M. Teresa Garcia

Biodegradable ionic liquids: Part I. Concept, preliminary targets and evaluation

The design, preparation and evaluation of biodegradable ionic liquids containing ester or amide groups in the alkyl side chain are presented. Factors improving the biodegradation of surfactants were successfully applied to ionic liquids. These novel ionic liquids can be prepared from readily available starting materials in high yield. The introduction of a group susceptible to enzymatic hydrolysis greatly improves the biodegradation (OECD 301D ‘Closed Bottle Test’) compared with the commonly used dialkylimidazolium ionic liquids, bmimBF4 and bmimPF6. For the 3-methyl-1-(alkyloxycarbonylmethyl)imidazolium bromide series, the greatest biodegradation was observed when alkyl = butyl, pentyl, hexyl and octyl. The corresponding amide analogs proved to be poorly biodegradable.

Biodegradable ionic liquids

Further research toward the discovery of biodegradable ionic liquids (ILs) is described herein. The biodegradability of the target ILs was evaluated using the ‘Closed Bottle’ and ‘CO2 Headspace’ tests (OECD 301D and ISO 14593). This research has identified the first ILs which can be classified as ‘readily biodegradable’ under aerobic conditions.

Self-aggregation and antimicrobial activity of imidazolium and pyridinium based ionic liquids in aqueous solution.

Two series of long-chain imidazolium and pyridinium based ionic liquids (1-alkyl-3-methylimidazolium and 1-alkylpyridinium bromides) were synthesised and the effect of the alkyl chain length and the nature of the cationic head group on micellization and antimicrobial activity of the ionic liquids (ILs) were investigated. Tensiometry, conductometry, spectrofluorimetry and PGSE-NMR were applied to study the self-aggregation of the amphiphilic ILs in aqueous solution. The ILs investigated displayed surface activity and the characteristic chain length dependence of the micellization process of surfactants. The antimicrobial activity was evaluated against Gram-negative and Gram-positive bacteria and fungi. ILs containing more than eight carbon atoms in the alkyl chain showed antimicrobial activity. Their efficiency as antimicrobial agents increased with the hydrophobicity of the amphiphilic cation being the C(14) homologous the most active compounds.

Biodegradable pyridinium ionic liquids: design, synthesis and evaluation

A range of ionic liquids (ILs) with a pyridinium cation were synthesised and their biodegradability was evaluated using the CO2 Headspace test (ISO 14593). ILs bearing an ester side chain moiety were prepared from either pyridine or nicotinic acid and showed high levels of biodegradation under aerobic conditions and can be classified as ‘readily biodegradable’. In contrast, pyridinium ILs with alkyl side chains showed significantly lower levels of biodegradability in the same test. The utility of the biodegradable IL 6c as a reaction solvent for the Diels–Alder reaction was also investigated.

Biodegradable, non-bactericidal oxygen-functionalised imidazolium esters: A step towards ‘greener’ ionic liquids

A series of imidazolium ionic liquids was prepared and screened against 7 bacterial strains. The incorporation of ether groups into the ester side-chain significantly reduced the toxicity compared with alkyl ester derivatives. Biodegradation data are also presented for 15 of the ionic liquids—including 6 examples which can be classed as readily biodegradable.

Aggregation Behavior and Antimicrobial Activity of Ester-Functionalized Imidazolium- and Pyridinium-Based Ionic Liquids in Aqueous Solution

Two series of long chain imidazolium- and pyridinium-based ionic liquids containing an ester functional group in the alkyl side chain, 3-methyl-1-alkyloxycarbonylmethylimidazolium bromides (C(n)EMeImBr) and 1-alkyloxycarbonylmethylpyridinium bromides (C(n)EPyrBr), were synthesized and their thermal stability, aggregation behavior in aqueous medium, and antimicrobial activity investigated. The introduction of an ester group decreased the thermal stability of the functionalized ILs compared to simple alkyl chain containing ILs (1-alkyl-3-methylimidazolium bromides and 1-alkylpyridinium bromides). Tensiometry, conductimetry, and spectrofluorimetry were applied to study the self-aggregation of the amphiphilic ILs in aqueous solution. The ILs investigated displayed surface activity and the characteristic chain length dependence of the micellization process of surfactants. As compared to simple alkyl chain containing ILs bearing the same hydrocarbon chain, ester-functionalized ILs possess higher adsorption efficiency (pC(20)) and significantly lower critical micelle concentration (cmc) and surface tension at the cmc (γ(cmc)), indicating that the incorporation of an ester group promotes adsorption at the air/water interface and micelle formation. The antimicrobial activity was evaluated against Gram-negative and Gram-positive bacteria and fungi. ILs containing more than eight carbon atoms in the alkyl chain showed antimicrobial activity. Their efficiency as antimicrobial agents increased with the hydrophobicity of the amphiphilic cation being the C(12) homologous the most active compounds. The incorporation of an ester group particularly increased the biological activity against fungi.

Cationic surfactants from lysine: Synthesis, micellization and biological evaluation

Biocompatible cationic surfactants from the amino acid lysine (hydrochloride salts of N(epsilon)-lauroyl lysine methyl ester, N(epsilon)-myristoyl lysine methyl ester and N(epsilon)-palmitoyl lysine methyl ester) have been prepared in high yields by lysine acylation in epsilon position with three natural saturated fatty acids. The micellization process of these surfactants has been studied using the PGSE-NMR technique. The compounds were tested as antimicrobial agents against Gram-positive and Gram-negative bacteria. The surfactants show moderate antimicrobial activity against the Gram-positive bacteria but Gram-negative bacteria are resistant to these surfactants in the concentration range tested. The haemolytic activity is considerably lower than those reported for other cationic N(alpha)-acyl amino acid analogues. The acute toxicity against Daphnia magna and biodegradability was studied. The toxicity is clearly lower than that reported for conventional cationic surfactants from quaternary ammonium and the three surfactants from lysine can be classified as ready biodegradable surfactants.

Further investigation of the biodegradability of imidazolium ionic liquids

In continuation of our earlier investigations, this report presents a rationale behind the design of a series of imidazolium based ionic liquids and their biodegradation using the CO2 headspace test (ISO 14593 method, OECD 310). The effect on biodegradability of these salts through variation of the N-substituted side chains of imidazolium ions was examined further through incorporation of various functional groups and increased alkyl chain lengths. A series of anions containing moieties known to be biodegradable were also incorporated into a number of imidazolium based salts and examined in a similar fashion.

Phosphonium ionic liquids: design, synthesis and evaluation of biodegradability

The biodegradability of a range of phosphonium ionic liquids (ILs) was assessed using the CO2 headspace test (ISO 14593). Tetraalkylphosphonium cations in which one of the alkyl substituents contained ester, ether, alcohol or alkene functionality in order to promote biodegradation were targeted. These cations were paired with halide, triflimide and octylsulfate anions. In contrast to previously studied dialkylimidazolium and alkylpridinium ILs with incorporated ester moieties and octylsulfate anions, the phosphonium ILs showed relatively low levels of biodegradability.

Antimicrobial toxicity studies of ionic liquids leading to a ‘hit’ MRSA selective antibacterial imidazolium salt

Imidazolium salts can be classed as surfactants, detergents, ionic liquids, reagents, catalysts or solvents. A study of the toxicity and ecotoxicity of these salts yields valuable information for their use as pharmaceuticals as well as impact on the environment. Our approach to screen a series of chiral imidazolium salts for toxicity to bacteria and fungi, including clinical pathogen strains, has led to the identification of a ‘hit’ MRSA selective antimicrobial compound. Preliminary structure–activity-relationship (SAR) information (required position of L-phenylalanine and L-valine group) is also elucidated within this first generation of compounds. Conversely, most of the imidazolium salts were nontoxic (IC95 > 2 mM) to the 12 fungi strains and 8 bacteria strains screened, and we propose that they are suitable candidates for ‘green chemistry’ applications. Ecotoxicity studies (Biodegradation ISO 14593 ‘CO2 Headspace Test’) of two bromide ionic liquids containing L-phenylalanine residues indicate that these ionic liquids passed the test (>60% in 28 days) and classed as readily biodegradable.