Studies on the synthesis, pungency and anti-biofouling performance of capsaicin analogues

Article abstract of DOI:10.1007/s11426-011-4307-x

Ten capsaicin analogues were synthesized and their pungency degrees were determined through Scoville Organoleptic Test. The relationship between the structure and pungency degree of these capsaicin analogues was discussed. Then four of these capsaicin analogues with higher pungency degree were picked out and added to anti-biofouling paints as repellents to study their anti-biofouling performance by shallow sea buoyant raft hung-plate experimentation. The results showed that capsaicin and dihydrocapsaicin exhibited equally good anti-biofouling performance while nordihydrocapsaicin and N-vanillylnonanamide had poor anti-biofouling performance. Experimental results also showed that the paints with only 0.1% capsaicin or dihydrocapsaicin as repellent without any other biocides had also exhibited good anti-biofouling performance, which provided a new idea for developing novel, more environment-friendly and Cu ₂O-free antifouling paints.

Full text of DOI:10.1007/s11426-011-4307-x

SCIENCE CHINA
Chemistry
•
ARTICLES •
March 2012 Vol.55 No.3: 435–442
doi: 10.1007/s11426-011-4307-x
Studies on the synthesis, pungency and anti-biofouling
performance of capsaicin analogues
1
*
2
3
4
1
PENG BiXian , WANG JunLian , PENG ZhengHong , ZHOU ShengZe , WANG FengQi ,
5
6
7
8*
2*
JI YongLiang , YE ZhangJi , ZHOU XiangFeng , LIN Tong & ZHANG XiaoBin
1
Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
2
State Key Laboratory of Silicon Materials, Department of Materials Science and Engineering; Zhejiang University, Hangzhou 310027, China
3
Beijing TianLongYaYuan International Biology Company of High and New Science and Technology, Beijing 102209
4
Beijing JiuZhouLongLing Company of Advanced Materials for Environmental Protection, Beijing 102209, China
5
Guangdong Shantou MingHong Chemicals Company Ltd, Shantou 515041
Ship Coating Testing Station of China Ship Industrial Xiamen, Xiamen 361002, China
6
7
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
8
School of Engineer Technology, Deakin University, Geelong Victoria 3217, Australia
Received December 4, 2010, accepted March 1, 2011; published online September 2, 2011
Ten capsaicin analogues were synthesized and their pungency degrees were determined through Scoville Organoleptic Test.
The relationship between the structure and pungency degree of these capsaicin analogues was discussed. Then four of these
capsaicin analogues with higher pungency degree were picked out and added to anti-biofouling paints as repellents to study
their anti-biofouling performance by shallow sea buoyant raft hung-plate experimentation. The results showed that capsaicin
and dihydrocapsaicin exhibited equally good anti-biofouling performance while nordihydrocapsaicin and
N-vanillylnonanamide had poor anti-biofouling performance. Experimental results also showed that the paints with only 0.1%
capsaicin or dihydrocapsaicin as repellent without any other biocides had also exhibited good anti-biofouling performance,
which provided a new idea for developing novel, more environment-friendly and Cu
2
O-free antifouling paints.
capsaicin analogues, pungency, relationship between structure and pungency degree, anti-biofouling performance
1
Introduction
age are fouled by various marine fouling organisms, for
instance, marine microorganisms, Calcarina, algae, mussels,
barnacles and oysters. Once these organisms attached to the
surfaces of these facilities, they grow and reproduce them-
selves rapidly. These fouling organisms increase the ship-
ping cost and influence maritime safety greatly, for they
could lead to high frictional resistance and an increase of
weight, clog the pipes and seal the meshes.
Among all the solutions proposed throughout the history
of navigation, antifouling paints with biocides have been the
most general in combating marine biofouling. When the
antifouling coatings are immersed in sea water, the biocides
release slowly which could kill the marine organisms or
prevent them from fouling of the artificial surfaces. At the
Mankind has more opportunities to develop and utilize the
ocean in the 21st Century. Marine and offshore engineering
such as warship, shipbuilding, maritime transport, fishery,
sea floor oil-gas extraction and marine aquiculture have also
been developing in an unprecedented manner. One of the
comprehensive and leading problems that mankind has is
that both the fixed deep-sea facilities (harbors, buoys, quays,
bridge piers, pipelines, fishing gears, etc.) and the hull of
dynamic ships (warships, merchant ships, etc.) on the voy-
*
Corresponding author (email: pengbx@mail.ipc.ac.cn )
©
Science China Press and Springer-Verlag Berlin Heidelberg 2011
chem.scichina.com www.springerlink.com

436
Peng BX, et al. Sci China Chem March (2012) Vol.55 No.3
end of last century, tributyltin (TBT) and DDT are prime
examples of biocides which have been eliminated one after
another at the beginning of the 21st century due to their
great harm to the environment and ecology. Alternative
biocides such as copper/zinc pyrithione, Zineb, Sea-nine
1. Among intermediates No.1, No.1-1 was bought from
chemical reagent company; No.1-2 and No.1-3 were syn-
thesized in the same method in which corresponding alde-
hydes were first turned to oximes [15] and then reduced by
LiAlH
4
as ref. [16] did; No.1-4 was synthesized by the way
2
11 and TCPM are then the most frequently used world-
in which 4-hydroxy-3-methoxy--nitrostyrene was first
wide. They are less toxic than TBT and DDT, but still dele-
terious for the marine organisms and environment. To seek
more effective, more environment-friendly and of longer
service life alternative biocides is one of the important task
to perform the Stockholm Convention on Persistent Organic
Pollutants [1–3].
In 1995 Watts, who was known as the originator of cap-
saicin antifouling paints, applied natural capsaicinoids in
paints [4]. After that, capsaicin’s anti-biofouling perfor-
mance was widely studied [5–9]. These studies were fo-
cused on either several limited marine organisms or natural
capsaicinoids which were a mixture of capsaicin, homocap-
saicin, dihydrocapsaicin, homodihydrocapsaicin, nordihy-
drocapsaicin and other components. Besides, the extraction
and separation process of natural capsaicinoids were com-
plicated and the cost was very high. For these reasons their
large-scale application was limited. As early as the late
obtained following the steps described in ref. [17, 18] and
then also reduced by LiAlH [16]. Among another main
4
intermediates No.2 series, No.2-1 and No.2-6 were bought
from chemical reagent company; No.2-2, No.2-3, No.2-4
and No.2-5 were synthesized in the method described in
Zhou’s patent [14]. Compound No.10 was obtained by
methylating compound No.9 in the way as ref. [19] reported
with DMC as methylating agent, K
2 3
CO as base and tet-
rabutyl ammonium bromide as phase transfer catalysis. All
the characterization data (such as melting point, elementary
1
13
analysis, IR, H NMR, C NMR) of the intermediates men-
tioned above were listed in Section 2.5 while the capsaicin
analogues’ (No.1–No.10) were listed in Section 2.6.
2
.2 Pungency degree determination
1
980s, some capsaicin analogues had been synthesized suc-
The pungency degrees of the capsaicin analogues were de-
termined through Scoville Organoleptic Test by Testing
Center for Nutrition and Food Safety, Hunan Agricultural
University according to <GB/T 21265-2007 Pungency de-
gree sensory evaluation method for capsicum>.
cessfully by scientists from University of Nebraska Medical
Center, USA [10] and Hokkaido University, Japan [11] and
these successes served as pioneers of synthesis of capsaicin
analogues. However, these works were of more academic
significance than pragmatic value, for they were hard to be
applied in large-scale production due to either low yield or
toxicity to the environment and ecology. In recent years,
Helsing and Bakstad [12] reported the synthetic method of
some capsaicin derivatives which were unable to be detect-
ed in native hot peppers. Du [13] studied the marine an-
ti-biofouling performance of a synthesized capsaicin of
which synthetic method was not mentioned. Zhou Shengze,
one of the authors of this article, revealed synthesis of sev-
eral capsaicinoids such as capsaicin, dihydrocapsaicin in
patent [14]. Using these methods we synthesized ten capsa-
icin analogues and determined their pungency degrees.
Then we picked out four analogues with higher pungency
degree, added them to anti-biofouling paints and studied
their anti-biofouling performance. We here report the syn-
thesis of these capsaicin analogues, their pungency degrees
and some examples of their application in antifouling paints
to show their potential as effective, non-toxic, long service
life repellents.
2.2.1 Principle
Capsaicin analogues were respectively blended with a sug-
ar-water solution, then the concoctions were sipped by a
panel of testers in increasingly diluted concentration until
the point was reached at which the solution no longer
burned the mouth. The degree of dilution gave its measure
on the Scoville scale (Scoville Heat Units, SHU).
2
.2.2 Panelists selection
The taste panelists should be sensitive to pungency. They
were identified as follows: First, as per <GB/T 21265–2007
Pungency degree sensory evaluation method for capsicum>,
prepared four different solutions of which one was 0.04
mg/L N-vanillylnonanamide solution, another was 0.08
mg/L N-vanillylnonanamide solution, the other two were
distilled water; then the candidates sipped these four solu-
tions respectively also according to the standard mentioned
above to identify whether they were pungent or not. This
test was repeated twice in a time internal of 30 mins and the
candidates who failed to identify correctly both times were
eliminated. An initial set of 8–10 candidates was selected
among which five were picked out randomly to enter the
pungency test. The pungency degree determination of the
same batch of samples was done by the same five taste pan-
elists.
2
Experimental
2
.1 Synthesis of capsaicin analogues
Ten capsaicin analogues (No.1–No.10) were synthesized
with corresponding amines (No.1-1 to No.1-4) and acyl-
chlorides (No.2-1 to No.2-6) which are listed in Table

Peng BX, et al. Sci China Chem March (2012) Vol.55 No.3
437
Table 1 Intermediates and reaction products in the synthesis of capsaicin analogues
Intermediates No.1
Intermediates No.2
Products
1
No. 2-1: 3, 7-dimethyl-6-octenoyl chloride
No. 2-2: 7-methylcaprylyl chloride
2
4
No. 2-3: 8-methyl-6-nonenoyl chloride
No. 2-4: 8-methyl-4- nonenoyl chloride
No. 2-5
5
7
No.1-1
8
-methylpelargonyl chloride
9
3
8
No. 2-6: pelargonyl chloride
No.1-2
No.1-3
No. 2-6: pelargonyl chloride
6
No.1-4
2
.2.3 Requirements of the organoleptic test process
cific content of Cu
were listed in Table 3 and Table 4. In order to obtain the
paints, Cu O, solvent and the other auxiliaries were mixed
2
O and expeller and the type of polymer
The taste panelists could drink water but not allowed to
smoke and eat anything within 1 h before pungency degree
test. They also should not be stimulated by any pepper sam-
ples or capsicum sauces within 90 min before pungency
degree test. During the test, the taste panelists should be in
normal physiological state. It would be preferable to start
the pungency test 1 h after meal in order to avoid the panel-
ists being hungry or engorged. It was prohibited that the
taste panelists used cosmetics or any other things with dis-
tinct odors during the test.
Each time before the panelists sipped the sample solution,
a blank solution must be sipped first. About 20~30 s later if
the sample solution stimulated the mouth different from the
blank solution and this sensation is ‘burn’, this sample solu-
tion was treated as pungent. The time interval of every two
test solutions was 5 min. To wash off the previous sample,
the panelist performed mouth washes with water at
2
and pulverized in ball mill usually for more than 36 h.
The obtained paints’ fineness degree should be below 60
μm and the viscosity should be less than 100 s according to
<GB/T6822-2007 Anticorrosive and Antifouling Paints
System for Ship Hull>. The test equipments and operational
norms were detailed in the above mentioned national stand-
ard. All the paints did not layer six months after storage in
hold-up tanks. The primer, if necessary, was all epoxy an-
ti-corrosive paint with thickness of 100–140 μm. The details
of capsaicin analogues added to the paints were shown in
Table 4 and Table 5.
2
.4 Shallow sea buoyant raft hung-plate experimenta-
tion
3
5–40 °C and later with salt-free soda crackers.
In accordance with the national standard, each of the pre-
pared paints was sprayed or brushed onto the primed steel
plates which were 300–350 mm long, 150–250 mm wide
and 3 mm thick. The coating thickness varied with its an-
ti-fouling lifetime, for example 100–150 μm for one year
and 150–300 m for three years. After the coatings dried in
the air, these steel plates were carefully packed and then
sent to Xiamen, Fujian of China to do the shallow sea
2
.3 Preparation of anti-biofouling paints
The basic formulation of anti-biofouling paints was shown
in Table 2 in which the expeller was capsaicin analogues
synthesized by ourselves and the polymers were also
self-made. This formulation was a general one, and the spe-

438
Peng BX, et al. Sci China Chem March (2012) Vol.55 No.3
Table 2 Basic formulation of anti-biofouling paints
2
.6.2 N-(4-hydroxy)nonanamide
Materials
solvent
polymer
Content (%)
Mp: 74.9–79.5 °C. Elementary anal.(%): C: 73.47 (calcd
1
moderate
15–20
5–15
20–50
2–8
0.01–0.05
0.1–0.5
1–3
7
(
2.97); H: 9.73(calcd 9.57); N: 5.05 (calcd 5.32). H NMR
CDCl )  (ppm): 0.876 (3H, t, CH ), 1.258–1.328 (10H,
-Me), 1.609–1.683 (2H, m, CH ), 2.202 (2H, t,
), 4.359 (2H, d, Ar-CH ), 5.692 (1H, br s), 6.791
2H, d, Ar-H), 7.137 (2H, d, Ar-H). DEPT 135° (CDCl ) δ
), 25.774 (–, CH ),
), 31.794
3
3
natural resin
Cu
Fe
2
O
O
3
(CH
CO-CH
2
)
5
2
2
2
2
surfactant (BYK-361N)
expeller
(
(
2
3
ppm): 14.081 (+, CH
9.127 (–, CH ), 29.258 (–, CH
–, CH ), 36.856 (–, CH
CH), 129.219 (+, CH).
3
), 22.629 (–, CH
2
2
other modifiers
2
2
), 29.273 (–, CH
2
(
2
2 2
), 43.268 (–, CH ), 115.699 (+,
buoyant raft hung-plate experimentation. This offshore area
is subjected to the influence of sub-tropical oceanic climate
and has regular semidiurnal tides with maximum flow speed
of 1.33 m/s and mean tidal range of 4.19 m. The monthly
mean salinity of the sea water is 2.48%–3.29% and the
monthly average temperature is 12.7–27.9 °C with annual
temperature difference of about 15 °C. In this sea area there
are more than 70 varieties of fouling organisms such as
bryozoan, calcarina, mussel and barnacle. The monthly var-
iation of species is influenced by the sea temperature and
more species occur from June to October. The steel plates
coated with the anti-fouling coatings were hung 1.2 m be-
low the sea surface. The antifouling results were observed,
recorded (or taken photographs), evaluated and made into
reports by professionals regularly.
2
.6.3 N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-trans-4-
enamide
See ref. [24].
2.6.4 N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]nonanamide
Mp: 85.1–85.9 °C (83–88 °C ref. [25]). Elementary anal.
(%): C: 70.69 (calcd 70.32); H: 9.41 (calcd 9.51); N: 4.68
1
(calcd 4.56). H NMR (CDCl
3
) δ (ppm): 0.876 (3H, t, CH
-Me), 1.571–1.603 (2H, m, CH
), 2.743 (2H, t, Ar-CH
-N), 3.880 (3H, s, Ar-OCH ), 5.430 (2H, br s, NH-CO,
Ar-OH), 6.665–6.860 (3H, Ar-H). DEPT 135° (CDCl ) δ
), 25.795 (–, CH ),
), 31.827
),
), 111.165 (+, CH), 114.401 (+, CH),
3
),
1.262 (10H, s, (CH
2.121 (2H, t, CO-CH
CH
2 5
)
2
),
2
2
), 3.489 (2H, q,
2
3
3
(
ppm): 14.094 (+, CH
9.144 (–, CH ), 29.297 (–, CH
–, CH ), 35.399 (–, CH
3
), 22.646 (–, CH
2
2
2
2
2
), 29.321 (–, CH
2
2
.5 Characterization data of intermediates
(
2
2
), 36.905 (–, CH
2
), 40.672 (–, CH
2
No.1-2
55.916 (+, OCH
121.346 (+, CH).
3
Elementary anal. (%): C: 52.27 (calcd 52.68); H: 6.32
calcd 6.31); N: 8.63 (calcd 8.78). H NMR (D
1
(
4
2
O) δ (ppm):
2
.6.5 N-(3-methoxybenzyl)nonanamide
.146 (2H, s, Ar-CH
2
), 6.983 (2H, d, Ar-H), 7.386 (2H, d,
O) δ (ppm): 42.692 (–, CH ),
15.930(+, CH), 130.785(+, CH). In which “+” means that
Ar-H). DEPT 135° (D
2
2
Mp: 48.0–49.0 °C (47–48 °C ref. [25]). Elementary anal.
1
(%): C: 73.75 (calcd 73.61); H: 9.93 (calcd 9.81); N: 5.13
1
absorption peaks are above baseline, while “–” means they
are below baseline (similarly hereafter).
No.1-3
(Cal. 5.05). H NMR (CDCl
3
)  (ppm): 0.876 (3H, t, CH
-Me), 1.608–1.661 (2H, m, CH
), 3.796 (3H, s, Ar-OCH
3
),
),
1.264–1.291 (10H, (CH
2.210 (2H, t, CO-CH
2 5
)
2
2
3
), 4.415 (2H,
Elementary anal. (%): C: 55.40 (calcd 55.34); H: 7.01
d, Ar-CH ), 5.727 (1H, br s, NH-CO), 6.809–7.243 (4H,
2
1
(
calcd 6.97); N: 7.83 (calcd 8.07). H NMR (D
2
O) δ (ppm):
),
O) δ (ppm):
), 114.456(+, CH),
Ar-H). DEPT 135° (CDCl )  (ppm): 14.077 (+, CH ),
3
3
3
7
4
1
.891 (3H, s, Ar-OCH
.090–7.489 (4H, Ar-H). DEPT 135° (D
2.983 (–, CH ), 55.445 (+, OCH
3
), 4.203 (2H, s, Ar-CH
2
2 2 2
22.638 (–, CH ), 25.787 (–, CH ), 29.148 (–, CH ), 29.309
(–, CH ), 29.328 (–, CH ), 31.807 (–, CH ), 36.832 (–, CH ),
2 2 2 2
43.557 (–, CH ), 55.232 (+, OCH ), 112.966 (+, CH),
2 3
113.389 (+, CH), 120.023 (+, CH), 129.745 (+, CH).
2
2
3
14.664(+, CH), 121.370(+, CH), 130.569(+, CH).
No.1-4
Elementary anal. (%): C: 52.94 (calcd 53.08); H: 6.93
2.6.6 N-vanillylnonanamide
1
(
2
calcd 6.93); N: 6.84 (calcd 6.88). H NMR (D
2
O) δ (ppm):
-N), 3.880 (3H, s,
), 6.820–6.989 (3H, Ar-H). DEPT 135° (D O) δ
ppm): 32.268 (–, Ar-CH ), 40.667 (–, CH -N), 55.929 (+,
), 113.045 (+, CH), 115.735 (+, CH), 121.687 (+, CH).
Mp: 55.5–56.8 °C. Elementary anal. (%): C: 69.55 (calcd
1
2 2
.939 (2H, t, Ar-CH ), 3.260 (2H, t, CH
6
9.59); H: 9.23 (calcd 9.27); N: 4.84 (calcd 4.77). H NMR
Ar-OCH
3
2
(
CDCl
3
)  (ppm): 0.877 (3H, t, CH
-Me), 1.617–1.669 (2H, m, CH
), 3.885 (3H, s, Ar-OCH ), 4.361 (2H, d, Ar-CH
.654 (2H, br s, NH-CO & Ar-OH)，6.758–6.877 (3H,
3
), 1.263–1.294 (10H,
), 2.203 (2H, t,
),
(
2
2
(CH
2
)
5
2
OCH
3
CO-CH
5
2
3
2
2
.6 Characterization data of capsaicin analogues
Ar-H). DEPT 135° (CDCl )  (ppm): 14.083 (+, CH ),
3
3
2
2.641 (–, CH
2
), 25.803 (–, CH
2
), 29.157 (–, CH
2
), 29.321
2
6
.6.1
-ena mide
N-(4-hydroxy-3-methoxy benzyl)-3,7-dimethyloct-
(
–, CH
2
), 31.811 (–, CH
2
), 36.909 (–, CH
2 2
), 43.559 (–, CH ),
5
5.964 (+, OCH
3
), 110.700(+, CH), 114.346 (+, CH),
See ref. [24].
120.837 (+, CH).

Peng BX, et al. Sci China Chem March (2012) Vol.55 No.3
439
2
.6.7 N-(3,4-dimethoxybenzyl)nonanamide
3.2 Structure-pungency degree relationships
Mp: 92.0–93.1 °C (92–94 °C) ref. [25]. Elementary anal.
Based on the structure and pungency degree of capsaicin
(
%): C: 69.93 (calcd 70.32); H: 9.59 (calcd 9.51); N: 4.57
1
(calcd 4.56). H NMR (CDCl )  (ppm): 0.880 (3H, t, CH ),
3
3
analogues listed in Table 5 (Some data were from refer-
ences), the possible structure-pungency degree relationships
could be concluded as follows:
1
2
.266–1.339 (10H, (CH
.207 (2H, t, CO-CH
), 5.736 (1H, br s, NH-CO), 6.820 (3H, s,
2
)
5
-Me), 1.620–1.694 (2H, m, CH
2
),
2
3
), 3.071 (6H, s, 2Ar-OCH ), 4.377
(
2H, d, Ar-CH
2
Firstly, among all the influence factors, the arrangement
Ar-H). DEPT 135° (CDCl )  (ppm): 14.069 (+, CH ),
3
3
of –OH and –OCH in the benzene ring of vanillyl was one
3
2
2
2.630 (–, CH ), 25.804 (–, CH
2
), 29.148 (–, CH
2
), 29.319
of the key factors in the structure-pungency degree rela-
(
-, CH
2
), 31.805 (–, CH
2
), 36.852 (–, CH
2
), 43.426 (–, CH
2
),
tionships. Any change of these two groups could influence
the pungency obviously. This conclusion was drawn on the
basis of the fact that the pungency degree of No.9 was
5
1
5.885 (+, OCH
11.255(+, CH), 120.094 (+, CH).
3
), 55.953 (+, OCH
3
), 111.213 (+, CH),
1
,550,000 SHU while No.8’s pungency degree dropped to
only 600,000 SHU due to the elimination of -OH in the
benzene ring and on the contrary No.3’s pungency degree
3
Results and discussion
sharply dropped to zero because of the removal of –OCH
even when the –OH was replaced by –OCH (No.10), the
pungency degree was 1,100,000 SHU, still lower than that
of No.9. So the –OH and –OCH interdependently had a
3
;
The anti-biofouling performance results of capsaicin ana-
logues were shown in Table 3 and Table 4. The pungency
degrees of capsaicin analogues were listed in Table 5.
3
3
decisive influence on the pungency degree.
3
.1 Synthesis of capsaicin analogues
Secondly, the length of the acyl chain at the right hand of
the amide plane was another key factor that influenced the
pungency degree. The pungency degree of dihydrocapsaicin
1
The data listed in Section 2.5 and 2.6 showed that H NMR,
1
3
C NMR and elementary analysis of intermediates No.1
(
No.7) was 15,000,000 SHU, while that of nordihydrocap-
saicin was merely 9,100,000 SHU. Just the difference of
one methylene (CH
) made the pungency degree drop more
than 5,400,000 SHU.
and No.2 series were in general accord with references or
results of theory analysis. And so were all the data of cap-
saicin analogues. So it could be concluded that ten capsaicin
analogues (No.1-10) had been successfully synthesized,
among which 2, 3, 4, 6, 7, 8, 9, 10 had been reported in ref-
erences while 1, 5 were new compounds.
2
Thirdly, the effect of the branched methyl on pungency
degree also could not be ignored. Capsaicin (No.4) and di-
Table 3 Anti-biofouling performance of paints with capsaicin as expeller
Results of hung-plate experimentation
Paints No.
Formulation code
Polymer
Capsaicin content (%)
2
007.3.22–2007.9.2
2007.9–2008.3
2008.3–2008.9
1
2
3
4
5
AFT4-1
AFT4-3
AFT4-4
AFF2-7
AFF2-8
P-8
P-10
0.1
0.1
0.5
10
Well, except one or two barnacles
well
well
well

well
well
well

Well
P-8
Well
acrylate
acrylate
Failed three months later
Failed three months later
1.3


Notes: P-8 was self-polishing copper acrylic copolymer prepared by ourselves; P-10 was copolymer of methyl methacrylate-butyl acrylate also made by
ourselves; “acrylate” was bought from the market. Paints No.4 and No.5 were Cu O-free; “well” means that there were no bubbling, no cracking, no shed-
2
ding and almost no fouling organisms adhered to; “failed” means that fouling area was more than 5%; “–” means that coatings had failed and observation
was no longer made (similarly hereafter). The blank plates were fouled 21% after four months and up to 82% two months later.
Table 4 Comparison of anti-biofouling performance of capsaicin, dihydrocapsaicin, nordihydrocapsaicin and N-vanillylnonanamide (Counting from
2
007.8.1 when the steel plates were put into water)
Capsaicin analogues
Fouling area (%)
In season Off season
6th month month (next year)
Paints
No.
Formulation
(LL-)
2
Cu O
(%)
Polymer
Content
%)
In season
1st month
10%
3%
1%
1%
30%
In season 9th
expeller
(
3rd month
1%
1
1
1
1
1
1
1
2
3
4
5
7
80801
80802
80803
80804
80805
80807
Hema
Hema
Hema
Hema
Hema
Hema
Capsaicin
Dihydrocapsaicin
Capsaicin
Dihydrocapsaicin
Nordihydrocapsaicin
N-vanillylnonanamide
0.1
0.1
0.1
0.1
0.1
0.1
25
25
0
0
25
25
2%
5%
<1%
4%
30%
20%
4%
5%
1%
2%
–
3%
1%
2%
30%
20%
20%
21%
Note: Hema was self-made copolymer of hydroxyethyl methacrylate- methyl methacrylate-butyl acrylate.

440
Peng BX, et al. Sci China Chem March (2012) Vol.55 No.3
Table 5 Structure and pungency degree of capsaicin analogues
Pungency degree
SHU)
No.
1
Chemical name
Structure
(
N-(4-hydroxy-3-methoxy ben-
zyl)-3,7-dimethyloct-6-enamide
3,000,000
9,100,000
0
2
3
4
nordihydrocapsaicin
N-(4-hydroxybenzyl)nonanamide
capsaicin
15,000,000
N-(4-hydroxy-3-methoxybenzyl)-8-methyln
5
6
12,000,000
650,000
on-trans-4-enamide
N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]no
nanamide
7
8
9
dihydrocapsaicin
N-(3-methoxybenzyl)nonanamide
N-vanillylnonanamide
15,000,000
600,000
1,550,000
1
0
N-(3,4-dimethoxybenzyl)nonanamide
1,100,000
hydrocapsaicin (No.7) were the most pungent, of which
pungency degrees were both 15,000,000 SHU. By contrast,
the pungency degree of N-vanillynonanamide (No.9) was
only one-tenth of dihydrocapsaicin (No.7) just because of
the difference of the branched methyl on 8-C.
Fourthly, the impact of the double bond in the acyl chain
on the pungency degree should be taken cautiously. Capsai-
cin and dihydrocapsaicin, between which the difference in
structure was the double bond at 6-C, were of the same
pungency degree which was 15,000,000 SHU. However,
this did not mean that the double bond in the acyl was in-
difference. If the double bond location changed, the pun-
gency degree would not be constant. For example, if its lo-
cation moved from 6-C to 4-C (No.5), the pungency degree
dropped from 15,000,000 SHU (No.4) to 12,000,000 SHU
SHU, namely dropped by 58%.
As far as we had known, it was hard to give a satisfying
explanation of the above mentioned preliminary conclusions
about the structure-pungency degree relationships. Nature
had created human beings and all the living materials. The
superiors were selected and survived while the inferiors
were eliminated. The organoleptic evaluation of pungency
degree was a complex multi-subject involved phytochemis-
try, phytophysiology, sensing or sensor chemistry, neuro-
science and even psychology.
Through the before-mentioned comparative study, the
pungency degrees of capsaicin analogues were arrayed in
descending order as follows: No.4/No.7 >No.5 >No.2 > No. 1
> No.9 > No.10 > No.6/No.8 > No.3. Among them No.4 tied
with No.7 for first place and No.6 and No.8 were of almost
the same pungency. Considering that high pungency degree
might lead to better anti-biofouling performance, we picked
No.4, No.7, No.2 and No.9 out and added them into an-
ti-fouling paints to investigate their anti-fouling performance
by shallow sea buoyant raft hung-plate experimentatizon.
(
No.5).
At last, great importance should also be attached to the
methylene between the benzene ring and the acyl chain. If
its number increased from 1 (No.9) to 2 (No.6), the pun-
gency degree would fall from 1,550,000 SHU to 650,000

Peng BX, et al. Sci China Chem March (2012) Vol.55 No.3
441
3
.3 Studies on anti-biofouling performance
and dihydrocapsain had almost equally good anti-biofouling
performance and this had important practical significance.
Three years ago, an article was published on <Chinese Sci-
ence Bulletin> about influence of copper in antifouling
paints on bio-accumulation in marine environment and ma-
rine organisms [21]. The before-mentioned results indicated
3
.3.1 Capsaicin
Results of shallow sea buoyant raft hung-plate experimenta-
tion listed in Table 3 showed that paints with capsaicin in
range of 0.1–0.5% exhibited good anti-biofouling perfor-
mance from the start although with different polymers. All
the coatings were well except one or two barnacles on them.
These coatings survived the first active growth season of
marine fouling organisms and also the second one next year
without any damage or fouling organisms. This condition
lasted for 18 months in all and at the 21st month they were
observed to be full of marine organisms. What had caused
the failure of anti-biofouling coatings, whether it was be-
cause of the cease self-polishing of polymers or the running
out of capsaicin analogues, or it was because the coatings
had run out, could not be found out ever for all the coatings
had been completely covered by biogum that marine organ-
isms had secreted when they adhered to the coatings. In
order to find out the real reason, the experiment with thicker
coatings was in progress.
2
that Cu O might not be the necessary biocide when capsai-
cin or dihydrocapsaicin was used as expeller in an-
ti-biofouling paints and this provided a novel idea for creat-
ing more effective and pollution-free anti-biofouling paints.
Besides, how to prevent organisms from fouling in marine
aquiculture was still a problem that had not been resolved
well and one of the key issues was the strong adhesion of
anti-bifouling coatings on netting gears, meshes and espe-
cially on coarse ropes made of nylon or polyurethane. The
content of Cu2O in anti-biofouling paints was usually more
than 30% or even up to 60%. The more Cu
more brittle the coatings would be, and it would also be
more difficult to adhere to the netting gears. So if Cu O was
2
O added, the
2
deleted from the paints, it would help to improve the coat-
ings flexibility.
3
.3.2 Other capsaicin analogues
3.4 Discussion on anti-biofouling mechanism of capsai-
cin analogues
The comparison of anti-biofouling performance of four dif-
ferent capsaicin analogues was done and the results were
listed in Table 4 which showed that capsaicin analogues
with different structure and pungency degree exhibited ap-
parently different anti-biofouling performance. In this ex-
perimentation the same batch of polymer Hema was used
When we knew about capsaicin analogues’ anti-biofouling
performance, we always recognized the pungency as the
bridge connecting structure and anti-biofouling performance.
However, marine fouling organisms such as mussels, bar-
nacles, sea squirts and oysters definitely had no taste buds,
gustation and olfactory nerves just as higher animals. In-
stead they had antennae and self-contained low level reticu-
lar diffuse ganglions [22]. So it was not completely right if
we only boiled the capsaicin analogues’ anti-biofouling
performance down to the sensitive index of pungency de-
gree. We should take the pungency as a point of penetration
to explore deeper reasons. It was worth to notice that novel
products and new ideas of expellers had been constantly
emerging in the recent five years. The new researches
showed that not only high pungent substances could be used
as expellers, much to our surprise, and some substances
with no pungency were also efficient expellers against ma-
rine fouling organisms. For example, scientists from the
Hong Kong University of Science and Technology reported
the anti-fouling performance of Genistien (4′,5,7-trihy-
droxyisoflavone) against barnacles at the 14th international
conference on marine corrosion and fouling held in Kobe,
Japan in 2008 [23]. They also synthesized a series of Genis-
tien analogues and analyzed the relationship between these
structures and anti-biofouling performance among which
the most critical point was that the hydroxyl in the benzene
ring, its ortho-group’s nature, size and the arrangement of
these groups all played important roles in the an-
ti-biofouling performance. As to the effects of hydroxyl and
methoxyl in the benzene ring of capsaicin analogues and
and the content of Cu O and other components was also the
2
same. The only difference was the expeller type, namely
different capsaicin analogues. Among the four tested capsa-
icin analogues, N-vanillylnonanamide and nordihydrocap-
saicin showed poor anti-biofouling performance of which
coatings were covered by fouling organisms up to 20% and
3
<
0% respectively from the first month. According to
GB/T6822-2007 Anticorrosive and Antifouling Paints
System for Ship Hull>, if the fouling area was more than
%, it was regarded as ineffectiveness. By contrast, capsai-
5
cin and dihydrocapsain exhibited much better an-
ti-biofouling performance of which coatings experienced
two active growth seasons of marine organisms and even at
the end of the ninth month the fouling area was still less or
equal to 5%. As to the fouling area of the capsaicin coatings
was up to 10% in the first month, the reason had not been
known. It might occur by chance. Meanwhile, it seemed that
the content of capsaicin expeller should be very low, or else
it might cause worse anti-biofouling performance (see Table
3
paints No.4&No.5). A special mention must also be made
that paints No.13 and No.14, both of which did not contain
Cu O and only used capsaicin or dihydrocapsaicin as ex-
peller, passed through two active growth seasons of marine
organisms and at the end of the ninth month the fouling area
was just 1% and 2% respectively. It seemed that capsaicin
2

442
Peng BX, et al. Sci China Chem March (2012) Vol.55 No.3
ment study with freshwater bacteria. Environ Sci Pollut Res, 2005,
2(5): 278–284
Shi H, Wang LM. Discussion on nontoxic sodium silicate antifouling
paint used in the netting of marine cage. Marine fisheries, 2004, 26(3):
239–242
Cope WG, Bartsch MR, Marking LL. Efficacy of candidate chemi-
cals for preventing attachment of zebra mussels (Dreissena polymor-
pha). Environ Toxicol Chem, 1997, 16(9): 1930–1934
Angarano MB, McMahon RF, Hawkins DL, Schetz JA. Exploration
of structure-antifouling relationships of capsaicin-like compounds
that inhibit zebra mussel (Dreissena polymorpha) macrofouling. Bio-
fouling, 2007, 23(5):295–305
Gannett PM, Nagel DL, Reilly PJ, Lawson T, Sharpe J, Toth B. The
capsaicinoids - their separation, synthesis, and mutagenicity. J Org
Chem, 1988, 53(5):1064–1071
their arrangement on pungency degree had been discussed
in Section 3.2. As we had known that marine organisms like
barnacles had sucked type of antennae which were sensitive
biochemical sensors of high susceptibility. When the chem-
ical sensors of host were compatible well with the clusters
of expeller’s anti-biofouling factors (such as nature, size
and short range etc.), organisms like barnacles would con-
stantly secrete biogum and settle down, even multiply. On
the contrary, these organisms would leave and go to find
new settlement if the signal sent by the clusters about its
nature, size and short range etc. did not match well with the
antennae, or even badly. The anti-biofouling mechanism of
expellers was an interesting issue which could not be ex-
plained well at present. It depended on full cooperation of
experts in many fields such as marine zoology, biochemis-
try and bionics.
1
7
8
9
1
0
1
1
1
2
Kaga H, Miura M and Orito K. A facile procedure for synthesis of
capsaicin. J Org Chem, 1989,54(14): 3477–3478
Torsten H, Einar B. Capsaicin derivatives and their synthetic methods
and applications. CN patent 1849068A, 2006
13 Du WN. Studies on the application of synthesized capsaicin in anti-
fouling paints. Shanghai coatings, 2009, 47(8): 1–4
1
4
Zhou SZ, Zhou XF, Peng BX. Synthetic methods of capsaicin ana-
logues. Application No. 2009100877050
This work is partially supported by the National HighTechnology Research
and Development Program of China (863 Program 2010AA065104). The
authors would like to thank HAN WenYa and ZHOU YunRui (Stockholm
Convention Implementation Office, Foreign Economic Cooperation Office,
SEPA), JIANG Feng (EnviSolve Consulting Co., Ltd., Beijing), REN
RunTao, JIN XiaoHong and YE MeiQi (Ship Coating Testing Station of
China Ship Industrial Xiamen), YU Jie and GUI TaiJiang (Development
Center of Marine Chemical Research Institute, Qingdao), LIAN YunHe
15 Zhan JX, Zhou XZ, Zou LP, Wu WJ. Synthesis of
4-hydroxy-3-methoxyphenyl oxime. J Nat Univ defense technol 2002,
24(2): 17-18, 26
16 Ramirez FA and Burger A. The reduction of phenolic be-
ta-nitrostyrenes by lithium aluminum hydride.
Soc,1950, 72(6): 2781–2782
J Am Chem.=
17 Milhazes N, Calheiros R, Marques MPM, Garrido J, Cordeiro MNDS,
Rodrigues C, Quinteira S, Novais C, Peixe L, Borges F. Be-
ta-nitrostyrene derivatives as potential antibacterial agents: A struc-
ture-property-activity relationship study. Bioorg Med Chem, 2006,
14(12): 4078–4088
18 McNulty J, Steere JA,Wolf S. The ultrasound promoted Knoevenagel
condensation of aromatic aldehydes. Tetrahedron Lett, 1998, 39(44):
8013–8016
19 Ouk S, Thiebaud S, Borredon E, Legars P, Lecomte L. O-methylation
of phenolic compounds with dimethyl carbonate under solid/liquid
phase transfer system. Tetrahedron Lett, 2002, 43(14): 2661–2663
20 Paluch G, Bartholomay L, Coats J. Mosquito repellents: A review of
chemical structure diversity and olfaction. Pest Management Sci,
2010, 66(9): 925–935
21 Wang JL, Wang FQ, Yu J, Zhuang Y, Zhou XF, Zhang XB, Peng BX.
A survey analysis of heavy metals bio-accumulation in internal or-
gans of sea shell animals affected by the sustainable pollution of an-
tifouling paints used for ships anchored at some domestic maritime
spaces. China Sci Bull, 2008. 53(16): 2471–2475
22 Huang ZG. Marine fouling organisms and their control (Part II). Bei-
jing: China Ocean Press, 2008
23 Zhou XJ, Qian PY. Ginestein and its derivatives against larval set-
tlement of the barnacles balanus amphitrite. The 14-th International
Congress on Marine Corrosion and Fouling. Japan, 2008
24 Wang JX, Zhou SZ, Peng ZH, Zhou XF, Zhang XB, Peng BX. Syn-
thesis and characterization of new members of capsaicinoids and pre-
liminary research on the relationship between the strcture and pun-
gency. Chinese J Org Chem, 2011, in press
25 Walpole CSJ, Wrigglesworth R, Bevan S, Campbell EA, Dray A,
James IF, Perkins MN, Reid DJ, Winter J. Analogs of capsaicin with
agonist activity as novel analgesic agents- structure activity studies. 1.
The aromatic A-region. J Med Chem, 1993, 36(16): 2362–237
(Company of Chenguang Natural Pigments, HeBei), JI QiuTing and JI
LinQing (Minghong Chemical Company, Shantou, Guangdong), Yang
HangSheng, Zhang AiLi and Wen ZhengFei (Department of Materials
Science and Engineering, Zhejiang University), CAI RuXing (College of
Life Sciences, Zhejiang University), CAO JingYi (Naval Institute of Tech-
nology and equipment), FANG ChangFu and LIN JiaFu (The Second In-
stitute of Oceanography, SOA) for the great help and support for this pa-
per.
1
Peng BX. A report on the survey and investigation on the interna-
tional and domestic development trends of the antifouling paints used
for oceanic ships. A review report on the workshop of “alternative to
DDT usage in the production of antifouling paint” organized by
SEPA. Beijing, 2006
2
3
Zhou SZ, Peng BX. A comparative study of the antifouling perfor-
mance of four different capsaicinoids as expellers in antifouling
paints. The 14th International Congress on Marine Corrosion and
Fouling. Japan, 2008
Peng BX. Some progress of anti-biofouling paints which used capsa-
icin as expeller. Conference of screening standard and method of the
substitution technology for DDT antifouling paint of alternatives to
DDT usage in the production of antifouling paint. Organized by
SEPA. Qingdao, 2008
4
5
Watts JL. Anti-fouling coating composition containing capsaicin. US
patent 5397385, 1995
Xu QW, Barrios CA, Cutright T, Newby BMZ. Evaluation of toxicity
of capsaicin and zosteric acid and their potential application as anti-
foulants. Environ Toxicol, 2005, 20(5): 467–474
6
Xu QW, Barrios CA, Cutright T, Newby BMZ. Assessment of anti-
fouling effectiveness of two natural product antifoulants by attach-