Nonclassical Crystallization Processes of Single-Crystalline Two-Dimensional Covalent Organic Frameworks.

Controlling the two-dimensional polymerization processes of two-dimensional covalent organic frameworks (2D COFs) is essential to fully realizing their distinct properties. Although most 2D COFs have been isolated as polycrystalline aggregates with only nanometer-scale crystalline domains, we have identified rapid, solvothermal conditions that provide micrometer-scale and larger single-crystal 2D polymers for a few 2D COFs. Yet it remains unclear why certain conditions produce far larger 2D polymers than others, which hinders generalizing these findings. The guiding principles for controlled two-dimensional polymerization in solution remain unclear. Here, we study the crystallization processes of both single-crystalline and polycrystalline 2D COFs using ultrasmall-angle X-ray scattering (USAXS) for the first time, through which we characterized COF formation conditions with scattering data collected every few seconds. In situ USAXS experiments revealed distinct growth mechanisms between single-crystalline and polycrystalline COFs and suggested a nonclassical particle fusion-based growth model for single-crystalline COFs that results in faceted, hexagonal particles. These findings were corroborated by in situ wide-angle X-ray scattering (WAXS) experiments and scanning electron microscopy (SEM). In contrast, polymerizations that provide polycrystalline COFs evolve as spherical aggregates that do not fuse in the same way. These insights into how micrometer-sized, crystalline 2D polymers are formed in solution point a way forward to establishing a robust connection between the 2D polymer structure and designed properties by controlling their polymerization processes.

Nitrous oxide as a diazo transfer reagent: the synthesis of triazolopyridines.

Nitrous oxide is a potential diazo transfer reagent, but its applications in organic chemistry are scarce. Here, we show that triazolopyridines and triazoloquinolines are formed in the reactions of metallated 2-alkylpyridines or 2-alkylquinolines with N2O. The reactions can be performed under mild conditions and give synthetically interesting triazoles in moderate to good yields.

Brønsted and Lewis acid adducts of triazenes.

The synthetic utility of triazenes rests on the fact that the triazene function can be cleaved by Brønsted or Lewis acids, liberating diazonium compounds. However, the preferred coordination site of the acid is still a matter of debate. We have analyzed triflic acid, B(C6F5)3, and PdCl2 adducts of triazenes by NMR spectroscopy and single crystal X-ray crystallography. In all cases, we observe coordination of the acid to the N1 atom of the triazene. This finding is not only of relevance for acid-induced cleavage reactions, but also for metal-catalyzed reactions with triazenes, which are increasingly being used in synthetic organic chemistry.

Synthesis and Properties of 1-Acyl Triazenes.

1-Acyl triazenes can be prepared by acid-catalyzed hydration, gold/iodine-catalyzed oxidation, or oxyhalogenation of 1-alkynyl triazenes. Crystallographic analyses reveal a pronounced effect of the acyl group on the electronic structure of the triazene function. 1-Acyl triazenes display high thermal stability, and only moderate sensitivity toward hydrolysis. They are compatible with basic and oxidative conditions, allowing subsequent transformation. Under acidic conditions, 1-acyl triazenes act as acylation reagents.

Red Light Activation of Ru(II) Polypyridyl Prodrugs via Triplet-Triplet Annihilation Upconversion: Feasibility in Air and through Meat.

Triplet-triplet annihilation upconversion (TTA-UC) is a promising photophysical tool to shift the activation wavelength of photopharmacological compounds to the red or near-infrared wavelength domain, in which light penetrates human tissue optimally. However, TTA-UC is sensitive to dioxygen, which quenches the triplet states needed for upconversion. Here, we demonstrate not only that the sensitivity of TTA-UC liposomes to dioxygen can be circumvented by adding antioxidants, but also that this strategy is compatible with the activation of ruthenium-based chemotherapeutic compounds. First, red-to-blue upconverting liposomes were functionalized with a blue-light sensitive, membrane-anchored ruthenium polypyridyl complex, and put in solution in presence of a cocktail of antioxidants composed of ascorbic acid and glutathione. Upon red light irradiation with a medical grade 630 nm PDT laser, enough blue light was produced by TTA-UC liposomes under air to efficiently trigger full activation of the Ru-based prodrug. Then, the blue light generated by TTA-UC liposomes under red light irradiation (630 nm, 0.57 W/cm²) through different thicknesses of pork or chicken meat was measured, showing that TTA-UC still occurred even beyond 10 mm of biological tissue. Overall, the rate of activation of the ruthenium compound in TTA-UC liposomes using either blue or red light (1.6 W/cm²) through 7 mm of pork fillet were found comparable, but the blue light caused significant tissue damage, whereas red light did not. Finally, full activation of the ruthenium prodrug in TTA-UC liposomes was obtained under red light irradiation through 7 mm of pork fillet, thereby underlining the in vivo applicability of the activation-by-upconversion strategy.