Multiple human diseases ensue from a hereditary or acquired deficiency of iron-transporting protein function that diminishes transmembrane iron flux in distinct sites and directions. Because other iron-transport proteins remain active, labile iron gradients build up across the corresponding protein-deficient membranes. Here we report that a small molecule natural product, hinokitiol, can harness such gradients to restore iron transport into, within, and/or out of cells. The same compound promotes gut iron absorption in DMT1-deficient rats and ferroportin-deficient mice, as well as hemoglobinization in DMT1- and mitoferrin-deficient zebrafish. These findings illuminate a general mechanistic framework for small molecule-mediated site- and direction-selective restoration of iron transport. They also suggest small molecules that partially mimic the function of missing protein transporters of iron, and possibly other ions, may have potential in treating human diseases.

SignificanceExploiting advanced 3D designs in micro/nanomanufacturing inspires potential applications in various fields including biomedical engineering, metamaterials, electronics, electromechanical components, and many others. The results presented here provide enabling concepts in an area of broad, current interest to the materials community––strategies for forming sophisticated 3D micro/nanostructures and means for using them in guiding the growth of synthetic materials and biological systems. These ideas offer qualitatively differentiated capabilities compared with those available from more traditional methodologies in 3D printing, multiphoton lithography, and stress-induced bending––the result enables access to both active and passive 3D mesostructures in state-of-the-art materials, as freestanding systems or integrated with nearly any type of supporting substrate.

The addition of lithium salts to ionic liquids causes an increase in viscosity and a decrease in ionic mobility that hinders their possible application as an alternative solvent in lithium ion batteries. Optically heterodyne-detected optical Kerr effect spectroscopy was used to study the change in dynamics, principally orientational relaxation, caused by the addition of lithium bis(trifluoromethylsulfonyl)imide to the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide. Over the time scales studied (1 ps-16 ns) for the pure ionic liquid, two temperature-independent power laws were observed: the intermediate power law (1 ps to approximately 1 ns), followed by the von Schweidler power law. The von Schweidler power law is followed by the final complete exponential relaxation, which is highly sensitive to temperature. The lithium salt concentration, however, was found to affect both power laws, and a discontinuity could be found in the trend observed for the intermediate power law when the concentration (mole fraction) of lithium salt is close to chi(LiTf(2)N) = 0.2. A mode coupling theory (MCT) schematic model was also used to fit the data for both the pure ionic liquid and the different salt concentration mixtures. It was found that dynamics in both types of liquids are described very well by MCT.

Vibrational sum-frequency generation spectroscopy (SFG) was used for in situ studies of the electrified interface of the negative electrode (anode) of a lithium battery analog. In a lithium battery, lithium is deposited interstitially in a carbon anode. In the model system, which facilitates the study of the solid-electrolyte interphase (SEI) the anode was Au and lithium was deposited on the anode surface. The electrolyte was LiClO4 plus ethylene carbonate (EC) and diluted with tetrahydrofuran (THF). The SEI created on the anode in this case consists primarily of lithium ethylene dicarbonate (LiEDC) and lithium salts. SFG experiments were run during multiple cycles of reduction and oxidation of a half-cell, corresponding to charging and discharging of a battery. The infrared (IR) pulses were tuned to EC carbonyl transitions or −CH2 transitions of LiEDC and THF. A model is introduced to describe potential-dependent SFG intensities at electrified interfaces when the electrolyte has intense IR transitions. The electrified interface is defined as consisting of the electrode–electrolyte (or electrode–SEI) interface, plus bulk material located within a Debye length of the electrode. We show that SFG can detect and characterize the underpotential deposition and stripping of lithium on the Au anode, and we observe the growth and structural evolution of the SEI at the anode. During the first three charge/discharge cycles, SEI growth is hindered by the presence of THF, but after the third cycle the THF has been expelled and SEI growth accelerates and then levels off.