Boronated derivatives of chlorin e 6 and fluoride-containing porphyrins as penetrating anions: a study using bilayer lipid membranes

Abstract

Boronated derivatives of porphyrins are studied extensively as promising compounds for boron-neutron capture therapy and photodynamic therapy. Understanding of the mechanism of their permeation across cell membranes is a key step in screening for the most efficient compounds. In the present work, we studied the ability of boronated derivatives of chlorin e(6) and porphyrins, which are mono-, di-, and tetra-anions, to permeate through planar bilayer lipid membranes (BLM). The translocation rate constants through the hydrophobic part of the lipid bilayer were estimated for monocarborane and its conjugate with chlorin e(6) by the method of electrical current relaxation. They were similar, 6.6 and 6.8 sec(-1), respectively. Conjugates of porphyrins carrying two and four carborane groups were shown to permeate efficiently through a BLM although they carry two charges and four charges, respectively. The rate of permeation of the tetraanion estimated by the BLM current had superlinear dependence on the BLM voltage. Because the resting potential of most mammalian cells is negative inside, it can be concluded that the presence of negatively-charged boronated groups in compounds should hinder the accumulation of the porphyrins in cells.

Effect of Alkyl Chain Length on Translocation of Rhodamine B n-Alkyl Esters across Lipid Membranes

“…In this work, we observed a severalfold increase in the flip-flop rate for a series of C n RB compounds having an almost planar xanthene group (Table 1). It has been observed previously in our group that the rate of flip-flop of anionic monocarborane having a spherical shape is equal to that of a conjugate with chlorine e6, BACE (48). These results are in line with the idea that in the case of permeation of a spherical molecule, the input of the rotational diffusion should be negligible.…”

Unsaturated lipids protect the integral membrane peptide gramicidin A from singlet oxygen

“…This approach is applicable to measure binding to BLM of those charged compounds, which are capable of permeating through lipid bilayers due to delocalization of their charge. This capability of BACE shown in our previous studies [32,36] is obviously associated with the presence of a polyhedral carborane in its structure. Fig.…”

“…With DOPC membranes, the current relaxation was a little slower (with the relaxation time constant being 120 ms upon application and 150 ms upon removal of the 50 mV voltage) than with DPhPC membranes (70 and 90 ms, respectively). However, the total number of ions moved through the bilayer during a single current transient, estimated from the area under the relaxation curve [35,36] in response to a voltage jump of 50 mV applied 20 min after the addition of BACE to the bathing solution, was similar for DOPC (37 ± 4 picoCoulombs) and DPhPC (38 ± 3 picoCoulombs) membranes (the mean value for 3 BLMs in each case). Therefore, the quantity of charged BACE molecules adsorbed on the bilayer boundary was the same for the unsaturated and the saturated lipid membranes, and thus a change in membrane binding of BACE could not be responsible for the decreased gA photoinactivation in DOPC membranes compared to DPhPC membranes.…”

“…2) to the difference in the membrane dipole potentials for bilayers formed from the unsaturated and saturated lipids [39]. Previously, we observed slowing down of the current relaxation kinetics for BACE in the presence of phloretin [36], the dipole modifier known to reduce the membrane dipole potential [45,46]. The sensitivity of transmembrane movement to the membrane dipole potential is a long established property of permeating ions, namely: the dipole potential facilitates permeation of lipophilic anions and mitigates permeation of hydrophobic cations through lipid bilayers [45–47].…”

“…In voltage‐jump current relaxation experiments [35–37], the voltage of 50 mV was applied to BLM or removed at the zero time, which resulted in current relaxation from I (0) to I (∞).The capacitive response of BLM in the absence of BACE was recorded in each experiment (control measurements of the current at voltage values used in the experiment). Then BACE was added to both sides of BLM and recordings of the current in the presence of BACE were analyzed after subtracting the control traces.…”