Synthesis, crystal structure, IR and Raman properties of 1,2-diacetamidocyclohexane and its complexes with ZnBr2 and HBr 3

Article abstract of DOI:10.1016/j.molstruc.2004.10.068

X-ray crystallography, infrared absorption and Raman scattering were applied to study the influence of Zn(II) or H⁺ on the amidic bond. (R,R)-1,2-diacetamidocyclohexane (DAACH) was chosen as a conformationally strained chiral building block inc

Full text of DOI:10.1016/j.molstruc.2004.10.068

Journal of Molecular Structure 738 (2005) 39–44
www.elsevier.com/locate/molstruc
Synthesis, crystal structure, IR and Raman properties of
,2-diacetamidocyclohexane and its complexes with ZnBr and HBr
1
2
3
a
A. Bekaert , P. Lemoine , B. Viossat , M. Jouan , P. Gemeiner , J.D. Brion
b,
b
c
c
a
*
a
UPRES-A CNRS 8076 BioCIS, Laboratoire de Chimie Th e´ rapeutique, Facult e´ de Pharmacie de Paris XI, 92290 Ch aˆ tenay-Malabry, France
b
Laboratoire de Cristallographie et de RMN Biologiques, UMR 8015 CNRS, Facult e´ des Sciences Pharmaceutiques
et Biologiques de Paris V, Paris 75006, France
Laboratoire S.P.M.S. UMR 8580 CNRS, Ecole Centrale Paris, Ch aˆ tenay-Malabry 92290, France
c
Received 15 July 2004; revised 11 October 2004; accepted 14 October 2004
Abstract
C
X-ray crystallography, infrared absorption and Raman scattering were applied to study the influence of Zn(II) or H on the amidic bond.
R,R)-1,2-diacetamidocyclohexane (DAACH) was chosen as a conformationally strained chiral building block including two amide
bonds; this model is hoped to be not too far from a peptide and gives easily crystalline complexes.
(
Crystallographic structures of DAACH molecule (1), DAACH/ZnBr (2) and DAACH/HBr (3) complexes were studied.
2
3
Complexation of Zn by DAACH is due to the hyperpolarization of the amidic bond. IR and Raman studies of 1–3 agree with the X-ray
results. This could be a model in the study of metal/proteins interactions or acidic denaturation of polypeptides.
q 2004 Elsevier B.V. All rights reserved.
C
Keywords: DAACH; Complexes with Zn(II) or H ; X-ray structures; IR; Raman
1
. Introduction
peptides, being capable of binding metals or cations in
crystalline complexes.
Secondary or tertiary native structure of proteins cannot
Our purpose was to study the influence of a metal on
the tautomeric forms of the amidic bond. As tools, X-ray
crystallography, infrared absorption and Raman scattering
were used to study these organometallic interactions.
(R,R)-1,2-diacetamidocyclohexane (DAACH) was
chosen as a chiral building block containing two amide
bonds; this conformationally preorganized model is hoped
to be not too far from a peptide and gives easily crystalline
complexes due to its strained geometry. As a model of
be predicted from the protein’s amino-acids sequence alone
whereas successive residues with identical or nearly
identical main chain conformation form a helices b sheets
or polyproline type II helices; adjacent residues with
enantiomeric main chain conformation form so-called
nests when the (f, f) values are close to K90.0 and
C90.08. This concept sets the stage for a general approach to
binding sites in proteins.
Main chain N–H groups form a binding site at the N
terminal of an a helix and amidic oxygen atoms behave
similarly to those of carboxylates; they can bind cations and
thus are named the catgrips [1], performed with the help of
protein structure databases [2].
metal/amide interaction Zn(II) as ZnBr has been chosen.
2
1
0
The electron configuration 3d of Zn(II) implies that the
stereochemistry of the complexes formed depend on size of
the ligand or electrostatic forces.
Peptide/zinc interactions are common in biochemistry.
Angiotensin Converting Enzyme is the prototype of a
Zn containing peptide and many metalloproteases are Zn
containing molecules. The action of hydroperbromic acid on
DAACH has been studied with the crystallized DAACH/
Following our work concerning the crystallographic
structure of amides/cations complexes [3–5], we decided to
build a synthetic chiral model as close as possible to
HBr complex as a model of a strong acid influence on a
3
*
Corresponding author. Tel.: C33 1 5373 9709; fax: C33 1 5373 9925.
E-mail address: pascale.lemoine@univ-paris5.fr (P. Lemoine).
peptide structure.
0022-2860/$ - see front matter q 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2004.10.068

40
A. Bekaert et al. / Journal of Molecular Structure 738 (2005) 39–44
In this paper, crystal structures of DAACH and DAACH/
HBr are reported and compared with a DAACH/ZnBr
Table 1
Crystal data of R,R-1,2-diacetamidocyclohexane(1) catena-poly(hydrogen-
ato)-m-(R,R)-1,2-diacetamidocyclohexane (3)
3
2
complex recently described by us [5]. IR and Raman studies
complete crystallographic results.
1
3
Amidification of 1,2-diacetamidocyclohexane (DAACH)
give flexibility in the side chain. Changes in configura-
Formula
C10H18N O
2
3 2 2
C10H19Br N O
2
Formula weight
Crystal system
˚
a (A)
˚
b (A)
˚
c (A)
198.26
439.00
C
tion are in relation with the interaction of Zn(II) or H and
Monoclinic
10.113(5)
4.825(5)
Orthorhombic
9.572(2)
the amidic bond. If crystalline DAACH is bounded as a
dimmer by two conventional hydrogen bonds, DAACH
dibromozinc is a catena-structure. Each DAACH is bounded
with another threw a three centers atomic bond including
double bounded oxygen Zn(II) and another double bounded
oxygen.
15.115(3)
11.340(5)
11.533(5)
96.644(5)
559.0(7)
b (8)
3
˚
V (A )
1640.7(9)
Space group
P2
1
C222
1
Z
2
4
K3
Dx (g cm
)
1.178
0.82
1.777
7.37
DAACH hydroperbromide complex is a catena-ionized
molecule. A three center atomic bond joins each DAACH to
another. This bond is formed with amide oxygen, external
K1
m (Mo Ka) (mm
Independent reflections
)
3253
1835
0.051
0.141
2405
Reflections number IO2s(I)
R
690
C
0.055
0.132
K0.62/0.55
H
and the amide oxygen of a second DAACH.
Rw
˚
Largest diff. peak and hole (e A
K3
)
K0.17/0.21
See crystal data of catena-poly[[dibromozinc(II)]-m-(R,R)-1,2-diacetami-
docyclohexane] (2) earlier published [5].
2
2
2
. Experimental
.1. Preparation of crystalline complexes
in the WINGX package [11]. The crystallographic data and
refinement parameters are shown in Table 1.
.1.1. Catena-(R,R)-1,2-diacetamidocyclohexane
(
DAACH) (1)
This compound was synthesized by acetylation of
2.3. Raman scattering and infrared absorption spectra
commercial (R,R)-1,2-diaminocyclohexane using triethy-
lamine (1/1) and acetic anhydride in excess (3/1).
Suitable crystals were grown from the saturated boiling
solution of 1 in the glacial acetic acid by slow cooling
Raman scattering spectra were obtained with a resolution
K1
of 1 cm using a Bruker IFS66CFRA106 interferometer
and a continuous YAG laser (1.06 mm) for excitation. Raman
spectra obtained on a Dilor Labram spectrometer with
excitation at 514.5 nm have not been used, because they were
of poor quality due to the fluorescence of the samples.
Infrared spectra were recorded on a Bruker IFS66 inter-
(
mpO240 8C).
2
.1.2. Catena-poly(hydrogenato)-m-(R,R)-1,2,diacetamido
cyclohexane (3)
K1
DAACH/HBr3 crystals were prepared as following:
an acetic solution of HBr3 is prepared by addition of
equimolecular quantities of bromine to a saturated solution
ferometer with a resolution of 1 cm on KBr pellets or on a
K1
Bruker Vector 22 using an ATR cell (resolution 4 cm ).
Table 2
of HBr in acetic acid. HBr and DAACH were then reacted
3
˚
˚
Selected geometric parameters (A,8) and hydrogen-bonding geometry (A,8)
for 1–3
in stoechiometric quantity to give the complex 3. A slow
evaporation of saturated acetic acid solution leads to
suitable crystals as orange needles (mpZ210 8C, dec.).
1
2
3
O2–C2
1.229(3)
1.328(3)
1.224(3)
1.333(3)
1.237(7)
1.339(7)
1.264(7)
1.324(7)
1.974(4)
1.970(4)
118.4(5)
118.6(5)
1.247(9)
2
.2. X-ray crystallographic study
N3–C2
1.297(10)
O11–C11
N10–C11
Data were collected on a Enraf–Nonius CAD4 diffract-
i
Zn–O2
ometer at 293 K, with graphite monochromated Mo Ka
radiation, with data collection and reduction using CAD4
Express Enraf–Nonius (1994) programs package [6] and
XCAD4 (1995) [7]. All data were corrected for Lorentz-
polarisation effects. All the structures were solved by direct
methods using SIR92 [8] and refined by least-squares
Zn–O11
O2–C2–N3
O11–C11–N10
122.3(2)
123.0(3)
2.864(4)
119.4(7)
i-
i
N10 H10 /O11
1
72
2.894(4)
69
i
N3–H3/O2
1
2
methods on F using SHELXL97 [9]. Hydrogen atoms were
N3–H3/O11
2.864(6)
127
inserted at calculated positions. The same isotropic thermal
parameter for all H atoms is refined. Drawings of these
molecules were obtained with the CAMERON program [10].
All programs used for structure refinement are incorporated
iii
O2/H2/O2
2.473(10)
1
79(11)
i: x, yK1, z; ii; x, y C1, z; iii: 1Kx, y, 5/2Kz.

A. Bekaert et al. / Journal of Molecular Structure 738 (2005) 39–44
41
Fig. 1. R,R-1,2-diacetamidocyclohexane (DAACH) (a) scheme, (b) perspective view showing 20% probability displacement ellipsoids. Hydrogen atoms are
omitted for clarity except for those involved in hydrogen bonding (dotted lines). Symmetry code i, x, yK1, z.
Deuterated derivatives were obtained by dissolution of
the compounds in deuterium oxyde followed by evapor-
ation of the solution under heating (DAACH, DAACH/
ZnBr ) or by dissolution in deuterated methanol (CH OD)
Inclusion of Zn in the structure is due to hyperpolariz-
ation of the amidic bond with subsequent changes in the
conformation. DAACH is in a chair conformation with the
two acetamid groups in equatorial positions. The difference
2
3
˚
between the two CaO bond lengths [C2–O2: 1.237(7) A
˚
and C11–O11: 1.264(7) A] can be explained by the
followed by evaporation of the methanol (DAACH,
DAACH/HBr3).
presence of the N –H/O intramolecular hydrogen bond
˚
[
N3/O11: 2.864(6) A, 1278] which causes the stretching of
3
. Results and discussion
3
.1. Crystal structures
Selected interatomic distances, bond angles and hydro-
gen bonds are given in Table 2.
3
.1.1. Catena-(R,R)-1,2-diacetamidocyclohexane
The two amidic bonds of this molecule are in a strained
conformation due to cyclohexane with the two nitrogens
at a distance close to that found in peptides. Molecules
of DAACH are found in the structure as pseudopeptide
backbone mimic (Fig. 1). Individual molecules are linked
into chains running parallel to b axis by two intermolecular
hydrogen bonds involving H3 and H10.
The intramolecular hydrogen bonds are impossible to
form due to the strained conformation of DAACH
˚
˚
[
N3/O11: 3.921(3) A or N10/O2: 3.953(3) A].
The bond lengths within the amide portions of DAACH
˚
1.224(3) and 1.229(3) A for CaO; 1.328(3) and 1.333(3) A
˚
[
for C–N], are in good agreement with distances found for
˚
free amide (1.24 and 1.325 A, respectively) [12].
3.1.2. Catena-poly[[dibromozinc(II)]-m-(R,R)-1,2-
diacetamidocyclohexane]
Fig. 2. Catena-poly[[dibromozinc(II)]-m-(R,R)-1,2-diacetamidocyclo-
hexane]. (a) Scheme, (b) perspective view showing 20% probability
displacement ellipsoids. Hydrogen atoms are omitted for clarity except
for those involved in hydrogen bonding (dotted lines). Symmetry codes i;
x, yK1, z; ii: 1Kx, Ky, 1Kz.
Crystallized complexes of 2 present a catena structure [5]
with Zn bridging two amides belonging to two molecules
(Fig. 2). It is to our knowledge the first example of such a
type of bridge with Zn.

42
A. Bekaert et al. / Journal of Molecular Structure 738 (2005) 39–44
Table 3
K1
Frequencies (cm ) of stretching or bending vibrations for the CaO or
N–H bonds
Compounds
Raman
(Deuterated IR
derivative)
(Deuterated
derivative)
(
a) Stretching vibration for the CaO bond
DAACH
1645
1616
1644
1617
1643
1644
1617
DAACH/ZnBr
2
1617
1592
1612
1
–
593
DAACH/HBr
3
–
1612
(
b) Stretching vibration for the N–H bond
DAACH
3285
3358
3151
2444
423
2495
3285
3220
3358
3300
3330
2438
2400
2454
2503
2500
2310
2
DAACH/ZnBr
2
2
–
423
DAACH/HBr
3
3
3
280
145
(
c) Bending vibration for the N–H bond
DAACH
1470
1506
–
1547
1561
1578
1471
1504
1514
DAACH/ZnBr
2
1567
1579
DAACH/HBr
3
3
.2. Raman and IR spectra
Comparative studies of 1 and 2 spectra show many
differences among which some can be directly related to
complexation.
If complexation creates a bond between the oxygen atom
of the carbonyl and the zinc cation, it should lead to a
diminution of the CaO stretching frequency.
In fact the comparison of the spectra is not straightfor-
ward since, in this region, deformation frequencies implying
the N–H bonds should also appear. In order to resolve this
ambiguity, we have deuteriated the N–H bonds and checked
which peaks remained almost unchanged and which one
were shifted.
Fig. 3. Catena-poly(hydrogenato)-m-(R,R)-1,2-diacetamidocyclohexane.
a) Scheme, (b) perspective view showing 20% probability displacement
(
ellipsoids. Hydrogen atoms are omitted for clarity except for those involved
in hydrogen bonding (dotted lines). Symmetry codes iii: 1Kx, y, 5/2Kz;
iv: x, 1Ky, 2Kz.
the C11–O11 bond. Moreover, the torsion angles C4–N3–
C2–O2 (4.9(8)8) is slightly different from C9–N10–
C11–O11 (1.4(8)8) which may be compared with the values
found in 1 (1.1(4) and 1.2(4)8, respectively).
3.1.3. Catena-poly(hydrogenato)-m-(R,R)-1,2-
diacetamidocyclohexane
Individual molecules of 3 are linked into chains running
parallel to c-axis by CO/H/OC intermolecular hydrogen
bonds involving H(O2) (Fig. 3). In this bond, the proton is
located on two-fold axis (4b position of C222 space group).
1
˚
This symmetric hydrogen bond is very short (2.473(10) A;
179(11)8); some examples of such bonds have been
described in the literature [13].
This proton comes from HBr , quite differently from
3
CO/H–N found in crystalline DAACH.
The CaO bond length is 1.247(9) A which is in
˚
accordance with an increasing of the amidic bond
polarization.
Fig. 4. Correlation between the bond length CaO and the stretching
vibration frequency.

A. Bekaert et al. / Journal of Molecular Structure 738 (2005) 39–44
43
Fig. 5. Raman spectra of the compounds.
3
.2.1. CaO stretching vibrations
In DAACH, we have attributed this vibration to the
3.2.2. NH stretching vibrations
The study of the structure also indicates the probability of
NH/O bonds. This can be checked by observing the
spectra in the NH stretching and deformation vibration
regions, the assignment being comforted by the effect of the
ND/NH isotopic substitution (Figs. 5 and 6).
K1
K1
Raman peak at 1645 cm (IR: 1633 cm ) which remains
unshifted by deuteriation (Table 3). In the complexes, this
K1
peak is shifted down to 1616 cm (Raman) and 1593 cm
K1
K1
IR) for 2, and 1612 cm (IR) for 3. The values of Table 3
(
have been completed by some other values from literature
14] and can be reported on a graph as a function of
corresponding CaO distances obtained by X-ray diffraction
Fig. 4). There is a good agreement between the two sets
of data.
N–H stretching vibrations give a Raman peak at
K1
3285 cm to which correspond two IR peaks at 3285 and
[
K1
3220 cm (Table 3). Upon deuteriation, these peaks shift
K1
K1
(
down 2444–2423 cm (Raman) and 2438, 2400 cm (IR,
two large bands).
Fig. 6. Infrared spectra of the compounds.

44
A. Bekaert et al. / Journal of Molecular Structure 738 (2005) 39–44
On the contrary, in 2, there is an increase of the N–H
with ZnBr and HBr particularly about metal/ligand inter-
2 3
K1
stretching frequency to 3358 cm (Raman: 2495, 2423 for
the deuteriated derivative). This is in good agreement with
the fact that due to the complexation one N–H of DAACH is
now free and hence stronger.
actions. Complexation induces conformation modifications
of 1 leading catena Zn or H bridged compounds. This could
be a model in the study of metal/proteins interactions or
acidic denaturation of polypeptides.
In 3, the Raman stretching frequencies are shifted
K1
down to 3151 cm
K1
and 3145 cm
and the IR frequency to 3330, 3280
(2500 and 2310 for the deuteriated
derivative) indicating an increase of the hydrogen bond
strength.
References
[
[
[
1] J.D. Watson, E.J. Milner-White, J. Mol. Biol. 315 (2002) 183.
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P. Lemoine, B. Viossat, Z. Kristallogr. NCS 218 (2003) 123.
3
.2.3. NH deformation frequencies
Peaks corresponding to the NH deformations differ from
the CaO stretching frequencies of similar values by the fact
that they may be shifted upon deuteriation.
[
Upon complexation, there is an increase of this
frequency: 1 to 2 and to 3. One can note that for 2, the
shifts of the NH deformation corresponds to an increase
of the NH bond strength, contrarily to what was observed
for the NH stretching frequency; this could be explained by
the free NH bond being visible in the stretching region and
the other one in the deformation region.
[5] A. Bekaert, P. Lemoine, J.D. Brion, B. Viossat, Acta Crystallogr. E59
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(
[
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[
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[
9] G.M. Sheldrick, SHELXL97, University of G o¨ ttingen, Germany,
997.
In the low frequency range, we expect vibrations
corresponding to Zn–O and Zn–Br stretching. In this
range, by comparison with the Raman spectra of DMF,
1
[
10] D.J. Watkin, C.K. Prout, L.J. Pearce, CAMERON, Chemical
Crystallography Laboratory, Oxford, England, 1996.
K1
ZnBr (261, 217 and 187 cm ) and with the frequency
2
[11] L.J. Farrugia, J. Appl. Cryst. 32 (1999) 837.
[12] H. Sigel, B. Martin, Chem. Rev. 82 (1982) 385.
ranges mentioned in the literature for the Zn–Br stretching
[
13] G.A. Jeffrey, An introduction to Hydrogen Bonding, Oxford
University Press Inc., Oxford, 1997. pp. 39.
[
assigned the peak at 313 cm to this vibration the peaks
15,16], the Zn–O stretching [17,18] and CH torsions, we
3
K1
[
14] E.R. Acuna-Cueva, R. Faure, N.A. Illan-Cabeza, S.B. Jimenez-
Pulido, M.N. Moreno-Carretero, Polyhedron 21 (2002) 1961.
at 248 and 210 to the Zn–Br stretching, and the peak at
1
K1
87 cm for the CH torsion.
3
[15] D.M. Adams, Metal-Ligand and Related Vibrations, Edward Arnold
Ltd, London, 1967. p. 79.
[
[
[
16] K. Golcuk, A. Altun, M. Kumru, Spectrochim. Acta A 59 (2003)
841.
1
4
. Conclusion
17] J.R. Ferraro, Low-Frequency Vibrations of Inorganic and Coordi-
nation Compounds, Plenum Press, New York, 1971.
X-ray crystallography, infrared and Raman spectro-
scopies were used to study DAACH and its complexes
18] K. Nakamoto, Infrared Spectra of Inorganic and Coordination
Compounds, second ed., Wiley, New York, 1970.