1. Introduction
In recent decades, there have been numerous research reports correlated with antimicrobial agents, which can be used in food industries, cosmetics, coatings, and personal care products, and it is still one of the most important topics in both chemistry and biology areas. Pathologic microorganisms (e.g., Listeria (L.) monocytogenes , Escherichia (E.) coli , salmonella ) are a severe threat to human health since they can cause severe infectious diseases. To inactivate these pathogens, numerous antimicrobial agents have been developed, however the efficacy of any specific antimicrobial agent varies across different bacteria because of their diversity of their cellular structures and components (Rodríguezet al. , 2004). Moreover, bacteria may evolve and gain antimicrobial resistance. This has become a global threat, and it has been getting worse during the last 20 years due to the overuse or misuse of antibiotics. In addition, most of the existing antimicrobials are synthetic agents, which elicits concerns about their potential negative impact on health and the environment. This leads to an urgent need for new, effective, and environment-friendly antimicrobial agents.
While many antimicrobial agents have been extracted from plants and synthesized via chemical reactions, sustainability and toxicity are two of the most crucial properties for new antimicrobials. Toxicity is even more important when they are used in food or personal care products. Ethyl lauroyl arginate (LAE®) is an example of a non-toxic and biodegradable antimicrobial that is derived from natural compounds (i.e., C12 linear- (n -) chain fatty acid and L-arginate amino acid) (Fig. 1 ). The lipid makes up the hydrophobic tail, and the arginine is the hydrophilic head group, which mimics lipoamino acids found in cell members (Epand et al ., 1998). It has been proved as a broad-spectrum antimicrobial against most of the food-borne pathogens including algae and fungi. Becerril et al . (2013) reported the antimicrobial tests of LAE and found that, it exhibited strong antimicrobial activity against five different strains of food-borne bacteria. The scanning electron micrographs of E. coli cells showed that LAE inhibited their growth by disrupting the cell membrane. For this reason, LAE is a popular product which is being used in many industrial applications (e.g., hand soaps, oral care products).
Infante and Marta Rosa comprised one of the pioneering research groups that developed a two-step aqueous process to produce LAE (Infante and Marta Rosa, 1995). The first step involved esterification of the amino acid carboxyl group using thionyl chloride, followed by condensation of the (C8-C14) fatty chloride intermediates to produce the desired fatty acid arginate derivatives at 80-85% yield (Infante and Marta Rosa, 1995). Ghare V.S., (2011) patented a similar aqueous process where L-arginine ethyl hydrochloride substrate was first dissolved in water, followed by continuous addition of sodium hydroxide and lauroyl chloride at a very specific pH of 7.5 and temperature at 8 oC. Under these conditions, white crystalline LAE product was obtained at 98% yield. Unfortunately, this approach is not sustainable because it is challenging to maintain the narrow pH range throughout the reaction. Mehta et al., (2014) patented a different approach where they dissolved the L-arginine ethyl hydrochloride in a solvent (e.g., chloroform or tetrahydrofuran) and then added triethylamine and lauroyl chloride to produce LAE between 90 and 94% with >99% purity.
Inspired by these lipoamino acid compounds, our group has pursued research on the synthesis of branched (iso -) C18-fatty acids conjugated to arginate hydrochloride (i.e., iso -oleic acid and isostearic acid) (Fig. 2 ). These selected iso- fatty acids are made up of a mixture of skeletal isomeric products with a methyl group on the fatty acid chain distributed on various positions (Ngo and Foglia, 2015). They have excellent thermostability and low temperature properties. While these are well-known lubricant ingredients for cosmetic and personal care products, these applications often require the addition of preservatives (antimicrobial, biocides) to extend the shelve life of the products. We propose that by introducing the arginine head to the iso -fatty acids, the resulting ethyl iso -fatty acid arginate derivatives can have both preservative and lubricant functionalities. Herein, a series of long-chain both iso - and linear- (n -) fatty acid arginate derivatives are synthesized using a simple synthetic protocol. Their intermediates and final compounds are characterized by attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FT-IR), nuclear magnetic resonance (NMR), and liquid chromatography-mass spectrometry (LC-MS). Finally, the antimicrobial properties of the synthesized products are evaluated against two different bacteria to determine their suitability as preservatives.