An Organometallic Strategy for Assembling Atomically Precise Hybrid Nanomaterials.

For decades, chemists have strived to mimic the intricate design and diverse functions of naturally occurring systems through the bioinspired synthesis of programmable inorganic nanomaterials. The development of thiol-capped gold nanoparticles (AuNPs) has driven advancement in this area; however, although versatile and readily accessible, hybrid AuNPs are rarely atomically precise, which limits control over their surface topology and therefore the study of complex structure-function relationships. Here, we present a bottom-up approach to the systematic assembly of atomically precise hybrid nanoclusters employing a strategy that mimics the synthetic ease with which thiol-capped AuNPs are normally constructed, while producing well-defined covalent nanoscale assemblies with diverse surface topologies. For the first time, using a structurally characterized cluster-based organometallic building block, we demonstrate the systematic synthesis of nanoclusters with multivalent binding capabilities to complex protein targets.

Multivalent Cluster Nanomolecules for Inhibiting Protein-Protein Interactions.

Multivalent protein-protein interactions serve central roles in many essential biological processes, ranging from cell signaling and adhesion to pathogen recognition. Uncovering the rules that govern these intricate interactions is important not only to basic biology and chemistry but also to the applied sciences where researchers are interested in developing molecules to promote or inhibit these interactions. Here we report the synthesis and application of atomically precise inorganic cluster nanomolecules consisting of an inorganic core and a covalently linked densely packed layer of saccharides. These hybrid agents are stable under biologically relevant conditions and exhibit multivalent binding capabilities, which enable us to study the complex interactions between glycosylated structures and a dendritic cell lectin receptor. Importantly, we find that subtle changes in the molecular structure lead to significant differences in the nanomolecule's protein-binding properties. Furthermore, we demonstrate an example of using these hybrid nanomolecules to effectively inhibit protein-protein interactions in a human cell line. Ultimately, this work reveals an intricate interplay between the structural design of multivalent agents and their biological activities toward protein surfaces.

Cross-linked porous polyurethane materials featuring dodecaborate clusters as inorganic polyol equivalents.

We report the discovery that a perhydroxylated dodecaborate cluster ([B12(OH)12]2-) can act as an inorganic polyol, serving as a molecular cross-linker in the synthesis of polyurethane-based materials. We further demonstrate how the inherent robustness of the utilized boron cluster can effectively enhance the thermal stability of the produced polyurethane materials incorporating [B12(OH)12]2- building blocks compared to analogous polymers made from carbon-based polyols. Ultimately, this approach provides a potential route to tune the chemical and physical properties of soft materials through incorporation of polyhedral boron-rich clusters into the polymer network.

Perfunctionalized Dodecaborate Clusters as Stable Metal-Free Active Materials for Charge Storage.

We report a class of perfunctionalized dodecaborate clusters that exhibit high stability towards high concentration electrochemical cycling. These boron clusters afford several degrees of freedom in material design to tailor properties including solubility and redox potential. The exceptional stability of these clusters was demonstrated using a symmetric flow cell setup for electrochemical cycling between two oxidation states for 45 days, with post-run analysis showing negligible decomposition of the active species (<0.1%). To further probe the limits of this system, a prototype redox flow battery with two different cluster materials was used to determine mutual compatibility. This work effectively illustrates the potential of bespoke boron clusters as robust material platform for electrochemical energy conversion and storage.

Tuning the electrochemical potential of perfunctionalized dodecaborate clusters through vertex differentiation.

We report a new class of redox-active vertex-differentiated dodecaborate clusters featuring pentafluoroaryl groups. These [B12(OR)11NO2] clusters share several unique photophysical properties with their [B12(OR)12] analogues, while exhibiting significantly higher (+0.5 V) redox potentials. This work describes the synthesis, characterization, and isolation of [B12(O-CH2C6F5)11NO2] clusters in all 3 oxidation states (dianion, radical, and neutral). Reactivity to post-functionalization with thiol species via SNAr on the pentafluoroaryl groups is also demonstrated.

Synthesis and Applications of Perfunctionalized Boron Clusters.

This Viewpoint describes major advances pertaining to perfunctionalized boron clusters in synthesis and their respective applications. The first portion of this work highlights key synthetic methods, allowing one to access a wide range of polyhedral boranes (B4 and B6-B12 cluster cores) that contain exhaustively functionalized vertices. The second portion of this Viewpoint showcases the historical developments in using these molecules for applications ranging from materials science to medicine. Last, we suggest potential new directions for these clusters as they apply to both synthetic methods and applications.

Atomically precise organomimetic cluster nanomolecules assembled via perfluoroaryl-thiol SNAr chemistry.

The majority of biomolecules are intrinsically atomically precise, an important characteristic that enables rational engineering of their recognition and binding properties. However, imparting a similar precision to hybrid nanoparticles has been challenging because of the inherent limitations of existing chemical methods and building blocks. Here we report a new approach to form atomically precise and highly tunable hybrid nanomolecules with well-defined three-dimensionality. Perfunctionalization of atomically precise clusters with pentafluoroaryl-terminated linkers produces size-tunable rigid cluster nanomolecules. These species are amenable to facile modification with a variety of thiol-containing molecules and macromolecules. Assembly proceeds at room temperature within hours under mild conditions, and the resulting nanomolecules exhibit high stabilities because of their full covalency. We further demonstrate how these nanomolecules grafted with saccharides can exhibit dramatically improved binding affinity towards a protein. Ultimately, the developed strategy allows the rapid generation of precise molecular assemblies to investigate multivalent interactions.

Rapid Synthesis of Redox-Active Dodecaborane B12(OR)12 Clusters Under Ambient Conditions.

We have developed a fast and efficient route to obtain perfunctionalized ether-linked alkyl and benzyl derivatives of the closo-[B12(OH)12]2- icosahedral dodecaborate cluster via microwave-assisted synthesis. These icosahedral boron clusters exhibit three-dimensional delocalization of the cage-bonding electrons, tunable photophysical properties, and a high degree of stability in air in both solid and solution states. A series of closo-[B12(OR)12]2-, hypocloso-[B12(OR)12]1- and hypercloso-[B12(OR)12]0 clusters have been prepared with reaction times ranging from hours to several minutes. This method is superior to previously reported protocols since it dramatically decreases the reaction times required and eliminates the need for inert atmosphere conditions. The generality of the new microwave-based method has been further demonstrated through the synthesis of several new derivatives, which feature redox potentials up to 0.6 V more positive than previously known B12(OR)12 cluster compounds. We further show how this method can be applied to a one-pot synthesis of hybrid, vertex-differentiated species B12(OR)11(OR) that was formerly accessible only via multi-step reaction sequence.

The impact of anti-apoptotic gene Bcl-2∆ expression on CHO central metabolism.

Anti-apoptosis engineering is an established technique to prolong the viability of mammalian cell cultures used for industrial production of recombinant proteins. However, the effect of overexpressing anti-apoptotic proteins on central carbon metabolism has not been systematically studied. We transfected CHO-S cells to express Bcl-2∆, an engineered anti-apoptotic gene, and selected clones that differed in their Bcl-2∆ expression and caspase activity. (13)C metabolic flux analysis (MFA) was then applied to elucidate the metabolic alterations induced by Bcl-2∆. Expression of Bcl-2Δ reduced lactate accumulation by redirecting the fate of intracellular pyruvate toward mitochondrial oxidation during the lactate-producing phase, and it significantly increased lactate re-uptake during the lactate-consuming phase. This flux redistribution was associated with significant increases in biomass yield, peak viable cell density (VCD), and integrated VCD. Additionally, Bcl-2∆ expression was associated with significant increases in isocitrate dehydrogenase and NADH oxidase activities, both rate-controlling mitochondrial enzymes. This is the first comprehensive (13)C MFA study to demonstrate that expression of anti-apoptotic genes has a significant impact on intracellular metabolic fluxes, especially in controlling the fate of pyruvate carbon, which has important biotechnology applications for reducing lactate accumulation and enhancing productivity in mammalian cell cultures.