Conversion from Heterometallic to Homometallic Metal-Organic Frameworks.

Two new heterometallic metal-organic frameworks (MOFs), LnZnTPO 1 and 2, and two homometallic MOFs, LnTPO 3 and 4 (Ln=Eu for 1 and 3, and Tb for 2 and 4; H3 TPO=tris(4-carboxyphenyl)phosphine oxide) were synthesized, and their structures and properties were analyzed. They were prepared by solvothermal reaction of the C3 -symmetric ligand H3 TPO with the corresponding metal ion(s) (a mixture of Ln3+ and Zn2+ for 1 and 2, and Ln3+ alone for 3 and 4). Single-crystal XRD (SXRD) analysis revealed that 1 and 3 are isostructural to 2 and 4, respectively. TGA showed that the framework is thermally stable up to about 400 °C for 1 and 2, and about 450 °C for 3 and 4. PXRD analysis showed their pore-structure distortions without noticeable framework-structure changes during drying processes. The shapes of gas sorption isotherms for 1 and 3 are almost identical to those for 2 and 4, respectively. Solvothermal immersion of 1 and 2 in Tb3+ and Eu3+ solutions resulted in the framework metal-ion exchange affording 4 and 3, respectively, as confirmed by photoluminescence (PL), PXRD, IR, inductively coupled plasma atomic emission spectroscopy (ICP-AES), and energy-dispersive X-ray (EDX) analyses.

Simultaneous enhancement of transition dipole strength and vibrational lifetime of an alkyne IR probe viaπ-d backbonding and vibrational decoupling.

Alkyne infrared (IR) probes 1-6 with Si and S (or Se) atoms incorporated into the C[triple bond, length as m-dash]C bond were synthesized, and the vibrational properties of their C[triple bond, length as m-dash]C stretch mode were studied using Fourier transform infrared (FTIR) and femtosecond IR pump-probe (IR PP) spectroscopies in combination with quantum chemical calculations. From FTIR studies, the transition dipole strengths (in units of 10-2 D2) of 1-3 having the Si atom were measured to be 1.85, 3.32, and 2.52, whereas those of 4-6 having no Si atom were measured to be 0.13, 0.20, and 0.17, respectively, in CHCl3. Thus, the increase in the transition dipole strength of the C[triple bond, length as m-dash]C stretch mode upon incorporation of the Si atom into the C[triple bond, length as m-dash]C bond is by a factor of about 14 or higher. The large increase in the transition dipole strength of the C[triple bond, length as m-dash]C stretch mode upon such Si incorporation is attributed to π-d backbonding between the C[triple bond, length as m-dash]C group's π and Si atom's d orbitals. From IR PP experiments, the vibrational lifetimes of the C[triple bond, length as m-dash]C stretch mode in 1-3 having none, S, and Se atoms were determined to be 5.7 ± 0.7, 13.0 ± 1.1, and 94.2 ± 5.8 ps, respectively, in CHCl3. Thus, the increase in the vibrational lifetime of the C[triple bond, length as m-dash]C stretch mode upon incorporation of the S (or Se) atom between the phenyl ring and the C[triple bond, length as m-dash]C bond is by a factor of about 2 (or 16) or higher. The large increase in the vibrational lifetime of the C[triple bond, length as m-dash]C stretch mode upon such S (or Se) incorporation is attributed to its heavy atom effect impeding vibrational couplings between the C[triple bond, length as m-dash]C stretch and phenyl ring vibrations. From two-dimensional infrared (2DIR) experiments, the large transition dipole strength and long vibrational lifetime of 3 containing the Si and S (or Se) atoms were shown to enable the measurement of its 2DIR spectra up to 500 ps. The strongly absorbing alkynes with long vibrational lifetimes will be a promising probe of molecular dynamics in nonlinear vibrational spectroscopy and imaging on an extended time scale.

Development of a COX-2-Selective Fluorescent Probe for the Observation of Early Intervertebral Disc Degeneration.

Cyclooxygenase-2 (COX-2) is a biomolecule known to be overexpressed in inflammation. Therefore, it has been considered a diagnostically useful marker in numerous studies. In this study, we attempted to assess the correlation between COX-2 expression and the severity of intervertebral disc (IVD) degeneration using a COX-2-targeting fluorescent molecular compound that had not been extensively studied. This compound, indomethacin-adopted benzothiazole-pyranocarbazole (IBPC1), was synthesized by introducing indomethacin-a compound with known selectivity for COX-2-into a phosphor with a benzothiazole-pyranocarbazole structure. IBPC1 exhibited relatively high fluorescence intensity in cells pretreated with lipopolysaccharide, which induces inflammation. Furthermore, we observed significantly higher fluorescence in tissues with artificially damaged discs (modeling IVD degeneration) compared to normal disc tissues. These findings indicate that IBPC1 can meaningfully contribute to the study of the mechanism of IVD degeneration in living cells and tissues and to the development of therapeutic agents.

Absolute oral and subcutaneous bioavailability of ortho-topolin riboside in mice.

Among essential phytohormones playing a pivotal role in regulating growth and development, ortho-topolin riboside (oTR) exerts the most substantial anti-tumor potency in various cancer cell lines. This study was designed to establish a quantitative determination method for oTR in mouse plasma using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), to validate the analytical method including stability, and to characterise its pharmacokinetic behaviour in mice. After simple protein precipitation with acetonitrile including kinetin riboside (internal standard), oTR was eluted on a reversed-phase column using a mobile phase of water and acetonitrile (3:7 v/v, including 0.1% formic acid). The protonated precursor ion [M+H]+ and major fragment ion were confirmed at m/z 374.06 and 241.99 for oTR, and 348.23 and 216.06 for the IS, respectively. oTR was stable under bench and storage conditions. The analytical method met the criteria of FDA-validated bioanalytical methods and was successfully applied to a pharmacokinetic study for the first time following oral, subcutaneous, and intravenous administrations. While oTR was merely absorbed by an oral route, 90% of the absolute subcutaneous bioavailability was observed.

Root Bark of Morus alba L. and Its Bioactive Ingredient, Ursolic Acid, Suppress the Proliferation of Multiple Myeloma Cells by Inhibiting Wnt/ß-Catenin Pathway.

The root bark of Morus alba L. has cytotoxic activity against several types of cancer cells. However, little is known about its chemopreventive mechanisms and bioactive metabolites. In this study, we showed that M. alba L. root bark extracts (MRBE) suppressed ß-catenin response transcription (CRT), which is aberrantly activated in various cancers, by promoting the degradation of ß-catenin. In addition, MRBE repressed the expression of the ß-catenin/T-cell factor (TCF)-dependent genes, cmyc and cyclin D1, thus inhibiting the proliferation of RPMI-8226 multiple myeloma (MM) cells. MRBE induced apoptosis in MM cells, as evidenced by the increase in the population of annexin VFITC- positive cells and caspase-3/7 activity. We identified ursolic acid in MRBE through LC/mass spectrum (MS) and observed that it also decreased intracellular ß-catenin, c-myc, and cyclin D1 levels. Furthermore, it suppressed the proliferation of RPMI-8226 cells by stimulating cell cycle arrest and apoptosis. These findings suggest that MRBE and its active ingredient, ursolic acid, exert antiproliferative activity by promoting the degradation of ß-catenin and may have significant chemopreventive potential against MM.

Ultrafast Chemical Exchange Dynamics of Hydrogen Bonds Observed via Isonitrile Infrared Sensors: Implications for Biomolecular Studies.

Local probes are indispensable to study protein structure and dynamics with site-specificity. The isonitrile functional group is a highly sensitive and H-bonding interaction-specific probe. Isonitriles exhibit large spectral shifts and transition dipole moment changes upon H-bonding while being weakly affected by solvent polarity. These unique properties allow a clear separation of distinct subpopulations of interacting species and an elucidation of their ultrafast dynamics with two-dimensional infrared (2D-IR) spectroscopy. Here, we apply 2D-IR to quantify the picosecond chemical exchange dynamics of solute-solvent complexes forming between isonitrile-derivatized alanine and fluorinated ethanol, where the degree of fluorination controls their H-bond-donating ability. We show that the molecules undergo faster exchange in the presence of more acidic H-bond donors, indicating that the exchange process is primarily dependent on the nature of solvent-solvent interactions. We foresee isonitrile as a highly promising probe for studying of H-bonds dynamics in the active site of enzymes.

Cyanamide as an Infrared Reporter: Comparison of Vibrational Properties between Nitriles Bonded to N and C Atoms.

Infrared (IR) probes based on terminally blocked ß-cyanamidoalanine (AlaNHCN) 1 and p-cyanamidophenylalanine (PheNHCN) 2 were synthesized, and the vibrational properties of their CN stretch modes were studied using Fourier transform infrared (FTIR) and femtosecond IR pump-probe spectroscopies in combination with quantum chemical calculations. From FTIR studies, it is found that the transition dipole strengths of the cyanamide (NHCN) group in 1 and 2 are much larger than those of the nitrile (CN) group but comparable to those of the isonitrile (NC) and azido (N3) groups in their previously studied analogs. The CN stretch frequencies in 1 and 2 are red-shifted from those in their nitrile analogs but more blue-shifted from the NC and N3 stretch frequencies in their isonitrile and azido analogs. The much larger transition dipole strength and the red-shifted frequency of the cyanamide relative to nitrile group originates from the n → π* interaction between the N atom's nonbonding (n) and CN group's antibonding (π*) orbitals of the NHCN group. Unlike aliphatic cyanamide 1, aromatic cyanamide 2 shows a complicated line shape of the CN stretch spectra. Such a complicated line shape arises from the Fermi resonance between the CN stretch mode of the NHCN group and one of the overtones of the phenyl ring vibrations and can be substantially simplified by deuteration of the NHCN into NDCN group. From IR pump-probe experiments, the vibrational lifetimes of the CN stretch mode in 1 were determined to be 0.58 ± 0.04 ps in D2O and 0.89 ± 0.09 ps in H2O and those in 2 were determined to be 1.64 ± 0.13 ps in CH3OD/dimethyl sulfoxide and 0.30 ± 0.05 and 2.62 ± 0.26 ps in CH3OH. The short time component (0.30 ± 0.05 ps) observed for 2 in CH3OH is attributed to the vibrational relaxation through Fermi resonance. These vibrational lifetimes are close to those of the nitrile and azido groups but shorter than those of the isonitrile group. Consequently, cyanamide behaves like an apparent vibrational hybrid of nitrile and isonitrile in that cyanamide is similar to nitrile in vibrational frequency and lifetime but to isonitrile in transition dipole strength. It is believed that cyanamide has the potential to be a strongly absorbing IR reporter of the conformational and environmental structure and dynamics of biomolecules in comparison to nitrile, a weak absorber.