Anna Komasa

A homologous series of but-2-ene-1,4-bis(N-alkyl-N,N-dimethylammonium bromides) containing C12, C14, C16, and C18 alkyl chains was investigated to determine the influence of hydrophobic-chain length and a semi-rigid unsaturated spacer on aggregation and antimicrobial properties. The critical micelle concentration decreased from the C12 to the C16 derivative, whereas further chain elongation to C18 resulted in an increase in CMC, indicating that micellization is governed not only by hydrophobicity but also by molecular packing effects. Negative standard Gibbs energies confirmed spontaneous micellization. Antimicrobial activity showed the opposite trend: the C12 derivative was the most active compound against all tested microorganisms, with MIC (minimum inhibitory concentration) values as low as 0.06 mM (12-4ene-12 against C. albicans). Increasing alkyl-chain length markedly reduced activity, particularly against Escherichia coli, for which the MIC increased from 0.12 mM for C12 to over 62.5 mM for C18, demonstrating a pronounced cut-off effect. Staphylococcus aureus remained more susceptible to longer-chain homologues than E. coli, while notable activity was also observed against yeast and filamentous fungi. DFT calculations further indicated that spacer unsaturation affects the electronic properties of the molecules. Overall, the results demonstrate a strong relationship between alkyl-chain length, micellization, spacer rigidity, and antimicrobial performance.

Praziquantel (PZQ), a broad-spectrum anthelmintic drug and the first-line treatment for schistosomiasis, is listed on the WHO Model List of Essential Medicines. Although highly effective, PZQ is characterized by poor aqueous solubility, motivating crystal engineering strategies to modulate its physicochemical properties. Here, we employed mechanochemical crystal engineering of PZQ with 5-hydroxyisophthalic acid (5HIP), benzene-1,3,5-tricarboxylic acid (TRI), and trans,trans-muconic acid (MUC) as coformers selected to provide diverse hydrogen-bonding patterns and supramolecular architectures. This approach yielded eight novel pharmaceutical solid forms, comprising cocrystals and cocrystal solvates. Mechanochemical synthesis enabled rapid and reproducible access to phase-pure multicomponent systems using limited amounts of solvents, while solution-based crystallization yielded single crystals for X-ray diffraction. Structural analysis revealed robust supramolecular synthons dominated by O-H···O hydrogen bonding. Thermal analysis and aqueous solubility measurements revealed distinct physicochemical properties among the multicomponent systems, related to their supramolecular organization. Cocrystallization also modulated the biological activity profile of PZQ, with selected systems exhibiting distinct antimicrobial effects. Overall, this work demonstrates that mechanochemical crystal engineering provides a rational approach to designing multicomponent pharmaceutical solid forms and establishes structure-property relationships linking crystal packing with the physicochemical and biological properties of PZQ.

A homologous series of but-2-ene-1,4-bis(N-alkyl-N,N-dimethylammonium bromides) containing C12, C14, C16, and C18 alkyl chains was investigated to determine the influence of hydrophobic-chain length and a semi-rigid unsaturated spacer on aggregation and antimicrobial properties. The critical micelle concentration decreased from the C12 to the C16 derivative, whereas further chain elongation to C18 resulted in an increase in CMC, indicating that micellization is governed not only by hydrophobicity but also by molecular packing effects. Negative standard Gibbs energies confirmed spontaneous micellization. Antimicrobial activity showed the opposite trend: the C12 derivative was the most active compound against all tested microorganisms, with MIC (minimum inhibitory concentration) values as low as 0.006 mM. Increasing alkyl-chain length markedly reduced activity, particularly against Escherichia coli, for which the MIC increased from 0.012 mM for C12 to >125 mM for C18, demonstrating a pronounced cut-off effect. Staphylococcus aureus remained more susceptible to longer-chain homologues than E. coli, while notable activity was also observed against yeast and filamentous fungi. DFT calculations further indicated that spacer unsaturation affects the electronic properties of the molecules. Overall, the results demonstrate a strong relationship between alkyl-chain length, micelliza-tion, spacer rigidity, and antimicrobial performance.

Cationic surfactants, accounting for approximately 7% of the global surfactant market, are widely used in applications such as fabric softeners, biocides, and corrosion inhibitors. Recently, gemini surfactants—comprising two amphiphilic units linked by a spacer—have attracted significant interest due to their superior surface activity, lower critical micelle concentrations, and strong antimicrobial properties. However, their poor biodegradability, resulting from their complex molecular structure, has raised environmental concerns. To address this, researchers have developed ester-based gemini surfactants incorporating biodegradable bonds. This study aimed to investigate the relationship between the structure of ester-based gemini surfactants (hydrophobic chain length and spacer type) and their antimicrobial activity against bacteria and fungi. Three series of compounds featuring different functional groups in the spacer were synthesized, along with a trimeric surfactant for comparative purposes. The results demonstrated that both the hydrophobic chain length and the presence of additional cationic groups significantly influence the CMC and antimicrobial performance. Quantum mechanical calculations were also performed to search for correlations between electronic properties and chemical reactivity of compounds. These findings highlight that ester-based gemini surfactants combine high surface and antimicrobial activity with the potential for improved biodegradability, making them promising candidates for use in environmentally friendly applications.

Cationic gemini surfactants are used due to their broad spectrum of activity, especially surface, anticorrosive and antimicrobial properties. Mixtures of cationic and anionic surfactants are also increasingly described. In order to investigate the effect of anionic additive on antimicrobial activity, experimental studies were carried out to obtain MIC (minimal inhibitory concentration) against E. coli and S. aureus bacteria. Two gemini surfactants (12-6-12 and 12-O-12) and two single quaternary ammonium salts (DTAB and DDAC) were analyzed. The most commonly used commercial compounds of this class, i.e., SDS and SL, were used as anionic additives. In addition, computer quantum mechanical studies were also carried out to confirm the relationship between the structure of the mixture and the activity. The obtained results of microbiological tests and quantum mechanical calculations are in agreement with each other and show the lack of synergism in catanionic mixtures in the case of antibacterial activity.

Cationic gemini surfactants are used due to their broad spectrum of activity, especially surface, anticorrosive and antimicrobial properties. Mixtures of cationic and anionic surfactants are also increasingly described. In order to investigate the effect of anionic additive on antimicrobial activity, experimental studies were carried out to obtain MIC (minimal inhibitory concentration) against E. coli and S. aureus bacteria. Two gemini surfactants (12-6-12 and 12-O-12) and two single quaternary ammonium salts (DTAB and DDAC) were analyzed. The most commonly used commercial compounds of this class, i.e. SDS and SL, were used as anionic additives. In addition, computer quantum-mechanical studies were also carried out to confirm the relationship between the structure of the mixture and the activity.