Racemic methyl 3,10-dioxa-2-aza­tri­cyclo­[6.2.1.02,6]undecane-4-carboxyl­ate

The structure of the racemic title compound, C10H15NO4, consists of a tricyclic skeleton comprising a six-membered piperidine ring and five-membered isoxazolidine and tetra­hydro­furan rings. The piperidine ring adopts a distorted chair conformation, while the isoxazolidine and tetra­hydro­furan rings have envelope conformations

Regioselective transformation of 6/5-fused bicyclic isoxazolidines to second-generation cyclic aldonitrones

The cycloaddition reactions of 4-(2-hydroxy-2-propyl)-3,4,5,6-tetrahydropyridine 1-oxide with mono- and di-substituted alkenes have been found to be highly stereo- as well as face-selective. In solution, the 6/5 fused bicyclic cycloadducts remain solely as the cis-fused invertomers in order to accommodate the bulky tertiary substituent 2-hydroxy-2-propyl in the equatorial orientation. The cycloadducts, upon peracid oxidation, leads to the exclusive formation of synthetically important second-generation cyclic aldonitrones. The stereo- and face-selectivity of the cycloaddition reactions of these second-generation nitrones bearing substituents at C(4) and C(6) have been briefly examined. One interesting finding was that treatment of the first generation nitrone i.e., 4-(2-hydroxy-2-propyl)-3,4,5,6-tetrahydropyridine 1-oxide, with mercury(II) oxide afforded a novel bicyclic nitrone, 1-oxa-5,6-dehydro-6-azabicyclo[3,2,1]heptan

pH Responsive Self-Assembly of Cucurbit[7]urils and Polystyrene-Block-Polyvinylpyridine Micelles for Hydrophobic Drug Delivery

Polystyrene-block-polyvinylpyridine (PS-b-P4VP) polypseudorotaxanes with cucurbit[7]urils (CB[7]) were prepared from water soluble PS-b-P4VPH+ polymer and CB[7] in aqueous solution at room temperature. At acidic and neutral pH, the pyridinium block of PS-b-P4VP is protonated (PS-b-P4VPH+) pushing CB[7] to preferably host the P4VP block. At basic pH (pH 8), P4VP is not charged and thus is not able to strongly complex CB[7]. This phenomenon was verified further by monitoring the release of pyrene, a hydrophobic cargo model, from a PS-b-P4VPH+/CB[7] micellar membrane. Release study of UV active pyrene from the membrane at different pH values revealed that the system is only operational under basic conditions and that the host-guest interaction of CB[7] with P4VPH+ significantly slows down cargo release

Functional Crypto-Adenylate Cyclases Operate in Complex Plant Proteins

Adenylyl cyclases (ACs) and their catalytic product cAMP are regulatory components of many plant responses. Here, we show that an amino acid search motif based on annotated adenylate cyclases (ACs) identifies 12 unique Arabidopsis thaliana candidate ACs, four of which have a role in the biosynthesis of the stress hormone abscisic acid (ABA). One of these, the 9-cis-epoxycarotenoid dioxygenase (NCED3 and At3g14440), was identified by sequence and structural analysis as a putative AC and then tested experimentally with two different methods. Given that the in vitro activity is low (fmoles cAMP pmol−1 protein min−1), but highly reproducible, we term the enzyme a crypto-AC. Our results are consistent with a role for ACs with low activities in multi-domain moonlighting proteins that have at least one other distinct molecular function, such as catalysis or ion channel activation. We propose that crypto-ACs be examined from the perspective that considers their low activities as an innate feature of regulatory ACs embedded within multi-domain moonlighting proteins. It is therefore conceivable that crypto-ACs form integral components of complex plant proteins participating in intra-molecular regulatory mechanisms, and in this case, potentially linking cAMP to ABA synthesis

Histidine–dialkoxyanthracene dyad for selective and sensitive detection of mercury ions

<p>Histidine-dialkoxyanthracene (HDA) was synthesised as a turn off type fluorescent sensor for fast and sensitive detection of mercury ions (Hg²⁺) in aqueous media. The two histidine moieties act as ‘claws’ to selectively complex Hg²⁺. The binding ratio of HDA to Hg²⁺ was 1:1 (metal-to-ligand ratio). The association constant for Hg²⁺ towards the receptor HDA obtained from Benesi–Hildebrand plot was found to be 3.22 × 10⁴ M⁻¹ with detection limit as low as 4.7 nM (0.94 μg/L).</p

Experimental and theoretical evaluation of nanodiamonds as pH triggered drug carriers

Nanodiamond (ND) and its derivatives have been widely used for drug, protein and gene delivery. Herein, experimental and theoretical methods have been combined to investigate the effect of pH on the delivery of doxorubicin (DOX) from fluorescein labeled NDs (Fc-NDs). In the endosomal recycling process, the nanoparticle will pass from mildly acidic vesicle to pH approximate to 4.8; thus, it is important to investigate DOX release from NDs at different pH values. Fc-NDs released DOX dramatically under acidic conditions, while an increase in the DOX loading efficiency (up to 6.4 wt%) was observed under basic conditions. Further theoretical calculations suggest that H+ weakens the electrostatistic interaction between ND surface carboxyl groups and DOX amino groups, and the interaction energies at pH 7 are 10.4 kcal mol(-1), 25.0 kcal mol(-1) and 27.0 kcal mol(-1) respectively. Cellular imaging experiments show that Fc-NDs are readily ingested by breast adenocarcinoma (BA) cells and cell viability tests prove that they can be utilized as a safe drug delivery vehicle. Furthermore, pH triggered DOX release has been tested in vitro (pH 7.4 and pH 4.83) in breast adenocarcinoma (BA) cells