title: Chloride Transport through Supramolecular Barrel-Rosette Ion Channels: Lipophilic Control and Apoptosis-Inducing Activity.
abstract: Despite the great interest in artificial ion channel design, only a small number of channel-forming molecules are currently available for addressing challenging problems, particularly in the biological systems. Recent advances in chloride-mediated cell death, aided by synthetic ion carriers, encouraged us to develop chloride selective supramolecular ion channels. The present work describes vicinal diols, tethered to a rigid 1,3-diethynylbenzene core, as pivotal moieties for the barrel-rosette ion channel formation, and the activity of such channels was tuned by controlling the lipophilicity of designed monomers. Selective transport of chloride ions via an antiport mechanism and channel formation in the lipid bilayer membranes were confirmed for the most active molecule. A theoretical model of the supramolecular barrel-rosette, favored by a network of intermolecular hydrogen bonding, has been proposed. The artificial ion-channel-mediated transport of chloride into cells and subsequent disruption of cellular ionic homeostasis were evident. Perturbation of chloride homeostasis in cells instigates cell death by inducing the caspase-mediated intrinsic pathway of apoptosis.
authors.affiliation: Department of Chemistry and ‡Department of Biology, Indian Institute of Science Education and Research Pune , Dr. Homi Bhabha Road, Pashan, Pune, Maharashtra 411008, India.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Saha
authors.affiliation: Department of Chemistry and ‡Department of Biology, Indian Institute of Science Education and Research Pune , Dr. Homi Bhabha Road, Pashan, Pune, Maharashtra 411008, India.
authors.forename: Amitosh
authors.initials: A
authors.lastname: Gautam
authors.affiliation: Department of Chemistry and ‡Department of Biology, Indian Institute of Science Education and Research Pune , Dr. Homi Bhabha Road, Pashan, Pune, Maharashtra 411008, India.
authors.forename: Arnab
authors.identifier: 0000-0001-5691-6120
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Chemistry and ‡Department of Biology, Indian Institute of Science Education and Research Pune , Dr. Homi Bhabha Road, Pashan, Pune, Maharashtra 411008, India.
authors.forename: Mayurika
authors.initials: M
authors.lastname: Lahiri
authors.affiliation: Department of Chemistry and ‡Department of Biology, Indian Institute of Science Education and Research Pune , Dr. Homi Bhabha Road, Pashan, Pune, Maharashtra 411008, India.
authors.forename: Pinaki
authors.identifier: 0000-0003-3951-4335
authors.initials: P
authors.lastname: Talukdar
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001554:Benzene / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007473:Ion Channels / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects*; D008051:Lipid Bilayers / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation
chemical_list: D002712:Chlorides; D007473:Ion Channels; D008051:Lipid Bilayers; D001554:Benzene