Determination of the binding constants and ionic mobilities of diquat complexes with randomly sulfated cyclodextrins by affinity capillary electrophoresis.

The enantiomers of diquats (DQs), a new class of functional organic molecules, were recently separated by capillary electrophoresis (CE) with high resolution up to 11.4 within 5-7 min using randomly sulfated α-, ß-, and γ-cyclodextrins (CDs) as chiral selectors. These results indicated strong interactions between dicationic diquats and multiply negatively charged sulfated CDs (S-CDs). However, the binding strength of these interactions was not quantified. For that reason, in this study, affinity CE was applied for the determination of the binding constants and ionic mobilities of the complexes of DQ P- and M-enantiomers with CD chiral selectors in an aqueous medium. The non-covalent interactions of 10 pairs of DQ enantiomers with the above CDs were investigated in a background electrolyte (BGE) composed of 22 mM NaOH, 35 mM H3PO4, pH 2.5, and 0.0-1.0 mM concentrations of CDs. The average apparent binding constant and the average actual ionic mobility of the DQ-CD complexes were determined by nonlinear regression analysis of the dependence of the effective mobility of DQ enantiomers on the concentration of CDs in the BGE. The complexes were found to be relatively strong with the averaged apparent binding constants in the range 13 600-547 400 L/mol.

Engineered human H-chain ferritin with reversed charge of the internal cavity exhibits RNA-mediated spongelike effect for loading RNA/DNA-binding molecules.

Ferritins are globular proteins with an internal cavity that enables the encapsulation of a plethora of low-mass compounds. Unfortunately, the overall negative surface charge of ferritin's internal cavity hampers efficient loading of negatively charged molecules. Therefore, we produced a genetically engineered human H-chain ferritin containing a cationic RKRK domain, reversing the natural net charge of the cavity to positive, thus allowing for efficient encapsulation of negatively charged siRNA. Due to the reversed, positive charge mediated by RKRK domains, the recombinant ferritin produced in E. coli inherently carries a load of bacterial RNA inside its cavity, turning the protein into an effective sponge possessing high affinity for DNA/RNA-binding substances that can be loaded with markedly higher efficiency compared to the wildtype protein. Using doxorubicin as payload, we show that due to its loading through the RNA sponge, doxorubicin is released in a sustained manner, with a cytotoxicity profile similar to the free drug. In summary, this is the first report demonstrating a ferritin/nucleic acid hybrid delivery vehicle with a broad spectrum of properties exploitable in various fields of biomedical applications.

The separation of the enantiomers of diquats by capillary electrophoresis using randomly sulfated cyclodextrins as chiral selectors.

Diquats, derivatives of the widely used herbicide diquat, represent a new class of functional organic molecules. A combination of their special electrochemical properties and axial chirality could potentially result in their important applications in supramolecular chemistry, chiral catalysis, and chiral analysis. However, prior to their practical applications, the diquats have to be prepared in enantiomerically pure forms and the enantiomeric purity of their P- and M-isomers has to be checked. Hence, a chiral capillary electrophoresis (CE) method has been developed and applied for separation of P- and M-enantiomers of 11 new diquats. Fast and better than baseline CE separations of enantiomers of all 11 diquats within a short time 5-7 min were achieved using acidic buffer, 22 mM NaOH, 35 mM H3 PO4 , pH 2.5, as a background electrolyte, and 6 mM randomly sulfated α-, ß-, and γ-cyclodextrins as chiral selectors. The most successful selector was sulfated γ-cyclodextrin, which baseline separated the enantiomers of all 11 diquats, followed by sulfated ß-cyclodextrin and sulfated α-cyclodextrin, which baseline separated enantiomers of 10 and nine diquats, respectively. Using this method, a high enantiopurity degree of the isolated P- and M-enantiomers of three diquats with a defined absolute configuration was confirmed and their migration order was identified.

Quantum enhanced feedback cooling of a mechanical oscillator using nonclassical light.

Laser cooling is a fundamental technique used in primary atomic frequency standards, quantum computers, quantum condensed matter physics and tests of fundamental physics, among other areas. It has been known since the early 1990s that laser cooling can, in principle, be improved by using squeezed light as an electromagnetic reservoir; while quantum feedback control using a squeezed light probe is also predicted to allow improved cooling. Here we show the implementation of quantum feedback control of a micro-mechanical oscillator using squeezed probe light. This allows quantum-enhanced feedback cooling with a measurement rate greater than it is possible with classical light, and a consequent reduction in the final oscillator temperature. Our results have significance for future applications in areas ranging from quantum information networks, to quantum-enhanced force and displacement measurements and fundamental tests of macroscopic quantum mechanics.

A preliminary trial of the sedation induced by intranasal administration of midazolam alone or in combination with dexmedetomidine and reversal by atipamezole for a short-term immobilization in pigeons.

OBJECTIVE: To assess the sedative and immobilization effect of intranasal administration (INS) of midazolam (MID) without or with INS dexmedetomidine (DXM), and some physiological changes induced by the drugs. The ability of INS atipamezole to reverse the DXM component was also assessed. STUDY DESIGN: Prospective 'blinded' experimental study. ANIMALS: In total, 15 pigeons. METHODS: Pigeons were sedated by INS MID alone at a dose of 5 mg kg(-1) (group MID, n = 6) or in combination with INS DXM at a dose 80 µg kg(-1) (group MID-DXM, n = 6). Measurements were made of heart rate (HR), respiratory rate (fR ) and cloacal temperature (CT). The degree of sedation was assessed at 15 minutes prior to, immediately after, and at intervals until 100 minutes after drug administrations. Following MID-DXM, INS atipamezole (250 µg kg(-1) ) was administered and the same indices measured 5 and 10 minutes later. RESULTS: MID had no effect on HR and fR , and although CT decreased, it remained within physiological range. MID-DXM caused significant falls in HR, fR and CT that persisted until the end of sedation. Atipamezole antagonized sedation and cardiorespiratory side effects of MID-DXM within 10 minutes of application. In addition, for MID compared to MID-DXM, the lowest sedation scores [10 (7-14) and 10.5 (5-14) versus 2 (1-4) and 2 (1-5)] were achieved in the 10th and 20th minute versus the 20th and 30th minute of the sedation, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: MID alone, given INS had minimal side effects on vital functions but caused inadequate immobilization of pigeons for restraint in dorsal recumbency. MID-DXM caused an effective degree of immobilization from 20 to 30 minutes after administration, at which time birds tolerated postural changes without resistance. Atipamezole antagonized both side effects and sedation, but complete recovery had not occurred within 10 minutes after its application.