Antimicrobial Properties and Cytotoxic Effect of Imidazolium Geminis with Tunable Hydrophobicity.

Antimicrobial, membranotropic and cytotoxic properties of dicationic imidazolium surfactants of n-s-n (Im) series with variable length of alkyl group (n = 8, 10, 12, 14, 16) and spacer fragment (s = 2, 3, 4) were explored and compared with monocationic analogues. Their activity against a representative range of Gram-positive and Gram-negative bacteria, and also fungi, is characterized. The relationship between the biological activity and the structural features of these compounds is revealed, with the hydrophobicity emphasized as a key factor. Among dicationic surfactants, decyl derivatives showed highest antimicrobial effect, while for monocationic analogues, the maximum activity is observed in the case of tetradecyl tail. The leading compounds are 2-4 times higher in activity compared to reference antibiotics and prove effective against resistant strains. It has been shown that the antimicrobial effect is not associated with the destruction of the cell membrane, but is due to specific interactions of surfactants and cell components. Importantly, they show strong selectivity for microorganism cells while being of low harm to healthy human cells, with a SI ranging from 30 to 100.

Polycentric binding in complexes of trimethylamine-N-oxide with dihalogens.

Dihalogens readily interact with trimethylamine-N-oxide under ambient conditions. Accordingly, herein, stable 1 : 1 adducts were obtained in the case of iodine chloride and iodine bromide. The crystal and molecular structure of the trimethylamine-N-oxide-iodine chloride adduct was solved. Furthermore, the geometry and electronic structure of the trimethylamine-N-oxide-dihalogen complexes were studied computationally. Only molecular ensembles were found in the global minimum for the 1 : 1 stoichiometry. The O⋯X-Y halogen bond is the main factor for the thermodynamic stability of these complexes. Arguments for electrostatic interactions as the driving force for this noncovalent interaction were discussed. Also, the equilibrium structures are additionally stabilised by weak C-H⋯X hydrogen bonds. Consequently, formally monodentate ligands are bound in a polycentric manner.

The structure - Activity correlation in the family of dicationic imidazolium surfactants: Antimicrobial properties and cytotoxic effect.

BACKGROUND: The development of new effective microbicide surfactants and the search for the structure-biological activity relationship is an important and promising problem. Surfactants containing imidazolium fragment attract attention of researchers in the field of chemotherapy, because these compounds often exhibit high antimicrobial activity. The aim of this work is to identify the newly synthesized surfactants from the viewpoint of their potential usefulness in pharmacology and medicine. For this purpose, a detailed study of antimicrobial, hemolytic and cytotoxic activity of dicationic alkylimidazolium surfactants of the m-s-m (Im) series with a variable length of a hydrocarbon tail (m = 10, 12) and a spacer fragment (s = 2, 3, 4) was carried out. METHODS: Aggregation of surfactants in solutions was estimated by tensiometry and conductivity. Antimicrobial activity was determined by the serial dilution technique. Cytotoxic effects of the test compounds on human cancer and normal cells were estimated by means of the multifunctional Cytell Cell Imaging system. Cell Apoptosis Analysis was made by flow cytometry. RESULTS: The test compounds show high antimicrobial activity against a wide range of test microorganisms and do not possess high hemolytic activity. Importantly, some of them display a bactericidal activity comparable to ciprofloxacin fluoroquinolone antibiotic against Gram-positive bacteria, including methicillin-resistant strains of S. aureus (MRSA). The cytotoxicity of the compounds against normal and tumor human cell lines has been tested as well, with cytotoxic effect and selectivity strongly controlled by structural factor and kind of cell line. Superior results were revealed for compound 10-4-10 (Im) in the case of HuTu 80 cell line (duodenal adenocarcinoma), for which IC50 value at the level of doxorubicin and a markedly higher selectivity index (SI 7.5) were demonstrated. Flow cytometry assay shows apoptosis-inducing effect of this compound on HuTu 80 cells, through significant changes in the potential of mitochondrial membrane. MAJOR CONCLUSIONS: Antibacterial properties are shown to be controlled by alkyl chain length, with the highest activity demonstrated by surfactants with decyl tail, with the length of the spacer fragment showing practically no effect. The results indicate that the mechanism of cytotoxic effect of the compounds can be associated with the induction of apoptosis via the mitochondrial pathway. GENERAL SIGNIFICANCE: Selectivity against pathogenic microorganisms and low toxicity against eukaryotic cells allow considering dicationic imidazolium surfactants as new effective antimicrobial agents. At the same time, high selectivity against some cancer cell lines indicates the prospect of their using as components of new anticancer drugs.

Multiple Noncovalent Bonding in Halogen Complexes with Oxygen Organics. I. Tertiary Amides.

The present work describes the structure and binding of adducts of N,N'-diacetylpiperazine with halogens and interhalogens based on combination of different experimental methods and quantum chemical calculations. On the basis of conductometric and spectro-photometric experimental results, behavior of complexes in the acetonitrile solution was described. The iodine adduct with N,N'-diacetylpiperazine fully degrades into components. Adducts of interhalogens I-X (X = Cl or Br) with N,N'-diacetylpiperazine in acetonitrile partially dissociate to anionic [X-I-X](-) and cationic species. In the solid state, molecules are connected via C═O···I, C-H···I, and Cl···Cl attractive interactions. N,N'-diacetylpiperazine···dihalogen complex is stabilized by simultaneous C═O···I and C-H···I interactions. Such binding mode allows to explain the problems of the direct halogenation of acetyl-containing compounds with molecular halogens as reagents. We believe that the observed binding pattern can be used as prototypical for future design of halogeno complexes.