Synthesis of the 3-sulfates of N-acetylcysteine conjugated bile acids (BA-NACs) and their transient formation from BA-NACs and subsequent hydrolysis by a rat liver cytosolic fraction as shown by liquid chromatography/electrospray ionization-mass spectrometry.

Previous work from this laboratory has reported the chemical synthesis of N-acetylcysteine (NAC) conjugates of natural bile acids (BAs) and shown that such novel conjugates can be formed in vivo in rats to which NAC has been administered. The subsequent fate of such novel conjugates is not known. One possible biotransformation is sulfation, a major pathway for BAs N-acylamidates in patients with cholestatic liver disease.

Chemical synthesis of N-acetylcysteine conjugates of bile acids and in vivo formation in cholestatic rats as shown by liquid chromatography/electrospray ionization-linear ion trap mass spectrometry.

N-Acetylcysteine (NAC) conjugates of the five major bile acids occurring in man were synthesized in order to investigate the possible formation in vivo of these conjugates. Upon collision-induced dissociation, structurally informative daughter ions were observed. The transformation of cholyl-adenylate and cholyl-CoA thioester into a N-acetyl-S-(cholyl)cysteine by rat hepatic glutathione S-transferase was confirmed by liquid chromatography/electrospray ionization-linear ion trap mass spectrometry (LC/ESI-MS(2)).

Syntheses of NPTX-594 analogs with thiol-containing fluorophores to develop a probe for analysis of binding mode between spider toxins and glutamate receptors.

NPTX-594 is a neurotoxic acylpolyamine isolated from a Madagascar Joro spider and acts as a specific blocker of glutamate receptors (GluRs). The present study reports the creation of novel NPTX-594 analogs with thiol-containing fluorophores for use as visualization probes for the analysis of the binding mode between spider toxins and GluRs, together with the result of their cricket bioassay.

Syntheses and biological activities of fluorescent-labeled analogs of acylpolyamine toxin NPTX-594 isolated from the venom of Madagascar Joro spider.

Acylpolyamine-type spider toxins are known to be potent and specific blockers against glutamate receptors (GluRs). The present study describes the syntheses and biological activities of several fluorescent-labeled analogs related to a Madagascar Joro spider toxin NPTX-594 to analyze visually the unknown interaction between spider toxins and GluRs.

Formation and biliary excretion of glutathione conjugates of bile acids in the rat as shown by liquid chromatography/electrospray ionization-linear ion trap mass spectrometry.

Acyl-adenylates and acyl-CoA thioesters of bile acids (BAs) are reactive acyl-linked metabolites that have been shown to undergo transacylation-type reactions with the thiol group of glutathione (GSH), leading to the formation of thioester-linked GSH conjugates. In the current study, we examined the transformation of cholyl-adenylate (CA-AMP) and cholyl-coenzyme A thioester (CA-CoA) into a cholyl-S-acyl GSH (CA-GSH) conjugate by rat hepatic glutathione S-transferase (GST). The reaction product was analyzed by liquid chromatography (LC)/electrospray ionization (ESI)-linear ion trap mass spectrometry (MS).

How the pi conjugation length affects the fluorescence emission efficiency.

How the pi conjugation length affects the fluorescence emission efficiency is elucidated by examination of the theoretical and experimental relationship between absolute quantum yield (Phi(f)) and magnitude (Api) of the pi conjugation length in the excited singlet state, which provides a novel concept for molecular design for highly fluorescent organic compounds. As a tool to predict Phi(f) from a structural model, (nu(a) - nu(f))1/2 x a3/2 (nu(a): wavenumber of absorption maximum, nu(f): wavenumber of emission maximum, a: molecular radius) could be used instead of Api. The concept should be valuable for potential applications to (1) examination of an excited singlet state structure (for example, coplanarity of excited-state molecules) and (2) molecular design of novel materials, in which the excited singlet state plays an important role, such as highly efficient fluorophores, electroluminescent materials, photoconducting materials, and nonlinear optical materials.

Photophysical properties of oligophenylene ethynylenes modified by donor and/or acceptor groups.

To create highly fluorescent organic compounds in longer wavelength regions, and to gain physical chemistry insight into the photophysical characteristics, we investigated photophysical properties (Phi(f), lambda(em), tau, lambda(abs), epsilon, k(r), and k(d)) and their controlling factor dependence of the following pi-conjugated molecular rods consisting of p-phenyleneethynylene units modified by donor (OMe) and/or acceptor (CN): (1) side-donor modification systems (SD systems), (2) side-acceptor modification systems (SA systems), and (3) systems consisting of donor block and acceptor block (BL systems). As a result, very high Phi(f) values (>0.95) were obtained for BL systems.

Block modification of rod-shaped pi conjugated carbon frameworks with donor and acceptor groups toward highly fluorescent molecules: synthesis and emission characteristics.

To create organic molecules that are highly fluorescent at a longer wavelength region, we investigated the synthesis (using Pd-catalyzed cross-coupling) and photophysical properties (Phi(f), lambda(em), tau, lambda(abs), and epsilon) of the following pi conjugated molecular rods consisting of p-phenyleneethynylene units modified by donor (OMe) and/or acceptor (CN) groups: (1) side-donor modification systems (SD systems), (2) side-acceptor modification systems (SA systems), and (3) systems consisting of a donor block and an acceptor block (BL systems). As a consequence, very high Phi(f) values (>0.95) were obtained for BL systems.

Biological evaluation of fluorinated p-boronophenylalanine derivatives as a boron carrier.

Boron neutron capture therapy (BNCT) and magnetic resonance imaging (MRI) are quite attractive techniques for treatment and diagnosis of cancer, respectively. In order to develop practical materials utilizing both for BNCT and MRI, fluorinated p-boronophenylalanines and their alcohol derivatives had already been designed and synthesized. In the present paper the cytotoxicity, the incorporated amount into cancer cells, and the tumor cell killing effects of these compounds were elucidated to evaluate their usefulness as a boron carrier.

Analysis of bile acid glutathione thioesters by liquid chromatography/electrospray ionization-tandem mass spectrometry.

The formation of thioester-linked glutathione (GSH) conjugates of bile acids (BAs) is presumed to occur via trans-acylation reactions between GSH and reactive acyl-linked metabolites of BAs. The present study examines the chemical reactivity of cholyl-adenylate and cholyl-CoA thioester, acyl-linked metabolites of cholic acid (CA), with GSH to form CA-GSH conjugate in vitro. The authentic specimen of CA-GSH was synthesized along with GSH conjugates of four common BAs found in the human body.

Synthesis and evaluation as MRI probe of the trifluoromethylated p-boronophenylalanine and its alcohol derivative.

Boron-neutron capture therapy (BNCT) and magnetic resonance imaging (MRI) are quite attractive techniques for treatment and diagnosis of cancer, respectively. In order to develop practical tools for BNCT and MRI, novel compounds containing both the trifluoromethyl group and 10B atom in a single molecule were designed. In the present study, p-boronophenylalanine and p-boronophenylalaninol with the trifluoromethyl group were synthesized, and 19F NMR measurements of these compounds were carried out.

Rigid molecular architectures that comprise a 1,3,5-trisubstituted benzene core and three oligoaryleneethynylene arms: light-emitting characteristics and pi conjugation between the arms.

In view of increasing interest in light-emitting materials, we have investigated the light-emitting characteristics and occurrence of conjugation between arms of star-shaped rigid molecules that comprise a 1,3,5-triethynylbenzene core and methoxy group-substituted oligo(p-phenylethynylene) arms. Consequently, we achieved the ultimate goal (Phif approximately 1.0, log epsilon > 5) for organic molecules with respect to light-emitting ability by creating very intense violet-blue (8, Phif = 0.

Quantitative analysis of the structure-hydrophobicity relationship for di- and tripeptides based on voltammetric measurements with an oil/water interface.

The transfer of 18 di- and 27 tripeptides with un-ionizable amino acid side chains at a nitrobenzene/water (NB/W) interface was studied by cyclic voltammetry. The reversible half-wave potential (E(r)(1/2)), i.e.

New fluorophores with rod-shaped polycyano pi-conjugated structures: synthesis and photophysical properties.

[reaction: see text] Novel rod-shaped polycyano-oligo(phenyleneethynylene)s were synthesized by Pd cross-coupling reaction. Polycyano groups were found to greatly improve the emission efficiency (Phi(f)) of OPEs. By the end donor modification, we achieved the creation of very intense blue light-emitting fluorophore with the SMe group (Phi(f) = 0.

Study on the compounds containing 19F and 10B atoms in a single molecule for the application to MRI and BNCT.

Magnetic resonance imaging (MRI) and boron-neutron capture therapy (BNCT) are quite attractive techniques for diagnosis and treatment of cancer, respectively. In order to progress the study on both MRI and BNCT, the novel compounds containing 19F and 10B atoms in a single molecule were designed and synthesized. In the present paper, the syntheses and the internalization rates into tumor cells of these compounds are elucidated.

Light-emitting efficiency tuning of rod-shaped pi conjugated systems by donor and acceptor groups.

In view of the increasing importance of highly efficient light-emitting materials in chemistry, biological science, and materials science, we investigated the light-emitting efficiency tuning of rod-shaped oligo(p-phenylene ethynylene)s (OPEs, trimeric to pentameric systems) by donor and acceptor groups, so that they emit the very intense fluorescence (Phif approximately 1.0, log epsilon approximately 5) at 460 nm as the desired wavelength region. This goal was achieved by side modification by MeO (donor) groups and end modification by a CN-substituted benzene ring or CF3-substituted pyridine ring (acceptor) of tetrameric p-phenylene ethynylene rod-shaped molecules (Phif = 0.

A study of a Calpha,beta-didehydroalanine homo-oligopeptide series in the solid-state by 13C cross-polarization magic angle spinning NMR.

The fully extended peptide conformation (2.0(5)-helix) has been investigated for the first time in the solid-state by 13C cross-polarization magic angle spinning NMR. The compounds examined are members of a terminally protected, homo-oligopeptide series (from monomer through hexamer) based on Calpha,beta-didehydroalanine.