Cationic surfactants are widely used in modern technologies as detergents, lubricants, corrosion inhibitors, solubilizers, carriers of drugs and diagnostic agents, and antimicrobial agents [1–4]. They play an important role as micellar catalysts influencing the rate and mechanism of practically important chemical transformations [5–8]. In particular, they significantly accelerate nucleophilic substitution processes, especially, ion–molecule reactions. Processes with the participation of charged nucleophiles such as halide, alkoxide, hydroxamate, and iodose benzoate anions in micellar media have been studied in detail [9–11]. Hydrolytic processes that occur in alkaline media in the presence of cationic surfactants deserve special consideration [8, 12–16]. The concentration of hydroxide ions at a positively charged micellar surface increases the likelihood of contact between a hydrophilic nucleophile and an organic substrate solubilized in the micelle, which leads to an acceleration of the process. In this case, a multicenter binding mechanism often takes place in micellar systems. It includes the simultaneous participation of electrostatic, hydrophobic, and in some cases specific interactions, which are a key component affecting the solubility and reactivity of reactants in the development of biomimetic systems [8, 17–19]. The catalytic action of cationic surfactants is widely used in the decomposition of organophosphorus ecotoxicants and neurotoxins [20–24]. However, a search for new micellar systems and a systematic study of structure–activity relationships considered in current scientific literature [25–28] remain of considerable interest.

Due to the fact that the functionalization of cationic surfactants (for example, the introduction of OH groups) leads to changes in their behavior and properties in solutions [29–31], in this work, attention was focused on the target-oriented design and testing of mono- and dihydroxy derivatives of alkylpiperidinium amphiphiles having substituents in different positions of the molecules. The structural formulas of the test unsubstituted and functionalized piperidinium surfactants with identical hydrophobic (hexadecyl) radicals—hexadecyl(methyl)piperidinium bromide (PM), hexadecyl(methyl)-3-hydroxypiperidinium bromide (3-HPM), hexadecyl(2-hydroxyethyl)piperidinium bromide PHE, and hexadecyl(2-hydroxyethyl)-4-hydroxypiperidinium bromide (4-HPHE)—are given below.

Formulas of the test hexadecylpiperidinium surfactants.

To establish structure–property relationships, the catalytic effect of surfactants on the rate of hydrolytic cleavage of phosphorus acid esters was studied. Ethyl p-nitrophenyl ethylphosphonate (armine), an irreversible cholinesterase inhibitor resistant to external influences, which is often used as a model compound in studying the effects of organophosphorus ecotoxicants, was chosen as a substrate [32, 33].

EXPERIMENTAL

Commercial samples of Tween 80, Orange OT, and armine (Sigma-Aldrich) with a purity of 99% were used in this study.

The hexadecylpiperidinium surfactants were synthesized by the interaction of corresponding piperidine derivatives with hexadecyl bromide in ethanol followed by recrystallization [34].

Water purified on a Direct-Q 5 UV system (Merck Millipore, Germany; pH 6.8–7, χ = 2–3 μS/cm) was used for the preparation of solutions.

The specific electrical conductivity of the samples was measured on a WTW inoLab Cond 720 conductometer (WTW, Germany). To determine the Kraft point, surfactant solutions with a concentration of 1 wt % were used. The solutions were cooled to the precipitation of the surfactant; then, as the solution was heated, the electrical conductivity of the supernatant was measured (heating rate, 0.5 K/min).

The absorption spectra of solutions were recorded in thermostatically controlled quartz cells with an optical path length of 1 cm on a Specord 250 Plus spectrophotometer (Analytik Jena AG, Germany).

The solubilizing effect of micellar systems with respect to the dye Orange OT was evaluated by determining the limiting concentration of the dye in surfactant solutions. For this purpose, the solutions of surfactants in a concentration range from 0.05 to 10 mM were prepared, and a fixed amount of crystalline Orange OT was added to them. The prepared samples were stirred for 2 h and left for 48 h at thermostatting (25°C) to achieve equilibrium. Then, the precipitate was separated, and the optical absorption of the solution (D) at 495 nm was determined; the dye concentration in the sample was estimated taking into account the molar absorption coefficient of the dye.

The surface potential of the aggregates was determined by a spectral method; changes in the acid–base properties of an indicator (p-nitrophenol) depending on the surfactant concentration were studied in accordance with a published procedure [35]. The observed value of pKa of p-nitrophenol (pKa,obs) was calculated using the Henderson–Hasselbach equation

$$p{{K}_{{{\text{a}}{\text{,obs}}}}} = p{\text{H}} + \log\frac{{\left[ {{\text{phenol}}} \right]}}{{\left[ {{\text{phenolate}}} \right]}}.$$

The dissociation constant observed at Csurfactant → ∞ was taken as the dissociation constant of p-nitrophenol in the micellar phase (Ka,m).

The kinetics of the alkaline hydrolysis of armine was investigated spectrophotometrically. The course of the process was monitored by changes in the optical absorption of the reaction solutions at a wavelength of 400 nm, which corresponds to the absorption maximum of the p-nitrophenolate anion. The initial concentration of the substrate was (2–5) × 10–5 mol/L, and the degree of conversion was higher than 90%. The observed rate constants (kobs) were determined from the relationship ln(D∞ – D) = –kobst + const, where D and D∞ are the optical absorption of the reaction solution at time t and at the end of the reaction, respectively. The values of kobs were calculated by the least squares method. The error in all of the experiments did not exceed 4%.

RESULTS AND DISCUSSION

The functional activity of surfactant solutions is manifested when certain concentration and temperature thresholds are reached. In this regard, at the first stage of this work, we investigated the aggregation behavior of hexadecylpiperidinium surfactants. The critical micelle concentrations (CMCs) and Kraft temperatures were determined by conductometry. Table 1 and Figs. 1 and 2 summarize the experimental data. It can be seen that the test surfactants have similar CMCs despite differences in their structures; however, the temperature limits of micelle formation decreased with the number of hydroxyl groups in the molecules. In addition, it was found that the presence of a hydroxyl group in piperidinium surfactants improves their solubility in water to expand their applicability.

Table 1.   Aggregation parameters of hexadecylpiperidinium surfactants and their solubilization capacity for the dye Orange OT
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Fig. 1.
figure 1

Concentration dependence of the electrical conductivity of hexadecylpiperidinium surfactants PM and 4-HPHE (25°C).

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Fig. 2.
figure 2

Temperature dependence of the electrical conductivity of 4-HPHE (1% solution).

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The ability of hexadecylpiperidinium surfactants to increase the solubility of low-polarity organic compounds was compared using the hydrophobic dye Orange OT, which is widely used as a spectral probe to characterize the solubilization effect of micellar solutions and to determine the CMCs of amphiphilic compounds. This dye is almost insoluble in water; the observed sharp increase in optical absorption at a surfactant concentration above the CMC reflects the solubilization of the dye and an increase in its concentration in micellar solutions. Figure 3 shows the graphs characterizing changes in the optical absorption of saturated solutions of Orange OT depending on the surfactant concentration; they were measured at an absorption maximum at 495 nm (the molecular extinction coefficient ε = 18720 L mol–1 cm–1), which formed a basis for the determination of solubilization capacity (S). The values of this parameter were calculated from the formula S = b/ε, where b is the slope of the linear part of the dependence of the reduced optical absorption on the surfactant concentration.

Fig. 3.
figure 3

Changes in the optical absorption of Orange OT solutions at an absorption maximum (495 nm) depending on the concentration of hexadecylpiperidinium surfactants (25°C).

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From the experimental results (Table 1), it follows that the solubilization capacity of hexadecylpiperidinium surfactants increases in the order PM < 3-HPM < PHE < 4-HPHE, and it is higher by a factor of 2–3 than that of CTAB, which traditionally serves as a reference compound in colloid chemistry. It is likely that the presence of a hydroxyl fragment, which can form a hydrogen bond, along with hydrophobic and electrostatic components additionally affects the solubilization mechanism of the hydrophobic dye. The introduction of the second hydroxyl group into the molecular structure enhances the observed effect.

To examine the effect of the structure of hexadecylpiperidinium surfactants on the rate of nucleophilic substitution in phosphorus acid esters, the kinetics of alkaline hydrolysis of the ethyl 4-nitrophenyl ester of ethylphosphonic acid (armine) was studied (Scheme 1).

Scheme 1 . Alkaline hydrolysis of armine.

It should be noted that armine in aqueous solutions is difficult to hydrolyze (the second-order rate constant of the alkaline hydrolysis is 0.155 L mol–1 s–1 [36]), and it is often used as a model in the development and testing of systems intended for the prevention and treatment of organophosphate poisoning [32].

The kinetic experiments were carried out in a 0.01 M solution of sodium hydroxide at a temperature of 25°C. Figure 4 shows the concentration dependences of the observed rate constant of armine hydrolysis in the micellar solutions of hexadecylpiperidinium surfactants. It can be seen that hydroxyl-containing surfactants were much more active than their unsubstituted analog, and the observed effect was higher if the OH group was in the substituent at the nitrogen atom rather than at the ring.

Fig. 4.
figure 4

Concentration dependences of the constants of alkaline hydrolysis of armine in the micellar solutions of hexadecylpiperidinium surfactants (СNaOH = 0.01 mol/L, 25°С).

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The curves (Fig. 4) have a shape typical for micellar-catalyzed processes: a sharp increase in the observed rate constant with increasing surfactant concentration and the subsequent flattening out of the curves. This allowed us to use the following equation of a pseudophase model of micellar catalysis [37] for the analysis of kinetic data:

$${{k}_{{{\text{obs}}}}} = \frac{{{{k}_{\text{m}}}{{K}_{\text{S}}}{{C}_{{{\text{surfactant}}}}} + {{k}_{0}}}}{{1 + {{K}_{\text{S}}}{{C}_{{{\text{surfactant}}}}}}},$$
(1)

where k0 and km (s–1) are the first-order rate constants in an aqueous medium and in a micellar phase, respectively; KS (L/mol) is the substrate binding constant; and C is the total surfactant concentration minus CMC. The ratio km/k0 is usually considered as a measure of the catalytic effect of the system. Table 2 summarizes quantitative characteristics obtained using Eq. (1). From these data, it follows that all of the test surfactants increased the rate of alkaline hydrolysis of armine by more than an order of magnitude. The introduction of a hydroxyl group into the piperidinium ring does not significantly change the catalytic action of the system, while the use of compounds with a hydroxyethyl substituent at the nitrogen atom makes it possible to accelerate reaction by almost two orders of magnitude with a decrease in the substrate binding constant in this case. It can be assumed that, in strongly alkaline media, surfactants containing a hydroxyethyl fragment in the head group can be converted into a zwitterionic form (рK = 12.4–12.6 [38]), which also acts as a nucleophile and interacts with the substrate to increase the observed rate of the process.

Table 2.   Kinetic parameters of the alkaline hydrolysis of armine in the presence of hexadecylpiperidinium surfactants (СNaOH = 0.01 mol/L, 25°С)
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The CMCs determined from the kinetic experiment were lower than the conductometric data (Table 1). It is believed that an alkali present in the reaction medium acts as electrolytes, which usually facilitate micelle formation processes in the solutions of cationic surfactants and decrease CMCs.

In order to find ways for regulating the catalytic action of the micellar solutions of hexadecylpiperidinium surfactants, we studied the rate of alkaline hydrolysis of armine in mixed compositions with Tween 80. The process was carried out under conditions of varying a ratio between cationic and nonionic surfactants, which ensured a change in the surface potential of the micelle and, as a consequence, influenced its interaction with reactants. The surface potential (Ψ) of individual and mixed micelles was evaluated for the 3‑HPM/Tween 80 and 4-HPHE/Tween 80 systems as examples in accordance with a published procedure [35] using p-nitrophenol as a hydrophilic probe. The essence of the method was that the acid–base equilibrium of p-nitrophenol strongly depends on the properties of the medium and shifts significantly on going from water to micellar solutions. The observed value of pKa for this probe in the solutions of cationic surfactants (pKa,m) depends on electrostatic interactions in the system, and it is determined by the surface potential of a micelle. These parameters are related to each other by the relation pKa,m = pKa,0 – FΨ/2.303RT, where pKa,0 is the nonelectrostatic component determined as the pKa of p-nitrophenol in micellar solutions based on nonionic surfactants (Tween 80, probe pKa = 7.6), F = 96 485 C/mol is the Faraday constant, and R = 8.314 J K–1 mol–1 is the gas constant. Thus, based on the values of pKa of p-nitrophenol determined from the spectrophotometric experiment performed in surfactant solutions at different pH, we calculated the surface potentials of individual and mixed micelles (Fig. 5). The values of Ψ for 3-HPM and 4‑HPHE are typical of cationic surfactants (for example, Ψ = 120–126 mV for CTAB [35]), and they decreased monotonically as the mole fraction of Tween 80 (α) in solution was increased.

Fig. 5.
figure 5

Changes in the surface potential of micelles upon varying a ratio between surfactants in binary systems (α is the mole fraction of a nonionic surfactant, 25°C).

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It might be expected that the rate constants of the alkaline hydrolysis of armine should also change in a similar way upon the addition of a nonionic surfactant to hexadecylpiperidinium surfactants. Figure 6 shows the results of studying the kinetics of this process in the 3-HPM/Tween 80 and 4-HPHE/Tween 80 systems. It can be seen that the rate of the process slowed down significantly as the concentration of nonionic surfactant in the system was increased. However, the rate decreased monotonically with 3-HPM similarly to a change in the surface potential, whereas a sharp drop in the catalytic effect was observed in the mixed system based on 4-HPHE even at a nonionic surfactant mole fraction of 0.3. This ratio smoothes a difference between the two cationic surfactants used, which is so obvious in the absence of Tween 80. This phenomenon may be explained by the fact that the fraction of the reactive zwitterionic form of 4-HPHE can decrease in the presence of a nonionic surfactant to affect the рKа of this compound and hence to decrease a contribution to the observed rate constant.

Fig. 6.
figure 6

Dependence of the observed rate constant of the alkaline hydrolysis of armine on the total surfactant concentration in the (a) 3-HPM/Tween 80 and (b) 4-HPHE/Tween 80 mixed systems with different cationic surfactant fractions (α1) at СNaOH = 0.01 mol/L and 25°С.

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Thus, using armine, which is a phosphonic acid ester resistant to hydrolytic cleavage, as an example, we found that hydroxypiperidinium surfactants can serve as a basis for the development of efficient catalytic systems suitable for the concentration and decomposition of toxic organophosphorus compounds. Hydrolysis in these micellar systems can be accelerated by two orders of magnitude. The effect observed is associated not only with the solubilization of a hydrophobic substrate inside the micelle and the concentration of a nucleophilic reagent on its positively charged surface but also with the ability of some hydroxypiperidinium surfactants to form a zwitterionic form in alkaline media. This zwitterionic form acts as a nucleophile and additionally affects the mechanism of the cleavage of toxic organophosphorus compounds.