New N-acylamino acids and derivatives from renewable fatty acids: Gelation of hydrocarbons and thermal properties

Article abstract of DOI:10.1016/j.tetlet.2012.03.015

This work reports the synthesis of new fatty N-acylamino acids and N-acylamino esters from the C16:0, C18:0, C18:1, and C18:1(OH) fatty acid families and demonstrates the activity of these compounds as organogel agents. Compounds were heated and dissolved in various solvents (n-hexane, toluene, and gasoline). Only saturated C16:0 and C18:0 derived from alanine were able to form gels in toluene, and saturated C16:0 derived from phenylalanine showed gelation in n-hexane. This is the first evidence that fatty N-acylamino esters and N-acylamino acid derivatives of l-serine and fatty acids C16:0, C18:0, and C18:1 are able to form gels with hexane. This observation confirms the importance of the hydroxyl group in the segment derivative of l-serine in forming good gels.

Full text of DOI:10.1016/j.tetlet.2012.03.015

Tetrahedron Letters 53 (2012) 2454–2460
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
New N-acylamino acids and derivatives from renewable fatty acids: gelation
of hydrocarbons and thermal properties
Rodrigo da Costa Duarte a, Renata Ongaratto a, Luciana Almeida Piovesan a, Vânia Rodrigues de Lima a,
Valdir Soldi b, Aloir Antônio Merlo c, Marcelo G. Montes D’Oca a,
⇑
a Laboratório Kolbe de Síntese Orgânica, Escola de Química e Alimentos, Universidade Federal do Rio Grande, Av. Itália Km 08 s/n, 96203-000 Rio Grande-RS, Brazil
b Grupo de Estudo em Materiais Poliméricos, Universidade Federal de Santa Catarina, Trindade 88040-900, Florianópolis-SC, Brazil
c Laboratório de Síntese Orgânica e Materiais Inteligentes, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, 91501-970 Porto Alegre-RS, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
This work reports the synthesis of new fatty N-acylamino acids and N-acylamino esters from the C16:0,
C18:0, C18:1, and C18:1(OH) fatty acid families and demonstrates the activity of these compounds as
organogel agents. Compounds were heated and dissolved in various solvents (n-hexane, toluene, and gas-
oline). Only saturated C16:0 and C18:0 derived from alanine were able to form gels in toluene, and sat-
urated C16:0 derived from phenylalanine showed gelation in n-hexane. This is the first evidence that
Received 2 December 2011
Revised 1 March 2012
Accepted 5 March 2012
Available online 10 March 2012
fatty N-acylamino esters and N-acylamino acid derivatives of
C18:1 are able to form gels with hexane. This observation confirms the importance of the hydroxyl group
in the segment derivative of -serine in forming good gels.
L-serine and fatty acids C16:0, C18:0, and
Keywords:
Low-molecular-weight gelators
Fatty amino acids
L
Ó 2012 Elsevier Ltd. All rights reserved.
L-Serine
Ricinoleic acid
Introduction
in the pharmacological field as carriers of drugs.10–13 A subcutane-
ous implant form of the organogelator N-stearyl alanine methyl es-
ter showed advantages over the known polymeric matrix for
delivering drugs, as it was easy to prepare and non-toxic.11
There are a few reports of fatty N-acylamino acid synthesis and
its various applications in the literature, but usually the main focus
is on the physical characteristics and the mechanisms of forming
gels from non-complex mixtures of hydrocarbons. However, there
is little information in the literature on variation in the hydropho-
bic portion, because most of the studies report the use of saturated
chains.
Here we describe the synthesis of new fatty N-acylamino ester
derivatives 1–5a–d and fatty N-acylamino acids 6–10a–d from
fatty acids with saturated and unsaturated chains derived from
vegetable oils (common substrates in the chemical industry) and
commercial amino acids. The gelation properties of 40 compounds
were evaluated using n-hexane, toluene, and gasoline (a complex
mixture of hydrocarbons) as organic solvents. We used the ther-
moanalytical technique of differential scanning calorimetry (DSC)
and infrared (IR) spectroscopy to characterize the structural factors
that affected the gels. Then we studied the structure–activity rela-
tionship of the new compounds in the gelation of organic solvents.
Fatty N-acylamino acid, fatty acid amides, and fatty N-acyla-
mino esters are noted for their ability to gelatinize organic
solvents1–3 and their role in important biological activities
(Fig. 1).4,5 Moreover, these gelators can selectively form gels in
water,6 and because they are biodegradable they are biocompatible
with biological systems.7 These compounds belong to a class of
materials called low-molecular-weight gelators, which include
derivatives of long-chain hydrocarbons, salts of organic com-
pounds, steroids, metallic complexes, and derivatives of fatty ureas
and amino acids.8
N-acylamino acids and their fatty derivatives harden organic
solvents at the supramolecular level, resulting in a network of
three-dimensional structures. The role of these compounds in the
gelation of organic solvents originates from intermolecular interac-
tions between gelator molecules such as dipole–dipole, Van der
Waals, p–p
-stacking, hydrogen bond interaction, and so on.9 How-
ever, researchers still do not understand how and why an organo-
gelator gelatinizes one particular solvent over another.
Low-molecular-weight gelators have attracted interest from
technicians as well as academics because they are present in many
commercial products (e.g., cosmetics, food, medicine) and are
involved in tissue engineering and effluent treatment.8,9
N-Acylamino acid derivatives and fatty derivatives are also used
Results and discussion
The structural design of the new fatty amino acids and esters
was based on the natural availability of the amino acids and fatty
⇑
Corresponding author. Tel.: +55 53 32336964; fax: +55 53 32336961.
E-mail address: dqmdoca@furg.br (G. M. D’Oca).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.03.015

R. C. Duarte et al. / Tetrahedron Letters 53 (2012) 2454–2460
2455
O
N
H
CO2Me
O
FattyN-acylamino ester
N
H
CO2H
O
FattyN-acylamino acid
R
N
H
OH
Fatty acid amides
Figure 1. Fatty acid organogels.
O
R1
O
R1
2
1-10a
1-10b
, R =
(
(
)
14
R2
N
H
CO2Me
R2
N
H
CO2H
2
, R =
)
)
16
1a-d (Gli) R1=H
6a-d (Gli) R1=H
2
1-10c
, R =
(
(
( )
7
1
7a-d (Ala) R1=CH3
7
2a-d
(Ala) R =CH3
(Val) R =CH(CH3)2
1
1
OH
3a-d
8a-d
9a-d
(Val) R =CH(CH3)2
(Fen) R =CH2C6H5
10a-d
4a-d (Fen) R1=CH2C6H5
5a-d (Ser) R1=CH2OH
1
2
1-10d
, R =
)
( )
5
1
7
(Ser) R =CH2OH
Figure 2. Fatty N-acylamino esters 1–5a–d and N-acylamino acids 6–10a–d.
acids, considering their biodegradability and their ability to solidify
organic solvents. We considered a large number of derivatives to
understand the mechanism of gelation as well as to determine
the structural motifs required by these systems to exhibit efficient
gelation behavior. In order to analyze the role of the lipophilic
chain in determining gelation properties, we synthesized fatty N-
acylamino acid and ester derivatives of the molecules with satu-
rated, unsaturated, and hydroxylated chains. Structural variation
was also considered for the amino acid moiety.
Fatty N-acylamino esters 1–5a–d were synthesized by reacting
fatty acids C16:0, 18:0, 18:1, and 18:1(OH) with amino esters, tri-
ethylamine, a catalytic amount of (dimethylamino)pyridine, and
dicyclohexyl carbodiimide in CH2Cl2 and stirring at room temper-
ature for 12 h (Fig. 2).4 Compounds 1–5a–d were purified using
column chromatography on a silica gel (with 7:3 n-hexane:ethyl
acetate as the eluent).
Almost all unsaturated and saturated fatty N-acylamino esters
obtained were soluble in the solvents studied.
The N-acylamino acids with unsaturated chains derived from
oleic and ricinoleic acids, C18:1 and C18:1(OH), respectively, were
soluble in all solvents, except for 6c, d derived from glycine, which
were insoluble in hexane (Table 1). In addition, unsaturated N-
Table 1
Gelation ability of fatty N-acylamino esters 1a–d and N-acylamino acids 6a–d derived
from glycine in various hydrocarbons at 25 °C
Compound Structurea
Physical characteristicsb
Toluene Hexane Gasoline
O
1a
S
S
S
S
S
S
S
S
S
N
CO2Me
CO2Me
14
H
O
As shown in Figure 2, fatty N-acylamino acids 6–10a–d were
obtained by basic hydrolysis. For this reaction, the respective fatty
N-acylamino esters 1–5a–d were dissolved in a 1:1 mixture of
methanol:THF.8 Then an aqueous solution of sodium hydroxide
was added. The mixture was stirred for 4 h at room temperature.
Compounds 6–10a–d were purified using column chromatography
with ethyl acetate as the eluent.
1b
N
16
7
H
O
N
1c
CO2Me
CO2Me
7
H
O
All of the compounds were analyzed by 1H NMR, 13C NMR and
IR spectral data and were consistent with their given structures.
(
)
N
7
H
1d
S
S
S
(
)
5
OH
Formation of physical gel
O
6a
6b
6c
S
S
S
I
I
I
P
P
S
Compounds 1–10a–d were tested for their ability to gelatinize
organic solvents. A total of 10 mg of each compound was heated
in 1 mL of a given solvent (n-hexane, toluene, or gasoline). Then
the vial containing the mixture was cooled to 25 °C. After 10 min
the vial was inverted to enable us to observe the gelation effect.3,8
Tables 1–5 show the gelation ability of fatty N-acylamino esters 1–
5a–d and N-acylamino acids 6–10a–d in various hydrocarbons at
25 °C.
N
H
CO2H
CO2H
14
O
N
H
16
O
N
CO2H
CO2H
7
7
H
O
Structure–activity relationship
(
)
N
H
7
6d
S
I
S
(
)
5
Tables 1–5 show that the ability to gelatinize organic solvents
was highly influenced by the nature of the long chain. In addition,
the substituent present in the amino acid moiety of some of the
derivatives was an important factor (Fig. 3).
OH
a
A gelator of 1 wt % was used for all tests.
S: soluble, I: insoluble, P: immediate precipitation.
b

2456
R. C. Duarte et al. / Tetrahedron Letters 53 (2012) 2454–2460
Table 2
Table 3
Gelation ability of fatty N-acylamino esters 2a–d and N-acylamino acids 7a–d derived
from alanine in various hydrocarbons at 25 °C
Gelation ability of fatty N-acylamino esters 3a–d and N-acylamino acids 8a–d derived
from valine in various hydrocarbons at 25 °C
Compound Structurea
Physical characteristicsb
Compound Structurea
Physical characteristicsb
Toluene Hexane Gasoline
Toluene Hexane Gasoline
O
O
3a8
2a
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
N
CO2Me
CO2Me
N
CO2Me
CO2Me
14
H
O
14
O
H
2b7,10
3b
3c
N
16
H
N
H
16
O
N
O
N
2c
CO2Me
CO2Me
7
7
H
CO2Me
CO2Me
7
7
H
O
O
(
)
N
H
7
2d
S
S
S
(
)
N
(
)
7
3d
S
S
S
H
5
OH
(
)
5
OH
O
7a8
7b1,8
7c
G
G
S
P
P
S
S
S
S
O
N
H
CO2H
CO2H
8a8
8b
8c
S
S
S
A
A
S
P
P
S
14
O
N
H
CO2H
CO2H
14
O
N
H
16
N
H
O
N
16
CO2H
CO2H
O
N
7
7
H
CO2H
CO2H
O
7
7
H
(
)
N
O
7
7d
H
S
S
S
(
)
5
(
)
N
H
7
8d
S
S
S
OH
(
)
5
OH
a
A gelator of 1 wt % was used for all tests.
G: good gel, S: soluble, P: immediate precipitation.
b
a
A gelator of 1 wt % was used for all tests.
S: soluble, P: immediate precipitation, A: aggregation leading to gradual
b
precipitation.
acylamino acid 10c derived from serine showed gelation in n-hex-
ane, and 10d was insoluble in hexane, toluene, and gasoline
(Table 5).
Most of the saturated fatty N-acylamino acids were soluble in
toluene, but only saturated 7a, b derived from alanine were able
to form gels in this aromatic hydrocarbon (Table 2).1,8 In addition,
saturated fatty N-acylamino acid 9a derived from phenylalanine
showed gelation in n-hexane, but its respective homologous 9b
formed precipitate, unlike previous reports in the literature
(Table 4).8
derivative of the amino acid. This is implied by the fact that fatty
N-acylamino esters 5a, b, derivatives of L
-serine14 (Table 5), were
able to form gels with hexane. In this case, the formation of the
gel can be attributed to the presence of a hydroxyl group in the
amino ester; the lipophilic saturated chain of the palmitic and stea-
ric acids, C16:0 and C18:0, respectively; and the polarity of the
solvent.
The experiments also demonstrated that the presence of differ-
ent substituents near the carboxyl group plays a crucial role in the
formation of gel. The bulkier isopropyl group, as in derivatives of L-
Moreover, unsaturated fatty N-acylamino acid 10c, a derivative
of serine and oleic acid also formed gel in hexane.13 This observa-
tion confirms the importance of the hydroxyl group in the segment
derivative of the amino acid in forming good gels (Table 5).
However, saturated fatty N-acylamino acids 10a, b derived from
serine were insoluble in hexane, unlike reports in the literature
indicating that 10b forms partial gels in hexane.13 According to lit-
valine 3a–d and 8a–d, prevented the formation of the effective
intermolecular hydrogen bonds that are crucial for the formation
of bilayers that make up the framework of hydrocarbon gelation
(Table 3). However, the presence of methyl and benzyl groups near
the carboxyl group was important for forming good gels (e.g., see
7a, b in Table 2 and 9a in Table 4). This behavior has been observed
among N-dodecanoyl derivatives of amino acids.3
These observations of gelation underscore the importance of the
presence of a stereogenic center in the segment derivative of the
amino acid. This is implied by the fact that derivatives of glycine
1a–d and 6a–d (Table 1) do not possess chirality, as none of these
derivatives were able to gel in the solvents studied.
erature the L-serine amphiphiles have also been used to produce
solid gels in CHCl3, CH2Cl2 and also in CCl4.15
Therefore, the balance between gelator structure, intermolecu-
lar interaction, and gelation properties are very important for
forming good gels.
Figure 4a and b show gels obtained from hexane with 5a and
from toluene with 7a, respectively.
In addition, the results demonstrate that the presence of a polar
stereogenic center is crucial for the gelation of hydrocarbons. This
polar stereogenic center establishes strong intermolecular interac-
tions during the self-assembling of the gelators in the segment
IR spectroscopy
IR spectroscopy was carried out to understand the role of amino
acid residue and fatty chains of 5a, b, and 7a in gelating non-polar

R. C. Duarte et al. / Tetrahedron Letters 53 (2012) 2454–2460
2457
Table 4
Table 5
Gelation ability of fatty N-acylamino esters 4a–d and N-acylamino acids 9a–d derived
from phenylalanine in various hydrocarbons at 25 °C
Gelation ability of fatty N-acylamino esters 5a–d and N-acylamino acids 10a–d
derived from serine in various hydrocarbons at 25 °C
Compound Structurea
Physical characteristicsb
Compound Structurea
Physical characteristicsb
Toluene Hexane Gasoline
Toluene Hexane Gasoline
Ph
OH
O
O
4a8
S
S
S
S
S
S
S
S
S
5a14
S
S
S
G
G
S
A
S
S
N
CO2Me
Ph
N
CO2Me
OH
14
H
14
O
H
O
4b8
4c
5b14
N
H
CO2Me
N
CO2Me
16
16
7
H
Ph
OH
O
N
O
N
5c
CO2Me
Ph
CO2Me
OH
7
7
7
H
H
O
O
(
)
( )
N
CO2Me
N
H
CO2Me
7
7
4d
S
S
S
5d
S
S
S
H
(
)
5
OH
( )
5
OH
Ph
OH
O
O
9a8
9b8
9c
S
S
S
G
P
S
A
P
S
10a14
S
S
S
I
P
P
S
N
H
CO2H
Ph
N
H
CO2H
OH
14
O
14
O
10b13,14
I
N
H
CO2H
N
H
CO2H
16
16
OH
Ph
O
N
O
N
10c13
G
CO2H
OH
CO2H
Ph
7
7
7
7
H
H
O
O
(
)
N
H
CO2H
(
)
N
H
CO2H
7
7
10d
I
I
I
9d
S
S
S
(
)
5
OH
(
)
5
OH
a
a
A gelator of 1 wt % was used for all tests.
G: good gel, S: soluble, I: insoluble, P: immediate precipitation, A: aggregation
A gelator of 1 wt % was used for all tests.
G: good gel, S: soluble, P: immediate precipitation, A: aggregation leading to
b
b
leading to gradual precipitation.
gradual precipitation.
interaction. The ester carbonyl band showed at 1730 and
1732 cmÀ1, respectively, and the amide carbonyl band showed at
1656 cmÀ1 for two structures. The IR spectra of N-acylamino esters
5a, b solubilized in CHCl3 revealed that the profile underwent great
changes. Characteristic amide N–H bands showed up weaker at
3622 cmÀ1, a region of higher energy. The O–H band of the side
organic solvents. Samples of 5a, b gel produced in hexane and 7a
gel produced in toluene were dried under a vacuum, and the
resulting solids were examined by IR spectroscopy as KBr pellets.
The same compounds had previously been dissolved in 1 mL chlo-
roform (in conditions in which they were not able to form gel) to
observe the changes in absorption bands related to intermolecular
interactions (Figs. 5 and 6).
group of methyl serinate also appeared weaker at 3433 cmÀ1
,
showing the weakening of the intermolecular hydrogen bonds.
This proves the importance of intermolecular interactions of
hydrogen bonds in the amino acid residue for the auto-organiza-
tion of three-dimensional structures of these molecules (Fig. 7).
In IR spectra of gels derived from fatty N-acylamino esters 5a, b,
amide N–H asymmetric stretching appeared at 3518 and
3520 cmÀ1 and the O–H of amino acid residue of methyl serinate
at 3338 and 3340 cmÀ1, respectively, showing a strong molecular
OH
OH
OH
O
O
O
N
H
5a
CO2Me
CO2H
N
H
5b
CO2Me
CO2H
N
H
CO2H
14
16
7
7
10c
Ph
CO2H
O
O
O
N
H
N
H
N
H
16
14
14
7a
7b
9a
Figure 3. Molecular structures of fatty N-acyl organogels 5a, b, 9a, 7a, b, and 10c.

2458
R. C. Duarte et al. / Tetrahedron Letters 53 (2012) 2454–2460
boxyl acid C@O at 1645 cmÀ1. Moreover, an analysis of the IR spec-
tra of compound 7a in CHCl3 showed different values of bands and
signals: the amide N–H band showed a weak stretch at 3433 cmÀ1
,
and the C@O stretch was absorbed at 1755 cmÀ1. This behavior en-
sured the energy increase necessary for bond vibrations and could
signal a decrease in intermolecular interactions due to the absence
of carboxyl acid dimmers, as has been described for other fatty N-
acylamino acid derivatives of L
-alanine.1,8
Figure 4. Gels obtained from various compositions: (a) hexane with 10 mg 5a, (b)
toluene with 10 mg 7a.
Thermotropic behavior of the organogels
Properties of the gels were investigated using DSC. The transi-
tion temperatures and enthalpics of compounds 5a, b, 9a, 7a, b,
and 10c are summarized in Table 6 and Figure 8. The gel-to-sol
IR spectra of the derivative gel of compound 7a showed a strong
interaction between the groups able to form hydrogen bonds,
namely strong stretches of amide N–H at 3311 cmÀ1 and of car-
Figure 5. Infrared spectra I: (a) compound 5a in CHCl3, (b) compound 5a in gel form.
Figure 6. Infrared spectra II: (c) compound 5b in CHCl3, (d) compound 5b in gel form.

R. C. Duarte et al. / Tetrahedron Letters 53 (2012) 2454–2460
2459
H
H
N
H
O
O
O
O
O
O
O
O
O
O
H
H
O
N
H
H
H
N
H
O
O
O
O
O
H
H
N
H
H
H
N
H
O
O
O
O
O
O
O
O
H
N
H
H
Figure 7. Physical gelation of hexane by fatty N-acylamino ester 5a derivatives of L-serine.
Table 6
Thermotropic behavior of the organogels as measured by differential scanning calorimetry
Entry
Solvent
Hexane
Compound
Heating Tg–s (°C)a
Freezing Ts–g (°C)b
D
Hg–s (mcal)c
D
Hs–g (mcal)d
1
2
3
4
5a
5b
9a
7a
59.82
65.49
54.37
57.10
53.86
58.37
36.30
40.52
8.37
7.35
20.79
0.36
18.46
1.83
8.66
Toluene
9.35
a
b
c
Tg–s: gel-to-sol temperature.
Ts–g: sol-to-gel temperature.
D
D
H
H
g–s: gel-to-sol enthalpy variation.
s–g: sol-to-gel enthalpy variation.
d
Figure 8. Gel-to-sol (Tg–s) and sol-to-gel (Ts–g) variation for gels of compounds 5a, b, 9a, 7a, b, and 10c.
(Tg–s) melting temperatures of compounds 5a, b, 9a, 7a, b, and 10c
were higher than the freezing temperatures for the sol-to-gel (Ts–g
The large peaks of Tg–s transition observed in the DSC curves for
heating for compounds 5a (Fig. 9) and 5b may be associated with
the higher energy required to phase change, according to values
)
transition (Fig. 8, Table 6). Furthermore, in the DSC thermograms
the peaks for Tg–s transitions were less pronounced than those
for Ts–g. Figure 9 shows the DSC thermogram for compound 5b.
For organogels 5a, b, the Tg–s and Ts–g temperatures increased
with an increase in the fatty chain, and the same characteristics
obtained for
DH
g–s. For gelator 5b the enthalpy in hexane was
greater than for 5a because of an increase in carbon atoms in the
lipophilic chain. The increase in carbon atoms favored the self-
assembling of the gelator and the apolar solvent hexane. This result
confirms that lipophilic characteristics play an important function
in the stabilization of the gel.
were observed for the gel-to-sol enthalpy variation (
DH
g–s) and
sol-to-gel enthalpy variation (
D
H
s–g; Table 6, entries 1 and 2).

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R. C. Duarte et al. / Tetrahedron Letters 53 (2012) 2454–2460
Figure 9. Thermogram for the gel-derived hexane of N-octadecenoyl methyl serinate (5b). DSC, differential scanning calorimetry.
The transition temperatures of organogels of hexane and N-
Aperfeiçoamento de Pessoal de Nível Superior (CAPES/PROCAD),
and Conselho Nacional de Desenvolvimento Científico e Tecnológ-
ico (CNPq) for financial support. Fellowships from CAPES (to R.C.D.
and L.A.P.) and CNPq (to R.O.) are also acknowledged.
acylamino acid derivatives of serine 10c were not detected because
of the lower thermal stability of the material formed (due to the cis
configuration of the double bond) and the nature of the head polar
group, which was not appropriate for the gelation of apolar
solvents.
Supplementary data
Conclusion
Supplementary data (detailed experimental procedures, charac-
terization data, 1H NMR spectra, and DSC thermograms of com-
pounds 5a, b, 7a, b, and 9a) associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.
2012.03.015.
This study reports the synthesis of new fatty N-acylamino acids
and N-acylamino esters from renewable fatty acids with saturated
and unsaturated chains and amino acids. The gelation properties of
40 compounds were evaluated using n-hexane, toluene, and gaso-
line (a complex mixture of hydrocarbons) as organic solvents. The
formation of gel was attributed to the presence of a hydroxyl group
in the amino acid serine, and the lipophilic saturated chain of the
palmitic and stearic acids, C16:0 and C18:0, respectively. In addi-
tion, the fatty N-acylamino acid derivative of serine and oleic acid,
although it had an unsaturated side chain, formed gel in hexane.
These observations confirm the importance of the hydroxyl group
in the segment derivative of the amino acid in forming good gels.
Finally, the results reveal that these derived gels can be synthe-
sized very easily from naturally occurring sources (e.g., fatty acids
and amino acid—common substrates in the chemical industry),
making these low-molecular-weight gelators excellent materials
for use in various applications.
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The authors would like to thank the Ministério da Ciência e
Tecnologia/Research and Projects Financing, Coordenação de