Journal of Molecular Structure 1024 (2012) 142–145

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Journal of Molecular Structure

journal homepage: www.elsevier.com/locate/molstruc

Complexation of the lithium cation with beauvericin: Experimental and DFT study
Emanuel Makrlík a,⇑, Petr Toman b, Petr Vaňura c
a
Faculty of Environmental Sciences, Czech University of Life Sciences, Prague, Kamýcká 129, 165 21 Prague 6, Czech Republic
b
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovského Sq. 2, 162 06 Prague 6, Czech Republic
c
Department of Analytical Chemistry, Institute of Chemical Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic

h i g h l i g h t s

" Water-LiCl–nitrobenzene-beauvericin-dicarbollide system was investigated.

+
" Stability constant of the Li beauvericin complex in nitrobenzene was determined.
" Quantum mechanical DFT calculations were carried out.
+ +
" Structures of the beauvericinLi and beauvericin Li 3H2O complexes were predicted.

a r t i c l e i n f o a b s t r a c t

Article history: From extraction experiments and c-activity measurements, the extraction constant corresponding to the
Received 29 February 2012 equilibrium Li+(aq) + 1Na+(nb) ¡ 1Li+(nb) + Na+(aq) taking place in the two-phase water–nitrobenzene
Received in revised form 3 May 2012 system (1 = beauvericin; aq = aqueous phase, nb = nitrobenzene phase) was evaluated as log Kex (Li+,
Accepted 3 May 2012
1Na+) = 0.5 ± 0.1. Further, the stability constant of the 1Li+ complex in nitrobenzene saturated with
Available online 12 May 2012
water was calculated for a temperature of 25 °C as log bnb (1Li+) = 5.6 ± 0.2. By using DFT calculations,
the most probable structures of the non-hydrated 1Li+ and hydrated 1Li+3H2O complex species were
Keywords:
predicted.
Extraction
DFT
Ó 2012 Elsevier B.V. All rights reserved.
Complexation
Lithium
Beauvericin
Structure

1. Introduction
Beauvericin (abbrev. 1; see Scheme 1) is a cyclic hexadepsipep-
tide with alternating methyl-phenylalanyl and hydroxy-iso-valeryl
residues [1]. For the first time, beauvericin was isolated from the
fungus Beauveria bassiana. It was further found that the antibiotic
beauvericin was produced by many other fungi (e.g. by some
Fusarium species) [2] so that this compound, which belongs to
the enniatin family, can occur very often in grain contaminated
with these fungi [2–4]. Its ion-complexing capability allows beau-
vericin to transport alkaline earth metal and alkali metal ions
across cell membranes evidently in the same way as in the case
of other related antibiotics [5].
The dicarbollylcobaltate anion [6] and some of its halogen
derivatives are very useful reagents for the extraction of various
metal cations (especially Cs+, Sr2+, Ba2+, Eu3+ and Am3+) from aque-
ous solutions into a polar organic phase, both under laboratory
conditions for purely theoretical or analytical purposes [7–13],
and on the technological scale for the separation of some high-
activity isotopes in the reprocessing of spent nuclear fuel and
acidic radioactive waste [14,15].
In the current communication, the stability constant of the
beauvericinLi+ complex (1Li+) in nitrobenzene saturated with
water was determined. Furthermore, applying DFT calculations,
the most probable structures of the mentioned cationic complex
species were derived. At this point it is necessary to emphasize that
the main reasons for our research work were expected, very inter-
esting structures of these complex species. It is apparent that the
considered structures may be an important contribution to the
theoretical study of antibiotics as well.
2. Experimental

⇑ Corresponding author. Tel.: +420 377 632 377; fax: +420 377 634 802. Beauvericin (1; see Scheme 1) was purchased from Aldrich. Ce-
E-mail address: makrlik@centrum.cz (E. Makrlík). sium dicarbollylcobaltate (CsDCC) was synthesized by means of

0022-2860/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2012.05.009
 E. Makrlík et al. / Journal of Molecular Structure 1024 (2012) 142–145 143

the exchange extraction constant Kex (Li+, Na+) was simply calcu-
lated from Eq. (2) as log Kex (Li+, Na+) = 0.7.
Previous results [22–27] indicated that the two-phase water-
LiCl–nitrobenzene-1 (beauvericin)-NaDCC extraction system (see
Section 2), chosen for determination of the stability constant of
the complex 1Li+ in water-saturated nitrobenzene, can be charac-
terized by the main chemical equilibrium:

þ þ þ
Li ; ðaqÞ þ 1  Naþ ðnbÞ¡1  Li ðnbÞ þ Naþ ðaqÞ; K ex ðLi ; 1  Naþ Þ ð3Þ

with the respective equilibrium extraction constant Kex (Li+, 1Na+):

þ
þ ½1  Li nb ½Naþ aq
K ex ðLi ; 1  Naþ Þ ¼ þ ð4Þ
½Li aq ½1  Naþ nb

It is necessary to emphasize that 1 is a considerably hydropho-

bic ligand, practically present in the nitrobenzene phase only,
Scheme 1. Structural formula of beauvericin (abbrev. 1). where it forms – with Li+ and Na+ – the relatively stable complexes
1Li+ and 1Na+. Taking into account the conditions of electroneu-
trality in the organic and aqueous phases of the system under
the method published by Hawthorne et al. [16]. The other chemi- study, the mass balances of the univalent cations studied at equal
cals used (Lachema, Brno, Czech Republic) were of reagent grade volumes of the nitrobenzene and aqueous phases, as well as the
purity. A nitrobenzene solution of hydrogen dicarbollylcobaltate measured equilibrium distribution ratio of sodium,
(HDCC) [6] was prepared from CsDCC by the procedure described DNa = [1Na+]nb/[Na+]aq, combined with Eq. (4), we obtain the final
elsewhere [17]. The equilibration of the nitrobenzene solution of expression for Kex (Li+, 1Na+) in the form:
HDCC with stoichiometric NaOH, which was dissolved in an aque-
ous solution of NaCl (0.2 M), yielded the corresponding NaDCC þ 1 C in;nb
solution in nitrobenzene. The radionuclide 22Na+ was supplied by
K ex ðLi ; 1  Naþ Þ ¼ NaDCC
ð5Þ
DNa ð1 þ DNa ÞC in;aq  C in;nb
NaDCC
LiCl
DuPont, Belgium.
The extraction experiments were carried out in 10 mL glass
test-tubes with polyethylene stoppers: 2 mL of an aqueous solu- where C in;aq
LiCl is the initial concentration of LiCl in the aqueous phase

tion of LiCl (1  102–3  102 M) and microamounts of 22Na+ and C in;nb

were added to 2 mL of a nitrobenzene solution of 1 and NaDCC,
whose initial concentrations varied also from 1  102 to
3  102 M (in all experiments, the initial concentration of 1 in
nitrobenzene, C in;nb
1 , was equal to the initial concentration of NaD-
CC in this medium, C in;nb
NaDCC ). 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 mL
samples were taken from each phase and their c-activities were
measured using a well-type NaI(Tl) scintillation detector con-
nected to a c-analyzer NK 350 (Gamma, Budapest, Hungary).
The equilibrium distribution ratios of sodium, DNa, were deter-
mined as the ratios of the measured radioactivities of 22Na+ in the
nitrobenzene and aqueous samples.
3. Results and discussion
3.1. Extraction experiments
Regarding the results of previous papers [6,18–21], the two-
phase water-LiCl–nitrobenzene-NaDCC extraction system can be
described by the following equilibrium:
þ þ þ
Li ðaqÞ þ Naþ ðnbÞ¡Li ðnbÞ þ Naþ ðaqÞ; K ex ðLi ; Naþ Þ
NaDCC denotes the initial concentration of NaDCC in the organic
phase of the system under consideration.
In this study, from the extraction experiments and c-activity
measurements (see Experimental) by means of Eq. (5), the follow-
ing value of the constant Kex (Li+, 1Na+) was determined as log Kex
(Li+, 1Na+) = 0.5 ± 0.1 (see Table 1).
Moreover, with respect to previous results [22–27], for the
extraction constants Kex (Li+, Na+) and Kex (Li+, 1Na+) defined
above, as well as for the stability constants of the complexes
1Li+ and 1Na+ in nitrobenzene saturated with water, denoted by
bnb (1Li+) and bnb (1Na+), respectively, one gets:
þ þ
logbnb ð1  Li Þ ¼ logbnb ð1  Naþ Þ þ logK ex ðLi ; 1  Naþ Þ
þ
 logK ex ðLi ; Naþ Þ ð6Þ
+ + + +
Using the constants log Kex (Li , Na ) and log Kex (Li , 1Na ) gi-
ven above, the value log bnb (1Na+) = 4.4 ± 0.1 [28], and applying
Eq. (6), we obtain the stability constant of the 1Li+ complex in
water-saturated nitrobenzene at 25 °C as log bnb
(1Li+) = 5.6 ± 0.2. This means that in the mentioned nitrobenzene
medium, the stability of the 1Li+ complex under study is some-
what higher than that of the cationic complex species 1Na+.
ð1Þ

with the corresponding exchange extraction constant Kex (Li+, Na+); Table 1
aq and nb denote the presence of the species in the aqueous and Experimental data concerning the determination of log Kex (Li+, 1Na+) on the basis of
nitrobenzene phases, respectively. For the constant Kex (Li+, Na+) Eq. (5).
one can write [18]: C in;aq (M) C in;nb DNa log Kex (Li+, 1Na+)
LiCl NaDCC (M)
þ
logK ex ðLi ; Naþ Þ ¼ logK iLiþ  logK iNaþ ð2Þ 1.0  102 1.0  102 0.54 0.5
1.5  102 1.5  102 0.48 0.6
where K iLiþ and K iNaþ are the individual extraction constants for Li+ 2.0  102 2.0  102 0.55 0.5
2.5  102 2.5  102 0.50 0.6
and Na+, respectively, in the water–nitrobenzene system [18].
3.0  102 3.0  102 0.60 0.4
Knowing the values logK iLiþ ¼ 6:7 [18] and logK iNaþ ¼ 6:0 [18],
144 E. Makrlík et al. / Journal of Molecular Structure 1024 (2012) 142–145

3.2. DFT calculations

The theoretical calculations were carried out at the density

functional level of theory (DFT, B3LYP functional) using the Gauss-
ian 03 suite of programs [29]. The 6-31G(d) basis set was used and
the optimizations were unconstrained. In order to increase the
numerical accuracy and to reduce oscillations during the molecular
geometry optimization, two-electron integrals and their deriva-
tives 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’’.
Although a possible influence of a polar solvent on the detailed
structures of 1 and the 1Li+ complex species could be imagined,
our quantum mechanical calculations in similar cases, performed
in an analogous way, showed very good agreement of experiment
with theory [30–37].
Recently, the hydration number of the 1Li+ complex in the or-
ganic phase of the water–nitrobenzene extraction system was
determined as h(1Li+) = 3.1 ± 0.1 (P. Selucký, 2010, private com-
munication) by means of the method published elsewhere [17].
Hence, in this study, let us consider further both the ‘‘non-hy-
drated’’ state (1Li+) and the ‘‘hydrated‘‘ state (1Li+3H2O) of this
lithium complex.
In the model calculations, we optimized the molecular geome-
tries of the parent beauvericin ligand 1 and its complex species

Fig. 2. Two projections of the DFT optimized structure of the 1Li+ complex (B3LYP/
6-31G(d)): (a) side view and (b) top view. The Li+O distances: 1.93, 3.61, 3.62,
1.93, 3.61, 3.62, 1.93, 3.61, and 3.62 Å.

Fig. 1. Two projections of the DFT optimized structure of free ligand 1 (B3LYP/6-
31G(d)): (a) side view and (b) top view.
with Li+. The optimized structure of the free ligand 1 with C3 sym-
metry is illustrated in Fig. 1.
In Fig. 2, the structure obtained by the full DFT optimization of
the 1Li+ complex having also C3 symmetry is depicted, together
with the lengths of the corresponding bonds (in Å; 1 Å = 0.1 nm).
As follows from this figure, the complexation with the Li+ cation
changes the overall shape of the parent ligand 1 only slightly. In
the resulting non-hydrated 1Li+ cationic complex species, which
is most energetically favoured, the ‘‘central’’ cation Li+ is bound
by nine bond interactions to nine oxygen atoms (1.93, 3.61, 3.62,
1.93, 3.61, 3.62, 1.93, 3.61, and 3.62 Å) of the parent beauvericin li-
gand 1. The calculated binding energy of the complex 1Li+ is
515.6 kJ/mol.
Finally, the optimized structure of the hydrated 1Li+3H2O com-
plex species with C3 symmetry is presented in Fig. 3. In this com-
plex, the ‘‘central‘‘ Li+ ion is bound by three strong bonds to
three oxygen atoms of the respective water molecules (1.90,
1.90, and 1.90 Å) and besides, the 1Li+3H2O cationic complex sys-
tem is evidently stabilized by six strong hydrogen bonds OHO
(1.91, 1.88, 1.91, 1.88, 1.91, and 1.88 Å), as also illustrated in detail
in Fig. 3. From this point of view, it is necessary to emphasize that
the optimized structure of the 1Li+3H2O cationic complex species
stabilized by the mentioned hydrogen bonds is apparently much
more real than that of the non-hydrated complex 1Li+. This fact
is confirmed by the calculated binding energy of the 1Li+3H2O
species (754.6 kJ/mol), which is substantially higher than the bind-
ing energy given above corresponding to the 1Li+ complex.
 E. Makrlík et al. / Journal of Molecular Structure 1024 (2012) 142–145
Fig. 3. Two projections of the DFT optimized structure of the 1Li+3H2O complex
(B3LYP/6-31G(d)): (a) side view and (b) top view. The Li+O (of the three water
molecules) distances: 1.90, 1.90, and 1.90 Å; the hydrogen bond OHO lengths:
1.91, 1.88, 1.91, 1.88, 1.91, and 1.88 Å.
4. Conclusions
In summary, we have demonstrated that a complementary the-
oretical and experimental approach can provide important infor-
mation on the beauvericin ligand (1) complexation with the
lithium cation. From the experimental investigation of the result-
ing complex 1Li+ in the two-phase water–nitrobenzene system,
the strength of the considered 1Li+ cationic complex species in
nitrobenzene saturated with water was characterized quantita-
tively by the stability constant, log bnb (1Li+) = 5.6 ± 0.2 (for a tem-
perature of 25 °C). By using the theoretical DFT calculations, the
structural details of the non-hydrated 1Li+ and hydrated
1Li+3H2O complex species were obtained. In the non-hydrated
1Li+ cationic complex species with C3 symmetry, the ‘‘central’’ cat-
ion Li+ is bound by nine bond interactions to nine oxygen atoms of
the parent beauvericin ligand 1. On the other hand, in the hydrated
1Li+3H2O cationic complex system having also C3 symmetry,
which is apparently much more real than the non-hydrated 1Li+
complex, the ‘‘central’’ Li+ ion is bound by three strong bonds to
three oxygen atoms of the respective water molecules, and besides,
the 1Li+3H2O complex system is evidently stabilized by six hydro-
gen bonds OHO.
Acknowledgements
This work was supported by the Grant Agency of Faculty of
Environmental Sciences, Czech University of Life Sciences, Prague,
145
Project No. 42900/1312/3114 ‘‘Environmental Aspects of Sustain-
able Development of Society’’, by the Czech Ministry of Education,
Youth and Sports (Project MSM 6046137307) and by the Czech Sci-
ence Foundation (Project P 205/10/2280). The computer time at
the MetaCentrum (Project LM 2010005), as well as at the Institute
of Physics (computer Luna/Apollo), Academy of Sciences of the
Czech Republic, is gratefully acknowledged.
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.molstruc.2012.
05.009.
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