RESUMO
Binding of anions using macrocyclic structures with a nonpolar interior using the CH···anion interaction as the recognition motif has gained popularity in the past few years, and such receptors often rely on a subtle interplay between enthalpic and entropic factors. For these types of receptors solvation of both the anion and the binding pocket of the macrocyclic host play important roles in the overall energetic picture of the binding event. Systematic chemical modifications of synthetic receptors that are able to bind anions in a variety of solvents is an important tool to gain understanding of the factors that determine the supramolecular chemistry of anions. Here we present the chiral macrocyclic structure biotin-l-sulfoxide[6]uril as a host molecule that binds anions in both water and in organic solvents. Biotin-l-sulfoxide[6]uril is prepared in a highly diastereoselective one-pot synthesis from the macrocycle biotin[6]uril. We compare the binding properties with that of biotin[6]uril, also studied in acetonitrile and in aqueous buffer at neutral pH. The biotin-l-sulfoxide[6]uril generally exhibits stronger recognition of anions in acetonitrile, but weaker binding in water as compared to the biotin[6]uril macrocycle. We have studied the binding events using a combination of NMR spectroscopy, isothermal titration calorimetry (ITC), and computational methods.
RESUMO
BACKGROUND: To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent 18F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia. MATERIAL AND METHODS: Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology. Beforehand all patients underwent a comprehensive clinical, neuropsychiatric and laboratory examination as well as imaging by means of magnetic resonance imaging (MRI) and fluorodeoxyglucose-PET. The working diagnoses before and after FBB-PET imaging were compared. RESULTS: 17 out of 33 patients were scored as FBB-PET positive. In four cases the initial diagnosis had to be changed to Alzheimer's disease (three cases) and cerebral amyloid angiopathy (one case) due to the positive FBB-PET scan. 16 patients showed a negative FBB-PET scan. In three patients the initial diagnosis of Alzheimer's disease could be ruled out due to the negative FBB-PET scan. Overall, in 7 out of 33 examined patients the initial diagnosis had to be changed because of the findings of the FBB-PET scan. In 24 patients the initial diagnosis was confirmed by the results of the FBB-PET scan. CONCLUSION: Amyloid-PET is currently no standard procedure in the diagnosis of dementia; however, it can be a helpful additional diagnostic tool when used according to the "Appropriate Use Criteria" and the S3 guidelines on dementia in cases of unclear clinical presentation, atypically early age of onset as well as in patients with persistent or progressive unexplained mild cognitive impairment. By facilitating early diagnosis amyloid-PET imaging allows patient selection for therapeutic drug trials.