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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 nonconventional 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.

This report summarizes studies on pyridinium, imidazolium, and quinuclidinium oximes, which were prepared in laboratories in Croatia since the middle of the 1970s. The prepared compounds, 176 in all, include 157 new compounds. The majority of prepared compounds are monoquaternary and bisquaternary pyridinium oximes. In vitro studies comprised reversible inhibition of cholinesterases, protection of cholinesterases from phosphylation by organophosphorus compounds (OP), and reactivation of the phosphylated enzyme. In vivo studies of the oximes as antidotes in experimental poisoning by OP compounds are also reviewed. The OP compounds were predominantly chemical warfare (CW) nerve agents but also included some related pesticides.

In this paper, new synthesized oxime derivatives of imidazole and quinuclidines were tested in vitro using human erythrocyte AChE inhibited by soman and in vivo using soman poisoned mice. The inhibitory power (IC50, concentration of the test compounds, oximes, that inhibit to 50 % of the AChE activity), acute toxicity (LD 50 ), as well as reactivating and protective capacities, with respect to soman-inhibited AChE were tested for each of the synthesized oximes. Antidotal characteristics of the new syntesized oximes were compared and related to their chemical structures. Derivatives of imidazoles demonstrated mostly weak reactivating and protective characteristics, both for the in vitro and in vivo cases. These characteristics were independent of the substituents on N phenyl imidazolium oximes. Of the imidazoles, only BMR-3 oxime strongly reactivated the soman inhibited AChE (55%), i.e., in vitro, for human erythrocytes. BMR-4 oxime, in combination with atropine sulfate, provided effective protection in vivo (for mice) against 1.8 and 2.2 LD50 of soman. On the contrary, all tested quinuclidine oximes showed very good protection in vivo (for example, BM-1 protects against 4 x LD 50 of soman), but were ineffective in vitro, i.e., against soman-inhibited human erythrocyte AChE. The results indicate that in vivo effectiveness of quinuclidine oximes against soman poisoning is not telated to their reactivating or protective potentials for AChE measured in in vitro experiments ; their good protective effect is more likely to be related to other mechanisms of the cholinergic system.

The efficiency of newly synthesized oxime derivatives of quinuclidinium were tested in vitro on soman inhibited acetylcholinesterase (AChE) of human erythrocytes and in vivo using soman poisoned mice. For this purpose, the inhibitory power of oximes (IC50), acute toxicity (LD50) as well as reactivating and protective capacities with respect to soman-inhibited AChE were determined for each of the oximes. All oximes tested were ineffective in vitro but protected mice very efficiently (BM-1 protects against 4LD50 of soman). The results indicate that the in vivo effectiveness of quinuclidinium oximes against soman poisoning may not be related to reactivation or protection of AChE but rather to some other mechanism of the cholinergic system.

In this paper, new synthesized oxime derivatives of imidazoles and quinuclidines were tested in vitro using human erythrocyte AChE inhibited by soman and in vivo using soman poisoned mice. The inhibitory power (IC50, concentration of the tes compounds, oximes, that inhibit to 50 % of the AChE activity), acute toxicity (LD50), as well as reactivating and protective capacities, with respect to soman-inhibited AChE were tested for each of the synthesized oximes. Antidotal characteristics of the new synthesized oximes were compared and related to their chemical structures. Derivatives of imidazoles demonstrated mostly weak reactivatin and protective characteristics, both for the in vitro and in vivo cases. These characteristics were indempendent of the substituents on N phenyl imidazolium oximes. Of the imidazoles, only BMR-3 oxime strongly reactivated the soman-inhibited AChE (55%), i.e., in vitro, for human erythrocutes. BMR-4 oxime, in combination with atropine sulfate, provided effective protection in vivo (for mice)against 1.8 and 2.2 LD 50 of soman. Ont he contrary, all tested quinuclidine oximes showed very good protection in vivo (for example, BM-1 protects agains 4 LD 50 of soman), but were ineffective in vitro, i.e., against soman-inhibited human erythrocyte AChE. The results indicate that in vivo effectiveness of quinuclidine oximes against soman poisoning is not related to their reactivating or protective potentials for AChE measured in in vitro experiments ; their good protective effect is more likely to be related to other mechanisms of the cholinergic system.

New synthesized oximes derivatives of imidazole and quinuclidines were tested in vitro using human erythrocyte acetylcholinesterase (AChE) inhibited by soman and in vivo using soman poisoned mice. The inhibitory power of oximes (IC 50), acute toxicity (LD 50) as well as reactivating and protecitve capacities with respect to soman-inhibted AChE were tested for each of the synthesized oximes. Derivatives of imidazoles demonstrated mostly weak reactivating and protective characteristics, both in vitro and in vivo. Only BMR-3 oxime was powerful reactivator of soman inhibte human AChe (55 %). BMR-4 oxime given together with atropine sulfate, provided a good in vivo protection against 1.8 and 2.2 x LD 50 of soman. On the contrary, all tested quinuclidne compounds are protective agents against soman in vivo (PP-1, PP-2, PP-3, PP-4 protect against 2-2.5 x LD 50 of soman). Bm-1 oxime has the best protection against soman inhibition of the AChE of all tested compounds (protect against 4 LD 50 of soman). Quinuclidines in vitro activity as reactivators of soman inhibited AChE, and their protective power against soman inhibition of AChE in vitro are negligible. The results indicate that in vivo effectiveness of quinuclidine oximes against soman poisoning is not related to their reactivatin or protective potentials for AChE ; their good protective effect is more likely to be related to other mechanisms of the cholinergic system.