Substitution of bridge carbons for sulphur in calix[4]arene-bis-α-hydroxymethylphosphonic acid transformed mobile carrier into ionic channel accompanied with evoked muscle contraction and impaired neurotransmission powered by membrane action of resulting thiocalix[4]arene-bis-α-hydroxymethylphosphonic acid.

The action of calix[4]arenes C-424, C-425 and C-1193 has been investigated on suspended cholesterol/egg phosphatidylcholine lipid bilayer in a voltage-clamp mode. Comparative analysis with the membrane action by calix[4]arene-bis-α-hydroxymethylphosphonic acid (C-99) has shown that the substitution of bridge carbons for sulphur and addition of another methyl group to two alkyl tales in the lower rim of former dipropoxycalix[4]arene C-99 transformed mobile carrier that C-99 created in lipid bilayer (Shatursky et al., 2014) into a transmembrane pore as exposure of the bilayer membrane to sulphur-containing derivative dibutoxythiocalix[4]arene C-1193 resulted in microscopic transmembrane current patterns indicative of a channel-like mode of facilitated diffusion. Within all calix[4]arenes tested a net steady-state voltage-dependent transmembrane current was readily achieved only after addition of calix[4]-arene C-1193. In comparison with the membrane action of C-99 the current induced by calix[4]-arene C-1193 exhibited a much weakened anion selectivity passing slightly more current at positive potentials applied from the side of bilayer membrane to which the calix[4]-arene was added. Testing C-1193 for the membrane action against smooth muscle cells of rat uterus or swine myometrium and synaptosomes of rat brain nerve terminals revealed an increase in intracellular concentration of Ca2+ with reduction of the effective hydrodynamic diameter of the smooth muscle cells and enhanced basal extracellular level of neurotransmitters (glutamate and γ-aminobutyric acid) after C-1193-induced depolarization of the nerve terminals.

Membrane action of polyhexamethylene guanidine hydrochloride revealed on smooth muscle cells, nerve tissue and rat blood platelets: A biocide driven pore-formation in phospholipid bilayers.

A well-known cationic biocide of guanidine polymer family, polyhexamethylene guanidine hydrochloride (PHMG) has been tested against smooth muscle cells isolated from swine myometrium, synaptosomes of rat brain nerve terminals and rat blood platelets for the membrane action. It was established that PHMG blocked the activity of Na+,K+-ATPase of smooth muscle cells plasma membrane by 82.2 ±â€¯0.9% at a concentration of 7 ppm, whilst a dose-dependent depolarization of synaptosomes and platelets became appreciable at 100-500 ppm. Comparative studies by the methods of mass spectrometry (MALDI-TOF and PDMS-TOF), viscosimetry, dynamic light scattering and model phospholipid membranes revealed PHMG oligomers with various number of repeat units (8-16) that formed K+-selective potential-dependent pores in sterol-free phosphatidylethanolamine-containing phospholipid bilayers at a concentration of 1 ppm. Obtained results suggest that besides acidic lipids and membrane proteins phosphatidylethanolamine and cholesterol are the other major factors responsible for the differences between PHMG-induced plasma membrane depolarization of microbial and eukaryotic cells and thus, diverse modes of PHMG membrane action.