Synthesis of azabicyclo[2.2.n]alkane systems as analogues of 3-[1-methyl-2-(S)-pyrrolidinyl- methoxy]pyridine (A-84543)

This work is connected with the epibatidine field and describes the synthesis of several analogues of compounds that present affinity for nicotinic acetylcholine receptors, such as 3-[1-methyl-2-(S)-pyrrolidinylmethoxy]pyridine (A-84543). These analogues bear a 3-pyridyl ether substituent at the bridgehead carbon of the azabicyclo[2.2.n]alkane system. Particularly, in the case of the 1-substituted 2-azabicyclo[2.2.2]octane system, a new synthetic route has been developed, which involves the synthesis of a novel rigid sulfamidate that allows the straightforward introduction of nucleophiles.     

Topological Polymer Chemistry Enters Surface Science: Linear versus Cyclic Polymer Brushes

The cyclic polymer topology strongly alters the interfacial, physico‐chemical properties of polymer brushes, when compared to the linear counterparts. In this study, we especially concentrated on poly‐2‐ethyl‐2‐oxazoline (PEOXA) cyclic and linear grafts assembled on titanium oxide surfaces by the “grafting‐to” technique. The smaller hydrodynamic radius of ring PEOXAs favors the formation of denser brushes with respect to linear analogs. Denser and more compact cyclic brushes generate a steric barrier that surpasses the typical entropic shield by a linear brush. This phenomenon, translates into an improved resistance towards biological contamination from different protein mixtures. Moreover, the enhancement of steric stabilization coupled to the intrinsic absence of chain ends by cyclic brushes, produce surfaces displaying a super‐lubricating character when they are sheared against each other. All these topological effects pave the way for the application of cyclic brushes for surface functionalization, enabling the modulation of physico‐chemical properties that could be just marginally tuned by applying linear grafts.     

An electrochemically driven molecular shuttle controlled and monitored by C60

Herein we describe a fullerene rotaxane, in which shuttling between two well-defined and distant co-conformations is both induced and monitored by the C60 stopper.     

Copper(II) interaction with unstructured prion domain outside the octarepeat region: speciation, stability, and binding details of copper(II) complexes with PrP106-126 peptides

Copper(II) complexes of the neurotoxic peptide fragments of human and chicken prion proteins were studied by potentiometric, UV-vis, CD, and EPR spectroscopic and ESI-MS methods. The peptides included the terminally blocked native and scrambled sequences of HuPrP106-126 (HuPrPAc106-126NH2 and ScrHuPrPAc106-126NH2) and also the nona- and tetrapeptide fragments of both the human and chicken prion proteins (HuPrPAc106-114NH2, ChPrPAc119-127NH2, HuPrPAc109-112NH2, and ChPrPAc122-125NH2). The histidyl imidazole-N donor atoms were found to be the major copper(II) binding sites of all peptides; 3N and 4N complexes containing additional 2 and 3 deprotonated amide-N donors, respectively, are the major species in the physiological pH range. The complex formation processes for nona- and tetrapeptides are very similar, supporting the fact that successive deprotonation and metal ion coordination of amide functions go toward the N-termini in the form of joined six- and five-membered chelates. As a consequence, the peptide sequences investigated here, related to the neurotoxic region of the human PrP106-126 sequence, show a higher metal-binding affinity than the octarepeat fragments. In the case of the HuPrP peptide sequences, a weak pH-dependent binding of the Met109 residue was also detected in the 3N-coordinated complexes.     

Environmental effects on a prion's helix II domain: copper(II) and membrane interactions with PrP180-193 and its analogues

An abnormal interaction between copper and the prion protein is believed to play a pivotal role in the pathogenesis of prion diseases. Copper binding has been mainly attributed to the N-terminal domain of the prion protein, but this hypothesis has recently been challenged in some papers which suggest that the C-terminal domain might also compete for metal anchoring. In particular, the segment corresponding to the helix II region of the prion protein, namely PrP180-193, has been shown both to bind copper and to exhibit a copper-enhanced cytotoxicity, as well as to interact with artificial membranes. The present work is aimed at extending these results by choosing the most representative model of this domain and by determining its copper affinity. With this aim, the different role played by the electrostatic properties of the C- and N-termini of PrP180-193 (VNITIKQHTVTTTT) in determining its conformational behaviour, copper coordination and ability to perturb model membranes was investigated. Owing to the low solubility of PrP180-193, its copper affinity was evaluated by using the shorter PrPAc184-188NH2 (IKQHT) analogue as a model. ESI-MS, ESR, UV/Vis, and CD measurements were carried out on the copper(II)/PrPAc184-188NH2 and copper(II)/PrP180-193NH2 systems, and showed that PrPAc184-188NH2 is a reliable model for the metal interaction with the helix II domain. The affinity of copper(II) for the helix II fragment is higher than that for the octarepeat and PrP106-126 peptides. Finally, the different ability of PrP180-193 analogues to perturb the DPPC model membrane was assessed by DSC measurements. The possible biological consequences of these findings are also discussed briefly.     

Density and Volume Properties of Ethane-1,2-diol + 1,2-Dimethoxyethane + Water Ternary Mixtures from −10° to 80°

Thermodynamic interactions in the ethane-1,2-diol (1) + 1,2-dimethoxyethane(2) + water (3) ternary system have been investigated in terms of the excessmolar volume, derived from density measurements at 19 different temperaturesfrom –10;dg to 80;dgC. Fourteen three-component mixtures have been considered,covering the entire composition range. The excess molar volumes are discussedin terms of conformational changes induced in each component by the presenceof another one. The results obtained support the hypothesis of the absence of anythree-component complex adducts under all experimental conditions investigated.     

New cyclodextrin derivatives as chiral selectors in capillary electrophoresis

The separation of three pairs of enantiomeric herbicides has been successfully achieved by capillary electrophoresis at two different pH values in the presence of cyclodextrin derivatives previously synthesized in our laboratory. Two of these derivatives constitute a new class of receptor, the hemispherodextrins, in which a trehalose capping moiety is bonded to β-cyclodextrin. Because of their peculiar structure hemispherodextrins have very promising characteristics and the low receptor concentration required to achieve separation deserves particular interest.