Ion mobility mass spectrometry with molecular modelling to reveal bioactive isomer conformations and underlying relationship with isomerization.

RATIONALE: In medicine and drug development, molecular modelling is an important tool. It is attractive to develop a platform connecting the theoretical structural modelling and the results from experimental measurement. In addition, the separation and structural analysis of bioactive constituent isomers are still challenging tasks. METHODS: Drift tube ion mobility (IM) mass spectrometry (MS) provides the experimental collision cross section (CCS) which contains the structural information. The experimental CCS can be compared with the calculated CCS of the molecular modelling structures. This technique is especially useful for bioactive constituents in herbal medicine because active isomers with the same chemical formula are common in these samples. IM helps separate and identify these isomers and reveals details about their structures and conformations. RESULTS: Two model bioactive constituents, caffeoylquinic acids (CQAs) and dicaffeoylquinic acids (di-CQAs), were selected to systematically investigate the influence of solution, ion source conditions and ion heating on the isomer CCS distributions. By comparing the calculated CCS with the experimental value, we identified the favorable conformations of CQAs. The most compact conformation of a CQA was less likely to isomerize than the more extended conformation. It was found that the isomerization tendency was in accord with the conformation favorability. CONCLUSIONS: This study offers an effective approach to predict and demystify the conformation and isomerization of the active constituents in herbal medicines.

Amorphous carbon dots with high two-photon fluorescence for cellular imaging passivated by hyperbranched poly(amino amine).

Amorphous carbon dots (C-Dots) with high two-photon fluorescence were prepared by using citric acid (CA) as the carbon source and hyperbranched poly(amino amine) (HPAA) as the surface passivation agent through a facile hydrothermal approach. The C-Dots with an average diameter about 10 nm were readily dispersed in water. They exhibited excellent fluorescence properties and excitation-dependent fluorescence behavior with the corresponding quantum yield (QY) of 17.1% in aqueous solution. Interestingly, the C-Dots emitted bright fluorescence even in the solid state with a QY of 16.3%, which is the highest value obtained for carbon-based nanomaterials. Using the MTT assay, the C-Dots showed low cytotoxicity against L929 normal cells. Furthermore, they were easily internalized by HeLa cells and presented high quality one- and two-photon cellular imaging, suggesting significant potential for application in biological imaging.

Preparation of coenzyme Q10 liposomes using supercritical anti-solvent technique.

Coenzyme Q(10) (CoQ(10)) proliposomes were prepared using the supercritical anti-solvent (SAS) technique to encapsulate CoQ(10). The mixture of cholesterol and soya bean phosphatidylcholine (PC) was chosen as wall materials. The effects of operation conditions (temperature, pressure and components) on the recovery of CoQ(10) and the CoQ(10) loading in CoQ(10) proliposomes were studied. At the optimum conditions of pressure of 8.0 MPa, temperature of 35°C, the weight ratio of 1/10 between CoQ(10) and PC, and the weight ratio of 1/3 between cholesterol and PC, the CoQ(10) loading reached 8.92%. CoQ(10) liposomes were obtained by hydrating CoQ(10) proliposomes and the entrapment efficiency of CoQ(10) reached 82.28%. The morphologies of CoQ(10) proliposomes were characterized by scanning electron microscope, and their solid states were characterized by X-ray diffractometer. The structures of CoQ(10) liposomes were characterized by transmission electron microscope. The particle size distribution of CoQ(10) liposomes was determined by dynamic light scattering instrument. The results indicate that CoQ(10) liposomes with particle sizes about 50 nm can be easily obtained from hydrating CoQ(10) proliposomes prepared by SAS technique.

Synthesis and gene delivery of poly(amido amine)s with different branched architecture.

A general strategy to improve the transfection efficiency as well as lower the cytotoxicity for polycationic vectors has been developed. Through the polycondensation addition of N,N'-methylene bisacrylamide and 1-(2-aminoethyl)piperazine in a water/N,N-dimethylformamide cosolvent, a series of cationic poly(amido amine)s with same repeating units but different branched architecture have been prepared. With the increase in branched architecture, the cationic polymers become more and more compact, accompanied by the enhancement of primary and tertiary amino groups. Therefore, the buffering capacities and DNA condensation capabilities of cationic poly(amido amine)s are strengthened greatly, whereas the correspondent cytotoxicity decreases. Correspondingly, the transfection efficiency is improved by more than three orders of magnitude. The results of this study indicate that the gene delivery can be readily regulated by only changing the branched architecture of polycations.