Normal copper homeostasis is essential for human growth and development. Copper mutations, inadequate diet or surgical interventions, may lead to cardiac hypertrophy, poor neuronal myelination, blood vessel abnormalities and impaired immune response. Copper overload is associated with morphological and metabolic changes in tissues and, if untreated, eventual death. Recent reports also indicate that changes in the expression of copper transporters alter the sensitivity of cancer cells to major chemotherapeutic drugs, such as cisplatin, although the mechanism behind this important phenomenon remains unclear. This review summarizes current information on the molecular characteristics of copper transporters CTR1, CTR2, ATP7A and ATP7B, their roles in mammalian copper homeostasis and the physiological consequences of their inactivation. The mechanisms through which copper transporters may influence cell sensitivity to cisplatin are discussed. Regulation of human copper homeostasis has significant therapeutic potential and requires the detailed understanding of copper transport mechanisms.

The human copper-transporting ATPases (Cu-ATPases) are essential for dietary copper uptake, normal development and function of the CNS, and regulation of copper homeostasis in the body. In a cell, Cu-ATPases maintain the intracellular concentration of copper by transporting copper into intracellular exocytic vesicles. In addition, these P-type ATPases mediate delivery of copper to copper-dependent enzymes in the secretory pathway and in specialized cell compartments such as secretory granules or melanosomes. The multiple functions of human Cu-ATPase necessitate complex regulation of these transporters that is mediated through the presence of regulatory domains in their structure, posttranslational modification and intracellular trafficking, as well as interactions with the copper chaperone Atox1 and other regulatory molecules. In this review, we summarize the current information on the function and regulatory mechanisms acting on human Cu-ATPases ATP7A and ATP7B. Brief comparison with the Cu-ATPase orthologs from other species is included.

Soft chemical reactions such as ion-exchange and acid-base reactions have been extensively investigated to synthesize novel metastable layered inorganic solids, to exfoliate them into individual nanosheets, and to re-assemble them as thin films and nanocomposite materials. These reactions proceed at relatively low temperature and enable the synthesis of a rich variety of structures by stepwise reactions. In recent years, the toolbox of soft chemical reactions has been utilized to rationally design and tailor the properties of functional layered transition metal oxides. Layer-by-layer assembly and intercalation chemistry have provided insight into covalent interactions that stabilize oxide-supported nanoparticle catalysts. In addition, topochemical reactions have been utilized to tune the compositions of layered perovskite oxides in order to break inversion symmetry, resulting in piezoelectric and ferroelectric properties. This review focuses on the use of soft chemical approaches to design functional layered transition metal oxides with tunable properties. Soft chemical reactions enable the design of functional materials for diverse applications that include artificial photosynthesis, catalysis, energy storage, fuel cells, optical sensors, ferroics, and high-k dielectrics.

In contrast to polar cation displacements driving oxides into noncentrosymmetric and ferroelectric states, inversion-preserving anion displacements, such as rotations or tilts of oxygen octahedra about cation coordination centers, are exceedingly common. More than one nonpolar rotational mode in layered perovskites can lift inversion symmetry and combine to induce an electric polarization through a hybrid improper ferroelectric (HIF) mechanism. This form of ferroelectricity expands the compositional palette to new ferroelectric oxides because its activity derives from geometric rather than electronic origins. Here, the new Ruddlesden-Popper HIF Sr 3 Zr 2 O 7 , which is the first ternary lead-free zirconate ferroelectric, is reported and room-temperature polarization switching is demonstrated. This compound undergoes a first-order ferroelectric-to-paraelectric transition, involving an unusual change in the "sense" of octahedral rotation while the octahedral tilt remains unchanged. Our experimental and first-principles study shows that the paraelectric polymorph competes with the polar phase and emerges from a trilinear coupling of rotation and tilt modes interacting with an antipolar mode. This form of hybrid improper "antiferroelectricity" is recently predicted theoretically but has remained undetected. This work establishes the importance of understanding anharmonic interactions among lattice degrees of freedom, which is important for the discovery of new ferroelectrics and likely to influence the design of next-generation thermoelectrics.