Acid-Dependent Charge Transport in a Solution-Processed 2D Conductive Metal-Organic Framework.

The development of conductive metal-organic frameworks (MOFs) presents a unique challenge in materials chemistry because it is unclear how to dope them. Here, we demonstrate that the inclusion of pendant amines on hexahydroxytriphenylene linkages results in two-dimensional (2D) polycrystalline frameworks Cu3(HHTATP)2, isostructural to its Cu3(HHTP)2 parent, and exhibits the highest electrical conductivity of 1.21 S/cm among 2D MOFs featuring CuO4 metal nodes. Moreover, the bulk material can be treated with acid, resulting in a protonation-dependent increase in the conductivity. By spin-coating the acidic solution, we fabricated large-area thin films and collectively demonstrated an intuitive route to solution-processable, dopable, conductive MOFs.

Programming "Atomic Substitution" in Alloy Colloidal Crystals Using DNA.

Although examples of colloidal crystal analogues to metal alloys have been reported, general routes for preparing 3D analogues to random substitutional alloys do not exist. Here, we use the programmability of DNA (length and sequence) to match nanoparticle component sizes, define parent lattice symmetry and substitutional order, and achieve faceted crystal habits. We synthesized substitutional alloy colloidal crystals with either ordered or random arrangements of two components (Au and Fe3O4 nanoparticles) within an otherwise identical parent lattice and crystal habit, confirmed via scanning electron microscopy and small-angle X-ray scattering. Energy dispersive X-ray spectroscopy reveals information regarding composition and local order, while the magnetic properties of Fe3O4 nanoparticles can direct different structural outcomes for different alloys in an applied magnetic field. This work constitutes a platform for independently defining substitution within multicomponent colloidal crystals, a capability that will expand the scope of functional materials that can be realized through programmable assembly.

Chemical Vapor Deposition of Edge-on Oriented 2D Conductive Metal-Organic Framework Thin Films.

We demonstrated the synthesis of a conductive two-dimensional metal-organic framework (MOF) thin film by single-step all-vapor-phase chemical vapor deposition (CVD). The synthesized large-area thin film of Cu3(C6O6)2 has an edge-on-orientation with high crystallinity. Cu3(C6O6)2 thin film-based microdevices were fabricated by e-beam lithography and had an electrical conductivity of 92.95 S/cm. Synthesis of conductive MOF thin films by the all-vapor-phase CVD will enable fundamental studies of physical properties and may help to accomplish practical applications of conductive MOFs.

Probing the Consequences of Cubic Particle Shape and Applied Field on Colloidal Crystal Engineering with DNA.

In a magnetic field, cubic Fe3 O4 nanoparticles exhibit assembly behavior that is a consequence of a competition between magnetic dipole-dipole and ligand interactions. In most cases, the interactions between short hydrophobic ligands dominate and dictate assembly outcome. To better tune the face-to-face interactions, cubic Fe3 O4 nanoparticles were functionalized with DNA. Their assembly behaviors were investigated both with and without an applied magnetic field. Upon application of a field, the tilted orientation of cubes, enabled by the flexible DNA ligand shell, led to an unexpected crystallographic alignment of the entire superlattice, as opposed to just the individual particles, along the field direction as revealed by small and wide-angle X-ray scattering. This observation is dependent upon DNA length and sequence and cube dimensions. Taken together, these studies show how combining physical and chemical control can expand the possibilities of crystal engineering with DNA.

Isoreticular Linker Substitution in Conductive Metal-Organic Frameworks with Through-Space Transport Pathways.

The extension of reticular chemistry concepts to electrically conductive three-dimensional metal-organic frameworks (MOFs) has been challenging, particularly for cases in which strong interactions between electroactive linkers create the charge transport pathways. Here, we report the successful replacement of tetrathiafulvalene (TTF) with a nickel glyoximate core in a family of isostructural conductive MOFs with Mn2+ , Zn2+ , and Cd2+ . Different coordination environments of the framework metals lead to variations in the linker stacking geometries and optical properties. Single-crystal conductivity data are consistent with charge transport along the linker stacking direction, with conductivity values only slightly lower than those reported for the analogous TTF materials. These results serve as a case study demonstrating how reticular chemistry design principles can be extended to conductive frameworks with significant intermolecular contacts.

High Li+ and Mg2+ Conductivity in a Cu-Azolate Metal-Organic Framework.

A Cu-azolate metal-organic framework (MOF) uptakes stoichiometric loadings of Groups 1 and 2 metal halides, demonstrating efficient reversible release and reincorporation of immobilized anions within the framework. Ion-pairing interactions lead to anion-dependent Li+ and Mg2+ transport in Cu4(ttpm)2·0.6CuCl2, whose high surface area affords a high density of uniformly distributed mobile metal cations and halide binding sites. The ability to systematically tune the ionic conductivity yields a solid electrolyte with a Mg2+ ion conductivity rivaling the best materials reported to date. This MOF is one of the first in a promising class of frameworks that introduces the opportunity to control the identity, geometry, and distribution of the cation hopping sites, offering a versatile template for application-directed design of solid electrolytes.

Selective Vapor Pressure Dependent Proton Transport in a Metal-Organic Framework with Two Distinct Hydrophilic Pores.

The mechanism of proton conductivity in porous solids (i.e., Grotthuss or vehicular) is related to the structure and chemical environment of the pores. Direct observation of structure-function relationships is difficult because state-of-the-art solid proton conductors are often amorphous. Here, we present a systematic elucidation of two distinct proton transport pathways within MIT-25, a mesoporous metal-organic framework that exhibits parallel channels of ∼27 Šand ∼4.5 Šwidth. We characterize transport through these pores using temperature- and humidity-dependent proton conductivity measurements and density functional theory. Through control of vapor pressure we are able to sequentially fill the small and large pores, promoting proton conductivity with distinct activation energies at low and high relative humidity, respectively.

Tunable Mixed-Valence Doping toward Record Electrical Conductivity in a Three-Dimensional Metal-Organic Framework.

Partial oxidation of an iron-tetrazolate metal-organic framework (MOF) upon exposure to ambient atmosphere yields a mixed-valence material with single-crystal conductivities tunable over 5 orders of magnitude and exceeding 1 S/cm, the highest for a three-dimensionally connected MOF. Variable-temperature conductivity measurements reveal a small activation energy of 160 meV. Electronic spectroscopy indicates the population of midgap states upon air exposure and corroborates intervalence charge transfer between Fe2+ and Fe3+ centers. These findings are consistent with low-lying Fe3+ defect states predicted by electronic band structure calculations and demonstrate that inducing metal-based mixed valency is a powerful strategy toward realizing high and systematically tunable electrical conductivity in MOFs.

Activation of the IGF1 pathway mediates changes in cellular contractility and motility in single-suture craniosynostosis.

Insulin growth factor 1 (IGF1) is a major anabolic signal that is essential during skeletal development, cellular adhesion and migration. Recent transcriptomic studies have shown that there is an upregulation in IGF1 expression in calvarial osteoblasts derived from patients with single-suture craniosynostosis (SSC). Upregulation of the IGF1 signaling pathway is known to induce increased expression of a set of osteogenic markers that previously have been shown to be correlated with contractility and migration. Although the IGF1 signaling pathway has been implicated in SSC, a correlation between IGF1, contractility and migration has not yet been investigated. Here, we examined the effect of IGF1 activation in inducing cellular contractility and migration in SSC osteoblasts using micropost arrays and time-lapse microscopy. We observed that the contractile forces and migration speeds of SSC osteoblasts correlated with IGF1 expression. Moreover, both contractility and migration of SSC osteoblasts were directly affected by the interaction of IGF1 with IGF1 receptor (IGF1R). Our results suggest that IGF1 activity can provide valuable insight for phenotype-genotype correlation in SSC osteoblasts and might provide a target for therapeutic intervention.

Single-Ion Li+, Na+, and Mg2+ Solid Electrolytes Supported by a Mesoporous Anionic Cu-Azolate Metal-Organic Framework.

A novel Cu(II)-azolate metal-organic framework (MOF) with tubular pores undergoes a reversible single crystal to single crystal transition between neutral and anionic phases upon reaction with stoichiometric amounts of halide or pseudohalide salts. The stoichiometric transformation between the two phases allows loading of record amounts of charge-balancing Li+, Na+, and Mg2+ ions for MOFs. Whereas the halide/pseudohalide anions are bound to the metal centers and thus stationary, the cations move freely within the one-dimensional pores, giving rise to single-ion solid electrolytes. The respective Li+-, Na+-, and Mg2+-loaded materials exhibit high ionic conductivity values of 4.4 × 10-5, 1.8 × 10-5, and 8.8 × 10-7 S/cm. With addition of LiBF4, the Li+ conductivity improves to 4.8 × 10-4 S/cm. These are the highest values yet observed for MOF solid electrolytes.

The Organic Secondary Building Unit: Strong Intermolecular π Interactions Define Topology in MIT-25, a Mesoporous MOF with Proton-Replete Channels.

The structure-directing role of the inorganic secondary building unit (SBU) is key for determining the topology of metal-organic frameworks (MOFs). Here we show that organic building units relying on strong π interactions that are energetically competitive with the formation of common inorganic SBUs can also play a role in defining the topology. We demonstrate the importance of the organic SBU in the formation of Mg2H6(H3O)(TTFTB)3 (MIT-25), a mesoporous MOF with the new ssp topology. A delocalized electronic hole is critical in the stabilization of the TTF triad organic SBUs and exemplifies a design principle for future MOF synthesis.

Exome sequencing identifies a recurrent de novo ZSWIM6 mutation associated with acromelic frontonasal dysostosis.

Acromelic frontonasal dysostosis (AFND) is a rare disorder characterized by distinct craniofacial, brain, and limb malformations, including frontonasal dysplasia, interhemispheric lipoma, agenesis of the corpus callosum, tibial hemimelia, preaxial polydactyly of the feet, and intellectual disability. Exome sequencing of one trio and two unrelated probands revealed the same heterozygous variant (c.3487C>T [p. Arg1163Trp]) in a highly conserved protein domain of ZSWIM6; this variant has not been seen in the 1000 Genomes data, dbSNP, or the Exome Sequencing Project. Sanger validation of the three trios confirmed that the variant was de novo and was also present in a fourth isolated proband. In situ hybridization of early zebrafish embryos at 24 hr postfertilization (hpf) demonstrated telencephalic expression of zswim6 and onset of midbrain, hindbrain, and retinal expression at 48 hpf. Immunohistochemistry of later-stage mouse embryos demonstrated tissue-specific expression in the derivatives of all three germ layers. qRT-PCR expression analysis of osteoblast and fibroblast cell lines available from two probands was suggestive of Hedgehog pathway activation, indicating that the ZSWIM6 mutation associated with AFND may lead to the craniofacial, brain and limb malformations through the disruption of Hedgehog signaling.

Measuring and Reporting Electrical Conductivity in Metal-Organic Frameworks: Cd2(TTFTB) as a Case Study.

Electrically conductive metal-organic frameworks (MOFs) are emerging as a subclass of porous materials that can have a transformative effect on electronic and renewable energy devices. Systematic advances in these materials depend critically on the accurate and reproducible characterization of their electrical properties. This is made difficult by the numerous techniques available for electrical measurements and the dependence of metrics on device architecture and numerous external variables. These challenges, common to all types of electronic materials and devices, are especially acute for porous materials, whose high surface area make them even more susceptible to interactions with contaminants in the environment. Here, we use the anisotropic semiconducting framework Cd2(TTFTB) (TTFTB4- = tetrathiafulvalene tetrabenzoate) to benchmark several common methods available for measuring electrical properties in MOFs. We show that factors such as temperature, chemical environment (atmosphere), and illumination conditions affect the quality of the data obtained from these techniques. Consistent results emerge only when these factors are strictly controlled and the morphology and anisotropy of the Cd2(TTFTB) single-crystal devices are taken into account. Most importantly, we show that depending on the technique, device construction, and/or the environment, a variance of 1 or even 2 orders of magnitude is not uncommon for even just one material if external factors are not controlled consistently. Differences in conductivity values of even 2 orders of magnitude should therefore be interpreted with caution, especially between different research groups comparing different compounds. These results allow us to propose a reliable protocol for collecting and reporting electrical properties of MOFs, which should help improve the consistency and comparability of reported electrical properties for this important new class of crystalline porous conductors.

Cation-dependent intrinsic electrical conductivity in isostructural tetrathiafulvalene-based microporous metal-organic frameworks.

Isostructural metal-organic frameworks (MOFs) M2(TTFTB) (M = Mn, Co, Zn, and Cd; H4TTFTB = tetrathiafulvalene tetrabenzoate) exhibit a striking correlation between their single-crystal conductivities and the shortest S···S interaction defined by neighboring TTF cores, which inversely correlates with the ionic radius of the metal ions. The larger cations cause a pinching of the S···S contact, which is responsible for better orbital overlap between pz orbitals on neighboring S and C atoms. Density functional theory calculations show that these orbitals are critically involved in the valence band of these materials, such that modulation of the S···S distance has an important effect on band dispersion and, implicitly, on the conductivity. The Cd analogue, with the largest cation and shortest S···S contact, shows the largest electrical conductivity, σ = 2.86 (±0.53) × 10(-4) S/cm, which is also among the highest in microporous MOFs. These results describe the first demonstration of tunable intrinsic electrical conductivity in this class of materials and serve as a blueprint for controlling charge transport in MOFs with π-stacked motifs.

A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome.

Auriculocondylar syndrome (ACS) is a rare, autosomal-dominant craniofacial malformation syndrome characterized by variable micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic "question-mark" ear malformation. Careful phenotypic characterization of severely affected probands in our cohort suggested the presence of a mandibular patterning defect resulting in a maxillary phenotype (i.e., homeotic transformation). We used exome sequencing of five probands and identified two novel (exclusive to the patient and/or family studied) missense mutations in PLCB4 and a shared mutation in GNAI3 in two unrelated probands. In confirmatory studies, three additional novel PLCB4 mutations were found in multigenerational ACS pedigrees. All mutations were confirmed by Sanger sequencing, were not present in more than 10,000 control chromosomes, and resulted in amino-acid substitutions located in highly conserved protein domains. Additionally, protein-structure modeling demonstrated that all ACS substitutions disrupt the catalytic sites of PLCB4 and GNAI3. We suggest that PLCB4 and GNAI3 are core signaling molecules of the endothelin-1-distal-less homeobox 5 and 6 (EDN1-DLX5/DLX6) pathway. Functional studies demonstrated a significant reduction in downstream DLX5 and DLX6 expression in ACS cases in assays using cultured osteoblasts from probands and controls. These results support the role of the previously implicated EDN1-DLX5/6 pathway in regulating mandibular specification in other species, which, when disrupted, results in a maxillary phenotype. This work defines the molecular basis of ACS as a homeotic transformation (mandible to maxilla) in humans.

The real-time in vivo electrochemical measurement of nitric oxide and carbon monoxide release upon direct epidural electrical stimulation of the rat neocortex.

This study reports real-time, in vivo functional measurement of nitric oxide (NO) and carbon monoxide (CO), two gaseous mediators in controlling cerebral blood flow. A dual electrochemical NO/CO microsensor enables us to probe the complex relationship between NO and CO in regulating cerebrovascular tone. Utilizing this dual sensor, we monitor in vivo change of NO and CO simultaneously during direct epidural electrical stimulation of a living rat brain cortex. Both NO and CO respond quickly to meet physiological needs. The neural system instantaneously increases the released amounts of NO and CO to compensate the abrupt, yet transient hypoxia that results from epidural electrical stimulation. Intrinsic-signal optical imaging confirms that direct electrical stimulation elicits robust, dynamic changes in cerebral blood flow, which must accompany NO and CO signaling. The addition of l-arginine (a substrate for NO synthase, NOS) results in increased NO generation and decreased CO production compared to control stimulation. On the other hand, application of the NOS inhibitor, l-N(G)-nitroarginine methyl ester (l-NAME), results in decreased NO release but increased CO production of greater magnitude. This observation suggests that the interaction between NO and CO release is likely not linear and yet, they are tightly linked vasodilators.

Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome.

BACKGROUND: Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, ß 4 (PLCB4) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development. RESULTS: We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients. CONCLUSIONS: These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.

Solvent-Induced Structural Rearrangement in Ultrasound-Assisted Synthesis of Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) are crystalline extended structures featuring permanent porosity, assembled from metal ions and organic ligands, often synthesized by the solvothermal method (50-260 °C, 12-72 h). Here, an alternative synthetic approach-solvent-induced structural rearrangement in ultrasound-assisted synthesis is presented. Six representative Zn-based MOFs, each composed of distinct secondary building units, are synthesized within 2-180 min consuming less solvent (>0.03 m) at room temperature. It is observed that ultrasonication induces the construction of a coordination network, and subsequent solvent exchange triggers structural rearrangement to yield MOFs of high crystallinity and porosity. Furthermore, the scalability of this method is demonstrated through the bulk synthesis of MOF-5, MOF-74, ZIF-8, and MFU-4l within 90 min. The initiation of nucleation through ultrasound and the subsequent transformation induced by solvent exchange offer an alternative method for efficiently synthesizing MOFs in bulk, potentially broadening their range of applications.

Chemically synthesized poly(3,4-ethylenedioxythiophene) conducting polymer as a robust electrocatalyst for highly efficient dye-sensitized solar cells.

Chemically synthesized PEDOT (poly(3,4-ethylenedioxythiophene)) nanomaterials, with various nanostructured morphologies as well as different intrinsic electrical conductivities and crystallinities, were compared as electrocatalysts for Co(III) reduction in dye-sensitized solar cells (DSSCs). Electrochemical parameters, charge transfer resistance toward the electrode/electrolyte interface, catalytic activity for Co(III)-reduction, and diffusion of cobalt redox species greatly depend on the morphology, crystallinity, and intrinsic electrical conductivity of the chemically synthesized PEDOTs and optimization of the fabrication procedure for counter electrodes. The PEDOT counter electrode, fabricated by spin coating a DMSO-dispersed PEDOT solution with an ordered 1D structure and nanosized fibers averaging 70 nm in diameter and an electrical conductivity of ∼16 S cm-1, exhibits the lowest charge transfer resistance, highest diffusion for a cobalt redox mediator and superior electrocatalytic performance compared to a traditional Pt-counter electrode. The photovoltaic performance of the DSSC using chemically synthesized PEDOT exceeds that of a Pt-electrode device because of the enhanced current density, which is directly related to the superior electrocatalytic ability of PEDOT for Co(III)-reduction. This simple spin-coated counter electrode prepared using cheap and scalable chemically synthesized PEDOT can be a potential alternative to the expensive Pt-counter electrode for cobalt and other redox electrolytes in DSSCs and various flexible electronic devices.