Because of their hollow interior, transmembrane channels are capable
of opening up pathways for ions across lipid membranes of living cells.
Here, we demonstrate ion conduction induced by a single DNA duplex
that lacks a hollow central channel. Decorated with six porpyrin-tags,
our duplex is designed to span lipid membranes. Combining electrophysiology
measurements with all-atom molecular dynamics simulations, we elucidate
the microscopic conductance pathway. Ions flow at the DNA–lipid
interface as the lipid head groups tilt toward the amphiphilic duplex
forming a toroidal pore filled with water and ions. Ionic current
traces produced by the DNA-lipid channel show well-defined insertion
steps, closures, and gating similar to those observed for traditional
protein channels or synthetic pores. Ionic conductances obtained through
simulations and experiments are in excellent quantitative agreement.
The conductance mechanism realized here with the smallest possible
DNA-based ion channel offers a route to design a new class of synthetic
ion channels with maximum simplicity.
Reactions of acetylenes derived from glyceraldehyde and propargyl aldehyde show remarkable reactivity in Kinugasa cycloaddition/rearrangement cascade process catalyzed by Cu(I) ion. Reactions proceed by formation of a rigid dinuclear copper(I) complex in which each copper ion is coordinated to one or both oxygen atoms in the acetylene molecule and to both triple bonds. It has been demonstrated that one oxygen atom can be replaced by the phenyl ring, which is able to coordinate the copper ion by the aromatic sextet. Kinugasa reactions that proceed in a high yield can also be performed in the presence of a catalytic amount of the copper salt to provide products in an acceptable yield without a decrease of diastereoselectivity.
Lipid liquid-crystalline nanoparticles (cubosomes) were used for the first time as a dual-modality drug delivery system for internal radiotherapy combined with chemotherapy. Monoolein (GMO)-based cubosomes were prepared by loading the anticancer drug, doxorubicin and a commonly used radionuclide, low-energy beta (β−)-emitter, 177Lu. The radionuclide was complexed with a long chain derivative of DOTAGA (DOTAGA-OA). The DOTAGA headgroup of the chelator was exposed to the aqueous channels of the cubosomes, while, concerning OA, the hydrophobic tail was embedded in the nonpolar region of the lipid bilayer matrix, placing the radioactive dopant in a stable manner inside the cubosome. The cubosomes containing doxorubicin and the radionuclide complex increased the cytotoxicity measured by the viability of the treated HeLa cells compared with the effect of single-drug cubosomes containing either the DOX DOTAGA-OA or DOTAGA-OA-177Lu complex. Multifunctional lipidic nanoparticles encapsulating the chemotherapeutic agent together with appropriately complexed (β−) radionuclide are proposed as a potential strategy for effective local therapy of various cancers.
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