ZK 756326

On the Structure-Property Relationships of Cation-Exchanged ZK-5 Zeolites for CO2 Adsorption.[Pubmed:28067993]

ChemSusChem. 2017 Mar 9;10(5):946-957.

The CO2 adsorption properties of cation-exchanged Li-, Na-, K-, and Mg-ZK-5 zeolites were correlated to the molecular structures determined by Rietveld refinements of synchrotron powder X-ray diffraction patterns. Li-, K-, and Na-ZK-5 all exhibited high isosteric heats of adsorption (Qst ) at low CO2 coverage, with Na-ZK-5 having the highest Qst (ca. 49 kJ mol(-1) ). Mg(2+) was located at the center of the zeolite hexagonal prism with the cation inaccessible to CO2 , leading to a much lower Qst (ca. 30 kJ mol(-1) ) and lower overall uptake capacity. Multiple CO2 adsorption sites were identified at a given CO2 loading amount for all four cation-exchanged ZK-5 adsorbents. Site A at the flat eight-membered ring windows and site B/B* in the gamma-cages were the primary adsorption sites in Li- and Na-ZK-5 zeolites. Relatively strong dual-cation adsorption sites contributed significantly to an enhanced electrostatic interaction for CO2 in all ZK-5 samples. This interaction gives rise to a migration of Li(+) and Mg(2+) cations from their original locations at the center of the hexagonal prisms toward the alpha-cages, in which they interact more strongly with the adsorbed CO2 .

K+ exchanged zeolite ZK-4 as a highly selective sorbent for CO2.[Pubmed:25072512]

Langmuir. 2014 Aug 19;30(32):9682-90.

Adsorbents with high capacity and selectivity for adsorption of CO2 are currently being investigated for applications in adsorption-driven separation of CO2 from flue gas. An adsorbent with a particularly high CO2-over-N2 selectivity and high capacity was tested here. Zeolite ZK-4 (Si:Al approximately 1.3:1), which had the same structure as zeolite A (LTA), showed a high CO2 capacity of 4.85 mmol/g (273 K, 101 kPa) in its Na(+) form. When approximately 26 at. % of the extraframework cations were exchanged for K(+) (NaK-ZK-4), the material still adsorbed a large amount of CO2 (4.35 mmol/g, 273 K, 101 kPa), but the N2 uptake became negligible (<0.03 mmol/g, 273 K, 101 kPa). The majority of the CO2 was physisorbed on zeolite ZK-4 as quantified by consecutive volumetric adsorption measurements. The rate of physisorption of CO2 was fast, even for the highly selective sample. The molecular details of the sorption of CO2 were revealed as well. Computer modeling (Monte Carlo, molecular dynamics simulations, and quantum chemical calculations) allowed us to partly predict the behavior of fully K(+) exchanged zeolite K-ZK-4 upon adsorption of CO2 and N2 for Si:Al ratios up to 4:1. Zeolite K-ZK-4 with Si:Al ratios below 2.5:1 restricted the diffusion of CO2 and N2 across the cages. These simulations could not probe the delicate details of the molecular sieving of CO2 over N2. Still, this study indicates that zeolites NaK-ZK-4 and K-ZK-4 could be appealing adsorbents with high CO2 uptake ( approximately 4 mmol/g, 101 kPa, 273 K) and a kinetically enhanced CO2-over-N2 selectivity.

A phase II trial of PTK787/ZK 222584 in recurrent or progressive radiation and surgery refractory meningiomas.[Pubmed:24449400]

J Neurooncol. 2014 Mar;117(1):93-101.

When surgery and radiation are no longer treatment options, salvage systemic therapy has been used for recurrent meningiomas with little compelling evidence to suggest effectiveness. Patients with surgery and radiation refractory recurrent meningiomas were treated with the oral multifunctional tyrosine kinase inhibitor PTK787/ZK 222584 (PTK787) at a dose of 500 mg twice a day. Each treatment cycle was 4 weeks with MRI done every 8 weeks. Twenty-five patients (14 men; 11 women) with a median age of 59 years and KPS of 80 were treated. Meningioma WHO Grade was I in 2 patients, II in 14 patients and III in 8 patients; 1 patient had a hemangiopericytoma. All patients had prior surgery, external beam radiation therapy or radiosurgery and 11 patients prior systemic chemotherapy. Median number of cycles of PTK 787 administered was 4 (range <1-22). Best response in the 22 evaluable patients was stable disease in 15 (68.2 %). Predominant PTK787 related toxicities included fatigue (60 %), hypertension (24 %) and elevated transaminases (24 %). Grade II patients had a progression free survival (PFS)-6 of 64.3 %, a median PFS of 6.5 months and an overall survival (OS) of 26.0 months; grade III patients had a PFS-6 of 37.5 %, median PFS of 3.6 months and OS 23 months. PTK787 was modestly toxic at the dose of 500 mg administered twice per day. Activity as determined by PFS-6 suggests that targeting PDGF/VEGF pathway warrants further investigation.

Development of an efficient electroporation method for iturin A-producing Bacillus subtilis ZK.[Pubmed:25837631]

Int J Mol Sci. 2015 Apr 1;16(4):7334-51.

In order to efficiently introduce DNA into B. subtilis ZK, which produces iturin A at a high level, we optimized seven electroporation conditions and explored an efficient electroporation method. Using the optimal conditions, the electroporation efficiency was improved to 1.03 x 10(70 transformants/mug of DNA, an approximately 10,000-fold increase in electroporation efficiency. This efficiency is the highest electroporation efficiency for B. subtilis and enables the construction of a directed evolution library or the knockout of a gene in B. subtilis ZK for molecular genetics studies. In the optimization process, the combined effects of three types of wall-weakening agents were evaluated using a response surface methodology (RSM) design, which led to a two orders of magnitude increase in electroporation efficiency. To the best of our limited knowledge, this study provides the first demonstration of using an RSM design for optimization of the electroporation conditions for B. subtilis. To validate the electroporation efficiency, a case study was performed and a gene (rapC) was inactivated in B. subtilis ZK using a suicide plasmid pMUTIN4. Moreover, we found that the rapC mutants exhibited a marked decrease in iturin A production, suggesting that the rapC gene was closely related to the iturin A production.

Identification and characterization of a potent, selective nonpeptide agonist of the CC chemokine receptor CCR8.[Pubmed:16221874]

Mol Pharmacol. 2006 Jan;69(1):309-16.

In this study, we report the first example of a nonpeptide chemokine receptor agonist, 2-{2-[4-(3-phenoxybenzyl)piperazin-1-yl]ethoxy}ethanol (ZK 756326), for the CC chemokine receptor CCR8. ZK 756326 inhibited the binding of the CCR8 ligand I-309 (CCL1), with an IC(50) value of 1.8 muM. Furthermore, ZK 756326 was a full agonist of CCR8, dose-responsively eliciting an increase in intracellular calcium and cross-desensitizing the response of the receptor to CCL1. In addition, ZK 756326 stimulated extracellular acidification in cells expressing human CCR8. The ability of ZK 756326 to induce a response was receptor-specific and mediated through Galpha(i), because it could be blocked by treatment with pertussis toxin. The CCR8 agonist activated cells expressing murine CCR8, eliciting their chemotaxis and inducing phosphorylation of extracellular signal-regulated kinase ERK1/2. Like CCL1, ZK 756326 inhibited human immunodeficiency virus (HIV) fusion of cells expressing CD4 and CCR8. Finally, unlike mCCL1, ZK 756326 bound to and activated a form of mCCR8 that was mutated to eliminate O-linked sulfation at tyrosines 14 and 15. Therefore, ZK 756326 is most probably not binding in the same manner as CCL1 but can activate the switch mechanism involved in transducing signaling events. In summary, we have identified a nonpeptide agonist of CCR8. This compound may be useful in evaluating the physiological role of CCR8 in HIV infection, as well as in the general study of CCR8 biology without the constraints inherent to the use of protein agonists such as its natural ligand.