Available online at www.sciencedirect.com
Journal of Molecular Structure 879 (2008) 14 24
www.elsevier.com/locate/molstruc
Spectroscopic, mass spectrometry, and semiempirical investigations
of a new 2-(2-methoxyethoxy)ethyl ester of Monensin A
and its complexes with monovalent cations
a a a,* b,c
Adam Huczyński , Daniel A
owicki , Bogumil Brzezinski , Franz Bartl
a
Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland
b
Institute of Medical Physics and Biophysics, Charité  Universitätsmedizin Berlin, Campus Charité Mitte, Ziegelstr. 5/9, 10117 Berlin, Germany
c
Zentrum für Biophysik und Bioiformatik, Invalidenstr. 42, 10115 Berlin, Germany
Received 25 July 2007; accepted 10 August 2007
Available online 17 August 2007
Abstract
A new 2-(2-methoxyethoxy)ethyl ester of Monensin A (MON7) has been synthesized and its capability of complex formation with
1 13
Li+, Na+, and K+ cations has been studied by ESI MS, H and C NMR, FT-IR, and PM5 semiempirical methods. ESI mass spectrom-
etry indicates that MON7 forms complexes with Li+, Na+, and K+ of exclusively 1:1 stoichiometry which are stable up to cv = 70 V. The
formation of complexes between MON7 and Na+ cations is strongly favored. Starting from about cv = 90 V fragmentation of the respec-
tive complexes is observed, primarily characterized by several dehydration steps. The structures of the MON7 complexes with Li+, Na+,
and K+ cations are stabilized by intramolecular hydrogen bonds in which the OH groups are always involved. The structures are visu-
alized and discussed in detail. It has been proved that the formation of a pseudo crown ring structure formed by MON7 is preferred in
complexes with Na+ cations.
Ó 2007 Elsevier B.V. All rights reserved.
Keywords: Ionophores; Esters; Complexes; Monovalent cations; Semiempirical calculations; Spectroscopy; Hydrogen bonds
1. Introduction lent metal cations by the esters of Monensin A and the
properties of these complexes have been described in detail.
Monensin A isolated from Streptomyces cinnamonensis As a continuation of our earlier works, we report here
1 13
is a well-known representative of naturally polyether iono- ESI MS, H and C NMR, FT-IR as well as semiempirical
phore antibiotics. It is able to form pseudomacrocyclic studies of complexes between a new 2-(2-methoxyeth-
complexes with mono and divalent cations and to transport oxy)ethyl ester of Monensin A and monovalent cations
these cations across cell membranes. Monensin A has very such as the Li+, Na+, and K+. This new ester, in compar-
important and useful biological activities such as growth ison with the esters studied earlier, contents additionally
inhibition of Gram-positive organisms and effective control two etheric oxygen atoms, which can influence the com-
of coccidiosis in chickens [1 6]. In our earlier works the plexation process. The structures of 2-(2-methoxyeth-
synthesis and the physicochemical characterization of oxy)ethyl ester of Monensin A and its complexes with
new esters of Monensin A has been reported [7 14]. In monovalent cations are discussed in detail.
these publications the complexation of the mono and diva-
2. Experimental
*
Monensin A sodium salt was purchased from Sigma
Corresponding author. Tel.: [phone].
E-mail address: [e-mail] (B. Brzezinski). (90 95%). The perchlorates LiClO4, NaClO4, and KClO4
0022-2860/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2007.08.004
A. Huczyński et al. / Journal of Molecular Structure 879 (2008) 14 24 15
were commercial products of Sigma and were used without separately and (b) the cations Li+, Na+, and K+ (5 · 10 5/
any further purification. The salts were hydrates, and it was 3 mol dm 3) taken together. The samples were infused into
necessary to dehydrate them by several (6 10 times) evap- the ESI source using a Harvard pump at a flow rate of
oration steps from a 1:5 mixture of acetonitrile and abso- 20 ll min 1. The ESI source potentials were: capillary
lute ethanol. The dehydration of the perchlorates was 3 kV, lens 0.5 kV, extractor 4 V. The standard ESI mass
followed by FT-IR spectroscopy in acetonitrile. spectra were recorded at cone voltages: 10, 30, 50, 70, 90,
CD3CN and CH3CN spectral-grade solvents were 110, and 130 V. The source temperature was 120 °C and
stored over 3 Å molecular sieves for several days. All the dissolvation temperature was 300 °C. Nitrogen was used
manipulations with the substances were performed in a as the nebulizing and dissolvation gas at flow-rates of 100
carefully dried and CO2-free glove box. and 300 dm3 h 1, respectively. Mass spectra were acquired
in the positive ion detection mode with unit mass resolution
2.1. Synthesis of 2-(2-methoxyethoxy)ethyl ester of at a step size of 1 m/z unit. The mass range for ESI experi-
Monensin A (MON7) ments was from 200 to 1000 m/z.
Monensin A sodium salt was dissolved in dichlorometh- 2.4. Spectroscopic measurements
ane and stirred vigorously with a layer of aqueous sulfuric
acid (pH = 1.5). The organic layer containing MONA was The FT-IR spectra of MON7 and its 1:1 complexes
washed with distilled water, and dichloromethane evapo- (0.07 mol dm 3) with LiClO4, NaClO4, and KClO4 were
rated under reduced pressure to dryness. recorded in the mid infrared region in acetonitrile solutions
A solution of MONA (500 mg, 0.75 mmol), 1,3-dic- using a Bruker IFS 113v spectrometer.
yclohexylcarbodiimide (140 mg, 0.90 mmol), 4-pyrrolidino- A cell with Si windows and wedge-shaped layers was
pyridine (50 mg, 0.33 mmol), 2-(2-methoxyethoxy)ethanol used to avoid interferences (mean layer thickness
(600 mg, 5.0 mmol), and 4-toluenesulfonic acid monohy- 170 lm). The spectra were taken with an IFS 113v FT-IR
drate (28.5 mg, 0.15 mmol) in dichloromethane (15 cm3) spectrophotometer (Bruker, Karlsruhe) equipped with a
was stirred at a temperature below 0 °C for 24 h. After this DTGS detector; resolution 2 cm 1. The Happ Genzel apo-
time the reaction mixture was stirred at room temperature dization function was used. All manipulations with the
for 24 h, diluted with H2O and extracted with CH2Cl2. The compounds were performed in a carefully dried and CO2-
extract was evaporated under reduced pressure to dryness. free glove box.
The residue was suspended in hexane and filtered off. The The NMR spectra of MON7 and its 1:1 complexes
filtrate was evaporated under reduced pressure and purified (0.07 mol dm 3) with LiClO4, NaClO4, and KClO4 were
by chromatography on silica gel (Fluka type 60) to give recorded in CD3CN solutions using a Varian Gemini
MON7 (420 mg, 72% yield) as a colorless oil showing ten- 300 MHz spectrometer. All spectra were locked to the deu-
dency to form a glass state. terium resonance of CD3CN.
1
Elemental analysis: Calcd C 63.71%, H 9.39%. Found: The H NMR measurements in CD3CN were carried
C = 63.69%, H = 9.43%. out at the operating frequency 300.075 MHz; flip angle,
pw = 45°; spectral width, sw = 4500 Hz; acquisition time,
2.2. Preparation of MON7 complexes with monovalent at = 2.0 s; relaxation delay, d1 = 1.0 s; T = 293.0 K and
cations using TMS as the internal standard. No window func-
tion or zero filling was used. Digital resolution was
The 0.07 mol dm 3 solutions of 1:1 complexes of MON7 0.2 Hz per point. The error of chemical shift value was
with monovalent cations (Li+, Na+, and K+) were 0.01 ppm.
13
obtained by adding equimolar amounts of MClO4 salt C NMR spectra were recorded at the operating fre-
(M = Li, Na, K) dissolved in acetonitrile to acetonitrile quency 75.454 MHz; pw = 60°; sw = 19000 Hz; at = 1.8 s;
solution of MON7. The solvent was evaporated under d1 = 1.0 s; T = 293.0 K and TMS as the internal standard.
reduced pressure to dryness and the oily residue was dis- Line broadening parameters were 0.5 or 1 Hz. The error of
solved in an appropriate volume of dry CH3CN or CD3CN chemical shift value was 0.01 ppm.
1 13
to obtain the complex at a 0.07 mol dm 3 concentration. The H and C NMR signals were assigned indepen-
dently for each species using one- or two-dimensional
2.3. Mass spectrometry (COSY, HETCOR) spectra.
The ESI (Electrospray Ionization) mass spectra were 2.5. Semiempirical calculations
recorded on a Waters/Micromass (Manchester, UK) ZQ
mass spectrometer equipped with a Harvard Apparatus syr- PM5 quantum calculations were performed using the
inge pump. All samples were prepared in acetonitrile. The Win Mopac 2003 program at the semiempirical level (Cache
measurements were performed with two types of samples; Work System Pro version 5.04  Fujitsu) [14 19]. PM5
solutions of MON7 (5 · 10 5 mol dm 3) with: (a) each of quantum semiempirical method use the Schrödinger equa-
the cations Li+, Na+, and K+ (2.5 · 10 4 mol dm 3) taken tion to determine bond strengths, atomic hybridizations,
16 A. Huczyński et al. / Journal of Molecular Structure 879 (2008) 14 24
Table 1
partial charges, and orbitals from the positions of the
The main peaks in the ESI mass spectra of the complexes of MON7 with
atoms and the net charge. For MON7 and its complexes
cations at various cone voltages
the initial optimization of the structures was carried out
Cation Cone voltage Main peaks (m/z)
using the molecular mechanics  extensive global minimum
[V]
energy conformation search with the Conflex/MM3 from
Li+ 10 780
WinMopac 2003 program. Global optimization runs were
30 780
carried out for all the MON7 complexes using about
50 780
4500 local minimizations in each global optimization.
70 780
The calculated energetically the most favorable structures
90 780, 762
110 780, 762, 744, 485, 467, 445, 427, 283
of conformers corresponding the global minimum points
130 780, 762, 744, 485, 467, 445, 427, 283
were further optimized by the PM5 quantum semiempirical
method with the energy gradient not exceeding 10 kcal/mol Na+ 10 796
30 796
in one step. In all cases full geometry optimization of
50 796
MON7 and its complexes was carried out without any sym-
70 796
metry constraints. The semiempirical calculations were per-
90 796, 778
formed using a computer equipped with an AMD Athlon
110 796, 778, 760, 507, 501, 489, 461, 443, 299
1.26 GHz processor and 2 GB operating memory. 130 796, 778, 760, 507, 501, 489, 483, 479, 461, 443,
299
2.6. Elemental analysis
K+ 10 812
30 812
50 812
The elemental analysis of MON7 was carried out on
70 812
Vario ELIII (Elementar, Germany).
90 812
110 812, 794, 776
3. Results and discussion 130 Many peaks
The structure of MON7 together with the atom number-
the abstraction of the OIVH or OXH hydroxyl groups
ing is shown in Scheme 1.
yielding cation structures B or H, respectively. Further
fragmentation of cation B, of MON7 with Li+ and Na+
3.1. Electrospray mass spectrometry (ESI) measurements
cations, is realized in two directions, whereas other types
of complexes (C, D, E, F, and finally G) are formed. Fur-
The main m/z peaks in the ESI mass spectra of MON7
thermore, cation B can undergo fragmentation to cation
with the Li+, Na+, and K+ cations used separately at var-
K due to complexation of the Li+ and Na+ cations by
ious cone voltages (cv) are collected in Table 1. One
the oxaalkyl chain of the ester part. Cation C is formed
exemplary ESI mass spectrum of the 1:1 complex of
from cation B by abstraction of a second water molecule.
MON7 with Na+ cation measured at various cone volt-
The formation of the D and E fragmentary complexes is
ages is shown in Fig. 1. The data summarized in Table
achieved by abstraction of the part of the molecule that
1 show that MON7 exclusively forms complexes of 1:1
includes the ester group. Cations F and G can be formed
stoichiometry with the monovalent cations that are very
from cations D and E by the abstraction of one C3H4
stable up to about cv = 70 V. Starting from about
group. Additionally, cation G can be formed by loss
cv = 90 V fragmentation of the respective complexes is
of one water molecule from cation F. For the complex
observed. Based on the analysis of the fragmentary m/z
of MON7 with K+ cation, no abstraction of the part of
signals the fragmentation pathways shown in Scheme 2
the molecule including the ester group was detected.
are proposed. The first step of the fragmentation is the
In the case of the MON7-Na complex the fragmentation
loss of one water molecule from cation A as a result of
of cation B yields cation L which after the abstraction of
one CO molecule forms cation M. Furthermore, cation
M undergoes fragmentations typical of other metal cations
IV
OH
with abstraction of water molecules in to steps yielding cat-
33 29 28 27
Me
II Me Me Me
III
32
ions F and G, respectively.
30-31
7
O MeO
Me
Et H
XI
35 Fig. 2 presents the ESI spectrum of the 1:1:1:3 mixture
5 25
21
13 17
26
R OH
9
1 of Li+, Na+, K+ cations and MON7 measured at
O O O
O O O
OH
H
H
H H
I
VIII cv = 30 V. In this figure only three characteristic signals
V VI VII IX X
Me Me
36 34
at m/z = 780, m/z = 796 and m/z = 812 assigned to the
XIII
3'
2'
1:1 complexes of MON7 with Li+, Na+, and K+ cations
OCH3
MONA R=H MON7 R=
O
5' are shown, respectively. The intensity of the MON7 Na+
1'
4'
XII
complex signal is the strongest, indicating clearly that
MON7 preferentially forms complexes with Na+ cations.
Scheme 1. The structures and atom numbering of MONA and MON7.
A. Huczyński et al. / Journal of Molecular Structure 879 (2008) 14 24 17
Fig. 1. ESI mass spectra of a 1:1 mixture of MON7 with Na+ at various cone voltages (cv).
1 13
The intensities of the signals of the MON7 Li+ and 3.2. H and C NMR measurements
MON7 K+ complexes are comparable, but significantly
1 13
lower than that of the MON7 Na+ complex, demonstrat- The H and C NMR data of MON7 in CD3CN and its
ing that MON7 shows much lower affinity to Li+ and K+ 1:1 complexes with Li+, Na+, and K+ cations all in CD3CN
cations. are shown in Tables 2 and 3, respectively. Unfortunately,
18 A. Huczyński et al. / Journal of Molecular Structure 879 (2008) 14 24
+ +
I
H
O
O
O
O
K
O -H2O O
O H
O
+
M
M
O
O
O
O OCH3
H
H M=Li+ m/z=744
H
O
O
M
M=Na+ m/z=760
O
M=K+ m/z=776
O O
O
O
O
O O
O O OCH3
O O OCH3
M=Li+ m/z=283
M=Na+ m/z=299
M=Li+ m/z=762
-H2O
M=Na+ m/z=778
M=K+ m/z=794
+ + +
B
A C
O O
O
O O
O
-H2O
-H2O
O O
O
O O
O
O O
M O M M
O O
O
O H
O H
H
H
H M=Li+ m/z=744
O
M=Na+ m/z=760
O O
O
M=K+ m/z=776
O O
O
O O
O O OCH3 OCH3
O O OCH3
M=Li+ m/z=780
M=Na+ m/z=796
M=K+ m/z=812
M=Li+ m/z=762
M=Na+ m/z=778
M=K+ m/z=794
+
+
+
L D
E
O O
O
O O
O
-H2O
O O
O
O
O
O
M
M O
O
M O
H O
O H
O H
H
H
H
O
M=Li+ m/z=467
M=Na+ m/z=483
M=Li+ m/z=485
- CO
M=Na+ m/z=507
M=Na+ m/z=501
+
+ +
M F
G
O
O O
O
O -H2O
-H2O O
O
O
O
O
O M
M
O O
O
O
M
H O
O H
O H
M=Li+ m/z=427
M=Li+ m/z=445
H H
M=Na+ m/z=479
M=Na+ m/z=443
M=Na+ m/z=461
Scheme 2. The proposed fragmentation pathways of MON7 complexes with monovalent cations.
Fig. 2. ESI mass spectrum of a 1:1:1:3 mixture of cation perchlorates LiClO4, NaClO4, and KClO4 with MON7 (cv = 30).
1 13
in contrast to the complexes described above, the respective almost insoluble in acetonitrile. The H and C signals
MON7 complexes with the RbClO4 and CsClO4 salts are were assigned using one- and two-dimensional (COSY,
A. Huczyński et al. / Journal of Molecular Structure 879 (2008) 14 24 19
Table 2 Table 3
1 13
H NMR chemical shifts (ppm) of MON7 and its complexes in CD3CN C NMR chemical shifts (ppm) of MON7 and its complexes in CD3CN
No. Chemical shift (ppm) Differences (D) No. Chemical shift (ppm) Differences (D)
Atom between chemical Atom between chemical
shifts (ppm) shifts (ppm)
MON7 MON7 MON7 MON7 D1 D2 D3 MON7 MON7 MON7 MON7 D1 D2 D3
Li+ Na+ K+ Li+ Na+ K+
1        1 176.01 176.45 177.06 176.41 0.44 1.05 0.40
2 2.63 2.63 2.69 2.66 0.00 0.06 0.03 2 41.52 41.64 41.45 41.86 0.12 0.07 0.34
3 3.58 3.65 3.63 3.52 0.07 0.05 0.06 3 82.29 81.85 81.71 82.06 0.44 0.58 0.23
4 2.00 2.06 2.04 1.99 0.06 0.04 0.01 4 37.89 37.74 37.97 38.32 0.15 0.08 0.43
5 4.01 4.41 3.95 3.88 0.40 0.06 0.13 5 68.60 69.42 68.94 68.14 0.82 0.34 0.46
6 1.79 1.79 1.80 1.78 0.00 0.01 0.01 6 37.00 36.97 36.91 36.94 0.03 0.09 0.06
7 3.68 3.96 3.91 3.82 0.28 0.23 0.14 7 71.95 70.05 70.73 71.00 1.90 1.22 0.95
8A 1.61 1.60 1.61 1.62 0.01 0.00 0.01 8 35.10 34.20 34.58 34.20 0.90 0.52 0.90
8B 1.99 2.08 2.02 2.00 0.09 0.03 0.01 9 108.52 107.97 108.31 107.87 0.55 0.21 0.65
9        10 39.79 39.61 39.84 39.96 0.18 0.05 0.17
10A 1.92 1.83 1.80 1.76 0.09 0.12 0.16 11 32.57 33.18 33.37 34.20 0.61 0.80 1.63
10B 1.92 2.05 2.01 1.88 0.13 0.09 0.04 12 86.99 87.06 86.59 86.09 0.07 0.40 0.90
11A 1.72 1.57 1.86 1.79 0.15 0.14 0.07 13 84.47 82.55 82.22 83.52 1.92 2.25 0.95
11B 1.96 2.05 1.97 1.87 0.09 0.01 0.09 14 28.51 27.55 27.24 28.27 0.96 1.27 0.24
12        15 32.05 32.11 30.71 32.08 0.06 1.34 0.03
13 3.65 3.68 3.62 3.52 0.03 0.03 0.13 16 88.03 87.93 86.68 86.83 0.10 1.35 1.20
14A 1.59 1.48 1.48 1.45 0.11 0.11 0.14 17 86.43 84.90 85.44 85.18 1.53 0.99 1.25
14B 1.78 1.90 1.88 1.77 0.12 0.10 0.01 18 35.92 34.52 34.99 35.71 1.40 0.93 0.21
15A 1.58 1.59 1.48 1.45 0.01 0.10 0.13 19 34.81 34.02 33.77 33.12 0.79 1.04 1.69
15B 2.12 2.19 2.26 2.18 0.07 0.14 0.06 20 78.03 79.46 76.91 78.00 1.43 1.12 0.03
16        21 77.37 74.63 75.53 75.91 2.74 1.84 1.46
17 3.86 4.38 3.95 3.94 0.52 0.09 0.08 22 34.03 33.29 32.17 32.99 0.74 1.86 1.04
18 2.25 2.44 2.31 2.35 0.19 0.06 0.10 23 37.67 36.39 35.74 36.81 1.28 1.93 0.86
19A 1.50 1.58 1.64 1.53 0.08 0.14 0.03 24 34.76 33.29 36.22 35.55 1.47 1.46 0.79
19B 2.14 2.35 2.16 2.20 0.21 0.02 0.06 25 97.90 99.56 98.73 98.85 1.66 0.83 0.95
20 4.20 4.41 4.42 4.37 0.21 0.22 0.17 26 67.42 66.45 67.09 67.08 0.97 0.33 0.34
21 3.58 3.83 3.73 3.65 0.25 0.15 0.07 27 16.47 15.89 16.11 16.56 0.58 0.36 0.09
22 1.33 1.37 1.48 1.33 0.04 0.15 0.00 28 17.87 17.40 16.64 17.36 0.47 1.23 0.51
23A 1.29 1.35 1.30 1.30 0.06 0.01 0.01 29 16.15 16.29 14.40 15.94 0.14 1.75 0.21
23B 1.44 1.52 1.49 1.50 0.08 0.05 0.06 30 30.12 30.14 30.15 30.47 0.02 0.03 0.35
24 1.50 1.87 1.67 1.69 0.37 0.17 0.19 31 8.30 8.43 8.11 8.53 0.13 0.19 0.23
25        32 26.33 28.43 28.26 27.96 2.10 1.93 1.63
26A 3.36 3.45 3.46 3.41 0.09 0.10 0.05 33 11.34 10.76 10.91 10.89 0.58 0.43 0.45
26B 3.36 3.45 3.66 3.61 0.09 0.30 0.25 34 12.62 13.10 13.20 12.89 0.48 0.58 0.27
27 0.82 0.92 0.82 0.85 0.10 0.00 0.03 35 58.56 58.59 58.81 58.65 0.03 0.25 0.09
28 0.86 0.85 0.82 0.85 0.01 0.04 0.01 36 12.12 11.53 12.19 12.54 0.59 0.07 0.42
29 0.94 1.00 0.87 0.95 0.06 0.07 0.01 10 64.51 64.55 64.69 64.71 0.04 0.18 0.20
30A 1.55 1.58 1.45 1.51 0.03 0.10 0.04 20 69.58 69.69 69.61 69.58 0.11 0.03 0.00
30B 1.55 1.68 1.76 1.67 0.13 0.21 0.12 30 70.96 70.76 70.86 70.78 0.20 0.10 0.18
31 0.90 0.94 0.88 0.92 0.04 0.02 0.02 40 72.48 72.34 72.43 72.21 0.14 0.05 0.27
32 1.34 1.56 1.47 1.45 0.22 0.13 0.11 50 58.86 58.90 58.87 58.94 0.04 0.01 0.08
33 0.89 0.93 0.91 0.91 0.04 0.02 0.02
D1=dMON7 Li+ dMON7, D2=dMON7 Na+ dMON7, D3=dMON7 K+
34 0.96 1.00 1.00 0.99 0.04 0.04 0.03
dMON7.
35 3.30 3.31 3.32 3.32 0.01 0.02 0.02
36 1.13 1.17 1.17 1.16 0.04 0.04 0.03
10 4.20 4.20 4.21 4.20 0.00 0.01 0.00
1
In the H NMR spectra of MON7 and its 1:1 complexes
20 3.64 3.60 3.65 3.67 0.04 0.01 0.03
30 3.57 3.60 3.59 3.60 0.03 0.02 0.03
with Li+, Na+ and K+ cations (Table 2), the signals of the
40 3.46 3.49 3.49 3.50 0.03 0.03 0.04
protons of all three OH groups are separated and their
50 3.29 3.30 3.30 3.31 0.01 0.01 0.02
chemical shifts strongly depend on the kind of the cation
OXIH 2.81 2.99 4.03 3.29 0.18 1.22 0.48
forming the complex as illustrated in Fig. 3. In the spec-
OIVH 4.12 5.88 3.91 3.78 1.76 0.21 0.34
trum of MON7 the OH proton signals observed at
OXH 3.81 4.60 4.34 4.21 0.79 0.53 0.40
2.81 ppm 3.81 ppm, and 4.12 ppm, are assigned to OXIH,
D1=dMON7 Li+ dMON7, D2=dMON7 Na+ dMON7, D3=dMON7:K+
OXH, and OIVH groups, respectively, whereas in the spec-
dMON7.
tra of the complexes between MON7 and the Li+, Na+,
and K+ cations these signals are shifted in different direc-
HETCOR) spectra as well as by the addition of CD3OD to tions depending on the kind of the cation. The most signif-
the sample. icantly shifted signal of all OH groups is found in the
20 A. Huczyński et al. / Journal of Molecular Structure 879 (2008) 14 24
1
Fig. 3. H NMR in region of OH proton signals of: (a) MON7, (b) MON7 Li+, (c) MON7 Na+, and (d) MON7 K+.
spectrum of MON7 with the Li+ cation at 5.88 ppm and it
100
is assigned to the OIVH proton involved in the strongest
intramolecular hydrogen bond relative to those of other
hydroxyl groups. In the spectra of the MON7 complexes
50
with Na+ and K+ cations, the signals of the OIVH protons
are shifted towards lower ppm values indicating that the
hydrogen bonds, in which the OIVH protons are involved,
are weaker. This demonstrates that depending on the cat-
0
4000 3500 3000 2500 2000 1500 1000 500
ion, the respective hydroxyl groups form different intramo-
lecular hydrogen bonds, which is probably related to the
100
formation of different structures of these complexes.
3455
13 3504
A comparison of the C NMR chemical shifts in the spec-
tra of the complexes with those observed in the spectrum of
50
MON7 suggests that not only the oxygen atoms but also the
3322
carbonic scaffold is affected by the complexation process.
3370
3502
For instance the D value of the C20 atom in the complex of
3469
MON7 with Li+ cation is positive, whereas it is negative
0
3800 3700 3600 3500 3400 3300 3200
for the complex of MON7 with Na+ cation and almost
unchanged for the MON7 K+ complex . This result indi-
100
cates that OVIII oxygen atom is involved in the coordination
only in the complex of MON7 with Na+ cation.
13
The C NMR chemical shifts of the carbon atoms of
1732
50
the oxaalkyl chain in the spectra of MON7 and its com-
1676
plexes (atoms 10 50) are almost independent of the kind
1705
of the cation indicating that this chain plays no role in
the complexation process.
0
1800 1750 1700 1650 1600
Wavenumber [cm-1]
3.3. FT-IR studies
Fig. 4. FT-IR spectra of: ( ) MON7, ( ) MON7 Li+, (ĆĆĆ) MON7-
In Fig. 4a the FT-IR spectrum of water-free MON7
Na+, and ( Ć ) MON7 K+ in the ranges of: (a) 4000 400 cm 1; (b)
Ć
(solid line) is compared with the corresponding spectra of m(OH) and (c) m(C@O) stretching vibrations.
Transmittance [%]
Transmittance [%]
Transmittance [%]
A. Huczyński et al. / Journal of Molecular Structure 879 (2008) 14 24 21
Table 4
its 1:1 complexes with Li+, Na+, and K+ cations, all
Heat of formation (kcal/mol) of MON7 and its complexes with the cations
recorded in acetonitrile solution. The bands of the m(OH)
without (A) and with (B) the engagement of carbonyl group in
and m(C@O) vibrations are shown in Fig. 4b and c, in an
coordination process calculated by PM5 method (WinMopac 2003)
expanded scale, because according to the NMR data, the
Complex HOF (kcal/mol) DHOF (kcal/mol)
most significant changes should be observed in these spec-
MON7 667.49 
tral regions. Most characteristic, in the FT-IR spectrum of
MON7 + Li+ (A) 544.25 169.34
uncomplexed
water-free MON7 (Fig. 4b, solid line), are the bands
MON7 + Li+ (A) 713.59
complexed
assigned to the m(OH) vibrations of the OXH and groups
MON7 + Li+ (B) 544.25 158.91
uncomplexed
at 3504 cm 1, and of OIVH group at ca. 3322 cm 1 as well
MON7 + Li+ (B) 713.16
complexed
MON7 + Na+ (A) 525.43 217.71
as the band assigned to the m(C@O) vibrations at uncomplexed
MON7 + Na+ (A) 743.14
complexed
1732 cm 1. In the spectrum of the MON7 Li+ complex
MON7 + Na+ (B) 525.43 165.82
uncomplexed
(Fig. 4b, dashed line) the band at 3504 cm 1 vanishes
MON7 + Na+ (B) 691.25
complexed
and two bands arise at 3455 cm 1 and 3370 cm 1 assigned
MON7 + K+ (A) 596.40 135.79
uncomplexed
to m(OXIH) and m(OXH) vibrations, respectively. This indi- MON7 + K+ (A) 686.34
complexed
MON7 + K+ (B) 524.27 90.66
cates that in the MON7 Li+ complex the hydrogen bonds uncomplexed
MON7 + K+ (B) 641.21
complexed
of the OXH and OXIH groups are slightly stronger com-
DHOF = HOFMON7+Mcomplexed HOFMON7+Muncomplexed, M metal
pared to those in uncomplexed MON7. The stretching
cation.
vibrations of the OIVH group at 3322 cm 1 are no longer
(A) Structure of MON7 complex in which the C1@O group is not involved
observed in the spectrum, indicating that also the proton
in coordination of metal cation.
of this group is stronger hydrogen-bonded within the com-
(B) Structure of MON7 complex in which the C1@O group is involved in
1
plex structure. This interpretation is consistent with the H
coordination of metal cation.
NMR data (Table 2 and Fig. 3).
In the spectrum of the MON7 Na+ complex (Fig. 4b,
dotted line) only one broad band with a maximum at ca. those of ESI measurements) are formed with Na+ >>
3469 cm 1 is observed demonstrating that the hydrogen Li+ >K+ cations. This result is in good agreement with
bonds formed by the OXH and OXIH groups become the ESI data discussed above. The DHOF values also show
slightly stronger and those of OIVH group slightly weaker that the structures of MON7 with cations in which the car-
compared to those in spectrum of MON7. This interpreta- bonyl group is involved in the complexation process (struc-
1
tion is also consistent with the H NMR data (Table 2 and ture B), are energetically less favorable than those in which
Fig. 3). the carbonyl group is not involved (structure A). Only for
Also in the spectrum of the MON7 K+ complex the MON7 Na+ and MON7 Li+ complexes the DHOF
(Fig. 4b, dashed-dotted line) only one band with a maxi- values of structure B are relatively high indicating that such
mum at 3502 cm 1 is observed indicating that the hydrogen structures should be taken into account. This result is in
bonds, in which the hydroxyl groups are involved, are good agreement with both the ESI data and with the FT-
almost unchanged as compared to those in the uncom- IR observations.
plexed MON7. The position of the band assigned to the The interatomic distances between the oxygen atoms of
m(C@O) vibrations at 1732 cm 1, in the spectrum of MON7 and the cations along with the partial charges at
MON7 and its complexes with K+ cations, is almost these atoms are given in Table 5. Analysis of these values
unchanged (Fig. 4c), demonstrating that the oxygen atom shows that some oxygen atoms, such as OIV, OVI, OVII,
of the C@O ester group is not engaged in the complexation and OIX are always involved in the coordination of differ-
process of these cations. ent metal cations, whereas the OI, OII, and OIII play no role
In contrast to this spectrum the spectra of MON7 with in this coordination process. The latter refers to the A type
Li+ and Na+ cations, additionally to the bands at ca structure in which the C1@O group is not involved in the
1732 cm 1, show new bands at 1676 cm 1 and complexation of the metal cation. If the OII oxygen atom
1705 cm 1, respectively. These bands can be assigned to from the C1@O carbonyl group participates in the
the m(C@O) vibrations of alternative complex structures coordination of the cation, the B type structure of the
in which the carbonyl group interacts with the metal cat- MON7 Na+ and MON7 Li+ complexes are formed. The
ion. The intensity of this band is however relatively low calculated coordination distances for both types of the A
indicating that these structures are not dominant. and B complexes are comparable. Thus, the formation of
the B type structure of the MON7 Na+ complex is very
3.4. PM5 calculations probable. This result is consistent with the FT-IR data
indicating the existence of this complex structure.
Based on the spectroscopic results, the heats of forma- Other oxygen atoms can be involved in the coordination
tion (HOF) of the structures of MON7 and its complexes process depending on the type of the cation due to their dif-
with Li+, Na+, and K+ cations were calculated (Table 4). ferent radii. The coordination distances and the number of
Their values imply that the most stable complexes in the coordinating oxygen atoms suggest that all cations studied
gas phase (under the experimental conditions similar to can undergo fast fluctuations within the structures of the
22 A. Huczyński et al. / Journal of Molecular Structure 879 (2008) 14 24
Table 5 Table 6
The interatomic distances (Å) and partial charges for O atoms of MON7 The lengths (Å) and angles (°) [values in brackets] of the hydrogen bond
coordinating metal cations in complexes structures calculated by PM5 for MON7 complexes calculated by PM5 method (WinMopac 2003)
method (WinMopac 2003)
Compound Oxygen Hydrogen bond length (Å) [Hydrogen
Complex Monovalent Coordinating Coordinating Distance atom bond angle (°)]
with cation atom atom (Å)
OIV H OX H OXI H
monovalent partial partial coordinating
MON7 OII  2.95 [159.9] 2.92 [131.2]
cation charge charge atom fi
OIX 2.69 [148.2]  
cation
MON7 Li+ (A) OIII  2.83 [131.4]
MON7 Li+ (A) +0.397 OIV H 0.430 2.11
OXII   2.72 [117.8]
OVI 0.386 2.04
OIX 2.49 [98.8]  
OVII 0.371 2.07
OI 2.71 [112.6]
OIX 0.382 2.09
MON7 Li+ (B) OIII  2.85 [141.4]
MON7 Li+ (B) +0.409 OII 0.419 2.24
OXII   2.71 [135.8]
OIV H 0.453 2.10
OIX 2.79 [117.8]  
OVI 0.391 2.21
OVII 0.387 2.22
MON7 Na+ OIV  2.56 [104.9] 
OIX 0.379 2.15
(A) OIII   2.82 [128.6]
MON7 Na+ (A) +0.303 OIV H 0.450 2.31
MON7 Na+ OI  2.69 [116.8] 
OVI 0.412 2.31
(B) OIII   2.69 [117.6]
OVII 0.375 2.31
OVIII 0.369 2.29 MON7 K+ (A) OI  2.74 [143.3] 2.94 [143.6]
OIX 0.402 2.32 OIII   2.64 [105.2]
OXI 0.414 2.29
(A) Structure of MON7 complex in which the C1@O group is not involved
in coordination of metal cation.
MON7 Na+ (B) +0.311 OII 0.342 2.38
(B) Structure of MON7 complex in which the C1@O group is involved in
OIV H 0.395 2.38
coordination of metal cation.
OVI 0.379 2.34
OVII 0.374 2.33
OVIII 0.350 2.32
OIX 0.380 2.35
OXI 0.394 2.34
MON7 K+ (A) +0.476 OIV H 0.423 2.93
OVI 0.398 2.78
OVII 0.387 2.86
OIX 0.394 2.88
OXI 0.416 2.81
(A) Structure of MON7 complex in which the C1@O group is not involved
in coordination of metal cation.
(B) Structure of MON7 complex in which the C1@O group is involved in
coordination of metal cation.
complexes as demonstrated for the complexes of crown
ethers with monovalent cations [20 23]. It is further con-
13
firmed by the signal of the C1 carbon atom in the C
NMR spectrum of the MON7 Na+ complex which is a
singlet.
The lengths and angles of the hydrogen bonds in which the
Scheme 3. The structure of MON7 calculated by PM5 method (WinM-
OH groups are engaged are summarized in Table 6. The cal-
opac 2003).
culated structure of MON7 indicates that OII oxygen atom
from the C@O ester group is engaged in a bifurcated intra-
tures indicates that only for the MON7 complex with Na+
molecular hydrogen bond with two OXH and OXIH hydro-
cation the MON7 molecule is able to form a pseudo-crown
xyl groups (Scheme 3). During the formation of the MON7
ether structure. This type of structure provides the most effi-
complexes with cations these hydrogen bonds are broken
cient interactions and therefore, the affinity of MON7 to
open. For this reason and also as a consequence of the coor-
13
Na+ cation is higher than that to the other cations.
dinating process the C NMR signals of the C1 carbon
atoms are shifted toward higher ppm values (Table 3).
The calculated structures of MON7 and its complexes 4. Conclusions
with the Li+, Na+, andK+ cations are visualized in Schemes
3 6. The hydrogen bonds and the coordination bonds are A new 2-(2-methoxyethoxy)ethyl ester of Monensin A
marked by dots. A comparison of all the calculated struc- is synthesized by an effective method and its ability to
A. Huczyński et al. / Journal of Molecular Structure 879 (2008) 14 24 23
Scheme 4. The structures of two types of MON7-Li+ complexes: (a)
Scheme 5. The structures of two types of MON7-Na+ complexes: (a)
without the engagement of the C1@O carbonyl group in coordination of
without the engagement of the C1@O carbonyl group in coordination of
the cation  type A, (b) with the engagement of the C1@O carbonyl group
the cation  type A, (b) with the engagement of the C1@O carbonyl group
in coordination of the cation  type B calculated by PM5 method
in coordination of the cation  type B calculated by PM5 method
(WinMopac 2003).
(WinMopac 2003).
form complexes with Li+, Na+, and K+ cations has been
studied. We provide evidence that MON7 preferentially
forms complex with Na+ cations. The formation of sta-
ble complexes of 1:1 stoichiometry up to cv = 70 V is
indicated by the electrospray ionization mass spectra.
With increasing cone voltage value the fragmentation
of the respective complexes is detected and is connected
primary with the dehydration process. The formation
of the complexes as well as the intramolecular hydrogen
1
bonds stabilizing their structures is demonstrated by H
13
and C NMR, FT-IR spectra and PM5 semiempirical
calculations. It is shown that in the structure of MON7
the oxygen atom of the C@O ester group is involved
in very weak bifurcated hydrogen bonds with two hydro-
Scheme 6. The structure of MON7 K+ complex calculated by PM5
xyl groups. Within the complexes of MON7 with cations
method (WinMopac 2003).
(type A), the C@O ester group is not hydrogen bonded,
whereas in the structures of type B it coordinates the Li+
or Na+ cations. Such structures are however not domi- plex structure. Despite of this fact the formation of a
nant. It is demonstrated that the strongest intramolecular
pseudo crown ring structure formed by MON7 prefer-
hydrogen bonds are formed within the MON7 Li+ com- ences the complexation of Na+ cations.
24 A. Huczyński et al. / Journal of Molecular Structure 879 (2008) 14 24
[9] A. Huczyński, D. Michalak, P. Przybylski, B. Brzezinski, F. Bartl, J.
Acknowledgements
Mol. Struct. 797 (2006) 99.
[10] A. Huczyński, D. Michalak, P. Przybylski, B. Brzezinski, F. Bartl, J.
Adam Huczyński wishes to thank the Foundation for
Mol. Struct. 828 (2007) 130.
Polish Science for fellowship. The authors thank the Polish
[11] A. Huczyński, P. Przybylski, B. Brzezinski, J. Mol. Struct. 788 (2006)
Ministry of Science and Higher Education for financial
176.
[12] A. Huczyński, P. Przybylski, G. Schroeder, B. Brzezinski, J. Mol.
support under Grant No. R 0501601.
Struct. 29 (2007) 111.
[13] A. Huczyński, D. A
owicki, B. Brzezinski, F. Bartl, J. Mol. Struct. 874
References
(2008) 89.
[14] A. Huczyński, P. Przybylski, B. Brzezinski, Tetrahedron 63 (2007)
[1] B.C. Pressman, Annu. Rev. Biochem. 45 (1976) 925. 8831.
[2] H.M. Mollenhauer, D.J. Morre, L.D. Rowe, Biochim. Biophys. Acta [15] J.J.P. Stewart, Method J. Comp. Chem. 10 (1989) 209.
1031 (1990) 225. [16] J.J.P. Stewart, Method J. Comp. Chem. 12 (1991) 320.
[3] J.W. Westley, Polyether Antibiotics, Naturally Occurring Acid [17] CAChe 5.04 UserGuide, Fujitsu, 2003.
Ionophores, vol. 2, Marcel Dekker Inc., New York, 1983, p. 51. [18] P. Przybylski, A. Huczyński, B. Brzezinski, J. Mol. Struct. 826 (2007)
[4] B.C. Pressman, M. Fahim, Annu. Rev. Pharm. Toxicol. 22 (1982) 465. 156.
[5] P. Butaye, L.A. Devriese, F. Haesebrouck, Clin. Microbiol. Rev. 16 [19] A. Huczyński, M. Ratajczak-Sitarz, A. Katrusiak, .B. Brzezinski, J.
(2003) 175. Mol. Struct. 832 (2007) 84.
[6] B. Stephen, M. Rommel, A. Daugschies, Veterinary Parasitology 69 [20] B. Brzezinski, J. Olejnik, G. Zundel, R. Krämer, Chem. Phys. Lett.
(1997) 19. 156 (1989) 213.
[7] A. Huczyński, P. Przybylski, B. Brzezinski, F. Bartl, Biopolymers 81 [21] B. Brzezinski, J. Olejnik, G. Zundel, Chem. Phys. Lett. 167 (1990) 11.
(2006) 282. [22] G. Zundel, B. Brzezinski, J. Olejnik, J. Mol. Struct. 300 (1993) 573.
[8] A. Huczyński, P. Przybylski, B. Brzezinski, F. Bartl, Biopolymers 82 [23] B. Brzezinski, G. Schroeder, A. Rabold, G. Zundel, J. Phys. Chem. 99
(2006) 491. (1995) 8519.