Synthesis, surface property and antimicrobial activity of cationic gemini surfactants containing adamantane and amide groups

Article abstract of DOI:10.1007/s11743-014-1580-7

A series of novel cationic gemini surfactants, namely 1,3- adamantanedicarboxylic acid bis(alkyldimethyl-3-ammoniopropyl amide) dibromide designated as [Ad-2(amC _n )] (n = 12, 14, 16), containing adamantane, two amide groups, and two hydrocarbon chains, were synthesized from 1,3-adamantanedicarboxylic acid. The surface-active properties of the surfactants were investigated through surface tension and electrical conductivity measurement. A series of thermodynamic parameters such as standard free energy (ΔG°_m), enthalpy (ΔH°_m), and entropy (ΔS°_m) of micellization were evaluated from electrical conductivity measurements in the temperature range from 288 to 308 K. The micellization for [Ad-2(amC _n )] is entropy-driven at low temperature and enthalpy-driven at high temperature. Further, the antimicrobial activity of the synthesized gemini surfactants against both Gram-positive and Gram-negative bacteria was also investigated, and this study showed that the compound [Ad-2(amC₁₂)] has excellent antibacterial activity against all studied bacteria.

Full text of DOI:10.1007/s11743-014-1580-7

J Surfact Deterg
DOI 10.1007/s11743-014-1580-7
ORIGINAL ARTICLE
Synthesis, Surface Property and Antimicrobial Activity
of Cationic Gemini Surfactants Containing Adamantane
and Amide Groups
•
Xing Zhong Jianwei Guo Shuqin Fu
•
•
•
Dongyu Zhu Jinping Peng
Received: 29 September 2013 / Accepted: 3 March 2014
Ó AOCS 2014
Abstract A series of novel cationic gemini surfactants,
acid
spacer in a molecule. gemini surfactants have been used as
detergents, gene delivery vector, antimicrobial agents, and
so on. Numerous gemini surfactants with different chemi-
cal structures have been synthesized and investigated
because these surfactants have superior properties with
respect to conventional surfactants [1–3]. Many works
have shown that the nature of the spacer plays an important
role in the surfactant properties of gemini surfactants, and
the spacer may be of various types: long or short, hydro-
philic or hydrophobic, flexible or rigid [4–6]. It is inter-
esting to investigate the effect of rigidity spacers on the
properties of gemini surfactants.
Adamantane (tricyclo[3.3.1.13,7]decane), C10H16, is a
very symmetric tricyclic hydrocarbon with three fused
chair-form cyclohexane rings, the same structure as a
diamond lattice (high rigidity) [7]. The particular structure
of adamantane displays many useful chemical and physical
properties, is a highly symmetric cage compound that
imparts many interesting chemical and physical properties,
such as high thermal and oxidative stability, extreme
lipophilicity, and innocuity, etc. [8]. Amino derivatives of
adamantane, such as aminoadamantanes which are known
to have interesting biological properties, are used medi-
cally to treat influenza. It is interesting to study the bio-
logical activity of adamantane derivatives. However, until
recently few studies have focused on the surfactants con-
taining adamantane [9, 10].
namely
1,3-adamantanedicarboxylic
bis(alk-
yldimethyl-3-ammoniopropyl amide) dibromide designated
as [Ad-2(amCn)] (n = 12, 14, 16), containing adamantane,
two amide groups, and two hydrocarbon chains, were
synthesized from 1,3-adamantanedicarboxylic acid. The
surface-active properties of the surfactants were investi-
gated through surface tension and electrical conductivity
measurement. A series of thermodynamic parameters such
À
Á
À
Á
as standard free energy DGꢀm , enthalpy DHmꢀ , and
À
Á
entropy DSꢀm of micellization were evaluated from elec-
trical conductivity measurements in the temperature range
from 288 to 308 K. The micellization for [Ad-2(amCn)] is
entropy-driven at low temperature and enthalpy-driven at
high temperature. Further, the antimicrobial activity of the
synthesized gemini surfactants against both Gram-positive
and Gram-negative bacteria was also investigated, and this
study showed that the compound [Ad-2(amC12)] has
excellent antibacterial activity against all studied bacteria.
Keywords Gemini surfactants ꢁ Adamantane ꢁ Critical
micelle concentration ꢁ Thermodynamic parameters ꢁ
Antimicrobial activity
Introduction
Some researchers have been realized the antimicrobial
activity of adamantane derivatives, and they were tested
against some microorganisms, such as Staphylococcus
aureus, Bacillus subtilis, Escherichia coli, Pseudomonas
aeruginosa and so on. As expected, the antimicrobial
activities of adamantane derivatives were relatively high
[11, 12]. As we known, the cationic surfactants have
proved themselves to have antimicrobial activities.
Gemini or dimeric surfactants consist of two conventional
single-chain surfactants which are chemically bonded by a
X. Zhong ꢁ J. Guo (&) ꢁ S. Fu ꢁ D. Zhu ꢁ J. Peng
School of Chemical Engineering and Light Industry,
Guangdong University of Technology, Guangzhou 510006,
People’s Republic of China
e-mail: guojw@gdut.edu.cn
123

J Surfact Deterg
Cationic gemini surfactants which consist of two sym-
metric quaternary ammonium groups exhibit much better
antimicrobial potency [1]. Herein, the adamantane combine
with the cationic gemini surfactants may have excellent
antimicrobial activities.
surface tension of aqueous solutions was measured by a KSV
Sigma 700 tensiometer at 298 K, and each sample was mea-
sured three times. This tensiometer works based on the Wil-
helmyplatemethod.Priortomeasurement, thesurfacetension
of the doubled distilled water was confirmed in the range of
72.0 0.3 mN/m. Electrical conductivity of surfactant
solutions was performed on a conductivity meter (Model
DDS-11A, Shanghai Precision & Scientific Instrument Co.
Ltd., accuracy of 2 %) at five different temperatures
(288–308 K) for each surfactant.
In this paper, we report a series of novel cationic gemini
surfactants containing amide groups and adamantane
spacer, namely 1,3-adamantanedicarboxylic acid bis(alk-
yldimethyl-3-ammoniopropyl amide) dibromide ([Ad-
2(amCn)]), where n is hydrocarbon chain length of 12, 14
and 16). The [Ad-2(amCn)] are synthesized from 1,3-ad-
amantanedicarboxylic acid by three-step reactions, their
surface-active properties (including CMC, cCMC, pC20,
Synthesis of 1,3-Adamantanedicarboxylic Acid Bis-
(N,N-Dimethyl-3-Aminopropyl amide) (3)
C
max, and PCMC), thermodynamic parameters of micelli-
À
Á À
Á
À
Á
zation (including b, DGꢀm , DHmꢀ and DSmꢀ ) and anti-
microbial activity are systematically investigated. The
synthetic route is shown in Scheme 1.
The mixture of 1,3-adamantanedicarboxylic acid (5.0 g,
22.3 mmol) and thionyl chloride (50 mL) was refluxed under
vigorous stirring for 3 h, and became transparent. The excess
thionyl chloride was removed by vacuum distillation. This
obtainedsolidwasdissolvedindistilledbenzene(70 mL), and
added dropwise to a being agitated solution of the N,N-
dimethyl-1,3-propanediamine (4.69 g, 46 mmol) in distilled
benzene (50 mL) over 30 min under a nitrogen atmosphere at
0 °C. The resultant mixture was stirred continuously over-
night then allowed to warm to room temperature, during
which a white solid was formed. The resultant white precip-
itate was isolated by filtration and dried in a vacuum, and then
recrystallized from acetone to give compound 2.
Compound 2: yield = 76 %, white crystal, 1H NMR
(300 MHz, D2O, dppm): 1.561 (br.s, 2H, Had-6, this ‘‘ad’’
means adamantane), 1.634–1.675 (m, 8H, Had-4, 8, 9, 10),
1.730 (br.s, 2H, Had-2), 1.767–1.841 (m, 4H, 2 9 CH2-
CH2CH2), 2.075 (br.s, 2H, Had-5, 7), 2.738 (s, 12H,
4 9 NCH3), 2.935–2.988 (t, 4H, 2 9 NCH2CH2), 3.133–
3.177 (t, 4H, 2 9 CONHCH2CH2).
Experimental Section
Materials and Instrumentation
The 1,3-adamantanedicarboxylic acid was synthesized and
purified as reported [13]. N,N-dimethyl-1,3-propanediamine,
1-bromododecane, 1-bromotetradecane, and 1-bromohexa-
decane were purchased from Aldrich and used without further
purification. Thionyl chloride, sodium hydroxide, magnesium
sulfate, dichloromethane, benzene, absolute ether, isopropa-
nol, and acetone were all purchased from Guangzhou
Chemical Reagent Factory (Guangzhou, China). Double-
distilled water was used in all the experimental procedures.
The products were characterized by melting point (WRS-
1B), 1H NMR (Varian Mercury-Plus 300 Spectrometer). The
Scheme 1 Synthesis of cationic
gemini surfactant
[Ad-2(amCn)]
H
H
O
N
N
O
N
N
HCl
COOH
1
8
9
5
i: SOCl2
2
6
NaOH
7
10
3
4
COOH
ii: H2N
N
O
N
N
O
N
H
N
N
HCl
H
1
3
2
H
N
O
CnH2n+1
2Br-
CnH2n+1Br
reflux,7 d
O
N
N CnH2n+1
H
[Ad-2(amCn)]
n=12, 14, 16
123

J Surfact Deterg
Then compound 2 was dissolved in water (100 mL), and
then sodium hydroxide solution (80 mL, 1 molꢁL-1) was
added, the mixture was stirred for 30 min at room tem-
1,3-Adamantanedicarboxylic acid bis(hexadecyldimeth-
yl-3-ammoniopropyl amide) dibromide ([Ad-2(amC16)]):
yield = 50 %, white crystal, mp = 135.5–135.8 °C, 1H
NMR (300 MHz, CDCl3, dppm): 0.859–0.903 (t, 6H,
2 9 CH2CH3), 1.255–1.346 (m, 52H, 2 9 CH2(CH2)13-
CH2), 1.693–1.795 (m, 10H, Had-6 and Had-4, 8, 9, 10),
perature
and
extracted
with
dichloromethane
(3 9 100 mL). The combined organic layers were washed
with brine and water, dried with anhydrous magnesium
sulfate and then rotary evaporated to give the compound 3.
1,3-Adamantanedicarboxylic acid bis-(N,N-dimethyl-3-
aminopropyl amide) (3): yield = 68 %, light yellow col-
ored oil, 1H NMR (300 MHz, DMSO, dppm):
1.475–1.521 (m, 4H, 2 9 CH2CH2CH2), 1.573 (br.s, 2H,
Had-6), 1.636–1.674 (m, 8H, Had-4, 8, 9, 10), 1.745 (br.s,
2H, Had-2), 2.042 (br.s, 2H, Had-5, 7), 2.099 (s, 12H,
4 9 NCH3), 2.145–2.195 (t, 4H, 2 9 NCH2CH2),
3.021–3.041 (m, 4H, 2 9 CONHCH2CH2), 7.501–7.537
(t, 2H, 2 9 CONH).
1.922–1.963
(m,
4H,
2 9 N?CH2CH2(CH2)13),
2.079–2.142 (m, 6H, Had-2 and 2 9 N?CH2CH2CH2-
NHCO), 2.337 (br.s, 2H, Had-5, 7), 3.318 (s, 12H,
4 9 N?CH3), 3.356–3.432 (m, 8H, 4 9 N?CH2CH2),
3.698–3.751 (m, 4H, 2 9 CONHCH2CH2), 7.633–7.670 (t,
2H, 2 9 CONH).
Antimicrobial Activity Test
Antimicrobial activity of the cationic gemini surfactants
[Ad-2(amCn)] were evaluated using the method for the
broth macro dilution test [14, 15]. The antimicrobial
activity of tested compounds was determined on the basis
of their MIC (Minimal Inhibitory Concentration) values.
The MIC means the lowest concentration of an antimi-
crobial agent that prevents visible growth of a microor-
ganism in the broth dilution susceptibility test. The target
gemini surfactants were dissolved in distilled water and
after sterilization, a half milliliter of each concentration of
the compound was added to the nutrient broth medium.
Then the nutrient broths were individually inoculated with
20 lL of bacterial suspensions each containing separately
bacteria cells. The concentration of the bacteria suspen-
sions were approximately 106cfu/mL.
Synthesis of 1,3-Adamantanedicarboxylic Acid
Bis(alkyldimethyl-3-Ammoniopropyl Amide)
Dibromide ([Ad-2(amCn)])
The solution of alkyl bromide (40 mmol of 1-bromodo-
decane, 1-bromotetradecane, or 1-bromohexadecane) in
isopropanol (50 mL) was added to a stirred solution of
compound 3 (10 mmol) in isopropanol (80 mL), the mix-
ture was refluxed for 7 days. Then the resulting mixture
was concentrated, washed with diethyl ether, and recrys-
tallized from acetone to give the target gemini surfactants
[Ad-2(amCn)].
1,3-Adamantanedicarboxylic acid bis(dodecyldimethyl-
3-ammoniopropyl amide) dibromide ([Ad-2(amC12)]):
yield = 69 %, white crystal, mp = 142.5–142.7 °C, 1H
NMR (300 MHz, CDCl3, dppm): 0.857–0.901 (t, 6H,
2 9 CH2CH3), 1.254–1.348 (m, 36H, 2 9 CH2(CH2)9-
CH2), 1.692–1.784 (m, 10H, Had-6 and Had-4, 8, 9, 10),
Five strains of a representative group of microorganisms
were used: two Gram-positive bacteria (G?): S. aureus, B.
subtilis, and three Gram-negative bacteria (G-): E. coli,
Pseudomonas aeruginosa and Vibrio parahaemolyticus.
Growth of the microorganisms was determined visually
after incubation for 24 h at 37 °C.
1.922–1.962
(m,
4H,
2 9 N?CH2CH2(CH2)9),
2.084–2.140 (m, 6H, Had-2 and 2 9 N?CH2CH2CH2-
NHCO), 2.340 (br.s, 2H, Had-5, 7), 3.323 (s, 12H,
4 9 N?CH3), 3.370-3.424 (m, 8H, 4 9 N?CH2CH2),
3.712–3.729 (m, 4H, 2 9 CONHCH2CH2), 7.639–7.674 (t,
2H, 2 9 CONH).
Results and Discussion
Surface Active Properties
1,3-Adamantanedicarboxylic acid bis(tetradecyldimeth-
yl-3-ammoniopropyl amide) dibromide ([Ad-2(amC14)]):
yield = 62 %, white crystal, mp = 145.2–145.7 °C, 1H
NMR (300 MHz, CDCl3, dppm): 0.863–0.907 (t, 6H,
2 9 CH2CH3), 1.259–1.353 (m, 44H, 2 9 CH2(CH2)11-
CH2), 1.699–1.809 (m, 10H, Had-6 and Had-4, 8, 9, 10),
The surface tension measurement is a classical method of
studying the critical micelle concentration (CMC) of sur-
factants. The variations of the surface tension (c) with the
surfactant concentration (C) at 298 K are shown in Fig. 1.
The plots of c versus Log C show a break at a concentration
corresponding to the CMC of the three gemini surfactants.
From Fig. 1, the values of CMC and the surface tension at
the CMC (cCMC) are listed in Table 1. It can be seen that
the gemini surfactants with longer hydrophobic chains
have a lower CMC value and a higher minimum surface
tension. The CMC value of [Ad-2(amC14)] is 1 9 10-4
1.929–1.966
(m,
4H,
2 9 N?CH2CH2(CH2)11),
2.098–2.171 (m, 6H, Had-2 and 2 9 N?CH2CH2CH2-
NHCO), 2.347 (br.s, 2H, Had-5, 7), 3.319 (s, 12H,
4 9 N?CH3), 3.366–3.457 (m, 8H, 4 9 N?CH2CH2),
3.730–3.748 (m, 4H, 2 9 CONHCH2CH2), 7.671–7.674 (t,
2H, 2 9 CONH).
123

J Surfact Deterg
ꢀ
ꢁ
1
dc
d log C
64
60
56
52
48
44
40
Cmax ¼ ꢂ
ꢃ
ð2Þ
ð3Þ
[Ad-2(amC12)]
[Ad-2(amC14)]
[Ad-2(amC16)]
2:303 nRT
T
Amax ¼ 1016 ꢃ ðNACmaxÞꢂ1
where R = 8.314 Jꢁmol-1ꢁK-1, T = 298 K with c expres-
sed in mNꢁm-1, NA = 6.02 9 1023 mol-1. The value of n
is taken as 3 for a gemini surfactant. (dc/dlogC)T is the
slope in the surface tension isotherm when the concentra-
tion is near the CMC. The values of Cmax, Amin are listed in
Table 1. The estimated Amin values are 1.64, 1.07, 0.92 for
[Ad-2(amC12)], [Ad-2(amC14)], and [Ad-2(amC16)],
respectively. The data of minimum surface area of
the short-chain surfactant molecules showed higher Amin
of these molecules than those of longer hydrophobic
chains.
-4.8
-4.4
-4.0
-3.6
-1
-3.2
-2.8
Log (C/mol L )
Fig. 1 Surface tension versus log C plot for the gemini surfactants
[Ad-2(amCn)] at 298 K
The adsorption efficiency can be characterized by the
value of the logarithm of the surfactant concentration C20
at which the surface tension of water is reduced by 20
mNꢁm-1 (pC20), the larger the pC20 value, the greater the
tendency of the surfactant to adsorb at the air–water
interface vs forming a micelle in solution [18]. The value of
pC20 is also listed in Table 1. It can be seen that the [Ad-
2(amCn)] with a longer hydrophobic chain has a higher
adsorption efficiency.
molꢁL-1, Compared with the monomeric surfactant with
amide group and the same hydrophobic alkyl chain length,
C13H27CONHCH2CH2CH2N?(CH3)2C2H5ꢁBr-(14monomer),
the CMC of 14monomer is 1 9 10-3 molꢁL-1, it is
apparent that the critical micelle concentrations of the
gemini surfactants have much lower values compared with
the conventional monomeric surfactant equivalents.
Moreover, compared with other gemini surfactants,
C13H27CONHCH2CH2CH2N?(CH3)2(CH2)N?H2CH2CH2
CHNOCC13H27ꢁ2Br-(14-6-14)
(CMC = 2.9 9 10-4
molꢁL-1) [16], it is interesting that the [Ad-2(amC14)]
with a rigid adamantane spacer has a lower CMC value. It
may result from the lipophilic adamantane in the middle of
the spacer of [Ad-2(amC14)], which can also be regarded
as the hydrophobic chain resulting in a lower CMC value.
To show the ability to decrease surface tension of
solutions, the effectiveness of the surface tension reduc-
tion, PCMC is determined as follows:
Thermodynamic parameters of [Ad-2(amCn)]
The electrical conductivity (j) of [Ad-2(amCn)] in aque-
ous solutions at five temperatures is shown in Fig. 2. In
each of the plots, two straight lines with different slopes
were obtained, which intersect at the point CMC. The
degree of counterion dissociation (a) can be obtained from
the ratio of the slopes above and below the break indicative
of the CMC. Normally, the degree of counterion binding
(b) and the degree of counterion dissociation have the
following relationship: b = 1-a. The b is an important
parameter since it is the expression of how many counte-
rions are contained in the Stern layer to counterbalance the
electrostatic force that opposes micelle formation [19]. All
the values of CMC and b at different temperatures are
listed in Table 2.
PCMC ¼ c0 ꢂ cCMC
ð1Þ
where c0 is the surface tension of water and cCMC is the
surface tension of the solutions when the concentration is
above the CMC. The PCMC values are all listed in Table 1.
The values of effectiveness are in the range of
27–31 mNꢁm-1
.
For the adsorption of [Ad-2(amCn)] at the air–water
interface, the maximum surface excess concentration
From Table 2, one can be seen that the CMC of all the
surfactants increased as the temperature increased. This
may be because the water structures surrounding the
hydrophobic chains are destroyed as the temperature
(Cmax) and the minimum surface area per molecule (Amin
at the air–water interface can be calculated using the Gibbs
)
adsorption equation [17].
Table 1 The surface properties
of the gemini surfactants [Ad-
2(amCn)] at 298 K
Surfactants
CMC
(mmolꢁL-1
cCMC
PCMC
Cmax 9 1010
Amin
(nm2)
pC20
)
(mNꢁm-1
)
(mNꢁm-1
)
(molꢁcm-2
)
[Ad-2(amC12)]
[Ad-2(amC14)]
[Ad-2(amC16)]
0.60 0.04
0.10 0.04
41.3 0.2
43.5 0.3
45.3 0.1
31.0
28.8
27.0
1.01 0.08
1.55 0.04
1.81 0.05
1.64 0.01
1.07 0.03
0.92 0.03
3.84
4.31
4.80
0.025 0.005
123

J Surfact Deterg
Fig. 2 Electrical conductivity
(j) versus the concentration
(C) of [Ad-2(amC12)], [Ad-
2(amC14)] and [Ad-2(amC16)]
at five temperatures: 308 K
(filled diamonds), 303 K (filled
inverted triangles), 298 K (filled
triangles), 293 K (filled circles),
288 K (filled squares)
240
210
180
150
120
90
80
70
60
50
40
30
20
10
0
[Ad-2(amC14 )]
[Ad-2(amC12 )]
308K
303K
298K
293K
288K
308K
303K
298K
293K
288K
60
30
0
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6
0.0
0.1
0.2
0.3
0.4
0.5
-1
-1
C/ mmol L
C/ mmol L
24
21
18
15
12
9
[Ad-2(amC16)]
308K
303K
298K
293K
288K
6
3
0
0.00
0.02
0.04
0.06
0.08
0.10
-1
C/ mmol L
Table 2 The thermodynamic parameters and CMC with error bars for [Ad-2(amCn)] determined by the electrical conductivity at five different
temperatures
À
Á
À
Á
DGꢀm (kJꢁmol-1
)
DHmꢀ (kJꢁmol-1
)
Surfactants
T (K)
CMC (mmolꢁL-1
)
b
ꢂTDSꢀm (kJꢁmol-1
)
[Ad-2(amC12)]
288
293
298
303
308
288
293
298
303
308
288
293
298
303
308
0.60 0.01
0.63 0.01
0.65 0.01
0.68 0.01
0.70 0.01
0.10 0.01
0.11 0.01
0.13 0.01
0.14 0.01
0.15 0.01
0.023 0.001
0.025 0.001
0.028 0.001
0.034 0.001
0.038 0.001
0.55 0.01
0.53 0.01
0.54 0.01
0.52 0.01
0.47 0.01
0.44 0.01
0.45 0.01
0.45 0.01
0.44 0.01
0.43 0.01
0.42 0.01
0.41 0.01
0.39 0.01
0.38 0.01
0.36 0.01
-28.74 0.232
-28.56 0.237
-29.25 0.242
-29.06 0.247
-28.02 0.253
-29.77 0.100
-30.38 0.116
-30.51 0.145
-30.52 0.160
-30.53 0.173
-32.37 0.257
-32.39 0.268
-31.97 0.281
-31.71 0.295
-31.25 0.306
-5.57 0.053
-5.65 0.055
-5.90 0.057
-5.99 0.059
-5.88 0.061
-23.18 0.179
-22.91 0.182
-23.35 0.185
-23.07 0.188
-22.13 0.192
-16.13 0.045
-16.12 0.034
-15.75 0.010
-15.42 0.001
-15.10 0.007
-20.67 0.130
-17.88 0.109
-14.73 0.087
-11.47 0.065
-8.17 0.037
[Ad-2(amC14)]
[Ad-2(amC16)]
-13.64 0.145
-14.27 0.150
-14.76 0.155
-15.10 0.161
-15.43 0.166
-11.70 0.127
-14.51 0.159
-17.24 0.194
-20.24 0.230
-23.09 0.269
DGꢀm ¼ RTð0:5 þ bÞ ln XCMC
ð4Þ
increases, which disfavors the formation of micelles and
increases the CMC [20]. It also can be observed that b
values decreases slightly with increasing hydrophobic
chain length at the same temperature.
where R = 8.314 Jꢁmol-1ꢁK-1, XCMC is the CMC in molar
fraction, XCMC = CMC/55.4, the 55.4 comes from 1 L of
water corresponding to 55.4 mol of water at 298 K, and b
is the degree of counterion binding which was calculated
previously. The standard enthalpy change of micellization,
According to the pseudophase model of micellization,
the standard Gibbs free energy change of micellization,
DGꢀm , can be calculated from the equation below [21]:
À
Á
123

J Surfact Deterg
MIC (lgꢁmL-1
S. aureus
(G?)
)
Table 3 The minimal
Compound
inhibitory concentration (MIC)
values of the target gemini
surfactants [Ad-2(amCn)]
B. subtilis
(G?)
E. coli
(G-)
P. aeruginosa
(G-)
V. Parahemolyticus
(G-)
[Ad-2(amC12)]
[Ad-2(amC14)]
[Ad-2(amC16)]
BACa
0.7
2.8
5.9
2.0
0.3
1.1
4.7
3.7
16
2.1
4.2
2.1
71.0
[300.6
3.7
71.0
94.0
29.9
32
71.0
150.3
a
Data from reference [24]
b
–
b
Not determined
DABBc
16
–
b
–
b
c
Data from reference [25]
À
Á
DHmꢀ , can be determined using the Gibbs–Helmholtz
equation for aqueous solutions,
And their antibacterial activities decrease with the
increase in alkyl chain length of [Ad-2(amCn)] (From
n = 12 to 16). As expected, the compound [Ad-
2(amC12)] had the lowest MIC value against all studied
bacteria and exhibited the strongest antimicrobial activity.
These results are in agreement with results obtained pre-
viously, which showed that the optimal length of the alkyl
chain has been noted to be twelve carbon atoms of cat-
ionic surfactants [23].
ꢂ
ꢃ
oðDGꢀm=TÞ
oð1=TÞ
d ln XCMC
dT
DHmꢀ
¼
¼ ꢂRT2ð0:5 þ bÞ
ð5Þ
À
Á
The standard entropy of micellization, DSꢀm , can be
calculated according to the following relation:
DSꢀm ¼ ðDHmꢀ ꢂ DGmꢀ Þ=T
ð6Þ
À
Á À
Á
All the values of DGꢀm , DHmꢀ , ꢂTDSꢀm calculated at
According to researchers dealing with the mode of
action of cationic amphiphiles compounds on different
microorganisms [24, 25], the most preferable explanation
is the adsorption of amphiphile molecules on the outer
cellular membrane of the microorganism due to their
amphipathic characteristics. The positively charged head-
groups of the cationic molecules interact with the nega-
tively charged bacterial cell membrane, thus disrupting it
with the aid of electrostatic and hydrophobic interactions
leading to the release of K? and cytoplasmic constituents
and finally cell death. The antibacterial activity depends on
the hydrophilic-hydrophobic balance of the cationic am-
phiphiles. When the further increases in the alkyl chain
length (traditionally n [ 12) increase the hydrophobic
character, which may be too high to facilitate transport
through the bacterial cell membrane. Additionally,
increasing the length of the alkyl chain decreases the sol-
ubility of water [26], the lower antibacterial activity of
dimeric amphiphiles [Ad-2(amC14)] and [Ad-2(amC16)]
also may be due to the poor solubility in water. That is
probably why the [Ad-2(amC12)] exhibits the best anti-
microbial activity compared with [Ad-2(amC14)] and [Ad-
2(amC16)].
five different temperatures are listed in Table 2. It can be
seen that all the standard Gibbs free energy changes DGmꢀ
are negative, indicating that the micellization is spontane-
À
Á
À
Á
ous. And the values of DGꢀm become more negative with
increasing hydrophobic chain length. The more negative of
À
Á
DGꢀm means the stronger aggregation at the air/water
interface. The increase in chain length is favorable to
forming micelles due to the increase in the hydrophobic
interactions between the hydrophobic chains. The values of
À
Á
standard enthalpy changes DHmꢀ for micellization are
negative as well, implying that the micelle formation pro-
cess is exothermic [22]. For [Ad-2(amC12)], the value of
À
Á
the standard entropy of micellization ꢂTDSꢀm is larger
À
Á
than enthalpy changes Dꢀm , indicating the micellization is
entropy-driven. But for [Ad-2(amC14)] and [Ad-
2(amC16)], when the temperature is more than 308 and
À
Á
298 K, respectively, the DHmꢀ is larger than TDSmꢀ , which
indicates that the micellization for [Ad-2(amCn)] is
entropy-driven at low temperature and enthalpy-driven at
high temperature.
For comparison, the MIC values of the gemini surfactant
also contain the amide groups and twelve carbon alkyl
chains, N,N-bis(N-dodecyl-N,N-dimethylglycine)-1,4-di-
aminobutane dihydrochloride (DABB) [23], are also listed
in Table 3, it is interesting that the surfactant [Ad-
2(amC12)] with adamantane spacer have much lower MIC
values for all studied bacteria, which indicates that the
adamantane may plays an important role in the antimi-
crobial activity.
Antimicrobial Activity
The antimicrobial activity of the cationic gemini surfac-
tants [Ad-2(amCn)] on various gram-positive bacteria
(G?) and gram-negative bacteria (G-) were evaluated by
determining the minimal inhibitory concentration
(lgꢁmL-1), the values for which were given in Table 3.
From Table 3, it can be seen that these target gemini
surfactants [Ad-2(amCn)] exhibit antimicrobial activities.
123

J Surfact Deterg
´
´
15. Chlebicki J, We˛grzynska J, Maliszewska I, Oswie˛cimska M
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Finally, this study showed that the compound [Ad-
2(amC12)] have excellent antibacterial activity. The MIC
values of all studied bacteria were lower than 5 lgꢁmL-1
(For S. aureus, B. subtilis, P. aeruginosa, V. Parahemo-
lyticus, and E. coli, the MIC for [Ad-2(amC12)] were 0.7,
0.3, 2.1, 4.2, and 2.1 lgꢁmL-1, respectively.), and also
lower than that of BAC (benzalkonium chloride) [27],
which is currently utilized for disinfectants in hospital. This
work, integrating adamantane and cationic gemini surfac-
tants, leads to possible advances in the formulation of new
types of bactericides.
16. Ghumare AK, Pawar BV, Bhagwat SS (2013) Synthesis and
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Acknowledgments The authors greatly appreciate the financial
support by the Key Program for Scientific and Technological Inno-
vations of Higher Education Institutes in Guangdong Province
(CXZD1022), and the Program for Scientific and Technological
Innovations in the Department of Education of Guangdong Province
(No. 2012KJCX0043).
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Xing Zhong received his B.Sc. from Guilin University of Technology
(2009) and is currently finishing his Ph.D. in applied chemistry at
Guangdong University of Technology, Guangzhou, China. His
interests are focused on the synthesis and application of surfactants,
adamantane chemistry and its biological relevance.
Jianwei Guo is a professor at the School of Chemical Engineering
and Light Industry at Guangdong University of Technology,
Guangzhou, China. He obtained an M.Sc. in organic chemical
industry (1995) at Tianjin University, a Ph.D. in industrial catalysis
(2001) at South China University of Technology and a post-doctorate
at Northwestern Polytechnical University (2003). His research is
focused on catalysts, surfactants, detergents, flame retardants, and
self-healing materials.
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Synthesis of functional derivatives of tricyclic hydrocarbons.
Synth Commun 14:113–119
Shuqin Fu received her B.Sc. from JiangXi University of Science and
Technology (2011) and is currently a Ph.D. student at Guangdong
University of Technology, Guangzhou, China. Her main field of
research is synthesis and properties of surfactants.
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Synthesis and properties of novel antifungal gemini compounds derived
from N-acetyl diethanolamines. J Surfactant Deterg 11:223–230
123

J Surfact Deterg
Dongyu Zhu earned her Ph.D. in polymer chemistry and physics in
June 2013 in Sun Yat-sen University. Now, she is a postdoctoral
research associate at the School of Chemical Engineering and Light
Industry, Guangdong University of Technology where she obtained
her masters degree in 2010. Her main research interests are focused
on surfactants, detergents, flame retardants, hydrogels, and self-
healing materials.
Jinping Peng is an associate professor at the School of Chemical
Engineering and Light Industry at Guangdong University of Tech-
nology, Guangzhou, China. He obtained a Ph.D. (2008) at Hohai
University. His research is focused on environmentally friendly
functional materials, and water environmental protection.
123