Heterostructured metal-organic framework (MOF)-on-MOF thin films have the potential to cascade the various properties of different MOF layers in as equence to produce functions that cannot be achieved by single MOF layers.A ni ntegration method that relies on van der Waals interactions,a nd whicho vercomes the lattice-matching limits of reported methods,has been developed. The method deposits molecular sieving Cu-TCPP (TCPP = 5,10,15,20-tetrakis-(4-carboxyphenyl)porphyrin) layers onto semiconductive Cu-HHTP (HHTP = 2,3,6,7,10,11-hexahydrotriphenylene) layers to obtain highly oriented MOF-on-MOF thin films. Fort he first time,t he properties in different MOF layers were cascaded in sequence to synergistically produce an enhanced device function. Cu-TCPP-on-Cu-HHTP demonstrated excellent selectivity and the highest response to benzene of the reported recoverable chemiresistive sensing materials that are active at room temperature.This method allows integration of MOFs with cascading properties into advanced functional materials.

g Toxoplasma gondii is a protozoan parasite that can damage the human brain and eyes. There are no curative medicines. Herein, we describe our discovery of N-benzoyl-2-hydroxybenzamides as a class of compounds effective in the low nanomolar range against T. gondii in vitro and in vivo. Our lead compound, QQ-437, displays robust activity against the parasite and could be useful as a new scaffold for development of novel and improved inhibitors of T. gondii. Our genome-wide investigations reveal a specific mechanism of resistance to N-benzoyl-2-hydroxybenzamides mediated by adaptin-3␤, a large protein from the secretory protein complex. N-Benzoyl-2-hydroxybenzamide-resistant clones have alterations of their secretory pathway, which traffics proteins to micronemes, rhoptries, dense granules, and acidocalcisomes/plant-like vacuole (PLVs). N-Benzoyl-2-hydroxybenzamide treatment also alters micronemes, rhoptries, the contents of dense granules, and, most markedly, acidocalcisomes/PLVs. Furthermore, QQ-437 is active against chloroquine-resistant Plasmodium falciparum. Our studies reveal a novel class of compounds that disrupts a unique secretory pathway of T. gondii, with the potential to be used as scaffolds in the search for improved compounds to treat the devastating diseases caused by apicomplexan parasites.T oxoplasma gondii is an apicomplexan, intracellular parasite that infects one third to one half of the world's population. It can cause eye and brain disease and death, and the presence of infection has been correlated with a variety of neurologic illnesses. Moreover, it is the most frequent cause of infectious uveitis worldwide. Disease can be especially severe in immunocompromised persons and in those infected congenitally (28).There is no perfect treatment for T. gondii infection in humans, as the few available medicines are limited by their side effects and target only the rapidly proliferating tachyzoite form of the parasite. Pyrimethamine and sulfadiazine, which are effective against the tachyzoite form, are currently used to treat active disease. However, treatment with these medicines can be associated with toxicity and hypersensitivity (29), and they do not eradicate the bradyzoite form of the parasite, which remains latent. There are few secondary medicines, and some of them have a delayed mechanism of killing the tachyzoites. No medicines have been reported to be effective against the latent, encysted bradyzoite stage. T. gondii remains in a person's body throughout life, leading to a risk for recurrence of active infection. Novel, effective, and nontoxic antiToxoplasma agents are urgently needed. Herein, we present a series of experiments to identify new lead compounds effective against T. gondii and to begin to understand how they act on this parasite. MATERIALS AND METHODSParasites and cell culture. Confluent monolayers of human foreskin fibroblasts (HFF) were maintained in Iscove's modified Dulbecco's medium supplemented with 10% fetal bovine serum, 1% Glutamax, and 1% penicillin-streptomycin-amp...

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