Innovation and Team Spirit: The Magic of Science Competitions Seen through the Lens of the Compound Challenge.

For five years now, Merck KGaA, Darmstadt, Germany has hosted The Compound Challenge-a global retrosynthesis competition. When the event kicked off in 2018 on the occasion of the 350th anniversary of the company, no one could have predicted the path it would take-from a novel competition to a pivotal event within the synthetic chemistry community. But what makes the Compound Challenge tick and what drives its popularity? And, more importantly, what lessons can be taken from the Compound Challenge and applied to other challenges in scientific education and outreach? In this Viewpoint Article we will tell the story of the Compound Challenge, from its inception to its current status. Through examining feedback following each of its iterations, we begin to define what makes an open innovation challenge so compelling. It is our hope that educators, leaders, and innovators will be able to learn from our successes as well as our mistakes and apply these lessons to their future outreach activities.

Near Quantitative Removal of Selenate and Sulfate Anions from Wastewaters by Cocrystallization with Chelating Hydrogen-Bonding Guanidinium Ligands.

Selenium (Se) has become an environmental contaminant of aquatic ecosystems as a result of human activities, particularly mining, fossil fuel combustion, and agricultural activities. By leveraging the high sulfate concentrations relative to Se oxyanions (i.e., SeO n 2-, n = 3, 4) present in some wastewaters, we have developed an efficient approach to Se-oxyanion removal by cocrystallization with bisiminoguanidinium (BIG) ligands that form crystalline sulfate/selenate solid solutions. The crystallization of the sulfate, selenate and selenite, oxyanions and of sulfate/selenate mixtures with five candidate BIG ligands are reported along with the thermodynamics of crystallization and aqueous solubilities. Oxyanion removal experiments with the top two performing candidate ligands show a near quantitative removal (>99%) of sulfate or selenate from solution. When both sulfate and selenate are present, there is near quantitative removal (>99%) of selenate, down to sub-ppb Se levels, with no discrimination between the two oxyanions during cocrystallization. Reducing the selenate concentrations by 3 orders of magnitude or more relative to sulfate, as found in many wastewaters, led to no measurable loss in Se removal efficiencies. This work offers a simple and effective alternative to selective separation of trace amounts of highly toxic selenate oxyanions from wastewaters, to meet stringent regulatory discharge limits.

Direct air capture of CO-2 - topological analysis of the experimental electron density (QTAIM) of the highly insoluble carbonate salt of a 2,6-pyridine-bis(iminoguanidine), (PyBIGH2)(CO3)(H2O)4.

Chemical bonding and all intermolecular interactions in the highly insoluble carbonate salt of a 2,6-pyridine-bis(iminoguanidine), (PyBIGH2)(CO3)(H2O)4, recently employed in the direct air capture of CO2 via crystallization, have been analyzed within the framework of the quantum theory of atoms in molecules (QTAIM) based on the experimental electron density derived from X-ray diffraction data obtained at 20 K. Accurate hydrogen positions were included based on an analogous neutron diffraction study at 100 K. Topological features of the covalent bonds demonstrate the presence of multiple bonds of various orders within the PyBIGH2 2+ cation. Strong hydrogen bonds define ribbons comprising carbonate anions and water molecules. These ribbons are linked to stacks of essentially planar dications via hydrogen bonds from the guanidinium moieties and an additional one to the pyridine nitro-gen. The linking hydrogen bonds are approximately perpendicular to the anion-water ribbons. The observation of these putative interactions provided motivation to characterize them by topological analysis of the total electron density. Thus, all hydrogen bonds have been characterized by the properties of their (3,-1) bond critical points. Weaker interactions between the PyBIGH2 2+ cations have similarly been characterized. Integrated atomic charges are also reported. A small amount of cocrystallized hydroxide ion (∼2%) was also detected in both the X-ray and neutron data, and included in the multipole model for the electron-density refinement. The small amount of additional H+ required for charge balance was not detected in either the X-ray or the neutron data. The results are discussed in the context of the unusually low aqueous solubility of (PyBIGH2)(CO3)(H2O)4 and its ability to sequester atmospheric CO2.

Selective binding of (thio)sulfate and phosphate in water by quaternary ammonium functionalized oligo-ureas.

Recognition of (thio)sulfate and phosphate in aqueous solutions has been demonstrated by using oligo-urea-based receptors functionalized with quaternary ammonium groups. The ammonium groups allow for increased aqueous solubility while simultaneously providing positive coulombic interactions and stronger hydrogen bonding through an inductive effect. This simple and generally applicable modification provides an effective way to bolster the anion binding and water solubility of oligo-urea-based receptors. With a water soluble receptor 2, selective binding of adenosine phosphates was achieved at physiological pH.

Surprisingly selective sulfate extraction by a simple monofunctional di(imino)guanidinium micelle-forming anion receptor.

We report a novel di(imino)guanidinium anion extractant with unparalleled selectivity for sulfate in a liquid-liquid separation system. In addition to a 4.4 order-of-magnitude enhancement in affinity compared to a standard benchmark, our alkylated di(imino)guanidinium receptor is economically synthesized and features good compatibility with application-relevant aliphatic solvents. Small-angle X-ray scattering results reveal the formation of reverse-micelles, which together with the significant organic-phase water content challenge traditional notions of selectivity in extraction of superhydrophilic anions.

CO2 Capture from Ambient Air by Crystallization with a Guanidine Sorbent.

Carbon capture and storage is an important strategy for stabilizing the increasing concentration of atmospheric CO2 and the global temperature. A possible approach toward reversing this trend and decreasing the atmospheric CO2 concentration is to remove the CO2 directly from air (direct air capture). Herein we report a simple aqueous guanidine sorbent that captures CO2 from ambient air and binds it as a crystalline carbonate salt by guanidinium hydrogen bonding. The resulting solid has very low aqueous solubility (Ksp =1.0(4)×10-8 ), which facilitates its separation from solution by filtration. The bound CO2 can be released by relatively mild heating of the crystals at 80-120 °C, which regenerates the guanidine sorbent quantitatively. Thus, this crystallization-based approach to CO2 separation from air requires minimal energy and chemical input, and offers the prospect for low-cost direct air capture technologies.

Sulfate Separation by Selective Crystallization with a Bis-iminoguanidinium Ligand.

A simple and effective method for selective sulfate separation from aqueous solutions by crystallization with a bis-guanidinium ligand, 1,4-benzene-bis(iminoguanidinium) (BBIG), is demonstrated. The ligand is synthesized as the chloride salt (BBIG-Cl) by in situ imine condensation of terephthalaldehyde with aminoguanidinium chloride in water, followed by crystallization as the sulfate salt (BBIG-SO4). Alternatively, BBIG-Cl is synthesized ex situ in larger scale from ethanol. The sulfate separation ability of the BBIG ligand is demonstrated by selective and quantitative crystallization of sulfate from seawater. The ligand can be recycled by neutralization of BBIG-SO4 with aqueous NaOH and crystallization of the neutral bis-iminoguanidine, which can be converted back into BBIG-Cl with aqueous HCl and reused in another separation cycle. Finally, (35)S-labeled sulfate and ß liquid scintillation counting are employed for monitoring the sulfate concentration in solution. Overall, this protocol will instruct the user in the necessary skills to synthesize a ligand, employ it in the selective crystallization of sulfate from aqueous solutions, and quantify the separation efficiency.

Aqueous Sulfate Separation by Sequestration of [(SO4 )2 (H2 O)4 ]4- Clusters within Highly Insoluble Imine-Linked Bis-Guanidinium Crystals.

Selective crystallization of sulfate with a simple bis-guanidinium ligand, self-assembled in situ from terephthalaldehyde and aminoguanidinium chloride, was employed as an effective way to separate the highly hydrophilic sulfate anion from aqueous solutions. The resulting bis-iminoguanidinium sulfate salt has exceptionally low aqueous solubility (Ksp =2.4×10-10 ), comparable to that of BaSO4 . Single-crystal X-ray diffraction analysis showed the sulfate anions are sequestered as [(SO4 )2 (H2 O)4 ]4- clusters within the crystals. Variable-temperature solubility measurements indicated the sulfate crystallization is slightly endothermic (ΔHcryst =3.7 kJ mol-1 ), thus entropy driven. The real-world utility of this crystallization-based approach for sulfate separation was demonstrated by removing up to 99 % of sulfate from seawater in a single step.

Aqueous Sulfate Separation by Crystallization of Sulfate-Water Clusters.

An effective approach to sulfate separation from aqueous solutions is based on the crystallization of extended [SO4(H2O)5(2-)]n sulfate-water clusters with a bis(guanidinium) ligand. The ligand was generated in situ by hydrazone condensation in water, thereby bypassing the need for elaborate syntheses, tedious purifications, and organic solvents. Crystallization of sulfate-water clusters represents an alternative approach to the now established sulfate separation strategies that involve encapsulation of the "naked" anion.

Concise synthesis of the hasubanan alkaloid (±)-cepharatine A using a Suzuki coupling reaction to effect o,p-phenolic coupling.

Suzuki coupling of 10 and 11 resulted in 9, which was O-alkylated to provide 12. Treatment of 12 with CsF in DMF resulted in the formation of the completed core structure 13 in a single step. Reductive amination of 13 completed the synthesis of (±)-cepharatine A, 4.