Porphyrin isomers: Geometry, tautomerism, geometrical isomerism, and stability

Density functional calculations have been carried out on free-base porphyrin (1) and its seven possible isomers (2-8) with an N-4-metal coordination core. A total of 27 structures resulting from geometrical isomerism ((E/Z)-configurations) and NH tautomerism were studied. Geometries were fully optimized with the nonlocal density functional approximation (BLYP) using the 3-21G and 6-31G{*}{*} basis sets. The calculated geometries compare favorably with the available X-ray crystal structures. Porphycene (2) is predicted to be the most stable among the eight isomers and is about 2 kcal/mol more stable than porphyrin due to its exceptionally strong hydrogen bonding. Compounds 5-8 are much less stable than porphyrin due to severe ring strain in these compounds. When a -(CH)(n)-linker is in a (Z)-configuration, each compound is planar or nearly planar with significant pi-delocalization; the corresponding (E)-configured structures are predicted to be somewhat distorted into bowl-like geometries in order to avoid severe steric interactions involving the inner hydrogens

A single sample GnRHa stimulation test in the diagnosis of precocious puberty

<p>Abstract</p> <p>Context</p> <p>Gonadotropin-releasing hormone (GnRH) has been the standard test for diagnosing central precocious puberty. Because GnRH is no longer available, GnRH analogues (GnRHa) are now used. Random LH concentration, measured by the third-generation immunochemiluminometric assay, is a useful screening tool for central precocious puberty. However, GnRHa stimulation test should be considered, when a basal LH measurement is inconclusive. However optimal sampling times for luteinizing hormone (LH) have yet to be established.</p> <p>Purpose</p> <p>To determine the appropriate sampling time for LH post leuprolide challenge.</p> <p>Methods</p> <p>A retrospective analysis of multi-sample GnRHa stimulation tests performed in 155 children (aged 1–9 years) referred for precocious puberty to Texas Children’s Hospital.</p> <p>After 20 mcg/kg of SQ leuprolide acetate, samples were obtained at 0, 1, 3, and 6 hours.</p> <p>Results</p> <p>Of 71 children with clinical evidence of central precocious puberty, fifty nine children had a peak LH >5 mIU/mL. 52 (88%) of these responders had positive responses at 1 hour (95% CI is 80–96%), whereas all 59 children (100%) had a peak LH response >5 mIU/mL at 3 hours (95% CI is 94-100%), P = 0.005.</p> <p>Conclusions</p> <p>A single serum LH sample collected 3 hours post GnRHa challenge is the optimal sample to establish the diagnosis of central precocious puberty.</p