Mechanism of aniline adsorption on post-crosslinked resins: pore structure and oxygen content.

A series of post-crosslinked resins were synthesized from macroporous chloromethylated styrene-divinylbenzene copolymer by controlling post-crosslinked reaction conditions. Adsorption study towards aniline showed that the three resins, ST-DVB-WH5, ST-DVB-WH6, and ST-DVB-WH7, prepared at different temperatures, and which had nearly identical static adsorption capacity, displayed great disparity in kinetic behavior. The rate constant of ST-DVB-WH7 by the pseudo-first-order model was 1.50 and 1.19 times higher than that of ST-DVB-WH5 and ST-DVB-ST-DVB-WH6. Further analysis of the diffusion model showed that the three resins exhibited different diffusion rates due to the difference in oxygen content and pore structure of each resin. The results showed that the adsorption capacity was mainly decided by the pore volume within 1.14 and 3.42 nm and the adsorption rate was mainly decided by the oxygen content of the resin. In addition, as the best synthetic resin for aniline adsorption, the equilibrium adsorption capacity of ST-DVB-WH7 was 1.57 times and 1.44 times higher than that of H-103 and NKA-II, respectively.

Effective adsorption of nitroaromatics at the low concentration by a newly synthesized hypercrosslinked resin.

In the present study, a series of hypercrosslinked resins (CH series) was prepared in systematically designed conditions for the adsorption of nitroaromatics from aqueous solution. The newly synthesized CH-10 possesses a Brunauer-Emmett-Teller (BET) surface area up to 1,329.3 m2/g which is larger than that of the widely used hypercrosslinked resin H-103 and it exhibits great advantage over H-103 when subjected to nitrobenzene at low concentrations. The adsorption capacity of CH-10 for nitrobenzene is 1.4 times as much as that of H-103 at the concentration of 100 mg/L. Kinetic study by film diffusion model and intra-particle diffusion model revealed that its distinctive mesoporous structure within pore diameters between 2 and 6 nm played significant role in the mass transfer at low concentrations, and these unique mesopores also resulted in better adsorption capacity, which was confirmed by adsorption thermodynamics study. Moreover, the CH series displayed a good affinity to a wide scope of nitroaromatics and exhibited excellent dynamic adsorption and desorption properties in fixed bed.

Pharmacokinetics in Vitro and in Vivo of Two Novel Prodrugs of Oleanolic Acid in Rats and Its Hepatoprotective Effects against Liver Injury Induced by CCl4.

Oleanolic acid (OA) is a well-known pentacyclic triterpenoid compound, which has been used as a dietary supplement and is supplied as an over-the-counter drug for the treatment of human liver diseases. These are reasons for the low bioavailability of OA which have restricted its wider application. In this study, two OA prodrugs (1,3-cyclic propanyl phosphate esters of OA) were designed and synthesized. The hepatoprotective effects of these prodrugs were evaluated against carbon tetrachloride (CCl4) induced liver injury in mice; the levels of alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and aspartate aminotransferase (AST) were significantly increased, and the level of the hepatic malondialdehyde (MDA) was increased. The metabolism, in vitro, of the prodrugs was studied by incubation in rat liver microsome; the plasma pharmacokinetics and the biodistribution in vivo after intravenous (iv) injection to six rats were investigated, respectively. The prodrugs diminished gradually with time; most of the parent drugs were released within 30 min in vitro, and the presumed mechanism of the in vitro metabolism was confirmed. The plasma-concentration data in vivo was analyzed by a compartmental method: both the prodrugs and the corresponding released parent drugs existed at up to 48 h in rats. The t1/2 improved after intravenous administration in rats compared with direct injection of the parent drugs. All analyte concentrations were highest in the liver, and most of the prodrugs were excreted in feces (>47.11%). Therefore, 1,3-cyclic propanyl phosphate esters of OA can serve as a promising lead candidate for drugs.

Comparison of protective effects of alprostadil with Salvia miltiorrhiza against myocardial ischemia-reperfusion injury in rats.

OBJECTIVES: Our study aimed to investigate the effects of alprostadil and Salvia miltiorrhiza extract on myocardial ischemia-reperfusion injury (IRI) and related underlying molecular mechanisms. METHODS: A myocardial IRI model was established in Wistar rats via surgical ligation of the left anterior descending coronary artery followed by loosening of the occlusion. The rats were divided into four groups: saline, sham, alprostadil, and S. miltiorrhiza. Rats in the saline and sham groups were injected with normal saline by tail vein once daily for 10 consecutive days. Rats in the S. miltiorrhiza and alprostadil groups were injected with S. miltiorrhiza extract (20 µg/kg) or alprostadil. Histological differences in myocardial tissues between rats in the sham group and in the myocardial IRI model were observed by hematoxylin and eosin staining. India ink perfusion was used to quantify the number of capillary microvessels. Real-time quantitative reverse transcription polymerase chain reaction was used to determine serum expression levels of soluble intercellular adhesion molecule (sICAM), soluble vascular adhesion molecule (sVCAM), CD11b and CD18. RESULTS: The alprostadil and S. miltiorrhiza groups had significantly higher numbers of microvessels than the saline group. Serum sICAM and sVCAM expression was significantly reduced in the alprostadil and S. miltiorrhiza groups. Meanwhile, sICAM and sVCAM in the alprostadil group were markedly lower than in the S. miltiorrhiza group. Moreover, the alprostadil group had markedly lower mRNA expression of CD11b and CD18, which were clearly lower than in the S. miltiorrhiza group. CONCLUSION: Alprostadil may have cardioprotective effects for myocardial IRI, with down-regulated expression of sICAM, sVCAM, CD11b, and CD18.

In vitro and in vivo pharmacokinetics of two novel 1,3-cyclic propanyl phosphate ester prodrugs of 18ß-glycyrrhetic acid in rats.

The in vitro metabolism of two novel phosphate prodrugs of glycyrrhetic acid (GA) was studied by the method of incubation in the rat liver microsome and the in vivo plasma pharmacokinetics after injecting intravenously (i.v.) into six rats was investigated, respectively. The prodrugs diminished gradually with time and most of the parent drugs were released in 30 min in vitro. In this paper, the in vivo plasma concentration data were analyzed by compartmental modeling. Both the prodrugs and the corresponding released parent drugs could be described by a two-compartment model, which existed for 48 h in rats. The t(1/2) increases remarkably after i.v. administration to rats when compared with injecting the parent drugs directly.

Synthesis of a novel isatin and ethylenediamine modified resin and effective adsorption behavior towards Orange G.

In this study, a novel crosslinked resin 135-I-EDA modified by isatin and ethylenediamine was synthesized through two continuous functionalization steps using chloromethylated styrene-divinylbenzene copolymer as the substrate. In the first step, the cross-linking reaction and isatin incorporation were realized in a creative one-pot reaction using Friedel-crafts reaction in the presence of isatin to give resin 135-I; in the second step, ethylenediamine was successfully introduced on the carbonyl of the modified isatin to further increase the chemically interacting sites. The double-modified resin 135-I-EDA displayed the best adsorption performance (113.38 mg g-1) towards Orange G, which is 1.99 times and 3.49 times as much as that of 135-I (56.94 mg g-1) and commercial resin H-103 (32.51 mg g-1) respectively. This is attributed to its superior porous structure formed in the Friedel-crafts reaction and multiple modified groups in isatin and ethylenediamine. π-π conjugation and hydrogen bonding are the main driving forces for the adsorption. The pseudo-second-order rate equation characterizes the adsorption kinetic curves well and 135-I-EDA displayed the fastest adsorption rate. The study also proved that the 135-I-EDA has a better adsorption capacity for OG in more acidic solution, at higher temperature and higher salinity, which provides a basis for the treatment of industrial dye wastewater.

Preparation of hypercrosslinked amine modification resin and its adsorption properties for nitroaromatics.

A nitrosation-reduction method had been applied for the modification of DCE-4 h. It was a kind of non-polar hypercrosslinked resin and synthesized by our group. The functional resin, NR-07, exhibited good adsorption performance for NACs (Nitroaromatics). The adsorption capacity of NR-07 for p-nitrobenzoic acid was almost 1.3 times as much as that of H-103 in 24 h. The adsorption rate of NR-07 calculated by the kinetic function was 1.6 times as much as that of DCE-4h. According to the EA analysis and IR spectrum, the amine and carbonyl group were introduced onto the polymer chains of NR-07. These hydrophilic chemical groups of NR-07 contributed to a higher liquid-film diffusion rate than that of DCE-4h. Besides, the pore volume within 0.46~4.3 nm increased after the modification process, which had a positive effect on the intra-particle diffusion process.

Exploring stereoselectivity of 3-indolyl cyclopent[b]indoles: a parallel synthesis and anti-EGFR study on human cancer cells.

We synthesized a series of novel 3-indolyl cyclopent[b]indoles by trifluoroacetic acid mediated cyclodimerizations. The reaction showed high stereoselectivity and moderate to good yields. The influencing factors for stereoselectivity were systematically analyzed and a stepwise reaction mechanism was proposed. The cell viability tests in two colon and two lung cancer cell lines indicated the 1-benzyl-2-phenyl-group in 3-indolyl cyclopent[b]indoles was critical for the observed lower IC50s in these compounds. Western blot analysis demonstrated that the compound inhibited the expression and phosphorylation of EGFR through altered HSP90 expression. Further cell cycle and cell cycle check point protein analyses showed expected anti-cellular proliferation and cell cycle arresting properties associated with suppressed EGFR expression and phosphorylation. These data revealed a novel molecular mechanism explaining the observed cytotoxicities for these compounds.

Design, synthesis, and sustained-release property of 1,3-cyclic propanyl phosphate ester of 18ß-glycyrrhetinic acid.

A new class of potential prodrugs, 1,3-cyclic propanyl phosphate esters of 18ß-glycyrrhetic acid, was designed and synthesized through the key reaction of 18ß-glycyrrhetic acid with 1,3-cyclic propanyl phosphate ester catalysed by lithium diisopropylamide. The sustained-release properties of 1,3-cyclic propanyl phosphate esters of 18ß-glycyrrhetic acid in vivo were also investigated. The animal experiments showed that 18ß-glycyrrhetic acid was released from 1,3-cyclic propanyl phosphate esters of 18ß-glycyrrhetic acid at a steady rate in rats and the plasma concentrations of 18ß-glycyrrhetic acid were nearly stable. The result indicated that 1,3-cyclic propanyl phosphate esters of 18ß-glycyrrhetic acid have sustained-release properties to avoid the quick metabolism of 18ß-glycyrrhetic acid. These prodrugs are highlighted as a promising new strategy to improve 18ß-glycyrrhetic acid metabolism.