The migratory insertion of carbon monoxide in pentamethylcyclopentadienyliridium (III) complexes. Structural effects on reactivity and mechanism for rhodium and iridium systems

The reactions of complex (C₅Me₅)Ir(Cl) (CO) (Me) (1a) with cyclohexylisocyanide and phosphines (L=CyNC, PHPh₂, PMePh₂, PMe₂Ph) give the products of alkyl migratory insertion (C₅Me₅Ir(Cl) (COMe) (L), in toluence or tetrahydrofuran at 323 K or higher temperature. The phenyl analogue (C₅Me₅)Ir(Cl)(CO)(Ph) or the iodide complexes (C₅Me₅)Ir(I) (CO) (R) (R=Me, Ph_are not reactive under the same conditions. The reaction of (C₅Me₅)Ir(Cl)(CO)(Me) with PMePh₂ and PMe₂Ph in acetonitrile yields the chloride substitution product [(C₅Me₅)Ir(CO)(L)(Me)]⁺Cl⁻. Kinetic measurements for the reactions of (C₅Me₅)Ir(Cl)(CO)(Me) in toluene are first order in the iridium complex and exhibit a saturation dependence on the incoming donors L. Analysis of the data suggests a two-step process involving (i) rapid formation of a molecular complex [(C₅Me₅)Ir(Cl)(CO)(Me), (L)], in which the structure of 1a is unperturbed within the limits of spectroscopic analysis, and (ii) rate determining methyl migration. The reaction parameters are K for the pre-equilibrium step (K = 1.5 (CyNC), 7.3 (PHPh₂), 7.1 (PMePh₂) dm³ mol⁻¹ at 323 K) and k₂ for the slow carbon---carbon bond formation (k₂ (10⁵) = 6.9 (CyNC), 1.2 (PHPh₂), 1.0 (PMePh₂) s⁻¹ at 323 K). The activation parameters for the methyl migration step in the reaction with PMePh₂ obtained between 308 and 338 K, are ΔH^≠ = 106±16 kJ mol⁻¹ and ΔS^≠ = − 14±5 J K⁻¹ mol⁻¹. The reaction of 1a with PMePh₂ proceeds at similar rates in tetrahydrofuran (K = 3.7 dm³ mol⁻¹, k₂ (10⁵) = 1.2 s⁻¹, 323 K). The crystal structure of (C₅Me₅)Ir(Cl)(COMe) (PMe₂Ph) has been determined by X-ray diffraction. C₂₀H₂₉ClOPIr: M_r = 544.1, monoclinic, P2₁/n, A = 8.084 (2), B = 9.030(2), C = 28.715 (3) Å, β = 91.41 (3)°, Z = 4, D_c = 1.71 g cm⁻³, V = 2095.5 ų, room temperatyre, Mo K, γ = 0.71069, μ = 65.55 cm⁻¹, F(000) = 1044, R = 0.037 for 2453 independent observed reflections. The complex shows a deformed tetrahedral coordination assuming the η⁵-C₅Me₅ molecular fragment as a single coordination site. The iridium-chlorine bond is staggered with respect to two adjacent C(ring)-methyl bonds, while the Ir---P and the Ir---COMe bonds are eclipsed with respect to C(ring)-methyl bonds.     

New regulatory mechanisms in the biosynthesis of pheomelanins: rearrangement vs. redox exchange reaction routes of a transient 2H-1,4-benzothiazine-o-quinonimine intermediate

Pheomelanins, the typical epidermal pigments of red haired, Celtic-type Caucasians, arise from oxidative cyclization of cysteinyldopas, mainly the 5-S-isomer CD, via 1,4-benzothiazines. However, the mechanism and the relative yields of formation of these intermediates have remained poorly defined. We have now examined the course of the oxidation of CD at physiological pHs, under different reaction conditions. Surprisingly, a consumption of CD far exceeding the stoichiometry of the oxidant was observed at low oxidant-to-substrate ratios, low temperatures and high substrate concentrations. The yields of the 3,4-dihydro-1,4-benzothiazine-3-carboxylic acid DHBCA vs. the non-carboxylated analogue DHB in the oxidation mixture, after NaBH₄ reduction, were also found to depend markedly on the reaction conditions. Based on these and other results, a reaction scheme is proposed involving a transient o-quinonimine generated by oxidative cyclization of CD to which three different paths are offered, namely redox exchange with CD to give DHBCA (path A) or intramolecular rearrangement with (path B) or without (path C) decarboxylation, leading to the benzothiazine BTZ and the 3-carboxy analogue BTZCA, respectively. The relative operation of path A vs. path C was assessed by deuterium labeling experiments. These findings point to new mechanisms of regulation of the initial steps of pheomelanogenesis, bearing significant implications on the structure of the final pigment.     

STAT3 modulates CD4+ T mitochondrial dynamics and function in aging

Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria-targeted STAT3 inhibitor, Mtcur-1 lowered complex II activity, prevented age-induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and function in T cells from older adults and partially recapitulated aging-related cytokine profiles. Our data show the mechanistic link among mitoSTAT3, mitochondrial dynamics, function, and T-cell cytokine production.     

Preliminary data on activation of the enzyme of the metabolism of phospholipid bases in various areas of the brain]

The scope of this work was to study the effect of imydazole on base-exchange enzymic system in selected cerebral areas. We have previously demonstrated that imydazole was an activator of phosphatidylserine synthesis in slices of caudate nucleus. This effect lacked in the omogenate we had supposed that this activation by imydazole was not directed on base-exchange enzymic system, but was induced by decrease of cellular cyclic nucleotides amount. Therefore we have investigated the effect of dibutirril-AMPciclic in selected cerebral areas. In addition it was useful to state if activation by imydazole was area-specific or not.     

Eco-ethological Factors Affecting the Scouting and Raiding Behaviour of the Slave-making Ant,Polyergus rufescens Latr. (Hymenoptera,Formicidae)

A dulotic colony of the obligatory slave-making ant Polyergus rufescens was monitored daily in the field (Parma, Italy) from 1100–2000 h over the summers of 1991 and 1992. The first P. rufescens workers to emerge from the nest each day were individually marked and their activity was accurately recorded. The path of 47 such individuals (21 over a complete trip) was followed in detail and mapped. Results confirm a clear scouting activity: the route of these workers away from the nest is generally tortuous and time consuming and is followed by a return trip along a different and straighter path. Observations also showed that these scouts recruit nestmates and lead raiding columns towards target nests, confirming their important role in the organization of slave raids. The similarity between routes taken by scouts and raiders during outbound trips indicates the close connection between scouting and raiding activity, which was also recorded in detail since 40 raids were observed. Some experiments analysing the orientation behaviour of inbound columns showed that raiders use a chemical trail (deposited during the outbound run) to lead them back home. The hypothesis of a multiple strategy for the location of host colonies operated by this slave-making species is also discussed.     

Immunocytochemical localization of S-100 beta beta protein in olfactory and supporting cells of lamb olfactory epithelium

By immunocytochemistry, we have identified two novel cell types, olfactory and supporting cells of lamb olfactory epithelium, expressing S-100 beta beta protein. S-100 immune reaction product was observed on ciliary and plasma membranes, on axonemes and in the cytoplasm adjacent to plasma membranes and to basal bodies of olfactory vesicles. A brief treatment of olfactory mucosae with Triton X-100 before fixation is necessary for detection of S-100 beta beta protein within olfactory vesicles. In the absence of such a treatment, the immune reaction product is restricted to ciliary and plasma membranes. On the other hand, irrespective of pre-treatment of olfactory mucosae, S-100 beta immune reaction product in supporting cells is restricted to microvillar and plasma membranes. The anti-S-100 beta antiserum used in these studies does not bind to basal cells of the olfactory epithelium or to cells of the olfactory glands, whereas it binds to Schwann cells of the olfactory nerve. An anti-S-100 alpha antiserum does not bind to cellular elements of the olfactory mucosa, Schwann cells, or axons of the olfactory nerve. The present data provide, for the first time, evidence for the presence of S-100 beta beta protein in mammalian neurons (olfactory cells).     

Free amino acids in some sponges

Most invertebrates, particularly those of marine origin, have relatively high concentrations of free amino acids which are considered an important constituent of their osmoregulatory mechanisms [1]. Very little information is available on the free amino acid distribution in Porifera [2,3]. Common amino acids in some sponges were recognised by paper chromatography by Inskip and Cassidy [4] and Ackermann et al. [5,6] included a few sponges in their survey of the occurence of nitrogen compounds in marine invertebrates. More recently Bergquist and Hartman [7] surveyed semiquantitatively the distribution of free amino acids in several sponges. In the present paper we report on the amino acid composition of 12 species of sponges belonging to the class Demospongiae as a part of a study on the metabolites of Porifera [8]. Fresh sponges were extracted with aqueous ethanol. The organic solvent was removed and the aqueous solution, after removal of the ether soluble compounds, was separated into cationic, anionic and neutral fractions by ion-exchange chromatography. The cation fraction was analysed for amino acids using an automatic amino acid analyser. The results, which are presented in Table 1, show that all species of sponges examined have a similar composition in common amino acids. Glycine almost always appears as the dominant protein amino acid, followed by high concentrations of alanine and glutamic acid, whereas relatively lower concentrations of basic amino acids are present. In Axinella cannabina, Chondrosia reniformis, Chondrilla nucula, Cliona viridis and Hymeniacidon sanguinea, glycine represents more than 77% of the total amino acids. The high percentage of free glycine (90.4%) in Chondrosia reniformis is noteworthy. The anionic and the neutral fractions were examined for sulfur-containing amino acids using PC. Taurine (Table 2) was detected in all the Porifera examined; this is in agreement with previous observations [5–7]. N-Methyltaurine was identified in some of the species examined, whereas neither N,N-dimethyltaurine nor N,N,N-trimethyltaurine were found.     

Biologic effect of 1,24(R)(OH)2D3 versus 1,25(OH)2D3 administration in chronic renal failure

1,24(R)(OH)2D3 is a synthetic analogue of 1,25(OH)2D3 which binds to the same receptors as the physiologic metabolite with a lower affinity. The aim of the present study was to compare the activity of 1,24(R)(OH)2D3 and 1,25(OH)2D3 on several target organs in patients with chronic renal failure. Treatment with 1,24(R)(OH)2D3 at doses of either 1 or 2 μg daily was carried out in two groups of 9 patients, with serum creatinine of 4.61 ± 1.59 and 4.66 ± 1.46 mg/dl, respectively. Doses of 1,25(OH)2D3 were 0.5 and 1 μg daily and were administered to 9 and 13 patients, serum creatinine of 4.52 ± 1.67 and 4.3 ± 1.16 mg/dl, respectively. Treatment periods were of 2 weeks. Administration of 1,25(OH)2D3, 1 μg, induced significant increments of intestinal calcium absorption (ICA), ionized calcium, osteocalcin, serum creatinine, urine Ca/GFR, and a decrease in iPTH. 1,25(OH)2D3, 0.5 μg, induced a significant increase in ICA and osteocalcin and a decrease in iPTH. Similarly 1,24(OH)2D3, 2 μg daily, significantly stimulated ICA and raised serum levels of osteocalcin and creatinine while lowering serum iPTH. In addition, 1,24(R)(OH)2D3 administration induced a significant fall of serum 1,25(OH)2D3. Following 1 μg, only osteocalcin increased. Therefore, the dose of 2 μg of 1,24(R)(OH)2D3 has biologic activity similar to 0.5 μg 1,25(OH)2D3 (4:1). However the activity ratio on osteocalcin production appears to be 2:1. In addition, 1,24(R)(OH)2D3 is able to inhibit renal tubular 1-hydroxylase. In conclusion 1,24(R)(OH)2D3 may prove to be useful in the treatment of metabolic bone disease.