Table of Contents

Abstract: Inhibitors of human NAD⁺-dependent protein deacetylases possess great value for deciphering the biology of these enzymes and as potential therapeutics for metabolic and agerelated diseases and cancer. In the current study, we have experimentally demonstrated that, the potent inhibition we obtained previously for one of these enzymes (i.e. sirtuin type 1 (SIRT1)) by simply replacing N^ε-thioacetyl-lysine for N^ε-acetyl-lysine in its peptide substrate, represented a general and efficient strategy to develop potent and selective inhibitors of human NAD⁺-dependent protein deacetylase enzymes. Indeed, by using this simple inhibition strategy, potent (low-micromolar) and selective (≤40-fold) SIRT2 and SIRT3 inhibitors, which were either comparable or superior to currently existing inhibitors, have also been quickly identified in the current study. These inhibitors could be used as chemical biological tools or as lead compounds for further focused structure-activity optimization.

Abstract: Six novel 3-alkyl(aryl)-4-(p-nitrobenzoylamino)-4,5-dihydro-1H-1,2,4-triazol-5- ones (2a-f) were synthesized by the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H- 1,2,4-triazol-5-ones (1a-f) with p-nitrobenzoyl chloride and characterized by elemental analyses and IR, ¹H-NMR, ¹³C-NMR and UV spectral data. The newly synthesized compounds 2 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as acetone, isopropyl alcohol, tert-butyl alcohol and N,Ndimethylformamide, and the half-neutralization potential values and the corresponding pKa values were determined for all cases. Thus, the effects of solvents and molecular structure upon acidity were investigated. In addition, isotropic ¹H and ¹³C nuclear magnetic shielding constants of compounds 2 were obtained by the gauge-including-atomic-orbital (GIAO) method at the B3LYP density functional level. The geometry of each compound has been optimized using the 6-311G basis set. Theoretical values were compared to the experimental data. Furthermore, these new compounds and five recently reported 3-alkyl-4-(2- furoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3a-c,e,f) were screened for their antioxidant activities.

Abstract: Inspired by the concept of ionic liquids (ILs), this study modified the original Mukaiyama’s reagent, 2-chloro-1-methylpyridinium iodide (m.p. 200-dec), from ionic solid into liquids by changing its anion. The esterification of N-acetyl-L-phenylalanine was investigated as a model reaction. The microwave irradiation was more effective in esterifying N-acetyl-L-phenylalanine than the conventional reflux method. The original Mukaiyama’s reagent was modified into ILs through manipulating its anion. However, only non-nucleophilic anions (such as EtSO₄^- and Tf₂N^-) were favorable since nucleophilic ones (such as CF₃COO^- and CH₃COO^-) could exchange with chlorine resulting in non-reactive coupling reagents. Two modified Mukaiyama’s compounds (i.e. hydrophilic [2- ClMePy][EtSO_4] and hydrophobic [2-ClMePy][Tf₂N]) have been identified as the best ILtype coupling reagents. The esterification reaction was greatly enhanced by using 1- methylimidazole as the base instead of conventional toxic tertiary amines, and by using excess amount of alcohols as solvents instead of dichloromethane. Overall, the method reported is effective and ‘greener’.

Abstract: A dihydroxotin(IV) porphyrin functionalized single-walled carbon nanotubes (SWNTs) nanohybrid is obtained. Solubility of the nanohybrid in organic solvents is determined by UV-Vis-NIR absorption spectroscopy. Electron absorption and fluorescence spectra investigations demonstrate that efficient electron transfer occurs within the nanohybrid at the photoexcited state and the charge-separated state of the nanohybrid is observed by transient absorption spectrum. The results illustrate that this soluble electron donor–acceptor nanohybrid might be a good candidate as a light harvesting material in molecular photoelectronic devices.

Abstract: TRAIL is a promising candidate for cancer therapeutics that preferentially induces apoptosis in cancer cells. The combined treatment flavonoids with TRAIL might be promising as a chemoprevention and/or new therapy against malignant tumors. We examined the cytotoxic effect of dietary flavonoids in combination with TRAIL on HeLa cells. It was found that treatment with noncytotoxic concentration of some flavonoids significantly sensititizes to TRAIL induced death in HeLa cells. Our study demonstrated that flavone, apigenin and genistein markedly augmented TRAIL mediated cytotoxicity against HeLa, whereas kaempferol and quercetin produced no effect.

Abstract: Protein-protein interactions are important for biochemical processes in biological systems. The 3D structure of the macromolecular complex resulting from the protein-protein association is a very useful source to understand its specific functions. This work focuses on computational study for protein-protein docking, where the individually crystallized structures of interacting proteins are treated as rigid, and the conformational space generated by the two interacting proteins is explored extensively. The energy function consists of intermolecular electrostatic potential, desolvation free energy represented by empirical contact potential, and simple repulsive energy terms. The conformational space is six dimensional, represented by translational vectors and rotational angles formed between two interacting proteins. The conformational sampling is carried out by the search algorithms such as simulated annealing (SA), conformational space annealing (CSA), and CSA combined with SA simulations (combined CSA/SA). Benchmark tests are performed on a set of 18 protein-protein complexes selected from various protein families to examine feasibility of these search methods coupled with the energy function above for protein docking study.

Abstract: The cellulose paper treated in proportional mixture systems showed higher liquid absorption compare to only EtOH and MeOH treatments. It was approximately 40-70% and 50-91% higher for EtOH-NaOH and MeOH-NaOH treated papers, respectively. All conditions apparently bring about an effect of decreased strength for papers. The lowest tensile strength of 13.0 N/mm was found with EtOH and NaOH treated samples after 5^th repeating wetting-drying stage. But, some conditions gave approximately 21-59.5% higher stretch than untreated samples. The pore size distributions of papers were evaluated with Simons stain procedure and experimental results usually consisted with sorption data. The less intense CH₂-CH₂- vibrations (1450-1700 cm^-1) and C-C and C-O-C peak areas in FTIR spectra indicates lowering H-bonds in solvent treated and dried paper network structure.

Abstract: Essential oils that contain large concentrations of germacrene D are typically accompanied by cadinane sesquiterpenoids. The acid-catalyzed cyclization of germacrene D to give cadinane and selinane sesquiterpenes has been computationally investigated using both density functional (B3LYP/6-31G*) and post Hartree-Fock (MP2/6-31G**) ab initio methods. The calculated energies are in general agreement with experimentally observed product distributions, both from acid-catalyzed cyclizations as well as distribution of the compounds in essential oils.

Abstract: 2-methylphenoxyacetic acid (2-MPA), 2-methyl-4-chlorophenxyacetic acid (MCPA) and 4-chlorophenoxyacetic acid (4-CPA) were imprinted to investigate the cross-selectivities of molecularly imprinted polymers (MIPs). The result indicates that 2-MPA, which is similar in shape, size and functionality with phenoxyacetic herbicides, are suitable to be used as a suitable template to prepare the MIPs for retaining phenoxyacetic herbicides. To study the ion-pair interactions between template molecules and functional monomer 4-vinylpiridine (4-VP), computational molecular modeling was employed. The data indicate that the cross-selectivities of MIPs for phenoxyacetic acid herbicides depend on the binding energies of complexes.