Structural, spectroscopic, and theoretical study of ferrocene ureidopeptides

Article abstract of DOI:10.1021/om700950r

Ferrocene ureidopeptides 3 and 4 and their derivatives 7 and 8 with a methyl ester substituent in 1′ position of the ferrocene have been prepared starting from ferrocenecarboxazide (1) or methyl 1′- azidocarbonylferrocene-1-carboxylate (5) via the corresponding isocyanatoferrocenes (2/6) and their coupling with alanine and alanylalanine methyl esters. Thorough spectroscopic and theoretical analyses revealed that in systems 4, 7, and 8 intramolecular hydrogen bonds play only a minor role, while self-assembly processes prevail in solution and in the solid state with urea NH groups acting as hydrogen donors and alanine amide and alanine ester CO groups acting as hydrogen acceptors. The ester substituent in the 1′ position of the ferrocene in compounds 7 and 8 does not engage in hydrogen bonding.

Full text of DOI:10.1021/om700950r

726
Organometallics 2008, 27, 726–735
Structural, Spectroscopic, and Theoretical Study of Ferrocene
Ureidopeptides
Jasmina Lapic´,† Gordana Pavlovic´,‡ Daniel Siebler,§ Katja Heinze,*,§ and Vladimir Rapic´*,†
Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, UniVersity of
Zagreb, PierottijeVa 6, HR-10000 Zagreb, Croatia, Department of Applied Chemistry, Faculty of Textile
Technology, UniVersity of Zagreb, Prilaz Baruna FilipoVic´a 30, HR-10000 Zagreb, Croatia, and
Department of Inorganic Chemistry, UniVersity of Heidelberg, Im Neuenheimer Feld 270,
69120 Heidelberg, Germany
ReceiVed September 25, 2007
Ferrocene ureidopeptides 3 and 4 and their derivatives 7 and 8 with a methyl ester substituent in 1′
position of the ferrocene have been prepared starting from ferrocenecarboxazide (1) or methyl
1′-azidocarbonylferrocene-1-carboxylate (5) via the corresponding isocyanatoferrocenes (2/6) and their
coupling with alanine and alanylalanine methyl esters. Thorough spectroscopic and theoretical analyses
revealed that in systems 4, 7, and 8 intramolecular hydrogen bonds play only a minor role, while self-
assembly processes prevail in solution and in the solid state with urea NH groups acting as hydrogen
donors and alanine amide and alanine ester CO groups acting as hydrogen acceptors. The ester substituent
in the 1′ position of the ferrocene in compounds 7 and 8 does not engage in hydrogen bonding.
Scheme 1. Turn Inducers (T) Constrain Parallel Ureidopeptide
Strands, Which Are Held Together by IHBs (arrows point
from N to C termini of peptide chains)
Introduction
(Oligo)urea peptidomimetics are formally derived from
peptides by replacement of amido groups with urea moieties
under addition of two methylene groups per repeating unit.
These molecules offer several advantages in comparison with
natural peptides regarding possible therapeutic applications.1–5
On the other hand Nowick and North showed that urea-derived
small molecules can act as molecular scaffolds for studies of
protein folding. Generally, such molecular scaffolds constrain
the attached peptide chains to adopt specific conformations; that
is, they are R-, ꢀ-, or γ-turn inducers. Such peptidomimetics
(“ureidopeptides”) may derive from T ) nornaboran-5-en-2,3-
diyl, cyclopropane-1,2-diyl (Scheme 1, type I) and T )
-CH2CH2-, R ) NCCH2CH2- (Scheme 1, type II), forming
ꢀ-sheet-like structures with parallel peptide strands. CO and NH
groups from both the peptide strands and the urea moieties can
be involved in intramolecular hydrogen bonds (IHBs).6–8
Ferrocene-containing peptides and peptide analogues (pep-
tidomimetics) play a vital role in highly active research areas
such as developing organometallic foldamers, designing mol-
ecules with potential biological applications, or mimicking
structural biological motifs.9,10 Oligoamides derived from
R-amino acids and Fn(COOH)2 (Fn ) ferrocene-1,1′-diyl)
(Scheme 2, type III)11–24 or H2N-Fn-COOH (Fca, 1′-amino-
* Corresponding authors. (K.H.) Fax: int + 49 6221 545707. Tel. int +
49 6221 548587. E-mail: katja.heinze@urz.uni-heidelberg.de. (V.R.) Fax:
int + 385 4836 082. E-mail: vrapic@pbf.hr.
† Department of Chemistry and Biochemistry, University of Zagreb.
‡ Department of Applied Chemistry, University of Zagreb.
§ University of Heidelberg.
(9) Moriuchi, T.; Hirao, T. Chem. Soc. ReV. 2004, 33, 294–301.
(10) van Staveren, D. R.; Metzler-Nolte, N. Chem. ReV. 2004, 104, 5931–
5986.
(11) Lapic´, J.; Siebler, D.; Heinze, K.; Rapic´, V. Eur. J. Inorg. Chem.
2007, 2014–2024.
(1) Liskamp, R. M. J. Angew. Chem., Int. Ed. Engl. 1994, 33, 305–
(12) Chowdhury, S.; Sanders, D. A. R.; Schatte, G.; Kraatz, H.-B. Angew.
Chem., Int. Ed. 2006, 45, 751–754.
307.
(2) Boeijen, A.; Liskamp, R. M. J. Eur. J. Org. Chem. 1999, 2127–
2135.
(13) Moriuchi, T.; Nagai, T.; Hirao, T. Org. Lett. 2005, 7, 5265–5268.
(14) Kirin, S. I.; Wissenbach, D.; Metzler-Nolte, N. New J. Chem. 2005,
29, 1168–1173.
(3) Boeijen, A.; van Ameijele, J.; Liskamp, R. M. J. J. Org. Chem. 2001,
66, 8454–8462.
(15) Chowdhury, S.; Schatte, G.; Kraatz, H.-B. Dalton Trans. 2004,
1726–1730.
(4) Kruijtzer, J. A. W.; Lefeber, D. J.; Liskamp, R. M. J. Tetrahedron
Lett. 1997, 38, 5335–5338.
(16) Appoh, F. E.; Sutherland, T. C.; Kraatz, H.-B. J. Organomet. Chem.
2004, 689, 4669–4677.
(5) Burgess, K.; Ibarzo, J.; Linthicum, D. S.; Russell, D. H.; Shin, H.;
Shitangkoon, A.; Totani, R.; Zhang, A. J. J. Am. Chem. Soc. 1997, 119,
1556–1564.
(17) Moriuchi, T.; Yoshida, K.; Hirao, T. Org. Lett. 2003, 5, 4285–
4288.
(6) North, M. J. Peptide Sci. 2000, 6, 301–313.
(7) Nowick, J. S. Acc. Chem. Res. 1999, 32, 287–296.
(8) Nowick, J. S.; Smith, E. M.; Noronha, G. J. Org. Chem. 1995, 60,
7386–7387.
(18) van Staveren, D. R.; Weyhermüller, T.; Metzler-Nolte, N. Dalton
Trans. 2003, 210–220.
(19) Moriuchi, T.; Nomoto, A.; Yoshida, K.; Hirao, T. Organometallics
2001, 20, 1008–1013.
10.1021/om700950r CCC: $40.75
2008 American Chemical Society
Publication on Web 01/26/2008

Ferrocene Ureidopeptides
Organometallics, Vol. 27, No. 4, 2008 727
Scheme 2. Parallel and Antiparallel Peptide Strands Tethered
to Ferrocene as Turn Inducer via Amide and Ureylene Groups
(X ) OMe, AA-OMe; Y ) Boc, Boc-AA; arrows point from N
to C termini of the peptide chains)
Scheme 3. Ferrocene-Containing Urea Derivatives
ferrocene-1-carboxylic acid) (Scheme 2, type IV)25–33 can fold
to ꢀ-strand analogous conformations with antiparallel or parallel
peptide chains. Conjugates of Fca and R-amino acids were
shown to bind anions via hydrogen bonding.26,31 Self-assembly
of amide-substituted ferrocenes into dimers, chains, and sheets
has been observed in the solid state as well as in solution.25,32
Generally, the interplay between intramolecular hydrogen bond-
ing (folding) and intermolecular hydrogen bonding (self-
assembly, guest binding) depends on the environment (solid
state, solution, solvent, temperature, etc.). For ferrocene deriva-
tives it is furthermore largely determined by the special rigidity/
flexibility of the metallocene scaffold.
By replacing an amido group with a ureylene unit in type IV
compounds ureidopeptides V are derived. In these analogues
of type I compounds parallel strands are expected. Like the
amide group, the ureylene moiety is highly suitable for the
formation of hydrogen bonds, as it can act both as hydrogen
donor and hydrogen acceptor. This property has been exploited
in anion binding chemistry and self-assembly processes.34,35
Anion binding and anion sensing with ferrocene urea receptors
(usually ferrocenylureas or symmetrically disubstituted (fer-
rocene-1,1′-diyl)bisureas, Scheme 3, A) has been pioneered by
Tucker,36 Beer,37,38 Kaifer,39 and Tárraga and Molina40–43 with
ferrocene as an electrochemical detection unit. Self-assembly
of urea derivatives based on the complementary hydrogen donor
NH and hydrogen acceptor CO groups has been utilized for
example in the construction of ion channels.44 The ureylene
group has been studied by Kraatz as a linker between two
ferrocene moieties (Scheme 3, B45) with respect to electron
transfer and charge delocalization.46 A chiral conjugate of
ferrocene and Leu (Scheme 3, C) has been suggested by Schögl
as model chromophor for the labeling of chiral amino com-
(20) Moriuchi, T.; Nomoto, A.; Yoshida, K.; Ogawa, A.; Hirao, T. J. Am.
Chem. Soc. 2001, 123, 68–75.
(21) Moriuchi, T.; Nomoto, A.; Yoshida, K.; Hirao, T. J. Organomet.
Chem. 1999, 589, 50–58.
(34) Gale, P. A. Amide- and Urea-Based Anion Receptors, in Encyclo-
pedia of Supramolecular Chemistry; Taylor & Francis, 2004; p 31–41
(35) Kang, S. O.; Begum, R. A.; Bowman-James, K. Angew. Chem.,
Int. Ed. 2006, 45, 7882–7894.
(22) Nomoto, A.; Moriuchi, T.; Yamazaki, S.; Ogawa, A.; Hirao, T.
Chem. Commun. 1998, 1963–1964.
(23) Herrick, R. S.; Jarret, R. M.; Curran, T. P.; Dragoli, D. R.; Flaherty,
M. B.; Lindyberg, S. E.; Slate, R. A.; Thornton, L. C. Tetrahedron Lett.
1996, 37, 5289–5292.
(24) Oberhoff, M.; Duda, L.; Karl, J.; Mohr, R.; Erker, G.; Fröhlich,
R.; Grehl, M. Organometallics 1996, 15, 4005–4011.
(25) Heinze, K.; Siebler, D. Z. Anorg. Allg. Chem. 2007, 633, 2223–
2233.
(36) Miyaji, H.; Collonson, S. R.; Prokeš, I.; Tucker, J. H. R., Chem.
Commun. 2003, 64–65.
(37) Evans, A. J.; Matthews, S. E.; Cowley, A. R.; Beer, P. D. Dalton
Trans. 2003, 4644–4650.
(38) Pratt, M. D.; Beer, P. D. Polyhedron 2003, 22, 649–653.
(39) Moon, K.; Kaifer, A. E. J. Am. Chem. Soc. 2004, 126, 15016–
15017.
(26) Heinze, K.; Wild, U.; Beckmann, M. Eur. J. Inorg. Chem. 2007,
617–623.
(40) Otón, F.; Tárraga, A.; Espinosa, A.; Velasco, M. D.; Molina, P.
Dalton Trans. 2006, 3685–3692.
(27) Barišic´, L.; Rapic´, V.; Metzler-Nolte, N. Eur. J. Inorg. Chem. 2006,
4019–4021.
(41) Otón, F.; Tárraga, A.; Espinosa, A.; Velasco, M. D.; Molina, P. J.
Org. Chem. 2006, 71, 4590–4598.
(28) Barišic´, L.; àkic´, M.; Mahmoud, K, A.; Liu, Y.; Kraatz, H,.B.;
Pritzkow, H.; Kirin, S. I.; Metzler-Nolte, N.; Rapic´, V. Chem.-Eur. J. 2006,
12, 4965–4980.
(42) Otón, F.; Tárraga, A.; Velasco, M. D.; Molina, P. Dalton Trans.
2005, 1159–1161.
(43) Otón, F.; Tárraga, A.; Espinosa, A.; Velasco, M. D.; Bautista, D.;
Molina, P. J. Org. Chem. 2005, 70, 6603–6608.
(44) Cazacu, A.; Tong, C.; van der Lee, A.; Fyles, T. M.; Barboiu, M.
J. Am. Chem. Soc. 2006, 128, 9541–9548.
(29) Chowdhury, S.; Schatte, G.; Kraatz, H.-B. Angew. Chem., Int. Ed.
2006, 45, 6882–6884.
(30) Heinze, K.; Beckmann, M. Eur. J. Inorg. Chem. 2005, 3450–3457.
(31) Heinze, K.; Schlenker, M. Eur. J. Inorg. Chem. 2005, 66–71.
(32) Heinze, K.; Schlenker, M. Eur. J. Inorg. Chem. 2004, 2974–2988.
(33) Barišsic´, L.; Dropucˇic´, M.; Rapic´, V.; Pritzkow, H.; Kirin, S. I.;
Metzler-Nolte, N. Chem. Commun 2004, 2004–2005.
(45) Barišc, L.; Rapic´, V.; Kovacˇ, V. Croat. Chem. Acta 2002, 75, 199–
210.
(46) Mahmoud, K.; Long, Y.-T.; Schatte, G.; Kraatz, H.-B. J. Orga-
nomet. Chem. 2004, 689, 2250–2255.

728 Organometallics, Vol. 27, No. 4, 2008
Lapi´c et al.
Scheme 4a
Scheme 5. Possible Mechanism of the Formation of Sym-
metrical Ureas B from Isocyanates 2 and 6
Nucleophilic addition of these amines to 2/6 results in the
formation of symmetrical ureas of type B (Scheme 5).
a
(i) benzene, 80°C. (ii) n ) 1: H-Ala-OCH3 · HCl, NEt3, CH2Cl2;
Purification of 2 and 6 by chromatography proved to be
difficult, as 1/2 and 5/6 possess almost identical Rf values. Thus
crude product mixtures were employed in the coupling step with
alanine and alanylalanine methyl esters to give 3, 4, 7, and 8,
respectively. These products could be purified by thin-layer
chromatography. The ureidopeptides 3, 4, 7, and 8 were fully
characterized by multinuclear and two-dimensional NMR
spectroscopy, IR, UV/vis, and CD spectroscopy, as well as by
high-resolution mass spectrometry (Tables 1, 2, 3, and 4).
Spectroscopic Analysis of Ferrocene Ureidopeptides 3,
4, 7, and 8. For all ureidopeptides 3, 4, 7, and 8 the characteristic
ferrocene absorption band is observed at 448 nm in CH2Cl2
(Table 1). Its energy is independent of the solvents employed
[CH2Cl2, CH3CN, CH2Cl2/DMSO (20% v/v)]. Around this
absorption maximum the chiral compounds show either positive
(4) or negative Cotton effects (7, 8) in CH2Cl2, which cor-
roborates the chiral environment around the ferrocene chro-
mophores (Figure 1). For the leucine analogue of 3 (Scheme 3,
C) Schlögl has also reported a positive Cotton effect at 459 nm
in ethanol.47
n ) 2: H-Ala-Ala-OCH3 · HCl, NEt3, CH2Cl2.
pounds such as peptides and proteins for the investigation of
configurations with chiroptical methods.47
In this study we report the synthesis and conformational
analysis of ferrocene ureidopeptides containing alanine or
alanylalanine subunits, as well as of their 1′-methoxycarbonyl
derivatives, as an entry into enantiomerically pure ferrocene-
labeled anion receptors and ꢀ-strand models (organometallic
peptidomimetics10) (Scheme 1, type II, T ) Fn, and Scheme
2, type V). Folding versus self-assembly of the new ferrocene
ureidopeptides is investigated with the aid of spectroscopic
analysis (CD, IR, NMR spectroscopy), theoretical calculations,
and X-ray structure analysis.
Results and Discussion
Synthesis of Ferrocene Ureidopeptides 3, 4, 7, and 8. The
synthesis of ferrocene ureidopeptides 3, 4, 7, and 8 is depicted
in Scheme 4. The starting ferrocenecarboxazide 1 was prepared
in 75% yield from ferrocenecarboxylic acid Fc-COOH by the
successive action of ClCOOEt/NEt3 in acetone and an aqueous
solution of NaN3 via the intermediate mixed anhydride.48 Methyl
1′-azidocarboxylferrocene-1-carboxylate 5 was prepared in a
similar fashion from 1′-methoxycarbonylferrocene-1-carboxylic
acid, CH3OOC-Fn-COOH, in 73% yield. Curtius rearrange-
ment of 1 or 5 in benzene gave the corresponding isocyanates
2 and 6, respectively.48 The course of the reactions was easily
monitored by IR spectroscopy, as characteristic absorption bands
of 1/5 around (2138 and 1687 cm-1) decrease while the band
for the NCO substituent of 2/6 increases (2173 cm-1). As
prolonged heating results in formation of N,N′-diferrocenylureas
of type B (Scheme 3),45,46,49 the reactions could not be driven
to completion. The formation of byproduct of type B can be
explained by thermolysis of isocyanates 2/6 to the corresponding
iron-stabilized nitrenes,41 which then abstract hydrogen atoms
from the reaction medium to give the corresponding amines.
Generally, the CD maxima are found at lower energy than
the UV/vis maxima, which has been ascribed to the electronic
splitting of the ferrocene absorption band.47 In the presence of
DMSO the CD maxima shift to even lower energy by 280 cm-1
(4), 220 cm-1 (7), and 210 cm-1 (8), although the UV/vis
absorption maxima remain unchanged.
If a preferred folded conformation with intramolecular
hydrogen bonds existed in CH2Cl2 solution, one should expect
a decrease of the CD intensity in coordinating solvents which
can compete for hydrogen-bonding sites and thus disrupt IHBs.
This has been shown for several examples of chiral ferrocene
peptides.30 However, upon addition of DMSO, which is a strong
competitor for NH hydrogen-bonding sites, to CH2Cl2 solutions
of 4, 7, or 8, the CD signals increase by a factor of 2 (4) and
1.6 (7) and the signal even switches the sign for compound 8
(Figure 1, Table 1). The latter observation suggests that the
chromophore environment of 8 is substantially different in
CH2Cl2 and CH2Cl2/DMSO. These observations clearly point
to other ordering phenomena being responsible for the solvent-
dependent Cotton effects observed than stable conformations
with intramolecular hydrogen bonds in noncoordinating solvents.
In the solid state (KBr disk) 4 (X ) H) displays a positive Cotton
effect at 460 nm, while 8 (X ) COOCH3) exhibits a negative
(47) Falk, H.; Krasa, C.; Schlögl, K. Monatsh. Chem. 1969, 100, 1552–
1563.
(48) Schlögl, K.; Seiler, H. Naturwiss. 1958, 45, 337.
(49) Nesmeyanov, N. A.; Reutov, O. A. Dokl. Akad. Nauk SSSR 1957,
115, 518–521.

Ferrocene Ureidopeptides
Organometallics, Vol. 27, No. 4, 2008 729
Table 1. UV/Vis and CD Data (c ) 10-3 M) of 4, 7, and 8 in CH2Cl2 and CH2Cl2/DMSO (20% v/v)
solvent
4
7
8
λ
max/nm (ꢀ/M-1 cm-1
λδmax/nm (ꢀ/M-1 cm-1
)
CH2Cl2
CH2Cl2/DMSO
CH2Cl2
448 (370)
448 (360)
460 (+850)
466 (+1700)
448 (340)
448 (340)
478 (-2070)
483 (-3370)
448 (230)
448 (230)
483 (-1740)
488 (+1200)
)
λ
λ
max/nm (Mθ/deg M-1 cm-1
max/nm (Mθ/deg M-1 cm-1
)
)
CH2Cl2/DMSO
Table 2. IR (in CH2Cl2; c ) 10-3 M) and HR-FAB Mass Spectrometric Data of 3, 4, 7, and 8
3
4
7
8
νNH (free)/cm-1
3426
3367
1740
1675
C15H18N2O3Fe
330.0667
3426
3363
1742
1682, 1677
C18H23N3O4Fe
401.1038
3419
3370
1740, 1706
1679
C17H20N2O5Fe
388.0722
388.0732
3424
3360
νNH (assoc.)/cm-1
νCO (ester)/cm-1
νCO (amide I)/cm-1
molecular formula
m/z (obs)
1741, 1708
1683, 1677
C20H25N3O6Fe
459.1093
459.1062
m/z (calcd)
330.0667
401.1062
Table 3. 1H NMR Chemical Shifts of 3, 4, 7, and 8 in CD2Cl2 (c ) 10-2 M, 400 MHz, atom numbering according to Scheme 4)a
3
4
7
8
1-NH
5.63 (1H, s)
6.48 (1H, s)
6.40 (1H, s)
6.72 (1H, s)
NHAla1
NHAla2
CHR, Ala1
CHR, Ala2
H2, H5
5.70 (1H, d, 6.6 Hz)
4.46 (1H, dq, 6.6, 7.2 Hz)
4.37 (2H, bs)
6.09 (1H, d, 7.7 Hz)
7.07 (1H, d, 7.1 Hz)
4.47 (1H, dq, 7.1, 7.2 Hz)
4.49 (1H, dq, 7.7, 7.2 Hz)
4.38 (1H, bs), 4.35 (1H, bs)
5.60 (1H, d, 7.6 Hz)
4.49 (1H, dq, 7.6, 7.2 Hz)
4.47 (1H, pt), 4.42 (1H, pt)
4.06 (2H, pt)
5.79 (1H, d, 7.6 Hz)
7.12 (1H, d, 7.2 Hz)
4.48 (1H, dq, 7.2, 7.2 Hz)
4.50 (1H, dq, 7.6, 7.0 Hz)
4.52 (1H, ddd, 2.6, 1.2, 1.2 Hz), 4.40
(1H, ddd, 2.6, 1.2, 1.2 Hz)
4.04 (1H, ddd, 3.9, 2.6, 1.2 Hz), 4.02
(1H, ddd, 3.9, 2.6, 1.2 Hz)
4.81 (2H, pt)
4.43 (2H, pt)
3.72 (3H, s)
3.77 (3H, s)
1.41 (3H, d, 7.0 Hz)
1.40 (3H, d, 7.2 Hz)
H3, H4
4.14 (2H, bs)
4.05 (2H, bs)
4.21 (5H, s)
3.72 (3H, s)
H7, H10
H8, H9
1-OCH3
1′-OCH3
CH3, Ala1
4.27 (5H, s)
4.82 (2H, pt)
4.45 (2H, pt)
3.74 (3H, s)
3.78 (3H, s)
1.41 (3H, d, 7.2 Hz)
3.73 (3H, s)
1.40 (3H, d, 7.2 Hz)
1.40 (3H, d, 7.0 Hz)
1.39 (3H, d, 7.2 Hz)
CH3,
Ala2
a Chemical shifts and coupling constants of superimposed proton signals H2/H5 and CHR were obtained via spectral simulation of the multiplets. All
assignments are based on COSY, TOCSY, and NOESY spectra.
Table 4. 13C NMR Chemical Shifts of 3, 4, 7, and 8 in CD2Cl2 (c ) 10-2 M, 100 MHz, atom numbering according to Scheme 4)a
3a
4
7
8
FcCO
171.59 (s)
171.62 (s)
COester
COurea
COamide
CR, Ala1
CR, Ala2
C1
174.51 (s)
156.00 (s)
173.13 (s)
156.22 (s)
173.10 (s)
49.58 (s)
48.26 (s)
n.o.
62.74 (s), 62.54 (s)
65.22 (s)
n.o.
173.84 (s)
155.35 (s)
173.18 (s)
155.67 (s)
173.07 (s)
49.55 (s)
48.31 (s)
97.07 (s)
63.33 (s), 62.96 (s)
66.51 (s), 66.35 (s)
72.38 (s)
71.07 (s)
72.44 (s)
48.81 (s)
48.97 (s)
n.o.
96.47 (s)
C2, C5
C3, C4
C6
63.17 (s), 62.74 (s)
65.92 (s), 65.83 (s)
70.32 (s)
63.77 (s), 63.62 (s)
66.70 (s), 66.65 (s)
72.48 (s)
71.12 (s)
72.12 (s)
52.32 (s)
51.69 (s)
18.59 (s)
C7, C10
C8, C9
1-OCH3
1′-OCH3
CH3, Ala1
69.77 (s)
69.37 (s)
52.41 (s)
18.99 (s)
52.35 (s)
52.35 (s)
51.68 (s)
18.85 (s)
17.75 (s)
18.72 (s)
17.85 (s)
CH3,
Ala2
a In CDCl3.
Cotton effect at 483 nm, analogous to the effects observed in
CH2Cl2 solution (Figure 1 and Supporting Information).
To shed some light onto the possible folding or self-assembly
of ureidopeptides in solution, IR and detailed NMR spectro-
scopic analyses were undertaken (Tables 2, 3, 4, and 5). In
CH2Cl2 solution (c ) 10-3 M) signals for NH stretching
vibrations are observed around 3420 (m) and 3350 cm-1 (w),
indicative of free and hydrogen-bonded NH groups, respectively
(Table 2). In the solid state absorptions of NH stretching
vibrations are found below 3400 cm-1, showing that all NH
groups are involved in hydrogen-bonding interactions. The
carbonyl absorption of the amino acid esters are found at 1740
cm-1 in solution and below 1740 cm-1 in the solid state,
suggesting that in the solid state hydrogen bonds to these ester
groups are present. The CO stretching vibration of the 1′-
ferrocene ester group occurs around 1710 cm-1 both in solution
and in the solid, which indicates absence of hydrogen bonds to
that CO functional group. Thus hydrogen bonds (either intra-
or intermolecular) from NH groups to carbonyl substituents
could be formed with the amino acid part of the molecules.
1H and 13C NMR spectra of the ureidopeptides display all
signals expected for the proposed composition (Tables 3 and
4). Superimposed multiplets in the proton spectra have been
deconvoluted by spectral simulation techniques, and assignments
are based on two-dimensional NMR spectra. The chiral alanine
unit renders the protons H2/H5 and H3/H4 as well as the

730 Organometallics, Vol. 27, No. 4, 2008
Lapi´c et al.
CHR-NH-CO-Fn-NHCOCH3 [R ) CH(CH3)2, CH(CH3)-
(C2H5)].30 In these cases the hydrogen and carbon atoms of the
Cp ring with the chiral substitutent as well as the hydrogen and
carbon atoms of the NHCOCH3-substituted Cp ring are dias-
terotopic and give rise to distinctly dispersed signals in the 1H
NMR and 13C NMR spectra. This has been ascribed to IHBs
between the two substituents transferring chiral information to
both cyclopentadienyl rings. Thus for 7 and 8 the number of
signals observed does not support IHBs, which also fits to the
absence of any NOE cross-peak between the ferrocene ester
CH3 group and protons of the chiral substituent in the NOESY
spectra of 7 and 8. This interpretation is also in accordance with
the IR data showing that the 1′-ferrocene ester group does not
engage in hydrogen bonds at all.
Equilibration between hydrogen-bonded and non-hydrogen-
bonded states in CD2Cl2 for a given NH proton is usually fast
on the NMR time scale, and observed proton chemical shifts
are weighted averages of the chemical shifts of contributing
states. The proton chemical shifts of NH groups are found at δ
7.2 in dilute CD2Cl2 solution at 25 °C, suggesting only weak if
any hydrogen bonding under these conditions. Upon cooling,
all the NH signals are shifted to lower field with quite high
temperature dependence (Figure 2, Table 5), indicative of
intermolecular hydrogen bonds. Likewise in [D6]-DMSO all NH
signals are shifted to lower field due to the formation of
NH · · · OSMe2 hydrogen bonds (Table 5).
Dilution experiments conducted on CD2Cl2 solutions of 4,
7, and 8 showed a downfield shift of NH protons upon increasing
concentration, which is indicative of self-association through
intermolecular hydrogen bonds (Figure 3). No plateaus have
been observed in the concentration-dependent chemical shifts
of NH protons such that distinct oligomers with definite
stoichiometry are unlikely [which has been observed for
benzo(ureido) crown-ethers].44 We assume that the initial
process is the formation of a dimer from two monomers. The
data can be fit using this model with two chemical shifts,
δ(monomer) and δ(dimer), and one formation constant, KD, as
unknowns. Association constants KD and chemical shifts for
numerical fits to the monomer/dimer model are compiled in
Table 5. Interestingly, the association constants KD derived from
protons 1-NH and NHAla1 (the ureylene group) are all very
similar (4, 8: 90 M-1; 7: 30 M-1), while KD derived from proton
NHAla2 (in 4 and 8) is much lower. This indicates that both NH
protons of the urea group interact almost synchronously, while
the NHAla2 proton interacts to a lesser extent. However, it
appears that the second alanine moiety stabilizes the interaction
of the urea group with hydrogen acceptors, which points to some
cooperative hydrogen bonding involving all NH protons.
Thus, all the experimental data acquired suggest that 7 and 8
have no preferred conformation with IHBs in methylene chloride
solution but self-assemble via intermolecular hydrogen bonds
to dimers (and possibly finally to larger oligomers or polymers,
Vide infra) at higher concentrations. DMSO disrupts these
intermolecular hydrogen bonds and disassembles the dimer
(oligomer) to DMSO-solvated monomers. This interpretation
also accounts for the unusual changes of CD signals when
switching the solvent from CH2Cl2 to CH2Cl2/DMSO (Vide
supra) and is also in accord with the Cotton effects observed
in solution and in the solid state.
Figure 1. CD spectra of 4, 7, and 8 in CH2Cl2 and CH2Cl2/DMSO
(20% v/v).
corresponding carbon atoms C2/C5 and C3/C4 of the N-
substituted Cp ring diasterotopic, which is clearly visible in the
spectra of 7 and 8 and partially resolved in the spectra of 3 and
4. However, the signals of the proton pairs H7/H10 and H8/H9
in the 1,1′-disubstituted ferrocenes 7 and 8 are indistinguishable
(Table 3). The same holds for the corresponding resonances of
the carbon atoms C7/C10 and C8/C9 (Table 4). This contrasts
with findings for R-amino acid conjugates of the type CH3OOC-
DFT Calculations of 7 and 8. DFT calculations have been
quite successful in describing the energetics of IHBs in 1,1′-
disubstituted ferrocenes.11,25,26,30–32,50 Thus several conforma-
(50) Heinze, K.; Beckmann, M. J. Organomet. Chem. 2006, 691, 5576–
5584.

Ferrocene Ureidopeptides
Organometallics, Vol. 27, No. 4, 2008 731
Table 5. Temperature-Dependent, Solvent-Dependent, and Concentration-Dependend 1H NMR Data of NH Protons of 4, 7, and 8
compound
proton
∆δ/ppb K-1
δ/([D6]-DMSO) δ (CD2Cl2)/ppm
KD/M-1
δ(monomer)/ppm
δ(dimer)/ppm
R2
4
1-NH
-15.4
-11.1
-17.3
-14.6
-9.1
-16.8
-16.4
-20.2
1.25
0.08
1.37
1.34
0.77
1.10
0.40
1.25
115 ( 9
84 ( 7
41 ( 3
32 ( 5
35 ( 6
91 ( 13
81 ( 11
26 ( 3
5.55 ( 0.02
5.58 ( 0.01
6.61 ( 0.01
5.70 ( 0.01
5.23 ( 0.01
5.76 ( 0.03
5.19 ( 0.02
6.69 ( 0.01
6.51 ( 0.02
6.16 ( 0.02
7.33 ( 0.02
6.47 ( 0.06
5.62 ( 0.03
6.81 ( 0.05
6.08 ( 0.04
7.54 ( 0.05
0.9996
0.9996
0.9996
0.9994
0.9993
0.9982
0.9983
0.9986
NHAla1
NHAla2
1-NH
NHAla1
1-NH
7
8
NHAla1
NHAla2
tions of 7 and 8 with and without IHBs were calculated at the
B3LYP/Lanl2DZ level of theory (Figure 4). No energetically
preferred conformation could be located, as all calculated
geometries of 7 possess a similar energy within an energy band
of 8 kJ mol-1. This corroborates the interpretation based on
experimental data (IR, NMR) that intermolecular hydrogen
bonds are favored over IHBs.
For the alanylalanine derivative 8 additional IHBs involving
NHAla2 are in principle possible (Figure 5). However, the
conformations 8-A, 8-A′, 8-B, 8-B′, and 8-C are also not
significantly preferred over conformation 8-C′ without IHBs.
Thus in solution 7 and 8 are best described as a dynamic mixture
of energetically similar conformers.
are within expected values for all structural moieties within the
molecule (Cp rings, urea fragment, Ala and COOCH3 units).
As found in methylene chloride solution intramolecular hydro-
gen bonds are absent in the crystal. However, intermolecular
hydrogen bonds are found between molecules translated along
the a axis via N2-(H12N) and N3-(H13N) as hydrogen donor
groups to carbonyl oxygen atoms O4 and O5 as hydrogen
acceptors, giving rise to chains of molecules connected by 12-
membered rings (Figure 7, Table 6). The N1-(H1N1) · · · O4
distance is larger than 2.7 Å probably due to the formation of
this unstrained hydrogen-bonded ring. As the urea moiety is
almost planar with both NH groups oriented in the same
direction the N1-(H1N1) vector also points to O4. Thus in the
solid state only the peptide fragment is involved in hydrogen
bonding, while the ferrocene-substituted ester moiety does not
participate, which nicely fits the observations made in methylene
X-ray Crystal Structure of 8. 8 crystallized in the triclinic
space group P1 with a Flack parameter of 0.075(16). The
absolute configuration of the asymmetric carbon atoms C14 and
C17 of the two alanyl moieties is S (Figure 6). Bond distances
Figure 3. Partial concentration-dependent 1H NMR spectra of 8 in
CD2Cl2 (top, * denotes residual CHDCl2, 200 MHz) and δ versus
c plot of amide proton signals (the lines are fits to a dimerization
model).
Figure 2. Partial VT 1H NMR spectra of 8 in CD2Cl2 (top, * denotes
residual CHDCl2, 300 MHz) and δ versus T plot of amide proton
signals.

732 Organometallics, Vol. 27, No. 4, 2008
Lapi´c et al.
Figure 4. DFT-calculated minimum structures of 7 (relative energies in kJ mol-1 in parentheses; O · · · H distances in Å).
chloride solution. The bis(ferrocene) urea derivative CH3OOC-
Fn-NHCONH-Fn-COOCH3 also engages in intermolecular
hydrogen bonding in the crystal, however, involving interactions
between the methyl ester substitutent of one Cp ring to the urea
NH of an adjacent molecule, which results in the formation of
a one-dimensional chain.46 The hydrogen-bonded chain found
for the crystal of 8 also supports the model employed for the
concentration-dependent proton chemical shifts (Vide supra).
and alanine amide and ester CO groups play the role of hydrogen
acceptors. The ester substituent in the 1′ position of the ferrocene
is not involved in hydrogen bonding. Replacement of the 1′-
ferrocene ester moiety by a peptide fragment giving C2-
symmetric ferrocene ureidopeptides (Scheme 1, type II, T )
Fn; n ) m) and type V conjugates (Scheme 2) to possibly induce
IHBs with formation of stable conformations in solution is
currently in progress in our laboratories.
Experimental Section
Conclusion
General Procedures. The syntheses were carried out under
argon. CH2Cl2 used for synthesis and FT-IR spectroscopy was dried
(P2O5), distilled over CaH2, and stored over molecular sieves (4
Å). EDC, HOBt (Aldrich), and amino acid esters and amides
(Merck) were used as received. Products were purified by prepara-
tive thin-layer chromatography on silica gel (Merck, Kieselgel 60
HF254) using the mixtures CH2Cl2/EtOAc or CH2Cl2/MeOH.
Melting points were determined with a Bucchi apparatus. IR spectra
were recorded as CH2Cl2 solutions with a Bomem MB 100 mid
FT-IR spectrophotometer. 1H and 13C{1H} NMR spectra were
Synthesis and conformational analysis of ferrocene ure-
idopeptides containing a 1′-methoxycarbonyl group as potential
hydrogen acceptor in intra- or intermolecular hydrogen bonds
have been performed. Thorough spectroscopic and theoretical
studies of these systems revealed that (on the contrary to type
I and II compounds, Scheme 1) intramolecular hydrogen bonds
play only a minor role, while self-assembly processes prevail
in solution and in the solid state. In these intermolecular
hydrogen bonds urea NH groups are acting as hydrogen donors

Ferrocene Ureidopeptides
Organometallics, Vol. 27, No. 4, 2008 733
Figure 5. DFT-calculated minimum structures of 8 (relative energies in kJ mol-1 in parentheses; O · · · H distances in Å).
temperature.52 Data reduction has been performed by the same
program.52 The data have been corrected for Lorentz polarization
and scaled for absorption effects. The structure was solved by direct
methods.53 Refinement procedure by full-matrix least-squares
methods based on F2 values against all reflections has been
performed including anisotropic displacement parameters for all
non-H atoms.54 The positions of hydrogen atoms belonging to the
cyclopentadienyl Csp2 and methyl and tetrahedral Csp3 atoms were
geometrically optimized applying the riding model [Csp2-H,
Csp3(methyl)-H, Csp3(tetrahedral)-H 0.93, 0.98, and 0.96 Å,
respectively; Uiso(H) ) 1.2 (for Csp2 and Csp3 (tetrahedral) and
1.5 for Csp3(methyl) Ueq(C)]. The hydrogen atoms belonging to
the nitrogen atoms N1, N2, and N3 have been found in the electron-
density Fourier maps and refined freely [being in the range N-H )
(51) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Figure 6. Molecular structure of 8 in the crystal.
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, C.;
Pomelli, R.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels,
A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson,
B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03,
revision B.03; Gaussian, Inc.: Pittsburgh, PA, 2003.
recorded on a Varian EM 360 or Varian Gemini 300 spectrometer
in CD2Cl2, CDCl3, and [D6]-DMSO solutions with Me4Si as internal
standard or on a Varian Unity Plus 400 spectrometer. FAB and
HR-FAB mass spectra were recorded on a JEOL JMS-700. CD
spectra were recorded with a Jasco-810 CD spectrophotometer.
Computational Method. Density functional calculations were
carried out with the Gaussian03/DFT51 series of programs. The
B3LYP formulation of density functional theory was used employ-
ing the Lanl2DZ basis set.51 All points were characterized as
minima (Nimag ) 0) by frequency analysis.
(52) CrysAlis Software System, Version 171.23; Oxford Diffraction Ltd.,
2004.
(53) Sheldrick, G. M. Acta Crystallogr. 1990, 46, 467–473.
(54) Sheldrick, G. M.; SHELXL97 Program for the Refinement of Crystal
Structures; University of Göttingen: Germany, 1997.
X-ray Crystal Structure Analysis. The data collection was
carried out on an Xcalibur four-circle kappa geometry single-crystal
diffractometer with an Xcalibur Sapphire 3 CCD detector by
applying the CrysAlis Software system, Version 171.26, at ambient

734 Organometallics, Vol. 27, No. 4, 2008
Lapi´c et al.
Figure 7. Intermolecular hydrogen bonds in the crystal of 8.
84–86 °C. IR (CH2Cl2): ν 2138 (s, N3), 1687 (s, COazide) cm-1. 1H
NMR (CDCl3): δ 4.83 (s, 2H, H2,5), 4.52 (s, 2H, H3,4), 4.27 (s,
5H, Cp-H).
Table 6. Intermolecular Hydrogen Bonds in the Crystal of 8
symmetry
D-H/Å H · · · A/Å D · · · A/Å D-H · · · A/deg code
D-H · · · A
Isocyanatoferrocene Fc-NCO (2). A solution of ferrocenecar-
boxazide 1 (400 mg, 1.56 mmol) in dry benzene (20 mL) was heated
to 85 °C for 4 h. After cooling to 20 °C, the reaction mixture was
evaporated in Vacuo to dryness. This crude product was applied
for the following coupling reactions without further purification.
N2-H12N · · · O4 0.74(4) 2.11(4) 2.844(4)
N3-H13N · · · O5 0.83(8) 2.34(8) 3.138(5)
175(4)
162(7)
1+x, y, z
1+x, y, z
Table 7. Crystal Data for 8
formula
C20H25FeN3O6
IR (CH2Cl2): ν 2173 (s, NCO) cm-1
.
Mr
459.28
Fc-NH-CO-Ala-OCH3 (3). To a suspension of crude 2 (140 mg)
in dry methylene chloride was added H-Ala-OCH3 [obtained from
H-Ala-OCH3 · HCl (130 mg, 1 mmol) by treatment with Et3N in
CH2Cl2]. The mixture was stirred for 1 h at room temperature. The
reaction mixture was washed with saturated aqueous NaHCO3 and
water. The organic layer was dried over Na2SO4 and evaporated in
Vacuo. TLC purification with CH2Cl2/EtOAc (10:1) gave 47 mg
(36%) of orange crystals and 49 mg of compound 1. Mp: 154–157
°C. FAB-MS: m/z (%) 330 (100, M+), 315 (77), 298 (95).
Fc-NH-CO-Ala-Ala-OCH3 (4). A solution of Boc-Ala-Ala-
OCH3 (380 mg, 1.5 mmol) in AcOEt was deprotected by treating
with gaseous HCl. H-Ala-Ala-OCH3 · HCl resulting after evapora-
tion of the solvent was treated with Et3N in CH2Cl2 and coupled
with crude isocyanatoferrocene 2 (300 mg). The mixture was stirred
for 1 h at room temperature and washed with saturated aqueous
NaHCO3 and water. The organic layer was dried over Na2SO4 and
evaporated in Vacuo. TLC purification with CH2Cl2/EtOAc (10:1)
gave 180 mg (42%), yellow crystals, followed by 130 mg of 1.
Mp: 142–145 °C. IR (KBr): ν 3356, 3296 (m, NH, assoc.), 1735
(s, COester), 1636 (s, amide I), 1557 (s, amide II) cm-1. FAB-MS:
m/z (%) 401 (100, M+). Anal. Calcd for C18H23FeN3O4: C, 53.88;
H, 5.78; N, 10.50. Found: C, 54.00; H, 6.16; N, 10.56.
color and habit
cryst syst, space group
temp (K)
a (Å)
b (Å)
c (Å)
orange prism
triclinic, P1
295
5.9735(13)
8.0852(17)
10.8924(19)
101.770(16)
90.204(17)
95.378(18)
512.60(18)
1
1.488
0.8
240
4.5 to 30.0
R (deg)
ꢀ (deg)
γ (deg)
V (Å3)
Z
density (g cm-3
)
µ (mm-1
F(000)
)
θ range for data collection (deg)
h,k,l range
no. measd reflns
-8 to 7 ; -11 to 11 ; -15 to 14
7490
no. indep reflns (Rint
)
4977, 0.043
4611
0.0473, 0.1236
0.0509, 0.1278
1.05
no. obsd reflns, I g 2σ(I)
R, wR [I g 2σ(I)]
R, wR [all data]
goodness of fit on F2, S
max., min. electron density (e Å-3
Flack param
)
-0.54, 0.60
0.075(16)
Methyl 1′-azidocarbonylferrocene-1-carboxylate (5). In a
similar way to the preparation of ferrocenecarboxazide 1, starting
from 1′-methoxycarbonylferrocene-1-carboxylic acid (1.2 g, 4.2
mmol) 5 was obtained in the form of red crystals (947 mg, 73%).
Mp: 101–102 °C. IR (CH2Cl2): ν 2138 (s, N3), 1717 (s, COester),
0.74(4) to 0.85(5) Å]. CCDC-659841 contains the supplementary
crystallographic data of 8. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request.cif.
1
1687 (s, COazide) cm-1. H NMR (CDCl3): δ 4.87 (2H, s, H2′,5′),
Ferrocenecarboxazide Fc-CO-N3 (1). Ferrocenecarboxylic acid
(400 mg, 1.74 mmol) was suspended in water (0.3 mL), and
sufficient acetone was added to dissolve it. After cooling to 0 °C,
triethylamine (202 mg, 2.0 mmol) in acetone (3.3 mL) was added.
While maintaining the temperature at 0 °C, a solution of ethyl
chloroformate (242 mg, 2.23 mmol) in the same solvent (0.9 mL)
was added. After stirring for 30 min at 0 °C a solution of sodium
azide (173 mg, 2.63 mmol) in water was added. After stirring for
1 h at 0 °C the mixture was poured into ice–water and extracted
with methylene chloride. The extracts were washed with 5%
aqueous solution of NaHCO3 and a saturated aqueous solution of
NaCl, dried over NaSO4, and evaporated in Vacuo at room
temperature to dryness to leave red crystals (332 mg, 75%). Mp:
4.85 (2H, s, H2,5), 4.54 (2H, s, H3-4), 4.45 (2H, s, H3′,4′), 3.83
(3H, s, COOCH3). 13C NMR, APT (CDCl3): δ 175.90 (s, COazide),
170.29 (s, COester), 74.07 (s, C1′), 73.66 (s, C2,5), 73.04 (s, C1),
72.72 (s, C2′,5′), 71.81 (s, C3,4), 71.75 (s, C3′,4′), 51.96 (s, CH3).
Methyl-1′-isocyanatoferrocene-1-carboxylate (6). Similarly to
the preparation of isocyanatoferrocene 2 a benzene solution of 5
(180 mg, 0.632 mmol) gave 170 mg of crude compound 6
contaminated with 5. IR (CH2Cl2): ν 2173 (s, NCO), 1717 (s,
COester) cm-1
.
CH3OOC-Fn-NH-CO-Ala-OCH3 (7). The crude compound 6
(170 mg) was suspended in dry methylene chloride and coupled
with H-Ala-OCH3 (obtained from H-Ala-OCH3 · HCl by treatment

Ferrocene Ureidopeptides
Organometallics, Vol. 27, No. 4, 2008 735
with Et3N in CH2Cl2). The mixture was stirred for 1 h. After
standard workup, the product was purified by TLC [CH2Cl2/EtOAc
(10:1)], yielding 90 mg (48%) of 7 (orange resin) followed by 40
mg of azide 5. FAB-MS: m/z (%) 388 (100, M+). Anal. Calcd for
C17H20FeN2O5: C, 52.60; H, 5.19; N, 7.22. Found: C, 52.19; H,
5.24; N, 7.07.
Acknowledgment. We thank the Ministry for Science,
Education and Sport of Croatia for support through a grant,
the Deutsche Forschungsgemeinschaft for a Heisenberg
Fellowship (to K.H.), and the Graduate College “Molec-
ular Probes” for a doctoral scholarship (to D.S.). We are
indebted to Ph.D. Leo Frkanec (Rudjer Boškovic´ Institute)
for measuring UV/vis and CD spectra.
CH3OOC-Fn-NH-CO-Ala-Ala-OCH3 (8). Coupling of crude
compound 6 (400 mg) in dry methylene chloride with 1.2 mmol of
H-Ala-Ala-OCH3 was performed similarly to the preparation of 4.
TLC purification of the product with CH2Cl2/EtOAc (10:1) gave
orange crystals (280 mg, 66%) and 110 mg of unreacted carboxazide
5. Mp: 140–143 °C. IR (KBr): ν 3387, 3357, 3321 (m, NH, assoc.),
Supporting Information Available: Gaussian fits of CD
spectra of 4, 7, and 8, an ORTEP view of the molecular structure
of 8, crystal packing of compound 8, the DFT-calculated
Cartesian coordinates of all conformers of 7 and 8, and CD
spectra of 4 and 8 in KBr disks. This material is available free
of charge via the Internet at http://www.pubs.acs.org.
1727, 1710 (s, COester), 1646 (s, amide I), 1549 (s, amide II) cm-1
.
FAB-MS: m/z (%) 459 (100, M+). Anal. Calcd for C20H25FeN3O6:
C, 52.30; H, 5.49; N, 9.15. Found: C, 52.24; H, 5.48; N, 9.01.
OM700950R