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The sol–gel nanoporous capturing technology represents a powerful approach where the sol–gel matrix constrains the motion of the encapsulated biomolecules (proteins, peptides, chemicals, antibodies, nucleotides, etc.) without physical adsorption or any modifications. This technology can be applied to multiplex immunoassay platform because several disease markers can be immobilized and tested at once. In this study, we have tested several thousand specimens using Hi3-1 Multiplex human immunodeficiency virus (HIV) 1/2 and hepatitis C virus (HCV) antibody detection kit at two clinical trials institutes. These results showed a highest sensitivity (100%, n = 500 HIV-positive specimens and n = 400 HCV-positive) and specificity (99.99% for HIV and 99.83% for HCV, n = 7706 negative specimens) by using Hi3-1 kit, which screens HIV1/2 and HCV antibodies simultaneously. Finally, we suggested that our screening technology was successfully utilized as a multiplex HIV and HCV diagnostic tool for blood bank screening.

A series of indole acrylamide derivatives were synthesized and evaluated for their inhibitory effects on hepatitis C virus (HCV) replication. Previously, we have identified (E)-N-(4-tert-butylphenyl)-3-(5-cyano-1H-indol-3-yl)-2-methylacrylamide (6c) as one of the promising leads for anti-HCV chemotherapy. Based on the structural features of indole acrylamide, we have explored extended structure–activity relationship study using analogs with substituted indoles, various amides, and N-substitution at the indole ring. Among the newly synthesized series, 5-cyanoindole acrylamide analog with N-acetyl substitution (13c) (EC50 = 0.98 μM, CC50 = 40.74 μM, and SI = 41.6) exhibited the most potent antiviral activity with reasonable cytotoxicity in a cell-based J6/JFH1 reporter assay using Huh7.5 cells. In addition, improved water solubility of 13c compared to 6c further merits consideration of 13c as a valuable candidate for anti-HCV therapeutics development.

2'-β-C-Methylneplanocin A (3) was synthesized via 2-β-C-methylribonolactone, prepared by a modified Whistler and BeMiller's method developed by our laboratory, as potential anti-HCV agent. Reduction of 14 with Dibal-H afforded 26 in a good yield with a trace of 25, whereas a Luche reduction gave 26/25=4/1 mixture. Several attempts were made to chemoselectively remove TBS group in the presence of TBDPS group and treatment with both PPTS and TsOH showed the best result. Condensation of 26 with 6-chloropurine under Mitsunobu conditions produced an S N 2 product 27 along with an S N 2' product 28.

Eleven novel oxiranyl and thiiranyl phenolic compounds were synthesized as potential antitumor agents using epichlorohydrin and epithiohydrin in the presence of K2CO3. Cytotoxicities were found in range of IC50 values of 2.5-14.8 µM, which was partially attributed to topoisomerase II inhibition. Bis-thiiranyl anthraquinone analog, 19 showed more cytotoxicity against MDA-MB-231 (breast cancer cell) and PC3 (prostate cancer cell) after 24 and/or 48 h and more potent topoisomerase II inhibitory activity than etoposide.

E-mail: djjang@snu.ac.krReceived September 17, 2013, Accepted September 26, 2013Key Words : Core-shell, Extinction spectrum, Mie theory, Nanobubble, NanosphereThe controlled fabrication, characterization, and appli-cation of nanometer-sized materials with functional proper-ties have been studied widely.

This paper describes first development and validation of pentafluorophenylprophyl ligand-based liquid chromatography coupled to tandem mass spectrometry (PFPLC-MS/MS) method to determine metformin, a highly polar compound, in human plasma. Metformin and Phenformin (internal standard) were extracted from human plasma 50 with a single-step protein precipitation. The chromatographic separation was performed using a linear gradient elution of mobile phase involving 5.0 mM ammonium formate solution with 0.1% formic acid (A) and acetonitrile (B) over 3.0 min of run time on a Phenomenex Luna PFP column. The detection was performed using a triple-quadrupole tandem mass spectrometer (Waters Quattro micro) with electrospray ionization in the mode of positive ionization and multiple-reaction monitoring (MRM). The developed method was validated with 5.0 ng/mL of lower limit of quantification (LLOQ). The calibration curve was linear over 5-3000 ng/mL of the concentration range ( > 0.99). The specificity, selectivity, carry-over effect, precision, accuracy and stability of the method met the acceptance criteria. The method developed in this study had had rapidness, simplicity and ruggedness. The reliable method was successfully applied to high throughput analysis of real samples for a practical purpose of a pharmacokinetic study.

A simple, fast and robust analytical method was developed to determine imatinib in human plasma using liquid chromatography-tandem mass spectrometry with electrospray ionization in the positive ion mode. Imatinib and labeled internal standard were extracted from plasma with a simple protein precipitation. The chromatographic separation was performed using an isocratic elution of mobile phase involving 5.0 mM ammonium formate in water–5.0 mM ammonium formate in methanol (30:70, v/v) over 3.0 min on reversed-stationary phase. The detection was performed using a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring mode. The developed method was validated with lower limit of quantification of 10 ng/mL. The calibration curve was linear over 10-2000 ng/mL (R 2 > 0.99). The method validation parameters met the acceptance criteria. The spiked samples and standard solutions were stable under conditions for storage and handling. The reliable method was successfully applied to real sample analyses and thus a pharmacokinetic study in 27 healthy Korean male volunteers.

The separation and capture process of carbon dioxide from power plants is garnering interest as a method to reduce greenhouse gas emissions. In this study, aqueous alkanolamine solutions were studied as absorbents for CO2 capture. The solubility of CO2 in aqueous alkanolamine solutions was investigated with a continuous stirred reactor at 313, 333 and 353 K. Also, the heat of absorption (−ΔHabs) between the absorbent and CO2 molecules was measured with a differential reaction calorimeter (DRC) at 298 K. The solubility and heat of absorption were determined at slightly higher than atmospheric pressure. The enthalpies of CO2 absorption in monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), and 2-amino-2-methyl-1-propanol (AMP) were 88.91, 70.44, 44.72, and 63.95, respectively. This investigation showed that the heat of absorption is directly related to the quantity of heat for absorbent regeneration, and is dependent on amine type and CO2 loading.

The geometrical parameters, vibrational frequencies, and binding energies for (H2O3)n (n = 1-5) have been investigated using various quantum mechanical techniques. The possible structures of the clusters (n = 2-5) are fully optimized and the binding energies are predicted using energy differences at each optimized geometry. The harmonic vibrational frequencies are also determined and zero-point vibrational energies (ZPVEs) are considered for the better prediction of the binding energy. The best estimation of the binding energy for the dimer is 8.65 kcal/mol. For n = 2 and 3, linear structures with all trans forms of the HOOOH monomers are predicted to be the lowest conformations in energy, while the cyclic structures with all cis-HOOOH monomers are preferable structures for n = 4 and 5.

To quantify the presence of mercuric ions in aqueous solution, double-stranded DNA (dsDNA) of poly(dT) was employed using a light switch compound, (1) which is reported to intercalate into dsDNA of a right-handed B-form. Addition of mercuric ions induced the dehybridization of poly(dT)poly(dA) duplexes to form a hairpin structure of poly(dT) at room temperature and the metal-to-ligand charge transfer emission derived from the intercalation of 1 was reduced due to the dehybridization of dsDNA. As the concentration of was increased, the emission of 1 progressively decreased. This label-free emission method had a detection limit of 0.2 nM. Other metal ions, such as , , , , , , , , , , , , had no significant effect on reducing emission. This emission method can differentiate matched and mismatched poly(dT) sequences based on the emission intensity of dsDNA.

On the basis of potent HDAC-inhibitory activity and anticancer activity of SAHA, novel SAHA derivatives 3a-d and 7 with a bulky cap such as p-dimethylaminophenyl, 4-phenylaminophenyl, 4-phenyloxyphenyl, 9H-fluorenyl or naphthalenyl ring were synthesized starting from the corresponding aryl amines or naphthalenyl acetic acid using an EDC-mediated amide coupling reaction in the presence of HOBt followed by a nucleophilic addition-elimination reaction with hydroxylamine. Compounds 3b, 3c and 3d showed more potent inhibitory activity on total HDACs (14~27-fold), HDAC1 (8~15-fold), HDAC2 (1.3~25-fold) and HDAC7 (1~3-fold) and more potent anticancer activity (2~22-fold) against MCF-7, MDA-MB-231, MCF-7/Dox, MCF-7/Tam, SK-OV-3, LNCaP and PC3 human cancer cell lines than SAHA.

5"-Iodoneplanocin A (1) and its analogues 2 and 3 were designed and synthesized as potential SAHH inhibitor via iodocyclopentenol 6, which was prepared using a Michael addition-iodination-elimination process. All final compounds did not show antiviral activity, maybe due to a steric hindrance induced by 5"-iodo substituent.

Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, KoreaReceived July 28, 2008Novel bicyclo[3.1.0]hexanyl purine nucleoside analogues were synthesized as potential antiherpetic agents viaa bicyclo[3.1.0]hexanol (±)- 8, which was prepared using a highly efficient carbenoid cycloaddition reaction. Ahighly diastereoselective reduction of ketone and a Mitsunobu reaction for the condensation of glycosyl donor(±)-12 with 6-chloropurine were employed. Key Words : Bicyclo[3.1.0]hexanone, Intramolecular carbenoid cycloaddition, Mitsunobu reaction, Diastereo-selective reduction, North conformationIntroductionSince the discovery of acyclovir

It has been well known that two enantiomers of chiral drugs often show different pharmacological activity. In this instance, exact determination of the enantiomeric composition of chiral drugs is essential for the development of chiral drugs and for the better insight into the in vivo distribution and metabolism of the two enantiomers. Among various methods, liquid chromatographic separation of enantiomers on HPLC chiral stationary phases (CSPs) has been demonstrated as very attractive means for the analysis of enantiomeric composition of chiral compounds including chiral drugs. A series of 3-substituted 1,4-benzodiazepin-2-ones such as camazepam, lorazepam, lormetazepam and oxazepam belongs to a class of widely used anxiolytics and/or tranquilizer. The pharmacological activity of a series of 3substituted 1,4-benzodiazepin-2-ones has been shown to be enantiodependent. Consequently some efforts have been devoted to the development of the liquid chromatographic separation of the two enantiomers of 3-substituted 1,4benzodiazepin-2-ones. Among others, Pirkle-type CSPs have been found to be quite useful in the resolution of racemic 3-substituted 1,4-benzodiazepin-2-ones. Especially, CSP 1 (Figure 1) derived from (S)-N-(3,5-dinitrobenzoyl)leucine has been most successfully utilized in the resolution 3-substituted 1,4-benzodiazepin-2-ones. As an improved CSP, we recently developed CSP 2 (Figure 1) by simply replacing the superfluous adsorption site, the N-H hydrogen of the connecting tether of CSP 1, with a phenyl group. CSP 2 has shown greater enantioselectivities than CSP 1 for the enantiomers of π-acidic or π-basic derivatives of a-amino acids. However, CSP 2 has not been applied in the resolution of racemic 3-substituted 1,4-benzodiazepin-2ones. In this study, as an effort to extend the use of CSP 2, we wish to elucidate that CSP 2 is also useful in the resolution of 3-substituted 1,4-benzodiazepin-2-ones and wish to compare the chiral recognition efficiency of CSP 2 with that of CSP 1. 3-Substituted 1,4-benzodiazepin-2-ones (3 and 4) used in this study (Figure 1) were prepared via the reported procedure. For the purpose of comparison, 3-substituted 1,4-benzodiazepin-2-ones (3 and 4) prepared in our laboratory were resolved on CSP 1 and CSP 2 under an identical chromatographic condition and the resolution results were summarized in Table 1. The representative chromatograms on CSP 2 are shown in Figure 2. As shown in Table 1 and Figure 2, the resolutions of 3substituted 1,4-benzodiazepin-2-ones (3 and 4) are excellent on both CSP 1 and CSP 2. Interestingly, the retention factors (k) on CSP 2 are always smaller than those on CSP 1. Even when the content of isopropyl alcohol in mobile phase was varied within the range of 3% to 20%, the retention factors (k) on CSP 2 were still always smaller than those on CSP 1. This means that CSP 2 is better than CSP 1 in terms of reducing analytical time and saving solvent. The smaller retention factors (k) on CSP 2 might be rationalized by considering the chiral recognition mechanism. A chiral recognition mechanism for the resolution of 3substituted 1,4-benzodiazepin-2-ones on CSP 1 was