title: Structure-property relationship of quinuclidinium surfactants--Towards multifunctional biologically active molecules.
abstract: Motivated by diverse biological and pharmacological activity of quinuclidine and oxime compounds we have synthesized and characterized novel class of surfactants, 3-hydroxyimino quinuclidinium bromides with different alkyl chains lengths (CnQNOH; n=12, 14 and 16). The incorporation of non conventional hydroxyimino quinuclidinium headgroup and variation in alkyl chain length affects hydrophilic-hydrophobic balance of surfactant molecule and thereby physicochemical properties important for its application. Therefore, newly synthesized surfactants were characterized by the combination of different experimental techniques: X-ray analysis, potentiometry, electrical conductivity, surface tension and dynamic light scattering measurements, as well as antimicrobial susceptibility tests. Comprehensive investigation of CnQNOH surfactants enabled insight into structure-property relationship i.e., way in which the arrangement of surfactant molecules in the crystal phase correlates with their solution behavior and biologically activity. The synthesized CnQNOH surfactants exhibited high adsorption efficiency and relatively low critical micelle concentrations. In addition, all investigated compounds showed very potent and promising activity against Gram-positive and clinically relevant Gram-negative bacterial strains compared to conventional antimicrobial agents: tetracycline and gentamicin. The overall results indicate that bicyclic headgroup with oxime moiety, which affects both hydrophilicity and hydrophobicity of CnQNOH molecule in addition to enabling hydrogen bonding, has dominant effect on crystal packing and physicochemical properties. The unique structural features of cationic surfactants with hydroxyimino quinuclidine headgroup along with diverse biological activity have made them promising structures in novel drug discovery. Obtained fundamental understanding how combination of different functionalities in a single surfactant molecule affects its physicochemical properties represents a good starting point for further biological research.
authors.affiliation: Department of Biology, Faculty of Science, University of Split, Teslina 12, 21 000 Split, Croatia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Skočibušić
authors.affiliation: Department of Chemistry, Faculty of Science, University of Split, Teslina 12, 21 000 Split, Croatia.
authors.forename: Renata
authors.initials: R
authors.lastname: Odžak
authors.affiliation: Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10 000 Zagreb, Croatia.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Štefanić
authors.affiliation: Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10 000 Zagreb, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Križić
authors.affiliation: Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10 000 Zagreb, Croatia.
authors.forename: Lucija
authors.initials: L
authors.lastname: Krišto
authors.affiliation: Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10 000 Zagreb, Croatia.
authors.forename: Ozren
authors.initials: O
authors.lastname: Jović
authors.affiliation: Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10 000 Zagreb, Croatia.
authors.forename: Tomica
authors.initials: T
authors.lastname: Hrenar
authors.affiliation: Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10 000 Zagreb, Croatia. Electronic address: ines.primozic@chem.pmf.hr.
authors.forename: Ines
authors.initials: I
authors.lastname: Primožič
authors.affiliation: Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10 000 Zagreb, Croatia. Electronic address: djurasin@irb.hr.
authors.forename: Darija
authors.initials: D
authors.lastname: Jurašin
mesh_terms: D000327:Adsorption; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000145:classification / Q000187:drug effects / Q000254:growth & development*; D018360:Crystallography, X-Ray; D004553:Electric Conductivity; D006090:Gram-Negative Bacteria / Q000145:classification / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000145:classification / Q000187:drug effects / Q000254:growth & development; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011812:Quinuclidines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013500:Surface Tension; D013501:Surface-Active Agents / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D011812:Quinuclidines; D013501:Surface-Active Agents
keywords: Antimicrobial efficacy; Biologically active compounds; Cationic surfactants; Crystal structure; Quinuclidinium oximes; Structure-property relationship