Spectroscopic, mass spectrometry and semiempirical investigation of a new 2-methoxyethyl ester of monensin A and its complexes with Li+, Na+ and K+ cations

Article abstract of DOI:10.1016/j.molstruc.2007.03.043

A new 2-methoxyethyl ester of monensin A (MON5) 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 MON5 forms complexes with Li⁺, Na⁺ and K⁺ of exclusively 1:1 stoichiometry which are stable up cv = 90 V. The formation of complexes between MON5 and Na⁺ cations is strongly favoured. Starting from cv = 110 V the fragmentation of the respective complexes is observed, primarily characterized by several dehydration steps. The structures of the MON5 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 MON5 is preferred in complexes with Na⁺ cations.

Full text of DOI:10.1016/j.molstruc.2007.03.043

Available online at www.sciencedirect.com
Journal of Molecular Structure 874 (2008) 89–100
www.elsevier.com/locate/molstruc
Spectroscopic, mass spectrometry and semiempirical investigation of
a new 2-methoxyethyl ester of monensin A and its complexes with Li+,
Na+ and K+ cations
a
a
a,
b
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
Received 28 February 2007; accepted 15 March 2007
Available online 30 March 2007
Abstract
A new 2-methoxyethyl ester of monensin A (MON5) has been synthesized and its capability of complex formation with Li+, Na+ and
1
K+ cations has been studied by ESI MS, H and 13C NMR, FT-IR and PM5 semiempirical methods. ESI mass spectrometry indicates
that MON5 forms complexes with Li+, Na+ and K+ of exclusively 1:1 stoichiometry which are stable up cv = 90 V. The formation of
complexes between MON5 and Na+ cations is strongly favoured. Starting from cv = 110 V the fragmentation of the respective com-
plexes is observed, primarily characterized by several dehydration steps. The structures of the MON5 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 MON5 is preferred in com-
plexes with Na+ cations.
ꢀ 2007 Elsevier B.V. All rights reserved.
Keywords: Monensin A; Ionophore; 2-Methoxyethyl ester; Complexes: monovalent cations; Spectroscopy; Electrospray mass spectrometry; Semiem-
pirical calculations; Hydrogen bonds
1. Introduction
the methyl ester of monensin A, has been shown to be able
to form hydrates with three hydrogen bonded water mole-
cules inside a pseudo-ring structure. By a self-assembly
process this hydrate species forms a proton channel in
which the proton can move within the whole channel [4].
As a continuation of our earlier works, we report here
The polyether antibiotic monensin A belongs to the
group of ionophorous antibiotics representing bioactive
molecules able to transport monovalent and bivalent metal
cations across natural and artificial lipid membranes. In
practice monensin A, together with other ionophor antibi-
otics is used as an anticoccidial agent for cattle, sheep and
chicken [1–3].
In our earlier works the synthesis and the physico-chem-
ical characterization of new esters of monensin A has been
reported [4–10]. In these publications the complexation of
mono- and di-valent metal cations by esters of monensin
A and the properties of these complexes have been
described in detail. Interestingly one of these esters, namely
1
ESI MS, H and 13C NMR, FT-IR as well as PM5 studies
of complexes between a new 2-methoxyethyl ester of
monensin A and biologically important monovalent cat-
ions such as the Li+, Na+ and K+ cations. The structures
of monensin A 2-methoxyethyl ester and its complexes with
monovalent cations are discussed in detail.
2. Experimental
Monensin A sodium salt was purchased from Sigma
(90–95%). The perchlorates LiClO4, NaClO4 and KClO4
were commercial products of Sigma and were used without
*
Corresponding author. Fax: +48 61 865 8008.
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.2007.03.043

90
A. Huczyn´ski et al. / Journal of Molecular Structure 874 (2008) 89–100
Table 1
any further purification. Because the salts were hydrates, it
was necessary to dehydrate them in several (6–10 times)
evaporation steps from a 1:5 mixture of acetonitrile and
absolute ethanol. The dehydration of the perchlorates
was monitored by recording their FT-IR spectra in
acetonitrile.
The main peaks in the ESI mass spectra of the complexes of MON5 with
cations at various cone voltages
Cation Cone voltage
[V]
Main peaks m/z
Li+
Na+
K+
10
30
50
70
90
736
736
736
736
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.
736
110
130
736, 718, 700, 485, 467, 445, 427
718, 718, 700, 485, 467, 445, 427
10
30
50
70
90
752
752
752
752
2.1. Synthesis of 2-methoxyethyl ester of monensin A
(MON5)
Monensin A sodium salt was dissolved in dichloro-
methane and stirred vigorously with a layer of aqueous
sulphuric acid (pH 1.5). The organic layer containing
monensin A (monensic acid, MONA) was separated
and washed several times with distilled water. Finally
the solvent was evaporated under reduced pressure to
dryness.
752
110
130
752, 734, 507, 501, 461
752, 734, 716, 507, 501, 489, 483, 479, 461, 443
10
30
50
70
90
768
768
768
768,
768,
768, 750, 732
768, 750, 732
A
mixture of 1-bromo-2-methoxyethane (200 mg,
110
130
1.44 mmol), MONA (500 mg, 0.75 mmol), and 1,8-diazabi-
cyclo[5.4.0]undec-7-en (DBU) (137 mg, 0.9 mmol) and
40 ml toluene was heated at 90 ꢁC for 5 h. After cooling,
the precipitate DBU-hydrobromide (DBU-HBr) was fil-
tered off. The filtrate was combined and evaporated under
reduced pressure. The residue was purified by chromatog-
raphy on silica gel (Fluka type 60) to give MON5
(405 mg, 74% yield) as a colourless oil showing a tendency
to form a glass state.
solved in an appropriate volume of dry CH3CN or
CD3CN to obtain the complex at a 0.07 mol dmꢀ3
concentration.
2.3. Mass spectrometry
Elementary analysis: calculated: C 64.26%; H 9.40%,
found C 64.19%; H 9.55%.
The ESI (electrospray ionisation) mass spectra were
recorded on a Waters/Micromass (Manchester, UK) ZQ
mass spectrometer equipped with a Harvard Apparatus
syringe pump. All samples were prepared in acetonitrile.
The measurements were performed with two types of sam-
ples being solutions of MON5 (5 · 10ꢀ5 mol dmꢀ3) with:
(a) each of the cations Li+, Na+ and K+
(2.5 · 10ꢀ4 mol dmꢀ3) taken 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 Har-
2.2. Synthesis of MON5 complexes with monovalent cations
The 0.07 mol dmꢀ3 solutions of 1:1 complexes of
MON5 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 MON5. The solvent was evaporated under
reduced pressure to dryness and the oily residue was dis-
IV
OH
28
Me
27
Me
29
33
Me
Me
30-31
Et
23
II
7
32
Me 14
III
22
21
24
25
6
5
8
9
18
19
15
O
10
11
OMe
H
H
XI
35
OH
20
16
17
12 13
3
1
R
O
O
IX
O
VII
2
4
26
O
VI
O
I
O
V
H
H
H
OH
VIII
X
Me
36
Me
34
CH2CH2
MON5 R =
O
CH3
MONA R = H
'
1
'
2
'
3
XII
Scheme 1. The structures and atom numbering of MONA and MON5.

A. Huczyn´ski et al. / Journal of Molecular Structure 874 (2008) 89–100
91
Fig. 1. ESI mass spectra of a 1:1 mixture of MON5 with Na+ at various cone voltages (cv).
vard pump at a flow rate of 20 ll minꢀ1. The ESI source
2.4. Spectroscopic measurements
potentials were: capillary 3 kV, lens 0.5 kV, extractor 4 V.
The standard ESI mass spectra were recorded at the cone
voltages: 10, 30, 50, 70, 90, 110 and 130 V. The source tem-
perature was 120 ꢁC and the dessolvation temperature was
300 ꢁC. Nitrogen was used as the nebulizing and dessolva-
tion 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 step size of 1 m/z unit.
The mass range for ESI experiments was from m/z = 300
to m/z = 1000.
The FT-IR spectra of MON5 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
, NSS = 125. The

92
A. Huczyn´ski et al. / Journal of Molecular Structure 874 (2008) 89–100
+
O
O
O
O
M
O
I
H
+
M=Li m/z=700
O
M=Na+ m/z=716
M=K+ m/z=732
O
+
-H2O
or
-H2O
O
O
O
O
H
OCH3
+
O
O
M
O
O
O
O
H
O
O
O
M
O
O
H
+
M=Li m/z=718
M=Na+ m/z=734
M=K+ m/z=750
J
H
O
O
O
+
M=Li m/z=700
O
M=Na+ m/z=716
M=K+ m/z=732
OCH3
-H2O
O
O
OCH3
+
+
+
O
O
O
H
O
O
O
-H2O
-H2O
O
O
O
O
O
O
O
M
O
H
O
M
M
O
O
O
O
H
O
H
H
O
C
A
B
+
O
O
O
M=Li m/z=700
M=Na+ m/z=716
M=K+ m/z=732
M=Li+ m/z=736
M=Na+ m/z=752
M=K+ m/z=768
O
+
M=Li m/z=718
M=Na+ m/z=734
M=K+ m/z=750
O
O
O
O
O
OCH3
OCH3
OCH3
+
+
+
-H2O
O
O
O
O
O
O
O
O
O
O
O
O
O
M
O
H
M
O
H
D
M
H
O
O
H
O
H
E
H
O
+
- CO
M=Li m/z=467
K
+
M=Na+ m/z=483
M=Li m/z=485
M=Na+ m/z=501
M=Na+ m/z=507
+
+
+
-H2O
-H2O
O
O
O
O
O
O
O
O
O
O
M
O
O
O
M
M
O
O
H
H
O
O
H
O
H
G
F
H
+
+
M=Li m/z=427
L
M=Li m/z=445
M=Na+ m/z=461
M=Na+ m/z=443
M=Na+ m/z=479
Scheme 2. The proposed fragmentation pathways of MON5 complexes with monovalent cations.
Happ-Genzel apodization function was used. All manipu-
lations with the compounds were performed in a carefully
dried and CO2-free glove box.
The NMR spectra of MON5 and its 1:1 complexes
(0.07 mol Lꢀ1) with LiClO4, NaClO4 and KClO4 were
recorded in CD3CN solutions using a Varian Gemini

A. Huczyn´ski et al. / Journal of Molecular Structure 874 (2008) 89–100
93
Fig. 2. ESI mass spectrum of a 1:1:1:3 mixture of cation perchlorates LiClO4, NaClO4 and KClO4 with MON5 (cv = 30).
300 MHz spectrometer. All spectra were locked to deute-
rium resonance of CD3CN.
3.1. Electrospray mass spectrometry (ESI) measurements
1
The H NMR measurements in CD3CN were carried
The main m/z signals in the ESI mass spectra of MON5
with the Li+, Na+ and K+ cations used separately at vari-
ous cone voltages are collected in Table 1. One exemplary
ESI mass spectrum of the 1:1 complex of MON5 with Na+
cation measured at various cone voltages is shown in
Fig. 1. According to the data summarised in Table 1,
MON5 forms exclusively complexes of 1:1 stoichiometry
with the cations used in this study. These complexes are
very stable up to about cv = 90 V. Starting from
cv = 110 V a fragmentation of the respective complexes is
observed. The proposed fragmentation pathways starting
from structure A are shown in Scheme 2. The first step of
the fragmentation is the loss of one water molecule as a
result of the abstraction of the OIVH or OXH hydroxyl
groups yielding the B or H cation structures, respectively.
Further fragmentation of cation B, with Li+ and Na+, is
realized in two directions forming other types of complexes
(C, D, E, F and finally G). Cation C is formed from cation
B by abstraction of a second water molecule. The forma-
tion of the D and E fragmentary complexes is achieved
by abstraction of the part of the molecule containing the
ester group. Cations F and G are formed from cations D
and E by abstraction of one C3H4 group. Additionally, cat-
ion G is formed by loss of one water molecule from cation
F. For the complex of MON5 with K+ cation no abstrac-
tion of the part of the molecule containing the ester group
was detected.
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 function
or zero filling was used. Digital resolution was 0.2 Hz per
point. The error of chemical shift value was 0.01 ppm.
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.
2.5. PM5 calculations
PM5 semiempirical calculations were performed using
the WinMopac 2003 program. In all cases full geometry
optimisation of MON5 and its complexes was carried out
without any symmetry constraints [11–14].
2.6. Elementary analysis
The elementary analysis of MON5 was carried out on
Vario ELIII (Elementar, Germany).
In the case of the MON5–Na complex the fragmenta-
tion of cation B yields cation K which, after the abstraction
of one CO molecule, forms cation L. Further, cation L
undergo fragmentations typical for other metal cations
3. Results and discussion
The structure of MON5 together with the atom number-
ing is shown in Scheme 1.

94
A. Huczyn´ski et al. / Journal of Molecular Structure 874 (2008) 89–100
Table 2
1H NMR chemical shifts (ppm) of MON5 and its complexes in CD3CN
No. atom
Chemical shift (ppm)
Differences (D) between chemical shifts (ppm)
MON5
MON5:Li+
MON5:Na+
MON5:K+
D1
D2
D3
1
—
—
—
—
—
—
—
2
3
4
5
6
7
8A
8B
9
2.62
3.57
2.00
4.02
1.77
3.67
1.63
1.99
—
2.62
3.67
2.05
4.17
1.79
3.96
1.56
2.04
—
2.69
3.63
2.04
3.95
1.82
3.92
1.62
2.02
—
2.68
3.55
1.98
3.91
1.79
3.84
1.64
2.02
—
0.00
0.10
0.05
0.15
0.02
0.07
0.06
0.04
0.06
ꢀ0.02
ꢀ0.02
ꢀ0.11
0.02
0.17
0.01
ꢀ0.07
0.05
0.29
0.25
ꢀ0.07
ꢀ0.01
0.05
0.03
0.03
—
—
—
10A
10B
11A
11B
12
1.90
1.90
1.79
1.96
—
1.84
2.06
1.85
1.88
—
1.81
2.02
1.83
1.96
—
1.75
1.89
1.78
1.89
—
ꢀ0.06
ꢀ0.09
ꢀ0.15
ꢀ0.01
ꢀ0.01
ꢀ0.07
—
0.16
0.12
0.06
0.04
0.00
—
ꢀ0.08
—
13
3.65
1.58
1.76
1.60
3.68
1.48
1.90
1.50
3.64
1.44
1.88
1.50
3.67
1.46
1.76
1.46
0.03
ꢀ0.01
ꢀ0.14
0.12
ꢀ0.10
0.02
14A
14B
15A
15B
ꢀ0.10
ꢀ0.12
0.14
0.00
ꢀ0.10
ꢀ0.14
2.10
—
2.18
—
2.26
—
2.20
—
0.08
—
0.16
—
0.10
—
16
17
18
19A
19B
3.86
2.28
1.52
4.37
2.45
1.55
3.95
2.30
1.64
3.94
2.35
1.52
0.51
0.17
0.03
0.09
0.02
0.12
0.08
0.07
0.00
2.16
4.20
3.61
1.31
1.32
1.44
1.51
—
2.33
4.41
3.84
1.33
1.38
1.52
1.90
—
2.16
4.42
3.72
1.50
1.32
1.50
1.68
—
2.02
4.37
3.65
1.35
1.32
1.50
1.69
—
0.17
0.21
0.23
0.02
0.06
0.08
0.39
—
0.00
0.22
0.11
0.19
0.00
0.06
0.17
—
ꢀ0.14
0.17
0.04
0.04
0.00
0.06
0.18
—
20
21
22
23A
23B
24
25
26A
26B
27
28
29
30A
30B
31
32
33
3.36
3.36
0.87
0.83
0.93
1.54
1.54
0.89
1.34
0.87
0.97
3.30
1.13
4.18
4.18
3.56
3.31
2.81
4.11
3.80
3.43
3.43
0.89
0.82
0.95
1.44
1.69
0.96
1.56
0.93
1.00
3.30
1.17
4.24
4.26
3.60
3.41
2.97
5.91
4.65
3.46
3.69
0.82
0.84
0.91
1.46
1.63
0.89
1.46
0.93
1.00
3.32
1.17
4.22
4.22
3.61
3.34
3.81
4.02
4.24
3.41
3.64
0.84
0.86
0.94
1.50
1.67
0.92
1.46
0.89
0.97
3.31
1.15
4.22
4.22
3.61
3.35
3.51
3.65
4.11
0.07
0.07
0.02
ꢀ0.01
0.02
ꢀ0.10
0.15
0.07
0.22
0.06
0.03
0.00
0.04
0.06
0.08
0.04
0.10
0.16
1.80
0.85
0.10
0.33
ꢀ0.05
0.01
ꢀ0.02
ꢀ0.08
0.09
0.00
0.12
0.06
0.03
0.02
0.04
0.04
0.04
0.05
0.03
1.00
ꢀ0.09
0.44
0.05
0.28
ꢀ0.03
0.03
0.01
ꢀ0.04
0.13
0.03
0.12
0.02
0.00
0.01
0.02
0.04
0.04
0.05
0.04
0.70
ꢀ0.46
0.31
34
35
36
10A
10B
20
30
OXI
OIV
H
H
OXH
D1 = dMON5:Li+ ꢀ dMON5, D2 = dMON5:Na+ ꢀ dMON5, D3 = dMON:K+ ꢀ dMON5
.
including abstraction of water molecules in two steps,
yielding cations F and G, respectively.
Fig. 2 presents the ESI spectrum of the 1:1:1:3 mixture
of Li+, Na+, K+ cations with MON5 measured at
cv = 30 V. In this Figure only three characteristic signals
at m/z = 736, m/z = 752 and m/z = 768 assigned to the
1:1 complexes of MON5 with Li+, Na+ and K+ cations
respectively, are shown,. The intensity of the MON5–Na+

A. Huczyn´ski et al. / Journal of Molecular Structure 874 (2008) 89–100
95
Table 3
13C NMR chemical shifts (ppm) of MON5 and its complexes in CD3CN
No. atom
Chemical shift (ppm)
Differences (D) between chemical shifts (ppm)
D1 D2 D3
0.58 1.31 0.52
MON5
MON5:Li+
MON5:Na+
MON5:K+
1
2
3
4
5
6
7
8
9
175.75
41.45
82.26
37.95
68.50
37.04
71.87
35.10
108.35
39.77
32.54
86.89
84.34
28.51
32.05
88.03
86.32
35.89
34.82
77.94
77.29
34.06
37.66
34.76
97.76
67.35
16.45
17.86
16.15
30.11
8.31
176.33
41.18
81.80
37.57
69.52
36.88
70.11
34.23
108.01
39.63
33.20
87.10
82.57
27.55
32.11
87.94
84.89
34.08
33.71
79.45
74.77
33.27
36.53
36.71
99.51
66.58
15.92
17.40
16.29
30.14
8.42
177.06
41.35
81.74
38.07
69.00
36.96
70.85
34.58
108.37
39.88
33.39
86.64
82.27
27.29
30.74
86.75
85.49
35.04
33.79
76.92
75.65
32.19
35.80
36.25
98.78
67.17
16.09
16.68
14.43
30.20
8.12
176.27
41.44
82.02
38.39
68.07
37.15
70.80
34.21
107.78
39.91
34.21
85.99
83.34
28.18
31.96
86.70
85.04
35.47
33.08
77.88
75.78
32.91
36.75
35.74
98.70
66.92
16.52
17.33
15.89
30.44
8.49
ꢀ0.27
ꢀ0.46
ꢀ0.38
1.02
ꢀ0.16
ꢀ1.76
ꢀ0.87
ꢀ0.34
ꢀ0.14
0.66
ꢀ0.10
ꢀ0.52
0.12
ꢀ0.01
ꢀ0.24
0.44
0.50
ꢀ0.43
ꢀ0.08
ꢀ1.02
ꢀ0.52
0.02
0.11
0.85
0.11
ꢀ1.07
ꢀ0.89
ꢀ0.57
0.14
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
1.67
0.21
ꢀ0.25
ꢀ2.07
ꢀ1.22
ꢀ1.31
ꢀ1.28
ꢀ0.83
ꢀ0.85
ꢀ1.03
ꢀ1.02
ꢀ1.64
ꢀ1.87
ꢀ1.86
1.49
ꢀ0.90
ꢀ1.00
ꢀ0.33
ꢀ0.09
ꢀ1.33
ꢀ1.28
ꢀ0.42
ꢀ1.74
ꢀ0.06
ꢀ1.51
ꢀ1.15
ꢀ0.91
0.98
ꢀ1.77
ꢀ0.96
0.06
ꢀ0.09
ꢀ1.43
ꢀ1.81
ꢀ1.11
1.51
ꢀ2.52
ꢀ0.79
ꢀ1.13
1.95
1.75
1.02
0.94
ꢀ0.77
ꢀ0.53
ꢀ0.46
0.14
ꢀ0.18
ꢀ0.36
ꢀ1.18
ꢀ1.72
0.09
ꢀ0.43
0.07
ꢀ0.53
ꢀ0.26
0.33
0.03
0.11
2.17
ꢀ0.19
0.18
1.81
26.26
11.34
12.60
58.50
12.12
64.24
70.90
58.80
28.43
10.73
13.09
58.54
11.44
64.28
71.13
58.92
28.29
10.89
13.16
58.78
12.06
64.53
71.05
59.05
28.07
10.85
12.56
58.61
12.24
64.24
71.06
58.95
2.03
ꢀ0.61
ꢀ0.45
0.56
0.28
ꢀ0.49
ꢀ0.04
0.11
0.49
0.04
ꢀ0.68
ꢀ0.06
0.12
0.00
0.04
0.29
20
30
0.23
0.15
0.16
0.12
0.25
0.15
D1 = dMON5:Li+ ꢀ dMON5, D2 = dMON5:Na+ ꢀ dMON5, D3 = dMON5:K+ ꢀ dMON5
.
complex signal is the strongest, clearly indicating that
MON5 preferentially forms complexes with Na+ cations.
The intensities of the signals of the MON5–Li+ and
MON5–K+ complexes are comparable, but significantly
lower than that of the MON5–Na+ complex.
In the 1H NMR spectra of MON5 and its 1:1 complexes
with Li+, Na+ and K+ cations (Table 2), the signals of the
protons of all three OH groups are separate 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 MON5 the OH proton signals observed at 2.81,
3.80 and 4.11 ppm, are assigned to OXIH, OXH and OIVH
groups, respectively, whereas in the spectra of the com-
plexes between MON5 and the Li+, Na+ and K+ cations
these signals are shifted in different directions depending
on the kind of the cation. The most significantly shifted sig-
nal of all OH groups is found in the spectrum of MON5
with the Li+ cation at 5.91 ppm. It is assigned to the OIVH
proton involved in the strongest intramolecular hydrogen
bond compared to those of other hydroxyl groups. In the
spectra of the MON5 complexes with Na+ and K+ cations,
the signals of the OIVH protons are shifted towards lower
1
3.2. H and 13C NMR measurements
The 1H and 13C NMR data of MON5 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, in
contrast to the complexes described above, the respective
MON5 complexes with the RbClO4 and CsClO4 salts are
1
almost insoluble in acetonitrile. The H and 13C signals
were assigned using one- and two-dimensional (COSY,
HETCOR) spectra as well as by the addition of CD3OD
to the sample.

96
A. Huczyn´ski et al. / Journal of Molecular Structure 874 (2008) 89–100
Fig. 3. 1H NMR in region of OH proton signals of: (a) MON5, (b) MON5–Li+, (c) MON5–Na+ and (d) MON5–K+.
ppm values indicating that the hydrogen bonds, in which
the OIVH protons are involved, are weaker. This spectral
feature demonstrates that depending on the cation, the
respective hydroxyl groups form different intramolecular
hydrogen bonds, which is probably related to the forma-
tion of different structures of these complexes.
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
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 MON5 (Fig. 4b, solid line), are the bands
assigned to the m(OH) vibrations of the OXH and OXIH
groups at 3508 cmꢀ1, and to the OIVH group at ca.
3302 cmꢀ1, as well as the band assigned to the m(C@O)
vibrations at 1733 cmꢀ1. In the spectrum of the MON5–
Li+ complex (Fig. 4b, dashed line) two broad bands with
maxima at ca. 3438 cm and 3351 cmꢀ1 are observed indi-
cating that the OXH and OXIH groups are involved in
slightly stronger intramolecular hydrogen bonds compared
to those in uncomplexed MON5. The stretching vibrations
of the OIVH group are no more observed in the spectrum at
3302 cmꢀ1, indicating that also the proton of this group is
stronger hydrogen-bonded. In the spectrum of MON5–
Na+ complex (Fig. 4 b, dotted line) only one broad band
with a maximum at ca. 3463 cmꢀ1 is observed demonstrat-
ing that the hydrogen bonds formed by the OXH and OXIH
groups become slightly stronger and those of OIVH group
slightly weaker. This interpretation is consistent with the
1H NMR data (Table 2 and Fig. 3).
1
In the H NMR spectrum of the MON5 complex with
Li+ cation the proton signals of the C1, H2 group are
observed separately at 4.24 and 4.26 ppm. This fact can
be explained by the existence of a pseudo-cyclic structure,
in which this methylene group is involved, due to the for-
mation of a hydrogen bond between OXI–H as a proton
donor and OXII as a proton acceptor.
A comparison of the 13C NMR chemical shifts in the spec-
tra of the complexes with those observed in the spectrum of
MON5 suggests that not only the oxygen atoms are involved
in the cationscoordination, butalso indicates a complex con-
formational change, evoked by the complexation process.
For instance the D value of the C20 atom in the complex of
MON5 with Li+ cation is positive, whereas it is negative
for the complex of MON5 with Na+ cation and almost
unchanged for the MON5–K+ complex. This result indicates
that OVIII oxygen atom is only involved in the coordination
in the complex of MON5 with Na+ cation.
3.3. FT-IR studies
Also in the spectrum of MON5–K+ complex (Fig. 4b,
dashed-dotted line) only one band with a maximum at
3497 cmꢀ1 is observed indicating that the hydrogen bond,
in which the OIVH hydroxyl group is involved, is weaker
In Fig. 4a the FT-IR spectrum of water free MON5
(solid line) is compared with the corresponding spectra of

A. Huczyn´ski et al. / Journal of Molecular Structure 874 (2008) 89–100
97
Table 4
100
50
0
Heat of formation (kcal/mol) of MON5 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)
MON5
ꢀ620.07
ꢀ496.83
ꢀ643.91
ꢀ496.83
ꢀ572.39
ꢀ478.01
ꢀ662.70
ꢀ478.01
ꢀ623.56
ꢀ503.13
ꢀ644.90
ꢀ503.13
ꢀ559.86
–
MON5 þ LiþuncomplexedðAÞ
MON5 þ LiþcomplexedðAÞ
MON5 þ LiþuncomplexedðBÞ
MON5 þ LiþcomplexedðBÞ
MON5 þ NaþuncomplexedðAÞ
MON5 þ NaþcomplexedðAÞ
MON5 þ NaþuncomplexedðBÞ
MON5 þ NaþcomplexedðBÞ
MON5 þ KþuncomplexedðAÞ
MON5 þ KþcomplexedðAÞ
MON5 þ KþuncomplexedðBÞ
MON5 þ KþcomplexedðBÞ
ꢀ147.09
ꢀ75.56
ꢀ184.70
ꢀ145.55
ꢀ141.77
ꢀ56.73
4000
3500
3000
2500
2000
1500
1000
500
100
50
0
3508
3302
3351
3438
3497
3463
DHOF = HOFMON5 + M complexed ꢀ HOFMON5 + M uncomplexed; M, metal
cation.
3800
3700
3600
3500
3400
3300
3200
(A) Structure of MON5 complex in which the C1@O group is not
involved in coordination of metal cation.
(B) Structure of MON5 complex in which the C1@O group is involved in
coordination of metal cation.
100
50
0
this leads to a gain of entropy for the MON5–Na+ com-
plex. This might explain that Na+ forms the most stable
complexes with MON5 as also indicated by the ESI exper-
iments (Fig. 2).
1706
1733
1800
1750
1700
-1
1650
Wavenumber [cm
]
3.4. PM5 calculations
Fig. 4. FT-IR spectra of: (—) MON5, (- -) MON5–Li+, (ꢃ ꢃ ꢃ) MON5-Na+,
and (-ÆÆ-) MON5–K+ in the ranges of : (a) 4000–400 cmꢀ1; (b) m(OH) and
(c) m(C@O) stretching vibrations.
On the basis of the spectroscopic results, the heats of
formation (HOF) of the structures of MON5 and its com-
plexes with Li+, Na+ and K+ cations were calculated
(Table 4). Their values imply that the most stable com-
plexes in the gas phase (under the experimental conditions
similar to those of ESI measurements) are formed with
Na+ ꢁ Li+ ꢂ K+ cations. This result is in good agreement
with the ESI data discussed above. The DHOF values also
show that the structures of MON5 with cations in which
the carbonyl group is involved in the complexation process
are energetically less favourable than those in which the
carbonyl group is not involved. Only for the MON5–Na+
complexes the DHOF value of the structure involving the
carbonyl group in the complexation process is relatively
high indicating that such a structure should be taken into
account. This result is in good agreement with both the
ESI data and with the FT-IR observations.
The interatomic distances between the oxygen atoms
of MON5 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 coordina-
tion of different 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
compared to the Li+ and the Na+ complex and only
slightly stronger as in the uncomplexed MON5. The posi-
tion of the band assigned to the m(C@O) vibrations at
1733 cmꢀ1, in the spectra of MON5 and its complexes with
Li+ and K+ cations, is almost unchanged (Fig. 4c), demon-
strating that the oxygen atom of the C@O ester group is
not engaged in the complexation process of these cations.
The spectrum of the MON5–Na+ complex is intriguing.
Besides the band at ca. 1733 cmꢀ1, representing structure
A (Scheme 5a), in which the C@O ester group does not
contribute to the complexation process, a new less intense
band at ca. 1706 cmꢀ1 appears. This band can be assigned
to the m(C@O) vibrations in structure B of the MON5–Na+
complex in which the carbonyl group interacts with the
Na+ cation (Scheme 5b). The low intensity of this new
band, however, indicates that structure B is not predomi-
nant in acetonitrile solution. The presence of these two
bands suggests the existence of an dynamic equilibrium
between structure A and structure B of the MON5–Na+
complex.
These two structures are only two extreme conforma-
tions among many others realized with different probabili-
ties. In contrast to all other complexes investigated here,

98
A. Huczyn´ski et al. / Journal of Molecular Structure 874 (2008) 89–100
Table 5
˚
The interatomic distances (A) and partial charges for O atoms of MON5 coordinating metal cations in complexes structures calculated by PM5 method
(WinMopac 2003)
˚
Complex with monovalent
cation
Monovalent cation partial
charge
Coordinating
atom
Coordinating atom partial
charge
Distance (A) coordinating
atom fi cation
MON5: Li+ (A)
MON5: Na+ (A)
MON5: Na+ (B)
MON5: K+ (A)
+0.427
+0.308
+0.310
+0.475
OI
OII
OIII
–
–
–
–
–
–
2.07
–
2.02
2.06
–
2.14
–
OIV–H
ꢀ0.406
OV
–
OVI
OVII
OVIII
OIX
OX
ꢀ0.369
ꢀ0.371
–
ꢀ0.355
–
–
OXI
–
OI
OII
OIII
–
–
–
–
–
–
2.33
–
2.32
2.29
2.29
2.30
–
OIV–H
ꢀ0.449
OV
–
OVI
OVII
OVIII
OIX
OX
ꢀ0.426
ꢀ0.381
ꢀ0.367
ꢀ0.402
–
ꢀ0.431
–
OXI
2.30
OI
OII
–
2.38
–
2.34
–
2.34
2.33
2.32
2.35
–
ꢀ0.342
OIII
OIV–H
OV
OVI
OVII
OVIII
OIX
OX
–
ꢀ0.395
–
ꢀ0.379
ꢀ0.374
ꢀ0.350
ꢀ0.381
–
ꢀ0.394
–
OXI
2.34
OI
–
OII
OIII
–
–
–
–
O
OV
IV–H
ꢀ0.422
2.93
–
–
OVI
OVII
OVIII
OIX
OX
ꢀ0.398
ꢀ0.391
–
2.78
2.86
–
2.89
–
ꢀ0.391
–
OXI
ꢀ0.418
2.80
(A) Structure of MON5 complex in which the C1@O group is not involved in coordination of metal cation.
(B) Structure of MON5 complex in which the C1@O group is involved in coordination of metal cation.
participates in the coordination of the cation, the B type
structure of the MON5–Na+ complex is formed. The
calculated coordination distances for both types of the
A and B complexes are comparable. Thus, the forma-
tion of the B type structure of the MON5–Na+ complex
is very probable. This result is consistent with the FT-
IR data indicating the existence of this complex
structure.
ferent radii. The coordination distances and the number of
coordinating oxygen atoms suggest that all the cations
studied can undergo fast fluctuations within the structures
of the complexes as demonstrated for the complexes of
crown ethers with monovalent cations [15]. It is further
confirmed by the signal of the C1 carbon atom in the 13C
NMR spectrum of the MON5–Na+ complex being a
singlet.
Other oxygen atoms can be involved in the coordination
process depending on the type of the cation due to their dif-
The lengths and angles of the hydrogen bonds in which
the OH groups are engaged are summarized in Table 6. The

A. Huczyn´ski et al. / Journal of Molecular Structure 874 (2008) 89–100
99
Table 6
˚
The length (A) and angle (ꢁ) of the hydrogen bond for MON5 complexes calculated by PM5 method (WinMopac 2003)
˚
Compound
O-atom
Hydrogen bond length (A) [hydrogen bond angle (ꢁ)]
OIVH
OXH
OXIH
MON5
OII
OIX
–
2.96 [144.0]
–
2.94 [139.1]
–
2.70 [163.8]
MON5:Li+ (A)
OIII
OXII
OIX
–
–
2.71 [117.2]
–
–
2.68 [115.4]
–
2.45 [96.7]
MON5:Na+ (A)
MON5:Na+ (B)
MON5:K+ (A)
OIV
OIII
–
–
2.47 [157.5]
–
–
2.61 [160.8]
OI
OIII
–
–
2.69 [116.8]
–
–
2.69 [117.6]
OI
OIII
–
–
2.73 [144.5]
–
2.95[132.6]
2.63 [105.9]
(A), structure of MON5 complex in which the C1@O group is not involved in coordination of metal cation.
(B), structure of MON5 complex in which the C1@O group is involved in coordination of metal cation.
Scheme 3. The structure of MON5 calculated by PM5 method (WinM-
opac 2003).
Scheme 5. ThestructuresoftwotypesofMON5-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).
Scheme 4. The structure of MON5–Li+ complex calculated by PM5
method (WinMopac 2003).

100
A. Huczyn´ski et al. / Journal of Molecular Structure 874 (2008) 89–100
Na+ cation the MON5 molecule is able to form a
pseudo-crown ether structure. This type of structure pro-
vides the most efficient interactions and therefore, the
affinity of MON5 to Na+ cation is higher than to the other
cations.
References
[1] B.C. Pressman, Annu. Rev. Biochem. 45 (1976) 925.
[2] H.M. Mollenhauer, D.J. Morre, L.D. Rowe, Biochim. Biophys. Acta
1031 (1990) 225.
[3] J.W. Westley, Polyether Antibiotics Naturally Occurring Acid Ion-
ophores, vol. 2, Marcel Dekker Inc., New York, 1983, 51.
´
[4] A. Huczynski, P. Przybylski, B. Brzezinski, F. Bartl, J. Phys. Chem. B
110 (2006) 15615.
´
[5] A. Huczynski, P. Przybylski, B. Brzezinski, F. Bartl, Biopolymers 81
Scheme 6. The structure of MON5-K+ complex calculated by PM5
method (WinMopac 2003).
(2006) 282.
´
[6] A. Huczynski, P. Przybylski, B. Brzezinski, F. Bartl, Biopolymers 82
(2006) 491.
calculated structure of MON5 indicates that OII oxygen
atom from the C@O ester group is engaged in the bifur-
cated intramolecular hydrogen bonds with two OXH and
OXIH hydroxyl groups (Scheme 3). The formation of the
MON5 complexes with cations breaks these hydrogen
bonds. For this reason the 13C NMR signals of the C1 car-
bon atoms are shifted toward higher ppm values (Table 3).
The calculated structures of MON5 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-
tures indicates that only for the MON5 complex with
´
[7] A. Huczynski, D. Michalak, P. Przybylski, B. Brzezinski, F. Bartl, J.
Mol. Struct. 797 (2006) 99.
´
[8] A. Huczynski, D. Michalak, P. Przybylski, B. Brzezinski, F. Bartl, J.
Mol. Struct. 828 (2007) 130.
´
[9] A. Huczynski, P. Przybylski, B. Brzezinski 788 (2006) 176.
´
[10] A. Huczynski, P. Przybylski, G. Schroeder, B. Brzezinski, J. Mol.
Struct. 29 (2007) 111.
[11] J.J.P. Stewart, Method J. Comp. Chem. 10 (1989) 209.
[12] J.J.P. Stewart, J. Comp. Chem. 12 (1991) 320.
[13] CAChe 5.04 UserGuide, Fujitsu 2003.
[14] P. Przybylski, A. Huczyn´ski, B. Brzezinski, J. Mol. Struct. 826 (2007)
156.
[15] B. Brzezinski, G. Schroeder, A. Rabold, G. Zundel, J. Phys. Chem. 99
(1995) 8519.