Polycationic adamantane-based dendrons of different generations display high cellular uptake without triggering cytotoxicity.

Dendrons used as synthetic carriers are promising nanostructures for biomedical applications. Some polycationic dendritic systems, such as the commercially available polyethylenimine (PEI), have the ability to deliver genetic material into cells. Nevertheless, polycationic vectors are often associated with potential cellular toxicity, which prevents their use in clinical development. In this context, our research focused on the design and synthesis of a novel type of polycationic dendrons that are able to penetrate into cells without triggering cytotoxic effects. We synthesized first- and second-generation polycationic adamantane-based dendrons via a combined protection/deprotection strategy starting from different adamantane scaffolds. The linker between the adamantane cores is constituted of short ethylene glycol chains, and the periphery consists of ammonium and guanidinium groups. None of these dendritic structures, which we previously called HYDRAmers, displayed significant cytotoxicity effects on two different cell lines (RAW 264.7 and HeLa). Conjugation of the fluorescent probe cyanine 5 at their focal point via click chemistry permitted the evaluation of their cellular internalization. All of the dendrons penetrated through the membrane with efficient cellular uptake depending of the dendron generation and the nature of the peripheral groups. These results suggest that the polycationic HYDRAmers are potentially interesting as new vectors in biomedical applications, including gene and drug delivery.journal articleresearch support, non-u.s. gov't2014 Jan 152014 01 03importe

Free Vibration Analysis and Seismic Performance Assessment of Two Approach Viaducts of Bosphorus Suspension Bridge

The current study aims to determine the dynamic vibration characteristics and structural earthquake performance of the approach viaducts of Bosphorus Suspension Bridge. Ortakoy viaduct at European continent and Beylerbeyi viaduct at Asian continent have a length of 231 and 235 m, and five spans and four spans, respectively. The viaducts are side span of the bridge and are supported at the base instead of hanger elements. Based on the project specifications of the viaducts, 3-D detailed finite element model of the viaducts is developed by the use of frame-elements, and natural frequencies and corresponding mode shapes of the viaducts are presented in the study. Paying attention to these considerations, pushover (POA) and nonlinear time-history analysis (NTHA) are performed to attain structural-earthquake performance of the viaducts according to Turkish code for the earthquake design of railways bridges (TSC-R/2008) and Caltrans (CALTRANS-2001) seismic design of steel bridge. Accordingly, the earthquake performance of the bridge is presented for each non-linear analysis method considering these codes

Continued Progress Towards Efficient Functionalization of Natural and Non Natural Targets Under Mild Conditions. Oxygenation via C-H Bond Activation with Dioxiranes

The successful isolation and characterization of a dioxirane species in the 1988 opened up a one of the most attractive methods for the efficient oxidation of simple and/or structurally complex molecules. Dioxiranes today rank among the most powerful tools in organic chemistry, with numerous applications in commercially important processes. These are quickly and remarkably recognized as efficient oxygen transfer agents, especially for epoxidations and for a wide range of O-insertion into C-H bonds. Dioxiranes also appear as highly selective (chemo-, regio- and stereo-) oxidants, despite their reactivity under mild and strictly neutral conditions controlled by a combination of steric and electronic factors and possess catalytic activity. In this review, we discuss some of the most recent and significant developments in the selective homogeneous and heterogeneous oxyfunctionalization of non-activated C-H bonds in hydrocarbons of natural and non-natural targets using isolated dioxiranes or more generally, using the ketones (i.e., the dioxirane precursors) as organocatalysts

Adamantane-based dendrons for trimerization of the therapeutic P140 peptide.

Dendrons constituted of an adamantane core, a focal point and three arms, were synthetized starting from a multifunctional adamantane derivative. Maleimido groups at the periphery of the scaffold were used to covalently attach the peptide called P140, a therapeutic phosphopeptide controlling disease activity in systemic lupus, both in mice and patients. Biotinylation of the trimers at the focal point was performed using click chemistry and the conjugates were studied in terms of solubility, binding affinity to its receptor, the HSPA8/HSC70 chaperone protein, effect on HSPA8 folding property and in vivo activity. The results showed that the trimerization of P140 peptide does not trigger aggregation or steric hindrances during the interaction with HSPA8 protein. Compared to the monomeric cognate peptide, the trivalent P140 peptide displayed the same capacity, in vitro, to down-regulate HSPA8 activity and, in vivo in MRL/lpr lupus-prone mice, to reduce abnormal blood hypercellularity. The control trimer synthesized with the same scaffold and a scrambled sequence of P140 showed no effect in vivo. This work reveals that adamantane-based scaffolds with a well-defined spatial conformation are promising trivalent systems for molecular recognition and for biomedical applications.journal articleresearch support, non-u.s. gov't2014 Aug2014 06 02importe