHCOCHdCHC H NEt2)] (3) that exhibit a conjugated link between the ferrocene unit and
5
5
5
4
6 4
the nitrogen atom has been thoroughly examined. Compounds 2 and 3 have been structurally characterized by
single-crystal X-ray diffraction studies. The three related protonated species [1H][BF ] (4), [2H][BF ] (5), and [3H]-
4
4
[BF ] (6) have been isolated in a good yield. NMR experiments clearly established that calcium interaction occurs
4
in the vicinity of the carbonyl group, and mass spectrometry studies confirmed that this interaction, which involves
several ligand−Ca2+ adducts, is complex. A combination of electrochemical and NMR experiments highlighted an
original salt influence on the electrochemical calcium sensing result.
Introduction
of signaling units (electroactive and fluorescent), could be
the keystone of new families of ion chemosensors that can
either be able to sense different guests or display two or more
macroscopic observable events upon addition of a certain
analyte.2c,3 The fabrication of these systems and their
integration into different supports (e.g., matrixes: electroni-
cally conducting polymeric supports, optical fibers, etc.) will
probably lead to novel prototype molecular sensory devices
of commercial usage.2a,4 As part of our research program
aimed at the design of innovative sensors, we have recently
investigated the synthesis of electroactive receptors which
combine ferrocenyl units and a purely organic fluorescent
ion sensor subunit containing an R-amino complexing moiety
(-COCHdCHC6H4-pR, R ) NEt2 or aza-15-crown-5). We
have established that new electroactive and efficient fluo-
A plethora of redox-active or fluorescent receptors have
been designed for ion recognition in solution and have proved
the usefulness of electrochemistry and fluorescence in
chemistry, biology, and medicine.1 However, despite the
development of these two types of sensors, few examples
of fluorescent ferrocenyl ion sensors have been described in
the literature.2 These latter systems, which contain both types
* Author to whom correspondence should be adressed. E-mail:
delavaux@lcc-toulouse.fr. Fax: (33) 5 61 55 30 03.
† Laboratoire de Chimie de Coordination du CNRS.
‡ Laboratoire des Interactions Mole´culaires et Re´activite´ Chimique et
Photochimique.
(1) For examples in electrochemistry: (a) Beer, P. D. AdV. Inorg. Chem.
1992, 39, 79. (b) Beer, P. D.; Cadman J. Coord. Chem. ReV. 2000,
205, 131. (c) Medina, J. C.; Goodnow, T. T.; Rojas, M. T.; Atwood,
J. L.; Lynn, B. C.; Kaifer, A. E.; Gokel, G. W. J. Am. Chem. Soc.
1992, 114, 10583. (d) Delavaux-Nicot, B.; Mathieu, R.; de Montauzon,
D.; Lavigne, G.; Majoral, J.-P. Inorg. Chem. 1994, 33, 434. (e)
Delavaux-Nicot, B.; Bigeard, A.; Bousseksou, A.; Donnadieu, B.;
Commenges, G. Inorg. Chem. 1997, 36, 4789 and references therein.
For examples in fluorescence: (f) Prasanna de Silva, A.; Gunaratne,
H. Q. N.; Gunnlaugsson, T.; Huxley, A. J. M.; McCoy, C. P.;
Rademacher, J. T.; Rice, T. E. Chem. ReV. 1997, 97, 1515. (g) Czarnik,
A. Fluorescent Chemosensors for Ion and Molecule Recognition; ACS
Symposium Series 538; American Chemical Society, Washington, DC,
1993. (h) Tsien, R. Y. In Methods in Cell Biology; Taylor, D., Wang,
Y.-L., Eds.; Academic Press: London, 1989, 30, 127.
(2) (a) Beer, P. D.; Szemes, F.; Balzani, V.; Sala`, C. M.; Drew, M. G. B.;
Dent, S. W.; Maestri, M. J. Am. Chem. Soc. 1997, 119, 11864. (b)
Delavaux-Nicot, B.; Fery-Forgues, S. Eur. J. Inorg. Chem. 1999, 1821.
(c) Fery-Forgues, S.; Delavaux-Nicot, B. J. Photochem. Photobiol.,
A 2000, 132, 137.
(3) (a) Sancenon, F.; Benito, A.; Hernandez, F. J.; Lloris, J. M.; Martinez-
Manez, R.; Pardo, T.; Soto, R. Eur. J. Inorg. Chem. 2002, 866. (b)
Gan, J.; Tian, H.; Wang, Z.; Chen, K.; Hill, J.; Lane, P. A.; Rahn, M.
D.; Fox, A. M.; Bradley, D. D. C. J. Organomet. Chem. 2002, 645,
168.
(4) Maynadie, J.; Delavaux-Nicot, B.; Fery-Forgues, S.; Lavabre, D.;
Mathieu, R. Inorg. Chem. 2002, 41, 5002.
2064 Inorganic Chemistry, Vol. 43, No. 6, 2004
10.1021/ic0345828 CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/17/2004

Calcium Sensing by Ferrocenyl DeriWatiWes
Scheme 1. Synthetic Route for Compounds 1, 2, and 3
Figure 1. Molecular view of the structure of compound 2 (ORTEP 3)
with 50% thermal ellipsoids.
Results and Discussion
1. Synthesis and Characterization of Ligands 1, 2, and
3. As for compound 1,2b compounds 2 and 3 were obtained
in good isolated yield (72-82%) by reaction of acetyl
ferrocene and ferrocene carboxaldehyde with the appropriate
organic reactants in basic medium.
rescent species which contain only ferrocene as a metallic
moiety could be obtained,2b and that one of these compounds
[Fe(C5H4COCHdCHC6H4NEt2)2] behaves as a new type of
multiresponsive calcium-sensing device.4
In contrast to its disubstituted counterpart, compound
[(C5H5)Fe(C5H4COCHdCHC6H4NEt2)] (1) is not fluorescent
in CH3CN. But, preliminary results have shown that inter-
position of the conjugated sCOCHdCHC6H4s spacer
between the ferrocene unit and the NEt2 ionophore in this
compound could allow an electronic communication through
the link. This property is of real importance and suggested
that molecules containing the fluorescent organic fragment
could be electrochemical sensors. Furthermore, an electronic
communication through the link has also been demonstrated
for ferrocenyl systems incorporating a sCHdCHC6H4s
spacer.5 Other teams have also studied related compounds
(analogues of 1) incorporating a CO function directly linked
to a ferrocenyl moiety,6 however none of these compounds
was evaluated toward electrochemical sensing. Recently, such
related ferrocenyl chalcone systems attracted a revival of
interest and were tested toward antimalarial activity7 or as
potential anticancer drugs.8
Here we report on the synthesis, characterization, reactiv-
ity, and electrochemical properties of compound [(C5H5)-
Fe(C5H4COCHdCHC6H4NEt2)] 1 and of its two new mono-
substituted derivatives 2 and 3 containing an olefinic
fragment after and before the carbonyl group (Scheme 1).
Compounds 2 and 3 were synthesized to get a better
understanding of the factors which could influence the
electronic communication in this family and consequently
the cation detection. We were particularly interested in
understanding and quantifying the interaction processes
which occur with the Ca2+ cation and the pathway between
interaction and signaling.
New experimental conditions allowed a significant im-
provement in the isolated yield of 1 when compared to our
precedent published procedure.2b The reverse aldol condensa-
tion reaction could be suppressed in absence of water. The
IR spectra of molecules 1, 2, and 3 exhibit vibrations at 1647,
1646, and 1642 cm-1 in CH3CN, respectively, assigned to
stretching CO vibrations.9a-c This low value is due to the
conjugation of the CO group with the π system (sCHd
CHC6H4s) in the molecule.2b,9d These vibrational assign-
ments are presently under theoretical investigation.10
The structure of these molecules was first deduced from
spectroscopic data. 2D NMR experiments (HMQC and
NOESY) clearly verified the assignments. Elemental analyses
and mass spectra are also in agreement with the proposed
1
formula (see Experimental Section). In the H NMR, for
compound 2, the olefinic protons Ha and Hb in R and â
position toward the CO function presented an upfield shift
when compared to those of 1 and 3 (+ 0.20 ppm). In
compound 3, as for the symmetrical related compound
[(C5H5)Fe(C5H4CHdCHCOCHdCHC5H4)Fe(C5H5)]9a and
the [Fe-Cr] compound [(C5H5)Fe(C5H4CHdCHCOCHd
CHC6H5Cr(CO)3)]9b very similar shifts are observed for the
Ha and Hi protons in R position to the CO function and for
the Hb and Hj protons in â position.
Crystal of 2 and 3 suitable for X-ray structural analysis
were obtained by slow recrystalization in CH3CN. Perspec-
tive views of the molecules are shown in Figures 1 and 2,
respectively. Crystallographic data for compounds 2 and 3
are provided in Table 1. Selected bond lengths and bond
angles are listed in Table 2. In both compounds the Cp rings
are nearly eclipsed with twist angles of 3° and 9.3° for 2
and 3, respectively (see S10 and S11 in the Supporting
Information). The bond lengths within the ferrocenyl
(5) Andrews, M. P.; Blackburn, C.; McAleer, J. F.; Patel, V. D. J. Chem.
Soc., Chem. Commun. 1987, 1122.
(6) For example: (a) Nagy, A. G.; Toma, S. J. Organomet. Chem. 1984,
266, 257. (b) Nagy, A. G. J. Org. Chem. 1984, 291, 335. Dubosc, J.
P. C. G. U.S. Patent 3,335,008, 1967. (c) Nesmeyanov, A. N.; Shulp’in,
G. B.; Rybin, L. V.; Gubenko, N. T.; Rybinskaya, M. I.; Petrovkii, P.
V.; Robas, V. I. Zh. Obshch. Khim. (J. Gener. Chem. USSR) 1974,
44, 1994. (d) Toma, S.; Perjessy, A. Chem. ZVesti 1969, 23, 343. (e)
Boichard, J.; Monin, J. P.; Tirouflet, J. Bull. Soc. Chim. Fr. 1963, 4,
851.
(7) Wu, X.; Wilairat, P.; Go, M.-L. Biorg. Med. Chem. Lett. 2002, 12,
2299.
(8) Ferle-Vidovic, A.; Poljak-Blazi, M.; Rapic, V.; Skare, D. Cancer
Biother. Radiopharm. 2000, 15, 617.
(9) (a) Harvey, P. D.; Sharman, J. G. Can. J. Chem. 1990, 68, 223. (b)
Prim, D.; Auffrant, A.; Plyta, Z. F.; Tranchier, J. P.; Rose-Munch, F.;
Rose, E. J. Organomet. Chem. 2001, 624, 124. (c) Ansorge, M.;
Polborn, K.; Mu¨ller, T. J. J. Eur. J. Inorg. Chem. 2000, 2003. (d)
Silverstein, R. M.; Bassler G. C.; Morril T. C. In Spectrometric
Identification of Organic Compounds, 4th edition; J. Wiley and
Sons: New York, 1981; Ch. 3, pp 117-118.
(10) Delavaux, B.; Lepetit, C.; Chermette, H. unpublished results.
Inorganic Chemistry, Vol. 43, No. 6, 2004 2065

Maynadie´ et al.
located around the C5-C6 bound for 2; the C4-C5-C6-
C7 torsion angle being indeed 20.5°, whereas in compound
3, the highest observed torsion angle is 11.4° for C11-C12-
C13-C14. The organic substituent appears as slightly folded
around the CO function: the dihedral angle between the two
Cp- -CO and CO- -Ph average planes is approximately 13.7°.
To our knowledge, the unique example of monosubstituted
compound presenting a C5H4COCHdCHC6H4s linkage and
structurally characterized is the complex [(C5H5)Fe(C5H4-
COCHdCHC6H4NO2)] (A).11a This compound is also roughly
planar, and the CO and CdC functions are also cis. The
observed conformation is the most reasonable for steric
reasons. The C-N distances in 2 and 3, 1.385(4) and 1.384-
(5) Å, respectively, are close to the value observed in
[(C5H5)Fe(C5H4COC6H4NH2)]:9c 1.368(9) Å. As expected,
these distances are longer than that of A: 1.224(11) Å
bearing an electron-withdrawing NO2 function.
Figure 2. Molecular view of the structure of compound 3 (ORTEP 3)
with 50% thermal ellipsoids.
Table 1. Crystallographic Data for Compounds
[(C5H5)Fe(C5H4CO(CHdCH)2C6H4NMe2)] 2 and
[(C5H5)Fe(C5H4((CHdCH)CO(CHdCH)C6H4NEt2)] 3a
2
3
chemical formula
fw
C23H23NOFe
385.27
C25H27NOFe
413.33
cryst syst
space group
a, Å
b, Å
c, Å
monoclinic
P21/n
monoclinic
P21/a
5.7050(10)
26.841(5)
12.086(2)
90.55(3)
1850.6(6)
1.383
9.8308(11)
12.205(2)
16.792(2)
91.364(15)
2014.2(5)
1.363
The UV-vis spectrum of 1 recorded in CH3CN exhibits
an intense band at 404 nm attributed to a charge transfer
(CT) from the donor amino group to the acceptor carbonyl
group. The absorption spectra of 2 and 3 exhibit a similar
CT band at 412 and 418 nm, respectively. As for compound
1, these compounds are not fluorescent in this solvent.
However, in the solid state, the quasi planarity of the
ferrocene substituents is in favor of the existence of a π
conjugation that might induce a good electronic communica-
tion through the link in solution.
â°
V, Å3
F
calc, mg/m3
Z
4
4
µ (mm-1
T, K
)
0.826
160(2)
0.764
180(2)
R1 [I > 2σ(I)]
wR2[I > 2σ(I)]
R1 (all data)
0.0397
0.0927
0.0621
0.0488
0.0930
0.0946
wR2 (all data)
0.1014
0.1058
2
2
a R1 ) ∑||Fï| - |Fc||/∑|Fï|; wR2 ) {∑[w(Fï - Fc )2/∑[w(Fï2)2]}1/2
.
2. Electrochemical Studies. A. Characterization of
Compounds 1, 2, and 3. The electrochemical properties of
the ligands 1, 2, and 3 have been investigated in CH3CN
(Table 3) and typical voltammograms of these species are
presented in Figure 3. For compounds 1 and 3 the first wave
was observed in cyclic voltammograms (CV) at anodic peak
potential (Epa) ) 0.70 and 0.60 V, respectively. This is due
to the oxidation of the ferrocene moiety and corresponds to
a quasi-reversible process whose half wave potential (E1/2)
value was determined by linear voltammetry. In CV, other
irreversible processes observed at more anodic potentials
values are attributed to the oxidation of the organic sub-
stituent of the molecules. In contrast, the CV of compound
2 exhibits a first peak corresponding to an irreversible
oxidation process, followed by the quasi-reversible Fe(II/
III) oxidation process calculated at E1/2 ) 0.72 V. For the
three compounds, a single wave was observed in reduction
below cathodic peak potential (Epc) ) -1.55 V.
Table 2. Selected Bond Lengths (Å) and Angles (deg) for Compounds
2 and 3 with Esd’s in Parentheses
bond lengths (Å)
bond angles (deg)
Compound 2
O(1)-C(1)-C(2)
C1a-C(1)
1.474(4)
1.231(3)
1.472(4)
1.339(4)
1.441(4)
1.343(4)
1.454(4)
1.384(5)
1.385(4)
1.445(5)
122.0(2)
120.4(2)
125.7(3)
127.8(3)
121.3(3)
122.1(3)
122.3(3)
117.8(4)
116.3(3)
120.2(3)
O(1)-C(1)
C(1)-C(2)
C(2)-C(3)
C(3)-C(4)
C(4)-C(5)
C(5)-C(6)
C(7)-C(8)
C(9)-N(1)
N(1)-C(13)
O(1)-C(1)-C(1a)
C(2)-C(3)-C(4)
C(4)-C(5)-C(6)
C(8)-C(7)-C(6)
C(7)-C(8)-C(9)
C(8)-C(9)-N(1)
C(9)-N(1)-C(12)
C(8)-N(1)-C(12)
C(9)-N(1)-C(13)
Compound 3
C1-C(11)
1.443(10)
1.320(8)
1.252(7)
1.463(9)
1.327(9)
1.454(9)
1.374(8)
1.384(5)
1.440(9)
1.459(8)
C(1)-C(11)-C(12)
C(11)-C(12)-C(13)
C(12)-C(13)-O(1)
O1-C(13)-C(14)
C(14)-C(15)-C(151)
C(15)-C(151)-C(152)
C(152)-C(153)-C(154)
C(153)-C(154)-N(1)
C(154)-N(1)-C(113)
C(154)-N(1)-C(111)
127.7(5)
123.4(5)
120.8(6)
121.4(6)
127.2(5)
120.5(5)
119.9(7)
120.5(6)
121.6(5)
119.7(6)
C(11)-C(12)
O(1)-C(13)
C(13)-C(14)
C(14)-C(15)
C(15)-C(151)
C(152)-C(153)
C(154)-N(1)
N(1)-C(113)
N(1)-C(111)
Electrochemical cation recognition is mainly based on the
variation of the iron (II/III) oxidation potential upon ion
addition. To gain a better understanding of the above-
described electrochemical processes for 1, 2, and 3, elec-
moieties,11 as well as the CdO, C5H4-C, and CdC
distances, compare well with values reported in the litera-
ture.12,13 For each compound, the olefinic bonds are always
cis to the CO function. In both compounds, the organic chain
is almost planar. The largest deviation from planarity is
(12) For CpCOCdC linkage: (a) Shottenberger, H.; Buchmeiser, M. R.;
Angleitner, H.; Wurst, K.; Herber, R. H. J. Organomet. Chem. 2000,
605, 174. (b) Be´nyei, A. C.; Glidewell, C.; Lightfoot, P.; Royles, B.
J. L.; Smith, D. M. J. Organomet. Chem. 1997, 539, 177. (c) Gyepes,
E.; Glowiak, T.; Toma, S. J. Organomet. Chem. 1986, 316, 163.
(13) For CpCdCCO linkage: (a) Constable, E. C.; Edwards, A. J.;
Martinez-Manez, R.; Raithby, P. R. J. Chem. Soc., Dalton Trans. 1995,
3253. (b) Constable, E. C.; Edwards, A. J.; Marcos, M. D.; Raithby,
P. R.; Martinez-Manez, R.; Tendero, M. J. L. Inorg. Chim. Acta 1994,
224, 11. (c) Sato, M.; Mogi, E. J. Organomet. Chem. 1996, 517, 1.
(11) (a) Lindeman, S. V.; Bozak, R. E.; Hicks, R. J.; Husebye, S. Acta
Chem. Scand. 1997, 51, 966. (b) Allen, F. H.; Kennard, O.; Watson,
D. G.; Brammer, L.; Orpen, G. A.; Taylor, R. J. Chem. Soc., Perkin
Trans. 2 1987, 12, S1.
2066 Inorganic Chemistry, Vol. 43, No. 6, 2004

Calcium Sensing by Ferrocenyl DeriWatiWes
Table 3. Electrochemical Properties of Compounds 1, 2, and 3 in CH3CNa
compd
Epa(Fe)
E1/2 (P)
∆Ep
RIp
Epa(Org.)
0.92; 1.60
0.68; 0.98; 1.36
0.87; 1.56
E1/2 (P)b
Epc(Red.)
E1/2
1
2
3
0.70
0.79
0.60
0.64 (52)
0.72c
0.55 (53)
63
1.0
0.84 (47); 1.50
-1.78
-1.68
-1.58
-1.69
-1.52
-1.48
85
1.0
0.82 (49); 1.35
a P, ∆EP (mV); E1/2, Epa (V). ∆Ep ) Ep (forward) - Ep (backward) ) Epa - Epc. RIp ) |Ip (forward)/Ip (backward)| ) |Ipox/Ipred|. P ) slope of the linear
regression of E ) f(log|i/id-i|). Org. ) oxidation processes of the organic part of the molecule. Red. ) lone process observed in reduction for the organic
part. b For the first oxidation process of the organic part. c Calculated as the average of anodic (Epa) and cathodic (Epc) peak potentials. Conditions: [complexes],
10-3 M; Pt electrode (1 mm diameter); scan rate in cyclic voltammetry, 100 mV s-1; scan rate in linear voltammetry: 5 mV s-1; solution of 0.1 M nBu4NBF4
in CH3CN; reference electrode SCE.
anodic shift of the Fe(II)/Fe(III) potential when compared
to ferrocene.14 In contrast, our results are in agreement with
previously reported data of related compounds.6a Moreover,
as an example, Dowling et al.15 have shown that insertion
of a sCHdCHs group in the Fc-CN bond induced a
cathodic shift (210 mV) of the Fe(II)/Fe(III) couple, which
can be compared with our findings.
As far as the irreversible reduction process is concerned,
it is well-known that when an electroreducible group is
conjugated with olefinic groups, the molecule becomes under
comparable conditions more easily reducible, as well il-
lustrated by R,â-unsaturated carbonyl.16 The reduction mech-
anisms of the R,â-unsaturated carbonyls depends on many
factors such as acid-base reactions, preceding, accompany-
ing, and following electron transfer or on the cathode
material. The E1/2 values (below -1.50 V) found here for
the reduction of 1, 2, and 3 are therefore attributed to a
reduction process mainly located on the CO function. Let
us remark that for compound [CH3COCHdCHC6H4NEt2]
the reduction process was absent in CH2Cl2, whereas in CH3-
CN the use of an Au electrode allowed the clear E1/2
determination at -1.84 V.
Figure 3. Cyclic voltammograms of (a) compounds 1 (dashed line) and
3 (solid line) and (b) compounds 1 (dashed line) and 2 (solid line).
Studies of the oxidation of organic amines have shown
that the primary electrode process for amines is the transfer
Experimental conditions: Pt electrode (1 mm diameter) in 0.1 M solution
of nBu4NBF4 in CH3CN, scan rate 100 mV s-1, ligand concentration 10-3
of an electron from the lone pair of nitrogen to the anode to
form a cationic radical.17 Oxidation of aliphatic amines
typically involves the formation of the amine or ammonium
salt which arises from hydrogen abstraction from the solvent
by the generated radical, whereas radical coupling is favored
by aromatic amines.18 Ferrocenyl aliphatic amines may have
the same behavior as their organic counterparts.1e,19,20 These
results suggest that different and/or competitive mechanisms
may be responsible for the second (and third) irreversible
organic oxidation wave observed for our compounds. More-
over, it must also be underlined that in these latter cases the
spacer between the ferrocene moiety and the organic part is
unsaturated, which certainly also affects the oxidation amine
response.
M; reference electrode SCE.
trochemical properties of some related iron and organic
compounds have been investigated in the same experimental
conditions. Among them, the new compounds [(C5H5)Fe(C5H4-
CO(CHdCH)2C6H4NEt2)] (7) and [(C5H5)Fe(C5H4(CHdCH)2-
CO(CHdCH)C6H4NEt2)] (8) were synthesized and charac-
terized as described in the Experimental Section. The results
are reported in Table 4, and the following trends appear. (i)
Introduction of a sCHdCHs function before the CO group
induces a noticeable cathodic shift (ca 100 mV) of the iron
oxidation potential (E1/2 Fe). (ii) An anodic shift of the
organic irreversible reduction process (E1/2 Red) occurs
simultaneously, and is more important for a double sCHd
CHs insertion. This last phenomenon is also observed for
the organic compounds. (iii) For the compounds bearing an
amino group, an irreversible oxidation process whose E1/2
value is found between 0.63 and 1.10 V is observed. This
may be attributed to the oxidation potential of the organic
amine moiety (E1/2 Org) because it lies in the range of values
reported for the oxidation of some aza ferrocenyl com-
pounds.5
(14) Beer, P. D.; Kocian, O.; Mortimer, R. J. J. Chem. Soc., Dalton Trans.
1990, 3283.
(15) Dowling, N.; Henry, P. M.; Lewis, N. A.; Taube, H. Inorg. Chem.
1981, 20, 2345.
(16) In Organic Electrochemistry: An Introduction and a Guide; Baizer,
M., Ed.; Marcel Dekker: New York, 1973.
(17) Ross, S. D.; Finkelstein, M.; Rudd, E. J. Anodic Oxidation; Academic
Press: New York, 1975; Vol. 32, Ch. 8, p 189.
(18) (a) Prins, R.; Koorswagen, A. R.; Kortbeek A. G. T. G. J. Organomet.
Chem. 1972, 39, 335. (b) Prins, R. Mol. Phys. 1970, 19, 603.
(19) (a) Spescha, M.; Duffy, N. W.; Robinson, B. H.; Simpson, J.
Organometallics 1994, 13, 4895.
Conjugation of an electron-withdrawing olefinic fragment
with a ferrocene moiety has been reported to induce an
Inorganic Chemistry, Vol. 43, No. 6, 2004 2067

Maynadie´ et al.
Table 4. Selected Electrochemical Characteristics of Related Iron or Organic Compounds in CH3CNa
compound
E1/2 Fe
E1/2 Org. (Epa)
E1/2 Red. (Epa)
FcCOMe
Fc(CHdCH)CHO
Fc(CHdCH)COC6H5
0.69
0.58
0.56
- - -
- - -
xb
- - -
-1.77
x
6a
Fc(CHdCH)CO(CHdCH)C6H5
0.55
0.55
0.50
0.69
- - -
-1.34
-1.48
-1.35
x
Fc(CHdCH)CO(CHdCH)C6H4NEt2 (3)
Fc(CHdCH)2CO(CHdCH)C6H4NEt2 (8)
0.82
0.79
x
6a
FcCO(CHdCH)C6H5
FcCO(CHdCH)C6H4NEt2 (1)
FcCO(CHdCH)2C6H5
0.64
0.68
0.84
-1.69
-1.42
-1.53
-1.58
- - -
- - -
-1.62
-1.81
(-1.89)
-1.31
-1.48
x
- - -d
(0.68)
(0.66)
0.71
FcCO(CHdCH)2C6H4NMe2 (2)
FcCO(CHdCH)2C6H4NEt2(7)
0.72e
0.74e
- - -
- - -
- - -
- - -
- - -
- - -
- - -
0.34
c
CH3C6H4NEt2
CHOC6H4NEt2
1.11
0.85
0.84
0.78
0.75
0.68
0.63
0.73
CHO(CHdCH)C6H4NMe2
CHO(CHdCH)C6H4NEt2
CH3CO(CHdCH)C6H4NEt2
C6H5(CHdCH)CO(CHdCH)C6H4NEt2
CO((CHdCH)C6H4NEt2)2
43
Fc(CHdCH)C6H4NMe2
2b
Fc(COCH2)2CHC6H4NEt2
0.96
- - -
a In our standard conditions. Fc ) C5H5FeC5H4-. Org. ) first oxidation process of the organic part. Red. ) process observed in reduction for the organic
part. b x ) not mentioned. c Quasi-reversible process. d - - - ) not observed. e Calculated as the average of anodic (Epa) and cathodic (Epc) peak potentials.
For the synthesis of the compounds see Experimental Section.
B. Electrochemical Calcium Detection by Compounds
1, 2, and 3. Electrochemical tests were first performed with
1 (10-3M) in acetonitrile in the presence of various cations
(Li+, Na+, K+, Ba2+, Mg2+, Ca2+, Cu+, Cu2+, and Zn2+).
Complex and particular changes occurred in the presence of
the copper cations and are not described here. Compound 1
was poorly sensitive to the presence of cations other than
Mg2+ and Ca2+. In addition, the design of interesting
chemosensors which are specific to these latter biologically
relevant cations represents a challenging task for many
groups.21 As the Ca2+ electrochemical sensing was very clear
for compound 1 we were especially interested in it. Com-
pounds 2 and 3 were also evaluated toward this cation in
the same conditions. Addition of 1 equiv of Ca(CF3SO3)2 to
compounds 1, 2, and 3 induced a clear shift of the Fe(II/III)
couple toward anodic potential for 1 and 3 (∆E1/2 ) 58 and
32 mV, respectively) and toward cathodic potential for 2
(∆E1/2 ) -24 mV) (Figure 4).
In cyclic voltammetry, upon calcium addition, the shifted
waves corresponding to the iron (II) oxidation processes are
still quasi-reversible processes. Simultaneously, the waves
corresponding to the oxidation processes of the organic part
of the molecule disappeared. The “CO” reduction process
becomes poorly defined: an important broadening of the
Figure 4. Segmented cyclic voltammograms of compounds (a) 1, (b) 3,
and (c) 2, before (dashed lines) and after (solid lines) addition of 1 equiv
wave accompanied with a variable anodic shift of the
reduction potential could be observed. The main reproducible
feature observed in reduction for each of compounds 1, 2,
and 3 was the appearance of a new irreversible process
situated at E1/2 ) -0.16, -0.17, and -0.22 V, respectively,
and presenting an important ∆Ep value: 210, 240, and 440
mV, respectively (vide infra). Under our experimental
conditions, it was also determined that the reduction of the
of Ca(CF3SO3)2. Experimental conditions: Pt electrode (1 mm diameter)
n
in 0.1 M solution of NBu4BF4 in CH3CN, scan rate 100 mV s-1, ligand
concentration 10-3 M; reference electrode SCE.
Ca(CF3SO3)2 salt could occur in two principal ranges of
potential varying with the salt concentration. For example,
the reduction processes observed for 1 equiv (10-3
M
concentration) were situated at E1/2 ) -0.09 V (∆Ep ) 349
mV) and -1.03 V (∆Ep ) 539 mV).
Generally, addition of a metal cation induces a classical
anodic shift of the iron potential.1 To our knowledge, only
one cathodic iron shift has been reported upon cation addition
(20) Duffy, N. W.; Harper, J.; Ramani, P.; Ranatunge-Bandarage, R.;
Robinson, B. H.; Simpson, J. J. Organomet. Chem. 1998, 564, 125.
(21) (a) Ajayaghosh, A.; Arunkumar, E.; Daub, J. Angew. Chem., Int. Ed.
2002, 41, 1766. (b) Chesney, A.; Bryce, M. R.; Batsanov, A. S.;
Howard, J. A. K.; Goldenberg, L. M. Chem. Commun. 1998, 677.
2068 Inorganic Chemistry, Vol. 43, No. 6, 2004

Calcium Sensing by Ferrocenyl DeriWatiWes
Table 5. NMR Shift Variations (∆ (δ), ppm) of Selected Groups of Compounds 1, 2, and 3 upon (a) Calcium Addition (1 equiv) and (b) Protonation
(1 equiv); [L] ) 5 × 10-3 Ma
compd
CHa
CHb
CHc
CHd
N-CH
CHe
CHf
CHg
CHh
CHi
CHj
CO
(a) Calcium Addition
1 H
C
2 H
C
3 H
C
-0.01
-1.07
0.01
-0.83
0.06
0.17
2.67
0.14
2.18
0.24
3.72
0.01
0.71
-0.01
0.35
0.02
1.02
-0.02
0.03
-0.02
0.06
-0.03
0.11
0
0.07
0
0
0
0.11
0.68
0.09
0.60
0.01
0.59
0.09
1.16
0.09
1.06
0.06
0.93
2.77
2.19
1.93
0.01
-0.24
0.03
1.60
0.07
-0.83
0.24
4.24
-1.02
0.13
(b) Protonation
1 H
C
0.31
8.46
0.21
4.09
0.48
7.07
0.11
-3.50
-0.01
-1.92
0.09
0.40
-0.07
0.29
0.26
0.42
0.82
11.62
0.83
8.93
0.81
0.23
9.96
0.35
7.45
0.17
0.05
0.35
0.02
0.31
0.04
0.39
0.10
1.01
0.04
0.74
0.05
0.77
-0.07
0.61
2 H
C
0.31
7.33
0.07
-3.66
3 Hb
Cb
-0.03
-0.55
0.18
3.59
-3.68
-0.08
11.75
10.07
0.38
a See group labeling in Scheme 1. H ) 1H NMR {400 MHz}, ∆ (δH) for the proton(s) in CD3CN at 293K. C ) 13C NMR {100.6 MHz}, ∆ (δC) for the
carbon atom(s) in CD3CN at 293K. - ) Upfield shift. b At 233K (see main text).
in CH3CN (for K+, ∆E1/2 ) -30 mV) and was assigned to
an important electronic reorganization of the molecule.22 In
case of the ligand 2, the nature of this uncommon cathodic
shift is developed in section 5.
Andrews et al.,5 studying the electrochemical properties
of the free CO related complex [(C5H5)Fe(C5H4CHdCHC6H4-
NMe2)], bearing an unsaturated link, have shown that the
complexation of the Li+ cation by the nitrogen atom induced
the disappearance of the dialkylamine oxidation wave. This
electrochemical behavior is reminiscent of that obtained with
compounds 1, 2, and 3 in the presense of Ca2+ and indicates
that such a nitrogen complexation could also occur with
compounds 1-3.
itself. The aim of this study was to clarify, as suggested by
the electrochemical analysis, that the amine moiety and/or
the CO function could be involved in this process, and to
quantify this interaction by determining its association
constant(s).
3. NMR Study. A. Ca2+ Interaction with Compounds
1, 2, and 3 and their Protonation Reaction. When treated
with 1 equiv of Ca(CF3SO3)2 salt, an orange solution of
compound 1 or a red solution of compound 2 or 3 in CH3-
CN instantaneously turned deep red. When this mixture was
1
evaporated to dryness and the H NMR spectra of the red
residue were recorded in CDCl3, only the free ferrocenyl
ligand L (1, 2, or 3) was recovered. In contrast, in CD3CN,
NMR spectra were indicative of a ligand-Ca2+ interaction.
To properly ascertain the variations of the shift observed,
2D NMR (400 MHz, CD3CN) experiments were performed
in a 1:1 ligand/Ca2+ ratio. The atom labeling used is
Addition of Li+ to ferrocene bis-tertiary amide [Fe(C5H4-
CONR2)2] also resulted in a shift of the ferrocene oxidation
wave to more positive potentials (<65 mV).23 Also when
this compound incorporates a nitrogen atom and a CO
function, the Li+ cation is binding the ligand through
carbonyl oxygen donor atoms. In contrast, the monosubsti-
tuted compound [(C5H5)Fe(C5H4CONMe2)] was insensitive
to the presence of this cation. From these studies, it appears
that cation interaction with analogues complexes of 1, 2, and
3 is not always predictable as illustrated by the versatile
electrochemical affinity of the CO function toward Li+. These
latter examples indicated to us that a Ca2+-CO complexation
could also occur with compounds 1-3.
So far, no results have been reported regarding the
electrochemical ability of these three literature-cited com-
pounds toward Ca2+ addition. However, considering (i) the
aboved mentionned results established in refs 5 and 23, and
(ii) the changes observed by cyclic voltammetry for our
compounds upon calcium addition, it appears that the Ca2+
complexation process could involve the whole organic part
of these molecules because both their oxidation and reduction
processes were entirely perturbed. A thorough NMR study
was therefore undertaken in order to get further insight into
the direct ligand-Ca2+ complexation (or interaction) process
1
indicated in Scheme 1. After analysis, in H NMR spectra
(see Table 5 (a) calcium addition), the main feature observed
was the clear deshielding of the Hb proton of the olefinic
group (0.14-0.24 ppm), whereas the corresponding Ha
proton moved only slightly (0.01-0.06 ppm). For com-
pounds 1 and 2 the deshieldings observed for the He and Hf
protons are nearly identical, and significantly more important
than that observed for compound 3. Considering now the
second olefinic group, in molecule 2 proton Hh was more
affected by the interaction than proton Hg. In molecule 3,
Hi and Hj protons presented very close 1H NMR character-
istics when compared with the Ha and Hb protons. Consider-
ing now the 13C NMR spectra, significant variations were
also noticed: for example, the CO group and the olefinic
carbon CHb shifted downfield. For the three ligands, the NEt2
and NMe2 groups (N-CH protons) were the only groups to
be insensitive to the Ca2+ addition, showing they were not
involved in this interaction. All these features clearly
indicated how the unsaturated C5H4CO(CHdCH)n (n ) 1,
2) or C5H4CHdCHCOCHdCHs part of the molecule,
including the Cp rings, contributes to the electronic interac-
tion with the cation through the link. The electrostatic
attraction between the Ca2+ and the negative electron density
of the carbonyl group is the key point of this interaction.24
(22) Beer, P. D.; Danks, J. P.; Hesek, D.; McAleer, J. F. J. Chem. Soc.,
Chem. Commun. 1993, 1735.
(23) Beer, P. D.; Sikanyika, H.; Blackburn, C., McAleer, J. F. J. Organomet.
Chem. 1988, 350, C15.
Inorganic Chemistry, Vol. 43, No. 6, 2004 2069

Maynadie´ et al.
To investigate the complexation at the nitrogen atom,
compounds 1, 2, and 3 were then protonated. In CH3CN,
reaction of compounds 1, 2, and 3 with HBF4‚Et2O in 1:1
stoichiometry turned the solution from orange or red to pink
and afforded the protonated species [1H][BF4] (4), [2H][BF4]
(5), and [3H][BF4] (6), respectively. The compounds 4-6
were isolated in good yields (78-90%). Their characteriza-
tion was fully achieved by 1H and 13C 2D NMR experiments.
In the 1H NMR spectra (CD3CN, 400 MHz) the protonation
reaction has been confirmed by the appearance of a new
signal at δ ) 8.64, 9.05, and 8.79 ppm, respectively,
attributed to the proton of the NH+ group.1e,25a In molecules
4 and 6, the NCH2-groups appeared at downfield shift
position compared with 1 and 3 respectively, as complex
multiplets (i.e., δ ) 3.69 (dm), 3.62 (dm)), which was
consistent with an additive coupling with the acidic proton
and the ammonium quaternarization. In the solid state (IR
spectrum, KBr), the ν (NH+) elongation vibrations are
located in the 3030-3100 cm-1 expected range of val-
ues.1e,2b,25b Elemental analyses and mass spectra are also in
agreement with the proposed formula as described in the
Experimental Section.
Figure 5. Chemical shift variations of the mentioned protons of 1 (7.4 ×
10-3 M) (top), and of 2 (1 × 10-2 M) (bottom), versus the Ca(CF3SO3)2
concentration in CD3CN. See atom labeling in Scheme 1. Experimental
values (dots) and calculated (lines) curves obtained by fitting the data.
Considering more specifically Table 5(b) (protonation),
several NMR characteristic features appeared. In each case
the molecules were totally affected by this event as shown
by all 1H and 13C NMR shift variations. For 3, the reported
data at 233 K are very close to those obtained at 293 K, but
the assignment was clearer for some groups. The CHc, CHe,
CHf, and CO groups presented the smallest 13C NMR
variations. As expected, strong perturbations occurred in the
1
vicinity of the nitrogen site. In H NMR, the phenyl ring
was seriously perturbed, the same ∆(δHd) value of 0.82 ((
0.01) ppm was observed for the three compounds. The NCH
protons were shifted downfield (+ 0.17 to 0.35 ppm) but
this perturbation was as important as that observed for the
Ha proton (0.31 to 0.48 ppm). For both the compounds 2
and 3, the olefinic group next to the phenyl group is more
affected than the other.
To sum up, these results clearly highlight that compounds
1, 2, and 3 have similar NMR behaviors toward protonation
that strongly contrast with the one observed upon interaction
with calcium.
B. Treatment of the NMR Data and Proposition of a
Ca2+ Interaction Model. To determine the stoichiometry
of the calcium adduct(s) and the number of species involved,
1
the interaction process was further studied by H NMR
spectroscopy. The chemical shift variations of all the protons
of 1, 2, and 3 were plotted versus the Ca(CF3SO3)2
concentration in CD3CN. In Figure 5 (points), a similar
decreasing effect following the order ∆δHb> ∆δHe and
Figure 6. Chemical shift variations of the mentioned protons of 3 (7.6 ×
10-3 M) (top) versus the Ca(CF3SO3) 2 concentration in CD3CN, and detailed
view (bottom) for the Ha, Hi, Hc, He, and Cp protons. See atom labeling
in Scheme 1. Experimental values (dots) and calculated (lines) curves
obtained by fitting the data.
(24) (a) Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J. J.; Ibers, J. A.
Organomet. Chem. 1974, 65, 253. (b) Marcotte, N.; Fery-Forgues,
S.; Lavabre, D.; Marguet, S.; Pivovarenko, V. G. J. Phys. Chem. A
1999, 103, 3163.
(25) (a) Silverstein, R. M.; Bassler, G. C.; Morril, T. C. Spectrometric
Identification of Organic Compounds, 4th ed.; J. Wiley and Sons: New
York, 1981; Ch. 3, p 198. (b) Bru¨gge, H.-J.; Carboo, D.; von Deuten,
K.; Kno¨chel, A.; Kopf, J.; Dreissig, W. J. Am. Chem. Soc. 1986, 108,
107.
∆δHf > (∆δHh)> ∆δCp> ∆δHa is observed for 1 and 2.
The shift variations are often weaker for the other protons
and null for the alkyle protons. As provided in Figure 6, in
the case of compound 3 the shift variation is rather symmetric
with respect to the CO function; see in particular, the couples
of curves (Ha, Hi), (Hb, Hj), and (Hc, He).
2070 Inorganic Chemistry, Vol. 43, No. 6, 2004

Calcium Sensing by Ferrocenyl DeriWatiWes
Table 6. Association Constants Related to the LM, L2M, LM2, and
L3M Species for Ligands 1, 2, and 3 with Calcium in Acetonitrile
Determined by Processing the NMR Dataa
LM
L2M
LM2
L3M
compound
K1, M-1
K2, M-1
K3, M-1
K4, M-1
1
2
3
11.1
81.0
40.9
0
6.6
0
3.8
40.9
308.0
0
0
3.34 × 103
a Values given with (15% error.
In fact, ligands 1-3 exhibited clear NMR spectra, and a
continuous shift of their sharp peaks is observed during the
calcium titration experiments. This indicates the presence
of fast equilibria on the NMR time-scale. So, for each
calcium concentration, only a time-averaged spectrum of the
ligand and/or the ligand-calcium complexes is observed.
Any observed chemical shift δHx is, in reality, a mole
fraction weighted average of the shifts observed in the free
and complexed molecules.
Figure 7. Concentration of the formed species versus calcium concentra-
tion, [3] ) 7.6 × 10-3 M.
compounds after treatment of UV-vis data.24b It is note-
worthy that substoichiometric compounds L2M and L3M are
minor species in the case of 1, and L2M is present at low
concentration (<1 equiv Ca2+) for 3. In the range of
concentration considered (7.4 × 10-3 to 10-2 M) for the three
compounds several species compete and an example is
provided in Figure 7 for compound 3.
δH )
δH X ) δH LX + δH LMXLM
+
∑
x
x
x
L
x
2δHxL MXL M + δHxLM XLM + 3δHxL MXL M
2
2
3
2
2
3
The lack of unique stoichiometry may appear as somewhat
troubling and is still uncommon in the literature for ferro-
cenyl compounds. The existence of several species in
equilibrium reflects different possible interactions between
the ligand’s donor atoms and the Ca2+ ion. A screening of
the Cambridge data file indicates that the Ca2+ may interact
with six to nine donor atoms in the case of organic ligand
exhibiting the sCdC-CdO linkage, which could account
for the presence of substoichiometric compounds of LnM
type where L ) 1, 2.28 The triflate ion may also interact
with the Ca2+ ion, thereby increasing the number and nature
of possible donor atoms and thus existing interactions, which
could help understand the formation of LMm species.29
However, in the reported equilibria, weak intermolecular
interactions (for example with adjacent phenyl group) or
electrostatic interactions, rather than classical complexation
reactions, may also be considered.
where L is the ferrocenyl ligand 1, 2, 3, M is the calcium
cation, and X is the mole fraction of the considered species.
The curve-fitting method presents the clear advantage that
it can accommodate several LnMm complex binding models.26
A previously reported method24b,27 was used to determine
the association constants for the different LnMm complexes
present in solution. The following equilibria were considered.
L + M {kk } LM
K1 ) k1/k-1
K2 ) k2/k-2
K3 ) k3/k-3
K4 ) k4/k-4
1
-1
LM + L {kk } L2M
2
-2
LM + M {kk } LM2
3
-3
L2M + L { k } L3M
4
k-4
To have experimental proof of the existence of these
species from an additional technique, mass spectra were
recorded with samples 1, 2, and 3 containing 0.5, 1, and 2
equiv of salt, respectively, in the same conditions. The
positive FAB technique using an MNBA matrix revealed
all the expected peaks for the three compounds (see
Experimental Section), confirming thus that strong enough
interactions exist between the different ligands and Ca(CF3-
SO3)+.
In Figures 5 and 6, the points are experimental and the curves
were fitted to the experimental data. Complete fits could not
be obtained without taking into account the existence of three
species of different stoichiometries for 1 and 3 and of two
species of different stoichiometries for compound 2. The
species were for 1, LM, L2M, L3M; for 3, LM, L2M, LM2;
and for 2, LM, LM2. The corresponding association constants
are reported in Table 6. For each ligand the calculated
concentrations of the species formed versus calcium con-
centration indicate that 2M and 3M are formed more
quantitatively than 1M but that the LM species is always
present in a large Ca2+ concentration range (see S5, S6, and
Figure 7). Let us remark that LM2 association constants are
quite weaker than those of their LM corresponding species.
LM2 species have already been proposed for related organic
Furthermore, NMR tests performed with 1 in the presence
of other cited cations (vide supra) resulted in no (Li+) or
weak proton shift variations when compared to those due to
(28) For example: (a) Sato, T.; Takeda, H.; Sakai, K.; Tsubomura, T. Inorg.
Chim. Acta 1996, 246, 413. (b) Arunasalam, V.-C.; Baxter, I.; Drake,
S. R.; Hurtouse, M. B.; Malik, K. M. A.; Miller, S. A. S.; Mingos, D.
M. P.; Otway, D. J. J. Chem. Soc., Dalton Trans. 1997, 1331.
(29) (a) Lawrance, G. A. Chem. ReV. 1986, 86, 17. (b) Frankland, A. D.;
Hitchcok, P. B.; Lappert, M. F.; Lawless, G. A. J. Chem. Soc., Chem.
Commun. 1994, 2435. (c) Onoda, A.; Yamada, Y.; Doi, M.; Okamura,
T.; Ueyama, N. Inorg. Chem. 2001, 40, 516.
(26) (a) Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311. (b) Fielding,
L. Tetrahedron 2000, 56, 6151.
(27) Fery-Forgues, S.; Lavabre, D.; Rochal, D. New J. Chem. 1988, 22,
1531.
Inorganic Chemistry, Vol. 43, No. 6, 2004 2071

Maynadie´ et al.
Let us remark, whereas insertion of an olefinic fragment
in 1 before the CO function drastically decreases the
oxidation potential of the organic part (Figure 3b), this
modification induces no change of the oxidation potential
of the iron couple in its protonated form [1H+]: 4 and 5
have approximatively the same E1/2 value (0.70 V). But, the
electronic communication which exists between the nitrogen
atom and the ferrocene center decreases as shown by the
lowering of the |∆E1/2| observed values for 4-6. Moreover,
considering the C1-N1 and C1a-N1 longer than 13 Å
distances in molecules 2 and 3, the existence of an intramo-
lecular through-space interaction according to Plenio et al.’s
model has been ruled out.30
Figure 8. Segmented cyclic voltammograms of compound 3 before
(dashed line) and after (solid line) addition of 1 equiv of HBF4‚Et2O.
Experimental conditions: Pt electrode (1 mm diameter) in 0.1 M solution
of nNBu4BF4 in CH3CN, scan rate 100 mV s-1, ligand concentration 10-3
M; reference electrode SCE.
In conclusion, in contrast to NMR studies, when consider-
ing Ca2+ or H+ addition, electrochemical measurements gave
nearly the same data for the three compounds 1, 2, and 3.
To clarify this apparent discrepancy a detailed series of
complementary NMR experiments was undertaken.
interaction with calcium. In parallel, when an equimolar
mixture of Li+, Na+, K+, Ba2+, (4 equiv) in the presence of
1 equiv of Ca2+ was added to an acetonitrile electrochemical
solution of 1, the same electrochemical characteristics as
induced by Ca2+ alone were obtained. These last NMR and
electrochemical results are in favor of selectivity for elec-
trochemical detection of Ca2+ by 1. Finally, repeated attempts
to isolate calcium-ligand complexes of these receptors in
the solid phase were unsuccessful.
4. Electrochemical Properties of the Protonated Com-
pounds 4, 5, and 6. In Section 2, according to electrochem-
istry studies, both the CO and the amino functions could be
suspected to be involved in the detection process. Examina-
tion of the ligand-Ca2+ interaction has shown in Section 3
that only the CO function was effectively involved in this
process. It was then important to study the electrochemical
properties of ligands 4, 5, and 6 whose the nitrogen sites
were protonated.
The electrochemical properties of compounds 4, 5, and 6
were investigated under the previously reported conditions.
In oxidation, for each compound, the results obtained for
the protonated species are similar to those obtained with their
corresponding deprotonated forms (1, 2, and 3) in the
presence of one equiv of calcium. In reduction, the currents
corresponding to the “CO” reduction processes observed in
the range from -1.79 to -1.53 V are weak and cannot be
quantified. Passivation phenomena attributed to nonconduct-
ing deposits have been observed. The main characteristic
feature is the appearance of the new irreversible reduction
process around -0.20 V as in the case of calcium addition
(vide supra). This last reduction process was attributed to
the reduction of the NH+ function. To verify this hypothesis,
the stepwise addition of H+ (until 1 equiv) to a solution of
each compound was also undertaken. In CV, these experi-
ences allowed again the recovery of the same phenomena
in oxidation or in reduction. In each case, the final intensity
of the wave observed for the NH+ reduction process was as
high as that obtained for the corresponding Fe(II/III) oxida-
tion process, which is in agreement with our attribution. This
is illustrated in Figure 8 in the case of compound 3.
5. Complementary NMR and Electrochemical Inves-
tigations: Link between Calcium Interaction and its
Detection? A. NMR Study. At this point, the paramount
question is as follows: how could calcium interaction with
the ligand and the protonation, involving different molecular
sites, lead to the same electrochemical detection? A peculiar
role of the electrolyte was suspected. Therefore, the calcium
interaction process was first reexamined in the presence of
electrolyte. It has been verified that addition of Et4NBF4 (or
nBu4NBF4) to an orange solution of compound 1 (1 × 10-2
M) in 1:1 salt/ligand or 5:1 ratio has no effect (over a 48 h
period). Subsequent addition of one equiv of Ca(CF3SO3)2
to these solutions turned them red and Ca2+ interaction could
be observed. After a 4 h period, the solution became pink
and the protonated compound [1H]+ was the unique iron
compound detected in solution (see Figure 9). It exhibits a
broad downfield shift around 9.2 ppm, which exchanges at
low rate (see S7). This signal is sensitive to the presence of
other components of the mixture: as small amount of water
and CF3SO3 anion. This anion can compete with BF4 to
yield the [1H][CF3SO3] species whose NH+ shift is 9.5 ppm
in CD3CN (the other NMR shifts are the same than those of
4).
When the Ca(CF3SO3)2 salt was added first to a solution
of compound 1 in 1:1 ratio, the ligand interaction was stable
over a 48 h period and the solution stayed red. Subsequent
addition of Et4NBF4 in 1:1 salt/ligand ratio or in 0.2:1 ratio
to this mixture led to a pink solution of the protonated
compound after 5 and 17 h, respectively.
-
-
Compounds 2 and 3 behaved as compound 1. When 1
equiv of Ca(CF3SO3)2 was added to a 1:1 mixture of ligand/
Et4NBF4 salt, the red solutions turned deep violet after 4 h.
Their respective protonated forms were identified as final
and unique iron products.
n
The triflate supporting electrolyte salt Bu4NCF3SO3 did
not react with a solution of compound 1. In contrast with
previous results, subsequent addition of Ca(CF3SO3)2 led to
(30) Plenio, H.; Yang, J.; Diodone, R.; Heinze, J. Inorg. Chem. 1994, 33,
4098.
2072 Inorganic Chemistry, Vol. 43, No. 6, 2004

Calcium Sensing by Ferrocenyl DeriWatiWes
Figure 9. 1H NMR (250 MHz, CD3CN) spectra in the 0.5-8.5 ppm range of (a) 1, (b) 1 + 1 equiv Et4NBF4, (c) mixture (b) + 1 equiv of Ca2+, (d) mixture
(c) after 4 h. * H2O.
the stable red ligand-Ca2+ interaction solution over a 24 h
allowed Ca(CF3SO3)2 electrochemical detection especially
by a ∆E1/2 variation of the Fe(II)/Fe(III) couple of ≈60 mV
for compound 1. Changing the supporting electrolyte by
nBu4NCF3SO3 or nBu4NClO4 induced no significant shift of
the iron potential; even in Ca2+ excess (15 equiv). Water
has also been added to the [1-Ca2+-nBu4NClO4] mixture
but no change was observed. Changing now the nature of
the calcium salt by using Ca(ClO4)2 but keeping the BF4
supporting electrolyte also allowed the same clear detection.
period. In this case, no protonation reaction was observed.
-
Consequently, it appears that a small quantity of BF4 ion
is required to induce a clean protonation of the iron
compounds when they interact with Ca2+ at NMR concentra-
tions in the presence of ammonium salt. These results clearly
highlight why electrochemical detection of Ca(CF3SO3)2 may
give rise to the same voltammograms as those obtained with
the corresponding isolated protonated products or by their
in situ protonation.
B. Electrochemical Study. Concerning cation electro-
chemical detection, competition between complexation and
protonation has already been reported but scarcely devel-
oped.31 In our case, it was important to see whether our NMR
conclusions could support electrochemical conditions, espe-
cially with an important electrolyte salt/ligand ratio. Detection
of the Ca2+ cation was reinvestigated by varying the nature
of the supporting electrolyte or of the Ca2+compound. As
explained earlier, the use of BF4 salts (Et4NBF4 or nBu4NBF4)
n
This last detection became inefficient if Bu4NCF3SO3 or
nBu4NClO4 supporting electrolytes were used.
We have also noticed that clean detection of Ca(BF4)2 was
operative whatever the supporting electrolyte used (nBu4NBF4
or nBu4NCF3SO3) and gave the same iron potential shift (60
mV) as in the previously reported conditions. Addition of
Ca(BF4)2 to an orange solution of 1 in 1:1 stoichiometry
immediately led to a pink solution of the protonated
compound 4. In this case, addition of the supporting
electrolyte is not required, probably because of the low
(31) Beer, P. D.; Smith, D. K. J. Chem. Soc., Dalton Trans. 1998, 417.
Inorganic Chemistry, Vol. 43, No. 6, 2004 2073

Maynadie´ et al.
degree of purity of this calcium salt (70%) when compared
to the others.
thus a stronger interaction than with other tested cations. This
interaction gives rise to the formation of several species of
different stoichiometries in equilibria, which is uncommon
for ferrocenyl compounds. In electrochemistry the detection
process is signaled by drastic changes, among them the
characteristic shift of the half wave potential of the Fe(II)/
Fe(III) couple (∆E1/2). In parallel, it has also been shown
that protonation of 1, 2, and 3 arises at the R group and that
a through-bond electronic communication along the conju-
gated chain leads to modifications in cyclic voltammetry
similar to those resulting from direct calcium interaction. The
combination of different studies led us to the following
explanation: Under our standard electrochemical conditions,
calcium interaction is followed by protonation and this
phenomenon requires the presence of small quantities of
In conclusion, in the electrochemical conditions the (Ca2+,
-
BF4 ) couple is required for the formation of the protonated
species, which allows the calcium detection. The traces of
acid introduced by the nBu4NCF3SO3 electrolyte or the
presence of a hydrated perchlorate electrolyte salt are not
sufficient to induce this sensing in our standard conditions,
contrary to previously reported studies on this topic.31
It has already been reported that Ca2+ cation can protonate
a receptor due to the use of hydrated metal perchlorate salts
with ionizable protons.31 As shown by NMR and electro-
chemistry, our ligands are stable in solution in the presence
of electrolytes, and their electrochemical characteristics are
the same whatever the electrolyte used. Therefore, there is
no ligand-electrolyte interaction. The ligand-Ca2+ species
may interact with the oxygen atom of a water molecule
whose one proton becomes more acid. This proton, in the
-
BF4 anion and of a proton source, probably water. It is
noteworthy that the CO function (i) plays a crucial role as
coordination site for the interaction, and (ii) does not interrupt
the electronic communication between the terminal N donor
and the redox ferrocenyl center which could sense the
variation of the electronic density. This last remark strength-
ens the same observation made for organic nonconventional
keto spaced chromophores.32 Considering now that proto-
nation is the ultimate step of the Ca2+ electrochemical
detection, the Ca2+ sensing results obtained for 1 and 3 are
now clearer. Actually, it has also been reported that through-
bond effects are reduced for related compounds that contain
a longer conjugated link between the ferrocene center and
the binding site.33 Thus, increasing the distance between the
redox center and the complexing site could decrease the ∆E1/2
value. This assumption relies on knowledge of the exact
nature of the complexation site and its distance to the redox
center. The cathodic shift observed in the case of 2 is in
connection with its very nature: the oxidation potential of
the initial Fe(II)/Fe(III) couple belongs to a [Fe(II)N+•]
species and is more important than that of the final protonated
form [Fe(II)NH+]. We have illustrated in detail, with
compounds 1, 2, and 3, how detection or sensing is here not
a simple Ca2+ molecular interaction or recognition process,
as it may occur elsewhere.34 Some elements concerning the
pathway from Ca2+ interaction to its detection have been
clarified. These results also highlight some dependence of
this sensing on experimental conditions: a good example is
the choice of the different salts used, i.e., reactants and
supporting electrolytes. The ligands used are thus capable
of detecting the “Ca-BF4” pair.
-
presence of the BF4 anion, is then able to protonate the
amino part of the ligand, which is not involved in the ligand-
Ca2+ interaction process. As previously explained (NMR
experiment), a sub-stoichiometric amount of BF4- electrolyte
could be used to induce ligand protonation in the presence
of Ca2+ salt. Protonation does not occur if the BF4- anion is
-
-
replaced by CF3SO3 or ClO4 anion.
How could we now explain the unexpected cathodic shift
observed upon calcium addition with ligand 2? In section
2B, the E1/2 shifts observed for ligands 1, 2, and 3 upon Ca2+
addition correspond, in fact, to those induced by ligands
protonation. Thus, for ligands 1 and 3, the ∆E1/2 of the Fe-
(II)/Fe(III) couple is positive and represents the difference
of the oxidation potential between the protonated form, [Fe-
(II)NH+] (E1/2 ) 0.70 and 0.57 V), and the neutral form,
[Fe(II)N] (E1/2 ) 0.64 and 0.54 V), for each compound. In
compound 2, the first oxidation potential of the molecule is
attributed to the organic amino moiety, and it precedes now
the iron oxidation potential. Consequently, oxidation of 2
first leads to the formation of a cationic radical species: [Fe-
(II)N+•] whose E1/2(Fe) value (0.72 V) is in this case more
important than that observed for its corresponding [Fe(II)-
NH+] form (0.69 V), where the calculated ∆E1/2 is negative,
and the observed shift is cathodic. So the unexpected cathodic
shift observed for the iron couple of molecule 2 is in
connection with its uncommon nature when compared to
classical electrochemical ferrocenyl sensors such as 1 and
3, whose first oxidation potential is due to the iron couple
in the protonated and neutral forms.
Experimental Section
Concluding Remarks
Materials. Toluene was distilled over sodium/benzophenone.
Pentane, dichloromethane, and CH3CN (pure SDS) were distilled
over CaH2 and stored under argon. EtOH analytical grade (purex
Noticeable electrochemical Ca2+ detection was possible
when using new ligands 1, 2, and 3 containing a purely
organic and original ion sensor subunit with an R-amino
complexing moiety (sCOCHdCHC6H4spR, R ) NEt2 or
NMe2). This sensing relies on an interaction that occurs
between Ca2+ and CO moiety of the receptors as demon-
strated by a thorough NMR study. This preferred Ca2+
interaction could be partially explained in terms of high
charge density and oxygen affinity of Ca2+, which induces
(32) Maertens, C.; Detrembleur, C.; Dubois, P.; Je´roˆme, R.; Boutton, C.;
Persoons, A.; Kogej, T.; Bredas, J. L. Chem. Eur. J. 1999, 5, 369.
(33) (a) Carr, J. D.; Coles, S. J.; Hurthouse, M. B.; Light, M. E.; Munro,
E. L.; Tucker J. H. R.; Westwood, J. Organometallics 2000, 19, 3312.
(b) Chambron, J. C.; Coudret, C.; Sauvage, J. P. New J. Chem. 1992,
16, 361. (c) Bhadhade, M. M.; Das, A.; Jeffery, J. C.; McCleverty, J.
A.; Navas Badiola, J. A.; Ward, M. D. J. Chem. Soc., Dalton Trans.
1995, 2769.
(34) Frabbrizzi, L. Coord. Chem. ReV. 2000, 205, 1.
2074 Inorganic Chemistry, Vol. 43, No. 6, 2004

Calcium Sensing by Ferrocenyl DeriWatiWes
SDS) was simply degassed. (C5H5)Fe(C5H4CHO) (98%), (C5H5)Fe-
(C5H4COMe) (95%), (Aldrich), CHOC6H4NEt2 (99%), CHOCHd
CHC6H5 (98%) (Fluka), MeCOCHdCHC6H5 (99%), CHOCHd
CHC6H4NMe2 (98%), CHOCHdCHC6H4NEt2 (99%), HBF4 54%
in Et2O (Aldrich). Calcium salts: Ca(CF3SO3)2 (96%) (Strem), Ca-
(ClO4)2 4H2O (99%), CaBF4‚xH2O (70%) (Aldrich) were used
without purification. Other salts: LiCF3SO3 (99%) (Strem), NaCF3-
SO3 (97%), Ba(CF3SO3)2 (97%) (Fluka), KCF3SO3 (99%) (Acros),
Zn(CF3SO3)2 (98%) (Aldrich), Mg(CF3SO3)2 (98%) (Fluka). (C6H5-
CHdCH)CO(CHdCHC6H4NEt2), MeCOCHdCHC6H4NEt2, and
CO(CHdCHC6H4NEt2)2 were prepared according to the general
procedure of Olomucki and Le Gall35 and recrystallized in
experimental conditions already described.36 (C5H5)Fe(C5H4CHd
CHCHO) was prepared according a published procedure.37
(C5H5)Fe(C5H4CHdCHCOCHdCHC6H5) was prepared by reaction
of (C5H5)Fe(C5H4CHO) and MeCOCHdCHC6H5 according to our
published procedure.2b
With the above reference, E1/2 ) 0.45 V vs SCE was obtained for
1 mM ferrocene (estimated experimental uncertainty of (10 mV).
Cyclic voltammetry was performed in the potential range -2 to 2
V versus SCE scanning from 0 toward 2 V/SCE for oxidation
studies (and from 0 toward -2 V/SCE for reduction studies) at 0.1
V s-1, at room temperature. Before each measurement, the electrode
was polished with Emery paper (Norton A621). To calculate the
half wave potential (E1/2), the method is as follows: a quasi steady
state behavior (at Pt working electrode of 1-mm diameter) is
obtained by the use of linear voltammetry at 5 mV s-1
.
Proton NMR Titration Studies. Proton NMR titrations were
typically performed as follows. A solution (500 µL) of the receptor
in a deuterated solvent (10-2 M) was added (using a microsyringe)
into NMR tubes containing the appropriate quantities of solid Ca-
(CF3SO3)2 salt under inert atmosphere, while the NMR spectrum
of the receptor was monitored. The samples of solid calcium were
prepared by evaporating the corresponding calculated volumes of
a calcium guest solution (10-2 M) in acetonitrile. Stability constants
were evaluated from titration data using the indicated method in
the main text.
Warning. Perchlorate salts are hazardous because of the pos-
sibility of explosion!
General Instrumentation and Procedures. All syntheses were
performed under a nitrogen atmosphere using standard Schlenk tube
techniques. IR spectra were recorded on a Perkin-Elmer GX FT-
IR spectrophotometer. Samples were run as KBr pellets. Elemental
analyses were carried out on a Perkin-Elmer 2400 B analyzer at
the L. C. C. Microanalytical Laboratory in Toulouse. Mass spectra
were obtained at the Service Commun de Spectrome´trie de Masse
de l’Universite´ Paul Sabatier et du CNRS de Toulouse (fast atom
bombardment, FAB>0; or desorption chemical ionization, DCI)
were performed on a Nermag R 10-10H spectrometer. A 9 kV
xenon atom beam was used to desorb samples from the 3-nitroben-
zyl alcohol matrix. Other spectra were performed on a triple
quadrupole mass spectrometer (Perkin-Elmer Sciex API 365) using
electrospray as the ionization mode. The infusion rate was 5 µL/
min. 1H and 13C NMR spectra have been performed on Bruker AC
[(C5H5)Fe(C5H4CO(CHdCH)2C6H5)]. A mixture of (C5H5)Fe-
(C5H4COMe) (2.19 × 10-3 mol) and of NaOH (1.1 × 10-2 mol)
was solved in ethanol (15 mL). A 300-µL aliquot of CHOCHd
CHC6H5 (2.41 × 10-3 mol) was slowly added to the light-protected
stirred solution. The mixture was evaporated to dryness and the
residue was dissolved in CH2Cl2 (40 mL). The solution was filtered.
After evaporation, the product was washed with pentane (50 mL
× 2). The red-violet powder was dried under vacuum and obtained
in 78% yield. MS-FAB: 342 [M] +. Anal. Calcd for 1, C21H18-
1
OFe: C, 73.71; H, 5.30; N. Found: C, 73.52; H, 5.18. H NMR
(300 MHz, CDCl3, 298 K): δ 4.23 (s, 5 H, C5H5); (4.59, 4.89)
(each t, 2 H, 3J ) 2.1 Hz, C5H4); 6.72 (d, 1 H, 3J ) 15.0 Hz, CH);
7.03 (m, 2 H, C6H5); 7.37 (m, 3 H, C6H5, CH); 7.58 (m, 3 H, C6H5,
CH).
200, AM 250, DPX 300, and AMX 400 spectrometers. 1H and 13
C
Syntheses of Ferrocenyl Compounds 1, 2, and 3. In a typical
procedure, a mixture of the appropriate reactants in 1:1 stoichiom-
etry (10-3 M) and 5 equiv of NaOH was dissolved in ethanol (30
mL) and stirred for 20 h for 1 and 2, or 5 h for 3, at room
temperature. The mixture was evaporated to dryness and the residue
was dissolved in dichloromethane (50 mL). The solution was filtered
off and evaporated to dryness. The product was purified by column
chromatography on alumina (eluent: pentane/CH2Cl2). After evapo-
ration of the solvent, the product was washed with pentane (50 ×
2 mL) and dried for several hours to afford the desired products as
deep orange, red-violet, and violet powders, respectively. Com-
pounds 1, 2, and 3 were obtained in 82, 77, and 72% yield,
respectively.
NMR spectra are referenced to external tetramethylsilane. For 2D
NMR experiments, the observation frequencies were in the range
400.13 MHz for 1H and 100.62 MHz for 13C. (JHH ) JHCH2HCH3) for
compounds 1, 2, and 3.
Electrochemical Studies. Voltammetric measurements were
carried out with a homemade potentiostat38 using the interrupt
method to minimize the uncompensated resistance (iR drop).
Experiments were performed at room temperature in an airtight
three-electrode cell connected to a vacuum/argon line. The reference
electrode consisted of a saturated calomel electrode (SCE) separated
from the solution by a bridge compartment filled with the same
solvent and supporting electrolyte solution. The counter electrode
was a platinum wire of ca. 1 cm2 apparent surface. The working
electrode was a Pt electrode (1 mm diameter). The supporting
[(C5H5)Fe(C5H4COCHdCHC6H4NEt2)] (1). 1H NMR (400
MHz, CD3CN, 293 K): δ 1.19 (t, 6 H,3JHH ) 6.8 Hz, CH3), 3.46
(q, 4 H,3JHH ) 6.8 Hz, CH2), 4.22 (s, 5 H, C5H5), 4.59 (t, 2 H,
n
electrolyte Bu4NBF4 (99%) (Fluka electrochemical grade), Et4-
3
3JHeHf ) 1.6 Hz, Hf), 4.93 (t, 2 H, JHeHf ) 1.6 Hz, He), 6.76 (d,
n
NBF4 (99%), or Bu4NCF3SO3 (99%) (Aldrich), were melted and
3
3
dried under vacuum for 1 h, and nBu4NClO4 (99%) (Fluka
electrochemical grade) was used as received and simply degassed
under argon. All solutions measured were 1.0 × 10-3 M in the
organometallic complex and 0.1 M in supporting electrolyte. The
solutions were degassed by bubbling argon before experiments.
2H, JHcHd ) 8.8 Hz, Hd), 7.09 (d, 1 H, JHaHb ) 15.2 Hz, Ha),
7.62 (d, 2 H, 3JHcHd ) 8.8 Hz, Hc), 7.63 (d, 1 H, 3JHaHb ) 15.2 Hz,
Hb).13C{1H} NMR (100.6 MHz, CD3CN, 293 K): δ 12.25 (s, CH3),
44.51 (s, CH2), 69.76 (s, CΗe), 70.19 (s, C5H5), 72.56 (s, CHf),
82.09 (s, CipsoC5H4), 111.69 (s, CΗd), 118.06 (s, CHa), 122.11 (s,
Cipso-C), 130.84 (s, CHc), 141.24 (s, CHb), 149.84 (s, Cipso-N),
192.52 (s, CO). MS-DCI: 388 [M + H]+. Anal. Calcd for 1, C23H25-
NOFe: C, 71.33; H, 6.51; N, 3.62. Found: C, 71.26; H, 6.60; N,
3.53.
(35) Olomucki, M.; Le Gall, J. Y. Bull. Soc. Chim. Fr. 1976, 9-10, 1467.
(36) Fery-Forgues, S.; Delavaux-Nicot, B.; Lavabre, D.; Rurack, K. J.
Photochem. Photobiol., A 2003, 155, 107.
(37) Mongin, C.; Ortin, Y.; Lugan, N.; Mathieu, R. Eur. J. Inorg. Chem.
1999, 5, 739.
(38) Cassoux, P.; Dartiguepeyron, R.; de Montauzon, D.; Tommasino, J.
B.; Fabre, P. L. Actual. Chim. 1994, 1, 49.
[(C5H5)Fe(C5H4CO(CHdCH)2C6H4NMe2)] (2). 1H NMR (400
MHz, CD3CN, 293 K): δ 3.01 (s, 6 H, CH3), 4.22 (s, 5 H, C5H5),
3
3
4.60 (t, 2 H, JHeHf ) 1,1 Hz, Hf), 4.85 (t, 2 H, JHeHf ) 1.1 Hz,
Inorganic Chemistry, Vol. 43, No. 6, 2004 2075

Maynadie´ et al.
3
3
He), 6.77 (d, 2H, JHcHd ) 9.0 Hz, Hd), 6.78 (dd, 1 H, JHaHb
)
[(C5H5)Fe(C5H4CHdCHCOCHdCHC6H4NHEt2)][BF4] (6).
3
15.4 Hz, 4JHaHg ) 0.6 Hz, Ηa), 6.94 (ddd, 1 H, 3JHgHh ) 15.4 Hz,
1H NMR (400 MHz, CD3CN, 233 K): δ 1.06 (t, 6 H, JHH ) 7.0
Hz, CH3), 3.62 (md, 4 H, 3JHH ) 7.0 Hz, CH2), 4.20 (s, 5 H, C5H5),
4.55 (s large, 2 H, Hf), 4.71 (s large, 2 H, He), 6.75 (d, 1H, 3J HiHj
) 15.9 Hz, Hi), 7.38 (d, 1 H, 3JHaHb ) 15.9 Hz, Ha), 7.56 (d, 2 H,
3JHH ) 8.5 Hz, Hd), 7.71 (d, 1 H, 3JHaHb ) 15.9 Hz, Hb), 7.78 (d,
1 H,3J HiHj ) 15.9 Hz, Hj), 7.97 (d, 2 H, 3JHcHd ) 8.5 Hz, Hc), 8.79
(s large, 1 H, N+H). 13C{1H} NMR (100.6 MHz, CD3CN, 233 K):
δ 10.35 (s, CH3), 54.59 (s, CH2), 69.56 (s, CHe), 70.23 (s, C5H5),
72.15 (s, CHf) 79.37 (s, CipsoC5H4), 123.48 (s, CHi), 123.48 (s,
CHd), 127.47 (s, CHa), 130.71 (s, CHc), 137.78 (s, Cipso-N), 137.86
(s, Cipso-C), 139.45 (s, CHb), 146.92 (s, CHj), 187.97 (s, CO).
(KBr, ν, cm-1): 3106, 3055, (ν, NH+). MS-FAB: 414 [M -
BF4]+. Anal. Calcd for 6, C25H28NOFe BF4: C, 59.92; H, 5.63; N,
2.79. Found: C, 59.84; H, 5.58; N, 2.71.
4
3
3JHgHb ) 10.6 Hz, JHaHg ) 0.6 Hz, Ηg), 7.03 (d, 1 H, JHgHh
)
15.4 Hz, Hh), 7.45 (dd, 2 H,3JHcHd ) 9.0 Hz, 4JHhHc ) 0.6 Hz, Hc),
7.47 (dd, 1 H, JHaHb ) 15.4 Hz, JHbHg ) 10.6 Hz, Hb).13C{1H}
NMR (100.6 MHz, CD3CN, 293 K): δ 39.83 (s, CH3), 69.73 (s,
CHe), 70.25 (s, C5H5), 72.76 (s, CHf), 81.79 (s, CipsoC5H4), 112.54
(s, CHd), 122.85 (s, CHg), 124.72 (s, Cipso-C), 124.91 (s, CHa),
3
3
128.91 (s, CHc), 141.72 (s, CHb), 141.86 (s, CHh), 151.65 (s, Cipso
-
N), 192.73 (s, CO). MS-DCI: 386 [M + H]+. Anal. Calcd for 2,
C23H23NOFe: C, 71.63; H, 5.97; N, 3.63. Found: C, 71.47; H,
5.63; N, 3.58.
[(C5H5)Fe(C5H4CHdCHCOCHdCHC6H4NEt2)] (3). 1H NMR
(400 MHz, CD3CN, 293 K): δ 1.18 (t, 6 H,3JHH ) 7.0 Hz, CH3),
3.45 (q, 4 H,3JHH ) 7.0 Hz, CH2), 4.20 (s, 5 H, C5H5), 4.50 (t, 2
Mass Spectrometry: Interaction of Compounds 1, 2, and 3
with Ca2+. The samples were prepared as for the NMR titrations.
3
3
H, JHeHf ) 1.8 Hz, Ηf), 4.67 (t, 2 H, JHeHf ) 1.8 Hz, Ηe), 6.75
3
3
(d, 2H, JHcHd ) 8.5 Hz, Hd), 6.78 (d, 1 H, JHiHj ) 15.7 Hz, Hi),
6.90 (d, 1 H, 3JHaHb ) 15.8 Hz, Ha), 7.55 (d, 2 H, 3JHcHd ) 8.5 Hz,
Hc), 7.60 (d, 1 H,3JHiHj ) 15.7 Hz, Hj), 7.62 (d, 1 H, 3JHaHb ) 15.8
Hz, CHb).13C{1H} NMR (100.6 MHz, CD3CN, 293 K): δ 12.24
(s, CH3), 44.52 (s, CH2), 69.17 (s, CHe), 70.00 (s, C5H5), 71.38 (s,
CHf), 80.21 (s, CipsoC5H4), 111.73 (s, CHd), 120.40 (s, CHa), 122.01
(s, Cipso-C), 124.03 (s, CHi), 130.79 (s, CHc), 143.13 (s, CHb),
143.33 (s, CHj), 150.00 (s, Cipso-N), 187.59 (s, CO). MS-DCI:
414 [M + H]+. Anal. Calcd for 3, C25H27NOFe: C, 72.65; H, 6.58;
N, 3.39. Found: C, 72.58; H, 6.48; N, 3.27.
-
For Compound 1. [1M-CF3SO3-] ) 576, [(1)2M-CF3SO3
]
) 963, [(1)3M-CF3SO3-] )1350.
For Compound 2. [2M-CF3SO3-] ) 574, [(2)M2-HCF3SO3]+
) 911, [(2)M2]+ ) 1061.
-
For Compound 3. [3M-CF3SO3-] ) 602, [(3)2M-CF3SO3
]
) 1015, [(3)M2-HCF3SO3]+ ) 939, [(3)M2]+ ) 1089.
[(C5H5)Fe(C5H4CO(CHdCH)2C6H4NEt2)] (7). This compound
was prepared by the same procedure as previous compounds with
FcCOMe (1.48 10-3 mol) and CHOCHdCHC6H4NEt2 as reactants
in 1:1 stoichiometry and isolated in 92% yield. 1H NMR (250 MHz,
Synthesis of [Tetrafluoroborate (1-)] Compounds of 1, 2,
and 3: 4, 5 and 6. HBF4‚Et2O (1 equiv) was slowly syringed into
a stirred solution of 1 or 2 or 3 (4 × 10-4 M) in acetonitrile (15
mL). The light-protected mixture solution was stirred for 4 h. After
solvent evaporation, the product was washed with ether (30 mL)
and pentane (40 mL) and dried under vacuum. A violet powder
was obtained in 90, 85, and 72% yield, respectively.
3
CD3CN, 297 K): δ 1.18 (t, 6 H, JHH ) 7.0 Hz, CH3); 3.44 (q, 4
3
H, JHH ) 7.0 Hz, CH2); 4.22 (s, 5 H, C5H5); (4.59, 4.85) (each t,
3
3
2 H, JHH ) 2.1 Hz, C5H4); (6.73, 7.41) (each d, 2H, JHH ) 9.0
Hz, C6H4); (6.77, 7.02) (each d, 1 H, 3JHH ) 15.3 Hz, CH); (6.91,
7.47) (each dd, 1 H, JHH ) 15.3 Hz, JHH ) 10.4 Hz, CH). 13C-
{1H} NMR (75.5 MHz, CD3CN, 298 K): δ 12.27 (s, CH3); 44.45
(s, CH2); (69.71, 72.69) (each s, C5H4); 70.23 (s, C5H5); 81.86 (s,
3
3
[(C5H5)Fe(C5H4COCHdCHC6H4NHEt2)][BF4] (4). 1H NMR
(400 MHz, CD3CN, 293 K): δ 1.15 (t, 6 H, 3JHH ) 7.2 Hz, CH3),
C
ipsoC5H4); (111.92, 129.24) (each s, C6H4); 123.82 (s, Cipso-C);
148.98 (s, Cipso-N); (122.24, 124.54, 141.87, 142.00) (each s, CH);
192.66 (s, CO). MS-FAB: 413 [M - H]+. Anal. Calcd for 7,
C25H27NOFe: C, 72.65; H, 6.58; N, 3.39. Found: C, 72.60; H,
6.62; N, 3.31.
3
3.69 (md, 4 H, JHH ) 7.2 Hz, CH2), 4.25 (s, 5 H, C5H5), 4.69 (t,
2 H, 3JHeHf ) 1.7 Hz, Hf), 4.98 (t, 2 H, 3JHeHf ) 1.7 Hz, He), 7.40
3
3
(d, 1 H, JHaHb ) 15.7 Hz, CHa), 7.58 (d large, 2 H, JHcHd ) 7.9
Hz, Hd), 7.74 (d, 1 H, 3JHaHb ) 15.7 Hz, Hb), 8.02 (d, 2 H, 3JHcHd
) 7.9 Hz, Hc), 8.64 (s large, 1 H, N+H).13C{1H} NMR (100.6
MHz, CD3CN, 293 K): δ 10.18 (s, CH3), 54.74 (s, CH2), 70.11 (s,
CHe), 70.46 (s, C5H5), 73.57 (s, CHf), 81.07 (s, CipsoC5H4), 123.31
(s, CHd), 126.52 (s, CHa), 130.77 (s, CHc), 137.74 (s, CHb), 138.00
(s, Cipso-N), 138.19 (s, Cipso-C), 192.45 (s, CO). (KBr, ν, cm-1):
3079, 3029 (ν, NH+). MS-DCI: 388 [M - BF4]+. Anal. Calcd for
4, C23H26NOFeBF4: C, 58.14; H, 5.52; N, 2.95. Found: C, 58.19;
H, 5.26; N, 2.90.
[(C5H5)Fe(C5H4(CHdCH)2CO(CHdCH)C6H4NEt2)] (8). A
mixture of (C5H5)Fe(C5H4CHdCHCHO), MeCOCHdCHC6H4-
NEt2, and NaOH in 1:1:1 stoichiometry (6.25 10-3 M) was dissolved
in ethanol (10 mL) and stirred for 24 h at room temperature. The
mixture was evaporated to dryness and the residue was dissolved
in dichloromethane (40 mL). The solution was filtered off and
evaporated to dryness. The residue was washed with pentane (2 ×
50 mL) and the product was extracted with hexane to afford a red-
violet powder in 69% yield. 1H NMR (300 MHz, CDCl 3, 298 K):
δ 1.22 (t, 6 H, 3JHH ) 6.9 Hz, CH3); 3.43 (q, 4 H, 3JHH ) 6.9 Hz,
[(C5H5)Fe(C5H4CO(CHdCH)2C6H4NHMe2)][BF4] (5). 1H NMR
(400 MHz, CD3CN, 293 K): δ 3.28 (s, 6 H, CH3), 4.22 (s, 5 H,
C5H5), 4.64 (t, 2 H, 3JHeHf ) 1.6 Hz, Hf), 4.87 (t, 2 H, 3JHeHf ) 1.6
3
CH2); 4.16 (s, 5 H, C5H5); (4.39, 4.49) (each t, 2 H, JHH ) 1.8
Hz, C5H4); 6.54 (d, 1 H, 3JHH ) 15.5 Hz, CH); 6.58 (dd, 1 H, 3JHH
3
3
3
Hz, He), 6.99 (d, 1 H, JHaHb ) 14.8 Hz, Ha), 7.10 (broad d, 1 H,
) 15.0 Hz, JHH ) 11.1 Hz, CH); (6.67, 7.49) (each d, 2 H, JHH
) 8.7 Hz, C6H4); (6.79, 7.68) (each d, 1 H, 3JHH ) 15.5 Hz, CH);
6.83 (d, 1 H, 3JHH ) 15.0 Hz, CH); 7.42 (dd, 1 H, 3JHH ) 15.5 Hz,
3JHH ) 11.1 Hz, CH). 13C{1H} NMR (100.6 MHz, CDCl3, 293 K):
δ 13.03 (s, CH3); 44.93 (s, CH2); (68.16, 70.69) (each s, C5H4);
70.00 (s, C5H5); 81.83 (s, CipsoC5H4); (111.65, 130.97) (each s,
C6H4); (121.06, 125.24, 127.10, 143.11, 141.71, 143.94) (each s,
CH); 122.20 (s, C ipso-C); 149.88 (s, C ipso-N); 189.55 (s, CO).
MS-DCI: 440 [M + H]+. Anal. Calcd for 8, C27H29NOFe: C,
73.81; H, 6.65; N, 3.19. Found: C, 73.99; H, 6.56; N, 3.12.
Crystallographic Study of Compounds 2 and 3. For these two
compounds data were collected at low-temperature T (180 K) on a
3JHgHh ) 15.6 Hz, CHh), 7.25 (dd, 1 H, JHgHh ) 15.6 Hz, JHbHg
3
3
3
3
) 10.9 Hz, Hg), 7.46 (dd, 1 H, JHaHb ) 14.8 Hz, JHgHb ) 10.9
Hz, Hb), 7.60 (d, 2H, 3JHcHd ) 8.7 Hz, Hd), 7.74 (d, 2 H,3JHcHd
)
8.7 Hz, Hc), 9.05 (s large, 1 H, NH+).13C{1H} NMR (100.6 MHz,
CD3CN, 293 K): δ 47.28 (s, CH3), 70.04 (s, CHe), 70.48 (s, C5H5),
73.50 (s, CHf), 81.42 (s, CipsoC5H4), 121.47 (s, CHd), 129.00 (s,
CHa), 129.17 (s, CHc), 130.18 (s, CHg), 138.20 (s, CHh), 138.84
(s, Cipso-C), 139.80 (s, CHb), 142.42 (s, Cipso-N), 193.34 (s, CO).
(KBr, ν, cm-1): 3095, 3033 (ν, NH+). MS-DCI: 386 [M - BF4]+.
Anal. Calcd for 5, C23H24NOFeBF4: C, 58.39; H, 5.11; N, 2.96.
Found: C, 58.37; H, 4.81; N, 3.08.
2076 Inorganic Chemistry, Vol. 43, No. 6, 2004

Calcium Sensing by Ferrocenyl DeriWatiWes
Stoe imaging plate diffraction system (IPDS), equipped with an
Oxford Cryosystems cryostream cooler device and using a graphite-
monochromated Mo KR radiation (λ ) 0.71073 Å). Final unit cell
parameters were obtained by means of a least-squares refinement
of a set of 8000 reflections. Crystal decay was monitored in the
course of data collection by measuring 200 reflections by image.
No significant fluctuations of intensities were observed during
measurements. Concerning compound 3 the crystal was found to
be twinned. However, the two domains could be indexed and the
two orientation matrixes were used in the integration process
(STOE, 1996) to produce a set of nonoverlapped reflections for
each domain. Only the data from the domain with the strongest
intensities were considered. The rejection of all overlapped reflec-
tions resulted in a very poor completeness around 57%. Structures
were solved by means of direct methods using the program SIR
9239 and subsequent difference Fourier maps. The models were
refined by least-squares procedures on a F2 using SHELXL-97.40
Atomic scattering factors were taken from International Tables for
X-ray Crystallography.41 All hydrogen atoms were located on
difference Fourier maps, but introduced in the refinement as fixed
contributors by using a riding model and with an isotropic thermal
parameter fixed at 20% (or 50% for CH3 group) higher than those
of the carbon atoms to which they were connected. For the two
structures, all non-hydrogen atoms were anisotropically refined, and
in the last cycles of refinement weighting schemes were used, where
weights were calculated from the following formula: w ) 1/[σ2-
(Fï2) + (aP)2 + bP] where P ) (Fï2 + 2Fc2)/3. Drawings of
molecules were plotted using the program ORTEP 342 with 50%
probability displacement ellipsoids for non-hydrogen atoms.
Acknowledgment. We are thankful to Professor Dr. Paul-
Louis Fabre (Toulouse) for fruitful discussion. We gratefully
acknowledge the reviewers for constructive remarks.
Supporting Information Available: Figures S1-S4 giving the
compared NMR spectra of compound L (L ) 1, 2, and 3) with 1
equiv of Ca2+ and H+, respectively. Figures S5 and S6 presenting
concentrations of the formed species versus the calcium concentra-
tion for ligands 1 and 2, respectively. Figure S7 giving the compared
spectra of compound 4 and of mixture from Figure 9d in the 1-9.5
ppm range. S8 and S9 presenting crystal data of complexes 2 and
3, and one X-ray crystallographic file, in CIF format. Figures S10
and S11 showing overhead view of molecules 2 and 3, respectively.
(39) Altomare, A.; Cascarano, G.; Giacovazzo, G.; Guagliardi, A. SIR92-A
program for crystal structure solution. J. Appl. Crystallogr. 1993, 26,
343.
(40) Sheldrick, G. M. SHELXL-97, Program for the Refinement of Crystal
Structures; Institu¨t fu¨r Anorganische Chemie der Universita¨t, Tam-
manstrasse 4, D-3400, Go¨ttingen, Germany, 1997.
(41) International Tables for X-ray Crystallography, Vol IV; Kynoch
Press: Birmingham, England, 1974.
S12, NMR data, interaction of compounds 1, 2, and 3 with Ca2+
.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(42) Farrugia, L. J. ORTEP3 for Windows. J. Appl. Crystallogr. 1997, 30,
565.
(43) Beer, P. D.; Blackburn, C.; McAleer, J. F.; Sikanyika, H. Inorg. Chem.
1990, 29, 378.
IC0345828
Inorganic Chemistry, Vol. 43, No. 6, 2004 2077