On the complexation of the sodium cation with beauvericin: Experimental and theoretical study

Article abstract of DOI:10.1007/s00706-011-0499-1

From extraction experiments in the two-phase water/nitrobenzene system and γ-activity measurements, the stability constant of the beauvericin·Na⁺ complex species dissolved in nitrobenzene saturated with water was determined. By using quantum me

Full text of DOI:10.1007/s00706-011-0499-1

Monatsh Chem (2011) 142:779–782
DOI 10.1007/s00706-011-0499-1
ORIGINAL PAPER
On the complexation of the sodium cation with beauvericin:
experimental and theoretical study
•
Petr Toman Emanuel Makrlık Petr Vanura
•
´
ˇ
Received: 11 March 2011 / Accepted: 30 March 2011 / Published online: 21 April 2011
Ó Springer-Verlag 2011
Abstract From extraction experiments in the two-phase
water/nitrobenzene system and c-activity measurements,
the stability constant of the beauvericinꢀNa? complex
species dissolved in nitrobenzene saturated with water was
determined. By using quantum mechanical density func-
tional level of theory (DFT) calculations, the most probable
structure of this complex species was derived.
mycobacteria, and it is also capable of inducing pro-
grammed cell death in mammals [1]. Chemically,
beauvericin is a cyclic hexadepsipeptide with alternating
methyl-phenylalanyl and hydroxy-isovaleryl residues. Its
ion-complexing capability allows beauvericin to transport
alkaline earth metal and alkali metal ions across cell
membranes [4].
Recently, experimental evidences for a valinomycin–
proton complex [5] and some unusual divalent metal cation
complexes of valinomycin [6] have been reported in detail.
Furthermore, the theoretical structures of the valinomycin
complexes with Li?, K?, NH4?, Mg2?, Ca2?, and Zn2?
have also been solved [7–12].
Keywords Antibiotics ꢀ Macrocycles ꢀ Complexation ꢀ
Stability constant ꢀ DFT calculations ꢀ Complex structure
Introduction
In the current work, the stability constant of the beau-
vericin complex with the sodium cation (1ꢀNa?) is
determined in the organic phase of the water/nitrobenzene
extraction system. In this context it should be noted that the
sodium cation was chosen for this study because it is a
typical representative of the ‘‘light’’ univalent cations, and
therefore the Na? ion was chosen for this study. Moreover,
quantum mechanical density functional theory (DFT) cal-
culations were used to predict the most probable structure
of the 1ꢀNa? cationic complex species.
Beauvericin (1; Scheme 1) is a depsipeptide with antibiotic
and insecticidal effects belonging to the enniatin family. It
was isolated from the fungus Beauveria bassiana, but it is
also produced by other fungi, including several Fusarium
species [1]; it may therefore occur in grain (such as corn,
wheat, and barley) contaminated with these fungi [1–3].
Beauvericin is active against Gram-positive bacteria and
P. Toman
Institute of Macromolecular Chemistry,
Academy of Sciences of the Czech Republic,
Prague, Czech Republic
Results and discussion
Extraction experiments
´
E. Makrlık (&)
Faculty of Applied Sciences,
Previous results [13–16] have shown that the two-phase
water–NaA (A- = picrate)/nitrobenzene extraction system
can be described by the following equilibrium (1) with the
corresponding extraction constant Kex(Na?, A-); aq and nb
denote the presence of the species in the aqueous and
nitrobenzene phases:
University of West Bohemia, Pilsen, Czech Republic
e-mail: makrlik@centrum.cz
ˇ
P. Vanura
Department of Analytical Chemistry,
Institute of Chemical Technology,
Prague, Czech Republic
123

780
P. Toman et al.
[Na?]aq, combined with Eq. (4), we get the final expression
in,aq
for the above-mentioned extraction constant (Eq. 5); C
NaA
is the initial concentration of NaA in the aqueous phase and
Ci1n,nb denotes the initial concentration of 1 in the organic
phase of the system under consideration.
ꢀꢁ
ꢂ
DNa
in;aq
NaA
Kexð1 ꢀ Naþ; AꢁÞ ¼ DN2 a
C1in;nb
ꢁ
C
ð5Þ
1 þ DNa
In this study, from the extraction experiments and c-
activity measurements (see ‘‘Experimental’’), and by using
Eq. (5), the following value of the constant Kex (1ꢀNa?,
A-) was determined: log Kex (1ꢀNa?, A-) = -0.8 0.1.
Furthermore, with respect to Refs. [17–21], for the sta-
bility constant of the 1ꢀNa? complex in water-saturated
nitrobenzene, denoted by bnb (1ꢀNa?), corresponding to the
equilibrium 1ðnbÞ þ NaþðnbÞ ꢁ 1 ꢀ NaþðnbÞ, as well as for
the extraction constants Kex(Na?, A-) and Kex(1ꢀNa?, A-)
defined above, one can formulate Eq. (6):
Scheme 1
NaþðaqÞ þ AꢁðaqÞ ꢀ NaþðnbÞ þ AꢁðnbÞ;
KexðNaþ; AꢁÞ
The constant log Kex(Na?, A-) can be written as shown
in Eq. (2), where KNi aþ and KAi ꢁ are the individual
extraction constants for Na? and A- ions in the water/
nitrobenzene system [13–16].
log bnbð1 ꢀ NaþÞ ¼ log Kexð1 ꢀ Naþ; AꢁÞ
ð1Þ
ꢁ log KexðNaþ; AꢁÞ
ð6Þ
Using the constants log Kex(Na?, A-) and log
Kex(1ꢀNa?, A-) defined above, and applying Eq. (6), we
obtain the stability constant of the considered cationic
complex species 1ꢀNa? in nitrobenzene saturated with
water at 25 °C as log bnb (1ꢀNa?) = 4.4 0.1. At this
point it should be noted that the stability constant of the
complex species NaL?, where L is valinomycin, in water-
saturated nitrobenzene is log bnb (NaL?) = 6.7 [19]. This
means that in the mentioned nitrobenzene medium, the
stability of the 1ꢀNa? complex under study is substantially
lower than that of the cationic complex species NaL?
(L = valinomycin).
log KexðNaþ; AꢁÞ ¼ log KNi aþ þ log KAi ꢁ
Knowing log KNi aþ ¼ ꢁ6:0 [14] and log KAi ꢁ ¼ 0:8
(A- = picrate) [14], the extraction constant Kex(Na?,
A-) was simply calculated from Eq. (2) as log Kex(Na?,
A-) = -5.2.
ð2Þ
Previous results [17–21] indicated that the two-phase
water–NaA (A- = picrate)/nitrobenzene–1(beauvericin)
extraction system, chosen for determination of the stability
constant of the complex 1ꢀNa? in nitrobenzene saturated
with water (see ‘‘Experimental’’), can be characterized by
the main equilibrium (3) to which the equilibrium extrac-
tion constant (4) corresponds.
Quantum mechanical calculations
The quantum mechanical calculations were carried out at
the density functional level of theory (DFT, B3LYP func-
tional) [22, 23] using the Gaussian 03 suite of programs
[24]. The 6-31G(d) basis set was used and the optimiza-
tions were unconstrained. In order to increase the
numerical accuracy and to reduce oscillations during the
molecular geometry optimization, two-electron integrals
and their derivatives were calculated by using the pruned
(99,590) integration grid, having 99 radial shells and 590
angular points per shell, which was requested by means of
the Gaussian 03 keyword ‘‘Int = UltraFine.’’
NaþðaqÞ þ AꢁðaqÞ þ 1 ðnbÞ ꢀ 1 ꢀ NaþðnbÞ þ AꢁðnbÞ;
Kexð1 ꢀ Naþ; AꢁÞ
ð3Þ
ð4Þ
½1 ꢀ Naþꢂnb½Aꢁꢂnb
½Naþꢂaq½Aꢁꢂaq½1ꢂnb
Kexð1 ꢀ Naþ; AꢁÞ ¼
It is necessary to emphasize that 1 is a considerably
hydrophobic ligand, practically present in the nitrobenzene
phase only, where this ligand forms—with Na?—the
relatively stable 1ꢀNa? complex species.
Although a possible influence of a polar solvent on the
detailed structures of 1 and its complex with Na? could be
imagined, our quantum mechanical calculations in similar
cases, performed in an analogous way, showed very good
agreement of experiment with theory [25–31].
Taking into account the conditions of electroneutrality in
the organic and aqueous phases of the system under study,
the mass balances of 1 and NaA at equal volumes of the
nitrobenzene and aqueous phases, as well as the measured
equilibrium distribution ratio of sodium, DNa = [1ꢀNa?]nb/
123

On the complexation of the sodium cation with beauvericin
781
Fig. 2 Two projections of the DFT-optimized structure of the 1ꢀNa?
Fig. 1 Two projections of the DFT-optimized structure of free ligand
1 [B3LYP/6-31G(d)]
complex [B3LYP/6-31G(d)]
Conclusions
In the model calculations, we optimized the molecular
geometries of the parent beauvericin ligand 1 and its
complex with the sodium cation. The optimized structure
of the free ligand 1 with C3 symmetry is illustrated in
Fig. 1.
In conclusion, we have demonstrated that a complementary
theoretical and experimental approach can provide impor-
tant information on the beauvericin ligand (1)
complexation with the sodium cation. From the experi-
mental investigation of the resulting complex 1ꢀNa? in the
two-phase water/nitrobenzene system, the strength of the
considered 1ꢀNa? cationic complex species in nitrobenzene
saturated with water was characterized quantitatively by
the stability constant, log bnb (1ꢀNa?) = 4.4 0.1 (for a
temperature of 25 °C). By using the theoretical quantum
mechanical DFT calculations, the structural details of the
1ꢀNa? complex, such as position of the Na? ion in the
parent beauvericin ligand 1 as well as the interatomic
distances within the complex species under study, were
obtained.
Figure 2 shows the structure obtained by the full DFT
optimization of the 1ꢀNa? complex, which also has C3
symmetry, together with the lengths of the corresponding
˚
˚
bonds (in A; 1 A = 0.1 nm). As follows from this figure,
the complexation with the Na? cation changes the overall
shape of the parent ligand 1 only slightly. In the resulting
1ꢀNa? cationic complex species, which is most energeti-
cally favored, the ‘‘central’’ cation Na? is bound by nine
bond interactions to nine oxygen atoms (2.23, 3.80, 3.95,
˚
2.23, 3.80, 3.95, 2.23, 3.80, and 3.95 A) of the parent
beauvericin ligand 1.
Finally, the interaction energy, E(int), of the 1ꢀNa?
complex (calculated as the difference between electronic
energies of the complex 1ꢀNa? and isolated 1 and Na?
species: E(int) = E(1ꢀNa?) - E(1) - E(Na?)) was found
to be -419.4 kJ mol-1, which confirms the formation of
the considered cationic complex 1ꢀNa?.
Experimental
Beauvericin (1; Scheme 1) was purchased from Aldrich.
The other chemicals used (Lachema, Brno, Czech
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P. Toman et al.
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8. Makrlık E, Dybal J, Vanura P (2009) Monatsh Chem 140:1289
Republic) were of reagent grade purity. A solution of
sodium picrate (NaA) in water was prepared by dissolving
a stoichiometric amount of picric acid in an aqueous
solution of NaOH. The radionuclide 22Na? (DuPont, Bel-
gium) was of standard radiochemical purity.
´
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The extraction experiments were carried out in 10-cm3
glass test tubes with polyethylene stoppers: 2 cm3 of an
aqueous solution of NaA (concentration in the range from
1 9 10-3 to 5 9 10-3 M) and microamounts of 22Na?
were added to 2 cm3 of a nitrobenzene solution of 1,
the concentration of which varied from 2 9 10-3 to
1 9 10-2 M (in all experiments, the initial concentration
of 1 in nitrobenzene, Ci1n,nb, was always higher than the
initial concentration of NaA in water, CiNna,aAq). The test tubes
filled with the solutions were shaken for 2 h at 25 1 °C,
using a laboratory shaker. Then the phases were separated
by centrifugation. Afterwards, 1-cm3 samples were taken
from each phase and their c-activities were measured using
a well-type NaI(Tl) scintillation detector connected to a c-
analyzer NK 350 (Gamma, Budapest, Hungary).
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Acknowledgments This work was supported by the Czech Ministry
of Education, Youth and Sports (projects MSM 4977751303 and
MSM 6046137307) and by the Czech Science Foundation (project
P205/10/2280). The computer time at the MetaCentrum (project
MSM 6383917201), as well as at the Institute of Physics (computer
Luna/Apollo), Academy of Sciences of the Czech Republic, is
gratefully acknowledged.
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