Tritiation of several intrinsically activated photoaffinity agents at high specific activity

The tritiation of natural photoffinity ligands chlorpromazine and cytochalasin B is described.     

Trace amine receptor ligands: tritiation at high specific activity

d-amphetamine and tyramine are both amines which are active at the recently discovered trace amine-associated receptor 1 (TAAR1) and analogues of these compounds labelled with tritium would be useful reagents for neurochemistry investigators. This paper describes the tritiation and characterization of these substances. d-amphetamine was radiolabelled by a direct tritium catalytic method and characterized by proton decoupled tritium NMR. For tyramine, a bromination??catalytic tritium debromination approach worked best to afford a tritiated analogue at high specific activity.     

Unexpected stereocontrolled access to 1α,1'β-disaccharides from methyl 1,2-ortho esters

Mannopyranose-derived methyl 1,2-orthoacetates (R = Me) and 1,2-orthobenzoates (R = Ph) undergo stereoselective formation of 1α,1'β-disaccharides, upon treatment with BF(3)·Et(2)O in CH(2)Cl(2), rather than the expected acid-catalyzed reaction leading to methyl glycosides by way of a rearrangement-glycosylation process of the liberated methanol.     

Enantioenrichment in sublimed amino acid mixtures

A real amplification of an initial enantiomeric excess can be detected when two amino acids are sublimed at high temperature, even if one of the components is a racemic compound that does not convert into a conglomerate by sublimation.     

Applied biological and physicochemical activity of isoquinoline alkaloids: oxoisoaporphine and boldine

The aim of this study was to determine the electronic influence of substituent groups and annelated rings such as oxazole-oxazinone on the physicochemical and photoprotection, antioxidant capacity, toxicity and singlet oxygen photosensitization biological properties of isoquinoline alkaloid frameworks. Thus, oxoisoaporphine derivatives 1-5 and 3-azaoxoisoaporphine (6), some of them with phenolic structures, did not present any antioxidant capacity, possibly either by formation of keto-enol tautomerism species or the formation of unstable free radicals. Due to the singlet oxygen quantum yields (F_D) near to unity, and greater photostability than phenalenone, oxoisoaporphines 4-6 may be considered as photosensitizers for singlet oxygen production and can be used as new universal study tools. The biological application as antibacterial agents is an important and possible tool in the study of compounds with low cytotoxicity and high reactivity in antineoplastic chemotherapy. On the other hand, when boldine and its annelated derivatives B1-4 are irradiated, a photoprotector effect is observed (SPF = 2.35), even after 30 minutes of irradiation. They also act as photoprotectors in cell fibroblast cultures. No hemolysis was detected for boldine hydrochloride and its salts without irradiation. In solutions irradiated before incubation (at concentrations over 200 ppm) photoproducts were toxic to the nauplii of Artemia salina.     

Do Docking Sites Persist Upon Fluorination? The Diadamantyl Ether-Aromatics Challenge for Rotational Spectroscopy and Theory

Fluorinated derivatives of biological molecules have proven to be highly efficient at modifying the biological activity of a given protein through changes in the stability and the kind of docking interactions. These interactions can be hindered or facilitated based on the hydrophilic/hydrophobic character of a particular protein region. Diadamantyl ether (C₂₀H₃₀O) possesses both kinds of docking sites, serving as a good template to model these important contacts with aromatic fluorinated counterparts. In this work, an experimental study on the structures of several complexes between diadamantyl ether and benzene as well as a series of fluorinated benzenes is reported to analyze the effect of H→F substitution on the interaction and structure of the resulting molecular clusters using rotational spectroscopy. All experimentally observed complexes are largely dominated by London dispersion interactions with the hydrogen-terminated surface areas of diadamantyl ether. Already single substitution of one hydrogen atom with fluorine changes the preferred docking site of the complexes. However, the overall contributions of the different intermolecular interactions are similar for the different complexes, contrary to previous studies focusing on the difference in interactions using fluorinated and non-fluorinated molecules.     

Nanomedicine Reformulation of Chloroquine and Hydroxychloroquine

The chloroquine family of antimalarials has a long history of use, spanning many decades. Despite this extensive clinical experience, novel applications, including use in autoimmune disorders, infectious disease, and cancer, have only recently been identified. While short term use of chloroquine or hydroxychloroquine is safe at traditional therapeutic doses in patients without predisposing conditions, administration of higher doses and for longer durations are associated with toxicity, including retinotoxicity. Additional liabilities of these medications include pharmacokinetic profiles that require extended dosing to achieve therapeutic tissue concentrations. To improve chloroquine therapy, researchers have turned toward nanomedicine reformulation of chloroquine and hydroxychloroquine to increase exposure of target tissues relative to off-target tissues, thereby improving the therapeutic index. This review highlights these reformulation efforts to date, identifying issues in experimental designs leading to ambiguity regarding the nanoformulation improvements and lack of thorough pharmacokinetics and safety evaluation. Gaps in our current understanding of these formulations, as well as recommendations for future formulation efforts, are presented.     

Confidence bands in nonparametric regression with length biased data

In this paper we deduce a confidence bands construction for the nonparametric estimation of a regression curve from length biased data, where a result from Bickel and Rosenblatt (1973,The Annals of Statistics,1, 1071–1095) is adapted to this new situation. The construction also involves the estimation of the variance of the local linear estimator of the regression, where we use a finite sample modification in order to improve the performance of these confidence bands in the case of finite samples.