Available online at www.sciencedirect.com
Journal of Molecular Structure 888 (2008) 224 229
www.elsevier.com/locate/molstruc
Molecular structure of rubidium six-coordinated dihydrate
complex with monensin A
*
Adam Huczyński, Małgorzata Ratajczak-Sitarz, Andrzej Katrusiak, Bogumil Brzezinski
Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland
Received 15 November 2007; accepted 8 December 2007
Available online 15 December 2007
Abstract
Crystal structure of monensin A rubidium salt dihydrate, [Rb(C36H61O11) 2H2O], has been studied by X-ray diffraction, FT-IR spec-
troscopy and PM5 semiempirical methods. The crystal space group is P212121 with a = 12.6153(7), b = 16.4841(10), c = 19.4840(12) and
Z = 4. The Rb O bond lengths are between 2.788(7) and 2.901(6) Å. The carboxyl group of monensin A is deprotonated and engaged in
two intramolecular O(11) H O(1) of 2.52(1) Å and O(10) H O(2) of 2.60(1) Å hydrogen bonds with hydroxyl groups, accompanied
with formation of a pseudo-cyclic structure. This structure is stabilised by the coordination of the Rb+ cation by oxygen atoms. Two
water molecules are involved in the weak intermolecular hydrogen bond between the different species forming a supramolecule. The
IR spectrum of the crystal is consistent with the results obtained by the X-ray study and provides spectroscopic evidence for the complex
formation. The calculated structure and the structural parameters of the monensin A rubidium salt are comparable with those deter-
mined by the X-ray study.
Ó 2007 Elsevier B.V. All rights reserved.
Keywords: Ionophores; Monensin A rubidium salts; X-ray; Rb+ complex; FT-IR; Semiempirical calculations
1. Introduction The crystal structures of monensin complexes with sev-
eral cations have been determined by X-ray diffraction
Ionophorous antibiotics belong to a group of highly bio- [17 25]. In these structures the coordination of the cation
active molecules, because they are able to transport mono- by monensin A was always accompanied with the appear-
valent and bivalent metal cation across natural and ance of a pseudo-cyclic structure stabilized by the intramo-
artificial lipid membranes. Monensin A (see Scheme 1) iso- lecular hydrogen bonds.
lated from Streptomyces cinnamonensis is a well-known Recently, we have studied the crystal structures of
representative of this class of compounds. It is able to form monensin A sodium salt as well as monensin A lithium salt
pseudomacrocyclic complexes with monovalent cations [24,25]. As a continuation of the studies a new crystal of
and to transport these cations across cell membranes. monensin A rubidium dihydrate has been obtained and
Monensin regulates many cellular functions, including studied by X-ray diffraction and FT-IR spectroscopy. In
apoptosis. It causes collapse of sodium and potassium gra- this report, the structure of rubidium complex of monensin
dients at the plasma membrane, blocks intracellular protein A determined by X-rays is compared with that calculated
transport, and exhibits antibiotic, antimalarial, and other using the PM5 semiempirical method.
important biological activities [1 11]. Monensin A is used
as a growth-promoting agent and as a coccidiostat in beef
2. Experimental
cattle, sheep, chickens and turkeys [4,12 16].
Monensin A sodium salt (90 95%) was purchased from
*
Sigma. CH3CN spectral-grade solvent was stored over 3 Å
Corresponding author. Tel.: [phone].
E-mail address: [e-mail] (B. Brzezinski). molecular sieves for several days. All manipulations with
0022-2860/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2007.12.005
A. Huczyński et al. / Journal of Molecular Structure 888 (2008) 224 229 225
O(4)
OH
33 29 28 27
Me
O(2)
Me
O(3) Me Me
32
30-31
7
O MeO
Me
Et H
O(11)
35
5 25
21
13 17
26
OH
9
1
Rb O O O
O O O
OH
H
H
H H
O(1)
O(5) O(6) O(7) O(8) O(9)
Me Me O(10)
36 34
MON-Rb
Scheme 1. The structure and atom numbering of MON Rb.
the substances were performed in a carefully dried and
Table 2
CO2-free glove box. Rubidium hydroxide hydrate
Atomic coordinates ( 104) and equivalent isotropic displacement param-
eters (Å2 103), (U(eq) is defined as one third of the trace of the
RbOH xH2O (99.995%) was purchased from Aldrich.
orthogonalized Uij tensor)
xy z U(eq)
2.1. Synthesis of MON Rb
Rb(1) 8200(1) 3769(1) 8332(1) 80(1)
O(1) 6398(6) 3467(5) 7095(5) 108(4)
Monensin A sodium salt was dissolved in dichlorometh-
O(2) 7529(6) 2465(4) 7085(4) 75(3)
ane and stirred vigorously with a layer of aqueous sulphu-
O(3) 4690(5) 1012(4) 7318(3) 62(2)
ric acid (pH 1.5). The organic layer containing monensin A
O(4) 8875(5) 2224(5) 8752(4) 65(2)
(monensic acid, MONA) was separated and washed several O(5) 6210(5) 2124(4) 9353(4) 53(2)
O(6) 7335(5) 3204(5) 9559(3) 62(2)
times with distilled water and finally the solvent was evap-
O(7) 7894(5) 4879(4) 9452(3) 55(2)
orated under reduced pressure to dryness.
O(8) 9944(5) 4635(4) 8899(3) 54(2)
A mixture of MONA (500 mg, 0.75 mmol), and rubid-
O(9) 9877(5) 4380(4) 7454(4) 51(2)
O(10) 9411(5) 3114(4) 7047(3) 58(2)
ium hydroxide hydrate (185 mg) in methanol was stirred
O(11) 7865(5) 4505(4) 7013(4) 76(3)
vigorously for 1 h. After this time the solvent was evapo-
C(1) 6632(10) 2739(7) 7078(6) 58(3)
rated under reduced pressure to dryness. The residue was
C(2) 5662(8) 2137(6) 6985(6) 57(3)
dissolved in acetonitrile. The solution was allowed to evap-
C(3) 5626(7) 1479(6) 7511(6) 50(3)
C(4) 5483(6) 1723(5) 8281(6) 46(3)
orate at room temperature. After 2 weeks the crystals were
C(5) 6516(8) 1952(6) 8660(5) 53(3)
formed in 17% yield.
C(6) 7390(7) 1286(7) 8645(5) 56(3)
C(7) 8312(8) 1576(6) 9089(5) 56(3)
C(8) 7977(9) 1851(6) 9774(5) 65(3)
C(9) 6992(10) 2403(6) 9776(6) 58(3)
C(10) 6558(10) 2508(6) 10.469(6) 76(4)
Table 1
C(11) 6420(9) 3430(8) 10.600(6) 93(4)
Crystal data and structure refinement
C(12) 6758(8) 3822(6) 9913(5) 55(3)
Empirical formula [Rb(C36H61O11)] 2H2O C(13) 7519(8) 4544(7) 10.071(6) 56(3)
Formula weight 791.35 C(14) 8527(9) 4370(7) 10.437(6) 80(4)
Temperature (K) 293(2) C(15) 9260(8) 5029(7) 10.240(6) 65(3)
Wavelength (Å) 0.71073 C(16) 8766(8) 5406(6) 9625(6) 53(3)
Crystal system, space group Orthorhombic, P212121 C(17) 9447(8) 5412(6) 8980(5) 51(3)
Unit cell dimensions (Å) C(18) 10.435(9) 6009(7) 8909(6) 73(3)
a 12.6153(7) C(19) 10.985(8) 5603(6) 8318(6) 72(3)
b 16.4841(10) C(20) 10.842(8) 4686(6) 8482(5) 54(3)
c 19.4840(12) C(21) 10.751(9) 4138(6) 7837(5) 60(3)
Volume (Å3) 4051.7(4) C(22) 11.798(8) 4110(6) 7404(5) 52(3)
Z 4 C(23) 11.598(7) 3668(5) 6759(5) 50(3)
Calculated density 1.297 g cm 3 C(24) 10.617(8) 3960(5) 6375(5) 49(3)
Absorption coefficient 1.281 mm 1 C(25) 9655(8) 3959(5) 6847(5) 48(3)
F(00 0) 1688 C(26) 8671(9) 4370(6) 6577(7) 73(4)
Crystal size 0.225 0.200 0.125 mm C(27) 10.406(9) 3545(6) 5698(5) 89(4)
h Range for data collection 2.29 29.99° C(28) 12.742(7) 3736(8) 7783(6) 96(4)
Limiting indices 176h611, 226k621, 276l626 C(29) 11.107(9) 6121(8) 9525(6) 93(4)
Reflections collected/unique 41.620/10.795 Rint = 0.2616 C(30) 8331(10) 6266(7) 9758(6) 93(4)
Completeness to h = 29.86 93.3% C(31) 7599(10) 6623(7) 9255(9) 145(7)
Refinement method Full-matrix least-squares on F2 C(32) 5842(8) 4122(7) 9470(7) 104(5)
Data/restraints/parameters 10.795/10/466 C(33) 6978(9) 468(6) 8929(6) 81(4)
Goodness-of-fit on F2 0.813 C(34) 4657(7) 2394(5) 8360(6) 63(3)
Final R indices [I >2r (I)] R1 = 0.0765, wR2 = 0.1496 C(35) 4813(10) 143(7) 7440(8) 113(5)
R indices (all data) R1 = 0.3489, wR2 = 0.2250 C(36) 5736(9) 1774(8) 6230(6) 108(5)
Absolute structure parameter 0.039(14) O(1W) 7639(6) 6108(5) 7407(4) 88(3)
Largest diff. peak and hole 0.445 and  0.527 e Å 3 O(2W) 10.424(6) 1876(5) 7807(4) 89(3)
226 A. Huczyński et al. / Journal of Molecular Structure 888 (2008) 224 229
2.2. X-ray measurements tion and refinement are given in Table 1, the fractional
atomic coordinates are listed in Table 2. The crystallo-
The crystals selected for the single-crystal X-ray diffrac- graphic-information-file (CIF) has been deposited with
tion measurement had the form of colourless parallelepi- the Cambridge Crystallographic Database Centre as a sup-
peds with well-developed faces. They were stable in plementary Publication No. CCDC 667503.
normal conditions and the X-ray diffraction measurements
were carried out on a Kuma KM-4 CCD diffractometer at 2.3. FT-IR measurements
room temperature. The structure has been solved by direct
methods [26] and refined by full-matrix least squares [27]. The FT-IR spectrum of the crystals of monensin A
One H-atom at O(4) was located from difference Fourier rubidium salt dihydrate was recorded in the mid infrared
maps and refined with isotropic temperature factors, all region in KBr pallets (2.0/200.0 mg) at 300 K. The spec-
the other H-atoms were calculated from molecular geome- trum was taken with an IFS 113v FT-IR spectrophotome-
try (C H 0.98 0.96 and O H 0.82 Å) and their Uiso were ter (Bruker, Karlsruhe) equipped with a DTGS detector;
related to the thermal vibrations of their carriers. The resolution 2 cm 1, NSS = 64. The Happ Genzel apodiza-
details of the cell data, data collection and structure solu- tion function was used.
Fig. 1. (a) A perspective view of MON Rb 2H2O complex in the crystal structure. For clarity the hydrogen bonds have been indicated by thin dashed
lines; (b) The structure of MON Rb complex calculated by the PM5 method.
A. Huczyński et al. / Journal of Molecular Structure 888 (2008) 224 229 227
Table 3
2.4. PM5 calculations
Selected bond lengths (Å) and angles (°) determined from X-ray studies
and calculated by the PM5 semiempirical method
PM5 semiempirical calculations were performed using
Parameters X-ray PM5
the Cache WorkSystem Pro Version 6.1.1 program. In all
Rb(1) O(4) 2.807(8) 2.85
cases full geometry optimization of MON Rb was carried
Rb(1) O(6) 2.788(7) 2.82
out without any symmetry constraints [24,25,30 33].
Rb(1) O(7) 2.874(7) 2.89
Rb(1) O(8) 2.847(6) 2.87
Rb(1) O(9) 2.901(6) 2.92
3. Results and discussion
Rb(1) O(11) 2.875(8) 2.86
O(1) C(1) 1.237(11) 1.25
O(2) C(1) 1.219(12) 1.24
3.1. X-ray crystallography
O(6) Rb(1) O(7) 60.6(2) 58.4
O(4) Rb(1) O(7) 113.41(19) 109.9
As expected, the rubidium cation is complexed by the
O(8) Rb(1) O(7) 59.30(18) 57.4
O(6) Rb(1) O(11) 148.2(2) 150.3
monensin A anion, as shown in Fig. 1. The cation is sixfold
O(4) Rb(1) O(11) 133.5(2) 130.1
coordinated, by four tetrahydrofurane oxygen atoms and
O(8) Rb(1) O(11) 104.43(19) 107.5
two hydroxyl oxygen atoms, the Rb O distances range
O(7) Rb(1) O(11) 112.96(19) 115.3
O(6) Rb(1) O(9) 155.1(2) 149.1 between 2.788 and 2.901 Å (Table 3). The anion, with the
O(4) Rb(1) O(9) 105.4(2) 109.0
carboxyl group deprotonated is present in the pseudo-ring
O(8) Rb(1) O(9) 59.4(2) 58.7
conformation. The selected torsion angles describing the
O(7) Rb(1) O(9) 108.9(2) 111.9
monensin A anion conformation are listed in Table 4.
O(11) Rb(1) O(9) 55.5(2) 59.1
O(6) Rb(1) O(7) 60.6(2) 57.5 The terminal carboxylate and two hydroxyl groups clasp
O(4) Rb(1) O(7) 113.41(19) 109.7
the long molecule into a pseudo-ring around the Rb+ cat-
O(8) Rb(1) O(7) 59.30(18) 57.4
ion. Each of the hydroxyl groups forms a hydrogen bond,
O(10)H to O(1) and O(11)H to O(2). The dimensions of the
hydrogen bonds are listed in Table 5: they are strong
Table 4
Selected torsion angles (°) determined from X-ray studies and calculated by the PM5 semiempirical method
Parameters MON Rb 2H2Oa MON Rbb MON Li:CH3CNc MON Na:CH3CNd MON Nae
O(2) C(1) C(2) C(3) 56.5(14) 55.4 63.2(3) 58.4(2) 58.6(4)
C(1) C(2) C(3) C(4) 62.5(12) 64.5 61.3(3) 61.5(2) 62.5(4)
C(2) C(3) C(4) C(5) 84.5(10) 79.5 80.4(3) 82.3(2) 85.9(4)
C(3) C(4) C(5) O(5) 178.0(7) 176.4 176.9(2) 176.7(1) 177.2(3)
O(5) C(5) C(6) C(7) 56.0(11) 58.1 56.7(2) 58.4(2) 59.1(4)
O(6) C(12) C(13) O(7) 62.3(10) 59.7 62.5(2) 64.0(2) 60.7(4)
O(7) C(16) C(17) O(8) 70.2(10) 69.2 66.9(2) 69.2(2) 70.6(4)
O(8) C(20) C(21) O(9) 60.2(10) 58.6 41.0(2) 50.1(2) 50.4(4)
O(9) C(25) C(26) O(11) 47.5(11) 51.5 51.6(2) 55.5(2) 60.4(4)
O(7) C(16) C(30) C(31) 48.7(15) 56.0 48.4(3) 48.1(3) 52.7(7)
a
X-rays  this work.
b
PM5  this work.
c
X-rays  Ref. [25].
d
X-rays  Ref. [24].
e
X-rays  Ref. [23].
Table 5
Dimensions of the hydrogen bonds (Å,°) determined from X-ray studies and calculated by the PM5 semiempirical method
D H A d(D H) d(H A) d(D A) <(DHA)
X-ray O(11) H(11O) O(1) 0.82 1.72 2.52(1) 166
O(10) H(10O) O(2) 0.82 1.83 2.60(1) 156
O(4) H(4O) O(2W) 1.16(8) 1.90(1) 2.74(1) 125(6)
O(1W) H(1W1) O(11) 1.00(1) 1.90(1) 2.77(1) 143(2)
O(2W) H(2W1) O(10) 1.11(2) 2.00(4) 2.83(1) 129(3)
O(2W) H(2W2) O(1W)i 1.04(2) 1.86(4) 2.78(1) 146(4)
O(1W) H(1W2) O(3)ii 1.00(1) 2.48(9) 2.99(1) 112(7)
PM5 O(11) H(11O) O(1) 0.99 1.67 2.58 154
O(10) H(10O) O(2) 1.03 1.83 2.71 143
The applied symmetry codes are: (i) 2 x, 0.5+y, 1.5 z; (ii) 1 x, 0.5+y, 1.5 z.
228 A. Huczyński et al. / Journal of Molecular Structure 888 (2008) 224 229
hydrogen bonds. It can be noted, that the hydrogen bond 100
to the hydroxyl group O(11)H, involved in coordinating
Rb+, is slightly shorter than that to O(10)H, not interacting
1920
with Rb+. The hydroxyl group O(10)H acts as an H-accep-
50
tor for the hydrogen bond to water molecule H2O(2W),
3277
2700
which in turn is hydrogen bonded to the hydroxyl group
3513
O(4)H of the same anion. Similarly, the hydroxyl group
3380
O(11)H acts as an H-acceptor for the H-bond to the water
1564
0
molecule H2O(1W). There is also a hydrogen bond O(2W)
4000 3500 3000 2500 2000 1500 1000 500
H(2W2) O(1W)0 linking the water molecules of two sym-
Wavenumber [cm-1]
metry independent units (Table 5). These dimensions of
Fig. 3. FT-IR spectrum of MON Rb in KBr pallet.
the water H-bonds are comparable to those in H2O ice Ih
[28]. The water molecule H2O(1W) forms also a longer
hydrogen bond to the ether oxygen O(3)00of a neighbouring
spond to the asymmetrical and symmetrical stretching
anion. Thus each of the water molecules H2O(1W) and
vibrations of the hydrogen bonded water molecules. As a
H2O(2W) forms three hydrogen bonds (Table 5). Apart
shoulder on the second band at 3277 cm 1 an absorption
from the water-mediated hydrogen bonds, there are no
strong intermolecular interactions between the Rb+ of the protonic vibrations of hydrogen bonded O(4)H
group is also observed. The band at ca. 2700 cm 1 corre-
[Monensin A] units, as illustrated in Fig. 2.
sponds to the proton vibrations in a medium short intra-
molecular hydrogen bond formed between the O(11)H
group and the O(1) oxygen atom of the carboxylate group.
3.2. FT-IR studies
This assignment is consistent with our previous studies of
Fig. 3 presents the FT-IR spectrum of monensin A monensin A lithium and sodium salts. The spectral features
rubidium salt dihydrate in KBr pellet. This spectrum shows of this band indicate that the hydrogen bond can be
described by a potential curve with an unsymmetrical dou-
two broadened bands with maxima at 3513 cm 1 and
3380 cm 1 as well as one broad band with a maximum at ble minimum, in which the proton slightly fluctuates as
ca. 2700 cm 1. The positions of the first two bands corre- indicated by the Fermi resonance band arising at ca.
Fig. 2. Autostereogram [29] of the arrangement of MON Rb 2H2O complex in the crystal lattice, projected along [0 10] crystal direction.
Transmittance [%]
A. Huczyński et al. / Journal of Molecular Structure 888 (2008) 224 229 229
[4] T.S. Edrington, T.R. Callaway, P.D. Varey, Y.S. Jung, K.M.
1920 cm 1 and a very low intense continuous absorption in
Bischoff, R.O. Elder, R.C. Anderson, E. Kutter, A.D. Brabban,
the whole region.
D.J. Nisbet, J. App. Microbiol. 94 (2003) 207.
The deprotonation of the carboxylic group within the
[5] T. Martinek, F.G. Riddell, C. Wilson, C.T. Weller, J. Chem. Soc.,
structure of the crystal is indicated in the IR spectrum
Perkin Trans. 2 (2000) 35.
by the band at 1564 cm 1 assigned to the m(COO )
[6] M. Rochdi, A.M. Delort, J. Guyot, M. Sancelme, S. Gibot, J.G.
Gourcy, G. Dauphin, C. Gumila, H. Vial, G. Jeminet, J. Med. Chem.
vibrations.
19 (1996) 588.
[7] A. Iacoangeli, G. Melucci-Vigo, G. Risuleo, Biochimie 82 (2000) 35.
3.3. PM5 calculations
[8] W.H. Park, J.G. Seol, E.S. Kim, W.K. Kang, Y.H. Im, C.W. Jung,
B.K. Kim, Y.Y. Lee, Br. J. Hemat. 119 (2002) 400.
On the basis of the spectroscopic as well as X-ray
[9] W.H. Park, E.S. Kim, C.W. Jung, B.K. Kim, Y.Y. Lee, Int. J. Oncol.
22 (2003) 377.
results, the structure of the complex of the monensin rubid-
[10] M.S. Shaik, A. Chatterjee, M. Singh, J. Pharm. Pharmacol. 56 (2004)
ium salt was calculated by the PM5 semiempirical method.
899.
This calculated structure is compared with that determined
[11] B.C. Pressman, Antibiotics and their Complexes, Marcel Dekker Inc.,
by the X-ray diffraction in Fig. 1b. The interatomic dis-
New York, 1985, p. 1.
tances between the oxygen atoms of the monensin molecule
[12] V.C. Langston, F. Galey, R. Lovell, W.B. Buck, Vet. Med. 80 (1985)
75 84.
and the rubidium cation as well as the selected bond
[13] Y. Miyazaki, M. Shibuya, M. Sugasawa, O. Kawaguchi, C. Hirose, J.
lengths and angles are given in Table 3. and the selected
Nagatsu, S. Esumi, J. Antibiot. 27 (1974) 814.
torsion angles are given in Table 4. The parameters of
[14] B.C. Granzin, G.McL. Dryden, Anim. Feed Sci. Tech. 120 (2005) 116.
the hydrogen bonds existing within the structure are col-
[15] V. Rada, M. Marounek, Ann. Zeotech. 45 (1996) 283.
lected in Table 5. The calculated interatomic distances
[16] B. Kohler, H. Karch, H. Schmidt, Microbiology 146 (2000) 1085.
[17] W.L. Duax, G.D. Smith, P.D. Strong, J. Am. Chem. Soc. 102 (1980)
between the oxygen atoms of the monensin molecule and
6725.
the rubidium cation, the torsion angles as well as parame-
[18] D.L. Ward, K.T. Wei, J.C. Hoogerheide, A.I. Popov, Acta Crystal-
ters of the hydrogen bonds are in a relatively good agree-
logr. B 34 (1978) 110.
ment with the X-ray data demonstrating that the PM5
[19] M. Pinkerton, L.K. Steinrauf, J. Mol. Biol. 49 (1970) 533.
semiempirical method is reliable for visualization of the
[20] W. Pangborn, W. Duax, D. Langs, J. Am. Chem. Soc. 109 (1987)
2163.
structures also in the solid state. The differences between
[21] P.Y. Barrans, M. Alleume, G. Jeminet, Acta Crystallogr. B 38 (1982)
the calculated and experimentally determined structures
1144.
are probably related to the neglect of the presence of two
[22] D.M. Walba, M. Hermsmeier, R.C. Haltiwanger, J.H. Noordik, J.
water molecules within the crystal structure in the calcula-
Org. Chem. 51 (1986) 245.
tions. The two water molecules bind the species into a mac- [23] F.A. Almeida Paz, P.J. Gates, S. Fowler, A. Gallimore, B. Harvey,
N.P. Lopes, C.B.W. Stark, J. Staunton, J. Klinowskia, J.B. Spencera,
rostructure in the crystal, which cannot be taken into
Acta Crystallogr. E 59 (2003) 1050.
account in the calculations.
[24] A. Huczyński, M. Ratajczak-Sitarz, A. Katrusiak, B. Brzezinski, J.
Mol. Struct. 832 (2007) 84.
Acknowledgement
[25] A. Huczyński, M. Ratajczak-Sitarz, A. Katrusiak, B. Brzezinski, J.
Mol. Struct. 871 (2007) 92.
[26] G. Sheldrick, SHELXS-97. Program for Crystal Structure Solution,
Adam Huczyński wishes to thank the Foundation for
University of Goettingen, 1997.
Polish Science for fellowship.
[27] G. Sheldrick, SHELXL-97. Program for Crystal Structure Refine-
ment, University of Goettingen, 1997.
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