Ferutinin as a Ca²⁺complexone: lipid bilayers, conductometry, FT-IR, NMR studies and DFT-B3LYP calculations

Abstract

Calcium ionophoretic properties of ferutinin were re-evaluated in solvent-containing bilayer lipid membranes. The slopes of conductance-concentration curves suggest that in the presence of a solvent in the membrane the majority of complexes appear to consist of a single terpenoid molecule bound to one Ca ion. By contrast, the stoichiometry of ferutinin-Ca(2+) complexes in acetone determined using the conductometric method was 2 : 1. While the cation-cation selectivity of ferutinin did not change, the cation-anion selectivity slightly decreased in solvent containing membranes. FT-IR and NMR data together with DFT calculations at the B3LYP/6-31G(d) level of theory indicate that in the absence of Ca ions ferutinin molecules are hydrogen-bonded at the phenol hydroxyl groups. The variations of absorption assigned to -OH and -C-O stretching mode suggest that ferutinin interacts strongly with Ca ions via the hydroxyl group of ferutinol and carboxyl oxygen of the complex ether bond. The coordination through the carbonyl group of ferutinin was demonstrated by theoretical calculations. Taken together, ferutinin molecules form H-bonded dimers, while complexation of Ca(2+) by ferutinin ruptures this hydrogen bond due to spatial re-orientation of the ferutinin molecules from parallel to antiparallel alignment.

Ferutinin Induces Membrane Depolarization, Permeability Transition Pore Formation, and Respiration Uncoupling in Isolated Rat Liver Mitochondria by Stimulation of Ca2+-Permeability

“…4, 8). One can suggest that ferutinin acts as Ca 2+ -ionophore that directly increases the inner mitochondrial membrane permeability to Ca 2+ -ions, which was earlier shown for planar lipid bilayer membranes and liposomes (Zamaraeva et al 1997;Abramov et al 2001;Dubis et al 2015).…”

“…Similarly, earlier works showed that ferutinin at concentrations of 1-50 µM considerably increased Ca 2+ -permeability of thymocytes, platelets, Jurkat T-cell, erythrocytes, mitochondria, and sarcoplasmic reticulum (Zamaraeva et al 1997(Zamaraeva et al , 1999(Zamaraeva et al , 2010Macho et al 2004;Gao et al 2013). Ferutinin interacts strongly with Ca 2+ -ions via the hydroxyl group of ferutinol and the carboxyl oxygen of the complex ether bond (Dubis et al 2015). It was demonstrated previously using FT-IR and NMR data together with theoretical calculations that in the absence of Ca 2+ ions ferutinin molecules formed H-bonded dimers while complexation of Ca 2+ by ferutinin ruptured this hydrogen bond due to spatial re-orientation of the ferutinin molecules from parallel to antiparallel alignment (Zamaraeva et al 1997;Abramov et al 2001;Dubis et al 2015).…”

“…Ferutinin interacts strongly with Ca 2+ -ions via the hydroxyl group of ferutinol and the carboxyl oxygen of the complex ether bond (Dubis et al 2015). It was demonstrated previously using FT-IR and NMR data together with theoretical calculations that in the absence of Ca 2+ ions ferutinin molecules formed H-bonded dimers while complexation of Ca 2+ by ferutinin ruptured this hydrogen bond due to spatial re-orientation of the ferutinin molecules from parallel to antiparallel alignment (Zamaraeva et al 1997;Abramov et al 2001;Dubis et al 2015). According to the conductometry data, the stoichiometry of the complex of ferutinin with calcium ion in acetone was 2:1.…”

“…On the other hand, ferutinin acts as an electrogenic Ca 2+ -ionophore that has been shown to use planar lipid bilayers membranes and liposomes (Zamaraeva et al 1997;Abramov et al 2001;Dubis et al 2015). Similarly, earlier works showed that ferutinin at concentrations of 1-50 µM considerably increased Ca 2+ -permeability of thymocytes, platelets, Jurkat T-cell, erythrocytes, mitochondria, and sarcoplasmic reticulum (Zamaraeva et al 1997(Zamaraeva et al , 1999(Zamaraeva et al , 2010Macho et al 2004;Gao et al 2013).…”

Controllable P Doping of the LaCoO3 Catalyst for Efficient Propane Oxidation: Optimized Surface Co Distribution and Enhanced Oxygen Vacancies

“…With time prolonging, there are obviously different intermediates on the surface of the two catalysts. For LaCoO 3 , the intensities of the carboxyl group (1468 cm –1 ), CC species (1557 cm –1 ), enolate species (1629 cm –1 ), and carbonyl group (1683, 1733 cm –1 ) , are increased from 8 min and then disappear at 22 min, whereas the CO 2 (2360 cm –1 ) signal remains stable. This demonstrates that the decomposition rate of intermediates is not easy.…”