ABSTRACT
A series of naphthyl-bridged amino-borane derivatives, namely 1-(dimethylamino)-8-naphthylboranes (1, 3, 5, 7) and 5-(dimethylamino)-6-acenaphthylboranes (2, 4, 6, 8, 10, 11), differing in the steric and electronic properties of the boryl moiety, have been synthesized and fully characterized by spectroscopic and crystallographic means. Structural X-ray analysis of the peri-atom displacement and ring torsion angles served to experimentally assess the presence and magnitude of the B-N interactions. The reversible quaternarization of nitrogen has been explored and was found to provide an efficient switch corresponding to different molecular organizations. The electronic characteristics of the nature of B-N interactions were further studied by Natural Bonding Orbital analysis derived from the theoretically calculated electron densities. This real-space bonding indicator discriminates the bonding B-N contact in 5 from the nonbonding in 8, which correlates with the flexibility of the naphthyl scaffold to respond to the Lewis acidity of boron allowing shorter peri interactions. Whereas, the steric shielding imposed by the two mesityl groups, and/or the rigidity of the acenaphthene framework disrupt B-N interaction. Thus, this communication reports on the modulation of the B-N bonding continuum by means of structural tuning leading to a molecular switch, as well as its implications towards revealing FLP reactivities through the isolation of intermediates of a stepwise mechanism.
ABSTRACT
Neurodegenerative disorders including Alzheimer's disease (AD) are drawing scientists' attention within various fields, being one of the most serious diseases mankind will have to fight against in the very near future. AD is multi-factorial and is characterized by two histopathological hallmarks: the senile plaques made of amyloid-ß (Aß) peptide fibrils which also contain high levels of transition metal ions and the neurofibrillary tangles of Tau protein. Aß aggregation, possibly modulated by metal ions, is now considered as an important factor in AD aetiology. Hence, chemists are studying the details of molecular features at the origin of the disease with special interest in Aß aggregation and in the design of new molecules for the early diagnosis of AD or with curative properties. In this context, the benzazole molecular scaffold, included for instance in Thioflavin-T, an Aß fibril specific dye, or the PIB imaging agent, appears to be very attractive and exhibits multiple uses. In the present review, we have thus focused our interest on the applications of benzazole derivatives for understanding, diagnosing and curing AD. After having analysed the synthetic access to 2-arylbenzazoles, we have described a selection of recent applications of such compounds aiming to combat AD. They include the use of Thioflavin-T for the monitoring of Aß aggregation, the investigations of new PET and SPECT imaging agents for the detection of the senile plaques, the development of bi-functional molecules, encompassing the 2-arylbenzazole moiety for Aß binding and a chelating unit for metal ions coordination for instance.
Subject(s)
Alzheimer Disease/therapy , Amyloid beta-Peptides/chemistry , Benzimidazoles/chemistry , Benzothiazoles/chemistry , Benzoxazoles/chemistry , Alzheimer Disease/diagnosis , Benzene/chemistry , HumansABSTRACT
PET cat. While the copper(II) tren ketoprofenate precatalyst 1 (see picture) is inactive at room temperature in methanol, it is quantitatively and rapidly reduced to its cuprous state upon light irradiation to provide a highly reactive click catalyst. By simply introducing air into the reaction medium the catalysis can be switched off and then switched on again by bubbling argon followed by irradiation.
