Solvent effects on the redox properties of ferrocenoyl-dipeptides

Article abstract of DOI:10.1039/b005125j

The preparation and characterization of the novel ferrocenoyl-dipeptides, Fc-Asp(OBzl)-Asp(OBzl)-OBzl (5), Fc-Asp(OBzl)-Glu(OEt)-OEt (6) and Fc-Asp(OBzl)-Cys(Bzl)-OMe (7) are reported. In addition, Fc-Asp(OBzl)-OBzl (4) and its free acid, Fc-Asp(OH)-OH (8), were prepared. A crystal structure determination of 8 revealed an extensive H-bonding network involving a solvent molecule and adjacent molecules of 8 and suggests that these complexes are able to form strong hydrogen bonds with solvent molecules. All compounds show reversible one-electron oxidations in solution. The half-wave potential is strongly influenced by the nature of the solvent and correlates with the hydrogen donor ability α of the Kamlet-Taft formalism.

Full text of DOI:10.1039/b005125j

View Article Online / Journal Homepage / Table of Contents for this issue
Solvent e†ects on the redox properties of ferrocenoyl-dipeptides
Murray V. Baker,a Heinz-Bernhard Kraatz*b and J. Wilson Quailb
a Department of Chemistry, T he University of W estern Australia, Crawley, W A 6907, Australia
b Department of Chemistry, 110 Science Place, University of Saskatchewan, Saskatoon,
SK S7N 5C9, Canada. E-mail: kraatz=skyway.usask.ca;
http.//www.usask.ca/chemistry/kraatz.html; Fax: ]1 (306) 966-4730
Received (in Gainesville, FL, USA) 23rd June 2000, Accepted 8th December 2000
First published as an Advance Article on the web 14th February 2001
The preparation and characterization of the novel ferrocenoyl-dipeptides, Fc-Asp(OBzl)-Asp(OBzl)-OBzl (5),
Fc-Asp(OBzl)-Glu(OEt)-OEt (6) and Fc-Asp(OBzl)-Cys(Bzl)-OMe (7) are reported. In addition, Fc-Asp(OBzl)-OBzl
(4) and its free acid, Fc-Asp(OH)-OH (8), were prepared. A crystal structure determination of 8 revealed an
extensive H-bonding network involving a solvent molecule and adjacent molecules of 8 and suggests that these
complexes are able to form strong hydrogen bonds with solvent molecules. All compounds show reversible
one-electron oxidations in solution. The half-wave potential is strongly inÑuenced by the nature of the solvent and
correlates with the hydrogen donor ability a of the KamletÈTaft formalism.
The redox potential of ferrocenoyl-peptides (Fc-peptides) has
been shown to be sensitive to changes in the length and
primary structure of the peptide chain, and, perhaps more
importantly, the secondary structure of the peptide chain.1
Furthermore, H-bonding interactions between substrates such
as 3-aminopyrazole (3-apzl) derivatives and the peptide back-
bone have been detected electrochemically.2 Importantly, sub-
strate binding was found to be directly related to the rigidity
of the peptide and to the nature of the solvent.3 Interactions
between the substrate and the peptide backbone occurred
only in non-polar and non-protic solvents, which could not
compete with H-bonding sites on the backbone. Polar sol-
vents prevented substrate binding completely.
These solvent e†ects prompted us to investigate the redox
behavior of Fc-dipeptides in various solvents in more detail.
Our Ðndings may help to further the understanding of peptide
secondary structure, but in a much broader context, may help
to improve understanding of the e†ects of ““solvationÏÏ on bio-
logical redox centers. For example, both high and low poten-
tial [4Fe-4S] ironÈsulfur proteins contain the structurally
robust ironÈsulfur cubane cluster linked to the protein
through ironÈcysteine thiolate linkages.4 In view of the struc-
tural similarity of clusters in these proteins, the reason for the
dramatic di†erence in redox potential between HiPIP (high
potential iron proteins) and other [4Fe-4S]-ferredoxins is not
apparent. Changes in the immediate non-coordinative
environment of the [4Fe-4S]-cluster may explain these redox
variations. Studies of a series of blue copper proteins by
Loppnow and co-workers have shown that the protein
environment, which was not involved in coordination to the
copper ion, caused strong variations in the electronic proper-
ties of the redox site.5
DMF, MeCN, DMSO, and MeOH).10 More recently, Black-
burn and Hupp showed that the redox potential of ferrocene
depends on the degree of association of the ferrocenium cation
with the counterion and its activity in a particular solvent.11a
Building on these results, Lay and coworkers have reported a
detailed study of solvation of ferrocene and decamethylferro-
cene.11b Direct interactions of the solvent with the iron center
and/or the cyclopentadienyl rings appear responsible for the
large solvent dependence of the reduction potential of ferro-
cene and its permethylated derivative and have been corre-
lated to solvation parameters Ðrst described by Kamlet et al.12
The KamletÈTaft linear solvation energy relationship
(LSER)12 has been successfully applied by them and others to
describe a variety of properties, such as the rate of a reaction,
the free energy and enthalpy of solvation and the solu-
bility.12h14
In the context of ferrocene-based receptors,15 calix[4]arene-
modiÐed ferrocenes exhibit a signiÐcant solvent dependence,
with the solvent being able to alter the anion recognition
properties of the receptor. In general, the binding constants
correlated well with solvent parameters, such as the relative
permittivity e, the solvent dipole moment k, and GutmannÏs
acceptor number AN.15e
In this study, we have prepared four novel ferrocenoyl-
peptides, characterized them fully and investigated their redox
properties in various solvents. Each dipeptide contains an
asparate residue directly bound to the ferrocenoyl group with
a second amino acid residue bound to the aspartate residue.
These short dipeptides are unable to adopt a stable secondary
structure. It was expected that in these dipeptides, the second
amino acid residue will not have any signiÐcant inÑuence on
the redox properties of the ferrocenoyl moiety, but that the
interaction of solvent molecules with the amide NH and
the carbonyl of the peptide backbone would be sensed by
the ferrocenoyl group. In particular, it was expected that the
interaction of the solvent molecules with the amide group
directly attached to the ferrocene should inÑuence the elec-
tronic properties signiÐcantly. We have used our results to
explore the applicability of free solvation relationships such as
the KamletÈTaft expression to the redox properties of
ferrocenoyl-dipeptides.
Whereas the aqueous solvation of peptides6h8 and redox
proteins9 has received signiÐcant attention, the e†ects of sol-
vation on simple redox-labeled peptides has not been studied.
On the other hand, solvent e†ects of ferrocenes and modiÐed
ferrocenes have received wide attention due to their impor-
tance as accepted standards in electrochemical experiments
and their wide use in biological receptor systems. The
ferrocene/ferrocenium couple has been recognized as having
an electrode potential that varies little with solvent (THF,
DOI: 10.1039/b005125j
New J. Chem., 2001, 25, 427È433
427
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2001

View Article Online
30.3 CH , 28.5 [C(CH ) ], 27.6 (CH ), 14.4 (CH CH ), 14.3
Experimental
2
3 3
2
2
3
(CH CH ).
2
3
General
Spectroscopic characterization of Boc-Asp(OBzl)-Cys(Bzl)-
Ferrocene carboxylic acid (Strem), 1-ethyl-3-(3-dimethyl-
aminopropyl)carbodiimide (EDC), H-Asp(OBzl)-OBzl, H-
Cys(Bzl)-OMe, Boc-Asp(OBzl)-OH, Boc-Glu(OBzl)-OH (all
Advanced ChemTech), hydroxybenzotriazole (HOBt) (Aldrich)
and H-Glu(OEt)-OEt (Aldrich) were used as received. For
synthetic purposes, CHCl was dried over CaH and distilled
OMe (3). Yield: 441 mg, 83%. MW for C
H
N O S: calc.
27 35
2 7
530, found 531 [M ] 1]`; HR-MS: calc. 531.2165 [M ] 1]`,
found 531.2154. 1H-NMR (d, CDCl ): 7.38È7.21 (11H, m,
3
2 ] Ph and Cys-NH), 5.72 (1H, d, J \ 8.1, NH of Asp), 5.14
HH
(2H, AB multiplet, J \ 12.3, CH Ph), 4.75 (1H, dt, J
\
HH
2
HH
7.8, J \ 5.6, CH of Asp), 4.60 (1H, br m, CH of Cys), 3.72
3
2
HH
prior to use. Et N was used without any further puriÐcation.
(3H, s, OCH ), 3.71 (2H, s, SCH Ph), 3.05 (1H, dd, J \ 17.2,
3
3
2
HH
1H and 13C NMR spectra were recorded at 300.135 and
J
\ 4.5, H of the diastereotopic CH of Asp), 2.86 (2H, m,
HH
2
HH
75.478 MHz, respectively, on a Bruker AMX 300 NMR
spectrometer. All chemical shifts are reported in ppm and
coupling constants (J) in Hz. CDCl and MeCN-d (Aldrich)
CHCH S), 2.75 (1H, dd, J \ 17.2, J \ 6.0, H of the dia-
2
HH
stereotopic CH of Asp), 1.47 [9H, s, C(CH ) ]. 13CM1HN-
2
3
3 3
NMR (d, CDCl ): 171.8, 171.0, 170.9 (all C2O), 155.7 (Boc
3
3
were stored over molecular sieves (4 A). 1H NMR shifts are
C2O), 137.9, 135.6, 129.2, 128.8, 128.6, 128.5, 127.5 (all C of
referenced to the non-deutero impurity in CDCl (d 7.24) or in
2 ] Ph), 80.8 [C(CH ) ], 67.1 (OCH Ph), 52.8 (CH ), 52.2 and
3
MeCN-d and are reported relative to tetramethylsilane (d
3
3 3
2
3
50.8 (CH), 36.7, 36.3, 33.3 (all CH ), 28.5 [C(CH ) ].
2
3 3
0.00). Assignments in the 1H and 13CM1HN-NMR spectra were
made using J-modulation and 1H-1H COSY experiments. All
measurements were carried out at 293 K unless otherwise
speciÐed. Mass spectrometry was carried out on a VG Ana-
lytical 70/20 VSE instrument. Elemental analyses were
obtained in-house on a PerkinÈElmer 2400 CHN elemental
analyzer.
Peptide coupling to ferrocene carboxylic acid
Preparation and spectroscopic characterization of Fc-
Asp(OBzl)-OBzl (4). The coupling of H-Asp(OBzl)-OBzl to
FcCOOH was carried out as described above for 1, on a 1
mmol scale. Yield: 454 mg; 86%. MW for C
calc. 525, found (FAB) 525 [M]`; HR-MS (FAB): calc:
H
NO Fe:
29 27
5
525.1239, found 525.1246. 1H-NMR (d, CDCl ): 7.36 (10H, m,
General procedure for the synthesis of Boc-dipeptides
3
aromatic H of Ph), 6.80 (1H, d, J \ 8.1, NH), 5.22 (2H, s,
HH
Preparation and spectroscopic characterization of Boc-
Asp(OBzl)-Asp(OBzl)-OBzl (1). To a cooled ([0 ¡C) solution
of Boc-Asp(OBzl)-OH (320 mg; 1 mmol) in CH Cl (20 mL),
CH Ph), 5.07 (2H, m, CH Ph), 5.06 (1H, m, H of Asp), 4.71
2
2
a
(1H, s, H of subst. Cp), 4.58 (1H, s, H of subst. Cp), 4.35 (2H,
o
o
m, H of subst. Cp), 4.19 (5H, s, unsubst. Cp), 3.19 (1H, dd,
2
2
m
solid HOBt (150 mg; 1.1 mmol) and solid EDC (210 mg; 1.1
mmol) were added. After 5 min, a clear solution of H-
Asp(OBzl)-OBzl É HCl (500 mg; 1.03 mmol) in CH Cl (5 mL)
J
\ 17.2, J \ 4.4, diastereotopic H of CH of Asp), 2.98
HH
HH
2
(1H, J \ 17.2, J \ 4.5, diastereotopic H of CH of Asp).
HH
HH
2
13CM1HN-NMR (d, CDCl ): 170.8, 170.6, 170.2 (all C2O), 135.2
2
2
3
and Et N (1 mL) were added. After overnight stirring at room
(C
Ph), 135.1 (C
ipso
Ph), 128.6, 128.5, 128.4, 128.3, 128.2,
3
ipso
temperature, the reaction mixture was extracted with satur-
127.7, 126.8, 127.5, 127.4 (all C of Ph), 74.7 (C
ipso
of subst. Cp), 69.7 (C of unsubstituted
of subst. Cp),
ated aqueous NaHCO solution, followed by 10% citric acid,
70.6, 70.5 (both C
3
meta
saturated aqueous NaHCO solution and Ðnally distilled
Cp), 68.4, 67.9 (both C of subst. Cp), 67.5 (ÈOCH Ph),
66.7(ÈOCH Ph), 48.4 (CH of Asp), 36.5 (ÈCH COOBzl).
3
2
water. The clear organic phase was then dried over anhydrous
2
2
Na SO , Ðltered and pumped to dryness to give a colorless
E
\ 216 mV (vs. Fc/Fc`; peak width 95 mV). j
nm
2
4
1@2
max
oil. Yield: 432 mg, 70%. MW for C
H
N O : calc. 618,
(e/dm3 mol~1 cm~1) \ 444 (1200).
34 38
2 9
found 619 [M ] 1]`; HR-MS: calc. 619.2656 [M ] 1]`,
found 619.2656. 1H-NMR (d, CDCl ): 7.44 (1H, d, J \ 8.4,
Spectroscopic characterization of Fc-Asp(OBzl)-Asp(OBzl)-
OBzl (5). On the 0.55 mmol scale, yield: 389 mg; 97%.
3
HH
NH of Asp-2), 7.34 (15H, m, aromatic H of Ph), 5.59 (1H, d,
J
\ 8.2, NH of Boc-Asp-1), 5.14 (2H, s, CH Ph), 5.12 (2H, s,
HR-MS (EI): calc. for C
730.1984. 1H-NMR (d, CDCl ): 7.58 (1H, d, J \ 8.2, NH of
Asp-2), 7.35 (15H, m, aromatic H of Ph), 6.94 (1H, d, J
H
N O Fe 730.1977, found
HH
2
40 38
2
8
CH Ph), 5.07 (2H, apparent doublet, CH Ph), 4.88 (1H, dt,
2
2
3
HH
J
\ 8.1, J \ 4.5, CH), 3.88 (1H, m, CH), 3.10È2.67 (4H, m,
\
HH
HH
HH
diastereotopic
H
of CH COOBzl). 13CM1HN-NMR (d,
8.3, NH of Fc-Asp-1), 5.15 (2H, s, OCH Ph), 5.13 (2H, s,
2
2
CDCl ): 170.8, 170.5, 170.3, 169.9 (all C2O), 162.3 (Boc C2O),
135.4, 135.3, 135.0, 128.5, 128.3, 128.2, 128.1, 127.7, 127.5, 126.8
OCH Ph), 5.10 (2H, s, OCH Ph), 4.96 (1H, m, CH of Asp),
3
2
2
4.92 (1H, dt, J \ 8.2, J \ 4.4, CH of Asp), 4.70 (1H, m, H
HH HH
of subst. Cp), 4.64 (1H, m, H of subst. Cp), 4.37 (2H, s, H of
o
(all
C of Ph), 67.4 (ÈOCH Ph), 67.0 (ÈOCH Ph), 66.7
2
2
o
m
(ÈOCH Ph), 66.5 [Me CC(O) of Boc], 51.2 (C of Asp-1), 48.8
subst. Cp), 4.21 (5H, s, unsubst. Cp), 3.20È2.71 (4H, m, dia-
2
3
a
(C of Asp-2), 38.7 (ÈCH of Asp-1), 36.0 (ÈCH of Asp-2), 28.1
stereotopic H of CH of Asp). 13CM1HN-NMR (d, CDCl ):
a
2
2
2
3
(CH of Boc).
172.3, 170.9, 170.8, 170.7, 170.2 (all C2O), 135.6, 135.5, 135.3,
128.8, 128.7, 128.6, 128.5 (all C of Ph), 75.1 (quaternary C of
subst. Cp), 71.0, 71.9 (both are C of subst. Cp), 70.1 (C of
unsubst. Cp), 68.8, 68.2 (both are C of subst. Cp), 67.8
(ÈOCH Ph), 67.2 (ÈOCH Ph), 67.1 (ÈOCH Ph), 49.3 (ÈCHÈ of
3
Spectroscopic characterization of Boc-Asp(OBzl)-Glu(OEt)-
OEt (2). Yield: 290 mg, 57%. MW for C
H
N O : calc.
25 36
2 9
508, found 509 [M ] 1]`; HR-MS: calc. 509.2499 [M ] 1]`,
2
2
2
found 509.2497. 1H-NMR (d, CDCl ): 7.35 (5H, m, Ph), 7.13
Asp-1), 49.2 (ÈCHÈ of Asp-2), 36.3 (ÈCH È of Asp-1), 36.2
3
2
(1H, d, J \ 7.7, NH of Glu), 5.68 (1H, d, J \ 8.6, NH of
(ÈCH È of Asp-2). E \ 194 mV (vs. Fc/Fc`; peak width 70
HH
HH
2
1@2
Asp), 5.14 (2H, apparent doublet, CH Ph), 4.56 (2H, m, CH of
mV; in MeCN). j /nm (e/dm3 mol~1 cm~1) \ 442 (1500).
2
max
Asp and CH of Glu), 4.18 (2H, q, J \ 7.3, CH CH ), 4.13
HH
2
3
(2H, q, J \ 7.3, CH CH ), 3.08 (1H, dd, J \ 17.2, J
\
\
Spectroscopic characterization of Fc-Asp(OBzl)-Glu(OEt)-
OEt (6). Yield: 890 mg, 72% (2 mmol scale). HR-MS (EI):
HH
2
3
HH
HH
HH
4.4, H of the diastereotopic CH of Asp), 2.72 (1H, dd, J
2
17.2, J \ 5.9, H of the diastereotopic CH of Asp), 2.37 (2H,
calc. for C
H
N O Fe 620.1821, found 620.1825. 1H-NMR
HH
HH
2
31 36
2
8
q,
J
\ 7.6, CHCH CH CO of Glu), 2.23 (1H, m,
(d, CDCl ): 7.35 (6H, m, Ph and overlapping peaks from NH
2
2
2
3
CHCHHCH CO of Glu), 1.98 (1H, m, CHCHHCH CO of
of Glu as conÐrmed by 1H-1H COSY NMR), 7.06 (1H, d,
2
2
2
2
Glu), 1.46, [9H, s, C(CH ) ]. 13CM1HN-NMR (d, CDCl ):
172.9, 172.0, 171.5, 170.9 (all C2O), 155.6 (Boc C2O), 135.6,
128.8, 128.6, 128.5 (all C of Ph), 80.8 [C(CH ) ], 67.1 (CH Ph),
J
\ 8.3, NH of Asp), 5.17 (2H, s, OCH Ph), 5.00 (1H, m,
3 3
3
HH
2
CH of Asp), 4.73 (2H, m, H of subst. Cp), 4.57 (1H, m, CH of
o
Glu), 4.37 (2H, apparent triplet, J \ 1.9, H of Cp), 4.20
(5H, s, H of subst. Cp), 3.16 (1H, dd, J \ 17.1, J \ 4.4, H
3 3
2
HH
m
61.8 (CH CH ), 60.8 (CH CH ), 52.0 and 50.8 (CH), 36.3 and
2
3
2
3
HH
HH
428
New J. Chem., 2001, 25, 427È433

View Article Online
Table 1 Crystal data and structure reÐnement for 8 É 1/3H O
4.38, N 4.06; found C 51.79, H 4.57, N 3.75%. MW for
2
C
H
NO Fe: calc. 345, found (FAB-MS) 346 [M ] 1]`;
15 15
5
Empirical formula
Formula weight
C
351.10
H
FeNO É 0.33H O
HR-MS(FAB): calc. 345.0300, found 345.0301. 1H-NMR (d,
15 15
5
2
MeCN-d ): 6.95 (1H, d, J \ 11.0, NH), 4.78 (1H, m, H of
T /K
Crystal system
123(2)
Monoclinic
3
HH
a
Asp), 4.71 (2H, apparent t, J \ 1.6, H of subst. Cp), 4.38
HH
m
o
(2H, apparent t, J \ 1.9, H of subst. Cp), 4.23 (5H, s,
Space group
P2
HH
1
a/A
b/A
c/A
a/¡
7.455(3)
unsubst. Cp), 2.90 (2H, m, diastereotopic Hs of CH of Asp).
2
10.0294(13)
10.568(5)
90
109.20(2)
90
746.2(5)
2
1.036
E
\ 198 mV (vs. Fc/Fc`; peak width 75 mV).
1@2
Electrochemical studies
b/¡
c/¡
All electrochemical experiments were carried out using a
CV-50W Voltammetric Analyzer (BAS) at room temperature
(23 ¡C). No special precautions were taken to exclude oxygen.
All solvents were dried using the appropriate drying agents
(CH Cl /CaH ; CHCl /CaH ; MeOH/Mg; MeCN/CaH ;
U/A
Ž
3
Z
k/mm~1
ReÑections collected
Independent reÑections
ReÑections observed [I [ 2p(I)]
Final R indices [I [ 2p(I)]
R indices (all data)
4589
2384 [R(int) \ 0.0216]
2
2
2
3
2
2
acetone/Na SO /molecular sieves; MeOH/Na; EtOH/Na;
2152
2
4
iPrOH/Na; THF/Na/benzophenone) and freshly distilled
prior to use. Tetrabutylammonium perchlorate (TBAP) was
used as supporting electrolyte (0.1 M). For the cyclic voltam-
metry studies a glassy carbon working electrode (BAS, diam-
eter 2 mm) and a platinum wire counter electrode were used.
The reference electrode was an Ag/AgCl electrode (BAS). iR
compensation was applied. Background scans of the solvent
containing 0.1 M TBAP were collected before each set of
experiments and then subtracted from the spectra.
R \ 0.0216, wR \ 0.0544
1
2
R \ 0.0296, wR \ 0.0565
1
2
of the diastereotopic CH of Asp), 2.76 (1H, dd, J \ 17.1,
2
HH
J
\ 6.1, H of the diastereotopic CH of Asp), 2.41 (2H, m,
HH
2
diastereotopic H of CH CH CO of Glu), 2.22 (1H, m, dia-
2
2
2
2
stereotopic H of CH CH CO of Glu), 2.01 (1H, m, diastereo-
2
2
topic H of CH CH CO of Glu). 13CM1HN-NMR (d, CDCl ):
X-Ray structural studies
2
2
2
3
173.0, 172.2, 171.4, 170.9, 170.8 (all C2O), 135.5, 128.8, 128.6,
128.5 (all C of Ph), 75.0 (C of subst. Cp), 70.9 (C of subst.
YellowÈorange single crystals of Fc-Asp(OH)-OH É 1/3
H O(8 É 1/3H O) were obtained from a solution of CH Cl
ipso
Cp), 70.0 (C of unsubst. Cp), 68.6, 68.4 (both C of subst. Cp),
2
2
2 2
layered with Et O and mounted on a glass Ðber using epoxy
67.1 (OCH Ph), 61.8 (OCH CH ), 60.9 (OCH CH ), 52.3 (CH
2
2
2
3
2
3
resin. Selected crystallographic information are summarized in
of Glu), 49.3 (CH of Asp), 36.1, 30.4, 27.2 (all CH ), 14.3, 14.3
2
Table 1. Data collection proceeded at 123 K on a Nonius
CAD4 di†ractometer (Mo-Ka). The data were collected up to
a h limit of 30.36¡, using the u-scan mode. Of 2384 unique
reÑections measured, 2152 were observed [I [ 2p(I)]. Absorp-
tion correction based on a psi-scan was applied. The cell
parameters were determined from 20 well-centered reÑections.
The structure was solved using XTAL 3.416a and reÐned using
SHELXL97.16b All non-hydrogen atoms were reÐned aniso-
tropically. The hydrogen atoms were located in the density
map and were reÐned with isotropic temperature factors. The
occupancy for the solvent water (O100) was reÐned to be
0.334. The H atoms on O100 could not be found in di†erence
maps and were not placed. The absolute conÐguration was
determined using the Flack parameter [0.001(13)]. Weights
(both CH of Et). j /nm (e/dm3 mol~1 cm~1) \ 440 (1100).
3
max
Spectroscopic characterization of Fc-Asp(OBzl)-Cys(Bzl)-
OMe (7). Yield: 39% (2 mmol scale reaction) after chroma-
tography (silica 200 mesh, EtOAcÈhexanes 1 : 1). Anal. calc.
for C
H
N O SFe: C 61.69, H 5.33, N 4.36; found C 62.03,
33 34
2 6
H 5.25, N 4.12%. MW for C
H
N O SFe: calc. 642, found
33 34
2 6
642 [M]`; HR-MS: calc. 642.1487 [M]`, found 642.1494.
1H-NMR (d, CDCl ): 7.52 (1H, d, J \ 7.8, Cys-NH), 7.21È
3
HH
HH
7.37 (10H, m, 2 ] Ph), 7.19 (1H, d, J \ 8.5, Asp-NH), 5.17
(2H, s, OCH ), 5.09 [1H, dt, J \ 8.0 (doublet splitting),
2
HH
J
\ 5.4 (triplet splitting), CH of Asp], 4.77 [1H, dt, J
\
HH
HH
7.8 (doublet splitting), J \ 5.7 (triplet splitting), CH of Cys],
HH
4.71 (1H, apparent q, splitting 1.6, 1 ] Cp-H), 4.69 (1H, appar-
based on statistics were used. The reÐnement (based on F2 )
obs
ent q, splitting 1.5, 1 ] Cp-H), 4.34 (2H, apparent t, splitting
converged to R \ 0.0216, wR \ 0.0544.
1
2
1.9, 2 ] Cp-H), 4.20 (5H, s, 5 ] Cp-H), 3.70 (2H, s, SCH Ph),
CCDC reference number 440/251. See http://www.rsc.org./
suppdata/nj/b0/b005125j/ for crystallographic Ðles in .cif
format.
2
3.68 (3H, s, OCH ), 3.14 (1H, dd, J \ 16.8, J \ 4.8, dia-
3
HH
HH
stereotopic H of CH of Asp), 2.8È2.9 (3H, m, overlapping
2
signals of the diastereotopic H of CH of Asp and Cys-CH ).
13CM1HN-NMR (d, CDCl ): 172.0, 171.06, 171.0, 170.9 (all
C2O), 137.8, 135.7, 129.2, 128.9, 128.8, 128.6, 128.55, 127.4 (all
2
2
Results and discussion
Synthesis and characterization
3
C of 2 ] Ph), 75.2 (quaternary C of subst. Cp) 71.1, 71.0, 68.7,
68.6 (all methine C of subst. Cp), 70.1 (unsubst. Cp), 67.1
(CH ), 52.9, 52.3, 49.5 (all CH), 36.7, 36.2, 33.4 (all CH ).
Our approach to the synthesis of ferrocenoyl-dipeptides is
summarized in Scheme 1. Following common peptide syn-
thetic strategies,17 Boc-Asp(OBzl)-OH was coupled in
dichloromethane solution with H-Asp(OBzl)-OBzl É HCl, H-
Glu(OEt)-OEt É HCl and H-Cys(Bzl)-OMe É HCl using EDC as
a coupling reagent, to form the expected dipeptides Boc-
Asp(OBzl)-Asp(OBzl)-OBzl (1), Boc-Asp(OBzl)-Glu(OEt)-OEt
(2) and Boc-Asp(OBzl)-Cys(Bzl)-OMe (3), respectively.
Removal of the Boc group and coupling of the resulting
dipeptide with ferrocene carboxylic acid gave the correspond-
ing ferrocenoyl-dipeptides Fc-Asp(OBzl)-Asp(OBzl)-OBzl (5),
Fc-Asp(OBzl)-Glu(OEt)-OEt (6) and Fc-Asp(OBzl)-Cys(SBzl)-
OMe (7) as orange oils, which solidiÐed upon standing. As
part of our study, we also prepared ferrocenoyl-aspartate-
dibenzyl ester (4) and the corresponding free acid ferrocenoyl-
aspartic acid (8), using similar coupling procedures.
2
2
j
/nm (e/dm3 mol~1 cm~1) \ 446 (1250).
max
Preparation and spectroscopic characterization of Fc-
Asp(OH)-OH (8). A slow stream of hydrogen gas was bubbled
through a vigorously stirred mixture of Fc-Asp(OBzl)-OBzl (4)
(195 mg, 0.37 mmol) and 5% Pd/C (0.1 g) in MeOH (40 ml).
The reaction was monitored by TLC (silica; CH Cl ) and was
2
2
complete after 20 min (8 has an R \ 0). Pd/C was removed by
f
Ðltration. Water (10 mL) was added and the pH of the solu-
tion was adjusted to pH 2 by addition of 1 N HCl. The
product was extracted into CH Cl (3 ] 50 mL). The com-
2
2
bined extracts were concentrated and layering with Et O gave
2
the product as X-ray quality orange crystals. Yield: 95 mg,
0.27 mmol, 73%. Anal. calc. for C
H
NO Fe: C 52.16, H
15 15
5
New J. Chem., 2001, 25, 427È433
429

View Article Online
to the meta protons of the substituted Cp ring are essentially
invariant with the peptide substituent. We would expect 13C
NMR to be a sensitive probe of the electronic e†ects in the
ferrocenoyl-dipeptides. If the peptides vary the electronic
properties of the Fc moiety, the ipso-C of the Cp ring carrying
the peptide substituent should be inÑuenced the most and its
signal should be shifted signiÐcantly in the 13C NMR spec-
trum; similar e†ects have been described previously for unre-
lated substituted aromatic systems.18 However, signals of the
ipso-C of the substituted Cp ring for all Fc-peptides were
observed around d 74.7È75.2, indicating only negligible elec-
tronic e†ects. Similarly, the visible spectra of 4È8 exhibit a
single weak and broad absorption (j ^ 440 nm), character-
max
istic of ferrocenes, which is independent of the peptide substit-
uent. Thus, our spectroscopic results indicate that the
electronic properties of the ferrocene group are not dramat-
ically perturbed by the peptide and thus that the redox poten-
tial should be independent of the peptide substituents.
Electrochemical studies
Initial cyclic voltammograms for 4È7 recorded in chloroform
exhibit fully reversible one-electron oxidations, as judged by
the peak separation between cathodic and anodic peaks,
which was in the range of 60È90 mV. In addition, the ratio of
cathodic and anodic peak areas, which is also a measure of
the reversibility of an electrochemical oxidation, was close to
unity. All electrode potentials are reported vs. the Ag/AgCl
reference electrode and occurred between 631 mV for 4 and
647 mV for 7 (Table 3).
Scheme 1 General scheme for the synthesis of ferrocenoyl-dipeptides.
(i) EDC, HOBt, Et N, CH Cl , RT; (ii) (a) TFA, CH Cl ; (b)
3
2
2
2 2
FcCOOH, EDC, HOBt, Et N, CH Cl , RT.
3
2 2
The 1H-NMR spectra of deuterochloroform solutions of
compounds 4È8 exhibit signals characteristic of mono-
substituted ferrocenes, with the two signals of the two mag-
netically inequivalent ortho protons of the substituted
cyclopentadienyl (Cp) ring downÐeld from the signal for the
meta protons. Selected 1H-NMR data are summarized in
Table 2. Like all proton signals of the Cp ring, those for the
ortho protons are observed in very narrow shift ranges, d
4.73È4.70 and d 4.5È4.69. In the case of Fc-Asp(OBzl)-
Glu(OEt)-OEt (6), the signals of the two ortho protons are
accidentally coincident. Similarly, the shifts of the signals due
Next we investigated the redox chemistry of compounds
4È7 in various solvents by cyclic voltammetry (CV) and found
that the electrode potentials are greatly solvent dependent.
The results of our CV study are summarized in Table 3. Com-
pounds 4È7 exhibited fully reversible one-electron oxidation
waves in most solvents with peak separations ranging from
65È85 mV, this being within the acceptable limits for
reversible one-electron processes.19 There were, however,
notable exceptions where the oxidation was only quasi-
reversible or even irreversible. For example, cathodic and
anodic peak separations of all compounds in 1-butanol and
2-butanol were large ([200 mV) at a scan speed of 100 mV
s~1. At higher scan rates (above 1000 mV s~1), the oxidation
became fully reversible, as expected for a quasi-reversible
process. Compound 7 only gave an irreversible oxidation
wave in 2-pyrrolidone at 702 mV at a scan speed of 100 mV
s~1. This result is in line with the known redox behavior of
ferrocene in strong donor solvents, such as dimethyl sulfoxide,
or in the presence of anionic ligands, such as Cl~. In both
cases, irreversibility of the oxidation process was observed,
presumably because the ferrocenium cation reacted rapidly
with a donor species (solvent or nucleophile) to form Fe3`
and products of the reaction of the Cp radical with the
solvent.20
When the solvent was changed, signiÐcant changes in the
position of the halfwave potential of the ferrocenoyl-peptides
4È7 were observed. We were particularly interested in evalu-
ating the redox behavior in protic solvents able to form strong
Table 2 Selected 1H-NMR spectroscopic data for ferrocenoyl-peptides 4È7
Compound
NH
6.80
CH
CH
CH
CH
a
o
m
Cp
Fc-Asp(OBzl)-OBzl (4)
5.06
4.71
4.58
4.70
4.64
4.73
4.35
4.37
4.37
4.34
4.19
4.21
4.20
4.20
Fc-[Asp(OBzl)] -OBzl (5)
7.58 (Asp-2)
6.94 (Asp-1)
7.35 (Glu)
7.06 (Asp)
7.52 (Cys)
7.19 (Asp)
4.96
4.92
5.00 (Asp)
4.57 (Glu)
4.77 (Cys)
5.09 (Asp)
2
Fc-Asp(OBzl)-Glu(OEt) (6)
2
Fc-Asp(OBzl)-Cys(SBzl)-OMe (7)
4.71
4.69
430
New J. Chem., 2001, 25, 427È433

View Article Online
Table
3
Halfwave potentials of Fc-Asp(OBzl)-OBzl (4), Fc-
cal ““solvent familyÏÏ or empirical coordinate covalency param-
eter f and the use of multilinear regression analysis in order to
Ðnd the dependence on both parameters b and f. The f
parameter is only used in conjunction with b. The parameter
n* describes the polarity and polarizability of the solvent.
Fig. 1 shows a plot of the electrode potential for the one-
electron redox process of the Fc group in 7 vs. the solventÏs
HBD ability a. Instead of a single linear relationship between
Eo and a, as we would expect if Eo were to depend solely on a,
we observe discontinuities, suggesting other contributing
inÑuences that are not accounted for. Attempts were made to
explore the dependence of Eo on more than one KamletÈTaft
parameter. However, plots of Eo vs. b, n*, or a/b, b/f com-
binations do not show any correlations and produce only a
scattering of points. It appears that these discontinuities may
be related to the di†erences in interactions that exist in solu-
tion between the ferrocenoyl-dipeptides and these three
groups of solvents. Protic acids and alcohols will strongly
interact with the carbonyl groups, whereas amide bases may
interact preferentially with the amide NH. Although we are
dealing with ““solvent familiesÏÏ in the broadest sense, the
empirical coordinate covalency f is not useful in this context.
In order to explore reasons for the correlation with a, we
replotted Lay et al.Ïs data of the formal oxidation potential for
ferrocene in alcoholic solvents11b and obtained a linear
relationship between a and the Eo. However, the slope is sig-
niÐcantly di†erent from that observed for the ferrocenoyl-
dipeptides 4È7, suggesting that the peptide substitutent is
modifying the redox potential of the Fc moiety by its inter-
action with the solvent. For ferrocenoyl-dipeptides in solvents
with a very large HBD ability a, such as triÑuoroethanol
(a \ 1.51) and 2-chloroethanol (a \ 1.28), the electrode poten-
tial experiences a cathodic shift, indicating more facile oxida-
tion of the Fc moiety and a net stabilization of Fe(III) over
Fe(II). This change in Eo is related to the di†erent strengths of
interaction of each redox state with the solvent molecules.21
The cathodic shifts of the electrode potentials that we observe
on moving from solvents with small a to ones with large a
indicate that the solvent molecules are more tightly bound for
solvents with large a once the ferrocenoyl group is oxidized.
This is consistent with the observations that the Fc` group
will increase the acidity of the adjacent amide NH23 and the
ability of the FcÈC2O to become a stronger electron pair
donor. In related ferrocenoyl-amidopyridine systems, proto-
nation of the pyridine nitrogen, and thus formation of a
cationic charge close to the Fc group, results in anodic
shifts.15h Cathodic shifts were observed, however, when the
ferrocenoylamidopyridine systems were studied in the pres-
ence of carboxylic acids.15g These cathodic shifts are
believed15g to be a consequence of strong hydrogen bonding
between the NÈH of a ferrocenoyl-amidopyridine and the
C2O of a carboxylic acid with the amide NH, as is proposed
for Fc-peptides.
[Asp(OBzl)] -OBzl (5), Fc-Asp(OBzl)-Glu(OEt)
(6) and Fc-
2
2
Asp(OBzl)-Cys(Bzl)-OMe (7) in various solvents. The solvents are
grouped into (a) alcohols, (b) amides, (c) acids and (d) others and
sorted by decreasing a in each group. All potentials are referenced to
the potential of the Ag/AgCl reference electrode
E
/mV
1@2
Solvent
4
5
6
7
a12,13
(a) Alcohols
1,1,1-TriÑuoroethanol
2-Chloroethanol
Methanol
Ethanol
1-Butanol
469
543
614
658
697
680
687
459
450
533
621
649
691
642
664
459
537
623
634
674
665
668
1.51
1.28
0.98
0.86
0.84
0.79
0.76
541
622
625
650
655
654
2-Butanol
2-Propanol
(b) Amides
Formamide
N-Methylformamide
N-Methylacetamide
2-Pyrrolidone
542
616
690
702(irr)
0.71
0.62
0.47
0.36
(c) Acids
Formic acid
Acetic acid
Propionic acid
550
589
621
1.23
1.12
1.12
(d) Others
Chloroform
Acetonitrile
Dichloromethane
Acetone
Tetrahydrofuran
N,N-Dimethylformamide
Chlorobenzene
631
657
677
638
644
647
616
674
683
724
685
719
0.20
0.19
0.13
0.08
0.00
0.00
0.00
660
688
711
672
683
702
H-bonds with the peptide backbone, such as alcohols or
amides. For example, the electrode potential for 7 exhibits a
strong solvent inÑuence on going from a non-protic to a
protic solvent and shifts from 724 mV in tetrahydrofuran to
459 mV in 1,1,1-triÑuoroethanol. This is a change of 265 mV
and corresponds to a net stabilization of the Fe3` over the
Fe2` oxidation state in 1,1,1-triÑuoroethanol by 25.4 kJ
mol~1! The obvious explanation for this behavior is a change
in the solvation energy between oxidized and reduced states of
the ferrocene group, as was described in detail by others.21
However, if unspeciÐc solvation e†ects of the ferrocene group
were solely responsible for the observed solvent e†ect we
would expect a dependence on solvent polarity only, as was
observed for ferrocene11 and the ferrocenemethylene ammon-
ium cation.22 Instead, we Ðnd that the redox potentials for
4È7 show a dependence on the solventÏs H-bond donor ability
(HBD) a as deÐned by the KamletÈTaft linear solvation
energy relationship (LSER; vide infra). The electrode poten-
tials relative to the Ag/AgCl electrode along with the a values
for the solvents are given in Table 3.13 The KamletÈTaft
LSER12,13 has been used very successfully to express solva-
tion e†ects on a range of properties, such as solubility or rates
and free energies of reactions:
XYZ \ XYZ ] aa ] bb ] sn* ] É É É
o
where XYZ , a, and b are solvent-independent coefficients,
o
which are characteristic of the solvation e†ects to be
described. For some processes, many of these coefficients can
be negligibly small, so that the corresponding terms are not
signiÐcant in the characterization of the solvent e†ects for
these processes. Thus, a process can be dominated by one
parameter. The two solvatochromic parameters a and b are
the H-bond donor ability (HBD) and the H-bond acceptor
ability (HBA) of the solvent, respectively. In many cases,
correlations involving the HBD ability b of the solvent show
discontinuities. This has led to the introduction of an empiri-
Fig. 1 InÑuence of the hydrogen bond donor ability a of various
families of solvents on the redox potential of Fc-Asp(OBzl)-Cys(Bzl)-
OMe (7): (+) protic solvents (alcohols and acids); (>) amides and
N-bases; (=) others.
New J. Chem., 2001, 25, 427È433
431

View Article Online
Table 4 Selected bond lengths (A) and angles (¡) for 8 É 1/3H O
2
C(1)ÈC(11)
1.471(2)
1.325(2)
1.205(3)
1.322(2)
NÈC(11)
1.328(2)
1.454(2)
1.209(3)
1.252(2)
O(1)ÈC(13)
NÈC(12)
O(2)ÈC(13)
O(3)ÈC(15)
O(4)ÈC(15)
O(5)ÈC(11)
C(11)ÈNÈC(12)
O(5)ÈC(11)ÈN
O(5)ÈC(11)ÈC(1)
121.68(16)
121.77(17)
120.52(18)
NÈC(11)ÈC(1)
O(2)ÈC(13)ÈO(1)
O(4)ÈC(15)ÈO(3)
117.70(18)
125.16(18)
123.42(19)
In this context, it is meaningful to interpret our results in
terms of hydrogen bonding interactions of solvent molecules
with the amide C2O of the Fc group and the peptide back-
bone. This is supported by NMR monitoring of additions of
aliquots of methanol to a solution of 7 in CDCl , which
3
showed large downÐeld shifts of the amide NH signal, indica-
tive of H-bonding.3 The presence or absence of H-bonding
has e†ects on the electronic properties. Addition of solvents
that will bond strongly with the amide C2Os or the ferro-
cenoyl C2O will cause changes in the electronic structure of
the ferrocenoyl group. This in turn should inÑuence the
chemical shift of the hydrogens on the Fc group. The ortho
hydrogens should be inÑuenced the most due to their proxim-
Fig. 3 ORTEP diagram for three adjacent molecules of 8 engaged in
H-bonding. Two acid OH are H-bonded with the FcÈC2O group. The
water molecule has been omitted for clarity.
ity to the peptide substitutent. In fact, addition of methanol
causes shifts of the proton signals of the ortho hydrogens from
d 4.71 and 4.69 in neat CDCl to d 4.57 after the addition of
3
methanol. The meta hydrogens and the hydrogens of the
unsubstituted Cp are also shifted after the addition of meth-
anol (from d 4.34 to 4.24 for the meta hydrogens and from d
4.20 to 4.05 for the protons of the unsubstituted Cp ring).
Crystallographic studies
Indirect evidence of the ability of the Fc-dipeptide to form
H-bonding interactions with solvents is provided by the X-ray
crystal structure of 8. Selected bond distances and angles are
Fig. 2 ORTEP diagram for Fc-Asp(OH)-OH É 1/3H O (8 É 1/3H O)
2
2
showing a single molecule of 8 and the water molecule occupying a
position allowing its interaction with CH(5) and the amide NH.
Fig. 4 Stereoscopic view of the extensive H-bonding network present in the solid state between the water molecule (O100) and three adjacent
molecules of 8. In addition to ““conventionalÏÏ OÉ É ÉHÈN and OÈHÉ É ÉO2C H-bonding, the water molecule is also involved in CÈHÉ É ÉO inter-
actions with the Cp ring.
432
New J. Chem., 2001, 25, 427È433

View Article Online
5
6
(a) E. Fraga and G. R. Loppnow, J. Phys. Chem. B, 1998, 102,
7659; (b) G. R. Loppnow and E. Fraga, J. Am. Chem. Soc., 1997,
119, 896; (c) M. A. Webb and G. R. Loppnow, J. Phys. Chem. B,
1998, 102, 8923.
(a) E. M. Cilli, E. Oliveira, R. Marchetto and C. R. Nakaie, J.
Org. Chem., 1996, 61, 8992; (b) M. Narita, J. S. Lee, S. Hayashi, Y.
Yamazaki and Y. Sugiyama, Bull. Chem. Soc. Jpn., 1993, 66, 500;
(c) M. Narita, J. S. Lee, S. Hayashi and M. Hitomi, Bull. Chem.
Soc. Jpn., 1993, 66, 489; (d) M. Narita, J. S. Lee, S. Hayashi, Y.
Yamazaki and M. Hitomi, Bull. Chem. Soc. Jpn., 1993, 66, 494; (e)
M. Narita, S. Honda and S. Obana, Bull. Chem. Soc. Jpn., 1989,
62, 342; ( f ) M. Narita, H. Umeyama and T. Yoshida, Bull. Chem.
Soc. Jpn., 1989, 62, 3582.
(a) M. Schaefer, C. Bartels and M. Karplus, J. Mol. Biol., 1998,
284, 835 and references therein; (b) H. Guo and M. Karplus, J.
Phys. Chem., 1994, 98, 7104.
(a) A. Cammers-Goodwin, T. J. Allen, S. L. Oslick, K. F.
McClure, J. H. Lee and D. S. Kemp, J. Am. Chem. Soc., 1996,
118, 3082; (b) D. S. Kemp, T. J. Allen, S. L. Oslick and J. G.
Boyd, J. Am. Chem. Soc., 1996, 118, 4240; (c) D. S. Kemp, S. L.
Oslick and T. J. Allen, J. Am. Chem. Soc., 1996, 118, 4249; (d) S.
Shimizu and K. Shimizu, J. Am. Chem. Soc., 1999, 121, 2387.
H. A. O. Hill, Coord. Chem. Rev., 1996, 151, 115.
summarized in Table 4 and an ORTEP24 representation of 8
is shown in Fig. 2. The geometric features of 8 are similar to
those of other Fc-peptides and Fc-amino acids.25 The two Cp
rings of the Fc group are parallel with a small bent angle25
CpÈFeÈCp of 1.1o and they adopt an eclipsed conformation.
The amide and Cp groups are coplanar with a twist of only
3.4o, which is small compared to that seen in related
systems.25 Compound 8 crystallizes with 1/3 molecule of
water, which occupies a position that enables H-bonding with
the Fc-amide NH and the AspÈC2O groups. The FcÈC2O
group is involved in hydrogen bonding interactions with the
acid groups of the Asp acid side chain as well as the a-
carboxyl group of two adjacent molecules, forming a bifur-
cated H-bond with OÈHÉ É ÉO2C(Fc) contacts of 2.678(2) and
2.605(2) A (Fig. 3). The H-bonding distance to the a-carboxy
group is shorter, indicating a stronger H-bond, which is in line
with the lower pK for this group (pK \ 1.88) compared to
7
8
a
a
the side chain carboxyl group (pK \ 3.65).26 Fig. 4 shows the
a
extensive hydrogen bonding network involving the water mol-
9
ecule and three Fc-aspartic acid molecules. The water mol-
ecule is nestled in a pocket created by the Fc-aspartic acid
moiety, which enables it to establish a series of H-bonding
contacts. Unfortunately, we were not able to obtain crystals of
the corresponding oxidized complex, which would enable us
to directly compare the H-bonding abilities of the oxidized
and reduced species.
10 H. Shalev and D. H. Evans, J. Am. Chem. Soc., 1989, 111, 2667.
11 (a) R. L. Blackburn and J. T. Hupp, J. Phys. Chem., 1990, 94,
1788; (b) I. Noviandri, K. N. Brown, D. S. Fleming, P. T. Gulyas,
P. A. Lay, A. F. Masters and L. Phillips, J. Phys. Chem. B, 1999,
103, 6713.
12 M. J. Kamlet, J. L. M. Abboud, M. H. Abraham and R. W. Taft,
J. Org. Chem., 1983, 48, 2877.
13 Y. Marcus, Chem. Soc. Rev., 1993, 409.
14 (a) L. Engman, J. Persson, C. M. Anderson and M. Berglund, J.
Chem. Soc., Perkin T rans. 2, 1992, 1309; (b) M. Jonsson, J. Lind,
T. Reitberger, T. E. Eriksen and G. Merenyi, J. Phys. Chem.,
1993, 97, 11278; (c) M. Jonsson, J. Lind, G. Merenyi and T. E.
Eriksen, J. Chem. Soc., Perkin T rans. 2, 1995, 67; (d) M. Jonsson,
D. D. M. Wayner and J. Lusztyk, J. Phys. Chem., 1996, 100,
17539.
15 (a) P. D. Beer, Z. Chen, A. J. Goulden, S. E. Stokes and T. Wear,
J. Chem. Soc., Chem. Commun., 1993, 1834; (b) P. D. Beer, Z.
Chen, M. G. B. Drew, J. Kingston, M. Ogden and P. Spencer, J.
Chem. Soc., Chem. Commun., 1993, 1046; (c) P. D. Beer, Chem.
Commun., 1996, 689; (d) Z. Chen, A. R. Graydon and P. D. Beer,
J. Chem. Soc., Faraday T rans., 1996, 92, 97; (e) P. D. Beer and M.
Shade, Chem. Commun., 1997, 2377; ( f ) P. D. Beer, A. R.
Graydon, A. O. M. Johnson and D. K. Smith, Inorg. Chem., 1997,
36, 2112; (g) J. D. Carr, L. Lambert, D. E. Hibbs, M. B. Hurs-
thouse, K. M. Malik and J. H. R. Tucker, Chem. Commun., 1997,
1649; (h) J. D. Carr, S. J. Coles, W. W. Hassan, M. B. Hursthouse,
K. M. A. Malik and J. H. R. Tucker, J. Chem. Soc., Dalton T rans.,
1999, 57.
Summary
Ferrocenoyl-dipeptides are readily synthesized from ferrocene
carboxylic acid and various C-protected dipeptides. The
ferrocenoyl-dipeptides each exhibit a reversible one-electron
oxidation wave. The position of this oxidation wave is greatly
dependent on the hydrogen bonding ability of the solvent,
shows a correlation with the KamletÈTaft parameter a, and
exhibits a ““solvent familyÏÏ behavior. In general, an increase in
the HBD ability a of the solvent causes a cathodic shift of the
redox potential. However, it appears that other solvent e†ects,
not yet accounted for, are inÑuencing the redox potential. An
X-ray study of Fc-Asp(OH)-OH shows a highly H-bonded
structure, a result that suggests that the Fc-dipeptides would
interact with H-bonding solvents. Solvent coordination most
likely will involve the amide NÈH and the carbonyl C2O, as
was reported before.2,3
16 (a) S. R. Hall, G. S. D. King and J. M. Stewart, T he XT AL 3.4
UserÏs Manual, University of Western Australia, Perth, Australia,
1995; (b) G. M. Sheldrick, SHELXL97, Program for the ReÐne-
ment of Crystal Structures, Universitat Gottingen, Gottingen,
Germany, 1997.
Acknowledgements
We thank the National Science and Engineering Research
Council of Canada for Ðnancial support in the form of oper-
ating grants to H. B. K. (d218857-99) and J. W. Q.
(d108071). M. V. B. thanks The University of Western Aus-
tralia for a sabbatical leave. We thank Mr K. Thoms for the
elemental analyses and MS measurements. We would also like
to thank Dr R. S. Reid for discussions regarding multilinear
regression analysis.
17 J. Jones, T he Chemical Synthesis of Peptides, Clarendon Press,
Oxford, 1991.
18 A. Weisman, M. Gozin, H.-B. Kraatz and D. Milstein, Inorg.
Chem., 1996, 35, 1792.
19 A. J. Bard and L. R. Faulkner, Electrochemical Methods, Wiley,
New York, 1980.
20 R. Prins, A. R. Korswagen and A. G. T. G. Kortbeek, J.
Organomet. Chem., 1972, 39, 335.
21 (a) C. D. Hall, N. W. Sharpe, I. P. Danks and Y. P. Sang, J.
Chem. Soc., Chem. Commun., 1989, 419; (b) J. C. Medina, T. T.
Goodnow, S. Bott, J. L. Atwood, A. E. Kaifer and G. W. Gokel,
J. Chem. Soc., Chem. Commun., 1991, 290.
References
1
H.-B. Kraatz, D. M. Leek, A. Houmam, G. D. Enright, J. Lusztyk
and D. D. M. Wayner, J. Organomet. Chem., 1999, 589, 38.
P. Saweczko and H.-B. Kraatz, Coord. Chem. Rev., 1999, 190–
192, 185.
P. Saweczko, M.Sc. Thesis, University of Saskatchewan, 2001.
I. Bertini, H. B. Gray, S. J. Lippard and J. S. Valentine, Bio-
inorganic Chemistry, University Science Books, Mill Valley, CA,
1994.
22 H.-B. Kraatz, J. Organomet. Chem., 1999, 579, 222.
23 M. H. Abraham, Chem. Soc. Rev., 1993, 22, 73.
24 C. K. Johnson, ORTEPII, Report ORNL-5138, Oak Ridge
National Laboratory, Oak Ridge, TN, 1976.
2
3
4
25 L. Lin, A. Berces and H.-B. Kraatz, J. Organomet. Chem., 1998,
556, 11.
26 CRC Handbook of Chemistry and Physics, ed. D. R. Linde, 80th
edn., CRC Press, Boca Raton, FL, 1999, sect. 7-1, 2.
New J. Chem., 2001, 25, 427È433
433