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A practical solid-phase strategy for the synthesis of Delta(5)-2-oxopiperazines via N-acyliminium ion cyclization has been developed. A key step in the library synthesis is tandem acidolytic cleavage with subsequent in situ iminium formation, followed by stable enamide transformation. This approach is exemplified by the preparation of a 192-member pilot library using bromoacetal resins without further purification.

A solid phase strategy has been developed for the synthesis of tetrahydro-β-carboline alkaloid library. The key transformation is an acid-catalyzed tandem intramolecular Pictet–Spengler cyclization from l -tryptophan which forms acyl iminiums with synchronous cleavage of products from the acid-labile SASRIN™ solid support. A pilot library with two diversity points has been successfully synthesized in high purity to demonstrate this strategy.

Inherited and somatic mutations in the APC gene, a human tumor-suppressor, occur in a large percentage of colon cancers, leading to elevated levels of nuclear beta-Catenin, and to activation of TCF/beta-Catenin-responsive genes including cyclin D1 and c-myc. To identify small molecule antagonists of this pathway, we screened transformed colorectal cells with a secondary structure-templated chemical library, in search of compounds that attenuated a TCF/beta-Catenin-responsive reporter gene. From this library we selected ICG-001 (IC50=3 microM) as a lead compound. Design and synthesis of the chemical library and some preliminary biological evaluation is described.

The degree of diffusion, characterized by the “scattering coefficient” of surface materials, has been known to be one of the most important factors in determining the acoustical qualities of concert halls. Based on the suggested ISO method, which measures the random-incidence scattering coefficient of surfaces in a diffuse field, the scattering coefficients of different sizes and densities of wooden hemispheres and cubes were measured in model-scale reverberation rooms. The results show that hemispheres with a height of more than 15 cm have the highest average (500 Hz to 4 kHz) scattering coefficient. It was also found that the scattering coefficient becomes higher when the diffuser density reaches about 50% for hemispheres and 30% for cubes.

The dynamics of cellular heat production and propagation remains elusive at a subcellular level. Here we report the first small molecule fluorescent thermometer selectively targeting the endoplasmic reticulum (ER thermo yellow), with the highest sensitivity reported so far (3.9%/°C). Unlike nanoparticle thermometers, ER thermo yellow stains the target organelle evenly without the commonly encountered problem of aggregation and successfully demonstrates the ability to monitor intracellular temperature gradients generated by external heat sources in various cell types. We further confirm the ability of ER thermo yellow to monitor heat production by intracellular Ca2+ changes in HeLa cells. Our thermometer anchored at nearly-zero distance from the ER, i.e. the heat source, allowed the detection of the heat as it readily dissipated and revealed the dynamics of heat production in real time at a subcellular level.

The pathophysiological processes of inflammation can lead to a host of diseases, such as periodontitis, atherosclerosis, rheumatoid arthritis, and even cancer. The dysregulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) activation play important roles in the development of certain inflammatory diseases. Here, we investigated the effects of CDr10b which is originally developed for a microglia staining probe on inflammation, by modulating NF-κB activation and iNOS and COX-2 expression induced by lipopolysaccharide (LPS) in murine macrophages. The CDr10b suppressed NF-κB activation and iNOS and COX-2 expression induced by LPS. All the results suggest that CDr10b is a promising novel agent for the treatment of inflammatory diseases.

Small molecule fluorescent probes offer significant advantages over conventional antibody and fluorescent protein labeling techniques. Here we present CDr10a and CDr10b, dyes that label live microglia specifically. They may be applied to the isolation and imaging of live microglia when investigating their role in neuroinflammatory diseases.

The first fluorescent sensor for an illicit date rape drug, GBL, was developed and named Green Date. It shows high fluorescence enhancement to GBL and allows its detection in different drinks. The mechanism between GBL and Green Date was explored. This discovery may help to prevent the drug-facilitated sexual assault problems.

Novel structures of an near-infrared (NIR) tetraarylazadipyrromethene (aza-BODIPY) series have been prepared. We designed the core structure containing two amido groups at the para-position of the aromatic rings. The amido group was incorporated to secure insensitivity to pH and to ensure a bathochromic shift to the NIR region. Forty members of aza-BODIPY compounds were synthesized by substitution of the acetyl group with commercial amines on the alpha bromide. The physicochemical properties and photostability were investigated and the fluorescence emission maxima (745~755 nm) were found to be in the near infrared (NIR) range of fluorescence.

Solid-phase methodologies have been widely used in the context of sensor development. Initial applications came after the expansion of solid-phase peptide synthesis and primarily made use of the immobilization process to facilitate the screening of potential peptide-based sensors in a high-throughput manner. Their subsequent adjustment to nonpeptidic biomolecules considerably spread out their scope from the preparation of resins to label bioactive molecules to combinatorial approaches to accelerate the derivatization of fluorescent scaffolds. Once combinatorial chemists succeeded in adapting fluorescent heterocycles to solid-phase synthesis, small molecule fluorescent dyes started to be increasingly implemented in sensor discovery programs as powerful bioimaging probes (Figure 14.1). Diversity-oriented fluorescent libraries (DOFLs) have been successfully prepared by solid-phase synthesis and demonstrated that subtle structural modifications within a fluorescent core can be distinguishable by largemacromolecules and hence lead to selective fluorescent probes. This chapter will review the progress of solid-phase approaches for the preparation of sensors over the last years and outlook the role that these methodologies will play in probe development in the near future.

Inherited and somatic mutations in the APC gene, a human tumor-suppressor, occur in a large percentage of colon cancers, leading to elevated levels of nuclear beta-Catenin, and to activation of TCF/beta-Catenin-responsive genes including cyclin D1 and c-myc. To identify small molecule antagonists of this pathway, we screened transformed colorectal cells with a secondary structure-templated chemical library, in search of compounds that attenuated a TCF/beta-Catenin-responsive reporter gene. From this library we selected ICG-001 (IC50=3 microM) as a lead compound. Design and synthesis of the chemical library and some preliminary biological evaluation is described.

A multistep, practical solid-phase strategy for the synthesis of natural product-like diaza-bridged heterocycles was developed. A key step in the library synthesis is tandem acidolytic cleavage with subsequent in situ iminium formation followed by the Pictet-Spengler intramolecular cyclization. The Pictet-Spengler-type intramolecular cyclization step was regioselective and diastereoselective to give final products as single diastereomers in exceptional yields and purities, which was confirmed by NMR structural study and LC/MS analysis. This approach is exemplified by the preparation of a 384-member library of 3,9-diazabicyclo[3.3.1]non-6-en-2-one skeletons, fused with indole and dihydroxybenzene and diversified at two bridging nitrogen atoms, using the solid-phase parallel synthetic methodology without further purification. In this pilot library, two diastereomerically enriched diaza-bridged core skeletons were modified by amide and urea bond formation on bridging nitrogen atoms, and this scheme exhibits the potential for expansion to obtain further diversification.

This study investigated a piezoelectric energy-harvesting system for a mechanical switch device. Piezoelectric ceramics of 0.4Pb(Mg1/3Nb2/3)O3–0.25PbZrO3–0.35PbTiO3 were prepared by using a conventional solid-state reaction method. Li2O, Bi2O3, and CuO additions were used as sintering aids to develop piezoelectric ceramics for low-temperature sintering. Multilayer piezoelectric ceramics with 10×10×3 mm3 sizes and with Ag–Pd inner electrodes were manufactured by using the conventional tape-casting method with the prepared powder. A prototype of a piezoelectric batteryless switch device using the multilayer ceramics was produced. It showed an output peak-to-peak voltage of 3.8 V and an output power per strike of 18 µW. The performance of the device was good enough for practical use.

A novel ratiometric biothiol probe Glutathione Green was developed. It allows quantitative measurement of glutathione in cell extracts and direct visualization of changes in glutathione levels in live cells. Remarkably, this is the first reported biothiol probe which can detect the carcinoma region of liver tissue based on the differences in the glutathione level.

In the present study, annoyance caused by diverse construction noises was evaluated through surveys and laboratory experiments. A survey with a total of 100 construction workers was carried out to investigate annoyance from construction noises at different construction phases. Then, a number of noises from machinery that were evaluated in the survey as highly annoying were recorded from construction sites in Korea. Recorded construction noises were classified into four groups: stationary, fluctuating, intermittent, and impulsive, according to the temporal, psychoacoustical and spectral characteristics of the noises. A laboratory auditory experiment was then performed in order to quantify the total annoyance caused by individual construction noise and multiple construction noises. From the experiment, synthesis curves were derived for the relationship between noise levels and the percentage of highly-annoyed (%HA) and the percentage of annoyed (%A) for the combined noise sources.

We report the first fluorescent diamino-chalcone library and its application in the discovery of a mouse embryonic stem cell (mESC) probe. CDg4, a novel green fluorescent mESC probe was discovered through a high-content image based screening of 160 members of the chalcone library. Interestingly, the molecular binding target of CDg4 was identified as the glycogen of the stem cell colony surface, rather than a conventional protein target from an intracellular source.

A bodipy probe was developed for site-specific labeling of tagged proteins inside live cells which displays a large spectral change upon covalent coupling to the designed peptide that contains two pairs of Arg-Cys.

A novel and efficient strategy has been developed to synthesize privileged tetrahydro-1,4-benzodiazepines with excellent yields and purities; this synthetic pathway was established by the revitalization of the Leuckart-Wallach (LW) reaction via solid-phase synthesis.