Arylboronic esters can be used as versatile reagents in organic synthesis, as represented by Suzuki-Miyaura cross-coupling. Here we report a serendipitous finding that simple arylboronic esters are phosphorescent in the solid state at room temperature with a lifetime on the order of several seconds. The phosphorescence properties of arylboronic esters are remarkable in light of the general notion that phosphorescent organic molecules require heavy atoms and/or carbonyl groups for the efficient generation of a triplet excited state. Theoretical calculations on phenylboronic acid pinacol ester indicated that this molecule undergoes an out-of-plane distortion at the (pinacol)B-C moiety in the T excited state, which is responsible for its phosphorescence. A compound survey with 19 arylboron compounds suggested that the phosphorescence properties might be determined by solid-state molecular packing rather than by the patterns and numbers of boron substituents on the aryl units. The present finding may update the general notion of phosphorescent organic molecules.

Reverse transcriptases (RTs) from avian myeloblastosis virus (AMV) and Moloney murine leukaemia virus (MMLV) have been most extensively used as a tool for conversion of RNA to DNA. In this study, we compared the thermal stabilities of AMV RT and MMLV RT by observing their irreversible thermal inactivation. The temperatures reducing initial activity by 50% in 10-min incubation, T(50), of AMV RT were 47 degrees C without the template-primer (T/P), poly(rA)-p(dT)(12-18), and 52 degrees C with the T/P (28 microM). T(50) of MMLV RT were 44 degrees C without the T/P and 47 degrees C with the T/P (28 microM). Unexpectedly, AMV RT was considerably activated when incubated with the T/P at 45 and 48 degrees C. Such activation was not observed in MMLV RT. These results suggest that AMV RT and MMLV RT are different in the following: (i) The intrinsic thermal stability of AMV RT is higher than that of MMLV RT; (ii) AMV RT is activated by thermal treatment with the T/P at 45-48 degrees C; and (iii) AMV RT is stabilized by the T/P more potently than MMLV RT. Thermodynamic analysis indicates that thermal inactivation of AMV RT and MMLV RT is due to the large entropy change of activation for thermal inactivation.

Imeglimin is an orally administered first‐in‐class drug to treat type 2 diabetes mellitus (T2DM) and is mainly excreted unchanged by the kidneys. The present study aimed to define the pharmacokinetic (PK) characteristics of imeglimin using population PK analysis and to determine the optimal dosing regimen for Japanese patients with T2DM and chronic kidney disease (CKD). Imeglimin plasma concentrations in Japanese and Western healthy volunteers, and patients with T2DM, including patients with mild to severe CKD with an estimated glomerular filtration rate (eGFR) greater than 14 ml/min/1.73 m 2 were included in a population PK analysis. PK simulations were conducted using a population PK model, and the area under concentration‐time curve (AUC) was extrapolated with power regression analysis to lower eGFR. The influence of eGFR, weight, and age on apparent clearance and of dose on relative bioavailability were quantified by population PK analysis. Simulations and extrapolation revealed that the recommended dosing regimen based on the AUC was 500 mg twice daily (b.i.d.) for patients with eGFR 15–45 ml/min/1.73 m 2 , and 500 mg with a longer dosing interval was suggested for those with eGFR less than 15. Simulations revealed that differences in plasma AUCs between Japanese and Western patients at the same dose were mainly driven by a difference in the eGFR and that the plasma AUC after 1000 and 1500 mg b.i.d. in Japanese and Western patients, respectively, was comparable in the phase IIb studies. These results indicate suitable dosages of imeglimin in the clinical setting of T2DM with renal impairment.

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