Amino acid-based surfactants

Amino acid-based surfactants are derived from simple amino acids or mixed amino acids from synthesis or protein hydrolysates. They are composed of amino acid as the hydrophilic part and a long hydrocarbon chain as the hydrophobic part. The hydrophobic chain can be introduced through acyl, ester, amide, or alkyl linkage. Interest in amino acid surfactants is not new, as shown by early work in the area. In 1909, Bondi performed the first research on the introduction of a hydrophobic group to obtain A-acylgiycine and A-acyla-lamine [18], Subsequent work in this area focused on A-acylamino acids, as reported by Funk [19], Izar [20], Karrer [21], Staudinger and Becker [22],... 

The foregoing is an example of many kinds of amino acid-based surfactants that are being produced either for investigative research or for commercialization. They have potential wide application in the cosmetic, personal care, food, and drug industries. 

Structurally, amino acid-based surfactants may be depicted as shown nearby. The fundamental stmctures may be considered as (1) N-acylated amino acid, which is essentially an anionic surfactant, or modified as in (b), where the carboxylic group is converted to ester or amide, as seen in cationic surfactants. The structures in (c) and (d) represent those of amphoteric surfactants, in which both amino and carboxyl groups represent hydrophilic moieties. 

There are various synthetic routes to introduce hydrocarbon long chains into amino acid-based surfactants. For example, a long-chain fatty acyl group is introduced on the amino part of amino acids by using an acid chloride. To obtain amino acid esters or amides, the carbonyl parts of amino acids are reacted with fatty alcohol or amines, respectively. For example, C-alkylation of an amino acid is obtained by the reaction of a-bromo fatty acid with ammonia or by a transmission reaction of the amino part of the amino ester with a stable Schiff base followed by deprotonation with a strong base. This is followed by alkylation with an alkyl halide. N-Alkylation of an amino acid is generally obtained by the reaction of fatty amines with monochloroacetic acid, methyl acrylate, or maleic acid or by the addition of 1,2-epoxy alkane to amino acids. 

The authors are very grateful to Prof. Nakanishi of Okayama University for providing information and discussions on enzymatic synthesis of acylated amino acids. The experiments on synthesis of amino acid-based surfactants referred to in the text are now under way in collaboration with Prof. Nakanishi, supported partially by a Grant-in-Aid from the Program for Promotion of Basic Research Activities for Innovative Bioscience in Japan. The authors wish to thank Prof. Shimizu of Tokyo University and Prof. Kato of Yamaguchi University for discussions relating to the text. 

Published results on the toxicological properties of different lipoaminoacids suggest that amino acid-based surfactants are excellent nontoxic surfactants for a great variety of potential applications [33-36]. Ocular irritation by Ci2ArgGly, CijArg pp, LAM, and lauryl dimethyl amino betaine (LDAB), a commercial amphoteric surfactant, has been evaluated in male albino rabbits by a double-blind method. The eyes were examined after 24 h of administration and then each day for a week. The ocular damage was evaluated in accordance with the criteria of Draize [37]. 

Interactions of Amino Acid-Based Surfactants with Other Compounds... 

Studies on a mixture composed of amino acid-based surfactants have not been extensively made as compared to other surfactants, such as sodium do-decyl sulfate (SDS), and nonionics. To the best of our knowledge, there are few publications dealing with mixtures where amino acid-based surfactants, especially amino acid-based surfactants/polymers, are involved. With this in mind, this chapter first discusses methods for examining a mixture containing amino acid surfactants, essentially to provide prospective methods to smdy surfactant mixture systems. In addition, interactions of amino acid-based surfactants with other components, including inorganic and organic molecules, are reviewed. 

III. INTERACTION OF AMINO ACID-BASED SURFACTANTS WITH OTHER MATERIALS... 

Like a conventional surfactant such as SDS, amino acid-based surfactants can interact with other surfactants, solvents, electrolytes, polymers, proteins, and membrane of cells to show specific behavior. In view of the unique structure of amino acids, where an amino group and a carboxyl group are combined in one molecule, the interaction of amino acid-based surfactants with other ingredients is of great interest to fundamental study and practical applications. 

The behavior of solutions of either small or large molecules is considerably influenced by the nature of the solvent itself. For example, water plays a very important role in determining the properties of a surfactant, such as micelle formation and surface-tension reduction. It is well known that protein folding occurs in water in acquiring the native structure, and the final conformation is influenced by the solvent [85]. Similarly, the properties of amino acid-based surfactants are strongly dependent on the nature of the solvent. In water. 

Vinardell and co-workers [135] studied the irritation of rabbit eye and skin from cationic amino acid-derived surfactants iV-acyl-L-arginine methylesters. They found that amino acid-based surfactants are less irritant than a conventional cationic surfactant, cetrimide. Also, the degree of irritation depends on the chain length of the alkyl group, and a maximum of irritation was observed for Ci2 surfactant. The similar effect was reported for alkyl sulfates before [136], being ascribed to the high monomer concentration of surfactant. 

II. SINGLE-CHAIN AMINO ACID-BASED SURFACTANTS... 

Contrarily to fatty add salts (i.e., sodium laurate soap), the long-chain iV -acyl amino adds have excellent water solubility (due to the presence of additional CO-NH linkages), quick biodegradability and good lime resistance (i.e., caldum ion tolerance) [11]. The surfactant properties of pure sodium salts of iV -acyl amino acids (anionic surfactants) with different alkyl chains (saturated and unsaturated with 10-18 carbon atoms) and amino acid residues have been described and compared with those of sodium lauryl sulfate (SLS) and sodium laurate [11-14]. The authors showed that the critical micelle concentration (CMQ of the amino acid-based surfactants was lower than that of the SLS but higher than that of sodium laurate. The surface activity increased and the CMC decreased by raising the alkyl chain... 

One important milestone in our research is the design and development of new amino acid-based surfactants with antimicrobial properties, which mimic natural amphiphilic cationic peptides [42,43]. To this end, Lys and Arg derivatives of long-chain A -acyl, COO-ester, and A-alkyl amide have been prepared. In particular, the A -acylarginine methyl ester derivatives series 1 (Scheme 1) have turned out to be an important class of cationic surface active compounds with a wide bactericidal activity, high biodegradability, and low toxicity profile. We have shown that essential structural factors for their antimicrobial activity include both the length of the fatty residue (akin with their solubility and surface activity) and the presence of the protonated guanidine function [43,44]. 

More recently, we have developed an alternative chemoenzymatic route to the preparation of a variety of amino acid-based surfactants ranging from simple monoesters to more complex gemini amphiphiles [79], This approach was based on the observation that some lipases, notable immobilized Candida antartica and Rhizomucor miehei, readily accept N-Cbz amino acids as substrates and catalyze their esterification/amidation with a,(o-diols/a,to-diamines in excellent yields. The resulting alkanediyl-a,co-bis-(A -Cbz-amino acid) was further modified to obtain a range of amino acid-based gemini surfactants. Some examples of the products obtained in this work are shown in Fig. 8. 

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