(13)C/(15)N-Enriched l-Dopa as a Triple-Resonance NMR Probe to Monitor Neurotransmitter Dopamine in the Brain and Liver Extracts of Mice.

In an attempt to monitor µm-level trace constituents, we applied here (1)H-{(13)C-(15)N} triple-resonance nuclear magnetic resonance (NMR) to (13)C/(15)N-enriched l-Dopa as the inevitable precursor of the neurotransmitter dopamine in the brain. The perfect selectivity (to render endogenous components silent) and µm-level sensitivity (700 MHz spectrometer equipped with a cryogenic probe) of triple-resonance allowed the unambiguous and quantitative metabolic and pharmacokinetic analyses of administered l-Dopa/dopamine in the brain and liver of mice. The level of dopamine generated in the brain (within the range 7-76 µm, which covers the typical stimulated level of ∼30 µm) could be clearly monitored ex vivo, but was slightly short of the detection limit of a 7 T MR machine for small animals. This work suggests that µm-level trace constituents are potential targets of ex vivo monitoring as long as they contain N atom(s) and their appropriate (13)C/(15)N-enrichment is synthetically accessible.

Pharmacokinetics of Chiral Dendrimer-Triamine-Coordinated Gd-MRI Contrast Agents Evaluated by in Vivo MRI and Estimated by in Vitro QCM.

Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs), which showed longitudinal relaxivity (r1) values about four times higher than that of clinically used Gd-DTPA (Magnevist(®), Bayer). In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T). In this study, the association constants (K(a)) of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA), measured and calculated with a quartz crystal microbalance (QCM) in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The K(a) values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo.

Correction: Efficient singlet oxygen generation from sugar pendant C60 derivatives for photodynamic therapy.

Correction for 'Efficient singlet oxygen generation from sugar pendant C60 derivatives for photodynamic therapy' by Shigenobu Yano et al., Chem. Commun., 2015, DOI: 10.1039/c5cc07353g.

Efficient singlet oxygen generation from sugar pendant C60 derivatives for photodynamic therapy.

The amidation reaction between C60 with an activated ester group (1) and acetylated Glc (AcGlc) with an amino group (2) was performed to yield the target AcGlc-pendant C60 compound (3). The water soluble deacetylated compound, Glc-pendant C60 compound (4), exhibited high photocytotoxicity against HeLa cells due to the more efficient singlet oxygen generation as compared with that of Glc-pendant azafulleroids.

Magnetic resonance imaging of tumor with a self-traceable polymer conjugated with an antibody fragment.

A (13)C-enriched phosphorylcholine polymer ((13)C-PMPC) as a self-traceable MR (magnetic resonance) tag was conjugated with a fragment (scFv) of Herceptin, a clinical antibody against antigen Her2. When injected in model mice bearing Her2(+) (gastric) and Her2(-) (pancreatic) tumors, the antibody-tag conjugate (13)C-PMPC-scFv selectively accumulated in the Her2(+) tumor with a rapid build-up/decay (accumulation/clearance) profile and, with the use of the (1)H-(13)C double-resonance (heteronuclear correlation) technique, the Her2(+) gastric tumor was clearly MR imaged.

Magnetic resonance imaging of tumor with a self-traceable phosphorylcholine polymer.

Polymers are concentration-amplified with respect to the monomeric units. We show here that a phosphorylcholine polymer enriched with (13)C/(15)N at the methyl groups is self-traceable by multiple-resonance (heteronuclear-correlation) NMR in tumor-bearing mice inoculated with the mouse rectal cancer cell line (colon 26). Preliminary measurements indicated that the present polymeric nanoprobe was satisfactorily distinguished from lipids and detectable with far sub-micromolar spectroscopic and far sub-millimolar imaging sensitivities. Detailed ex vivo and in vivo studies for the tumor-bearing mice administered the probe with a mean molecular weight of 63,000 and a mean size of 13 nm, revealed the following: (1) this probe accumulates in the tumor highly selectively (besides renal excretion) and efficiently (up to 30% of the injected dose), (2) the tumor can thus be clearly in vivo imaged, the lowest clearly imageable dose of the probe being 100 mg/kg or 2.0 mg/20-g mouse, and (3) the competition between renal excretion and tumor accumulation is size-controlled; that is, the larger (higher molecular-weight) and smaller (lower molecular-weight) portions of the probe undergo tumor accumulation and renal excretion, respectively. The observed size dependence suggests that the efficient tumor-targeting of the present probe is stimulated primarily by the so-called enhanced permeability and retention (EPR) effect, that is, size-allowed invasion of the probe into the tumor tissue via defective vascular wall. Self-traceable polymers thus open an important area of magnetic resonance imaging (MRI) of tumors and may provide a highly potential tool to visualize various delivery/localization processes using synthetic polymers.

Size-controlled and biocompatible Gd2 O3 nanoparticles for dual photoacoustic and MR imaging.

The synthesis, characterization, and functional evaluation of new size-controlled and biocompatible Gd(2) O(3) nanoparticles as a bimodal contrast agent for use in photoacoustic (PA) and magnetic resonance (MR) imaging are reported. These nanoparticles show a clear PA image by themselves, without conjugation with gold, rare earth metals, or dyes. Relaxivity measurement by MR imaging clearly shows that their relaxivity, r(1) , is twice that of clinically available Gd-DTPA.

Rhodium-catalyzed linear codimerization and cycloaddition of ketenes with alkynes.

A novel rhodium-catalyzed linear codimerization of alkyl phenyl ketenes with internal alkynes to dienones and a novel synthesis of furans by an unusual cycloaddition of diaryl ketenes with internal alkynes have been developed. These reactions proceed smoothly with the same rhodium catalyst, RhCl(PPh(3))(3), and are highly dependent on the structure and reactivity of the starting ketenes.

Sigmasigma* transition in anti,cisoid alternating oligosilanes: clear-cut evidence for suppression of conjugation effect by a cisoid turn.

On the basis of the UV absorption spectra of the anti,cisoid alternating oligosilanes, the first experimental clear-cut evidence was presented for the generally accepted idea that the sigma conjugation in polysilanes does not effectively extend through a tetrasilane fragment with a small dihedral angle such as a cisoid turn.