WZB117 (2-fluoro-6-(m-hydroxybenzoyloxy) phenyl m-hydroxybenzoate) inhibits passive sugar transport in human erythrocytes and cancer cell lines and, by limiting glycolysis, inhibits tumor growth in mice. This study explores how WZB117 inhibits the erythrocyte sugar transporter glucose transport protein 1 (GLUT1) and examines the transporter isoform specificity of inhibition. WZB117 reversibly and competitively inhibits erythrocyte 3-O-methylglucose (3MG) uptake with K = 6 μm but is a noncompetitive inhibitor of sugar exit. Cytochalasin B (CB) is a reversible, noncompetitive inhibitor of 3MG uptake with K = 0.3 μm but is a competitive inhibitor of sugar exit indicating that WZB117 and CB bind at exofacial and endofacial sugar binding sites, respectively. WZB117 inhibition of GLUTs expressed in HEK293 cells follows the order of potency: insulin-regulated GLUT4 ≫ GLUT1 ≈ neuronal GLUT3. This may explain WZB117-induced murine lipodystrophy. Molecular docking suggests the following. 1) The WZB117 binding envelopes of exofacial GLUT1 and GLUT4 conformers differ significantly. 2) GLUT1 and GLUT4 exofacial conformers present multiple, adjacent glucose binding sites that overlap with WZB117 binding envelopes. 3) The GLUT1 exofacial conformer lacks a CB binding site. 4) The inward GLUT1 conformer presents overlapping endofacial WZB117, d-glucose, and CB binding envelopes. Interrogating the GLUT1 mechanism using WZB117 reveals that subsaturating WZB117 and CB stimulate erythrocyte 3MG uptake. Extracellular WZB117 does not affect CB binding to GLUT1, but intracellular WZB117 inhibits CB binding. These findings are incompatible with the alternating conformer carrier for glucose transport but are consistent with either a multisubunit, allosteric transporter, or a transporter in which each subunit presents multiple, interacting ligand binding sites.
Electromigration in Cu Damascene lines with bamboo-like grain structures, either capped with Ta/TaN, SiNx, SiCxNyHz layers, or without any cap, was investigated. A thin Ta/TaN cap on top of the Cu line surface significantly improves electromigration lifetime when compared with lines without a cap and with lines capped with SiNx or SiCxNyHz. The activation energy for electromigration increased from 0.87 eV for lines without a cap to 1.0–1.1 eV for samples with SiNx or SiCxNyHz caps and to 1.4 eV for Ta/TaN capped samples.
We describe a liner' for Cu-Damascene multilevcl ULSI interconnects, which satisfies all the important requirements for a high performance and reliable Cu interconnect technology. This liner is implemented in the first manufacturing process to produce and ship CMOS chips with Cu interconnects'. The liner is a bilayer from a family of hcp/bcc-TaN followed by bcc-Ta (a-Ta), deposited sequentially in a single PVD chamber from a pure Ta target, using Ar and Nz sputtering gases. This bilayer simultaneously maximizes adhesion to the interlevel dielectric and the Cu fill, and has very low in-plane resistivity (-30-60 M-cm, depending on TaN/Ta thicknesses). These qualities produce high-yield, highly reliable, and electromigration-redundant Cu interconnects. Introduction Many liners have been implemented in experimental Cu integration schemes. The family of Ta-based compounds has emerged prominently. Ta (P-phase) was first shown to be an excellent Cu diffusion barrier in 1986 by Hu et d 3 . It was since found4 that a low background level (e.g. < l o 7 Torr) of O2 or H 2 0 was responsible for decreasing Cu diffusivity through Ta grain boundaries. (Presumably, current studies that fmd reduced Ta barrier performance stem fiom the low base pressures of modem PVD systems, and could be helped by a controlled leak of 02.) Such a P-Ta(0) barrier was used in the first multilevel Cu integration in polyimide ILD', due to its optimal adhesion to the materials used6. For dualDamascene integration in Si022 however (see fig. 1 .), Ta and Ta2N7 lack adequate adhesion to SO2, whereas TaN/SiO2 adhesion is excellent ( fig. 2). On the other hand, Cu/TaN adhesion is relatively poor. In fact, the liner/ILD and Cdliner adhesion have conflicting dependencies on N% in TaN,. We believe it is essential to maximize adhesion at all interfaces, especially the Cu/liner one. This is both to resist delamination during processing or thermal stressing, and for electromigration resistance in fine Cu lines, where interfacial and surface migration play a large role*. As confirmed elsewhere', Cu E-M lifetimes are lower when against a TaN vs. a Ta liner. Unlike CdTaN, /W, and /TiN, the CdTa interface exhibits high wetting" and atomic-scale mixing". This occurs without alloying, which would consume Cu atoms. The Cu/Ta interface is thus uniquely optimal among the commonly studied candidates.Another essential liner quality which has not been addressed generally elsewhere and which is lacking in TaN or TiN, is the capacity for current-strapping (electromigration rcdundancy) by a suitably thin liner. In thc event of Cu defects or elcctromigration wearout, a propcr liner should prevent or dclay open-circuit failurc, cvcn at maximum rated currcnt concentrated in the liner. Such rcdundancy is achieved by the TiAh alloy ovedunder cladding in our AI(Cu) interconnects, and is a reliability requirement for our Cu interconnccts as well. DiscussiodData Our evaluation factors for designing a Cu Damascenc liner are shown in Table I, with results from screening of many candidat...
The effects of impurities, Mn or Al, on interface and grain boundary electromigration (EM) in Cu damascene lines were investigated. The addition of Mn or Al solute caused a reduction in diffusivity at the Cu/dielectric cap interface and the EM activation energies for both Cu-alloys were found to increase by about 0.2 eV as compared to pure Cu. Mn mitigated and Al enhanced Cu grain boundary diffusion; however, no significant mitigation in Cu grain boundary diffusion was observed in low Mn concentration samples. The activation energies for Cu grain boundary diffusion were found to be 0.74 ± 0.05 eV and 0.77 ± 0.05 eV for 1.5 μm wide polycrystalline lines with pure Cu and Cu (0.5 at. % Mn) seeds, respectively. The effective charge number in Cu grain boundaries Z*GB was estimated from drift velocity and was found to be about −0.4. A significant enhancement in EM lifetimes for Cu(Al) or low Mn concentration bamboo-polycrystalline and near-bamboo grain structures was observed but not for polycrystalline-only alloy lines. These results indicated that the existence of bamboo grains in bamboo-polycrystalline lines played a critical role in slowing down the EM-induced void growth rate. The bamboo grains act as Cu diffusion blocking boundaries for grain boundary mass flow, thus generating a mechanical stress-induced back flow counterbalancing the EM force, which is the equality known as the “Blech short length effect.”
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