Markus M. Herling

Porosity of Pillared Clays Studied by Hyperpolarized 129Xe NMR Spectroscopy and Xe Adsorption Isotherms

The influence of the layer charge on the microstructure was studied for a series of three hybrid pillared interlayered clays based on the organic dication Me(2)DABCO(2+) and charge reduced synthetic fluorohectorites. To get a detailed picture of the local arrangements within the interlayer space, multinuclear solid-state NMR spectroscopy was performed in conjunction with high-resolution (129)Xe MAS NMR, temperature-dependent wide-line 1D and 2D (129)Xe NMR, and Ar/Ar(l) and Xe/Xe(l) physisorption measurements. The resulting layer charge (x) for the three samples are 0.48, 0.44, and 0.39 per formula unit (pfu). The samples exhibit BET equivalent surfaces between 150 and 220 m(2)/g and pore volumes which increase from 0.06 to 0.11 cm(3)/g while the layer charge reduces. 1D and 2D (1)H, (13)C, (19)F, and (29)Si MAS data reveal that the postsynthetic charge reduction induces regions with higher defect concentrations within the silicate layers. Although the pillars tend to avoid these defect-rich regions, a homogeneous and regular spacing of the Me(2)DABCO(2+) pillars is established. Both the Ar/Ar(l) physisorption and (129)Xe NMR measurements reveal comparable pore dimensions. The trend of the temperature-dependent wide-line (129)Xe spectra as well as the exchange in the EXSY spectra is typical for a narrow 2D pore system. (129)Xe high-resolution experiments allow for a detailed description of the microstructure. For x = 0.48 a bimodal distribution with pore diameters between 5.9 and 6.4 Å is observed. Reducing the layer charge leads to a more homogeneous pore structure with a mean diameter of 6.6 Å (x = 0.39). The adsorption enthalpies ΔH(ads) determined from the temperature-dependent (129)Xe chemical shift data fit well to the ones derived from the Xe/Xe(l) physisorption measurements in the high-pressure limit while the magnitude of ΔH(ads) in the low-pressure limit is significantly larger. Thus, the (129)Xe data are influenced by adsorbate-adsorbent as well as adsorbate-adsorbate interactions.

Constant Volume Gate-Opening by Freezing Rotational Dynamics in Microporous Organically Pillared Layered Silicates

Microporous organically pillared layered silicates (MOPS) are a class of microporous hybrid materials that, by varying pillar density, allows for optimization of guest recognition without the need to explore different framework topologies. MOPS are found to be capable of discriminating two very similar gases, carbon dioxide and acetylene, by selective gate-opening solely through quenching pillar dynamics. Contrary to conventional gate-opening in metal organic frameworks, the additional adsorption capacity is realized without macroscopic volume changes, thus avoiding mechanical stress on the framework. Of the two gases studied, only CO2 can accomplish freezing of pillar dynamics. Moreover, the shape of the slit-type micropores in MOPS can easily be fine-tuned by reducing the charge density of the silicate layers. This concomitantly reduces the Coulomb attraction of cationic interlayer space and anionic host layers. Surprisingly, we found that reducing the charge density then alters the gate-opening mechanism to a conventional structural gate-opening involving an increase in volume.

Purely Physisorption-based CO-Selective Gate-Opening in Microporous Organically Pillared Layered Silicates

Separation of gas molecules with similar physical and chemical properties is challenging but nevertheless highly relevant for chemical processing. By introducing the elliptically shaped molecule, 1,4-dimethyl-1,4-diazabicyclo[2.2.2]octane, into the interlayer space of a layered silicate, a two-dimensional microporous network with narrow pore size distribution is generated (MOPS-5). The regular arrangement of the pillar molecules in MOPS-5 was confirmed by the occurrence of a 10 band related to a long-range pseudo-hexagonal superstructure of pillar molecules in the interlayer space. Whereas with MOPS-5 for CO2 adsorption, gate-opening occurs at constant volume by freezing pillar rotation, for CO the interlayer space is expanded at gate-opening and a classical interdigitated layer type of gate-opening is observed. The selective nature of the gate-opening might be used for separation of CO and N2 by pressure swing adsorption.

Targeting transcription-coupled nucleotide excision repair overcomes resistance in chronic lymphocytic leukemia

Treatment resistance becomes a challenge at some point in the course of most patients with chronic lymphocytic leukemia (CLL). This applies to fludarabine-based regimens, and is also an increasing concern in the era of more targeted therapies. As cells with low-replicative activity rely on repair that triggers checkpoint-independent noncanonical pathways, we reasoned that targeting the nucleotide excision repair (NER) reaction addresses a vulnerability of CLL and might even synergize with fludarabine, which blocks the NER gap-filling step. We interrogated here especially the replication-independent transcription-coupled-NER ((TC)-NER) in prospective trial patients, primary CLL cultures, cell lines and mice. We screen selected (TC)-NER-targeting compounds as experimental (illudins) or clinically approved (trabectedin) drugs. They inflict transcription-stalling DNA lesions requiring TC-NER either for their removal (illudins) or for generation of lethal strand breaks (trabectedin). Genetically defined systems of NER deficiency confirmed their specificity. They selectively and efficiently induced cell death in CLL, irrespective of high-risk cytogenetics, IGHV status or clinical treatment history, including resistance. The substances induced ATM/p53-independent apoptosis and showed marked synergisms with fludarabine. Trabectedin additionally perturbed stromal-cell protection and showed encouraging antileukemic profiles even in aggressive and transforming murine CLL. This proof-of-principle study established (TC)-NER as a mechanism to be further exploited to resensitize CLL cells.