Copper(I) complexes with tripodal nitrogen-containing neutral ligands such as tris(3,5-diisopropyl-1-pyrazolyl)methane (L1') and tris(3-tertiary-butyl-5-isopropyl-1-pyrazolyl)methane (L3'), and with corresponding anionic ligands such as hydrotris(3,5-diisopropyl-1-pyrazolyl)borate (L1-) and hydrotris(3-tertiary-butyl-5-isopropyl-1-pyrazolyl)borate (L3-) were synthesized and structurally characterized. Copper(I) complexes [Cu(L1')Cl] (1), [Cu(L1')(OClO3)] (2), [Cu(L1')(NCMe)](PF6) (3a), [Cu(L1')(NCMe)](ClO4) (3b), [Cu(L1')(CO)](PF6) (4a), and [Cu(L1')(CO)](ClO4) (4b) were prepared using the ligand L1'. Copper(I) complexes [Cu(L3')Cl] (5) and [Cu(L3')(NCMe)](PF6) (6) with the ligand L3' were also synthesized. Copper(I) complexes [Cu(L1)(NCMe)] (7) and [Cu(L1)(CO)] (8) were prepared using the anionic ligand L1-. Finally, copper(I) complexes with anionic ligand L3- and acetonitrile (9) and carbon monoxide (10) were synthesized. The complexes obtained were fully characterized by IR, far-IR, 1H NMR, and 13C NMR spectroscopy. The structures of both ligands, L1' and L3', and of complexes 1, 2, 3a, 3b, 4a, 4b, 5, 6, 7, and 10 were determined by X-ray crystallography. The effects of the differences in (a) the fourth ligand and the counteranion, (b) the steric hindrance at the third position of the pyrazolyl rings, and most importantly, (c) the charge of the N3 type ligands, on the structures, spectroscopic properties, and reactivities of the copper(I) complexes are discussed. The observed differences in the reactivities toward O2 of the copper(I) acetonitrile complexes are traced back to differences in the oxidation potentials determined by cyclic voltammetry. A special focus is set on the carbonyl complexes, where the 13C NMR and vibrational data are presented. Density functional theory (DFT) calculations are used to shed light on the differences in CO bonding in the compounds with neutral and anionic N3 ligands. In correlation with the vibrational and electrochemical data of these complexes, it is demonstrated that the C-O stretching vibration is a sensitive probe for the "electron richness" of copper(I) in these compounds.

This study focuses on the geometric (molecular) structures, spectroscopic properties, and electronic structures of copper(II)-nitrito complexes as a function of second coordination sphere effects using a set of closely related coligands. With anionic hydrotris(pyrazolyl)borate ligands, one nitrite is bound to copper(II). Depending on the steric demand of the coligand, the coordination mode is either symmetric or asymmetric bidentate, which leads to different ground states of the resulting complexes as evident from EPR spectroscopy. The vibrational spectra of these compounds are assigned using isotope substitution and DFT calculations. The results demonstrate that nu sym(N-O) occurs at higher energy than nu asym(N-O), which is different from the literature assignments for related compounds. UV-vis absorption and MCD spectra are presented and analyzed with the help of TD-DFT calculations. The principal binding modes of nitrite to Cu(II) and Cu(I) are also investigated applying DFT. Using a neutral tris(pyrazolyl)methane ligand, two nitrite ligands are bound to copper. In this case, a very unusual binding mode is observed where one nitrite is eta1-O and the other one is eta1-N bound. This allows to study the properties of coordinated nitrite as a function of binding mode in one complex. The N-coordination mode is easily identified from vibrational spectroscopy, where N-bound nitrite shows a large shift of nu asym(N-O) to >1400 cm-1, which is a unique spectroscopic feature. The optical spectra of this compound exhibit an intense band around 300 nm, which might be attributable to a nitrite to Cu(II) CT transition. Finally, using a bidentate neutral bis(pyrazolyl)methane ligand, two eta1-O coordinated nitrite ligands are observed. The vibrational and optical (UV-vis and MCD) spectra of this compound are presented and analyzed.

Much evidence now suggests that superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) may be a major intracellular protective enzyme against oxygen toxicity by catalyzing the removal of the superoxide radical. We examined the possible role this enzyme may have in determining the life-span of primate species. Superoxide dismutase specific activity levels were measured in cytoplasmic fractions of liver, brain, and heart of 2 rodent and 12 primate species. These species had maximum life-span potentials ranging from 3.5 to 95 years. Liver, brain, and heart had similar specific activity levels for a given species, but the levels for different species varied over 2-fold, with man having the highest level.No general correlation was found in the levels with life-span.However, the ratio of superoxide dismutase specific activity to specific metabolic rate of the tissue or of the whole adult organism was found to increase with increasing maximum lifespan potential for all the species. This correlation suggests that longer-lived species have a higher degree of protection against by-products of oxygen metabolism.A wide range exists in maximum life-span potential (MLP) of different mammalian species which may be the result of relatively small biological differences (1-3). Much of the evolution of mammalian species may have been the result of alterations in the temporal and quantitative expression of a conserved set of structural genes (4-6). Consistent with this view is the high rate of increase in MLP during the evolution of the primates, particularly along the hominid ancestral-descendant sequence (7). This high rate implies that relatively few genetic alterations may have been necessary to substantially prolong the period of general health maintenance (8, 9). These and other data have suggested that, as in the evolution of morphology and other characteristics of a species, modifications in gene regulation may be involved in the evolution of longevity or health maintenance (7, 10).We are testing this hypothesis by searching for a correlation between the level of expression of potentially important genetic repair and protective processes and the MLP of mammalian species. There is compelling evidence that superoxide dismutase (SODase; superoxide:superoxide oxidoreductase, EC 1.15.1.1) is a major protective enzyme against oxygen toxicity, which acts by catalyzing the removal of the superoxide radical (11-13). In this paper we show the relative level of SODase specific activity as a function of MLP in liver, brain, and heart for 2 rodent and 12 primate species. Results indicate an excellent positive correlation between the ratio of SODase specific activity to specific metabolic rate (SMR) and MLP for these species. MATERIALS AND METHODS

Stimulation of quiescent AKR-2B mouse embryo cells with epidermal growth factor (EGF) results in a rapid and specific induction of actin mRNA sequences. These mRNAs include those coding for both P-and y-cytoskeletal, but not a-skeletal muscle, actin isotypes. Elongation of nascent RNA chains in isolated nuclei (run-off transcription) demonstrates that the mRNA accumulation is preceded by an increase in actin gene transcription. This increase is transient, however, and is followed by a rapid attenuation of transcriptional activity. An inhibitor of protein synthesis, cycloheximide, was also found to induce 18-and r-actin mRNA accumulation. Furthermore, the simultaneous addition of EGF and cycloheximide produced a synergistic effect on actin sequences in both steady-state nuclear and polysomal RNA. Run-off transcription experiments demonstrate that this synergistic effect results from an increase in the magnitude and duration of actin gene transcription. It is also specific in that a-tubulin gene transcription is not similarly affected. These data suggest the existence of a specific labile repressor of actin gene transcription.The binding of epidermal growth factor (EGF) to specific receptors in the membranes of quiescent cells initiates a variety of biochemical events that can culminate in the initiation of DNA synthesis and cell division (reviewed in ref. 1). Inhibitors of RNA synthesis can block this process, implying that the transcription of certain genes is required for a quiescent cell to reenter the cell cycle (2). The molecular mechanisms that regulate these genes are poorly understood but do not appear to involve the nuclear translocation of the hormone-receptor complex. Indeed, the complex itself is rapidly internalized and degraded several hours prior to the initiation of DNA synthesis (3,4). This observation has led to speculation that a second messenger(s) of hormone action must be responsible for initiating the expression of specific genes required for cell proliferation (1).A major constraint on any proposed mechanism of EGF or second messenger action is the requirement for a high degree of specificity. This consideration arises from several studies that have shown that peptide growth factors regulate a very limited domain of specific genes (5-8). This specificity could be achieved by a specific DNA binding protein acting either as a positive or negative regulator of gene transcription. Although theoretical constraints have been imposed on specific protein-DNA interactions in the context of a mammalian nucleus, these constraints are not absolute and a variety of compensating strategies are available to a eukaryotic cell (9). Therefore, it may be noteworthy that recent studies have shown that inhibitors of protein synthesis can potentiate the induction of specific mRNA sequences by platelet-derived growth factor (7, 10). Although this observation is consistent with a protein repressor of growth-factor-regulated genes, a direct effect on gene transcription rates was not shown.Prompted by a rep...

The posterior and posteroinferior capsules were stiffer as well as thicker in the throwing shoulder of college baseball players compared with the nonthrowing shoulder. Posterior capsule elasticity appeared to have a greater effect on GIRD than did posterior capsule thickness. This technology could be used as a noninvasive screening method for throwing athletes to identify players at potential risk of shoulder injuries.

In the present study, we searched for genetic alterations of the entire coding region of PTEN/MMACl, a recently isolated candidate tumor suppressor gene, in 178 specimens from Japanese patients with various malignant tumors by the polymerase chain reaction‐single strand conformation polymorphism method. The samples consisted of 11 glioblastoma multiformes (GBMs), 14 astrocytomas, 47 breast cancers, 25 non‐small cell lung cancers, 9 small cell lung cancers, 8 pancreatic cancers, 24 renal cell carcinomas, 20 ovarian cancers, and 20 metastatic lung tumors from various organs. Only one somatic frameshift mutation at codon 319 was observed in one (9%) of eleven GBMs. Our results suggest that mutation of the PTEN/MMAC1 gene does not play a major role in carcinogenesis, at least in the tumor types from Japanese patients analyzed in this study.

A combination of spectroscopies and DFT calculations have been used to define the electronic structures of two crystallographically defined Cu II -phenolate complexes. These complexes differ in the orientation of the phenolate ring which results in different bonding interactions of the phenolate donor orbitals with the Cu II , which are reflected in the very different spectroscopic properties of the two complexes. These differences in electronic structures lead to significant differences in DFT calculated reactivities with oxygen. These calculations suggest that oxygen activation via a Cu I phenoxyl ligand-to-metal charge transfer (LMCT) complex is highly endergonic (> 50 kcal/mol), hence an unlikely pathway. Rather, the two electron oxidation of the phenolate forming a bridging Cu II peroxoquinone complex is more favorable (11.3 kcal/mol). The role of the oxidized metal in mediating this two electron oxidation of the coordinated phenolate and its relevance to the biogenesis of the covalently bound topa quinone in amine oxidase are discussed.

Twocases of acute eosinophilic pneumoniafollowing cigarette smoking are analyzed for characteristic features. The first patient noted dyspnea 14 days after initiation of smoking. The second patient noted dyspnea 12 days after beginning to smoke. Both cases had characteristic features including occurrence at an age younger than 30 years; less than 1 month duration of cigarette smoking before onset of disease ; and no identifiable cause of acute eosinophilic pneumoniaapart from smoking. Webelieve that acute eosinophilic pneumonia following cigarette smoking, which has characteristic features as described above, should be considered as a distinct subtype of AEP. (Internal Medicine 39: 830-833, 2000)