Spectroscopic, mass spectrometry, and semiempirical investigations of a new 2-(2-methoxyethoxy)ethyl ester of Monensin A and its complexes with monovalent cations

Article abstract of DOI:10.1016/j.molstruc.2007.08.004

A new 2-(2-methoxyethoxy)ethyl ester of Monensin A (MON7) has been synthesized and its capability of complex formation with Li⁺, Na⁺, and K⁺ cations has been studied by ESI MS, ¹H and ¹³C NMR, FT-IR, and PM5 semiempirical methods. ESI mass spectrometry 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 respective 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 visualized 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.

Full text of DOI:10.1016/j.molstruc.2007.08.004

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 Huczynski , Daniel Łowicki , Bogumil Brzezinski *, Franz Bartl
´
a
Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland
Institute of Medical Physics and Biophysics, Charite´ – Universita¨tsmedizin Berlin, Campus Charite´ Mitte, Ziegelstr. 5/9, 10117 Berlin, Germany
b
c
Zentrum fu¨r 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
Li+, Na+, and K+ cations has been studied by ESI MS, 1H and 13C 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.
ꢀ 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.
As a continuation of our earlier works, we report here
ESI MS, 1H and 13C NMR, FT-IR as well as semiempirical
studies of complexes between a new 2-(2-methoxyeth-
oxy)ethyl ester of Monensin A and monovalent cations
such as the Li+, Na+, and K+. This new ester, in compar-
ison with the esters studied earlier, contents additionally
two etheric oxygen atoms, which can influence the com-
plexation process. The structures of 2-(2-methoxyeth-
oxy)ethyl ester of Monensin A and its complexes with
monovalent cations are discussed in detail.
Monensin A isolated from Streptomyces cinnamonensis
is a well-known representative of naturally polyether iono-
phore antibiotics. It is able to form pseudomacrocyclic
complexes with mono and divalent cations and to transport
these cations across cell membranes. Monensin A has very
important and useful biological activities such as growth
inhibition of Gram-positive organisms and effective control
of coccidiosis in chickens [1–6]. In our earlier works the
synthesis and the physicochemical characterization of
new esters of Monensin A has been reported [7–14]. In
these publications the complexation of the mono and diva-
2. Experimental
*
Monensin A sodium salt was purchased from Sigma
(90–95%). The perchlorates LiClO4, NaClO4, and KClO4
Corresponding author. Tel.: +48 618291330.
E-mail address: bbrzez@main.amu.edu.pl (B. Brzezinski).
0022-2860/$ - see front matter ꢀ 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2007.08.004

A. Huczyn´ski 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 · 10ꢀ5
/
3 mol dmꢀ3) taken together. The samples were infused into
the ESI source using a Harvard pump at a flow rate of
20 ll minꢀ1. The ESI source potentials were: capillary
3 kV, lens 0.5 kV, extractor 4 V. The standard ESI mass
spectra were recorded at cone voltages: 10, 30, 50, 70, 90,
110, and 130 V. The source temperature was 120 ꢁC and
the dissolvation temperature was 300 ꢁC. Nitrogen was used
as the nebulizing and dissolvation gas at flow-rates of 100
and 300 dm3 hꢀ1, respectively. Mass spectra were acquired
in the positive ion detection mode with unit mass resolution
at a step size of 1 m/z unit. The mass range for ESI experi-
ments was from 200 to 1000 m/z.
any further purification. The salts were hydrates, and it was
necessary to dehydrate them by several (6–10 times) evap-
oration steps from a 1:5 mixture of acetonitrile and abso-
lute ethanol. The dehydration of the perchlorates was
followed by FT-IR spectroscopy in acetonitrile.
CD3CN and CH3CN spectral-grade solvents were
˚
stored over 3 A molecular sieves for several days. All
manipulations with the substances were performed in a
carefully dried and CO2-free glove box.
2.1. Synthesis of 2-(2-methoxyethoxy)ethyl ester of
Monensin A (MON7)
Monensin A sodium salt was dissolved in dichlorometh-
ane and stirred vigorously with a layer of aqueous sulfuric
acid (pH = 1.5). The organic layer containing MONA was
washed with distilled water, and dichloromethane evapo-
rated under reduced pressure to dryness.
2.4. Spectroscopic measurements
The FT-IR spectra of MON7 and its 1:1 complexes
(0.07 mol dmꢀ3) with LiClO4, NaClO4, and KClO4 were
recorded in the mid infrared region in acetonitrile solutions
using a Bruker IFS 113v spectrometer.
A cell with Si windows and wedge-shaped layers was
used to avoid interferences (mean layer thickness
170 lm). The spectra were taken with an IFS 113v FT-IR
spectrophotometer (Bruker, Karlsruhe) equipped with a
DTGS detector; resolution 2 cmꢀ1. The Happ–Genzel apo-
dization function was used. All manipulations with the
compounds were performed in a carefully dried and CO2-
free glove box.
A solution of MONA (500 mg, 0.75 mmol), 1,3-dic-
yclohexylcarbodiimide (140 mg, 0.90 mmol), 4-pyrrolidino-
pyridine (50 mg, 0.33 mmol), 2-(2-methoxyethoxy)ethanol
(600 mg, 5.0 mmol), and 4-toluenesulfonic acid monohy-
drate (28.5 mg, 0.15 mmol) in dichloromethane (15 cm3)
was stirred at a temperature below 0 ꢁC for 24 h. After this
time the reaction mixture was stirred at room temperature
for 24 h, diluted with H2O and extracted with CH2Cl2. The
extract was evaporated under reduced pressure to dryness.
The residue was suspended in hexane and filtered off. The
filtrate was evaporated under reduced pressure and purified
by chromatography on silica gel (Fluka type 60) to give
MON7 (420 mg, 72% yield) as a colorless oil showing ten-
dency to form a glass state.
The NMR spectra of MON7 and its 1:1 complexes
(0.07 mol dmꢀ3) with LiClO4, NaClO4, and KClO4 were
recorded in CD3CN solutions using a Varian Gemini
300 MHz spectrometer. All spectra were locked to the deu-
terium resonance of CD3CN.
1
Elemental analysis: Calcd C 63.71%, H 9.39%. Found:
C = 63.69%, H = 9.43%.
The H NMR measurements in CD3CN were carried
out at the operating frequency 300.075 MHz; flip angle,
pw = 45ꢁ; spectral width, sw = 4500 Hz; acquisition time,
at = 2.0 s; relaxation delay, d1 = 1.0 s; T = 293.0 K and
using TMS as the internal standard. No window func-
tion or zero filling was used. Digital resolution was
0.2 Hz per point. The error of chemical shift value was
0.01 ppm.
2.2. Preparation of MON7 complexes with monovalent
cations
The 0.07 mol dmꢀ3 solutions of 1:1 complexes of MON7
with monovalent cations (Li+, Na+, and K+) were
obtained by adding equimolar amounts of MClO4 salt
(M = Li, Na, K) dissolved in acetonitrile to acetonitrile
solution of MON7. The solvent was evaporated under
reduced pressure to dryness and the oily residue was dis-
solved in an appropriate volume of dry CH3CN or CD3CN
to obtain the complex at a 0.07 mol dmꢀ3 concentration.
13C NMR spectra were recorded at the operating fre-
quency 75.454 MHz; pw = 60ꢁ; sw = 19000 Hz; at = 1.8 s;
d1 = 1.0 s; T = 293.0 K and TMS as the internal standard.
Line broadening parameters were 0.5 or 1 Hz. The error of
chemical shift value was 0.01 ppm.
1
The H and 13C NMR signals were assigned indepen-
dently for each species using one- or two-dimensional
(COSY, HETCOR) spectra.
2.3. Mass spectrometry
The ESI (Electrospray Ionization) mass spectra were
recorded on a Waters/Micromass (Manchester, UK) ZQ
mass spectrometer equipped with a Harvard Apparatus syr-
inge pump. All samples were prepared in acetonitrile. The
measurements were performed with two types of samples;
solutions of MON7 (5 · 10ꢀ5 mol dmꢀ3) with: (a) each of
the cations Li+, Na+, and K+ (2.5 · 10ꢀ4 mol dmꢀ3) taken
2.5. Semiempirical calculations
PM5 quantum calculations were performed using the
Win Mopac 2003 program at the semiempirical level (Cache
Work System Pro version 5.04 – Fujitsu) [14–19]. PM5
quantum semiempirical method use the Schro¨dinger equa-
tion to determine bond strengths, atomic hybridizations,

16
A. Huczyn´ski et al. / Journal of Molecular Structure 879 (2008) 14–24
Table 1
partial charges, and orbitals from the positions of the
atoms and the net charge. For MON7 and its complexes
the initial optimization of the structures was carried out
using the molecular mechanics – extensive global minimum
energy conformation search with the Conflex/MM3 from
WinMopac 2003 program. Global optimization runs were
carried out for all the MON7 complexes using about
4500 local minimizations in each global optimization.
The calculated energetically the most favorable structures
of conformers corresponding the global minimum points
were further optimized by the PM5 quantum semiempirical
method with the energy gradient not exceeding 10 kcal/mol
in one step. In all cases full geometry optimization of
MON7 and its complexes was carried out without any sym-
metry constraints. The semiempirical calculations were per-
formed using a computer equipped with an AMD Athlon
1.26 GHz processor and 2 GB operating memory.
The main peaks in the ESI mass spectra of the complexes of MON7 with
cations at various cone voltages
Cation Cone voltage
Main peaks (m/z)
[V]
Li+
10
30
50
70
90
780
780
780
780
780, 762
110
130
780, 762, 744, 485, 467, 445, 427, 283
780, 762, 744, 485, 467, 445, 427, 283
Na+
10
30
50
70
90
796
796
796
796
796, 778
110
130
796, 778, 760, 507, 501, 489, 461, 443, 299
796, 778, 760, 507, 501, 489, 483, 479, 461, 443,
299
K+
10
30
812
812
2.6. Elemental analysis
50
70
90
812
812
812
The elemental analysis of MON7 was carried out on
Vario ELIII (Elementar, Germany).
110
130
812, 794, 776
Many peaks
3. Results and discussion
The structure of MON7 together with the atom number-
ing is shown in Scheme 1.
the abstraction of the OIVH or OXH hydroxyl groups
yielding cation structures B or H, respectively. Further
fragmentation of cation B, of MON7 with Li+ and Na+
cations, is realized in two directions, whereas other types
of complexes (C, D, E, F, and finally G) are formed. Fur-
thermore, cation B can undergo fragmentation to cation
K due to complexation of the Li+ and Na+ cations by
the oxaalkyl chain of the ester part. Cation C is formed
from cation B by abstraction of a second water molecule.
The formation of the D and E fragmentary complexes is
achieved by abstraction of the part of the molecule that
includes the ester group. Cations F and G can be formed
from cations D and E by the abstraction of one C3H4
group. Additionally, cation G can be formed by loss
of one water molecule from cation F. For the complex
of MON7 with K+ cation, no abstraction of the part of
the molecule including the ester group was detected.
In the case of the MON7-Na complex the fragmentation
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
with abstraction of water molecules in to steps yielding cat-
ions F and G, respectively.
3.1. Electrospray mass spectrometry (ESI) measurements
The main m/z peaks in the ESI mass spectra of MON7
with the Li+, Na+, and K+ cations used separately at var-
ious cone voltages (cv) are collected in Table 1. One
exemplary ESI mass spectrum of the 1:1 complex of
MON7 with Na+ cation measured at various cone volt-
ages is shown in Fig. 1. The data summarized in Table
1 show that MON7 exclusively forms complexes of 1:1
stoichiometry with the monovalent cations that are very
stable up to about cv = 70 V. Starting from about
cv = 90 V fragmentation of the respective complexes is
observed. Based on the analysis of the fragmentary m/z
signals the fragmentation pathways shown in Scheme 2
are proposed. The first step of the fragmentation is the
loss of one water molecule from cation A as a result of
IV
OH
33
27
29
28
Me
II
O
Me
Me
Me
III
MeO
32
30-31
7
Me
Et
H
XI
Fig. 2 presents the ESI spectrum of the 1:1:1:3 mixture
of Li+, Na+, K+ cations and MON7 measured at
cv = 30 V. In this figure only three characteristic signals
at m/z = 780, m/z = 796 and m/z = 812 assigned to the
1:1 complexes of MON7 with Li+, Na+, and K+ cations
are shown, respectively. The intensity of the MON7–Na+
complex signal is the strongest, indicating clearly that
MON7 preferentially forms complexes with Na+ cations.
35
5
25
21
13
17
26
R
OH
9
1
O
O
O
O
O
O
OH
X
H
H
H
H
I
VIII
V
VI
VII
IX
Me
36
Me
34
XIII
3'
2'
OCH3
5'
MONA R=H
MON7 R=
1'
O
XII
4'
Scheme 1. The structures and atom numbering of MONA and MON7.

A. Huczyn´ski 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
The intensities of the signals of the MON7–Li+ and
3.2. H and 13C NMR measurements
MON7–K+ complexes are comparable, but significantly
lower than that of the MON7–Na+ complex, demonstrat-
ing that MON7 shows much lower affinity to Li+ and K+
cations.
The 1H and 13C NMR data of MON7 in CD3CN and its
1:1 complexes with Li+, Na+, and K+ cations all in CD3CN
are shown in Tables 2 and 3, respectively. Unfortunately,

18
A. Huczyn´ski et al. / Journal of Molecular Structure 879 (2008) 14–24
+
+
I
H
O
O
O
H
O
H
K
O
O
-H2O
H
O
O
+
M
M
O
O
O
H
O
O
OCH3
M=Li+ m/z=744
M=Na+ m/z=760
M=K+ m/z=776
O
O
M
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
M=Na+ m/z=778
M=K+ m/z=794
-H2O
+
+
+
B
C
A
O
O
O
O
O
O
H
-H2O
O
-H2O
O
O
O
O
O
O
O
M
O
H
M
M
O
O
O
O
H
H
O
H
M=Li+ m/z=744
M=Na+ m/z=760
M=K+ m/z=776
O
O
O
O
O
O
O
O
O
OCH3
O
O
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
+
+
+
D
L
E
O
O
O
O
O
O
-H2O
O
O
O
O
O
O
M
M
O
H
O
O
M
H
O
O
H
O
H
H
H
O
M=Li+ m/z=467
M=Na+ m/z=483
M=Li+ m/z=485
M=Na+ m/z=501
- CO
M=Na+ m/z=507
+
+
+
F
M
G
O
O
O
O
O
-H2O
O
-H2O
O
O
O
O
M
O
M
O
O
O
H
O
M
H
O
O
H
H
O
H
M=Li+ m/z=427
M=Li+ m/z=445
M=Na+ m/z=461
M=Na+ m/z=479
M=Na+ m/z=443
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
in contrast to the complexes described above, the respective
MON7 complexes with the RbClO4 and CsClO4 salts are
almost insoluble in acetonitrile. The H and 13C signals
were assigned using one- and two-dimensional (COSY,

A. Huczyn´ski et al. / Journal of Molecular Structure 879 (2008) 14–24
19
Table 2
Table 3
1H NMR chemical shifts (ppm) of MON7 and its complexes in CD3CN
13C NMR chemical shifts (ppm) of MON7 and its complexes in CD3CN
No.
Atom
Chemical shift (ppm)
Differences (D)
between chemical
shifts (ppm)
No.
Atom
Chemical shift (ppm)
Differences (D)
between chemical
shifts (ppm)
MON7 MON7– MON7–
MON7– D1
D2
D3
MON7 MON7– MON7– MON7– D1
D2
D3
Li+
Na+
K+
Li+
Na+
K+
1
2
3
4
5
6
7
8A
8B
9
10A
10B
11A
11B
12
–
–
–
–
–
–
–
1
2
3
4
5
6
7
8
9
176.01 176.45
177.06
41.45
81.71
37.97
68.94
36.91
70.73
34.58
108.31
39.84
33.37
86.59
82.22
27.24
30.71
86.68
85.44
34.99
33.77
76.91
75.53
32.17
35.74
36.22
98.73
67.09
16.11
16.64
14.40
30.15
8.11
176.41
41.86
82.06
38.32
68.14
36.94
71.00
34.20
107.87
39.96
34.20
86.09
83.52
28.27
32.08
86.83
85.18
35.71
33.12
78.00
75.91
32.99
36.81
35.55
98.85
67.08
16.56
17.36
15.94
30.47
8.53
0.44
1.05
0.40
0.34
2.63
3.58
2.00
4.01
1.79
3.68
1.61
1.99
–
1.92
1.92
1.72
1.96
–
3.65
1.59
1.78
1.58
2.12
–
3.86
2.25
1.50
2.14
4.20
3.58
1.33
1.29
1.44
1.50
–
3.36
3.36
0.82
0.86
0.94
1.55
1.55
0.90
1.34
0.89
0.96
3.30
1.13
4.20
3.64
3.57
3.46
3.29
2.81
4.12
3.81
2.63
3.65
2.06
4.41
1.79
3.96
1.60
2.08
–
1.83
2.05
1.57
2.05
–
3.68
1.48
1.90
1.59
2.19
–
4.38
2.44
1.58
2.35
4.41
3.83
1.37
1.35
1.52
1.87
–
3.45
3.45
0.92
0.85
1.00
1.58
1.68
0.94
1.56
0.93
1.00
3.31
1.17
4.20
3.60
3.60
3.49
3.30
2.99
5.88
4.60
2.69
3.63
2.04
3.95
1.80
3.91
1.61
2.02
–
1.80
2.01
1.86
1.97
–
3.62
1.48
1.88
1.48
2.26
–
3.95
2.31
1.64
2.16
4.42
3.73
1.48
1.30
1.49
1.67
–
3.46
3.66
0.82
0.82
0.87
1.45
1.76
0.88
1.47
0.91
1.00
3.32
1.17
4.21
3.65
3.59
3.49
3.30
4.03
3.91
4.34
2.66
3.52
1.99
3.88
1.78
3.82
1.62
2.00
–
1.76
1.88
1.79
1.87
–
3.52
1.45
1.77
1.45
2.18
–
3.94
2.35
1.53
2.20
4.37
3.65
1.33
1.30
1.50
1.69
–
3.41
3.61
0.85
0.85
0.95
1.51
1.67
0.92
1.45
0.91
0.99
3.32
1.16
4.20
3.67
3.60
3.50
3.31
3.29
3.78
4.21
0.00 0.06 0.03
0.07 0.05 ꢀ0.06
0.06 0.04 ꢀ0.01
0.40 ꢀ0.06 ꢀ0.13
0.00 0.01 ꢀ0.01
0.28 0.23 0.14
41.52
82.29
37.89
68.60
37.00
71.95
35.10
41.64
81.85
37.74
69.42
36.97
70.05
34.20
0.12 ꢀ0.07
ꢀ0.44 ꢀ0.58 ꢀ0.23
ꢀ0.15
0.08
0.34 ꢀ0.46
0.43
0.82
ꢀ0.03 ꢀ0.09 ꢀ0.06
ꢀ1.90 ꢀ1.22 ꢀ0.95
ꢀ0.90 ꢀ0.52 ꢀ0.90
ꢀ0.55 ꢀ0.21 ꢀ0.65
ꢀ0.01 0.00 0.01
0.09 0.03 0.01
108.52 107.97
–
–
–
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
10
39.79
32.57
86.99
84.47
28.51
32.05
88.03
86.43
35.92
34.81
78.03
77.37
34.03
37.67
34.76
97.90
67.42
16.47
17.87
16.15
30.12
8.30
39.61
33.18
87.06
82.55
27.55
32.11
87.93
84.90
34.52
34.02
79.46
74.63
33.29
36.39
33.29
99.56
66.45
15.89
17.40
16.29
30.14
8.43
ꢀ0.18
0.05
0.80
0.17
1.63
ꢀ0.09 ꢀ0.12 ꢀ0.16
0.13 0.09 ꢀ0.04
ꢀ0.15 0.14 0.07
0.09 0.01 ꢀ0.09
0.61
0.07 ꢀ0.40 ꢀ0.90
ꢀ1.92 ꢀ2.25 ꢀ0.95
ꢀ0.96 ꢀ1.27 ꢀ0.24
–
–
–
0.06 ꢀ1.34
0.03
13
0.03 ꢀ0.03 ꢀ0.13
ꢀ0.10 ꢀ1.35 ꢀ1.20
ꢀ1.53 ꢀ0.99 ꢀ1.25
ꢀ1.40 ꢀ0.93 ꢀ0.21
ꢀ0.79 ꢀ1.04 ꢀ1.69
1.43 ꢀ1.12 ꢀ0.03
ꢀ2.74 ꢀ1.84 ꢀ1.46
ꢀ0.74 ꢀ1.86 ꢀ1.04
ꢀ1.28 ꢀ1.93 ꢀ0.86
14A
14B
15A
15B
16
17
18
19A
19B
20
21
22
23A
23B
24
ꢀ0.11 ꢀ0.11 ꢀ0.14
0.12 0.10 ꢀ0.01
0.01 ꢀ0.10 ꢀ0.13
0.07 0.14 0.06
–
–
–
0.52 0.09 0.08
0.19 0.06 0.10
0.08 0.14 0.03
0.21 0.02 0.06
0.21 0.22 0.17
0.25 0.15 0.07
0.04 0.15 0.00
0.06 0.01 0.01
0.08 0.05 0.06
0.37 0.17 0.19
ꢀ1.47
1.46
0.83
0.79
0.95
1.66
ꢀ0.97 ꢀ0.33 ꢀ0.34
ꢀ0.58 ꢀ0.36
0.09
ꢀ0.47 ꢀ1.23 ꢀ0.51
0.14 ꢀ1.75 ꢀ0.21
0.02
0.03
0.35
0.23
1.63
0.13 ꢀ0.19
25
–
–
–
26.33
11.34
12.62
58.56
12.12
64.51
69.58
70.96
72.48
58.86
28.43
10.76
13.10
58.59
11.53
64.55
69.69
70.76
72.34
58.90
28.26
10.91
13.20
58.81
12.19
64.69
69.61
70.86
72.43
58.87
27.96
10.89
12.89
58.65
12.54
64.71
69.58
70.78
72.21
58.94
2.10 1.93
26A
26B
27
28
29
30A
30B
31
32
33
0.09 0.10 0.05
0.09 0.30 0.25
0.10 0.00 0.03
ꢀ0.58 ꢀ0.43 ꢀ0.45
0.48
0.03
0.58
0.25
0.07
0.18
0.03
0.27
0.09
0.42
0.20
0.00
ꢀ0.01 ꢀ0.04 ꢀ0.01
0.06 ꢀ0.07 0.01
0.03 ꢀ0.10 ꢀ0.04
0.13 0.21 0.12
0.04 ꢀ0.02 0.02
0.22 0.13 0.11
0.04 0.02 0.02
0.04 0.04 0.03
0.01 0.02 0.02
0.04 0.04 0.03
0.00 0.01 0.00
ꢀ0.04 0.01 0.03
0.03 0.02 0.03
0.03 0.03 0.04
0.01 0.01 0.02
0.18 1.22 0.48
1.76 ꢀ0.21 ꢀ0.34
0.79 0.53 0.40
ꢀ0.59
0.04
20
0.11
30
ꢀ0.20 ꢀ0.10 ꢀ0.18
40
ꢀ0.14 ꢀ0.05 ꢀ0.27
50
0.04
0.01
0.08
D1 = dMON7–Li+ ꢀ dMON7, D2 = dMON7–Na+ ꢀ dMON7, D3 = dMON7–K+
ꢀ dMON7.
34
35
36
10
In the 1H NMR spectra of MON7 and its 1:1 complexes
with Li+, Na+ and K+ cations (Table 2), the signals of the
protons of all three OH groups are separated and their
chemical shifts strongly depend on the kind of the cation
forming the complex as illustrated in Fig. 3. In the spec-
trum of MON7 the OH proton signals observed at
2.81 ppm 3.81 ppm, and 4.12 ppm, are assigned to OXIH,
OXH, and OIVH groups, respectively, whereas in the spec-
tra of the complexes between MON7 and the Li+, Na+,
and K+ cations these signals are shifted in different direc-
tions depending on the kind of the cation. The most signif-
icantly shifted signal of all OH groups is found in the
20
30
40
50
OXI
IVH
OXH
H
O
D1 = dMON7–Li+ ꢀ dMON7, D2 = dMON7–Na+ ꢀ dMON7, D3 = dMON7:K+
ꢀ dMON7.
HETCOR) spectra as well as by the addition of CD3OD to
the sample.

20
A. Huczyn´ski et al. / Journal of Molecular Structure 879 (2008) 14–24
Fig. 3. 1H 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
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
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-
ion, the respective hydroxyl groups form different intramo-
lecular hydrogen bonds, which is probably related to the
formation of different structures of these complexes.
A comparison of the 13C NMR chemical shifts in the spec-
tra of the complexes with those observed in the spectrum of
MON7 suggests that not only the oxygen atoms but also the
carbonic scaffold is affected by the complexation process.
For instance the D value of the C20 atom in the complex of
MON7 with Li+ cation is positive, whereas it is negative
for the complex of MON7 with Na+ cation and almost
unchanged for the MON7–K+ complex . This result indi-
cates that OVIII oxygen atom is involved in the coordination
only in the complex of MON7 with Na+ cation.
100
50
0
4000
3500
3000
2500
2000
1500
1000
500
100
50
0
3455
3504
3322
3300
3370
3502
3469
3800
3700
3600
3500
3400
3200
100
50
0
The 13C NMR chemical shifts of the carbon atoms of
the oxaalkyl chain in the spectra of MON7 and its com-
plexes (atoms 10–50) are almost independent of the kind
of the cation indicating that this chain plays no role in
the complexation process.
1732
1676
1705
1700
1800
1750
1650
1600
Wavenumber [cm-1]
3.3. FT-IR studies
Fig. 4. FT-IR spectra of: (—) MON7, (ꢀ ꢀ) MON7–Li+, (ÆÆÆ) MON7-
Na+, and (ꢀÆ Æꢀ) MON7–K+ in the ranges of: (a) 4000–400 cmꢀ1; (b)
m(OH) and (c) m(C@O) stretching vibrations.
In Fig. 4a the FT-IR spectrum of water-free MON7
(solid line) is compared with the corresponding spectra of

A. Huczyn´ski et al. / Journal of Molecular Structure 879 (2008) 14–24
21
its 1:1 complexes with Li+, Na+, and K+ cations, all
recorded in acetonitrile solution. The bands of the m(OH)
and m(C@O) vibrations are shown in Fig. 4b and c, in an
expanded scale, because according to the NMR data, the
most significant changes should be observed in these spec-
tral regions. Most characteristic, in the FT-IR spectrum of
water-free MON7 (Fig. 4b, solid line), are the bands
assigned to the m(OH) vibrations of the OXH and groups
at 3504 cmꢀ1, and of OIVH group at ca. 3322 cmꢀ1 as well
as the band assigned to the m(C@O) vibrations at
1732 cmꢀ1. In the spectrum of the MON7–Li+ complex
(Fig. 4b, dashed line) the band at 3504 cmꢀ1 vanishes
and two bands arise at 3455 cmꢀ1 and 3370 cmꢀ1 assigned
to m(OXIH) and m(OXH) vibrations, respectively. This indi-
cates that in the MON7–Li+ complex the hydrogen bonds
of the OXH and OXIH groups are slightly stronger com-
pared to those in uncomplexed MON7. The stretching
vibrations of the OIVH group at 3322 cmꢀ1 are no longer
observed in the spectrum, indicating that also the proton
of this group is stronger hydrogen-bonded within the com-
plex structure. This interpretation is consistent with the 1H
NMR data (Table 2 and Fig. 3).
Table 4
Heat of formation (kcal/mol) of MON7 and its complexes with the cations
without (A) and with (B) the engagement of carbonyl group in
coordination process calculated by PM5 method (WinMopac 2003)
Complex
HOF (kcal/mol)
DHOF (kcal/mol)
MON7
ꢀ667.49
ꢀ544.25
ꢀ713.59
ꢀ544.25
ꢀ713.16
ꢀ525.43
ꢀ743.14
ꢀ525.43
ꢀ691.25
ꢀ596.40
ꢀ686.34
ꢀ524.27
ꢀ641.21
–
MON7 + Li+
MON7 + Li+
MON7 + Li+
MON7 + Li+
(A)
(B)
ꢀ169.34
uncomplexed
(A)
complexed
ꢀ158.91
ꢀ217.71
ꢀ165.82
ꢀ135.79
ꢀ90.66
uncomplexed
(B)
complexed
MON7 + Na+
MON7 + Na+
MON7 + Na+
MON7 + Na+
MON7 + K+
MON7 + K+
MON7 + K+
MON7 + K+
(A)
uncomplexed
(A)
complexed
(B)
uncomplexed
(B)
(A)
(A)
(B)
complexed
uncomplexed
complexed
uncomplexed
(B)
complexed
DHOF = HOFMON7+Mcomplexed ꢀ HOFMON7+Muncomplexed
,
M ꢀ metal
cation.
(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.
In the spectrum of the MON7–Na+ complex (Fig. 4b,
dotted line) only one broad band with a maximum at ca.
3469 cmꢀ1 is observed demonstrating that the hydrogen
bonds formed by the OXH and OXIH groups become
slightly stronger and those of OIVH group slightly weaker
compared to those in spectrum of MON7. This interpreta-
tion is also consistent with the 1H NMR data (Table 2 and
Fig. 3).
those of ESI measurements) are formed with Na+ >>
Li+ > K+ cations. This result is in good agreement with
the ESI data discussed above. The DHOF values also show
that the structures of MON7 with cations in which the car-
bonyl group is involved in the complexation process (struc-
ture B), are energetically less favorable than those in which
the carbonyl group is not involved (structure A). Only for
the MON7–Na+ and MON7–Li+ complexes the DHOF
values of structure B are relatively high indicating that such
structures should be taken into account. This result is in
good agreement with both the ESI data and with the FT-
IR observations.
Also in the spectrum of the MON7–K+ complex
(Fig. 4b, dashed-dotted line) only one band with a maxi-
mum at 3502 cmꢀ1 is observed indicating that the hydrogen
bonds, in which the hydroxyl groups are involved, are
almost unchanged as compared to those in the uncom-
plexed MON7. The position of the band assigned to the
m(C@O) vibrations at 1732 cmꢀ1, in the spectrum of
MON7 and its complexes with K+ cations, is almost
unchanged (Fig. 4c), demonstrating that the oxygen atom
of the C@O ester group is not engaged in the complexation
process of these cations.
The interatomic distances between the oxygen atoms of
MON7 and the cations along with the partial charges at
these atoms are given in Table 5. Analysis of these values
shows that some oxygen atoms, such as OIV, OVI, OVII
,
and OIX are always involved in the coordination of differ-
ent metal cations, whereas the OI, OII, and OIII play no role
in this coordination process. The latter refers to the A type
structure in which the C1@O group is not involved in the
complexation of the metal cation. If the OII oxygen atom
from the C1@O carbonyl group participates in the
coordination of the cation, the B type structure of the
MON7–Na+ and MON7–Li+ complexes are formed. The
calculated coordination distances for both types of the A
and B complexes are comparable. Thus, the formation of
the B type structure of the MON7–Na+ complex is very
probable. This result is consistent with the FT-IR data
indicating the existence of this complex structure.
In contrast to this spectrum the spectra of MON7 with
Li+ andꢀ1Na+ cations, additionally to the bands at ca
1732 cm
,
show new bands at 1676 cmꢀ1 and
1705 cmꢀ1, respectively. These bands can be assigned to
the m(C@O) vibrations of alternative complex structures
in which the carbonyl group interacts with the metal cat-
ion. The intensity of this band is however relatively low
indicating that these structures are not dominant.
3.4. PM5 calculations
Other oxygen atoms can be involved in the coordination
process depending on the type of the cation due to their dif-
ferent radii. The coordination distances and the number of
coordinating oxygen atoms suggest that all cations studied
can undergo fast fluctuations within the structures of the
Based on the spectroscopic results, the heats of forma-
tion (HOF) of the structures of MON7 and its complexes
with Li+, Na+, and K+ cations were calculated (Table 4).
Their values imply that the most stable complexes in the
gas phase (under the experimental conditions similar to

22
A. Huczyn´ski et al. / Journal of Molecular Structure 879 (2008) 14–24
Table 5
Table 6
˚
˚
The interatomic distances (A) and partial charges for O atoms of MON7
coordinating metal cations in complexes structures calculated by PM5
method (WinMopac 2003)
The lengths (A) and angles (ꢁ) [values in brackets] of the hydrogen bond
for MON7 complexes calculated by PM5 method (WinMopac 2003)
˚
Compound
Oxygen
atom
Hydrogen bond length (A) [Hydrogen
bond angle (ꢁ)]
Complex
with
monovalent
cation
Monovalent Coordinating Coordinating Distance
˚
cation
partial
charge
atom
atom
partial
charge
(A)
OIV–H
OX–H
OXI–H
coordinating
atom fi
cation
MON7
OII
–
2.95 [159.9] 2.92 [131.2]
OIX
2.69 [148.2]
–
–
MON7–Li+ (A) OIII
–
–
2.83 [131.4]
–
–
MON7–Li+ (A) +0.397
MON7–Li+ (B) +0.409
OIV–H
OVI
OVII
OIX
ꢀ0.430
ꢀ0.386
ꢀ0.371
ꢀ0.382
ꢀ0.419
ꢀ0.453
ꢀ0.391
ꢀ0.387
ꢀ0.379
ꢀ0.450
ꢀ0.412
ꢀ0.375
ꢀ0.369
ꢀ0.402
ꢀ0.414
ꢀ0.342
ꢀ0.395
ꢀ0.379
ꢀ0.374
ꢀ0.350
ꢀ0.380
ꢀ0.394
2.11
2.04
2.07
2.09
OXII
OIX
OI
2.72 [117.8]
–
2.49 [98.8]
2.71 [112.6]
MON7–Li+ (B) OIII
–
–
2.85 [141.4]
–
–
OII
OIV–H
OVI
OVII
OIX
2.24
2.10
2.21
2.22
2.15
OXII
OIX
2.71 [135.8]
–
2.79 [117.8]
MON7–Na+
(A)
OIV
OIII
–
–
2.56 [104.9]
–
–
2.82 [128.6]
MON7–Na+ (A) +0.303
OIV–H
OVI
OVII
OVIII
OIX
2.31
2.31
2.31
2.29
2.32
2.29
MON7–Na+
(B)
OI
OIII
–
–
2.69 [116.8]
–
–
2.69 [117.6]
MON7–K+ (A) OI
OIII
–
–
2.74 [143.3] 2.94 [143.6]
2.64 [105.2]
–
OXI
(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.
MON7–Na+ (B) +0.311
OII
OIV–H
OVI
OVII
OVIII
OIX
2.38
2.38
2.34
2.33
2.32
2.35
2.34
OXI
MON7–K+ (A) +0.476
OIV–H
OVI
OVII
OIX
ꢀ0.423
ꢀ0.398
ꢀ0.387
ꢀ0.394
ꢀ0.416
2.93
2.78
2.86
2.88
2.81
OXI
(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-
firmed by the signal of the C1 carbon atom in the 13C
NMR spectrum of the MON7–Na+ complex which is a
singlet.
The lengthsand angles of the hydrogen bonds in whichthe
OH groups are engaged are summarized in Table 6. The cal-
culated structure of MON7 indicates that OII oxygen atom
from the C@O ester group is engaged in a bifurcated intra-
molecular hydrogen bond with two OXH and OXIH hydro-
xyl groups (Scheme 3). During the formation of the MON7
complexes with cations these hydrogen bonds are broken
open. For this reason and also as a consequence of the coor-
dinating process the 13C NMR signals of the C1 carbon
atoms are shifted toward higher ppm values (Table 3).
The calculated structures of MON7 and its complexes
with the Li+, Na+, and K+ cations are visualized in Schemes
3–6. The hydrogen bonds and the coordination bonds are
marked by dots. A comparison of all the calculated struc-
Scheme 3. The structure of MON7 calculated by PM5 method (WinM-
opac 2003).
tures indicates that only for the MON7 complex with Na+
cation the MON7 molecule is able to form a pseudo-crown
ether structure. This type of structure provides the most effi-
cient interactions and therefore, the affinity of MON7 to
Na+ cation is higher than that to the other cations.
4. Conclusions
A new 2-(2-methoxyethoxy)ethyl ester of Monensin A
is synthesized by an effective method and its ability to

A. Huczyn´ski et al. / Journal of Molecular Structure 879 (2008) 14–24
23
Scheme 4. The structures of two types of MON7-Li+ complexes: (a)
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
in coordination of the cation – type B calculated by PM5 method
(WinMopac 2003).
Scheme 5. The structures of two types of MON7-Na+ complexes: (a)
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
in coordination of the cation – type B calculated by PM5 method
(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
and 13C 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-
xyl groups. Within the complexes of MON7 with cations
(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-
nant. It is demonstrated that the strongest intramolecular
hydrogen bonds are formed within the MON7–Li+ com-
Scheme 6. The structure of MON7–K+ complex calculated by PM5
method (WinMopac 2003).
plex structure. Despite of this fact the formation of a
pseudo crown ring structure formed by MON7 prefer-
ences the complexation of Na+ cations.

24
A. Huczyn´ski et al. / Journal of Molecular Structure 879 (2008) 14–24
´
[9] A. Huczynski, D. Michalak, P. Przybylski, B. Brzezinski, F. Bartl, J.
Acknowledgements
Mol. Struct. 797 (2006) 99.
´
[10] A. Huczynski, D. Michalak, P. Przybylski, B. Brzezinski, F. Bartl, J.
´
Adam Huczynski wishes to thank the Foundation for
Mol. Struct. 828 (2007) 130.
Polish Science for fellowship. The authors thank the Polish
Ministry of Science and Higher Education for financial
support under Grant No. R 0501601.
´
[11] A. Huczynski, P. Przybylski, B. Brzezinski, J. Mol. Struct. 788 (2006)
176.
´
[12] A. Huczynski, P. Przybylski, G. Schroeder, B. Brzezinski, J. Mol.
Struct. 29 (2007) 111.
´
[13] A. Huczynski, D. Łowicki, B. Brzezinski, F. Bartl, J. Mol. Struct. 874
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