Hyun-Mee Park

Application of micro-attenuated total reflectance FTIR spectroscopy in the forensic study of questioned documents involving red seal inks

Red seal inks from Korea (6), Japan (1) and China (6) were studied to investigate the feasibility of micro-attenuated total reflectance (ATR) FTIR spectroscopy as a tool in the forensic study of questioned documents involving seal inks. The technique was able to differentiate red seal inks of similar colors and different manufacturers. Blind testing has shown that micro-ATR FTIR can identify the origin of the red seal inks with accuracy. Data gathered were converted to a database for future reference. Also, the technique was also successful in determining the sequence of heterogeneous line intersection from a personal seal and a ballpoint pen. The results show that micro-ATR FTIR can be a valuable non-destructive tool for the objective analysis of questioned documents involving different red seal inks.

Structure-based optimization and biological evaluation of trisubstituted pyrazole as a core structure of potent ROS1 kinase inhibitors

Recently inhibition of ROS1 kinase has proven to be a promising strategy for several indications such as glioblastoma, non-small cell lung cancer (NSCLC), and cholangiocarcinoma. Our team reported trisubstituted pyrazole-based ROS1 inhibitors by which two inhibitors showed good IC₅₀ values in enzyme-based screening. To develop more advanced ROS1 inhibitors through SAR this trisubstituted pyrazole-based scaffold has been built. Consequently, 16 compounds have been designed, synthesized and shown potent IC₅₀ values in the enzymatic assay, which are from 13.6 to 283 nM. Molecular modeling studies explain how these ROS1 kinase inhibitors revealed effectively the key interactions with ROS1 ATP binding site. Among these compounds, compound 9a (IC₅₀=13.6 nM) has exerted 5 fold potency than crizotinib and exhibited high degree of selectivity (selectivity score value=0.028) representing the number of non-mutant kinases with biological activity over 90% at 10 μM.

NBO approach to evaluate origin of rotational barrier of diformylhydrazine

To evaluate the origin of rotational barrier and the structures of N; N 0 -diformylhydrazine as a model compound of azapeptide, the natural bond orbital (NBO) analysis was performed at the HF/6-31G* level. The rotational barrier energies as a function of structural isomers were dissected into structural, total exchange repulsion and delocalization energy changes. The preferred dihedral angles of CO– N – N– CO were known to be orthogonal minimizing the repulsion between nitrogen lone pairs, which means that nitrogen lone pair repulsion is dominant in determining the preferred angles of CO – N– N – CO. However, the dihedral angles are deviated from 908 within the range of ^ 208, and the NBO analysis reveals that these preferred dihedral angles of CO – N– N –CO as a function of rotamers are involved with many other individual terms of exchange and delocalization energy changes as well as nitrogen lone pair energy term of structural energy change. The pyramidality of nitrogen in transition states of N; N 0 -diformylhydrazine was simply explained by the repulsion of nitrogen lone pairs. However, NBO analysis shows that this pyramidalization of nitrogen atoms leads to decrease of structural energy change and increase of the total exchange repulsion and delocalization energies. The intramolecular hydrogen bonding energy could be important term in forming planar as found in crystal structure, but is not dominant energy term to lower the barrier in comparison to the amide resonance and total exchange repulsion. This NBO analysis to elucidate the origins of the perturbation of dihedral angles and pyramidality of nitrogen atoms as well as the role of intramolecular hydrogen bonding in hydrazine derivative will shed some lights on the understanding of the dynamics and structures of azapeptide analogues. q 2003 Elsevier B.V. All rights reserved.

Evaluation of natural crab shell as an adsorbent for preconcentrating airborne volatile organic compounds collected in a canister

Abstract A method has been developed for preconcentrating the volatile organic compounds (VOCs) in ambient air using a trap filled with natural crab shell powder without the need for extensive cryotrapping with liquid cryogens. Air samples collected in the canister were concentrated on the crab shell adsorbent trap without cryotrapping and then analysed using thermal desorption followed by capillary column (DB-5) gas chromatography with simultaneous ion trap mass detection. These analytical data on ambient air have been compared with those obtained by cryotrapping volatile compounds in glass beads followed by thermal desorption. The characteristics of natural crab shell as an adsorbent have been presented and its capacity for preconcentrating airborne VOCs has been tested by measuring breakthrough volume (l/g), detection limit (ppb, v/v) and reproducibility. The application of natural crab shell adsorbent trap for the analysis of ambient air samples collected in the canister has been proved to be useful.

Inhibition of gp 120-CD4 interaction by various plant extracts

Various assay methods have been developed to evaluate the effectiveness of substances against human immunodeficiency virus (HIV). One of them is the Syncytia formation inhibition assay, which is based on the inhibition of the interaction between the HIV-1 envelope protein gp 120 and the cellular membrane protein CD4. A variation of this assay using recombinant virus vPE 16 and CD4(+) HeLa cell was developed to find anti-HIV compounds in natural products that inhibit gp 120-CD4 binding. VPE 16 expresses glycoprotein gp 160, which is glycosylated then processed into gp 120 and gp 41 on its envelope. A total of 50 plant extracts were screened with this system. Extracts from Calicarpa japonica and Sedum sarmentosum were among those that showed strong inhibition of the gp 120-CD4 interaction.

Discovery of 1-(3-(benzyloxy)pyridin-2-yl)-3-(2-(piperazin-1-yl)ethyl)urea: A new modulator for amyloid beta-induced mitochondrial dysfunction

Herein, we report a new series of aliphatic substituted pyridyl-urea small molecules synthesized as potential modulators for amyloid beta (Aβ) induced mitochondrial dysfunction. Their blocking activities against Aβ-induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measures the change of mitochondrial membrane potential (ΔΨm). The inhibitory activity of sixteen compounds against Aβ-induced mPTP opening was superior or almost similar to that of the standard Cyclosporin A (CsA). Among them, 1-(3-(benzyloxy)pyridin-2-yl)-3-(2-(piperazin-1-yl)ethyl)urea (5x) effectively maintained mitochondrial function and cell viabilities on ATP assay, MTT assay, and ROS assay. Using CDocker algorithm, a molecular docking model presented a plausible binding mode for 5x with cyclophilin D (CypD) receptor as a major component of mPTP. Moreover, hERG and BBB-PAMPA assays presented safe cardiotoxicity and high CNS bioavailability profiles for 5x. Taken as a whole, this report presents compound 5x as a new nonpeptidyl mPTP blocker may hold a promise for further development of Alzheimers disease (AD) therapeutics.

LC-TOF/MS determination of phthalates in edible salts from food markets in Korea

Residual quantities of 12 phthalates have been monitored in edible salts (raw salts, refined salts, refined salts with additives and baked salts) available in Korean food markets. Liquid–liquid extraction followed by liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS) was used to analyse the samples. The method was validated and showed linear correlation (R 2 > 0.996) in the range 0.5–100 ng g−1 for all target analytes. Recoveries were 85.9–108.4%, except for diethyl phthalate (DEP). Relative standard deviations (RSDs) were 2.7–6.0% and the limits of detection (LODs) were 1.2–2.8 ng g−1. Although the contamination of phthalates in salt would be trivial in comparison to those of other main foods and below the reference dose of the Chronic Oral Exposure recommended by US-EPA, the availability of reference data could be valuable for food chemists and salt manufacturers.

Determination of free acetaldehyde in total blood for investigating the effect of aspartate on metabolism of alcohol in mice

To explore the effect of sodium L-aspartate monohydrate (aspartate) as a NAD+ regenerating agent for acetaldehyde in alcohol metabolism, a simple HPLC method has been developed for the measurement of free acetaldehyde in total mice blood digested with alcohol and aspartate. The blood samples were collected in EDTA Vacutainer tubes, and treated with 2,4-dinitrophenylhydrazine (DNP hydrazine) reagent in total blood. Acetaldehyde DNP hydrazone was extracted from total blood and analyzed by HPLC using an Ultrasphere ODS column. The compounds were separated using acetonitrile-water (50:50, v/v) as mobile phase and detected at 356 nm. The detection limit for acetaldehyde DNP hydrazone was 0.1 ppm. A blank determination was carried out for each analysis and subtracted from the results. The amount of acetaldehyde in blood has been determined as a function of time lapse after sole alcohol administration and aspartate ingestion followed by alcohol administration, respectively. This comparative analysis demonstrates that the ingestion of aspartate before the administration of alcohol dramatically decreases the aldehyde level in blood, and aspartate may be utilized as a prospective antagonist for acceleration of ethanol metabolism and prevention of acetaldehyde toxicity.

Determination of Heterocyclic Amines and Acrylamide in Agricultural Products with Liquid Chromatography-Tandem Mass Spectrometry

Heterocyclic amines (HCAs) and acrylamide are unintended hazardous substances generated by heating or processing of foods and are known as carcinogenic and mutagenic agents by the animal experiments. A simple method was established for a rapid and accurate determination of 12 types of HCAs (IQ, MeIQ, Glu-P-1, Glu-P-2, MeIQx, Trp-P-1, Trp-P-2, PhIP, AαC, MeAαC, Harman and Norharman) and acrylamide in three food matrices (non-fat liquid, non-fat solid and fat solid) by isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). In every sample, a mixture of internal standards including IQ-d3, MeIQx-d3, PhIP-d3, Trp-P-2-13C2-15N and MeAαC-d3 was spiked for quantification of HCAs and 13C3-acrylamide was also spiked for the analysis of acrylamide. HCAs and acrylamide in sample were extracted with acetonitrile and water, respectively, and then two solid-phase extraction cartridges, ChemElut: HLB for HCAs and Accucat: HLB for acrylamide, were used for efficiently removing interferences such as pigment, lipid, polar, nonpolar and ionic compounds. Established method was validated in terms of recovery, accuracy, precision, limit of detection, limit of quantitation, and linearity. This method showed good precision (RSD < 20%), accuracy (71.8~119.1%) and recovery (66.0~118.9%). The detection limits were < 3.1 ng/g for all analytes. The correlation coefficients for all the HCAs and acrylamide were > 0.995, showing excellent linearity. These methods for the detection of HCAs and acrylamide by LC-MS/MS were applied to real samples and were successfully used for quantitative monitoring in the total diet study and this can be applied to risk assessment in various food matrices.

Synthesis of new diarylamides with pyrimidinyl pyridine scaffold and evaluation of their anti-proliferative effect on cancer cell lines.

A new series of diarylamides, having a pyrimidinyl pyridine scaffold, was designed and synthesized. The target compounds were synthesized in three steps. A selected group from the target compounds was tested over a panel of 60 cancer cell lines at a single dose concentration of 10 μM, and the most active compound, 5j, was further tested in a five-dose testing mode to determine its IC50 value over the 60 cell lines. In single-dose testing mode, compound 5j showed the highest growth inhibition against the NCI-60 cancer cell lines, while other tested compounds showed a weak to moderate inhibitory activity against a range of different cancer cell lines. In five-dose testing mode, compound 5j showed strong inhibitory activity in micro molar range against many cancer cell lines. Its major activity was against melanoma cancer cell lines. Therefore, compound 5j is a promising hit compound targeting this severe form of cancer.