Prediction of molecular solvation free energy based on the optimization of atomic solvation parameters with genetic algorithm

We propose an improved solvent contact model to estimate the solvation free energy of an organic molecule from individual atomic contributions. The modification of the solvation model involves the optimization of three kinds of parameters in the solvation free energy function: atomic fragmental volume, maximum atomic occupancy, and atomic solvation parameters. All of these atomic parameters for 24 atom types are developed by the operation of a standard genetic algorithm in such a way as to minimize the difference between experimental and calculated solvation free energies. The data set for experimental solvation free energies is divided into a training set of 131 compounds and a test set of 24 compounds. Linear regressions with the optimized atomic parameters yield fits with the squared correlation coefficients (r2) of 0.89 and 0.86 for the training set and for the test set, respectively. Overall, the results indicate that the improved solvent contact model with the newly developed atomic parameters would be a useful tool for rapid calculation of molecular solvation free energies in aqueous solution.     

Continuous blood cell separation by hydrophoretic filtration

We propose a new hydrophoretic method for continuous blood cell separation using a microfluidic device composed of slanted obstacles and filtration obstacles. The slanted obstacles have a larger height and gap than the particles in order to focus them to a sidewall by hydrophoresis. In the successive structure, the height and gap of the filtration obstacles with a filtration pore are set between the diameters of small and large particles, which defines the critical separation diameter. Accordingly, the particles smaller than the criterion freely pass through the gap and keep their focused position. In contrast, the particles larger than the criterion collide against the filtration obstacle and move into the filtration pore. The microfluidic device was characterized with polystyrene beads with a minimum diameter difference of 7.3%. We completely separated polystyrene microbeads of 9 and 12 microm diameter with a separation resolution of approximately 6.2. This resolution is increased by 6.4-fold compared with our previous separation method based on hydrophoresis (S. Choi and J.-K. Park, Lab Chip, 2007, 7, 890, ref. 1). In the isolation of white blood cells (WBCs) from red blood cells (RBCs), the microfluidic device isolated WBCs with 210-fold enrichment within a short filtration time of approximately 0.3 s. These results show that the device can be useful for the binary separation of a wide range of biological particles by size. The hydrophoretic filtration as a sample preparation unit offers potential for a power-free cell sorter to be integrated into disposable lab-on-a-chip devices.     

Expeditious synthesis of indolizine derivatives via iodine mediated 5-endo-dig cyclization

Iodine-mediated 5-endo-dig cyclization of propargylic esters 2 at room temperature proceeded smoothly to give highly functionalized indolizines 3 in excellent yields. A pyridine group was employed as a nucleophilic partner in this facile process for the first time.     

Post-harvest HPLC determination of chlorfluazuron residues in pears treated with different programs

The present study was conducted to monitor the level of chlorfluazuron residues in pear samples in order to assess the risk posed by the presence of such residues to the consumer. Chlorfluazuron was sprayed onto pear trees at the recommended dose rate at two different times at 30 and 21 days prior to harvesting in one treatment, at 21 and 14 days prior to harvesting in another treatment, and three times at 30, 21 and 14 days prior to harvesting in a third treatment. Chlorfluazuron residues were extracted with acetonitrile and partitioned into ethyl acetate. The residue determination was performed on an Apollo C(18) column using HPLC with a UV detection of 254 nm following the clean-up of the extract by open column chromatography with Florisil. The versatility of this method was evidenced by its good linearity (>0.995) in the concentration range between 0.2 and 10 microg/mL. The majority of the mean recoveries at two different fortification levels, 0.05 and 0.25 ppm, ranged from 84.9 +/- 3.2 to 94.3 +/- 10.6, and the repeatability (as the relative standard deviation) from three repetitive determinations of recovery was between 3.8 and 11%. The calculated limit of detection (LOD) was 0.008 ppm and the limit of quantitation was 0.03 ppm. Trace amounts of chlorfluazuron were detectable when it was applied onto the pear trees at two or three times prior to harvesting; however, the levels of chlorfluazuron were not quantified. The excellent sensitivity and selectivity of this method allowed for quantitation and identification at low levels with a run time of less than 12 min. Chlorfluazuron can be used safely to protect pears when sprayed two or three times at 14 days prior to harvesting.     

Kinetics of hydrogen atom transfer from (eta(5)-C(5)H(5))Cr(CO)(3)H to various olefins: influence of olefin structure

Treating (etha(5)-C(5)H(5))Cr(CO)3H (1) or (etha(5)-C(5)H(5))Cr(CO)3D (1-d(1)) with an excess of olefin containing the opposite isotope generally leads to H/D exchange, although hydrogenation is also observed in some cases. Application of an appropriate statistical correction to the observed exchange rate gives kH and kD, the rate constants for H* (D*) transfer from (etha(5)-C(5)H(5))Cr(CO)(3)H (D) to various olefins. The values of kH and kD vary appreciably with the substituents on the double bond. Phenyl-substituted olefins accept H* more readily than do carbomethoxy-substituted olefins, although the latter accept H* more readily than do alkyl-substituted olefins. A methyl substituent on the incipient radical site increases k(H) at 323 K by a factor between 5 and 50. A methyl substituent on the carbon to which the H* is being transferred decreases kH substantially. On the whole, the rate constants for H* transfer reflect steric effects as well as the stability of the resulting carbon-centered radicals.     

A degradable hyperbranched poly(ester amine) based on poloxamer diacrylate and polyethylenimine as a gene carrier

Polyethylenimine (PEI) is a well-known cationic polymer which has high transfection efficiency due to its buffering effect. However, nondegradability, cytotoxicity, aggregation, and short-circulation time in vivo still need to be overcome for a successful gene delivery. Degradable, hyperbranched poly(ester amine)s (PEAs) based on poloxamer diacrylate and low molecular weight branched PEI, were successfully synthesized and evaluated as a nonviral gene carrier. The PEAs were obtained in significant yields through Michael type addition reaction of diacrylate monomers and low molecular weight branched PEI. Analysis of degradation products by the reduction in molecular weight demonstrated that PEAs degrade in a controlled fashion. The PEA showed good DNA binding ability and the sizes of complexes under physiological condition were below 150 nm, implicating its potential for intracellular delivery. It showed lower cytotoxicity in three different cell lines (A549, 293T, and HepG2) compared with PEI 25K. PEAs showed much higher transfection efficiencies in three cell lines compared with PEI 25K and PEI 1.8K, and revealed little serum dependency in A549 cell line when the content of poloxamer in the PEA was increased up to 30%.     

Frequency-dependent interpolation rules using first derivatives for oscillatory functions

We construct frequency-dependent rules to interpolate oscillatory functions y(x)$y(x)$ with frequency ω$\omega$ of the form,

y(x)=_f1(x)cos(ωx)+_f2(x)sin(ωx),$y(x)=f_1(x)\cos (\omega x)+f_2(x)\sin (\omega x)\text{,}$

A point mutant of apolipoprotein A-I, V156K, exhibited potent anti-oxidant and anti-atherosclerotic activity in hypercholesterolemic C57BL/6 mice

In our previous study, two point mutants of apolipoprotein A-I, designated V156K and A158E, revealed peculiar characteristics in their lipid-free and lipid-bound states. In order to determine the putative therapeutic potential of these mutants, several in vitro and in vivo evaluations were conducted. In the lipid-free state, V156K showed more profound antioxidant activity against LDL oxidation than did the wildtype (WT) or A158E variants in an in vitro assay. In the lipid-bound state, V156K-rHDL showed an enhanced cholesterol delivery activity to HepG2 cells in a time-dependent manner, as compared to WT-rHDL, A158E-rHDL, and R173C-rHDL. We assessed the physiological activities of the mutants in circulation, using hypercholesterolemic mice (C57BL6/J). Palmitoyloleoyl phosphatidylcholine (POPC)-rHDL preparations containing each of the apoA-I variants were injected into the mice at a dosage of 30 mg of apoA-I/kg of body weight. Forty eight hours after injection, the sera of the V156K-rHDL injected group showed the most potent antioxidant abilities in the ferric acid removal assay. The V156K-rHDL- or R173C-rHDL-injected mice showed no atherosclerotic lesions and manifested striking increases in their serum apo-E levels, as compared to the mice injected with WT-rHDL or A158E-rHDL. In conclusion, V156K-rHDL exhibited the most pronounced antioxidant activity and anti-atherosclerotic activity, both in vitro and in vivo. These results support the notion that HDL-therapy may prove beneficial due to its capacity to induce accelerated cholesterol excretion, as well as its enhanced antioxidant and anti-inflammatory effects and lesion regression effect.