Chalcogen-Expanded Unsaturated Silicon Clusters: Thia-, Selena-, and Tellurasiliconoids

Reactions of silylenes with heavier chalcogens (E) typically result in Si=E double bonds or their π-addition products. In contrast, the oxidation of a silylene-functionalized unsaturated silicon cluster (siliconoid) with Group 16 elements selectively yields cluster expanded siliconoids Si₇E (E=S, Se, Te) fully preserving the unsaturated nature of the cluster scaffold as evident from the NMR signatures of the products. Mechanistic considerations by DFT calculations suggest the intermediacy of a Si₆ siliconoid with exohedral Si=E functionality. The reaction thus may serve as model system for the oxidation of surface-bonded silylenes at Si(100) by chalcogens and their diffusion into the silicon bulk.     

Albumin-targeting of an oxaliplatin-releasing platinum(iv) prodrug results in pronounced anticancer activity due to endocytotic drug uptake in vivo

Oxaliplatin is a very potent platinum(ii) drug which is frequently used in poly-chemotherapy schemes against advanced colorectal cancer. However, its benefit is limited by severe adverse effects as well as resistance development. Based on their higher tolerability, platinum(iv) prodrugs came into focus of interest. However, comparable to their platinum(ii) counterparts they lack tumor specificity and are frequently prematurely activated in the blood circulation. With the aim to exploit the enhanced albumin consumption and accumulation in the malignant tissue, we have recently developed a new albumin-targeted prodrug, which supposed to release oxaliplatin in a highly tumor-specific manner. In more detail, we designed a platinum(iv) complex containing two maleimide moieties in the axial position (KP2156), which allows selective binding to the cysteine 34. In the present study, diverse cell biological and analytical tools such as laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS), isotope labeling, and nano-scale secondary ion mass spectrometry (NanoSIMS) were employed to better understand the in vivo distribution and activation process of KP2156 (in comparison to free oxaliplatin and a non-albumin-binding succinimide analogue). KP2156 forms very stable albumin adducts in the bloodstream resulting in a superior pharmacological profile, such as distinctly prolonged terminal excretion half-life and enhanced effective platinum dose (measured by ICP-MS). The albumin-bound drug is accumulating in the malignant tissue, where it enters the cancer cells via clathrin- and caveolin-dependent endocytosis, and is activated by reduction to release oxaliplatin. This results in profound, long-lasting anticancer activity of KP2156 against CT26 colon cancer tumors in vivo based on cell cycle arrest and apoptotic cell death. Summarizing, albumin-binding of platinum(iv) complexes potently enhances the efficacy of oxaliplatin therapy and should be further developed towards clinical phase I trials.

Albumin-targeting of a maleimide-containing oxaliplatin-releasing platinum(iv) prodrug results in tumor-specific drug delivery and activity as shown by LA-ICP-MS, isotope-labeling and NanoSIMS in cell culture and in vivo.     

Optical Chemical Hydrazine Sensor from Hybrid Organic-Inorganic Materials

Original hybrid organic-inorganic materials have been synthesised, characterised and used as optical chemical hydrazine sensors. Because of its optical and chemical properties, 4-(dimethyl)aminobenzaldehyde (DMAB) was chosen as indicator. DMAB has been immobilised by physical entrapment in a microporous silica network or by a chemical bonding on a colloidal silica network. The response time of the sensor was essentially governed by the diffusion of hydrazine in the host matrix whereas its life time was dependent on the retention of DMAB. These two features were controlled by the nature and the quantity of the network agent and the catalyst, by the ageing time of the sol, and the drying and thermal treatment of the films.     

Effects of microchannel geometry on pulsed flow mixing

Although the mixing of reagents is often crucial in many microfluidic devices, good mixing in these laminar, low Reynolds number, flows remains a challenge. It was shown in Refs. [Glasgow, I., Aubry, N., 2003. Lab on a Chip 3, p. 114; Glasgow, I., Batton, J., Aubry, N., 2004. Lab on a Chip 4, p. 558] that pulsing can induce mixing at the confluence of two inlet microchannels in an efficient manner. In this paper, we show that this mixing is affected by both the geometry of the confluence and the inclusion of features in the channels, which induce secondary flow. More specifically, we study mixing in 200 μm wide by 120 μm deep channels, at flow rates from 48 nl s⁻¹ to 4.8 μl s⁻¹, corresponding to Reynolds numbers of 0.3–30. For the parameter values studied, the pulsed flow technique is more effective at mixing than the secondary flow induced by the channel geometry features, and combining both methods leads to even better mixing. In addition, pulsing the reagents such that they pass multiple times through the spatial features, which induce secondary flow leads to mixing over shorter distances.