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1.D.199.  The Synthetic Porphyrin Box Monosaccharide Transporter (PB-MT) Family  

Lee et al. 2022 reported synthetic monosaccharide channels built with shape-persistent organic cages, porphyrin boxes (PBs), that allow facile transmembrane transport of glucose and fructose through their windows. PBs show a much higher transport rate for glucose and fructose over disaccharides such as sucrose. The transport rate can be modulated by changing the length of the alkyl chains decorating the cage windows. Insertion of a linear pillar ligand into the cavity of PBs blocks monosaccharide transport. In-vitro cell experiments showed that PBs transport glucose across the living cell membrane and enhance cell viability when natural glucose transporter GLUT1 is blocked. Time-dependent live-cell imaging and MTT assays confirmed the cyto-compatibility of PBs. Monosaccharide-selective transport of PBs is reminiscent of natural glucose transporters (GLUTs) (Lee et al. 2022).

The Kim group have described molecular containers as synthetic cation channels (Jung et al. 2008). In 2017, Kim, Roh and colleagues expanded the field by describing an organic polyhedron, porphyrin box 49, that selectively transports iodide into vesicles and cells (see the figure below; Benke et al. 2017). Experiments in planar lipid bilayers showed that 49 formed single channels. Porphyrin box 49 (Mw = 8327 amu), prepared in 95% yield in one-step, has appealing properties for a channel: (1) measuring 3.64 nm × 2.83 nm, it has a roomy interior; (2) its dimensions and hydrophobic sidechains enable it to insert into a lipid bilayer of d ∼ 4 nm; (3) its 12 openings, with portals of d ∼ 3.7 Å, should enable ions to enter and leave the cage and (4) being stable at pH 4.8–13, it is attractive for biological use.


Dimensions of porphyrin box 49. (d) Schematic for ion channel formed by 49 in lipid bilayer. Copyright 2017, American Chemical Society.

Transport experiments using lucigenin showed that 49 catalyses Cl/NO3 exchange across EYPC liposomes. A battery of assays using lucigenin and the pH-sensitive dye HPTS confirmed that 49 was anion-selective, with transport rates following the Hofmeister series (ktr for I > NO3 > Br > Cl). This indicates that ease of anion dehydration is key to transport. The authors suggested that anion selectivity might be due to CH⋯anion interactions with the cage's aromatic walls and/or aliphatic windows. They stressed that 49 was 60-fold better at transporting Ithan Cl across EYPC vesicles, underscoring the cage's potential to study iodide transport in cells. Voltage-clamp measurements in planar bilayers showed that 49 gave long-lived (5–10 s) single channels with distinct open and closed states.


References associated with 1.D.199 family:

Benke, B.P., P. Aich, Y. Kim, K.L. Kim, M.R. Rohman, S. Hong, I.C. Hwang, E.H. Lee, J.H. Roh, and K. Kim. (2017). Iodide-Selective Synthetic Ion Channels Based on Shape-Persistent Organic Cages. J. Am. Chem. Soc. 139: 7432-7435. 28538099
Jung, M., H. Kim, K. Baek, and K. Kim. (2008). Synthetic ion channel based on metal-organic polyhedra. Angew Chem Int Ed Engl 47: 5755-5757. 18576447
Lee, H.G., A. Dhamija, C.K. Das, K.M. Park, Y.T. Chang, L.V. Schäfer, and K. Kim. (2022). Synthetic Monosaccharide Channels: Size-Selective Transmembrane Transport of Glucose and Fructose Mediated by Porphyrin Boxes. Angew Chem Int Ed Engl e202214326. [Epub: Ahead of Print] 36382990