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.