Micellization and antimicrobial properties of N-alkyl-(2-hydroxypropyl)morpholinium bromides

Article abstract of DOI:10.1016/j.molliq.2021.116538

New ionic-liquid cationic surfactants have been synthesized on the basis of alkyl (C₉, C₁₀, C₁₂, C₁₄) bromides and 1-(4-morpholinyl)-2-propanol. Surface activity and specific electroconductivity of aqueous solutions of the obtained surfactants have been studied by tensiometric and conductometric methods. Depending on the length of the alkyl chain, the values of critical micellization concentration (CMC), maximum adsorption (Г_max), area of minimal cross-sectional surface of polar group of the surfactant (A_min), adsorption efficiency (pC₂₀), surface pressure (π_CMC), binding degree of the counter-ion (β), changes of Gibbs free energies of micellization and adsorption processes (ΔG_mic and ΔG_ad) have been determined. Antimicrobial properties of the synthesized ionic-liquid surfactants have been studied on the example of different bacteria and fungus.

Full text of DOI:10.1016/j.molliq.2021.116538

Journal Pre-proofs
Micellization and Antimicrobial Properties of N-alkyl-(2-hydroxypropyl)mor-
pholinium Bromides
Ravan A. Rahimov, Gulnara A. Ahmadova, Xuraman A. Huseinova, Sevda A.
Muradova, Rustam X. Mammadov, Inara V. Rustamova, Fatma I. Qasimova,
Fedor I. Zubkov
PII:
S0167-7322(21)01262-9
DOI:
https://doi.org/10.1016/j.molliq.2021.116538
MOLLIQ 116538
Reference:
To appear in:
Journal of Molecular Liquids
Received Date:
Revised Date:
Accepted Date:
21 February 2021
11 May 2021
17 May 2021
Please cite this article as: R.A. Rahimov, G.A. Ahmadova, X.A. Huseinova, S.A. Muradova, R.X. Mammadov,
I.V. Rustamova, F.I. Qasimova, F.I. Zubkov, Micellization and Antimicrobial Properties of N-alkyl-(2-
hydroxypropyl)morpholinium Bromides, Journal of Molecular Liquids (2021), doi: https://doi.org/10.1016/
j.molliq.2021.116538
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Micellization and Antimicrobial Properties of N-alkyl-(2-hydroxypropyl)morpholinium
Bromides
Ravan A. Rahimova,b,f*, Gulnara A. Ahmadovab, Xuraman A. Huseinovab, Sevda A. Muradovac,
Rustam X. Mammadovd, Inara V. Rustamovab, Fatma I. Qasimovab, Fedor I. Zubkove
aDepartment of Chemical Engineering, Baku Engineering University, Hasan Aliyev str. 120,
Baku, Absheron, AZ 0101, Azerbaijan
bInstitute of Petrochemical Processes of Azerbaijan National Academy of Sciences, Hojaly ave.
30, AZ 1025, Baku, Azerbaijan
cDepartment of Medical Microbiology and Immunology, Azerbaijan Medical University, str. S.
Vurgun 163, AZ 1078, Baku, Azerbaijan
dNakhchivan State University, University campus, AZ 7012, Nakhichivan AR, Azerbaijan
eOrganic Chemistry Department, Faculty of Science, Peoples’ Friendship University of Russia
(RUDN University), 6 Miklukho-Maklaya St., Moscow, 117198, Russian Federation
fDepartment of Chemical Engineering, School of Engineering and Applied Science, Khazar
University, 41 Mahsati Str., AZ 1096, Baku, Azerbaijan
Abstract
New ionic-liquid cationic surfactants have been synthesized on the basis of alkyl (C9, C10, C12,
C14) bromides and 1-(4-morpholinyl)-2-propanol. Surface activity and specific electroconductivity
of aqueous solutions of the obtained surfactants have been studied by tensiometric and
conductometric methods. Depending on the length of the alkyl chain, the values of critical
micellization concentration (CMC), maximum adsorption (Гmax), area of minimal cross-sectional
surface of polar group of the surfactant (Amin), adsorption efficiency (pC20), surface pressure
(πCMC), binding degree of the counter-ion (), changes of Gibbs free energies of micellization and
adsorption processes (Gmic and Gad) have been determined. Antimicrobial properties of the
synthesized ionic-liquid surfactants have been studied on the example of different bacteria and
fungus.
Key words: cationic surfactant, micellization, surface tension, adsorption, antimicrobial
*Corresponding author:
Dr. Ravan A. Rahimov
Department of Chemical Engineering, Baku Engineering University, Hasan Aliyev str. 120,
Baku, Absheron, AZ0101, Azerbaijan
Tel.: +99450 545 20 48
e-mail: rarahimov@beu.edu.az
revan_chem@mail.ru

Introduction
Cationic surfactants have attracted an attention of chemists for many years because of general
synthesis methods and wide application possibilities in various spheres [1-3]. These surfactants
are used in emulsion polymerization processes [4], minerals flotation [5], textiles processing [6],
as corrosion inhibitors. They also have a big importance in medicine being used as antimicrobial
substances [7], drugs [8], gene delivery agents [9], and in DNA extraction methods [10]. Under
the name of cationic surfactants, such compounds are meant which contain one or several
hydrophobic groups linked to positively charged nitrogen atom. These compounds are called
ammonium salts. In recent years, of obtainment and study of the surfactants containing
imidazolium, pyridinium, pyrrolidinium and morpholinium fragments as cationic groups have
induced a large interest [11-14]. One of the main reasons of such interest is an ionic-liquid nature
of this type surfactants due to bulkiness of the cationic group [12-15]. Ionic liquids are substances
consisting of only ions and melting of temperatures lower than 100 C, sometimes, even [16] in
room conditions. They have unique properties such as low melting temperatures, high thermal
stability, low vapor pressure and others. Varying the nature of the cation and anion, it is possible
to change the properties of these compounds in the needed direction. Among the above-mentioned
classes of ammonium-type ionic liquids, the least poisonous and the cheapest are morpholinium-
based salts [17]. They are used in design of ionic-liquid crystals [18, 19], as a solvent of cellulose
[20], catalyst in organic syntheses [21], a component of electrochemical processes [22]. Zh. Qian
and et al. [15] synthesized N-alkyl-N-methylmorpholinium bromide (CnMMB, n = 12, 14, 16)-
type ammonium salts and studied their surface activity properties. It was established that CMC of
CnMMB cationic surfactants is a little lower than these of N-alkyl-N-methylpiperidinium bromides
(CnPDB) and N-alkyl-N-methylpyrrolidinium bromides (CnMPB) surfactants. A. B.
Mirgorodskaya et al. [23] synthesized CnMMB (n =10, 12, 14, 16, 18) cationic surfactants and
studied their antimicrobial properties against different microorganisms. These surfactants were
also investigated as corrosion inhibitors in H2S and CO2 media. It was revealed that the surfactants
having the alkyl chain length n=14 and n=16 have stronger both corrosion-inhibiting and
antimicrobial properties than the others. Varying the alkyl chain length and the anion nature, a
number of properties of these compounds may be changed. Alkylation of nitrogen atom in
morpholine by hydroxy group-containing agents seriously affects the nature of the hydrophilic
part. When methyl group in the cationic surfactant N-cetyl-N-methylmorpholinium bromide is
replaced by 2-hydroxyethyl group, CMC of the surfactant decreases [23]. Therefore, addition of
hydroxy-group containing fragments to nitrogen atom will bring about a change in surfactivity
properties of this class surfactants. Conduction of researches in this direction is of practical
importance.
The present work is devoted to synthesis of new cationic surfactants based on 1-(4-
morpholinyl)-2-propanol and alkyl bromides, a study of their aqueous solutions by tensiometric
and conductometric methods as well as an investigation of antimicrobial properties of the obtained
surfactants.
Experimental part
Reagents and instrumentation
1
Bruker TOP SPIN spectrometer (300.13 MHz and 75.46 MHz) was applied for registering H
13
NMR and C NMR spectra. Values of chemical shift () in ppm are registered downfield with

regard to TMS. D2O was taken as a solvent. IR spectra were registered (in KBr disks) on an
ALPHA FT-IR (Bruker). The thermogravimetric (TG) analysis was carried out with a NETZSCH
STA 449F3 equipment at a scanning rate of 10 C per minute under N2 atmosphere. 1-
bromononane (Alfa Aesar GmbH  Co KG, Germany), 1-bromodecane (Alfa Aesar, England), 1-
bromododecane (Alfa Aesar, England), 1-bromotetradecane (Sigma Aldrich, Japan), morpholine
(98%, Alfa Aesar) and propylene oxide (98%, Alfa Aesar) of analytical grade were used.
Method of 1-(4-morpholinyl)-2-propanol synthesis
1-(4-morpholinyl)-2-propanol was synthesized by interaction of morpholine and propylene oxide
at 1:1 molar ratio according to the following scheme (Scheme 1):
CH2 CH
O
CH3
O
NH +
O
N
CH2 CH
OH
CH3
Scheme 1. Reaction scheme of the synthesis of 1-(4-morpholinyl)-2-propanol
To synthesize 1-(4-morpholinyl)-2-propanol, 0.1 mol of morpholine was introduced to a flat-
bottom flask and 0.1 mol of propylene oxide was added. The reaction was conducted at room
temperature, stirring with a magnetic mixer under the nitrogen atmosphere for 48 hours. As the
reaction is exothermal, the flask was placed into a water bath. Thus, appearance of high
temperature was prevented. By vacuum distillation of the final mixture, the reaction product was
purified from the admixtures. The yield of the reaction product was 98%. It is a yellowish
transparent liquid. It dissolves well in water, ethanol, acetone, partially-in hexane. The structure
of the synthesized 1-(4-morpholinyl)-2-propanol was confirmed by NMR- and IR-spectroscopy
methods. IR ν, сm-1: 3434  (OH), 2931, 2854 and 2809  (CH), 1454 and 1373  (CH), 1271
1
and 1208  (CN), 1139 and 1113  (CO). (Fig. S1). H NMR, (300.13 MHz, D2O), δ (ppm):
1.03-1.05 (CHCH3), 2.27-2.31 (N-CH2-CH), 2.45-2.46 (CH2N), 3.61-3.64 (CH2OCH2), 3.93
13
(CHOH) (Fig. S2). C NMR, (75.47 MHz, D2O), δ (ppm): 20.9, 44.5, 53.1, 64.0, 65.3, 66.0,
66.7. (Fig. S3) (see Figs. S1-S3 in Supporting Information).
Synthesis of cationic ionic-liquid surfactants based on 1-(4-morpholinyl)-2-propanol
0.1 mol of 1-(4-morpholinyl)-2-propanol and 30 mL acetonitrile were introduced into a flat-bottom
two-neck flask. After homogenizing the mixture 0.1 mol of 1-bromononane (1-bromodecane, 1-
bromododecane or 1-bromotetradecane) was added to it. The reaction was conducted using
magnetic mixer, reflux condenser and heater for 18-20 hours at the temperature of boiling of the
mixture.
The scheme of synthesis of ionic-liquid surfactants may be illustrated as following (Scheme 2):
R
+
CH3
RBr
O
N
Br
CH2 CH
CH3
O
N
CH2 CH
OH
OH
CnHMPB
R=C9H19, C10H21, C12H25, C14H29.
Scheme 2. Synthesis of cationic ionic-liquid surfactants by interaction of 1-(4-morpholinyl)-2-
propanol with 1-bromoalkanes

For isolation of the synthesized products from the reaction mixture, vacuum distillation
was used. Herewith, the obtained ionic-liquid surfactant was purified from the solvent and
unreacted 1-bromoalkane. To achieve high purity of the surfactants, they were recrystallized in
acetone three times. The yield of the obtained ionic-liquid surfactants was 90-94%. They dissolve
well in ethanol, acetone, ethyl acetate, partially-in water. Purity of the obtained cationic ionic-
liquid surfactants was determined by NMR- and IR-spectroscopy methods. IR ν, сm-1: 3281 
(OH), 2919 and 2851  (CH), 1466 and 1374  (CH), 1255  (CN), 1118 and 1051  (CO),
720  -(CH2)-x (Fig. 1). 1H NMR, (300.13 MHz, D2O), δ (ppm): 0.81 (CH2CH3), 1.12 (CHCH3),
1.22 (CH2 chain), 1.75 (CH2CH2N+), 2.98-3.16 (CH2CH2N+), 3.54 (CH2N+CH2), 3.86
(N+CH2CH(OH) CH3), 4.01 (CH2N+CH2), 4.32 (CH-OH) (Fig. 2). 13C NMR, (75.47 MHz,
CDCl3), δ (ppm): 13.8, 14.0, 20.1, 21.6, 21.8, 22.6, 22.7, 26.2, 29.2, 29.4, 29.6, 29.8, 29.9, 30.0,
31.9, 32.1, 32.6, 52.1, 58.8, 59.4, 60.4, 61.5, 61.6, 63.3, 64.4. (Fig. 3). Figs. S4-S5 (see in
Supporting Information) shows the results of thermogravimetric analysis of C12HMPB and
C14HMPB. As can be seen in the figures, C12HMPB begins to decompose at 212.5 C and
C14HMPB at 227.8 C. Most part of the surfactants (50%) are completely decomposed up to 300
C.
Determination of surface activity of the synthesized ionic-liquid surfactants
Surface tension of the synthesized ionic-liquid surfactants was determined using Du Nouy
tensiometer KSV Sigma 702 tensiometer (Attension Biolin Scientific, Finland). 0.00025-0.2% wt.
aqueous solutions of the ionic-liquid surfactants were prepared and, after 24 hours, their surface
tension were measured at 25 C [24]. For preparation of the aqueous solutions, distilled water was
used. The surface tension of this water at the border with air at 25 C was equal to 71.9 mN/m.
Those results of the measurements were taken into consideration where an error did not exceed
±0.2 mN/m.
Determination of specific electrical conductivity of the synthesized ionic-liquid surfactants
Specific electrical conductivities () of aqueous solution of the obtained ionic-liquid surfactants
were determined by means of “ANION-4120” conductometer (Russian Federation). For this
purpose, first, 0.0001%-0.4% wt. aqueous solutions of the surfactants were prepared and, after 24
hours, their specific electrical conductivities at 25 C were determined [25]. Specific electrical
conductivity of the distilled water for preparing aqueous solutions of the surfactants was 1.8-2.2
μS/cm at 25 C. In the studies, the results of the measurements with an error loss than ±0.3 μS/cm
were used.
Dynamic Light Scattering (DLS)
The size distribution of the aggregates, which formed by the synthesized cationic surfactants in
water was determined at 25 C by using the Particle Size Analyzer (HORIBA LB-550, Japan). As
a light source in the device is used a laser diode with the wave length of 650 nm and the power of
5 mW. The measuring range of the device was in the range from 1 nm to 6 μm. The density of the
samples, taken for the study are CMC and 3CMC. Each sample was measured by repetition at
least three times. The distribution of solvent diffusion coefficients (D) was obtained by analyzing

the correlation function of data scattering in the CONTIN process. Then was determined
hydrodynamic diameter (Dh) of the aggregates by using the Stokes-Einstein equation
Dh=kT/3πηD, where k is the Boltzmann constant, T is the absolute temperature, and η is the
solvent at that temperature.
Testing of antimicrobial properties of the obtained ionic-liquid surfactants
Two Gram-positive (Staphylococcus aureus, Bacillus anthracoides) bacteria, three Gram-negative
(Pseudomonas aeuroginosa, Escherichia coli, Klebsiella pneumoniae) bacteria and fungi
(Candida albicans) were included in the test cultures to study the antimicrobial effect of cationic
surfactants. Suspensions prepared at 106 mic./ml were evenly distributed on the surface of the
appropriate nutrient media using a spatula. The studied cationic surfactant and/or its solutions of
different concentrations were soaked in sterile discs made of filter paper with a diameter of 6 mm
and placed on the surface of the nutrient medium inoculated with microorganisms. The samples
were incubated at 37 °C for one day. The effect of cationic surfactants is determined by the
diameter of the sterile zone (expressed in mm) which the microorganism does not grow around the
disc. The diameter of the sterile zone in which the microorganism does not develop is inversely
proportional to the minimum inhibitory concentration of the chemical in the microorganism and
indicates the degree of sensitivity.
Results and Discussion
Surface properties of the synthesized ionic-liquid surfactants in aqueous solution
The surface tension at the border of aqueous solutions of the 1-(4-morpholinyl)-2-propanol-based
ionic-liquid surfactants with air was determined using tensiometric method. The obtained results
are presented in Fig.4 as surface tension isotherms. As is seen from the figure, surface tension
decreases as the concentration of all four surfactants increase. After reaching a certain
concentration, the surface tension values are stabilized. The concentration corresponding to the
beginning of this stabilization is taken as the CMC value.
In table 1, the CMC values of the synthesized surfactants are given. These values for
C9HMPB, C10HMPB, C12HMPB and C14HMPB ionic-liquid surfactants are respectively as
following: 3.40, 2.73, 1.27 and 0.355 mM. As is seen from the table, with elongation of the alkyl
chain from C9 to C14, the CMC values decrease. A similar regularity is observed in the case of the
cationic surfactants with another type head-group [26,27]. With lengthening of hydrocarbon chain,
hydrophobicity of the ionic-liquid surfactants rises. So, their CMC values are lowered. The nature
of surfactant head-group is one of the main factors impacting stability of micelles. For a
homological series of single alkyl chain-surfactants with such a chain of varying length, CMC
obeys Stauff-Klevens rule [28] prognosticating a logarithmic dependence between log CMC and
the number of carbon atoms in the alkyl group:
logCMC = A − Bn (1)
where A and B are constants for a certain homological series of surfactants at a given temperature.
Constant “A” varies depending on the nature and number of hydrophilic groups. “B” is the constant
describing an impact of each methylene group, added to the alkyl chain, on the CMC value. The
value of “B” is ~0.5 for nonionic surfactants, 0.28-0.30 for the surfactants containing paraffinic
chain and ionic head-group. In Fig. 5, for the synthesized ionic-liquid surfactants, the dependence
of CMC (in logarithm from moldm3 value) on the number of carbon atoms in the alkyl chain (at

25 C) is illustrated. As is seen from the graph, the dependence is a straight line with a slope (B)
0.2153, intercept (A) 0.4242 and a correlation coefficient 0.9994. Similar results are observed for
n-alkyl-3-methylpyridinium bromides [29] and n-alkyl-N-(2-hydroxypropyl)-N,N-(2-
hydroxyethyl) ammonium bromides [30] type cationic surfactants.
In Table 2, surfactivity parameters for the surfactants having N-methylmorpholinium
bromide [31] and N-(2-hydroxypropil)dimethylammonium bromide [32] head-groups and C12 or
C14 alkyl chains. From comparison of the CMC values from Tables 1 and 2, the following
consequency will be derived: CnMMB  CniPrOH  CnHMPB. When methyl group in N-
methylmorpholinium fragment is replaced by 2-hydroxypropyl group, CMC decreases, i.e., it is
smaller for CnHMPB-type surfactants.
For the synthesized ionic-liquid surfactants the value of maximum surface excess
concentration (Γmax) was determined using Gibbs adsorption isotherm equation (2):
1
nRT
d

dlnC
max = ―

lim
(2)
C→CCMC
Area of minimal surface occupied by the polar group Amin was computed by equation (3) [33]:
Amin = 1016/NAmax (3)
where R is the universal gas constant (8.314 J/mol K), T is the absolute temperature, and C is the
concentration of surfactant, NA is the Avogadro number. The value of n is accepted as 2 as there
is one counter-ion linked with each cationic head group.
The calculated values of Γmax and Amin are given in Table 1. As is seen from this table,
lengthening of the alkyl chain leads to a rise of Γmax values whereas Amin diminishes. The same
regularity is observed for cationic surfactants with other head-groups [26, 30]. From comparison
of Γmax and Amin values of the same alkyl chain-surfactants included into Tables 1 and 2, it is
noticeable that Γmax and Amin values for CnHMPB series are between those of CniPrOH and
CnMMB-type surfactants.
For characterization of surfactivity, important parameters are surface pressure (CMC) and
adsorption efficiency (pC20). These parameters are calculated using the following formulas:

CMC =0–CMC (4)
pC20 =−logC20 (5)
where 0 is the surface tension of solvent without a surfactant and CMC is the surface tension in
the presence of the surfactant at CMC [33].
C20 is the concentration of a surfactant consumed for lowering surface tension by 20 mN
m−1. In Table 1, the values of CMC and pC20 for the synthesized ionic-liquid surfactants are
presented. The surface pressure values diminish in the following series: C12HMPB  C10HMPB 
C9HMPB  C14HMPB. The values of pC20 rise with elongation of the alkyl chain. Similar
correlation is noticed in the surfactants having trimethylammonium head-group [33, 34].
According to Table 2, CMC and pC20 values of the surfactants containing N-
methylmorpholinium and N-(2-hydroxypropyl)dimethylammonium head-groups are smaller than
those of the surfactant with N-(2-hydroxypropyl)morpholinium head-group.
Critical packing parameter-CPP values of these surfactants are based on morphology of the
formed aggregates in water and calculated by the following formula:
푉퐻
(6)
퐶
퐶푃푃 = 푎 × 푙
0
where VH is the effective volume of hydrophobic chain, a0 is the area of the polar head-group
surface, lC is the length of the alkyl chain. At the maximum level of concentration, a0 may be

replaced by Amin. The value of VH changes depending on the number of carbon atoms in the
hydrophobic chain. It is calculated by the following formula:
Å3 (7)
푉퐻 = 27.4 + 26.9 × (푛 ― 1)
The value of lC may be computed by the following formula depending on the alkyl chain length:
(8)
푙퐶 ≤ 1.5 + 1.265 × (푛 ― 1) Å
In Table 3, the values of CPP are shown. As is noticed from the table, the CPP values are in the
interval 0 - 0.33. Therefore, in aqueous solution, the micelles of these ionic-liquid surfactants are
in spheroidal form.
Size of the aggregates
The dimensions of the aggregates, which formed by the synthesized cationic surfactants in the
aqueous solution were determined by the DLS method (Fig. 6). As can be seen from the images, a
peak is observed in the C9HMPB surfactant at both of CMC and in the concentration, which 3
times higher than CMC. The size of the aggregates of this surfactant at CMC is 260 nm and at the
density with 3 times higher than CMC is 1000 nm. Two peaks were observed in surfactants with
an alkyl chain length greater than C10. The first peak in CMC is 75 nm, 150 nm and 225 nm,
respectively for C10HMPB, C12HMPB and C14HMPB surfactants. The second peak is 1150 nm for
the C10HMPB, 1500 nm for the C12HMPB and 1730 nm for the C14HMPB. The first peak is the
presence of small vesicles, and the second peak is the presence of large vesicles or bilayer systems.
Aggregates diameter of surfactants in aqueous solution increase about two times with increasing
their alkyl length chains. This is because  increases with increasing alkyl chain length. As the 
increases, the micelles neutralize with the opposite ions, in the meantime they aggregate and form
large vesicles [35, 36]. In surfactants C10HMPB, C12HMPB and C14HMPB is observed the 3 times
higher concentration decreasing of the aggregates diameters than the CMC.
Specific electrical conductivity of the synthesized ionic-liquid surfactants
Specific electrical conductivity of the synthesized ionic-liquid surfactants was determined by
conductometric method at 25 C. Based on the obtained values  vs concentration (C) plots were
built (Figs. 7 and 8). As is seen from the figures, with an increase of concentration of the ionic-
liquid surfactants in water, the value of  rises.  vs C plots are characterized by two different
linear dependences at low and high concentrations. The point of intersection of these straight lines
is CMC. The ration of the slope after CMC (S1) and before CMC (S2) is equal to a dissociation
degree-α of the surfactant counter-ion:
=S1/S2=1- (9)
where  is the binding degree of the counter-ion. In Table 1, the values of  of the synthesized
ionic-liquid surfactants are given. As is clear from the Table 1, the value of  rises as the alkyl
chain in the surfactant lengthens. Its reason is lowering of charge density on the surface of the
micelles [37]. Longer alkyl chain-surfactants form larger aggregates. In very large structures, the
ratio of surface and volume is small. Therefore, polar groups become packed more tightly and are
surrounded by more counter-ions.
Antimicrobial properties of the synthesized ionic-liquid surfactants
The antimicrobial ability of the synthesized cationic surfactants was studied on Gram-positive
(Staphylococcus aureus, Bacillus anthracoides) bacteria, Gram-negative (Pseudomonas

aeuroginosa, Escherichia coli, Klebsiella pneumoniae) bacteria and fungi (Candida albicans). The
obtained results are given in Table 4. As can be seen from the table, the antimicrobial capacity of
the synthesized cationic surfactants is high and varies depending on the length of the alkyl chain.
As can be seen from the table, the synthesized cationic surfactants have a more effective action
against gram-positive bacteria. C14HMPB has a higher effect than other surfactants. Therefore,
cationic surfactants with a higher alkyl chain length have a higher impact. The antimicrobial effect
depends on the following surface parameters of surfactants: CMC, Gad, accumulation of
surfactants on the cell wall and diffusion size of surface active molecule. As can be seen from
Table 1, with the increasing length of the alkyl chain, the CMC and Gad decrease. Therefore,
there will be higher antibacterial capacity in the CnHMPB class surfactants with the lower CMC
and Gad values. The antibacterial ability of cationic surfactants is approximately close against the
Gram-negative bacteria. The surfactant C14HMPB showed the highest antibacterial properties
against the Escherichia coli bacteria. The surfactant C9HMPB, which has a small alkyl chain
length, is more effective against the development of Candida albicans. As the length of the chain
increases, this effect decreases slightly.
Thermodynamic parameters of the synthesized ionic-liquid surfactants
Using CMC and  values for the synthesized ionic-liquid surfactants, the standard Gibbs free
energies for micellization process were calculated by the following formula:
°
= (1+)RTlnXCMC
(10)
∆퐺푚푖푐
where XCMC is the CMC in molar fraction, XCMC = CMC/55.4, where CMC is in mol/L, 55.4
originates from 1 L of water corresponding to 55.4 mol of water at 25 C, - is the binding degree
of counter-ion, R is universal gas constant, and T is standard absolute temperature (298 K). The
values of standard Gibbs free energy for adsorption process at water-air border were computed
according to the following formula [33]:
°
= (1+)RTlnXCMC  0.6023CMCACMC
(11)
∆퐺푎푑
where ACMC has the unit Å2 per molecule, and CMC denotes the surface pressure (in mN/m) at
CMC at the border of surfactant in aqueous solution with air.
In Table 1, Gibbs free energy values for micellization process of the synthesized ionic-
liquid surfactants in aqueous solution and adsorption process at water-air border are presented. It
is seen that, for both micelle formation and adsorption processes, the values of standard Gibbs free
energies are negative. It means that, with these surfactants, micellization and adsorption processes
G
occur spontaneously. Mean while, more negative values of
show that the adsorption process
ad
G
G
on the length
precedes the micelle formation. In Fig. 9, graphs of dependence of
ad and
ad

G
of the alkyl chain of the ionic-liquid surfactants are illustrated. As is evident from the figure
mic
G
and
ad values decrease with elongation of the alkyl chain. Lengthening of this chain enhance
hydrophobic interaction between the alkyl chains and favour micelle formation.
Gibbs free energy of aggregation is contributed by transfer of the ionic liquid fragments
from solution to the aggregates, and therefore, displays the relative input of ionic-liquid
hydrophilic and hydrophobic parts to aggregation process. As was mentioned before [38], the


G
G
value of
micconsists of contributions from the surfactant head-group (
head-group),
mic

°
methylene group of the hydrophobic chain (
) and CH3- group from the alkyl chain top
∆퐺
푚푖푐, 퐶퐻2
°
(
∆퐺
푚푖푐, 퐶퐻 ):
3
°
°
∆G°mic = ∆Gm° ic, head group +∆G
+ 푛 ∆G
(12)
mic, CH3
퐶퐻2
mic, CH2
°
Then, the following may be written for
:
∆퐺푎푑
∆G°ad = ∆G°ad, head group +∆G
+ 푛 ∆G
퐶퐻2 ad, CH2
°
°
(13)
ad, CH3
where
is the number of CH2 groups in the hydrophobic chain of CnHMPB.
푛
퐶퐻2
°
°
From Fig. 9, it is noticed that (
equals 4.17 kJ/mol and, for
)
∆Gmic, head group +∆Gmic, CH
3
°
each methylene group,
is equal to 3.09 kJ/mol. For N-alkyl-N-methylpyrrolidinium
∆G
mic, CH2
bromide [26] and N-alkyl-N-methylimidazolium bromide [38] class ionic liquid surfactants,
∆
°
is 3.01 kJ/mol. Therefore, thermodynamics of methylene groups transfer from aqueous
G
mic, CH2
solution to micelle does not depend on cationic head-group. In the case of N-alkyl-N-
methylmorpholinium bromide, N-alkyl-N-methylpyrrolidinium bromide and N-alkyl-N-
°
°
methylimidazolium bromide class ionic-liquid surfactants,
equals
)
(∆Gmic, head group +∆Gmic, CH
3
respectively 3.50, 3.61 and 3.7 kJ/mol. For the synthesized N-alkyl-N-(2-
°
°
hydroxypropyl)morpholinium bromide class ionic-liquid surfactants,
(∆Gmic, head group +∆G
mic, CH3
value is smaller (-4.17 kJ/mol). This fact shows that, with this head-group ionic-liquid
)
surfactants, micellization occurs more readily. Therefore, in N-alkyl-N-methylmorpholinium
bromide class surfactants, replacement of methyl group connected to nitrogen atom by 2-
hydroxypropyl group enhances micellization capacity of the surfactant head-group. (
∆
G°ad, head group +∆G
∆G
°
°
) equals 8.91 kJ/mol, for each methylene group
is 2.95 kJ/mol.
ad, CH2
ad, CH3
°
The value of
is close to those of other classes of such surfactants [33].
∆G
ad, CH2
Conclusions
On the basis of 1-(4-morpholinyl)-2-propanol and alkyl bromides (nonyl-, decyl-, dodecyl- and
tetradecyl bromde), new ionic-liquid cationic surfactants were synthesized and characterized by
spectroscopic (1H, 13C NMR and IR) and thermogravimetric analysis methods. Micellization and
adsorption properties of these surfactants were studied by measurements of surface tension and
specific electrical conductivity. It was established that, with an elongation of the alkyl chain of the

G
G
ionic – liquid surfactants, the values of CMC, Amin,
mic and
decrease whereas the values
ad
of , max and pC20 rise. It was revealed that the CMC values are much less compared to surfactants
with the N-methylmorpholinium and N-(2-hydroxypropyl)-N,N-dimethyl ammonium similar
head-groups ionic-liquid surfactants. Antimicrobial properties of the obtained novel ionic-liquid
surfactants were studied. It was determined that the surfactant with C14-alkyl chain manifests the
strongest antimicrobial properties.
Acknowledgements. This paper has been supported by the RUDN University Strategic Academic
Leadership Program (Fedor I. Zubkov determined the degree of purity and analyzed the
spectroscopic results of the obtained surfactants). The authors thank the Institute of Petrochemical
Processes of National Academy of Sciences of Azerbaijan for supporting this research.
Credit Author Statement.
Ravan A. Rahimov: Writing - Review & Editing, Supervision, Methodology. Gulnara A.
Ahmadova: Investigation, Resources, Writing - Original Draft. Khuraman A. Huseynova:

Investigation, Resources, Writing - Original Draft. Sevda A. Muradova: Investigation, Data
curation. Rustam X. Mammadov: Investigation, Resources, Writing - Original Draft. Inara V.
Rustamova: Writing - Original Draft. Fatma I. Qasimova: Validation, Formal analysis. Fedor
I. Zubkov: Validation, Formal analysis.
Compliance with ethical standards
Conflict of interest. The authors declare that they have no conflict of interest.
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Table 1. Surfactivity parameters of 1-(4-morpholinyl)-2-propanol-based ionic-liquid surfactants
(25 C)

CMC103, max1010,
CMC
,
CMC
,
Gmic,
Gad,
Amin102,
Surfactants moldm3 molcm2
nm2
β
mN·m1 pC20 mNm1 kJmol1 kJmol1
C9HMPB
C10HMPB
C12HMPB
C14HMPB
3.40
2.73
1.27
0.355
1.40
1.45
1.52
1.55
118.5 0.335 26.6 4.03 45.4
-32.08
-35.14
-41.30
-47.41
-35.33
-38.41
-44.45
-50.05
114.3
109.1
107.0
0.43 24.5 4.25 47.5
0.56 24.0 4.47 48.0
0.60 31.0 4.60 41.0
Table 2. Surfactivity parameters of some cationic surfactants with C12 and C14 alkyl chain
(25C)
CMC103,
max1010,
Amin102, nm2

CMC, mNm1
n
pC20
moldm3
molcm2
CniPrO CnMM CniPrO CnMM CniPrO CnMM CniPrO CnMM CniPrO CnMM
H
B
H
B
H
B
H
B
H
B
12 11.70 16.11 0.987
14 1.47 3.96 0.883
2.51 168.19 66.20
2.78 188.05 59.73
37.8
37.9
29.02
29.14
3.5
2.7
2.11
2.69
Note.CnMMBN-alkyl-N-methylmorpholinium bromides [31]
CniPrOHN-alkyl-N-(2-hydroxypropyl)-N,N-dimethyl ammonium bromides [32]
Table 3. CPP of 1-(4-morpholinyl)-2-propanol-based ionic-liquid surfactants
Surfactants
C9HMPB
C10HMPB
C12HMPB
C14HMPB
CPP
0.18
0.18
0.19
0.20
Table 4. Antimicrobial properties of the synthesized surfactants by disk-diffusion method
Bacteria and fungi
C9HMPB
C10HMPB
C12HMPB
C14HMPB
Diameter of inhibition zone (mm)
Escherichia coli
Pseudomonas aeruginosa
Klebsiella pneumoniae
Staphylococcus aureus
Bacillus anthracoides
Candida albicans
12
-
7
17
11
20
13
13
14
19
18
17
11
12
15
16
16
17
14
10
9
23
22
18

Fig. 1. IR spectrum of C12HMPB
Fig. 2. 1H NMR spectrum of C12HMPB

Fig. 3. 13C NMR spectrum of C12HMPB
Fig. 4. Surface tension plots of C9HMPB (1), C10HMPB (2), C12HMPB(3) and C14HMPB(4) in
aqueous solution at 25C versus natural logarithmic concentration of surfactants
Fig. 5. Dependence of -log(CMC) for CnHMPB on the number of carbon atoms in the alkyl
chain

Fig. 6. The results of DLS measurements (25 ºC) for synthesized ionic liquid surfactants at
various concentrations
Fig. 7. Plots of specific electrical conductivity versus surfactant concentration for aqueous
solutions of C9HMPB (1) and C10HMPB (2) at 25C

Fig. 8. Plots of specific electrical conductivity versus surfactant concentration for aqueous
solutions of C12HMPB(a) and C14HMPB(b) at 25C
Fig. 6. Dependence of Gibbs free energy change for CnHMPB on the number of carbon atoms in
the alkyl chain

Credit Author Statement.
Ravan A. Rahimov: Writing - Review & Editing, Supervision, Methodology. Gulnara A.
Ahmadova: Investigation, Resources, Writing - Original Draft. Khuraman A. Huseynova:
Investigation, Resources, Writing - Original Draft. Sevda A. Muradova: Investigation, Data
curation. Rustam X. Mammadov: Investigation, Resources, Writing - Original Draft. Inara V.
Rustamova: Writing - Original Draft. Fatma I. Qasimova: Validation, Formal analysis. Fedor
I. Zubkov: Validation, Formal analysis.

Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
☐ The authors declare the following financial interests/personal relationships which may be
considered as potential competing interests:
The authors declare with certain confidence that no financial interests, personal relationships or
anything of similar nature that can have any kind of influence on the work presented in the current
paper are known to them.

Highlights
 New cationic surfactants were obtained throughout quaternization of 1-(4-morpholinyl)-
2-propanol.
 Physico-chemical parameters of the synthesized cationic surfactants have been
determined.
 The synthesized cationic surfactants determined CMC, which decreased by increasing
alkyl chain length.
 The prepared cationic surfactants have good antibiotic effect against microorganism.