Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis

Blood levels of the vitamin D₃ (D₃) metabolites 25-hydroxyvitamin D₃ (25(OH)D₃), 24R,25-dihydroxyvitamin D₃, and 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) are recognized indicators for the diagnosis of bone metabolism-related diseases, D₃ deficiency-related diseases, and hypercalcemia, and are generally measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS) using an isotope dilution method. However, other D₃ metabolites, such as 20-hydroxyvitamin D₃ and lactone D₃, also show interesting biological activities and stable isotope-labeled derivatives are required for LC-MS/MS analysis of their concentrations in serum. Here, we describe a versatile synthesis of deuterium-labeled D₃ metabolites using A-ring synthons containing three deuterium atoms. Deuterium-labeled 25(OH)D₃ (2), 25(OH)D₃-23,26-lactone (6), and 1,25(OH)₂D₃-23,26-lactone (7) were synthesized, and successfully applied as internal standards for the measurement of these compounds in pooled human serum. This is the first quantification of 1,25(OH)₂D₃-23,26-lactone (7) in human serum.     

Noncovalent Modification of Cycloparaphenylene by Catenane Formation Using an Active Metal Template Strategy**

The active metal template (AMT) strategy is a powerful tool for the formation of mechanically interlocked molecules (MIMs) such as rotaxanes and catenanes, allowing the synthesis of a variety of MIMs, including π-conjugated and multicomponent macrocycles. Cycloparaphenylene (CPP) is an emerging molecule characterized by its cyclic π-conjugated structure and unique properties. Therefore, diverse modifications of CPPs are necessary for its wide application. However, most CPP modifications require early stage functionalization and the direct modification of CPPs is very limited. Herein, we report the synthesis of a catenane consisting of [9]CPP and a 2,2′-bipyridine macrocycle as a new CPP analogue that contains a reliable synthetic scaffold enabling diverse and concise post-modification. Following the AMT strategy, the [9]CPP-bipyridine catenane was successfully synthesized through Ni-mediated aryl-aryl coupling. Catalytic C−H borylation/cross-coupling and metal complexation of the bipyridine macrocycle moiety, an effective post-functionalization method, were also demonstrated with the [9]CPP-bipyridine catenane. Single-crystal X-ray structural analysis revealed that the [9]CPP-bipyridine catenane forms a tridentated complex with an Ag ion inside the CPP ring. This interaction significantly enhances the phosphorescence lifetime through improved intermolecular interactions.     

Photo- and protonation-induced changes in structures and physical properties of azo-conjugated metal complex systems

Novel photo- and proton-coupled behavior of azo-conjugated metal complexes is described. The trans-to-cis isomerization of azoferrocene proceeds not only by the photoexcitation of the π-π* transition band but also by photoexcitation of the MLCT (d-π* transition) band, by a protonation-deprotonation cycle (proton-coupled isomerization), and by an oxidation-reduction cycle (redox isomerization). A platinum tolylazophenylenedithiolato complex shows reversible trans-to-cis photoisomerization, protochromism, and novel proton-coupled cis-to-trans isomerization.