-
Molecules (Basel, Switzerland) Nov 2020Synthetic anion transporters that facilitate chloride transport are promising candidates for channelopathy treatments. However, most anion transporters exhibit an...
Synthetic anion transporters that facilitate chloride transport are promising candidates for channelopathy treatments. However, most anion transporters exhibit an undesired side effect of facilitating proton transport via interacting with fatty acids present in the membrane. To address the limitation, we here report the use of a new tetrapodal scaffold to maximize the selective interaction with spherical chloride over binding the carboxylate headgroup of fatty acids. One of the new transporters demonstrated a high selectivity for chloride uniport over fatty acid-induced proton transport while being >10 times more active in chloride uniport than strapped calixpyrroles that were previously the only class of compounds known to possess similar selectivity properties.
Topics: Anion Transport Proteins; Anions; Chlorides; Chromatography, Thin Layer; Crystallography, X-Ray; Fatty Acids; Ion Transport; Lipid Bilayers; Magnetic Resonance Spectroscopy; Nitrates; Pyrenes; Sulfonic Acids
PubMed: 33172141
DOI: 10.3390/molecules25215179 -
Structural basis for assembly and lipid-mediated gating of LRRC8A:C volume-regulated anion channels.Nature Structural & Molecular Biology Jun 2023Leucine-rich repeat-containing protein 8 (LRRC8) family members form volume-regulated anion channels activated by hypoosmotic cell swelling. LRRC8 channels are...
Leucine-rich repeat-containing protein 8 (LRRC8) family members form volume-regulated anion channels activated by hypoosmotic cell swelling. LRRC8 channels are ubiquitously expressed in vertebrate cells as heteromeric assemblies of LRRC8A (SWELL1) and LRRC8B-E subunits. Channels of different subunit composition have distinct properties that explain the functional diversity of LRRC8 currents across cell types. However, the basis for heteromeric LRRC8 channel assembly and function is unknown. Here we leverage a fiducial-tagging strategy to determine single-particle cryo-EM structures of heterohexameric LRRC8A:C channels in multiple conformations. Compared to homomers, LRRC8A:C channels show pronounced differences in architecture due to heterotypic LRR interactions that displace subunits away from the conduction axis and poise the channel for activation. Structures and functional studies further reveal that lipids embedded in the channel pore block ion conduction in the closed state. These results provide insight into determinants for heteromeric LRRC8 channel assembly, activity and gating by lipids.
Topics: Membrane Proteins; Anions; Lipids
PubMed: 36928458
DOI: 10.1038/s41594-023-00944-6 -
Organic & Biomolecular Chemistry Oct 2022A new family of squaramide-based anionophores (L1-L8) have been synthesised and fully characterised with the aim to investigate the effect of indolyl substituents on...
A new family of squaramide-based anionophores (L1-L8) have been synthesised and fully characterised with the aim to investigate the effect of indolyl substituents on their anion binding and transmembrane transport properties. L1, L2, L6, and L8, bearing a 7-indolyl/indol-7-yl moiety as the substituent, were found to be the most efficient of the series in binding chloride with high stability constants. L1, L6, and L8 were also found to be the most potent anionophores of the series, able to mediate transmembrane anion transport. In particular, L6 bearing the 3,5-bis(trifluoromethyl)phenyl group was found to be the most active transporter, and its efficiency as an anionophore/anion transporter was favourably compared with that of their symmetrically-substituted squaramide analogues L9 and L10, previously reported in the literature.
Topics: Chlorides; Ion Transport; Anions; Quinine
PubMed: 36196986
DOI: 10.1039/d2ob01444k -
Molecules (Basel, Switzerland) Jun 2022Cyclic pentaphenylalanine was studied as an efficient anion sensor for halides, thiocyanate and oxoanions in acetonitrile and methanol. Stability constants of the...
Cyclic pentaphenylalanine was studied as an efficient anion sensor for halides, thiocyanate and oxoanions in acetonitrile and methanol. Stability constants of the corresponding complexes were determined by means of fluorimetric, spectrophotometric, H NMR, and microcalorimetric titrations. A detailed structural overview of receptor-anion complexes was obtained by classical molecular dynamics (MD) simulations. The results of H NMR and MD studies indicated that the bound anions were coordinated by the amide groups of cyclopeptide, as expected. Circular dichroism (CD) titrations were also carried out in acetonitrile. To the best of our knowledge, this is the first example of the detection of anion binding by cyclopeptide using CD spectroscopy. The CD spectra were calculated from the structures obtained by MD simulations and were qualitatively in agreement with the experimental data. The stoichiometry of almost all complexes was 1:1 (receptor:anion), except for dihydrogen phosphate where the binding of dihydrogen phosphate dimer was observed in acetonitrile. The affinity of the cyclopeptide receptor was correlated with the structure of anion coordination sphere, as well as with the solvation properties of the examined solvents.
Topics: Acetonitriles; Anions; Molecular Dynamics Simulation; Peptides, Cyclic; Phosphates
PubMed: 35745042
DOI: 10.3390/molecules27123918 -
The Journal of Physical Chemistry. A Jan 2023We have analyzed the low-energy electron attachment to wobble base pairs using the equation of motion coupled cluster method and extended basis sets. A doorway mechanism...
We have analyzed the low-energy electron attachment to wobble base pairs using the equation of motion coupled cluster method and extended basis sets. A doorway mechanism exists for the attachment of the additional electron to the base pairs, where the initially formed dipole-bound anion captures the incoming electron. The doorway dipole-bound anionic state subsequently leads to the formation of a valence-bound state, and the transfer of extra electron occurs by mixing of electronic and nuclear degrees of freedom. The formation of the valence-bound anion is associated with proton transfer in hypoxanthine-cytosine and hypoxanthine-adenine base pairs, which happens through a concerted electron-proton transfer process. The calculated rate constant for the dipole-bound to valence-bound transition in wobble base pairs is slower than that observed in the Watson-Crick guanine-cytosine base pair.
Topics: Base Pairing; Protons; Electrons; Anions; Cytosine; Guanine; Hydrogen Bonding
PubMed: 36622294
DOI: 10.1021/acs.jpca.2c07469 -
Chemphyschem : a European Journal of... May 2020Stable dimers aspartate-aspartate have been studied in aqueous and gas phase through theoretical simulations. The polarizable continuum model (PCM) has been applied to...
Stable dimers aspartate-aspartate have been studied in aqueous and gas phase through theoretical simulations. The polarizable continuum model (PCM) has been applied to simulate the effect of the hydration on monomers and complexes. The quantum theory of atoms in molecules (QTAIM) and the interacting quantum atoms (IQA) scheme has been used to inquire into if, in the aqueous phase, individual hydrogen bonds have attractive electrostatic components. In all cases a spontaneous formation of the complexes in the aqueous phase are observed, while in the gas phase a considerable energy barrier must be overcome (between 100.8 to 263.2 kJ mol ). The intermolecular distance at which this barrier is indicates when the hydrogen-bond interactions begin to take importance between the dimers and the corresponding molecular recognition among them. The IQA analysis shows that in aqueous phase, the hydrogen bonds N-H⋅⋅⋅O are mainly electrostatic in nature with a certain covalent character which increases linearly with the decrease of internuclear distances H⋅⋅⋅O. The H⋅⋅⋅H interactions observed are stabilizing and they are mainly quantum in nature.
Topics: Anions; Aspartic Acid; Dimerization; Hydrogen Bonding; Quantum Theory
PubMed: 32189438
DOI: 10.1002/cphc.201901200 -
Journal of the American Chemical Society Jun 2022Ion transport across lipid membranes in biology is controlled by stimuli-responsive membrane channels and molecular machine ion pumps such as ATPases. Here, we report a...
Ion transport across lipid membranes in biology is controlled by stimuli-responsive membrane channels and molecular machine ion pumps such as ATPases. Here, we report a synthetic molecular machine-like ion transport relay, in which transporters on opposite sides of a lipid bilayer membrane facilitate transport by passing ions between them. By incorporating a photo-responsive telescopic arm into the relay design, this process is reversibly controlled in response to irradiation with blue and green light. Transport occurs only in the extended state when the length of the arm is sufficient to pass the anion between transporters located on opposite sides of the membrane. In contrast, the contracted state of the telescopic arm is too short to mediate effective transport. The system acts as a stimuli-responsive ensemble of machine-like components, reminiscent of robotic arms in a factory assembly line, working cooperatively to mediate ion transport. This work points to new prospects for using lipid bilayer membranes as scaffolds for confining, orientating, and controlling the relative positions of molecular machines, thus enabling multiple components to work in concert and opening up new applications in biological contexts.
Topics: Anions; Biological Transport; Ion Channels; Ion Transport; Lipid Bilayers
PubMed: 35652660
DOI: 10.1021/jacs.2c02612 -
Pflugers Archiv : European Journal of... Aug 2020Many anion channels, frequently referred as Cl channels, are permeable to different anions in addition to Cl. As the second-most abundant anion in the human body, HCO... (Review)
Review
Many anion channels, frequently referred as Cl channels, are permeable to different anions in addition to Cl. As the second-most abundant anion in the human body, HCO permeation via anion channels has many important physiological roles. In addition to its classical role as an intracellular pH regulator, HCO also controls the activity and stability of dissolved proteins in bodily fluids such as saliva, pancreatic juice, intestinal fluid, and airway surface liquid. Moreover, HCO permeation through these channels affects membrane potentials that are the driving forces for transmembrane transport of solutes and water in epithelia and affect neuronal excitability in nervous tissue. Consequently, aberrant HCO transport via anion channels causes a number of human diseases in respiratory, gastrointestinal, genitourinary, and neuronal systems. Notably, recent studies have shown that the HCO permeabilities of several anion channels are not fixed and can be altered by cellular stimuli, findings which may have both physiological and pathophysiological significance. In this review, we summarize recent progress in understanding the molecular mechanisms and the physiological roles of HCO permeation through anion channels. We hope that the present discussions can stimulate further research into this very important topic, which will provide the basis for human disorders associated with aberrant HCO transport.
Topics: Animals; Anions; Bicarbonates; Biological Transport; Cell Membrane Permeability; Humans; Ion Channels
PubMed: 32621085
DOI: 10.1007/s00424-020-02425-x -
Molecules (Basel, Switzerland) May 2022Self-assembly of organic ions in aqueous solutions is a hot topic at the present time, and substances that are well-soluble in water are usually studied. In this work,...
Self-assembly of organic ions in aqueous solutions is a hot topic at the present time, and substances that are well-soluble in water are usually studied. In this work, aqueous solutions of sodium diclofenac are investigated, which, like most medicinal compounds, is poorly soluble in water. Classical MD modeling of an aqueous solution of diclofenac sodium showed equilibrium between the hydrated anion and the hydrated dimer of the diclofenac anion. The assignment and interpretation of the bands in the UV, NIR, and IR spectra are based on DFT calculations in the discrete-continuum approximation. It has been shown that the combined use of spectroscopic methods in various frequency ranges with classical MD simulations and DFT calculations provides valuable information on the association processes of medical compounds in aqueous solutions. Additionally, such a combined application of experimental and calculation methods allowed us to put forward a hypothesis about the mechanism of the effect of diclofenac sodium in high dilutions on a solution of diclofenac sodium.
Topics: Anions; Diclofenac; Ions; Solutions; Water
PubMed: 35630826
DOI: 10.3390/molecules27103350 -
Proceedings of the Japan Academy.... 2023The aromaticity and synthetic application of "heavy benzenes", i.e., benzenes containing a heavier Group 14 element (Si, Ge, Sn, and Pb) in place of skeletal carbon,... (Review)
Review
The aromaticity and synthetic application of "heavy benzenes", i.e., benzenes containing a heavier Group 14 element (Si, Ge, Sn, and Pb) in place of skeletal carbon, have been the targets of many theoretical and synthetic studies. Although the introduction of a sterically demanding substituent enabled us to synthesize and isolate heavy aromatic species as a stable compound by suppressing their high reactivity and tendency to polymerize, the existence of a protection group is an obstruction to the development of functional materials based on heavy aromatics. This review will delineate the most recent topics in the chemistry of heavy aromatics, i.e., the chemistry of "metallabenzenyl anions", which are the heavier Group 14 element analogs of phenyl anions stabilized by taking advantage of charge repulsion instead of steric protection.
Topics: Benzene; Anions; Carbon
PubMed: 38072454
DOI: 10.2183/pjab.99.027