Antimicrobial properties of 4-Aryl-3-(2-methyl-furan-3-yl) δ2-1,2,4-triazoline-5-thiones

Article abstract of DOI:10.1080/10426500802705297

Four 4-aryl-3-(2-methyl-furan-3-yl)- δ²-1,2,4-triazole-5- thiones were synthesized by intramolecular cyclization of 4-aryl-1-[(2-methyl- furan-3-yl)carbonyl]thiosemicarbazides in alkaline medium. The antimicrobial activity of the synthesized tr

Full text of DOI:10.1080/10426500802705297

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Antimicrobial Properties of
4-Aryl-3-(2-methyl-furan-3-
yl)-Δ2-1,2,4-triazoline-5-
thiones
Agata Siwek a , Monika Wujec a , Joanna Stefańska b
& Piotr Paneth c
a Department of Organic Chemistry, Faculty of
Pharmacy , Medical University , Lublin, Poland
b Department of Pharmaceutical Microbiology ,
Medical University , Warszawa, Poland
c Institute of Applied Radiation Chemistry, Technical
University of Lodz , Lodz, Poland
Published online: 18 Nov 2009.
To cite this article: Agata Siwek , Monika Wujec , Joanna Stefańska & Piotr
Paneth (2009) Antimicrobial Properties of 4-Aryl-3-(2-methyl-furan-3-yl)-Δ2-1,2,4-
triazoline-5-thiones, Phosphorus, Sulfur, and Silicon and the Related Elements,
184:12, 3149-3159, DOI: 10.1080/10426500802705297
To link to this article: http://dx.doi.org/10.1080/10426500802705297
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Phosphorus, Sulfur, and Silicon, 184:3149–3159, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802705297
Antimicrobial Properties of 4-Aryl-3-(2-methyl-furan-3-yl)-
ꢀ2-1,2,4-triazoline-5-thiones
1
1
2
´
Agata Siwek, Monika Wujec, Joanna Stefanska,
and Piotr Paneth3
1Department of Organic Chemistry, Faculty of Pharmacy, Medical
University, Lublin, Poland
2Department of Pharmaceutical Microbiology, Medical University,
Warszawa, Poland
3Institute of Applied Radiation Chemistry, Technical University of
Lodz, Lodz, Poland
Four
4-aryl-3-(2-methyl-furan-3-yl)-ꢀ2-1,2,4-triazole-5-thiones
were
syn-
thesized by intramolecular cyclization of 4-aryl-1-[(2-methyl-furan-3-
yl)carbonyl]thiosemicarbazides in alkaline medium. The antimicrobial activity of
the synthesized triazoles was evaluated. Semiempirical calculations of geometries,
energies, and QSAR parameters have been determined in the hope of gaining
insight into different biological activities of closely related isomers. New RM1
parameterization has been shown to perform very well for this class of compounds.
Keywords ꢀ2-1,2,4-triazoline-5-thione; antimicrobial activity; QSAR
INTRODUCTION
The biological activities of 1,2,4-triazoles have been extensively stud-
ied. In particular, their antimicrobial and central nervous system
(CNS) activities have been extensively documented.1 Although lim-
ited, there are also examples of the antibacterial, antinociceptive,
anti-inflammatory properties of furan derivatives.2 In a previous ar-
ticle,3 we presented the synthesis of compounds containing the fu-
ran moiety at the position 3 of 4-substituted-1,2,4-triazoline-5-thione
and examined their activity on the CNS in mice. Pharmacological
results have shown strong antinociceptive properties of tested tria-
zoles. Moreover, none of the compounds was found to show neurotoxic
Received 8 July 2008; accepted 10 December 2008.
Address correspondence to Agata Siwek, Department of Organic Chemistry, Fac-
ulty of Pharmacy, Medical University, 6 Staszica Str., 20-081, Lublin, Poland. E-mail:
agata.siwek@am.lublin.pl
3149

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A. Siwek et al.
SCHEME 1 Synthesis of the 4-aryl-1-[(2-methyl-furan-3-yl)carbonyl]
thiosemicarbazides 1a–1d and 4-aryl-3-(2-methyl-furan-3-yl)-ꢀ2-1,2,4-
triazoline-5-thiones 2a–2d.
activity. We have also hypothesized that 3-(2-methyl-furan-3-yl)-4-
substituted-ꢀ2-1,2,4-triazoline-5-thiones might show antibacterial and
antifungal activity. To test this hypothesis we have synthesized four
new analogues, 2a–2d, presented in Scheme 1. Unfortunately, ex-
cept for 2a, the minimal inhibitory concentration (MIC) values of
these compounds against tested microorganisms were higher than
500 µg/mL.
In order to understand why the tested triazoles 2b–2d are inac-
tive, in particular 2b, while 2a shows activity against Gram-positive
bacteria, the structural and physicochemical properties of 4-aryl-3-
(2-methyl-furan-3-yl)-ꢀ2-1,2,4-triazoline-5-thiones were compared to
pharmacokinetic properties of Fluconazole, which was used as standard
antifungal powder, and 3-[(5-methyl-2-benzoxazolinone-3-yl)methyl]-4-
phenyl-1H-1,2,4-triazole-5(4H)-thione, which is structurally similar to
the tested compounds and exhibits moderate inhibitory activities at
128 µg/mL (see Figure 1) against Candida crusei, Candida albicans,
and Candida parapsilosis.

4-Aryl-3-(2-methyl-furan-3-yl)-ꢀ2-1,2,4-triazoline-5-thiones
3151
FIGURE 1 Structures of 3-[(5-methyl-2-benzoxazolinone-3-yl)methyl]-4-
phenyl-1H-1,2,4-triazole-5(4H)-thione (a) and Fluconazole (b).
RESULTS AND DISCUSSION
Chemistry
The synthesis of the title compounds 2a–2d is illustrated in Scheme
1. The preparation of the intermediate thiosemicarbazides 1a–1d
was carried out by the reaction of 2-methyl-furan-3-carboxylic acid
hydrazide with aryl isothiocyanates. The 4-aryl-1-[(2-methyl-furan-
3-yl)carbonyl]thiosemicarbazides 1a–1d, when subjected to a reac-
tion with 2% NaOH, underwent intramolecular cyclization to furnish
the corresponding 4-aryl-3-(2-methyl-furan-3-yl)-ꢀ2-1,2,4-triazole-5-
thiones 2a–2d.
The structures of all compounds were confirmed by the results of ele-
mental analysis, as well as by IR and 1H-NMR. The 1H NMR spectra of
2a–2d show a sharp singlet at 13.98–14.09 ppm typical for the proton
linked to N1, indicating the presence of the thione tautomer. Domina-
tion of the thione form was observed also in the IR spectra of 2a–2d,
which showed absorption in the region 3400–3482 cm−1 attributed to
NH and at 1323–1332 cm−1 attributed to C=S, in agreement with our
earlier calculations for both tautomers.4 The spectral data of 1a–1d
and 2a, 2c, and 2d are presented in Table I.
The pharmacokinetic properties of 4-aryl-3-(2-methyl-furan-3-
yl)-ꢀ2-1,2,4-triazole-5-thiones 2a–2d were determined and com-
pared with structural and physicochemical properties of Flu-
conazole and 3-[(5-methyl-2-benzoxazolinone-3-yl)methyl]-4-phenyl-
1H-1,2,4-triazole-5(4H)-thione. All triazoles 2a–2d, Fluconazole, and
the reference triazole obey Lipinski’s “rule of five” and complemen-
tary criteria as shown in Table II. Except for lipophilicity, no major
differences between the pharmacokinetic and QSAR properties of Flu-
conazole and 2a–2d were observed.

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A. Siwek et al.
TABLE I Spectral Data of Compounds 1a–1d and 2a, 2c, and 2d
Compound
No.
Spectral data
1a
IR (KBr): 3348, 3156, 1605, 732, 2965, 1411, 1682, 1364, 1180, 804;
1H-NMR (DMSO): 2.28 s, 3H (CH3); 2.53 s, 3H (CH3); 6.92 d, 1H, J =
1.9 (CH); 7.11–7.32 m, 4H (4×CH); 7.55–7.56 d, 1H, J = 2.0 (CH); 9.53
s, 1H (NH); 9.69 s, 1H (NH); 10.03 s, 1H (NH).
1b
1c
IR (KBr): 3382, 3236, 3154, 1603, 1500, 737, 2963, 1461, 1404, 1666,
1355, 1185, 750; 1H-NMR (DMSO): 2.27 s, 3H (CH3); 2.53 s, 3H (CH3),
6.91 d, 1H, J = 1.9 (CH); 7.13–7.21 m, 4H (4×CH); 7.54 d, 1H, J = 1.9
(CH); 9.50 s, 2H (2×NH); 10.05 s, 1H (NH).
IR (KBr): 3353, 3232, 2961, 1602, 828, 2834, 1406, 1666, 1365, 1180,
795; 1H-NMR (DMSO): 2.53 s, 3H (CH3); 3.74 s, 3H (CH3); 6.87–6.90
dd, 2H, J = 2.0, J = 7.0 (2×CH); 6.92 d, 1H, J = 1.9 (CH); 7.27–7.30 d,
2H, J = 8.7 (2×CH); 7.55–7.56 d, 1H, J = 2.0 (CH); 9.50 s, 1H (NH);
9.64 s, 1H (NH); 10.02 s, 1H (NH).
1d
2a
2c
IR (KBr): 3347, 3162, 1601, 826, 2966, 1483, 1398, 1679, 1357; 1181,
796; 1H-NMR (DMSO): 2.53 s, 3H (CH3); 6.80–6.81 d, 1H, J = 1.7
(CH); 7.49 d, 1H, J = 1.8 (CH); 7.53–7.67 m, 4H (4×CH); 9.22 s, 1H
(NH); 9.27 s, 1H (NH); 10.06 s, 1H (NH).
IR (KBr): 3409, 3058, 1557, 1515, 1480, 820, 2919, 1412, 1384, 1230,
1607, 1329; 1H-NMR (DMSO): 2.38 s, 3H (CH3); 2.39 s, 3H (CH3);
5.63–5.64 d, 1H, J = 2.0 (CH); 7.21–7.34 m, 4H (4×CH); 7.43–7.44 d,
1H, J = 2.0 (CH); 13.99 s, 1H (NH).
IR (KBr): 3400, 3088, 1587, 1514, 833, 3041, 1230, 2928, 2836, 1466,
1454, 1442, 1386, 1610, 1332; 1H-NMR (DMSO): 2.40 s, 3H (CH3);
3.82 s, 3H (CH3); 5.65–5.66 d, 1H, J = 1.9 (CH); 7.03–7.08 m, 2H
(2×CH); 7.25–7.30 m, 2H (2×CH); 7.44–7.45 d, 1H, J = 2.0 (CH); 13.98
s, 1H (NH).
2d
IR (KBr): 3410, 3090, 1562, 825, 3048, 1233, 2930, 1488, 1383, 1606,
1327; 1H-NMR (DMSO) δ: 2.38 s, 3H (CH3); 5.72 d, 1H, J = 2.0 (CH);
7.17–7.21 m, 2H (2×CH), 7.46–7.47 d, 1H, J = 2.0 (CH); 7.87–7.92 m,
2H (2×CH); 14.06 s, 1H (NH).
Microbiology
The antimicrobial activities of the synthesized triazoles 2a–2d were
tested against a series of Gram-positive bacteria, Gram-negative bac-
teria, and yeasts. At first we performed tests using the disc-diffusion
method. Compounds that showed activity in these tests were then ex-
amined using the broth dilution method in order to determine their
MICs. Microbial susceptibility testing was performed according to the
CLSI guidelines.5
The results revealed that compounds 2b–2d were inactive against all
tested bacteria and yeasts. Only triazole 2a exhibited activity against

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A. Siwek et al.
TABLE III Antimicrobial Activity of 2a Expressed as the Growth In-
hibition Zone [giz, mm] and Minimal Inhibitory Concentration (MIC,
µg/mL)
2a
Ciprofloxacin
Fluconazole
Tested strain
giz
MIC
giz
MIC
giz
MIC
S. aureus NCTC 4163
S. aureus ATCC 25923
S. aureus ATCC 6538
S. aureus ATCC 29213
S. epidermidis ATCC 12228
B. subtilis ATCC 6633
B. cereus ATCC 11778
E. hirae ATCC 10541
M. luteus ATCC 9341
M. luteus ATCC 10240
E. coli ATCC 10538
E. coli ATCC 25922
E. coli NCTC 8196
P. vulgaris NCTC 4635
P. aeruginosa ATCC 15442
P. aeruginosa NCTC 6749
P. aeruginosa ATCC 27853
B. bronchiseptica ATCC 4617
C. albicans ATCC 10231
C. albicans ATCC 90028
C. parapsilosis ATCC 22019
11
12
—
—
—
12
—
—
11
11
200
100
200
200
200
100
100
> 400
50
26
26
28
22
30
40
20
—
22
24
34
35
35
36
25
26
23
31
0.500
0.500
0.500
0.500
0.500
< 0.125
1.000
4.000
4.000
2.000
< 0.125
< 0.125
< 0.125
< 0.125
0.500
0.500
1.000
1.000
nt∗∗
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
100
na∗
na
na
na
na
na
na
na
na
na
na
nt
nt
nt
22
32
22
1.000
1.000
2.000
∗na – no activity in disc diffusion test- denotes lack of the growth inhibition zone.
∗∗nt—not tested.
Ciprofloxacin (5 µg per disc); Fluconazole (25 µg per disc).
Gram-positive bacteria, especially against M. luteus ATCC 9341 (MIC
50 µg/mL), as illustrated in Table III.
Computational Methods
Geometries of Fluconazole, the reference triazole, and compounds
2a–2d were fully optimized at the semiempirical level using new RM1
parameterization.6 We have shown recently (Wujec, Siwek, and Paneth,
unpublished results) that this method yields correct relative energies
of thiol/thione tautomers and geometries in which bond lengths and
valence angles are in excellent agreement with DTF results. Observed
deviation in dihedral angles does not introduce significant contribution
to the energy. This finding enabled us to use this much faster theory

4-Aryl-3-(2-methyl-furan-3-yl)-ꢀ2-1,2,4-triazoline-5-thiones
3155
FIGURE 2 RM1 optimized structure of the compound 2a.
level instead of DFT calculations. We have shown that for all tria-
zoles studied, the thione tautomer is more stable by about 8–9 kcal/mol
(see Table II). The optimal conformation of the triazole molecules is
obtained for furan and triazole rings lying in the same plane and
phenyl ring being perpendicular to this plane as illustrated in Fig-
ure 2 on the example of compound 2a. Most of the QSAR proper-
ties are quite similar for all studied compounds, and their analysis
does not provide any indication as to why they exhibit such different
bioactivity.
In summary, four new 4-aryl-3-(2-methyl-furan-3-yl)-ꢀ2-1,2,4-
triazole-5-thiones have been investigated as antimicrobial agents.
Among them only compound 2a was found to have antimicrobial activ-
ity against Gram-positive bacteria, especially against M. luteus ATCC

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A. Siwek et al.
9341. Minute structural differences between 2a and 2b, which re-
sult in significant difference of pharmacological activity, cannot be
easily explained. It is probable that the structural characterizations
are more important for this kind of activity. Studies with analogues
of the title compounds aimed at understanding these differences are
underway.
EXPERIMENTAL
Chemistry
Melting points were determined in a Fischer-Johns block and are un-
corrected. IR spectra (ν, cm−1) were recorded in KBr using a Specord
1
IR-75 spectrophotometer. H-NMR spectra (δ, ppm) were recorded on
a Bruker Avance 300 in DMSO-d6 with TMS as internal standard. All
chemicals and reagents used were purchased from Lancaster.
4-Aryl-1-[(2-methyl-furan-3-yl)carbonyl]thiosemicarbazides 1a–1d
and their 1,2,4-triazole-thione analogs 2a–2d were prepared accord-
ing to the procedure reported previously.3
The characterization data of 1a–1d and 2a, 2c, and 2d are presented
in Table IV. Compound 2b is known (CAS:438231–54-0).
Microbiology
The assessment of the antimicrobial action of the synthesized com-
pounds was performed using the disc-diffusion method and the MIC.
MICs were defined as the lowest concentration of the compounds
that inhibited visible growth of microorganisms after 18 h incuba-
tion at 35◦C. Microorganisms used in this study were as follows:
Gram-positive bacteria: four strains of Staphylococcus aureus (NCTC
4163, ATCC 25923, ATCC 6538, ATCC 2921), Staphylococcus epider-
midis ATCC 12228, Bacillus subtilis ATCC 6633, Bacillus cereus ATCC
11778, Enterococcus hirae ATCC 10541, Micrococcus luteus ATCC 9341,
Micrococcus luteus ATCC 10240 and Gram-negative rods: three strains
of Escherichia coli (ATCC 10538, ATCC 25922, NCTC 8196), Proteus
vulgaris NCTC 4635, three strains of Pseudomonas aeruginosa (ATCC
15442, NCTC 6749, ATCC 27863), and Bordetella bronchiseptica ATCC
4617. For testing antifungal activities of the compounds, the following
reference strains were tested: Candida albicans ATCC 10231, Candida
albicans ATCC 90028, and Candida parapsilosis ATCC 22019. Antimi-
crobial activity was tested under standard conditions using Mueller-
Hinton II agar medium (Becton Dickinson) for bacteria and RPMI

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A. Siwek et al.
agar medium with 2% glucose (Sigma) for yeasts, according to CLSI
guidelines.
The compounds were dissolved in DMSO. Then, for the disc diffu-
sion assay, sterile filter paper discs (9 mm diameter, Whatman No. 3
chromatography paper) were soaked with solutions of tested compound
to load 400 µg per disc. Dry discs were placed on the surface of ap-
propriate agar medium. Diameter of the growth inhibition zone was
read after 18 h of incubation at 35◦C. For determination of MICs,
concentrations of tested compounds were in the range from 6.25 to
400 µg/mL in a solid medium. The final inoculum of all microorganisms
was 104 cfu/ml (colony forming units per mL), except the inoculum for
E. hirae ATCC 10541, which was 105 cfu/mL. The results (MICs) were
read after 18 h of incubation at 35◦C. Ciprofloxacin and Fluconazole
were used as standard antimicrobial powder.
Computational Methods
All calculations were carried out using new semiempirical parameter-
ization RM1 as implemented in HyperChem.7 Molecular geometries
were fully optimized in the gas phase. Vibrational analysis has been
carried out to confirm identity of the stationary points (3n-6 real vi-
brations). The QSAR module of the HyperChem and Molinspiration8
programs were used to the calculate parameters collected in Table II.
REFERENCES
¨
[1] (a) N. S. Gu¨nay, G. C¸ apan, N. Ulusoy, N. Ergenc¸, G. Otu¨k, and D. Kaya, Il Farmaco,
54, 826 (1999); (b) A. A. Ikizler, C. B. Johansson, O. Bekircan, and C. C¸ elik, Acta
Polon. Pharm.–Drug Research, 56, 283 (1999); (c) S¸. Demirayak, K. Benkli, and K.
Gu¨ven, Eur. J. Med. Chem., 35, 1073 (2000); (d) X-P. Hui, L-M. Zhang, Z-Y Zhang,
Q. Wang, and F. Wang, J. Chin. Chem. Soc., 47, 535 (2000); (e) N. N. Gulerman,
H. N. Dogan, S. Rollas, C. Johansson, and C. Celik, Farmaco, 56, 935 (2001); (f) B.
S. Holla, B. K. Sarojini, B. S. Rao, P. M. Akberali, N. S. Kumari, and V. Shetty,
Farmaco, 56, 565 (2001); (g) U. Kosikowska, A. Siwek, and M. Dobosz, Acta Polon.
Pharm.–Drug Research, 51, 460 (2004); (h) B. Tozkoparan, E. Kupeli, E. Yesilada,
S. Isik, M. Ozalp, and M. Ertan, Arzneimittelforschung, 55, 533 (2005); (i) O. A.
Al-Deeb, M. A. Al-Omar, N. R. El-Brollosy, E. E. Habib, T. M. Ibrahim, and A. A. El-
Emam, Arzneim. Forsch., 56, 40 (2006); (j) B. Shivarama Holla, B. Sooryanarayana
Rao, B. K. Sarojini, P. M. Akberali, and N. Suchetha Kumari, Eur. J. Med. Chem.,
¨
41, 657 (2006); (k) A. Gu¨rsoy, O. Ates, N. Karali, N. Cesur, and M. Kiraz, Eur.
J. Med. Chem., 31, 643 (1996); (l) Ch.-H. Chu, X.-P., Hui, Y. Zhang, Z.-Y. Zhang,
Z.-Ch. Li, and R.-A. Liao, J. Chin. Chem. Soc., 48, 121 (2001); (m) M. Wujec, M.
Pitucha, M. Dobosz, U. Kosikowska, and A. Malm, Acta Pharm., 54, 251 (2004);
(n) L. Savini, L. Chiasserini, C. Pellerano, W. Filippelli, and G. Falcone, Farmaco,
56, 939 (2001); (o) B. Tozkoparam, E. Yesilada, and M. Ertan, Bioorg. Med. Chem.,
15, 1808 (2007); (p) M. V. Kulkarni, V. D. Patil, V. N. Biradar, and S. Nanjappa,

4-Aryl-3-(2-methyl-furan-3-yl)-ꢀ2-1,2,4-triazoline-5-thiones
3159
Arch. Pharmacal. Res., 34, 435 (1981); (q) E. Palaska, G. S¸ahin, P. Kelicen, N. T.
Durlu, and G. Altinok, Il Farmaco, 57, 101 (2002); (r) L. Labanauskas, V. Kalcas,
E. Udrenaite, P. Gaidelis, A. Bruksˇtus, and V. Dauksˇas, Pharmazie, 56, 617 (2001);
(s) L. Labanauskas, E. Udrenaite, P. Gaidelis, and A. Bruksˇtus, Il Farmaco, 59,
255 (2004); (t) B. Modzelewska-Banachiewicz, J. Banachiewicz, A. Chodkowska, E.
Jagiełło-Wo´jtowicz, and L. Mazur, Eur. J. Med. Chem., 39, 873 (2004); (u) X-Y.
Sun, Y-Z. Jin, F-N. Li, G. Li, K-Y. Chai, and Z-S. Quan, Archives of Pharmacological
Research, 29, 1080 (2006); (v) W. R. Sherman, J. Org. Chem., 26, 88 (1961); (w) A.
R. Jalilian, S. Sattari, M. Bineshmarvasti, A. Shafiee, and M. Daneshtalab, Arch.
Pharm. Med. Chem., 333, 347 (2000).
[2] (a) E. B. Åkerblom and D. E. S. Campbell, Eur. J. Med. Chem., 16, 312 (1973); (b) H.
E. Paul and M. F. Paul, Exp. Chemother., 2, 322 (1964); (c) K. Hayes, J. Med. Chem.,
7, 819 (1964); (d) F. C. Meotti, D. Silva, A. R. S. dos Santos, G. Zeni, J. B. T. Rocha,
and C. W. Nogueira, Environ. Toxicol. Pharmacol., 37, 37 (2003).
[3] A. Siwek, M. Wujec, E. Jagiełło-Wo´jtowicz, A. Chodkowska, A. Kleinrok, P. Paneth,
and M. Dobosz, Cent. Eur. J. Chem., 6, 47 (2008).
[4] A. Siwek, M. Wujec, I. Wawrzycka-Gorczyca, M. Dobosz, and P. Paneth, Heteroatom
Chem., 19, 337 (2008).
[5] (a) Clinical and Laboratory Standards Institute. Performance Standards for Antimi-
crobial Disc Susceptibility Tests; Approved Standard M2-A9. Clinical and Laboratory
Standards Institute, Wayne, PA, USA, 2006; (b) Clinical and Laboratory Standards
Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That
Grow Aerobically; Approved Standard M7-A7. Clinical and Laboratory Standards
Institute, Wayne, PA, USA, 2006.
[6] G. B. Rocha, R. O. Freire, A. M. Simas, and J. J. P. Stewart, J. Comput. Chem., 27,
1101 (2006).
[7] HyperChem 8.0.3, HyperCube Inc., Gainsville, FL, USA, 2007.
[8] http://www.molinspiration.com/cgi-bin/properties.