Origins of Acid-Gas Stability Behavior in Zeolitic Imidazolate Frameworks: The Unique High Stability of ZIF-71.

Zeolitic imidazolate frameworks (ZIFs) are promising materials for industrial process separations, but recent literature reports have highlighted their vulnerability to acid gases (e.g., SO2, CO2, NO2, H2S), often present in practical applications. While previous work has documented the widely varying stability behavior of many ZIFs under varying (humid and dry) acid gas environments, efforts to explain or correlate these experimental observations via empirical descriptors have not succeeded. A key observation is that ZIF-71 (RHO topology) is an extraordinarily stable ZIF material, retaining both structure and porosity under prolonged humid SO2 exposure whereas many other well-known ZIFs with different linkers and topologies (such as ZIF-8) were shown to degrade. Through a combination of hybrid quantum mechanics/molecular mechanics (QM/MM) based methods and statistical mechanical models, we successfully explain this important experimental observation via atomistic investigations of the reaction mechanism. Our holistic approach reveals an ∼9 times lower average defect formation rate in ZIF-71 RHO compared to ZIF-8 SOD, leading to the conclusion that the observed experimental stability of this material rises from kinetic effects. Moreover, our analysis reveals that differing stability of the two materials is determined by the distributions of acid gas molecules, which is difficult to capture using empirical descriptors. Our results suggest wider applicability of the present approach, toward identifying tuned functional groups and topologies that move the acid gas distributions away from more reactive sites and thus allow enhanced kinetic stability.

Engineering Porous Organic Cage Crystals with Increased Acid Gas Resistance.

Both known and new CC3-based porous organic cages are prepared and exposed to acidic SO2 in vapor and liquid conditions. Distinct differences in the stability of the CC3 cages exist depending on the chirality of the diamine linkers used. The acid catalyzed CC3 degradation mechanism is probed via in situ IR and a degradation pathway is proposed and supported with computational results. CC3 crystals synthesized with racemic mixtures of diaminocyclohexane exhibited enhanced stability compared to CC3-R and CC3-S. Confocal fluorescent microscope images reveal that the stability difference in CC3 species originates from an abundance of mesoporous grain boundaries in CC3-R and CC3-S, allowing facile access of aqueous SO2 throughout the crystal, promoting decomposition. These grain boundaries are absent from CC3 crystals made with racemic linkers.

Direct Intranuclear Anticancer Drug Delivery via Polydimethylsiloxane Nanoparticles: in Vitro and in Vivo Xenograft Studies.

Direct delivery of anticancer drugs to nuclei of tumor cells is required to enhance the therapeutic activity, which can be achieved by a nuclear localization signal (NLS) or peptide-decorated nanovehicles. However, NLS/peptide-based approaches may create certain undesirable immunological responses and the utilized synthesis processes are generally labor intensive. To this end, we report ligand-free, enhanced intranuclear delivery of Doxorubicin (Dox) to different cancer cells via porous polydimethylsiloxane (PDMS) nanoparticles (NPs). PDMS NPs were prepared by sacrificial silica template-based approach and Dox was loaded into the pores of PDMS NPs. These Dox-loaded PDMS NPs show enhanced cytotoxicity and reduce the IC50 values by 84 and 54% for HeLa and PC-3, respectively, compared to free Dox. Further, DNA damage in HeLa cells was estimated using comet assay suggesting enhanced DNA damage (72%) with Dox-loaded PDMS NPs as compared to free Dox (12%). The therapeutic efficiency of PDMS-Dox drug delivery system was tested in prostate cancer (PC-3) xenografts in NOD/SCID mice which showed enhanced tumor reduction (∼66%) as compared to free Dox. Taken together, our PDMS-Dox delivery system shows efficient and enhanced transportation of Dox to tumor cells which can be harnessed to develop advanced chemotherapy-based approaches to treat prostate and other cancers.

Recovery of Acid-Gas-Degraded Zeolitic Imidazolate Frameworks by Solvent-Assisted Crystal Redemption (SACRed).

The acid stability of zeolitic imidazolate frameworks (ZIFs) is an important issue hindering their application. Acid-gas damage of ZIFs has been considered irreversible. However, we demonstrate a methodology called solvent-assisted crystal redemption (SACRed) to reverse acid-gas damage to ZIFs with a high degree of structural and functional recovery. For example, post-SACRed ZIF-8 is shown to be structurally and chemically near-identical with the original pristine ZIF-8 that suffered a large loss of surface area, porosity, and crystallinity during acid-gas exposure. We also provide mechanistic insight into the recovery process using deuterium-labeled linkers and 2H NMR spectroscopy. SACRed treatments could allow large extensions in the lifetime of ZIF-based membranes and adsorbents that degrade over time.

GPCR-Based Chemical Biosensors for Medium-Chain Fatty Acids.

A key limitation to engineering microbes for chemical production is a reliance on low-throughput chromatography-based screens for chemical detection. While colorimetric chemicals are amenable to high-throughput screens, many value-added chemicals are not colorimetric and require sensors for high-throughput screening. Here, we use G-protein coupled receptors (GPCRs) known to bind medium-chain fatty acids in mammalian cells to rapidly construct chemical sensors in yeast. Medium-chain fatty acids are immediate precursors to the advanced biofuel fatty acid methyl esters, which can serve as a "drop-in" replacement for D2 diesel. One of the sensors detects even-chain C8-C12 fatty acids with a 13- to 17-fold increase in signal after activation, with linear ranges up to 250 µM. Introduction of a synthetic response unit alters both dynamic and linear range, improving the sensor response to decanoic acid to a 30-fold increase in signal after activation, with a linear range up to 500 µM. To our knowledge, this is the first report of a whole-cell medium-chain fatty acid biosensor, which we envision could be applied to the evolutionary engineering of fatty acid-producing microbes. Given the affinity of GPCRs for a wide range of chemicals, it should be possible to rapidly assemble new biosensors by simply swapping the GPCR sensing unit. These sensors should be amenable to a variety of applications that require different dynamic and linear ranges, by introducing different response units.