Gemini surfactants and their antibacterial properties

In this paper, the antibacterial mechanism of Gemini surfactants was introduced. The word Surfactant comes from the English Surfactant, which is a condensation of the phrases Surface, Active and Agent [1]. Surfactants are substances that are active on surfaces and interfaces, have a very high ability and efficiency to reduce surface (boundary) tension, and form molecular ordered assemblages in solutions above a certain concentration, thus having a series of application functions. Surfactants have good dispersibility, wettability, emulsification ability and antistatic properties, and have become the key materials for the development of many fields, including fine chemical industry, and have a significant promoting effect on improving process, reducing energy consumption and improving production efficiency [2]. With the development of society and the continuous progress of the world's industrial level, the application of surfactants has gradually spread from daily chemicals to various fields of the national economy, such as antibacterial agents, food additives, new energy fields, pollutant treatment and biopharmaceuticals.

Traditional surfactants are "amphiphilic" compounds composed of polar hydrophilic groups and non-polar hydrophobic groups, whose molecular structure is shown in Figure 1(a) [7]. At present, with the refinement and systematic development of the manufacturing industry, the requirements for the performance of surfactants in the production process are gradually increasing, so it is of great significance to find and develop surfactants with higher surface properties and special structures. The discovery of Gemini surfactants fills the gap mentioned above and meets the requirements of industrial production. A common Gemini surfactant is a compound with two hydrophilic groups (usually ions or non-ions with hydrophilicity) and two hydrophobic alkyl chains [8]. As shown in Figure 1(b), in contrast to conventional single-chain surfactants, Gemini surfactants bind two hydrophilic groups together by a binding group (spacer). In short, the structure of Gemini surfactants can be understood as the formation of the hydrophilic head groups of two conventional surfactants by cleverly bonding together with binding groups. The special structure of the Gemini surfactant leads to its high surface activity. The main reasons are: (1) the hydrophobic effect of the Gemini surfactant is enhanced by the two hydrophobic tail chains, and the tendency of the surfactant to leave the aqueous solution is increased; (2) The tendency of separation between hydrophilic head groups, especially ionic head groups due to electrostatic repulsion, is greatly weakened by the influence of binding groups; (3) The special structure of the Gemini surfactant affects its aggregation behavior in aqueous solution, making it have a more complex and varied aggregation form. Compared with traditional surfactants, Gemini surfactants have higher surface (interface) activity, lower critical micelle concentration, better wettability, emulsification ability and antibacterial ability. Therefore, the development and utilization of Gemini surfactants is of great significance for the development and application of surfactants.

The "amphiphilic structure" of traditional surfactants gives them unique surface properties. As shown in Figure 1(c), when conventional surfactants are added to water, the hydrophilic head groups tend to dissolve inside the aqueous solution, while the hydrophobic groups inhibit the dissolution of the surfactant molecules in water. Under the combined action of these two trends, the surfactant molecules enrich at the gas-liquid interface and arrange in order to reduce the surface tension of water. Unlike conventional surfactants, Gemini surfactants are "dimers" that bind traditional surfactants together by spacer groups, which can more effectively reduce water surface tension and oil/water interfacial tension [9]. In addition, Gemini surfactants also have lower critical micelle concentration, better water solubility, emulsification, foaming, wetting and antibacterial properties.

Introduction to Gemini surfactants

In 1991 Menger and Littau [13] prepared the first dialkyl surfactant with rigid bonding groups and named "Gemini surfactant". Later, Zhao Guoxi translated "Gemini surfactant" into "Gemini surfactant", which has been adopted by domestic colleagues and has been used so far. In the same year, Zana et al. [14] prepared a series of quaternary ammonium type Gemini surfactants for the first time, and systematically studied the properties of these series of quaternary ammonium type Gemini surfactants. In 1996, researchers summarized and discussed the surface (interface) behavior, aggregation property, rheology of solution and phase behavior of different Gemini surfactants when mixed with traditional surfactants. In 2002, Zana [15] studied the influence of different binding groups on the aggregation behavior of Gemini surfactants in aqueous solution, which greatly promoted the development of surfactants and was of great significance. Later, Qiu et al. [16] invented a new method for synthesizing Gemini surfactants containing special structures using cetyl bromide and 4-amino-3, 5-dihydroxymethyl-1,2, 4-triazole as raw materials, which further enriched the synthesis methods of Gemini surfactants.

The study of Gemini surfactants started late in China. In 1999, Zhao Jianxi [17] from Fuzhou University made a systematic review of foreign research on Gemini surfactants and attracted the attention of many domestic research institutions. After that, domestic research on Gemini surfactants began to flourish and achieved fruitful results. In recent years, researchers have devoted themselves to the research and development of new Gemini surfactants and their related physicochemical properties. At the same time, the application of Gemini surfactants has gradually developed to the fields of sterilization and bacteriostatic, food production, defoaming and defoaming, drug slow release and industrial cleaning. According to whether the hydrophilic groups in the surfactant molecules are charged and the type of charge they carry, the Gemini surfactants can be divided into the following categories: cationic, anionic, non-ionic and zwitterionic Gemini surfactants. Among them, cationic Gemini surfactants generally refer to quaternary ammonium salt or ammonium salt Gemini surfactants, anionic Gemini surfactants mostly refer to hydrophilic groups are sulfonate, phosphate and carboxylate Gemini surfactants, and non-ionic Gemini surfactants are mostly polyoxyethylene Gemini surfactants.

1.1 Cationic Gemini surfactants

Cationic Gemini surfactants can dissociate cations in aqueous solution, mainly ammonium salt and quaternary ammonium salt Gemini surfactants. Cationic Gemini surfactants have good biodegradability, strong decontamination ability, stable chemical properties, low toxicity, simple structure, easy synthesis, easy separation and purification, and also have bactericidal, anti-corrosion, antistatic and soft properties.

Quaternary ammonium type Gemini surfactants are generally prepared by alkylation of tertiary amines [19]. There are two main synthesis methods: one is quaternization with dibromo-substituted alkanes and single long chain alkyl dimethyl tertiary amine as raw materials; The other is 1-bromoalkane and N,N,N ',N '-tetramethylalkyl diamine as raw materials, anhydrous ethanol as solvent, heating reflux, quaternization reaction. However, dibromo-substituted alkanes are more expensive, and the second method is commonly used to synthesize them. The reaction equation is shown in Figure 2.

1.2 Anionic Gemini surfactants

Anionic Gemini surfactants can dissociate anions in aqueous solution, mainly including sulfonate, sulfate salt, carboxylate and phosphate ester type Gemini surfactants. Anionic surfactants have good decontamination, foaming, dispersing, emulsifying and wetting properties, and are widely used as detergents, foaming agents, wetting agents, emulsifiers and dispersing agents.

1.2.1 Sulfonate

Sulfonate-type Gemini surfactants have the advantages of good water solubility, good wettability, good temperature and salt resistance, good decontamination performance, and strong dispersion ability. Besides, they have a wide range of raw materials, simple production process and low cost, and are widely used in petroleum, textile industry, daily chemical industry and other fields as detergents, foaming agents, wetting agents, emulsifiers and dispersing agents [20]. As shown in Figure 3, Li et al. [21] synthesized a series of novel dialkyl disulfonate Gemini surfactants (2Cn-SCT) by using trichloramine, fatty amine and taurine as raw materials in a three-step reaction, which is a typical sulfonate-type Gemini surfactant.

1.2.2 Sulfate salts

The Gemini surfactant of sulfate has the advantages of ultra-low surface tension, high surface activity, good water solubility, wide source of raw materials and relatively simple synthesis. At the same time, the washing performance and foaming ability are good, and the performance is stable in hard water, and the sulfate salt is neutral or slightly alkaline in aqueous solution [22]. As shown in Figure 4, Sun Dong et al. [23] took lauric acid and polyethylene glycol as the main raw materials, and added sulfate bond through substitution, esterification and addition reactions, thus synthesizing sulfate type Gemini surfactant GA12-S-12.

1.2.3 Carboxylate

Carboxylate type Gemini surfactants are generally mild in nature, green in environmental protection, easy to biodegrade, rich in natural raw materials, have high metal chelation, good hard water resistance and calcium soap dispersion [24], and have good foaming and wettability, which are widely used in medicine, textile, fine chemical industry and other fields. The introduction of amide groups into carboxylate type Gemini surfactants can enhance the biodegradability of surfactant molecules, and also make them have good wetting, emulsifying, dispersing and decontamination properties. As shown in Figure 5, a carboxylate type Gemini surfactant CGS-2 containing an amide group was synthesized by Maipinget [25] using dodecylamine, dibromoethane and succinic anhydride as raw materials.

1.2.4 Phosphate salt

Phosphate-type Gemini surfactants have similar structures to natural phospholipids, and are easy to form reverse micelles, vesicles and other structures [26]. Phosphate-type Gemini surfactants have been widely used in antistatic agents and laundry powders, and their emulsifying properties are high and their irritability is low, so they are widely used in personal skin care. Some phosphate esters can be anti-cancer, anti-tumor, antibacterial, there are dozens of drugs have been developed. Phosphate-type Gemini surfactants have strong emulsification performance for pesticides, which can not only be used as antibacterial and insecticidal agents, but also as herbicides [27]. Zheng Guo et al. [28] studied the synthesis of phosphate-type Gemini surfactants using P2O5 and n-quillyl oligodiol as raw materials. This kind of Gemini surfactant has good wetting effect, good antistatic performance, relatively simple synthesis process and mild reaction conditions. The molecular formula of potassium phosphate Gemini surfactant is shown in Figure 6.

1.3 Nonionic Gemini surfactants

Nonionic Gemini surfactants cannot dissociate in aqueous solution and exist in molecular form. So far, few studies have been conducted on this type of Gemini surfactants. At present, there are two types, one is sugar derivatives, and the other is alcohol ether and phenol ether [29]. Nonionic Gemini surfactants do not exist in ionic state in solution, so they have high stability, are not susceptible to strong electrolytes, and have good compatibility and solubility with other types of surfactants. Therefore, non-ionic surfactants have good washing property, dispersion, emulsification, foaming property, wettability, antistatic property and sterilization, and can be widely used in pesticides, coatings and other aspects. As shown in Figure 7, FitzGerald et al. [30] synthesized polyoxyethylene Gemini surfactants (non-ionic surfactants) in 2004, whose structure was expressed as (Cn-2H2n-3CHCH2O(CH2CH2O)mH)2(CH2)6 (or GemnEm).

02 Physicochemical properties of Gemini surfactants

2.1 Activity of Gemini surfactants

The most simple and direct way to evaluate the surface activity of a surfactant is to measure the surface tension of its aqueous solution. In principle, the surfactant reduces the surface tension of the solution by a directional arrangement on the surface (boundary) (Figure 1(c)) [35]. Compared with conventional surfactants with similar structures, the critical micelle concentration (CMC) of Gemini surfactants is more than two orders of magnitude smaller, and the C20 value is also significantly reduced. The Gemini surfactant molecule has two hydrophilic groups, which can help it maintain good water solubility while having a long hydrophobic chain. At the water/air interface, due to the steric hindrance effect and the influence of the same charge repulsion in the molecules, the traditional surfactants are loosely arranged, which weakens their ability to reduce the surface tension of water. The binding groups of the Gemini surfactant are combined by covalent bonds, so that the distance between the two hydrophilic groups is maintained in a small range (far less than the distance between the hydrophilic groups of traditional surfactants), so that the activity of the Gemini surfactant on the surface (interface) is better.

2.2 Assembly structure of Gemini surfactant

In aqueous solution, as the concentration of the Gemini surfactant increases, its molecules reach saturation on the surface of the solution, forcing other molecules to migrate to the interior of the solution to form micelles. The Concentration at which the surfactant begins to form micelles is called the Critical Micelle Concentration (CMC) [36]. As shown in Figure 9, when the concentration is greater than CMC, different from the traditional surfactants, which aggregate to form spherical micelles, Gemini surfactants will produce various micelle forms, such as linear and double-layer structures, due to their structural characteristics [37]. The size, shape and hydration of micelles have direct effects on the phase behavior and rheological properties of the solution, and also lead to changes in the viscoelasticity of the solution. Traditional surfactants, such as anionic surfactants (SDS), usually form spherical micelles and have little effect on the viscosity of the solution. However, due to the special structure of Gemini surfactants, the micelles formed by Gemini surfactants are more complex, and the properties of their aqueous solutions are different from those of traditional surfactants. The viscosity of the aqueous solution of the Gemini surfactant increases with the increase of the concentration of the Gemini surfactant, probably because the formed linear micelles intertwine into a network structure. However, the viscosity of the solution decreased by increasing the surfactant concentration, possibly due to the destruction of the network structure and the formation of other micellar structures.

03 Antimicrobial properties of Gemini surfactants

As a kind of organic antibacterial agent, the antibacterial mechanism of Gemini surfactant is mainly that it combines with the membrane surface anions of microorganisms, or reacts with sulfhydryl groups to destroy the production of their proteins and membranes, thereby destroying microbial tissues to inhibit or kill microorganisms.

3.1 Antibacterial properties of anionic Gemini surfactants

Antibacterial anionic surfactants are mainly determined by the properties of antibacterial groups carried by them. In natural latex, paint and other colloidal solutions, the hydrophilic chain is bound to the water-soluble dispersant, and the hydrophobic chain is bound to the hydrophobic dispersion by directional adsorption, thus transforming the two-phase interface into a dense molecular interface film. Bacteriostatic groups on this tight protective layer inhibit bacterial growth.

The bacteriostatic mechanism of anionic surfactant is fundamentally different from that of cationic surfactant. The bacteriostatic effect of anionic surfactant is related to its solution system and bacteriostatic group, so this type of surfactant will be limited. Such surfactants must reach sufficient content, so that every corner of the system has the presence of surfactants, in order to produce good microbial killing effect. At the same time, the lack of positioning and pertinancy of the sterilization of this surfactant not only causes unnecessary waste, but also produces resistance during long-term use.

Alkyl sulfonate-type Gemini surfactants, for example, have been used in clinical medicine. Alkyl sulfonates such as albuminol, Koji