KP-19
Study on relationship between the structure and
the Mol-toxicity of p-hydroxybenzoates
Yoshimi ISHIHARA (1), Keiichi KATAOKA*(2), Hiroshi SAITO (1), Jiro TAKANO (1)
(1) Department of Chemistry, School of Science, Tokai University, 1117 Kitakaname, Hiratsuka,
Kanagawa 259-1292, JAPAN
(2) Department of Chemistry, Graduate School of Science, Tokai University, 1117 Kitakaname,
Hiratsuka, Kanagawa 259-1292, JAPAN
1. Introduction
The p-hydroxybenzoates are used as preservatives of the foods, medicine, and cosmetics [1].
However, it is said that the p-hydroxybenzoates (Fig.1) is under suspicion of having with endocrine
disrupter pseudo action [2]. Furthermore, the p-hydroxybenzoates are absorbed by the body easily,
and are harmful to the human body like allergic reactions [3, 4]. Therefore, in the present study, the
Mol-toxicity of p-hydroxybenzoates to Bacillus subtilis subsp.
Subtilis was studied to living things. Furthermore, we investigated
HO
C OR
the relationship between the structure and the Mol-toxicity of
O
p-hydroxybenzoates by using physical parameter.
Fig.1 Structure of
p-hydroxybenzoates
2. Method
As shown in Table 1, seventeen kinds of p-hydroxybenzoates are used in this present study.
Bacillus subtilis subsp. Subtilis strain NBRC3007 was grown in 10mL of a broth. A broth was
consisted of tryptone, 10g/L; yeast extract, 5g/L; NaCl, 10g/L, pH7.4. The vegetative cells of
Bacillus subtilis subsp. Subtilis cultured at 37oC for over night were diluted 1 x 104 cells in 10mL of
a broth. Each p-hydroxybenzoate was added at a final concentration of from 0.0004mM to 20mM in
10mL of a broth suspended the vegetative cells 1 x 104 cells, and incubated at 37oC for 24h. The
vegetative cells were counted by CFU method every two hours. LC100 (mol/L) of each
p-hydroxybenzoate was determined as mol concentration of each p-hydroxybenzoate when the
vegetative cells number was no change of 1 x 104 cells for 24h. That is mol concentration of each
p-hydroxybenzoate when the vegetative cells were not increased completely. The Mol-toxicity of
each p-hydroxybenzoate was calculated by the logarithm of the reciprocal number LC100 of each
p-hydroxybenzoate.
Table 1 Mol-toxicity and physical parameter of p-hydroxybenzoates
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Compounds
Mol-toxicity
Connolly Molecular Surface Area / 10-20m2
Methyl p -hydroxybenzoate
Ethyl p -hydroxybenzoate
Allyl p -hydroxybenzoate
Isopropyl p -hydroxybenzoate
n -Propyl p -hydroxybenzoate
sec -Butyl p -hydroxybenzoate
Isobutyl p -hydroxybenzoate
n -Butyl p -hydroxybenzoate
Phenyl p -hydroxybenzoate
Isopentyl p -hydroxybenzoate
Benzyl p -hydroxybenzoate
n -Amyl p -hydroxybenzoate
n -Hexyl p -hydroxybenzoate
2-Ethylhexyl p -hydroxybenzoate
n -Heptyl p -hydroxybenzoate
n -Dodecyl p -hydroxybenzoate
n -Nonyl p -hydroxybenzoate
1.917
2.257
2.458
2.523
2.633
2.966
3.112
3.247
3.331
3.620
3.746
3.841
4.092
4.880
5.012
5.532
5.945
147.871
168.111
179.073
183.077
186.886
200.122
202.674
204.019
202.643
219.224
221.316
225.989
242.674
271.801
261.812
354.308
298.500
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Furthermore, p-hydroxybenzoates (17 kinds) have been done with multiple regression analysis
using criterion variable and explanatory variable. Mol-toxicity was used for criterion variables.
Molecular Weight, logPow, HOMO Energy, LUMO Energy, HOMO-LUMO Gap, Dipole Moment,
Principal Moments of Inertia, Connolly Molecular Surface Area, and Connolly Solvent-Excluded
Volume were used for explanatory variables respectively.
3. Results and Discussion
Strength of Mol-toxicity of p-hydroxybenzoates increased as the number of carbons of ester
groups increasing each p-hydroxybenzoate. And it has been also proved that Mol-toxicity differ
with the structure of the ester group. At the same number of carbons of ester groups, the
straight-chain structure of ester group showed strong Mol-toxicity than the branched-chain structure
and the ring-shaped structure of ester groups.
In these p-hydroxybenzoates (17 kinds), the difference of the structure of the ester group reflects
the whole molecule structure of each p-hydroxybenzoate. Then, it has been proved that the
correlation with Connolly Molecular Surface Area that remarkably shows the molecular structure
and Mol-toxicity of the p-hydroxybenzoates (17 kinds) showed high correlation of R2 = 0.9103
(Fig.2).
The Mol-toxicity of p-hydroxybenzoates (17 kinds) is associated with the difference of the
structure of the ester group. Furthermore, Mol-toxicity of other molecule that have different ester
group can be estimate by using Connolly Molecule Surface Area.
7
Mol-toxicity
6
5
4
3
2
1
0
100
Fig.2
150
200
250
300
350
400
Connolly Molecular Surface Area / 10-20m2
Relationship between Mol-toxicity and Connolly Molecular Surface Area of
p-Hydroxybenzoates
4. References
[1] Hossaini A, Larsen JJ, Larsen JC. Food Chem. Toxicol., 38, 319-323 (2000)
[2] Satoh K, FFI J., 212, 398-414 (2007).
[3] Terasaki M, Kamata R, Shiraishi F, Makino M. Environ. Toxicol. Chem., 28, 204-208 (2009).
[4] Soni MG, Burdock GA, Taylor SL, Greenberg NA, Food Chem. Toxicol., 39, 513-532 (2001)
E-mail
[email protected]