Synthesis and Characterization of Hydrophilic Trityl Radical TFO for Biomedical and Biophysical Applications

Tetrathiatriarylmethyl (TAM, trityl) radicals have found wide applications as spin probes/labels for EPR spectroscopy and imaging, and as polarizing agents for dynamic nuclear polarization. The high hydrophilicity of TAM radicals is essential for their biomedical applications. However, the synthesis of hydrophilic TAM radicals (e.g., OX063) is extremely challenging and has only been reported in the patent literature, to date. Herein, an efficient synthesis of a highly water-soluble TAM radical bis(8-carboxyl-2,2,6,6-tetramethylbenzo[1,2-d:4,5-d′]bis([1,3]dithiol-4-yl)-mono-(8-carboxyl-2,2,6,6-tetrakis(2-hydroxyethyl)benzo[1,2-d:4,5-d′]bis([1,3]dithiol-4-yl)methyl (TFO), which contains four additional hydroxylethyl groups, relative to the Finland trityl radical CT-03, is reported. Similar to OX063, TFO exhibits excellent properties, including high water solubility in phosphate buffer, low log P, low pK_a, long relaxation times, and negligible binding with bovine serum albumin. On the other hand, TFO has a sharper EPR line and higher O₂ sensitivity than those of OX063. Therefore, in combination with its facile synthesis, TFO should find wide applications in magnetic resonance related fields and this synthetic approach would shed new light on the synthesis of other hydrophilic TAM radicals.     

Consistency of the penalized MLE for two-parameter gamma mixture models

Two-parameter gamma distributions are widely used in liability theory, lifetime data analysis, financial statistics, and other areas. Finite mixtures of gamma distributions are their natural extensions, and they are particularly useful when the population is suspected of heterogeneity. These distributions are successfully employed in various applications, but many researchers falsely believe that the maximum likelihood estimator of the mixing distribution is consistent. Similarly to finite mixtures of normal distributions, the likelihood function under finite gamma mixtures is unbounded. Because of this, each observed value leads to a global maximum that is irrelevant to the true distribution. We apply a seemingly negligible penalty to the likelihood according to the shape parameters in the fitted model. We show that this penalty restores the consistency of the likelihoodbased estimator of the mixing distribution under finite gamma mixture models. We present simulation results to validate the consistency conclusion, and we give an example to illustrate the key points.     

Copper‐Catalyzed Annulation of 2‐Formylazoles with Aminoiodopyrazoles: Synthesis of New Heterocyclic Ring Systems

Various 2‐formylazoles underwent CuI/sparteine‐catalyzed annulation with 1‐substituted‐4‐iodo‐5‐aminopyrazoles to produce four new heterocyclic ring systems. The reaction was demonstrated for 2‐formylpyrroles, 2‐formylindoles, 2‐formylimidazole, and 3‐methyl‐5‐formylpyrazole. 3‐Substitution of the iodopyrazole was tolerated.