Breed-related differences in age-dependent down-regulation of the ß1-adrenoceptor and adenylate cyclase activity in atrial and ventricular myocardium of Cröllwitzer ("wild-type") turkeys.

In conventional meat-type (British United Turkey (B.U.T.) Big 6) turkey hearts, it has been shown that all cardiac chambers exhibit down-regulation of the ß1-adrenoceptors (ß1-AR) and concomitantly cAMP accumulation with increasing age regardless of sex. In this study we proved the hypothesis that breed differences exist in age-dependent alterations in the ß1-AR system. Right (RA) and left (LA) atrial as well as right (RV) and left (LV) ventricular tissues were collected from male and female Cröllwitzer "wild-type" turkey poults of increasing age (6 wk, 12 wk, 16 wk, 21 wk). The ß1-AR density and function were quantified by (-)-[125I]-iodocyanopindolol (ICYP) radioligand binding analysis in cell membranes from 4 cardiac chambers. Basal and stimulated cAMP production was determined as indicator of the receptor function. Wild-type turkeys showed significantly higher heart to body weight ratio than the meat-type B.U.T. Big 6 turkeys. In both sexes of Cröllwitzer turkey hearts, the ß1-AR density decreased with age but significance was reached in male cardiac chambers. The receptor affinity (KD) and subtype distribution were not altered. Sex had no effect on age-related decrease in receptor density but had an effect on adenylate cyclase (AC) activity and subsequently cAMP production. In male Cröllwitzer turkey hearts of all ages, cAMP remained at same level, whereas this was even increased in female cardiac chambers. Thus, breed affected age-related receptor-, G-protein and AC-stimulated cAMP formation in normal ventricles and atria, with females exhibiting pronounced increase with age. This suggests that the receptor signaling in wild-type turkey hearts is not as blunted as in hearts of meat-type turkey poults in which stressful farming conditions and fast growing lead to receptor down-regulation.

Differential regulation of the ß-adrenoceptor density and cyclic AMP level with age and sex in turkey cardiac chambers.

Decreased responses of the heart to ß-adrenoceptor stimulation with aging have been shown to occur merely in selected heart chambers in relation to increased catecholamine levels. However, there are no systematic studies that investigate all cardiac chambers with regard to receptor density and cAMP (adenosine 3', 5'-cyclic monophosphate) responses. We used meat-type turkey poults (British United Turkey (B.U.T.) Big 6) with increasing age because their heart seems to decrease in weight in relation to body weight and they are often used as an animal model for heart failure. The receptor density and distribution were quantified by radioligand binding analysis using (-)-[(125)I]-iodocyanopindolol and ß-adrenoceptor subtype-specific antagonists (ICI 118.551 and CGP 20712 A) in membranes of four cardiac chambers (right and left atria and ventricles) of 6-week-, 12-week-, 16/21-week-, and 57-week-old B.U.T. BIG 6 turkeys. Receptor function was determined by measuring basal and stimulated cAMP production. In both sexes, the ß-adrenoceptor density decreased significantly in all chambers with age without altered ß-adrenoceptor subtype distribution. The receptor affinity (KD) to the radioligand was similar in hearts of all age groups. ß-adrenoceptor-(isoproterenol and guanosine 5'-triphosphate), G-protein-(NaF) and catalytic unit of adenylate cyclase (forskolin, Mn(2+)) mediated cAMP responses were not chamber-dependent. Indeed, the cAMP level was significantly lower in 57-week-old hearts than in 6-week-, 12-week-, 16/21-week-old hearts. These data suggest that with increasing age and body weight, the ß-adrenoceptor signal transduction pathway was highly blunted in all cardiac chambers, occurring by decreased receptor density and cAMP responses.

Cationic Titanocene(III) Complexes for Catalysis in Single-Electron Steps.

By exploiting solvent and anion effects, [Cp2Ti](+) complexes for atom-economical catalysis in single-electron steps were developed and applied for the first time. These complexes constitute remarkably stable and active catalysts for radical arylations. The reaction kinetics and catalyst composition were studied by cyclic voltammetry and in situ IR spectroscopy.

Mechanistic study of the titanocene(III)-catalyzed radical arylation of epoxides.

An atom-economical and catalytic arylation of epoxide-derived radicals is described. The key step of the catalytic system is a sequential electron and proton transfer for the rearomatization of the radical σ-complex and catalyst regeneration. Kinetic, computational, spectroscopic, and cyclovoltammetric investigations highlight the key issues of the reaction mechanism and catalyst stabilization by collidine hydrochloride. Studies employing radicophiles rule out the participation of cations as reactive intermediates.

Highly regioselective and chemoselective titanocene mediated Barbier-type allylation reactions.

Titanocene carboxylate 1 is an excellent chemoselective reagent for unprecedented α-regioselective Barbier-type reactions. It constitutes the first titanocene(III) able to tolerate epoxides and readily reduced carbonyl compounds, such as aromatic and α,ß-unsaturated aldehydes.

Substituent effects and supramolecular interactions of titanocene(III) chloride: implications for catalysis in single electron steps.

The electrochemical properties of titanocene(III) complexes and their stability in THF in the presence and absence of chloride additives were studied by cyclic voltammetry (CV) and computational methods. The anodic peak potentials of the titanocenes can be decreased by as much as 0.47 V through the addition of an electron-withdrawing substituent (CO2Me or CN) to the cyclopentadienyl ring when compared with Cp2TiCl. For the first time, it is demonstrated that under the conditions of catalytic applications low-valent titanocenes can decompose by loss of the substituted ligand. The recently discovered effect of stabilizing titanocene(III) catalysts by chloride additives was analyzed by CV, kinetic, and computational studies. An unprecedented supramolecular interaction between [(C5H4R)2TiCl2](-) and hydrochloride cations through reversible hydrogen bonding is proposed as a mechanism for the action of the additives. This study provides the critical information required for the rational design of titanocene-catalyzed reactions in single electron steps.

Radical 4-exo cyclizations via template catalysis.

The mechanism of catalytic 4-exo cyclizations without gem-dialkyl substitution was investigated by a comparison of cyclic voltammetry, EPR, and computational studies with previously published synthetic results. The most active catalyst is a super-unsaturated 13-electron titanocene(III) complex that is formed by supramolecular activation through hydrogen bonding. The template catalyst binds radicals via a two-point binding that is mandatory for the success of the 4-exo cyclization. The computational investigations revealed that formation of the observed trans-cyclobutane product is not possible from the most stable substrate radical. Instead, the most stable product is formed with the lowest energy of activation from a disfavored substrate in a Curtin-Hammett related scenario.