A systematic evaluation of different hydrogen bonding patterns in unsymmetrical 1,n′-disubstituted ferrocenoyl peptides

Article abstract of DOI:10.1016/j.ica.2008.01.050

The synthesis and spectroscopic characterization of 21 l,l′-disubstituted ferrocenoyl peptides of the general formula [Fe(C₅H₄-CO-Aal-OR) (C₅H₄-CO-Aa2-OR′)] is reported, with Aal and Aa2 being different amino ac

Full text of DOI:10.1016/j.ica.2008.01.050

Available online at www.sciencedirect.com
Inorganica Chimica Acta 362 (2009) 894–906
www.elsevier.com/locate/ica
A systematic evaluation of different hydrogen bonding patterns
in unsymmetrical 1,n0-disubstituted ferrocenoyl peptides
Srecko I. Kirin *, Ulrich Schatzschneider a,b, S. David Ko¨ster a,b, Daniel Siebler a,
a,c,
´
Nils Metzler-Nolte a,b,
*
a Institut fu¨r Pharmazie und Molekulare Biotechnologie, Ruprecht-Karls-Universita¨t Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany
b Lehrstuhl fu¨r Anorganische Chemie I – Bioanorganische Chemie, Ruhr-Universita¨t Bochum, Universita¨tsstr. 150, D-44801 Bochum, Germany
c Division of Materials Chemistry, Ruder Bosˇkovic´ Institute, Bijenicˇka c. 54, HR-10002 Zagreb, Croatia
Received 8 December 2007; accepted 28 January 2008
Available online 23 February 2008
Dedicated to Bernhard Lippert.
Abstract
The synthesis and spectroscopic characterization of 21 l,l0-disubstituted ferrocenoyl peptides of the general formula [Fe(C5H4-CO-Aal-
OR) (C5H4-CO-Aa2-OR0)] is reported, with Aal and Aa2 being different amino acids. The one-pot synthesis from activated ferrocene-l,l0-
dicarboxylic acid and two different amino acid esters gives the unsymmetrical ferrocenoyl peptides in yields between 27% and 42%, which
can be easily separated from their symmetrical byproducts by column chromatography. All new compounds are comprehensively char-
acterized by mass spectrometry (El and FAB, including high-resolution EI-MS), 1H and 13C NMR, and UV/Vis spectroscopy. CD
1
spectroscopy in conjunction with H NMR is used to elucidate the solution structures. Using the achiral glycine (Gly) as Aal permits
to determine qualitatively the structure-determining influence of the different amino acids Aa2. Helically chiral structures in ferrocene
amino acids in this study are stabilized by hydrogen bonds. If one hydrogen bond partner is systematically moved away by the intro-
1
duction of methylene groups, then indeed the strength of the hydrogen bond decreases as indicated by H NMR chemical shifts of the
amide protons and the strength of characteristic CD bands. As proline (Pro) is the only naturally accuring secondary amino acid it
cannot contribute any amide proton to intra-strand hydrogen bonding. DFT calculations on the compound [Fe(C5H4-CO-Gly-
OMe)(C5H4-CO-Pro-OMe)] with one achiral and one secondary amino acid were therefore performed to quantify the more subtle
influence of the relative orientations of the ferrocene carbonyl groups and the cis-/trans-conformation of both amide bonds. Not unex-
pectedly, the conformations with both amide bonds in cis orientation are highest in energy. Surprisingly, the calculations suggest the
presence of a low-energy conformation with a non-classical hydrogen bond between the proline ester carbonyl oxygen and a glycine
Ha atom. However, a second conformation with no apparent intra-strand contacts but optimal positioning of all relevant groups is
similar in energy. Although two conformations were observed in solution for this compound, the experimental data did not permit to
assign those two conformations.
Ó 2008 Elsevier B.V. All rights reserved.
Keywords: Amino acids; Bioorganometallic chemistry; Density functional theory; Ferrocene; Hydrogen bonding; Peptides
*
1. Introduction
Corresponding authors. Addresses: Division of Materials Chemistry,
Ruder Bosˇkovic´ Institute, Bijenicˇka c. 54, HR-10002 Zagreb, Croatia (S.I.
Kirin); Lehrstuhl fur Anorganische Chemie I – Bioanorganische Chemie,
¨
In the development of new oligonucleotide and peptide-
based materials, the use of artificial building blocks is of
steadily increasing importance [1]. Non-natural monomers
can either form completely artificial oligomers or be com-
bined with natural ones to form sequences with interesting
Ruhr-Universita¨t Bochum, Universita¨tsstr. 150, D-44801 Bochum, Ger-
many (N. Metzler-Nolte). Tel.: +385 1 4561 189; fax: +385 1 4680 098
(S.I. Kirin), Fax: +49(0) 234 3214378 (N. Metzler-Nolte).
E-mail addresses: srecko.kirin@irb.hr (S.I. Kirin), nils.metzler-nol-
te@rub.de (N. Metzler-Nolte).
0020-1693/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2008.01.050

S.I. Kirin et al. / Inorganica Chimica Acta 362 (2009) 894–906
895
structural and functional properties. For example, unnatu-
O
ral amino acids containing norbornene [2], adamantane
[3], or ferrocene [4] (Fig. 1) can induce secondary turn
structures in oligo-peptides [5]. In this context, the rational
and predictable control over key properties is of crucial
interest.
O
O
OMe
OMe
N
H
OMe
OMe
N
H
O
O
Fe
O
O
H
N
Fe
H
N
Among artificial peptide building blocks, the 1,n0-disub-
stituted ferrocene scaffold has attracted particular interest
because of its unique properties. The low rotational
barrier of the two Cp rings against each other allows for
conformational flexibility that is not possible in rigid
organic frameworks like the norbornene or adamantane
amino acids shown in Fig. 1. This conformational flexibil-
ity has been exploited in derivatives of 10-amino-1-ferro-
cene carboxylic acid (Fca), which can mimic the exo and
endo transition states in Diels–Alder reaction, as artificial
haptens for the generation of stereospecific catalytic anti-
bodies [6]. After the pioneering preparation of ferrocene
peptides by Herrick, Jarret, Curran and coworkers [4a],
the helical chirality of this class of compounds was recog-
nized by Moriuchi and Hirao [7]. The rules that are gov-
erning the formation of either M- or P-helical structures
are meanwhile well understood [4,8]. The stability of these
helical structures depends critically on the number and
nature of intramolecular hydrogen bonds. By prudent
choice of the amino acid and other building blocks in
these compounds, we may achieve full control over the
structural parameters that will place C@O and N–H
bonds in suitable positions for the formation of hydrogen
bonds. It is the purpose of this work to further add to this
knowledge of structural control in ferrocenoyl peptides.
So far, ferrocene peptides were shown to adopt conforma-
tions with two, one, or no hydrogen bonds. These hydro-
gen bonds were confirmed in the solid state by X-ray
crystallography and IR spectroscopy, and in solution by
CD, NMR and IR spectroscopy. Their relative stabilities
were determined in the gas phase by DFT calculations
[8,9].
O
R
n
1, R = Me; (Gly, Ala)
2, R = Bzl; (Gly, Phe)
3, R = Ph; (Gly, Phg)
4, R = iPr; (Gly, Val)
5, n = 2; (Phe, βAla)
6, n = 3; (Phe, γAba)
O
O
OMe
N
OtBu
N
O
O
H
Fe
O
H
N
Fe
H
OMe
N
NHFmoc
O
R
n
O
7, n = 2; (Phe, en)
8, n = 3; (Phe, pn)
9, R = Me; (Pro, Ala)
10, R = Bzl; (Pro, Phe)
11, R = Ph; (Pro, Phg)
12, R = iPr; (Pro, Val)
O
R
O
n
R1
OMe
OMe
N
H
N
H
O
O
Fe
Fe
H
N
H
N
R1
n
O
R
O
13, R = H; (Gly, Gly)
14, R = Me; (Ala, Ala)
15, R = Bzl; (Phe, Phe)
15b, R = Bzl; (Phe, Phe)*
16, R = Ph; (Phg, Phg)
17, R = iPr; (Val, Val)
18, n = 2, R1 = CO2tBu; (βAla, βAla)
19, n = 3, R1 = CO2tBu; (γAba, γAba)
20, n = 2, R1 = NHFmoc; (en, en)
21, n = 3, R1 = NHFmoc; (pn, pn)
Symmetrical peptides derived from 1,10-ferrocene dicar-
boxylic acid have been studied in detail [7–11], while
reports on unsymmetrical peptide derivatives of l,l0-ferro-
cene dicarboxylic acid are only scarce [9c,12]. One impor-
tant finding from our earlier work [10,12c] was the
insight that different amino acids possess varying ‘‘helicity
inducing” power. In order to gain a deeper understanding,
we now wish to present a more systematic study. An NMR
and CD spectroscopy-based structural analysis of 12
unsymmetrical peptides 1–12 is performed with the sym-
metrical derivatives 13–21 used for comparison (Fig. 2).
Fig. 2. Ferrocene peptides 1–21 studied in this paper (* denotes the OtBu
ester).
Peptides 1–4 are used to study the influence of different chi-
ral amino acids on the helical chirality of the ferrocene core
while the other amino acid is achiral (glycine) in all cases.
In derivatives 2, 5 and 6 phenylalanine is held constant
as the chiral amino acid, while the distance to the carbonyl
group of the other amino acid is systematically increased
from glycine (Gly) to b-alanine (bAla) to c-amino-butyric
acid (cAba). Finally, although it is of course chiral, proline
is a secondary amino acid that is not able to contribute an
NH group for hydrogen bonding. It will be interesting to
compare the secondary structures of proline derivatives
9–12 (chiral, no hydrogen bonding possible) with those of
glycine derivatives 1–4 (achiral, hydrogen bonding).
CO2H
NH2
CO2H
NH2
Fe
CO2H
NH2
Fig. 1. Unnatural amino acids.

896
S.I. Kirin et al. / Inorganica Chimica Acta 362 (2009) 894–906
Aa1
H2N
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
OH
N
H
N
H
N
H
O
O
O
O
O
O
O
O
+
+
+
Fe
Fe
Fe
Fe
H
N
H
N
H
N
H2N
O
O
Aa2
Fc-Aa1Aa1
Fc-Aa1Aa2
Fc-Aa2Aa2
Scheme 1. One-pot synthesis of ferrocene peptides 1–21, an example with Aal = H-Ala-OMe and Aa2 = H-Gly-OMe is shown (reaction entry 1 in Table
1). Reaction conditions: (a) 1,10-ferrocene dicarboxylic acid (1 equiv.), HBTU (1 equiv.), HOBt (1 equiv.), DIPEA (4 equiv.), Aal (0.5 equiv.) and Aa2
(0.5 equiv.), CH2Cl2, 0 °C ? r.t, 6 h; (b) HBTU (1 equiv.), HOBt (1 equiv.), DIPEA (4 equiv.), Aal (0.5 equiv.) and Aa2 (0.5 equiv.), r.t, 16 h. For further
details see Table 1.
Table 2
Table 1
Chromatographic properties of compounds 1–21 on silica
Synthesis of ferrocenoyl peptides 1–21
Compound
Rf la
Rf 2b
Reaction Aal
entry
Aa2
Fc-
AalAal
Fc-
Fc-
AalAa2 Aa2Aa2
1 (Ala, Gly)
2 (Phe, Gly)
3 (Phg, Gly)
4 (Val, Gly)
5 (Phe, bAla)
6 (Phe, cAba)
7 (Phe*, en)
0.10
0.13
0.16
0.15
0.09
0.09
0.08
0.15
0.10
0.13
0.15
0.15
0.06
0.14
0.55
0.53
0.30
0.32
0.04
0.05
0.03
0.03
0.43
0.60
0.62
0.58
0.51
0.51
0.21c
0.67
0.38
0.53
0.56
0.52
0.34
0.52
0.89
0.87
0.77
0.72
0.24
0.22
0.32
0.28
Rl
H-Ala-OMe H-Gly-OMe
H-Phe-OMe H-Gly-OMe
H-Phg-OMe H-Gly-OMe
H-Val-OMe H-Gly-OMe
H-Phe-OMe H-bAla-OMe 15 (28%) 5 (22%) 18 (18%)
H-Phe-OMe H-cAba-OMe 15 (17%) 6 (23%) 19 (23%)
H-Phe-OtBu H-en-Fmoc
H-Phe-OtBu H-pn-Fmoc
H-Ala-OMe H-Pro-OMe
H-Phe-OMe H-Pro-OMe
H-Phg-OMe H-Pro-OMe
H-Val-OMe H-Pro-OMe
14 (18%) 1 (27%) 13 (16%)
15 (22%) 2 (30%) 13 (19%)
16 (24%) 3 (40%) 13 (24%)
17 (26%) 4 (41%) 13 (26%)
R2
R3
R4
R5
R6
R7
R8
R9
R10
R11
R12
a
8 (Phe*, pr)
15b (26%) 7 (41%) 20 (29%)
15b (25%) 8 (42%) 21 (23%)
9 (Pro, Ala)
10 (Pro, Phe)
11 (Pro, Phg)
12 (Pro, Val)
13 (Gly, Gly)
14 (Ala, Ala)
15 (Phe, Phe)
15b (Phe*, Phe*)
16 (Phg, Phg)
17 (Val, Val)
18 (bAla, bAla)
19 (cAba, cAba)
20 (en, en)
a
a
a
a
a
a
a
a
–
–
–
–
9 (19%)
10 (29%)
11 (59%)
12 (53%)
–
–
–
–
Not isolated/determined.
2. Results and discussion
2.1. Synthesis
The unsymmetrical 1,n0-disubstituted ferrocenoyl pep-
tides 1–12 were prepared in a one-pot reaction as shown
in Scheme 1 and Table 1 [12c]. Commercially available
1,10-ferrocene dicarboxylic acid was first activated with
1 equiv. of the coupling reagent HBTU and reacted with
a mixture of 0.5 equiv. of amino acid Aal and 0.5 equiv.
of amino acid Aa2. In a second step this procedure was
repeated, again activation with 1 equiv. of HBTU was fol-
lowed by reaction with a mixture of 0.5 equiv. of amino
acid Aal and 0.5 equiv. of amino acid Aa2. The one-pot
reaction thus gives a mixture of three products, namely
Fc-AalAal, Fc-AalAa2 and Fc-Aa2Aa2. If the parent
amino acids Aal and Aa2 differ sufficiently in polarity
[12c,13], the three-component mixture can be separated
by column chromatography using an ethyl acetate/n-hex-
ane gradient. The chromatographic properties using two
different compositions of the eluent mixture are listed for
all ferrocenoyl peptides in this work in Table 2. The total
isolated yields of Fc-AalAal, Fc-AalAa2 and Fc-Aa2Aa2
are generally above 70%, with the yields in reactions in
entries 7 and 8 being closest to the expected statistical dis-
tribution of 1:2:1, see Table 1. For most compounds, the
yield of the unsymmetrical product Fc-AalAa2 was less
21 (pr, pr)
Phe* denotes the tBu ester.
a
Eluent mixture: ethyl acetate:n-hexane 5:5.
Eluent mixture: ethyl acetate:n-hexane 9:1.
Eluent mixture: ethyl acetate:n-hexane 7:3.
b
c
than stoichiometrically expected. Surprisingly, however,
the reaction entries 11 and 12 (Table 1) with Pro as Aa2
yielded the unsymmetrical derivatives with total yields in
excess of 50%. Comparable yields were obtained in our ear-
lier study using this one-pot two step amidation [12c] as
well as by Skoda-Foldes et al. [12d], who used a one-pot
palladium-catalyzed aminocarbonylation starting from
l,l0-diiodoferrocene. The Skoda–Foldes protocol, however,
requires an additional catalyst and is performed at elevated
pressure (40 bar). Other known approaches require the iso-
lation of an unsymmetrically substituted ferrocenoyl inter-
mediate, Fe[C5H4-CO-Pron-OBzl][C5H4-CO-OBt] (n = 3,
4) [12a], or Fe[C5H4-CO2H][C5H4-CO2Me] [9c,14]. All fer-
rocene peptides prepared in this study were characterized
l
by H and 13C NMR spectroscopy, mass spectrometry
(including HR-EI MS), in addition to UV/Vis and CD
spectroscopy. Compounds 1–21 display the usual orange

S.I. Kirin et al. / Inorganica Chimica Acta 362 (2009) 894–906
897
colour of ferrocene conjugates, which results from a d–d
transition around 440 nm.
2.2. Structural studies in solution
The ferrocenoyl peptides 1–4 carry only one chiral
amino acid, while the second amino acid Gly is not chiral,
see Fig. 2. The amide protons in lH NMR (CDCl3) spectra
of 1–4 show resonances above 7 ppm which is clearly indic-
ative of the formation of two hydrogen bonds in solution.
Characteristic examples of CD spectra of the unsymmetri-
cal (Val, Gly)-derivative 4 and the corresponding symmet-
rical derivatives 13 and 17 are depicted in Fig. 3. Since no
other source of chirality is present in the (Gly, Gly)-deriv-
ative 13, a racemic mixture of M- and P-helical isomers is
formed during synthesis and no CD signal is observed
[12c]. The CD spectrum of the (Val, Val)-derivative 17
reveals a strong positive peak at 477 nm, characteristic of
the well-known ‘‘Herrick conformation” with two intramo-
lecular inter-strand hydrogen bonds, where the L-amino
acids induce a P-configuration of the ferrocene core
[4a,7,8]. The crystal structure of 17 showed an L,P,L-‘‘Her-
rick conformation” in the solid state as well [15,8]. The CD
spectrum of the unsymmetrical (Val, Gly)-derivative 4 is
qualitatively very similar to the spectrum of 17, as shown
in Fig. 3. All the unsymmetrical peptides 1–3 show features
similar to 4 in their CD spectra. It can therefore be con-
cluded that peptides 1–4 adopt the ‘‘Herrick conforma-
tion” in solution with two hydrogen bonds and an L,P-
configuration. One chiral amino acid in 1–4 is sufficient
to induce chirality at the 1,n0-disubstituted ferrocene moi-
ety, giving rise to a strong peak in the CD spectrum at
about 480 nm.
Fig. 4. CD (CH2Cl2) spectra of ferrocene peptides 2, 5 and 6.
pounds, only one chiral amino acid is present. The
l
chemical shift of the amide protons in the H NMR
(CDCl3) of 2 are both above 7.5 ppm, supporting their
involvement in hydrogen bonding. In the unsymmetrical
derivatives 5 and 6, the amide protons gradually move to
higher field, namely from 7.58 ppm (2) to 7.24–7.10 ppm
(5, both NH protons) and 7.00 ppm in 6. The CD spectra
of 5 and 6 display ‘‘Herrick” patterns with the expected
L,P-configuration, but the signals for both are again
weaker compared to those of 2, see Fig. 4. Both observa-
tions taken together, the conformational analysis of pep-
tides 2, 5 and 6 hence indicates that elongation of one
arm by subsequent introduction of additional methylene
groups in 1,n0-disubstituted ferrocene peptides weakens
the intramolecular hydrogen bonds. This situation is
depicted in Fig. 6a. It is well established from previous
work that a stable conformation is only achieved if two
intra-strand hydrogen bonds are present. When the hydro-
gen bond to the carbonyl group of the amino acid on the
lower Cp substituent is weakened, then this crucial second
Next, the solution conformation of peptides 2, 5 and 6
was examined. In these compounds, the a-amino acid
Gly in the (Phe, Gly)-derivative 2 is exchanged for b-amino
acid bAla in 5 or with the c-amino acid cAba in 6, while the
Phe substituent on the other ferrocene ring is kept con-
stant, as shown in Fig. 2. As in the previous set of com-
Fig. 3. CD (CH2Cl2) spectra of ferrocene peptides 4, 13 and 17.
Fig. 5. CD (CH2Cl2) spectra of ferrocene peptides 7, 8 and 15b.

898
S.I. Kirin et al. / Inorganica Chimica Acta 362 (2009) 894–906
hydrogen bond interaction is gradually weakend and con-
sequently, the helically chiral conformation loosens up.
In compounds 7 and 8, the ferrocene core is substituted
with one amino acid (Phe) and one diamine, namely ethyl-
ene (en) or propylene (pn) diamine, respectively (Fig. 2).
Peptides 7 and 8 are of interest because they have anti-par-
allel strands with orthogonal protection (Fmoc/tBu) and
could be used as precursors for solid phase peptide synthe-
sis of oligomers [16]. In Fig. 5, the CD spectra of 7 and 8
are compared to the CD spectrum of 15b. In contrast to
the CD spectra in Figs. 3 and 4, it is immediately apparent
that the unsymmetrical peptides 7 and 8 display much
weaker signals, although the ‘‘Herrick” pattern characteris-
tic for the expected L,P-configuration is preserved. The CD
spectra of 7 and 8 are practically superimposable. We thus
conclude that, contrary to the case of 2, 5 and 6, the num-
ber of methylene groups on the second strand (n = 2 for 7
and n = 3 for 8) has no influence on the intensity of the CD
signal. These results can be rationalized if one assumes only
one interstrand hydrogen bond between the Cp–CONH
amide proton of the diamine and the carbonyl oxygen atom
of the phenylalanine ester group. This interaction is
depicted in Fig. 6b.
In proline derivatives 9–12, three hydrogen bonds are
conceivable, see Fig. 6c–e. As proline is a secondary amino
acid with no NH group, only one hydrogen bond can form.
This will lead to a less stable conformation in solution, and
therefore was not studied in more detail experimentally. On
the other hand, the proline derivatives are well suited to
study the more subtle conformational effects that may
come into play in the absence of strong hydrogen bonding.
We have previously outlined all possible conformations
and suggested a suitable nomenclature [8]. They were, how-
ever, not studied in any further detail so far. To assess the
relative stability of all those possible conformations, we use
computational methods in the following.
2.3. Density functional calculations
Qualitatively, we have shown above how systematic
alteration of geometric factors may gradually weaken the
hydrogen bonding strength in ferrocene peptide turn mim-
ics. Previous calculations were carried out to determine the
stability of such systems with respect to the number of
hydrogen bonds and the difference in energy of the various
relative orientations of the substituents on the two Cp
rings, i.e. 1,10, 1,20 or 1,30 [9b]. As described in a recent
review article [8], these parameters represent the major
structural characteristics for 1,n0-disubstituted ferrocene
peptides with the heaviest influence on the total energy of
the system. More subtle variations will arise from the
trans
cis
a
b
vs.
vs.
O
O
O
O
H
N
O
N
O
H
c
O
O
vs.
N
COOCH3
N
H3COOC
Fig. 7. Conformations (a–c) studied in this paper.
a
b
O
R
O
R
OMe
OMe
OtBu
N
H
N
H
O
O
O
Fe
Fe
H
N
H
N
NHFmoc
n
n
O
R
O
R
Herrick
"semi"-Herrick
c
d
e
O
O
O
O
O
OMe
OMe
N
OMe
OMe
N
N
OMe
OMe
O
O
O
O
Fe
Fe
H
N
O
Fe
H
N
O
H
N
H
O
non-classical H-bond
"semi"-Herrick
van Staveren
Fig. 6. Hydrogen bonding patterns (a–e) for the ferrocenoyl peptides 1–21 analyzed in this study.

S.I. Kirin et al. / Inorganica Chimica Acta 362 (2009) 894–906
899
Table 3
stituent (cis versus trans), and (c) the proline carboxylate
substituent relative to the Pro amide group (see Fig. 7
and Table 3).
Relative orientations of conformations II–IX as indicated in Fig. 7
Structure (a) Glycine CO–NH (b) CO–CO (c) HisCOOCH3–HisCO
All optimizations lead to local minimum structures as
judged from the absence of imaginary modes among the
calculated analytical vibrational frequencies. The opti-
mized structures clearly cluster in three groups based on
their energy relative to the open form I arbitrarily set to
zero (Fig. 8).
II
trans
trans
cis
trans
trans
trans
trans
cis
cis
III
IV
V
trans
cis
cis
trans
cis
VI
VII
VIII
IX
trans
trans
cis
cis
cis
trans
cis
trans
cis
cis
The first group comprises II and III, which are substan-
tially more stable than the open reference conformation I,
with relative energies of ꢀ17.4 and ꢀ14.1 kJ molꢀ1, respec-
tively. The second set of conformations is made up of IV–
VII. Their stability is comparable to that of I (DErel of ꢀ5.1
to +5.1 kJ molꢀ1) while the two structures VIII and IX in
the third set are substantially destabilized compared to I
(by +26.2 and +22.0 kJ molꢀ1, respectively). Interestingly,
the energetic clustering of conformations correlates well
with specific relative orientations of functional groups as
shown in Fig. 7. As indicated in Table 3, the two most sta-
ble structures II and III both show a trans configuration of
the Gly amide group and a trans orientation of the two Fc
carbonyl groups while the orientation of the Pro substitu-
ent is variable. Also, the strongly destabilized structures
VIII and IX have both a cis amide and a cis carbonyl
group, while the four conformations IV, V, VI, and VII
comparable in energy to open structure I only have one
or the other orientation cis or trans. The metrical data of
cis-/trans-orientation of the amide bond and the relative
orientations of the carbonyl group (Fig. 7). To obtain a
more detailed insight in the relative influence of these fac-
tors, density functional theory (DFT) calculations were
carried out on different conformations possible for a model
compound with amino acids Pro and Gly at the B3LYP/
Lanl2DZ level. This treatment has previously been shown
to give geometries and relative energies in good accordance
with experimental data [9a,9b,16c,18]. A total of nine struc-
tures I–IX were fully optimized without constraints to
cover a considerable part of the conformational space of
(Pro, Gly). The different starting geometries were chosen
to represent all possible relative orientations of: (a) the 1-
versus 10-CO moieties, (b) the amide group of the Gly sub-
30
+26.2
˚
the ferrocene moiety (Fe–C distances of 2.10–2.15 A and
+22.0
˚
Cp(centroid)–Cp(centroid) distances of 3.45–3.47 A) are
20
as expected for ferrocene derivatives and essentially con-
stant throughout the series. Therefore, the following dis-
cussion of structural parameters will be restricted to the
Cp-amide dihedral angle b (Table 4) together with an
examination of close contacts between the two peptides
chains [8].
Though calculated to be the most stable conformation,
II exhibits a considerable deviation from coplanarity of
the mean plane of the Cp ring and the O@C–N–H unit nor-
mally found in ferrocene peptides as indicated by large
dihedral angles b of 18.3° for the glycine and 21.4° for
the proline substituent. Most surprisingly, however, closer
examination of the optimized structure of II does not show
the postulated ‘‘Semi-Herrick” or ‘‘van Staveren” confor-
mation (Fig. 6). Instead, a non-classical hydrogen bond is
present between the C@O oxygen atom of the proline sub-
10
+5.1
+0.5
0.0
-1.5
0
-10
-20
-5.1
-14.1
-17.4
II
I
III IV
V
VI VII VIII IX
Fig. 8. Relative energies of conformations I–IX optimized at the B3LYP/
Lanl2DZ level with I as the reference compound set to zero. All energies
were corrected for the ZPE.
Table 4
Comparison of metrical parameters and relative stabilities of conformations I–IX optimized at the B3LYP/Lanl2DZ level
I
II
III
IV
V
VI
VII
VIII
IX
O@C–N–H Gly (°)
O@C–N–CH2 Pro (°)
h (°)
3.6
1.1
1.4
11.6
7.9
3.0
11.4
5.4
18.3
21.4
6.2
ꢀ17.4
1.1
0.2
1.2
9.6
10.6
12.6
0.6
10.8
12.7
5.5
0.2
1.8
0.5
4.8
2.3
2.5
+0.5
8.6
8.2
6.9
20.3
14.9
2.5
ꢀ1.5
4.5
1.8
2.8
4.0
10.0
8.8
3.2
18.5
1.8
10.9
+26.2
1.6
2.3
5.2
9.8
6.1
44.9
+22.0
b (°) Cp-Gly
b (°) Cp-Pro
x (°)
2.7
3.5
144.5
0.0
11.4
ꢀ14.1
55.8
ꢀ5.1
DErel (kJ molꢀ1
)
+5.1

900
S.I. Kirin et al. / Inorganica Chimica Acta 362 (2009) 894–906
formation. Rather, at least two structures were suggested in
equilibrium by NMR methods.
In accord with these experimental findings, the second
most stable structure III is devoid of any obvious stabiliz-
ing intramolecular contacts (Fig. 10), but displays only
minimal distortions from coplanarity of the Cp and amide
moieties. Additionally, the amide O and N atoms from the
opposite substituents are in an almost perfect staggered
arrangement. Thus, a subtle interplay of several weak sta-
bilizing interactions and lack of energetically unfavourable
distortions of the substituents is likely to be responsible for
the relative stability of this structure.
Only three other structures IV, VII and VIII show close
intermolecular contacts. All of them are, however, consid-
erably higher in energy than II and III and therefore will be
only briefly described here. A detailed description with
coordinates of all atoms is included in Supplementary
material. In this set, the glycine amide bond in IV has a
cis configuration. Although the Oꢁ ꢁ ꢁH distance at
Fig. 9. Diamond 3.0 plot of the B3LYP/Lanl2DZ optimized geometry of
II.
˚
1.9947 A is even slightly shorter than in II, a C@Oꢁ ꢁ ꢁH
stituent ester group and a hydrogen atom from the methy-
angle of only 133.8° is clearly not a favourable hydrogen-
bonding interaction. In conformation VII, the distance
between the glycine NH proton and the proline substituent
lene group of the glycine (Fig. 9). With an Oꢁ ꢁ ꢁH distance
˚
of 2.0980 A and a C@Oꢁ ꢁ ꢁH angle of 165.5°, this is close to
the ideal values expected for a hydrogen bond [19]. Appar-
ently, the 12-membered macrocycle thus formed is more
stable than the 8- and 11-membered rings of the hypothetic
‘‘Semi-Herrick” or ‘‘van Staveren” conformations.
˚
carboxylate C@O at 3.1563 A is too long for an attractive
interaction. In addition, the C@Oꢁ ꢁ ꢁH angle of 87.2° is far
off from what is to be expected for a hydrogen bond. In
structure VIII, the Oꢁ ꢁ ꢁH distance of 2.0933 A would be
close enough for a hydrogen bond, but the C@Oꢁ ꢁ ꢁH angle
of 131.9° in combination with a cis arrangement of the gly-
cine amide bond results in this structure being rather high
in energy even with respect to open I.
Lippert and coworkers have described related non-clas-
sical hydrogen bonding involving an acidic C–H bond of
cytosine [20]. In their case, the hydrogen bond acceptor
was a deprotonated nitrogen of another nucleobase. Metal
coordination to Pt(II) fragments was used to block other
potential hydrogen bonding partners, thus enforcing the
‘‘non-classical” case. Unfortunately, we were unable to
grow single crystals of the Pro and Gly derivatives. Also,
NMR studies in solution (1D-NOE as well as 2D-NOESY
and ROESY) did not yield unambiguous proof of this con-
3. Conclusion
The one-pot synthesis of unsymmetrically substituted
1,n0-ferrocenoyl peptides is presented, starting from the
commercially available 1,10-ferrocene dicarboxylic acid
and two different amino acids Aal and Aa2. The three
intensively orange-coloured products, Fc-AalAal, Fc-
AalAa2 and Fc-Aa2Aa2, are easily separated by column
chromatography with an ethyl acetate:n-hexane gradient.
The viability of this methodology is shown on twelve differ-
ent examples, with combined isolated yields of Fc-AalAal,
Fc-AalAa2 and Fc-Aa2Aa2 above 65%.
The conformation of unsymmetrical ferrocenoyl pep-
1
tides 1–12 was studied in solution by H NMR and CD
spectroscopy. In all cases, ‘Herrick” CD-pattern with a
positive signal around 480 nm were obtained, indicating a
L,P-configuration. Therefore, one chiral amino acid is suf-
ficient to induce helical chirality in 1–12. The hydrogen
bonding patterns are summarized in Fig. 6. Two strong
H-bonds are found in peptides 1–4. Peptides 2, 5 and 6,
have one strong hydrogen bond, while the second one
weakens as the number of methylene groups on the second
strand increases from n = 1 (in 2) to n = 3 (in 6). On the
other hand, in 7 and 8 only one H-bond is present, inde-
pendent of the number of methylene groups on the second
Fig. 10. Diamond 3.0 plot of the B3LYP/Lanl2DZ optimized geometry of
III.

S.I. Kirin et al. / Inorganica Chimica Acta 362 (2009) 894–906
901
strand, as shown in Fig. 6b. The proline derivatives 9–12
can by nature of the secondary amino acid form only one
intra-strand hydrogen bond. They are therefore well suited
for the study of more subtle structural effects, which were
performed by DFT calculations. In the light of the biolog-
ical significance of proline as the only secondary amino
acid, and its possible involvement in conditions such as
Alzheimer’s disease, the study of secondary interactions
in Pro-containing ferrocene peptides seems worthwhile.
Indeed, novel and unusual hydrogen bonding motifs were
suggested computationally.
H-Aa2-OMe ꢂ HC1 (0.5 mmol) was added and stirring
was continued overnight. After this period, CH2Cl2
(40 ml) was added to the reaction mixture and it was
washed with NaHCO3 (sat. aq, 3 ꢂ 80 ml), citric acid
(10% aq, 3 ꢂ 80 ml) and water (80 ml). The organic phase
was dried over MgSO4, filtered and evaporated under
reduced pressure to yield an orange solid as crude product.
The crude mixture was purified by flash column chroma-
tography (silica, 50 g) using an ethyl acetate:n-hexane gra-
dient. Typically, the starting eluent has higher n-hexane
content. The separation of the intensively coloured prod-
ucts is monitored visually. The ethyl acetate content of
the eluent is increased when the separation is satisfying.
For isolated yields see Table 1; for Rf values, see Table 2.
4. Experimental
4.1. General remarks
4.2.1. Fe[C5H4-CO-Ala-OMe][C5H4-CO-Gly-OMe], 1
Mr (C19H22FeN2O6) = 430.23; MS (El): 430 [M]+;
HRMS (El): exp. 430.0829, calc. 430.0827; H (CDCl3): d
8.02–8.00 (m, 1H, NHGly), 7.66 (d, 1H, NHAla, J = 7.7),
4.93–4.90 (m, 2H, HFc-a), 4.87–4.86 (m, 1H, Ha,Fc), 4.78
(pseudo-quintet, 1H, Ha,Ala), 4.65–4.63 (m, 1H, Ha,Fc),
4.62–4.54 (m, 3H, Ha1,Gly and Hb,Fc), 4.36–4.35 (m, 2H,
Reactions were carried out in ordinary glassware and
chemicals used without further purification. All chemicals
were obtained from Aldrich, Iris, Fluka or Novabiochem.
Pure L amino acid methyl esters were used. NMR spectra
1
1
were determined on a Bruker AM 360 spectrometer, H
at 360.14 MHz and 13C at 90.56 MHz. Chemical shifts, d
ppm, indicate a downfield shift from tetramethylsilane,
TMS, the internal standard. Coupling constants, J, are
given in Hertz. Individual peaks are marked as: singlet
(s), doublet (d), triplet (t), quartet (q) or multiplet (m).
Mass spectra were measured on a Mat 8200 instrument,
only characteristic fragments are given. UV/Vis spectra
were measured on a Varian CARY 100 instrument in
1 cm quartz Suprasil cells thermostated at 20 °C. Absorp-
Hb,Fc), 3.83 (s, 6H, HOMe), 3.60 (dd, 1H, Ha2,Gly
,
J = 17.5 and 4.9), 1.37 (d, 3H, Hb,Ala, J = 7.5); 13C NMR
(CDCl3): d 176.7 (Cester), 173.2 (Cester), 170.5 (Camide),
169.9 (Camide), 75.7 (Ci,Fc) 75.5 (Ci,Fc), 72.1 (Ca,Fc), 72.0
(Ca,Fc), 71.3 (Ca,Fc), 7.2 (Ca,Fc), 70.6 (Cb,Fc), 70.5 (Cb,Fc),
70.4 (Cb,Fc), 70.2 (Cb,Fc), 52.8 (Ca,Ala), 52.6 (COMe,Ala
)
47.8 (COMe), 41.0 (Ca,Gly), 17.1 (Cb,Ala); CD (CH2C12):
kmax (Mh) 485 (+4.0), 418 (ꢀ1.5), 356 (ꢀ3.2), 309 (+7.4).
tion maxima, kmax, and molar absorption coefficients, emax
,
are given in nm and Mꢀ1 cmꢀ1, respectively. CD spectra
were recorded on a JASCO J-810 spectropolarimeter in
1 cm quartz Suprasil cells under argon thermostated at
20 °C. Ellipticity maxima, kmax, are given in nm. Molar
ellipticity coefficients, Mh, were calculated as Mh = 100h/
c ꢂ 1, where ellipticity h is in deg, concentration c in mM
and path length 1 in cm, thus giving deg mMꢀ1 cmꢀ1 for
Mh [17]. Stock solutions were obtained by accurately
weighting ca. 5 mg of substance on an analytical balance
and dissolving this amount in 5 ml of CH2Cl2 in a graded
analytical flask. Typically, concentrations of 1.5–2.5 mM
were used for the measurements.
4.2.2. Fe[C5H4-CO-Phe-OMe][C5H4-CO-Gly-OMe], 2
Mr (C25H26FeN2O6) = 506.33; MS (El): 506 [M]+;
HRMS (El): exp. 506.1143, and calc. 506.1140; 1H (CDCl3):
d 7.96–7.92 (m, 1H, NHGly), 7.58 (d, 1H, NHPhe, J = 8.2),
7.31–7.19 (m, 5H, HPh), 4.97 (ddd, 1H, Ha,Phe, J = 10.2,
8.2 and 5.0), 4.87–4.86 (m, 1H, Ha,Fc), 4.83–4.82 (m, 2H,
Ha,Fc), 4.62–4.55 (m, 2H, Ha,Gly and Ha,Fc), 4.54–4.51 (m,
2H, Hb,Fc), 4.35–4.32 (m, 2H, Hb,Fc), 3.86 (s, 3H, HOMe,Phe),
3.81 (s, 3H, HOMe,Gly), 3.70 (dd, 1H, Ha,Gly, J = 17.6 and
4.9), 3.11 (dd, 1H, Hb,Phe, J = 13.8 and 5.0), 2.84 (dd, 1H,
Hb,Phe, J = 13.8 and 10.3); 13C NMR (CDCl3): d 175.5
(Cester), 173.2 (Cester), 170.5 (Camide), 170.2 (Camide), 136.6
(Ci,Phe), 128.8 (Cm,Phe), 128.6 (Co,Phe), 127.0 (Cp,Phe), 75.7
(Ci,Fc), 75.6 (Ci,Fc), 72.0 (Ca,Fc), 71.7 (Ca,Fc), 71.3 (2C,
Ca,Fc), 70.6 (Cb,Fc), 70.5 (Cb,Fc), 70.3 (Cb,Fc), 70.1 (Cb,Fc),
53.9 (Ca,Phe), 52.8 (COMe), 52.6 (COMe), 41.0 (Ca,Gly), 37.2
(Cb,Phe); CD (CH2C12): kmax (Mh) 476 (+3.3), 413 (ꢀ1.3),
352 (ꢀ3.2), 308 (+2.3).
4.2. General synthetic procedure
1,10-Ferrocene dicarboxylic acid (274 mg, 1 mmol) was
dissolved in CH2C12 (40 ml) and cooled to 0 °C in an ice
bath. HBTU (379 mg, 1 mmol), HOBt ꢂ H2O (153 mg,
1 mmol) and DIPEA (700 ml, 4 mmol) were added and
stirring was continued for 30 min. A mixture of H-Aal-
4.2.3. Fe[C5H4-CO-Phg-OMe][C5H4-CO-Gly-OMe], 3
Mr (C24H24N2O6Fe) = 492.31; MS (El): m/z 492 [M]+Å;
OMe ꢂ HC1
(0.5 mmol)
and
H-Aa2-OMe ꢂ HC1
1
(0.5 mmol) was added and stirring was continued over-
night. After this period, HBTU (379 mg, 1 mmol),
HOBt ꢂ H2O (153 mg, 1 mmol) and DIPEA (700 ml,
4 mmol) were added again and stirring was continued for
30 min. A mixture of H-Aal-OMe ꢂ HC1 (0.5 mmol) and
HRMS (El): m/z exp. 492.0984, calc. 492.0984; H NMR
(CDCl3): d 7.89 (d, 2H, NH, J = 9.0), 7.54–7.16 (m, 5 H,
H
Ph,Phg), 5.84 (d, 1H, Ha,PhG, J = 6.0), 4.90 (m, 2H, Ha,Fc),
4.83 (m, 2H, Ha,Fc), 4.65 (m, 2H, Hb,Fc), 4.52 (m, 2H,
Hb,Fc), 4.30 (s, 2H, Ha,Gly), 3.84 (s, 3H, HOCH ;Gly), 3.34
3

902
S.I. Kirin et al. / Inorganica Chimica Acta 362 (2009) 894–906
(s, 3H, HOCH ;Phg); 13C NMR (CDCl3): d 174.46 (COester,Gly),
Hb,Phe and Ha,Aba), 2.44 (t, 2H, Hc,Aba, J = 7.1), 1.93
(qui, 2H, Hb,Aba, J = 7.1); 13C NMR (CDCl3): d 173.96
(COester), 172.85 (COester), 170.26 (COamide), 170.16
(COamide), 136.32 (Ci,Ph), 129.15 (Cm,Ph), 128.67 (Co,Ph),
127.24 (Cp,Ph), 78.39 (Ci,Fc), 76.90 (Ci,Fc), 71.82 (Ca,Fc),
71.46 (Ca,Fc), 71.36 (Ca,Fc), 71.28 (Ca,Fc), 71.20 (Cb,Fc),
69.88 (Cb,Fc), 69.61 (Cb,Fc), 53.32 (CHa,Phe), 52.49
(COCH ;Phe), 51.69 (COCH ;Aba), 39.08 (CHa,Aba), 37.55
(CHb,Phe), 31.61 (Cc,Aba), 24.83 (Cb,Aba); UV/Vis (CH2Cl2):
cmax (e) 342 (316), 443 (212); CD (CH2Cl2): kmax (Mh) 306
(+1.52), 351 (ꢀ2.01), 414 (ꢀ1.07), 474 (+2.40).
3
172.26 (COester,Phg), 170.50 (COamide,Gly), 170.10
(COamide,Phg), 135.21 (Ci,Phg), 128.84 (Cm,Phg), 128.47
(Cp,Phg), 127.62 (Co,Phg), 75.53 (Ci,Fc), 75.30 (Ci,Fc), 72.25
(Ca,Fc), 72.02 (Ca,Fc), 71.36 (Ca,Fc), 71.29 (Ca,Fc), 70.71
(Cb,Fc), 70.54 (Cb,Fc), 70.31 (Cb,Fc), 70.22 (Cb,Fc), 56.73
(Ca,Phg), 53.05 (COCH ), 52.32 (COCH ), 40.85 (Ca,Gly); UV/
3
3
Vis (CH2Cl2): kmax (e) 348 (0.39), 445 (0.25); CD (CH2Cl2):
kmax (Mh) 310 (+9.8), 357 (ꢀ4.5), 421 (ꢀ2.5), 478 (+4.5).
3
3
4.2.4. Fc[C5H4-CO-Gly-OMe][C5H4-CO-Val-OMe], 4
Mr (C21H26N2O6Fe) = 458.29; MS (El): m/z 458 [M]+Å;
1
HRMS (El): m/z exp. 458.1142, calc. 458.1140; H NMR
4.2.7. Fe[C5H4-CO-Phe-OtBu][C5H4-CO-en-Fmoc], 7
Mr (C42H43N3O6Fe) = 741.65; MS (FAB, NBA): 741
[M]+; 1H NMR (CDCl3): d 7.74 (d, 2H, Ha,Fmoc, J =
(CDCl3): d 7.85 (s, 1H, NHGly, 7.36 (d, 1H, NHVal
,
J = 6.0 Hz), 4.99 (m, 2H, Ha,Fc), 4.85 (m, 2H, Ha,Fc),
4.56 (m, 1H, Ha,Val), 4.42 (m, 2H, Hb,Fc), 4.30 (m, 2H,
Hb,Fc), 3.78 (s, 3H, OCH3), 3.75 (s, 3H, OCH3), 1.94
(ddd, 1H, Hb,Val), J = 6.0, 12.0 and 21.0), 0.90 (dd, 6H,
Hc,Val, J = 6.0 and 12.0); 13C NMR (CDCl3): d 175.95
(COester,Val), 172.77 (COester,Gly), 170.57 (COamide,Val),
170.52 (COamide,Gly), 75.81 (Ci,Fc), 75.57 (Ci,Fc), 72.13
(Ca,Fc), 71.91 (Ca,Fc), 71.38 (Ca,Fc), 71.32 (Ca,Fc), 70.58
(Cb,Fc) 70.48 (Cb,Fc), 70.34 (Cb,Fc), 70.12 (Cb,Fc), 58.14
7.6), 7.63 (d, 2H, Hb,Fmoc, J = 7.6), 7.37 (t, 2H, Hc,Fmoc
,
J = 7.4), 7.33–7.21 (m, 7H, Hd,Fmoc and HPh), 6.47 (d,
2H, J = 7.6), 4.94 (m, 1H, CHa,Phe), 4.65 (m, 1H, Ha,Fc),
4.58 (m, 1H, Ha,Fc), 4.44–4.30 (m, 8H, HFc and HFmoc),
4.26–4.20 (t, 1H, He,Fmoc), 3.60–3.39 (m, 4H, Ha,en and
Hb,en), 3.27–3.10 (m, 2H, CHb,Phe), 1.45 (s, 9H, CtBu);
UV (CH2Cl2): kmax (e) 344 (308), 442 (208); CD (CH2Cl2):
kmax (Mh) 350 (ꢀ1.16), 415 (ꢀ0.38), 468 (+1.26).
(Ca,Val), 52.49 (2C, COCH ), 41.07 (Ca,Gly), 30.32 (Cb,Val),
3
19.41 (Cc,Val), 18.71 (Cc,Val); UV/Vis (CH2Cl2): kmax (e)
346 (0.31), 444 (0.19); CD (CH2Cl2): kmax (Mh) 309
(+8.3), 356 (ꢀ4.0), 416 (ꢀ1.6), 483 (+4.5).
4.2.8. Fe[C5H4-CO-Phe-OtBu][C5H4-CO-pn-Fmoc], 8
Mr (C43H45N3O6Fe) = 755.68; MS (FAB, NBA): 755
[M]+; 1H NMR (CDCl3): d 7.76 (d, 2H, Ha,Fmoc
,
J = 7.5), 7.61 (d, 2H, Hb,Fmoc, J = 7.4), 7.39 (t, 2H,
Hc,Fmoc, J = 7.4), 7.33–7.21 (m, 7H, Hd,Fmoc and HPh),
6.58 (d, 1H, NH J = 7.8), 5.69 (t, 1H, NH, J = 6.0),
4.94–4.86 (q, 1H, CHa,Phe, J = 7.2), 4.63–4.59 (m, 2H),
4.50 (s, 1H), 4.43–4.34 (m, 6H), 4.33–4.29 (m, 1H), 4.21
(t, 1H, He,Fmoc, J = 7.2), 3.48–3.12 (m, 6H, Ha,pn, CHc,pn
and CHb,Phe), 1.73 (t, 2H, CHb,pn, J = 6.0), 1.47 (s, 9H,
4.2.5. Fc[C5H4-CO-Phe-OMe][C5H4-CO-bAla-OMe], 5
Mr (C26H28N2O6Fe) = 458.36; MS (El): m/z 458 [M]+;
1
HRMS (El): m/z exp. 502.1298, calc. 502.1298; H NMR
(CDCl3): d 7.34–7.25 (m, 5H, HPh), 7.24–7.10 (m, 2H,
NHPhe and NHAla), 5.00 (m, 1H, Ha,Phe), 4.63 (m, 2H,
Ha,Fc), 4.56 (m, 1H, Ha,Fc), 4.40 (m, 2H, Ha,b,Fc), 4.33
(m, 2H, Hb,Fc), 4.28 (m, 1H, Hb,Fc), 3.81 (s, 3H,
HOCH ;Phe), 3.73 (s, 3H, HOCH ;Ala), 3.70–3.50 (m, 2H,
H
tBu); 13C NMR (CDCl3): d 171.47 (COester), 170.55
(COamide), 170.10 (COamide), 156.86 (COFmoc), 143.98
(Ci,Fmoc), 141.27 (Ci,Fmoc), 136.32 (Ci,Ph), 129.31 (Cm,Ph),
128.56 (Co,Ph), 127.61 (CFmoc), 127.15 (Cp,Ph), 127.02
(CFmoc), 125.11 (CFmoc), 119.91 (CFmoc), 82.58 (Ci,tBu),
78.37 (Ci,Fc), 76.87 (Ci Fc), 71.48 (Ca,Fc), 71.37 (Ca,Fc),
71.33 (Ca,Fc), 71.24 (Ca,Fc), 71.04 (Cb,Fc), 70.97 (Cb,Fc),
70.20 (Cb,Fc), 70.02 (Cb,Fc), 66.69 (Ca,Fmoc), 53.55
3
3
Hb,Ala), 3.32–3.14 (m, 2H, Hb,Phe), 2.89–2.80 (m, 1H,
Hc,Ala), 2.68–2.50 (m, 1H, Hc,Ala); 13C NMR: (CDCl3): d
173.45 (COester), 173.41 (COester), 170.21 (COamide),
170.10 (COamide), 136.61 (Ci,Ph), 129.06 (Cm,Ph), 128.59
(Co,Ph), 127.05 (Cp,Ph), 77.89 (Ci,Fc), 76.72 (Ci,Fc), 71.62
(Ca,Fc), 71.49 (Ca,Fc), 71.45 (Ca,Fc), 71.20 (Ca,Fc), 71.16
(Cb,Fc), 71.10 (Cb,Fc), 70.03 (Cb,Fc), 69.33 (Cb,Fc), 53.46
(Ca), 52.60 (COCH ;Phe), 51.85 (COCH ;Ala), 37.34 (Cb,Phe),
(Ca,Phe), 47.31 (Ce,Fmoc), 38.00 (Ca,pn), 37.80 (Cb,Phe
)
36.00 (Cc,pn), 30.06 (Cb,pn), 28.00 (CtBu); UV/Vis (CH2Cl2):
kmax (e) 344 (319), 442 (214); CD (CH2Cl2): kmax (e) 350
(ꢀ1.16), 415 (ꢀ0.38), 468 (+1.30).
3
3
35.58 (Cb,Ala), 33.79 (CHb,Ala); UV/Vis (CH2Cl2): kmax (e)
341 (373), 442 (241); CD: (CH2Cl2): kmax (Mh) 307
(+2.96), 352 (ꢀ2.85), 413 (ꢀ1.21), 475 (+3.09).
4.2.9. Fe[C5 H4-CO-Ala-OMe][C5H4-CO-Pro-OMe], 9
Flash column chromatography (silica, 75 g), Rf = 0.38
(ethyl acetate:hexane = 9:1). Orange solid, yield 90 mg
(19%) in reaction R9. Mr (C22H26N2O6Fe) = 470.30; MS
(El): m/z 470 [M]+ 1H NMR (CDCl3): d 7.99 (d, 1H,
NHAla, J = 6.5 Hz), 4.92 (m, lH, Ha,Ala), 4.75–4.73 (m,
2H, Ha,Fc), 4.61–4.59 (m, 2H, Ha Fc), 4.59 (m, 1H, Ha,Pro),
4.50–4.44 (m, 2H, Hb,Fc), 4.40–4.36 (m, 2H, Hb,Fc), 3.99–
4.2.6. Fe[C5H4-CO-Phe-OMe][C5H4-CO-cAla-OMe], 6
Mr (C27H30N2O6Fe) = 534.38; MS (El): m/z 534 [M]+;
502, 449, 266, 232; HRMS (El): m/z exp. 534.1454, calc.
1
534.1453; H NMR (300 MHz, CDCl3): d 7.36–7.22 (m, 5
H, HPh), 7.00 (t, 1H, NHAba, J = 5.5), 6.83 (d, 1H, NHPhe
,
J = 8.0), 4.97 (m, 1H, CHa,Phe), 4.59–4.53 (m, 3H, Ha,Fc),
4.42–4.39 (m, 1H, Ha,Fc), 4.36–4.30 (m, 3H, Hb,Fc), 4.8–
4.25 (m, 1H, Hb,Fc), 3.80 (s, 3H, HOCH ;Phe), 3.68 (s, 3H,
3.88 (m, 1H, Hd2,Pro), 3.79 (s, 3H, HOCH ;Ala), 3.76 (s, 3H,
3
3
HOCH ;Aba), 3.48–3.40 (m, 1H, Ha,Aba), 3.33–3.14 (m, 3H,
HOCH ;Pro), 3.74–3.65 (m, 1H, Hd1,Pro), 2.38–1.85 (m, 4H,
3
3

S.I. Kirin et al. / Inorganica Chimica Acta 362 (2009) 894–906
903
Hb,v,Pro), 1.47 (d, 3H, HCH ;Ala, J = 7.3 Hz); 13C NMR
mg (53%) in reaction Rl2. Mr (C24H30N2O6Fe) = 498.36;
MS (El): m/z 498 [M]+Å; HRMS (El): m/z exp. 498.1454,
calc. 498.1453; 1H NMR (CDCl3): d 7.83 (d, 1H, NH,
J = 8.1), 4.89 (ddd, 1H, Ha,Fc, J = 1.2, 2.7 and 3.9), 4.73
3
(CDCl3): d 174.0 (COester,Ala), 173.4 (COester,Pro), 170.2
(COamide,Ala), 169.8 (COamide, Pro), 77.7 H (Ci,Fc), 77.2
(Ci,Fc), 73.0 (Ca,Fc), 71.9 (Ca,Fc), 71.3 (Ca,Fc), 71.3 (Ca,Fc),
71.1(Cb,Fc), 70.8 (Cb,Fc), 70.4 (Cb,Fc), 59.7 (Ca,Pro), 52.4
(COCH ), 52.1 (COCH ), 49.0 (Ca,Ala), 48.6 (Cd, Pro), 29.0
(ddd, 2H, Ha,Fc, J = 1.2, 2.7 and 3.9), 4.62 (ddd, 1H, Ha,Fc
J = 1.2, 2.7 and 3.9), 4.60 (dd, 1H, Ha,Pro, J = 5.7 and 8.4),
4.49 (dd, 1H, Ha,Val, J = 6.3 and 8.1), 4.46 (ddd, 2H, Hb,Fc
,
3
3
(Cb,Pro), 25.7 (Cv,Pro), 17.1 (CCH ;Ala).
,
3
J = 1.2, 2.4 and 3.9), 4.38 (ddd, 2H, Hb,Fc, J = 1.2, 2.4 and
4.2.10. Fe[C5H4-CO-Phe-OMe][C5H4-CO-Pro-OMe], 10
Flash column chromatography (silica, 80 g), Rf = 0.53
(ethyl acetate:hexane = 9:1). Orange solid, yield 165 mg
(29%) in reaction R10. Mr (C28H30N2O6Fe) = 546.39;
MS (El): 546 [M]+; HRMS (El): exp. 546.1452 and calc.
3.9), 3.77 (s, 3H, HOCH ), 3.76 (s, 3H, HOCH ), 2.34–1.87 (m,
3
3
6H, HCH ;Pro), 1.03 (dd, 6H, CCH ;Val, J = 6.9 and 9.6); 13C
2
3
NMR (CDCl3): d 173.01 (COester), 172.98 (COester),
170.59 (COamide), 169.51 (COamide), 77.99 (Ci,Fc), 77.82
(Ci,Fc), 72.33 (Ca,Fc), 71.94 (Ca,Fc), 71.92 (Ca,Fc), 71.41
(Ca, Fc), 71.34 (Cb,Fc) 71.17(Cb,Fc) 70.82 (Cb,Fc), 70.29
546.1453; 1H NMR (CDCl3): d 8.12 (d, 1H, NHPhe
,
J = 7.0 Hz), 7.42–7.18 (m, 5H, HPh), 4.94 (m, lH, Ha,Phe),
4.82–4.75 (m, 1H, Ca,Pro), 4.67–4.62 (m, 3H, Ha,Fc), 4.48–
4.47 (m, 1H, Ha,Fc), 4.44–4.43 (m, 2H, Hb,Fc), 4.34–4.29
(m, 2H, Hb,Fc), 3.95–3.85 (m, 1H, HHd2,Pro), 3.76 (s, 3H,
HOCH ;Phe), 3.72 (s, 3H, COCH ;Pro) 3.69–3.63 (m, 1H,
(Cb,Fc), 59.69 (Ca,Val), 58.40 (Ca,Pro), 52.19 (COCH ), 51.77
3
(COCH ) 48.86 (Cd,Pro), 30.39 (Cb,Val), 28.85 (Cb,Pro), 25.55
3
(Cd,Pro), 19.20 (Cd2,Val), 18.61 (Cd1,Pro); UV/Vis (CH2Cl2):
kmax (e) 343 (0.34), 442 (0.23); CD (CH2Cl2): kmax (Mh)
307 (+1.6), 350 (ꢀ1.7), 410 (ꢀ0.7), 473 (+2.2).
3
3
Hd1,Pro), 3.25–3.06 (m, 2H, Hb,Phe), 2.37–1.90 (m, 4H,
Hb,v,Pro); 13C NMR (CDCl3): d 173.2 (COester,Phe), 172.9
(COester,Pro), 170.4 (COamide,Phe), 169.7 (COamide,Pro),
137.2 (Ci,Phe), 129.2 (Cm,Phe), 128.4 (C0,Phe), 126.7 (Cp,Phe),
77.9 (Ci,Fc), 77.8 (Ci,Fc), 72.8 (Ca,Fc), 72.3 (Ca,Fc), 71.8
(Ca,Fc), 71.3 (Ca,Fc), 71.0 (Cb,Fc), 70.7 (Cb,Fc), 70.0 (Cb,Fc),
59.8 (Ca,Pro), 54.5 (Ca,Phe), 52.3 (COCH ), 52.1 (COCH ) 49.0
4.2.13. Fe[CO-C5H4-Gly-OMe]2, 13
[12c] Mr (C18H20N2O6Fe) = 416.21; MS (El): m/z 416
1
[M]+; HRMS (El): m/z exp. 416.0670, calc. 416.0671; H
NMR (CDCl3): 7.94 (t, 2H, NH, J = 6.0), 4.81 (t, 4H,
Ha,Fc, J = 2.0), 4.46 (t, 4H, Hb,Fc, J = 2.0), (d, 4H, Ha,Gly
,
J = 6.3), 3.82 (s, 6H, HOCH ;Gly); 13C NMR (CDCl3): 173.5
3
3
3
(Cd,Pro), 37.2 (Cb,Phe), 29.0 (Cb,Pro), 25.6 (Cv,Pro). CD
(CH2Cl2): kmax (Mh) 476 (+2.6), 413 (ꢀ1.0), 352 (ꢀ2.5),
308 (+1.7).
(COester), 170.4 (COamide), 75.5 (Ci,Fc), 71.6 (Ca,Fc), 70.5
(Cb,Fc), 52.8 (COCH ;Gly), 40.9 (Ca,Gly); UV/Vis (CH2Cl2):
3
kmax (e) 438 (228), 338 (454); CD (CH2Cl2): kmax (Mh)
479 (+0.1), 308 (+0.3).
4.2.11. Fe[C5H4-CO-Pro-OMe][C5H4-CO-Phg-OMe], 11
Flash column chromatography (silica, 50 g), Rf = 0.56
(ethyl acetate:hexane = 9:1). Orange solid, yield 312 mg
(59%) in reaction Rll. Mr (C27H28N2O6Fe) = 532.38; MS
(El): m/z 532 [M]+Å; HRMS (El): m/z exp. 532.1298, calc.
4.2.14. Fe[C5H4-CO-Ala-OMe]2, 14
[12c] Mr (C20H24N2O6Fe) = 444.26; MS (EI): m/z 444
[M]+; 342, 271; HRMS (EI): m/z exp. 444.0985, calc.
444.0984; 1H NMR (CDCl3): d 7.74 (d, 2H, NH,
J = 8.0), 4.91–4.90 (s, 2H, Ha,Fc), 4.86 (m, 2H, Ca,Ala),
4.76–7.75 (m, 2H, Ha,Fc), 4.56–4.54 (m, 2H, Hb,Fc), 4.35–
532.1297; 1H NMR (CDCl3): d 8.27 (d, 1H, NHPhg
J = 7.2 Hz), 7.51–7.35 (m, 5H, HPh), 5.69 (d, 1H, Ha,Phg
,
,
J = 7.2), 4.98–4.96 (m, 1H, Ha,Fc), 4.78–4.77 (m, 1H,
Ha,Fc), 4.70–4.69 (m, 1H, Ha,Fc), 4.62–4.61 (ddd, 1H,
Ha,Fc), 4.57 (dd, 1H, Ha,Pro, J = 5.7 and 7.8), 4.47–4.44
(m, 2H, Hb,Fc), 4.41–4.39 (m, 1H, Hb,Fc), 4.34–4.32 (m,
1H, Hb,Fc), 3.85–3.93 (m, 1H, Hd2,Fc) 3.76 (s, 3H,
HOCH ;Phg), 3.66–3.73 (s, 4H, HOCH ;Pro and Hd1,Pro), 2.32–
4.33 (m, 2H, Hb,Fc), 3.81 (s, 3H, HOCH ;Ala), 1.40 (d, 3H,
3
Hb,Ala, J = 7.5); 13C NMR (CDCl3): d 176.3 (COester),
170.0 (COamide), 75.7 (Ci,Fc), 71.9 (Ca,Fc), 71.3 (Ca,Fc),
70.3 (Cb,Fc), 70.1 (Cb,Fc), 52.7 (Ca,Ala), 51.5 (CCH ;Ala),
2
16.7 (Cb,Ala); UV/Vis (CH2Cl2): kmax (e) 437 (251), 340
(410); (CH2Cl2): kmax (Mh) 484 (+5.5), 416 (ꢀ1.8), 356
(ꢀ4.8), 310 (+10.0).
3
3
1.80 (m, 4H, Hb,c,Pro); 13C NMR (CDCl3): d 172.85
(COester,Phg), 171.70 (COester,Pro), 170.18 (COamide,Phg
169.54 (COamide,Pro), 136.23 (Ci,Phg), 128.67 (Cm, Phg),
128.30 (C0,Phg), 128.14 (Cp,Phg), 77.70 (Ci,Fc) 77.29 (Ci,Fc
)
4.2.15. Fe[C5H4-CO-Phe-OMe]2, 15
)
[12c] Mr (C32H32N2O6Fe) = 596.45; MS (EI): m/z 596
[M]+; 434, 271; HRMS (EI): m/z exp. 596.1613, calc.
596.1610; 1H NMR (CDCl3): d 7.73 (d, 2H, NH,
72.31 (Ca,Fc), 72.10 (Ca,Fc), 71.88 (Ca,Fc), 71.57 (Ca,Fc),
71.37 (2C, Cb,Fc), 70.95 (Cb,Fc) 70.38 (Cb,Fc), 59.57 (Ca,Phg),
57.28 (Ca,Pro), 52.43 (COCH ), 52.23 (COCH ), 48.90 (Cd,Pro),
J = 8.5), 7.33–7.20 (m, 10H, HPh), 5.04 (ddd, 2H, Ha,Phe
,
3
3
28.71 (Cb,Pro), 25.59 (Cc,Pro); UV/Vis (CH2Cl2): kmax (e) d
343 (0.34), 444 (0.23); CD (CH2Cl2): kmax (Mh) = 313
(+0.9), 353 (ꢀ1.5), 414 (ꢀ0.6), 480 (+1.1).
J = 10.5, 8.5 and 5.0), 4.80–4.79 (m, 2H, Ha,Fc), 4.68–
4.67 (m, 2H, Ha,Fc), 4.51–4.49 (m, 2H, Hb,Fc), 4.30–4.29
(m, 2H, Hb,Fc), 3.85 (s, 2H, HOCH ;Phe), 3.22 (dd, 2H, Hb,Phe
,
3
J = 14.0 and 5.0), 2.98 (dd, 2H, Hb,Phe, J = 14.0 and 10.5);
13C NMR (CDCl3): d 175.4 (COester), 170.3 (COamide),
136.7 (Ci,Phe), 128.9 (Cm,Phe), 128.6 (Co,Phe), 127.0 (Cp,Phe),
75.8 (Ci,Fc), 71.8 (Ca,Fc), 71.3 (Ca,Fc), 70.3 (Cb,Fc), 69.9
4.2.12. Fe[C5H4-CO-Phe-OMe][C5H4-CO-Pro-OMe], 12
Flash column chromatography (silica, 50 g), Rf = 0.52
(ethyl acetate:hexane = 9:1). Orange-red solid, yield 266

904
S.I. Kirin et al. / Inorganica Chimica Acta 362 (2009) 894–906
(Cb,Fc), 53.9 (Ca,Phe), 52.8 (COCH ;Phe), 37.0 (Cb,Phe); UV/Vis
J = 6.2); 13C NMR (CDCl3): d 173.14 (COester), 170.13
3
(CH2Cl2): kmax (e) 438 (249), 341 (411); CD (CH2Cl2): kmax
(Mh) 481 (+5.6), 415 (ꢀ2.0), 355 (ꢀ6.4), 311 (+7.9).
(COamide), 78.04 (Ci,Fc), 71.20 (Ca,Fc), 70.51 (Cb,Fc), 51.79
(COCH ), 35.45 (Ca), 33.95 (Cb). UV/Vis (CH2Cl2): kmax
3
(e) 338 (304), 441 (213).
4.2.16. Fe[C5H4-CO-Phe-OtBu]2, 15b
Mr (C38H44N2O6Fe) = 680.61; MS (EI): m/z 680 [M]+;
624, 568; HRMS (EI): m/z exp. 680.2548, calc. 680.2549;
1H NMR (CDCl3): d 7.91 (d, 2H, NH, J = 8.6), 7.33–
7.21 (m, 10H, HPh), 5.00–4.92 (m, 2H, Ha,Phe), 4.84 (m,
4.2.20. Fe[C5H4-CO-c-Aba-OMe]2, 19
Mr (C22H28N2O6Fe) = 472.31; MS (EI): m/z 472 [M]+;
440, 356, 316, 232; HRMS (EI): m/z exp. 472.1299, calc.
1
472.1297; H NMR (CDCl3): d 7.03 (t, 2H, NH, J = 5.0),
2H, Ha,Fc), 4.67 (m, 2H, Ha,Fc), 4.51 (m, 2H, Hb,Fc
,
4.49 (m, 4H, Ha,Fc), 4.36 (m, 4H, Hb,Fc), 3.69 (s, 6H,
J = 1.4), 4.30 (m, 2H, Hb,Fc), 3.19–3.03 (m, 4H, CHb,Phe),
1.47 (s, 18H, HtBu); 13C NMR (CDCl3): d 174.42 (COester),
170.14 (COamide), 136.99 (Ci,Ph), 129.06 (Cm,Ph), 128.45
(Co,Ph), 126.83 (Cp,Ph), 82.58 (Ci,tBu), 75.85 (Ci,Fc), 71.86
(Ca,Fc), 71.34 (Ca,Fc), 70.21 (Cb,Fc), 70.13 (Cb,Fc), 54.52
(Ca,Phe), 37.27 (CHb,Phe), 28.02 (CtBu); UV/Vis (CH2Cl2):
kmax (e) 347 (445), 445 (231); CD (CH2Cl2): kmax (Mh)
311 (+9.44), 355 (ꢀ6.42), 415 (ꢀ2.05), 482 (+5.87).
HOCH ), 3.44 (q, 4H, Ha, J = 6.8), 2.47 (t, 4H, Hc,
3
J = 7.2), 1.97 (qui, 4H, Hb); 13C NMR (CDCl3): d 174.03
(COester), 170.42 (COamide), 78.59 (Ci,Fc), 70.89 (Ca,Fc),
70.68 (Cb,Fc), 51.72 (COCH ), 39.28 (Ca) 31.68 (Cc), 24.70
3
(Cb). UV/Vis (CH2Cl2): kmax (e) 338 (326), 441 (231).
4.2.21. Fe[C5H4-CO-en-Fmoc]2, 20
Mr (C46H42N4O6Fe) = 802.69; MS (FAB, NBA): 803
[M]+; 1H NMR (CDCl3): d 7.73 (d, 4H, Ha,Fmoc
,
4.2.17. Fc[C5H4-CO-Phg-OMe]2, 16
Mr (C30H28N2O6Fe) = 568.41; MS (EI): m/z 568 [M]+Å;
HRMS (EI): m/z exp. 568.1299, calc. 568.1297; H NMR
J = 7.5), 7.57 (d, 4H, Hb,Fmoc, J = 7.4), 7.36 (t, 4H,
Hc,Fmoc, J = 7.3), 7.29–7.21 (t, 4H, Hd,Fmoc, J = 7.5), 7.04
(s, 2H, NH), 6.04 (s, 2H, NH), 4.53–4.36 (m, 12H, HFc
and HFmoc), 4.16 (m, 2H, He,Fmoc), 3.57–3.28 (m, 8H, Ha
and CHb). 13C NMR (CDCl3): d 170.81 (COamide), 157.29
(COFmoc), 143.83 (CFmoc), 141.26 (CFmoc), 127.69 (CFmoc),
127.02 (CFmoc), 125.04 (CFmoc), 120.07 (CFmoc), 77.87
(Ci,Fc), 71.21 (Ca,Fc), 70.71 (Cb,Fc), 66.78 (CFmoc), 47.31
(CFmoc), 40.94 (CHa,en), 40.58 (Cb,en); UV/Vis (CH2Cl2):
kmax (e) 342 (317), 441(217).
1
(CDCl3): d 7.92 (d, 2H, NH, J = 8.7), 7.32 (m, 10H, Ph),
5.99 (d, 2H, Ha, J = 8.7), 4.88 (ddd, 2H, Ha,Fc, J = 1.2,
2.4 and 3.9), 4.77 (ddd, 2H, Ha,Fc, J = 1.5, 2.7 and 3.9),
4.54 (ddd, 2H, Hb,Fc, J = 1.2, 2.4 and 3.9), 4.38 (ddd, 2
H, Hb,Fc, J = 1.2, 2.4 and 3.6), 3.67 (s, 6H, HOCH ); 13C
3
NMR (CDCl3): d 173.27 (COester), 170.20 (COamide),
135.86 (Ci,Phg), 128.79 (Cm,Phg), 128.46 (Co,Phg), 128.04
(Cp,Phg), 76.30 (Ci,Fc), 72.18 (Ca,Fc), 71.81 (Ca,Fc), 70.87
(Cb,Fc), 70.32 (Cb,Fc), 56.16 (Ca,Phg), 53.06 (COCH ). UV/
4.2.22. Fe[C5H4-CO-pn-Fmoc]2, 21
Mr (C48H46N4O6Fe) = 830.75; MS (FAB, NBA): m/z
3
Vis (CH2Cl2): kmax (e) 347 (0.43), 444 (0.27); CD (CH2Cl2):
kmax (Mh) 312 (+6.6), 356 (ꢀ5.8), 417 (ꢀ2.0), 481 (+3.8).
1
831 [M]+; H NMR (CDCl3): d 7.76 (d, 4H, Fmoc-Ha,
3
3J = 7.5 Hz), 7.60 (d, 4H, Fmoc-Hb, J = 7.5 Hz), 7.39 (t,
4.2.18. Fc[C5H4-CO-Val-OMe]2, 17
[15] Mr (C24H32N2O6Fe) = 500.37; MS (EI): m/z 500
4H, Fmoc-Hc, 3J = 7.5 Hz), 7.30 (t, 4H, Fmoc-Hd,
3
3J = 7.5 Hz), 5.56 (t, 2H, NH, J = 6.0 Hz), 4.55 (s, 4H),
1
[M]+Å; HRMS (EI): m/z exp. 500.1611, calc. 500.1610; H
4.44–4.38 (m, 8H), 4.24–4.18 (t, 2H, Fmoc-He,
3
NMR (CDCl3): d 7.51 (d, 2H, NH, J = 8.7), 4.85 (ddd,
3J = 6.8 Hz), 3.47–3.43 (q, 4H, CH2,a, J = 6.0 Hz), 3.43–
2H, Ha,Fc, J = 1.2, 2.7 and 3.9), 4.76 (ddd, 2H, Ha,Fc
,
3.26 (q, 4H, CH2,k,
3J = 6.0 Hz), 1.75 (m, 4H, CH2,b);
J = 1.2, 2.7 and 3.9), 4.65 (dd, 2H, Ha,Val, J = 7.2 and
8.7), 4.52 (ddd, 2H, Hb,Fc, J = 1.5, 2.7 and 4.2), 4.36
(ddd, 2H, Hb,Fc, J = 1.5, 2.7 and 3.6), 3.80 (s, 6H,
OCH3), 2.18 (ddd, 2H, Hb,Val, J = 6.9, 13.5 and 20.4),
1.00 (dd, 12H, Hc,Val, J = 2.4 and 6.9); 13C NMR (CDCl3):
d 175.15 (COester), 170.65 (COamide), 76.23 (Ci,Fc), 71.89
(Ca,Fc), 71.54 (Ca,Fc), 70.21 (Cb,Fc), 70.08 (Cb,Fc), 58.05
13C NMR (CDCl3): d 170.77 (COamide), 157.11 (COFmoc),
143.89 (Cq,Fmoc), 141.29 (Cq2,Fmoc), 127.67 (CFmoc),
127.01 (CFmoc), 125.00 (CFmoc), 119.95 (CFmoc), 78.51
(Ci,Fc), 71.04 (Ca,Fc), 70.67 (Cb,Fc), 66.64 (Cb,Fmoc), 47.28
(Ce,Fmoc), 37.83 (Ca,pn), 36.09 (Cc,pn), 29.84 (Cb,pn); UV
(CH2Cl2): kmax (e) 339 (312), 442 (217).
(Ca,Val), 52.32 (COCH ), 30.01 (Hb,Val), 19.39 (Cc,Val),
5. Computational methods
3
18.99 (Cc,Val); UV/Vis (CH2Cl2): kmax (e) 346 (0.39), 444
(0.25); CD (CH2Cl2): kmax (Mh) = 310 (+9.2), 355 (ꢀ5.8),
411 (ꢀ1.4), 477 (+5.6).
All calculations were performed with the GAUSSIAN 98
package on a Compaq ES40 parallel computer at the
Max-Planck-Institut fur Bioanorganische Chemie in Mul-
¨
¨
4.2.19. Fe[C5H4-CO-bAla-OMe]2, 18
heim an der Ruhr, Germany [21]. Geometries were opti-
mized without constrains using the RB3LYP exchange-
correlation functional and the double-zeta quality Lanl2DZ
basis set with ECPs on the heavy atoms due to the size of the
molecules and characterized as stationary points by analyt-
ical calculation of vibrational frequencies [22].
Mr (C20H24N2O6Fe) = 444.26; MS (EI): m/z 444 [M]+;
HRMS (EI): m/z exp. 444.0985, calc. 444.0984; 1H
NMR: (CDCl3): d 7.06 (t, 2H, NH, J = 5.4), 4.52 (m,
2H, Ha,Fc, J = 1.8), 4.36 (m, 2H, Hb,Fc, J = 1.8), 3.73 (s,
6H, HOCH ), 3.66 (q, 4H, Ha, J = 6.1), 2.71 (t, 4H, Hb,
3

S.I. Kirin et al. / Inorganica Chimica Acta 362 (2009) 894–906
905
(b) T. Moriuchi, A. Nomoto, K. Yoshida, A. Ogawa, T. Hirao, J.
Am. Chem. Soc. 123 (2001) 68.
Acknowledgements
[8] S.I. Kirin, H.-B. Kraatz, N. Metzler-Nolte, Chem. Soc. Rev. 35
(2006) 348.
Syntheses and the majority of physical characterization
of the new compounds were carried out at the IPMB, Uni-
versity of Heidelberg. The authors thank Tobias Timmer-
mann for NMR and Heiko Rudy for mass spectra. In
addition, U.S. would like to thank Prof. Dr. K. Wieghardt,
[9] (a) K. Heinze, M. Beckmann, Eur. J. Inorg. Chem. (2005) 3450;
(b) S.I. Kirin, U. Schatzschneider, X. De Hatten, T. Weyhermiiller,
N. Metzler-Nolte, J. Organomet. Chem. 691 (2006) 3451;
(c) J. Lapic´, D. Siebler, K. Heinze, V. Rapic´, Eur. J. Inorg. Chem.
(2007) 2014;
(d) K. Heinze, D. Siebler, Z. Anorg. Allg. Chem. 633 (2007)
2223.
[10] D.R. van Staveren, N. Metzler-Nolte, Chem. Rev. 104 (2004)
5931.
Max-Planck-Institut fur Bioanorganische Chemie, Mul-
¨
¨
heim an der Ruhr, Germany, for generous access to the
computational facilities of the institute.
[11] (a) T. Moriuchi, T. Nagai, T. Hirao, Org. Lett. 7 (2005) 5265;
(b) T. Moriuchi, T. Nagai, T. Hirao, Org. Lett. 8 (2006) 31;
(c) S. Cowdhury, G. Schatte, H.-B. Kraatz, Angew. Chem., Int. Ed.
45 (2006) 6882;
Appendix A. Supplementary material
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/
j.ica.2008.01.050.
(d) F.E. Appoh, D.S. Thomas, H.-B. Kraatz, Macromolecules 39
(2006) 5629;
(e) X. de Hatten, Z. Cournia, I. Hue, J.C. Smith, N. Metzler-Nolte,
Chem. Eur. J. 13 (2007) 8139.
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