Novel ionic liquids containing ampicillin as an active pharmaceutical ingredient anion were prepared with good yields by using a new, efficient synthetic procedure based on the neutralization of a moderately basic ammonia solution of ampicillin with different organic cation hydroxides. The relevant physical and thermal properties of these novel ionic liquids based on ampicillin were also evaluated.

Antibacterial activities of novel Active Pharmaceutical Ingredient Ionic Liquids (API–ILs) based on ampicillin anion [Amp] have been evaluated. They showed growth inhibition and bactericidal properties on some sensitive bacteria and especially some Gram-negative resistant bacteria when compared to the [Na][Amp] and the initial bromide and chloride salts. For these studies were analysed the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBIC) against sensitive Gram-negative bacteria Escherichia coli ATCC 25922 and Klebsiella pneumoniae (clinically isolated), as well as sensitive Gram positive Staphylococcus Aureus ATCC 25923, Staphylococcus epidermidis and Enterococcus faecalis and completed using clinically isolated resistent strains such as E. coli TEM CTX M9, E. coli CTX M2 and E. coli AmpC MOX. From the obtained MIC values of studied API–ILs and standard [Na][Amp] were derived RDIC values (relative decrease of inhibitory concentration). High RDIC values of [C₁₆Pyr][Amp] especially against two resistant Gram-negative strains E. coli TEM CTX M9 (RDIC >1000) and E. coli CTX M2 (RDIC >100) point clearly to a potential promising role of API–ILs as antimicrobial drugs in particular against resistant bacterial strains.

The preparation and characterization of ionic liquids and organic salts (OSILs) that contain anionic penicillin G [secoPen] and amoxicillin [seco-Amx] hydrolysate derivatives and their in vitro antibacterial activity against sensitive and resistant Escherichia coli and Staphylococcus aureus strains is reported. Eleven hydrolyzed β-lactam-OSILs were obtained after precipitation in moderate-to-high yields via the neutralization of the basic ammonia buffer of antibiotics with different cation hydroxide salts. The obtained minimum inhibitory concentration (MIC) data of the prepared compounds showed a relative decrease of the inhibitory concentrations (RDIC) in the order of 100 in the case of [C₂OHMIM][seco-Pen] against sensitive S. aureus ATCC25923 and, most strikingly, higher than 1000 with [C₁₆Pyr][seco-Amx] against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. These outstanding in vitro results showcase that a straightforward transformation of standard antibiotics into hydrolyzed organic salts can dramatically change the pharmaceutical activity of a drug, including giving rise to potent formulations of antibiotics against deadly bacteria strains.