New stereoselective routes to macrocyclic ligands

Reaction of bis(ethane-1,2-diamine)copper(II) with acetaldehyde and nitromethane in methanol leads, stereoselectively, to the new macrocyclic complex (trans-5(R),7(R),12(S),14(S))-tetramethyl-6,13-dinitro-1,4,8,11-tetraazacyclotetradecane)copper(II) perchlorate alpha-[CuL1](ClO4)(2) in good yield. Reduction of the nitro groups affords the hexaamine (L-2), which was crystallized as [H4L2](ClO4)(4) . 2H(2)O and characterized by an X-ray crystal structure study (monoclinic P2(1)/n, a = 9.763(2) Angstrom, b = 12.1988(7) Angstrom, c = 13.036(2) Angstrom, beta = 105.668(7)degrees, Z = 2) and complexed with Cu-II to produce the complex beta-[Cu(H2L2)](ClO4)(4) . 2H(2)O, which has also been characterized by X-ray crystallography (monoclinic P2(1)/n, a = 9.717(4) Angstrom, b = 12.174(2) Angstrom, c = 13.036(5) Angstrom, beta = 106.51(2)degrees, Z = 2). Reaction of alpha-[CuL1](2+) with either basic hydrogen peroxide or dilute nitrous acid leads to mild reduction of the nitro groups to afford the ketoxime L-3 as its N-based isomeric Cu-II complexes, trans-I [CuL3](ClO4)(2) and trans-II [Cu(L-3)Cl]Cl . 7H(2)O, the latter of which has been characterized structurally: triclinic, <P(1)over bar> a = 10.8441(5) Angstrom, b = 11.6632(9) Angstrom, c = 11.8723(9) Angstrom, alpha = 113.634(7)degrees, beta = 95.744(5), gamma = 94.851(5)degrees Z = 2. Variations in the configurations of the coordinated amines in [CuL1](2+), [CuL2](2+), and [CuL3](2+) have a profound effect on the spectroscopy and electrochemistry of their complexes.

Thermochromism and structure of piperazinium tetrachlorocuprate(II) complexes

The tetrachlorocuprate(II) ion can crystallize in two different structures with the piperazinium dication (pipzH(2)). Both structures contain discrete CuCl42- species. A yellow compound (pipzH(2))[CuCl4]. 2H(2)O (1) is monoclinic (C2/c, Z = 4, a = 10.538(3) Angstrom, b = 7.4312(5) Angstrom, c = 17.281(4) Angstrom, beta = 111.900(10)degrees) and contains the CuCl42- ion as a distorted tetrahedron. A green compound (pipzH(2))(2)[CuCl4]. Cl-2. 3H(2)O (2) is triclinic (P (1) over bar, Z = 2, a = 9.264(3) Angstrom, b = 10.447(2) Angstrom, c = 11.366(2) Angstrom, alpha = 68.38 degrees, beta = 82.86(2)degrees, gamma = 83.05(2)degrees) and contains the CuCl42- ion with a square planar geometry. This latter compound shows thermo/photochromism, changing from green to yellow upon heating or laser irradiation.

Heroin overdose: causes and consequences

Over the past decade fatal opioid overdose has emerged as a major public health issue internationally. This paper examines the risk factors for overdose from a biomedical perspective. while significant risk factors for opioid overdose fatality are well recognized, the mechanism of fatal overdose remains unclear. Losses of tolerance and concomitant use of alcohol and other CNS depressants clearly play a major role in fatality; howeve, such risk factors do not account for the strong age and gender patterns observed consistently among victims of overdose. There is evidence that systemic disease may be more prevalent in users at greatest risk of overdose. We hypothesize that pulmonary and hepatic dysfunction resulting from such disease may increase susceptibility to both fatal and non-fatal overdose. Sequelae of non-fatal overdose are recognized in the clinical literature but few epidemiological data exist describing the burden of morbidity arising from such sequelae. The potential for overdose to cause persisting morbidity is reviewed.

Impulse-response function of splanchnic circulation with model-independent constraints: theory and experimental validation

Modeling physiological processes using tracer kinetic methods requires knowledge of the time course of the tracer concentration in blood supplying the organ. For liver studies, however, inaccessibility of the portal vein makes direct measurement of the hepatic dual-input function impossible in humans. We want to develop a method to predict the portal venous time-activity curve from measurements of an arterial time-activity curve. An impulse-response function based on a continuous distribution of washout constants is developed and validated for the gut. Experiments with simultaneous blood sampling in aorta and portal vein were made in 13 anesthetized pigs following inhalation of intravascular [O-15] CO or injections of diffusible 3-O[ C-11] methylglucose (MG). The parameters of the impulse-response function have a physiological interpretation in terms of the distribution of washout constants and are mathematically equivalent to the mean transit time ( T) and standard deviation of transit times. The results include estimates of mean transit times from the aorta to the portal vein in pigs: (T) over bar = 0.35 +/- 0.05 min for CO and 1.7 +/- 0.1 min for MG. The prediction of the portal venous time-activity curve benefits from constraining the regression fits by parameters estimated independently. This is strong evidence for the physiological relevance of the impulse-response function, which includes asymptotically, and thereby justifies kinetically, a useful and simple power law. Similarity between our parameter estimates in pigs and parameter estimates in normal humans suggests that the proposed model can be adapted for use in humans.

Establishment and characterization of a new epithelial cell line, KC-1, from koala (Phascolarctos cinereus) conjunctiva

A novel, untransformed koala cell line (KC-1) was established by culturing koala conjunctival tissue in growth medium, which has permitted the study of the cell biology of this unique system. After the establishment of the KC-1 cell line, the cells were characterized by light microscopy, doubling time, and Western blot analysis. Light microscopy revealed that the cells have an epithelial morphology. Doubling times were significantly different (P < 0.015) depending on fetal calf serum (FCS) concentration (16.5 h in 10% FCS and 26.5 h in 2% FCS). Cells constricted while in suspension but were shown to attach to the coverslip (or flask) and flatten rapidly, less than 1 h after seeding. To confirm the epithelial nature of the cells, protein was extracted and Western blot analysis was performed. Subsequent probing with primary and secondary antibodies (monoclonal anticytokeratin clone C-11 IgG1 and anti-mouse IgG) revealed two bands at 45 and 52 kDa (compared against a protein molecular weight marker) that correspond to primary type I keratin and major type II keratin, respectively, expressed in simple epithelial cells. The koala cell line was adapted to grow continuously in Dulbecco modified Eagle medium containing 10% FCS for at least 30 passages. This unique cell line is an ideal toot for further investigation on koala cell biology and cytogenetics and for exploration of the pathophysiological mechanism of eye infections caused by different pathogens in koalas.

Cleaner shrimp use a to advertise cleaning rocking dance service to clients

Signals transmit information to receivers about sender attributes, increase the fitness of both parties, and are selected for in cooperative interactions between species to reduce conflict [1, 2]. Marine cleaning interactions are known for stereotyped behaviors [3-6] that likely serve as signals. For example, dancing and tactile dancing in cleaner fish may serve to advertise cleaning services to client fish [7] and manipulate client behavior [8], respectively. Cleaner shrimp clean fish [9], yet are cryptic in comparison to cleaner fish. Signals, therefore, are likely essential for cleaner shrimp to attract clients. Here, we show that the yellow-beaked cleaner shrimp [110] Urocaridella sp. c [11] uses a stereotypical side-to-side movement, or rocking dance, while approaching potential client fish in the water column. This dance was followed by a cleaning interaction with the client 100% of the time. Hungry cleaner shrimp, which are more willing to clean than satiated ones [12], spent more time rocking and in closer proximity to clients Cephaiopholis cyanostigma than satiated ones, and when given a choice, clients preferred hungry, rocking shrimp. The rocking dance therefore influenced client behavior and, thus, appears to function as a signal to advertise the presence of cleaner shrimp to potential clients.

A novel group of allenic hydrocarbons from five Australian (Melolonthine) beetles

Allenic hydrocarbons, previously unknown as a molecular class from insects, are represented by CH3(CH2)(n)-CH=. =CH-(CH2)(7)CH3 (n = 11-15, 17, 19) in several Australian melolonthine scarab beetles and with demonstrated (R)-chirality when n = 11 and 13.

Metabolic activation of polycyclic aromatic hydrocarbons and other procarcinogens by cytochromes P450 1A1 and P4501B1 allelic variants and other human cytochromes P450 in Salmonella typhimurium NM2009

A variety of polycyclic aromatic hydrocarbons and their dihydrodiol derivatives, arylamines, heterocyclic amines, and nitroarenes, were incubated with cDNA-based recombinant (Escherichia coli or Trichoplusia ni) systems expressing different forms of human cytochrome P450 (P450 or CYP) and NADPH-P450 reductase using Salmonella typhimurium, tester strain NM2009, and the resultant DNA damage caused by the reactive metabolites was detected by measuring expression of umu gene in the cells. Recombinant (bacterial) CYP1A1 was slightly more active than any of four CYP1B1 allelic variants, CYP1B1*1, CYP1B1*2, CYP1B1*3, and CYP1B1*6, in catalyzing activation of chrysene-1,2-diol, benz[a]anthracene-trans-1,2-, 3,4-, 5,6-, and 8,9-diol, fluoranthene-2,3-diol, dibenzo[a]pyrene, benzo[c]phenanthrene, and dibenz[a,h]anthracene and several arylamines and heterocyclic amines, whereas CYP1A1 and CYP1B1 enzymes had essentially similar catalytic specificities toward other procarcinogens, such as (+)-, (-)-, and (+/-)-benzo[a]pyrene-7,8-diol, 5-methylchrysene-1,2-diol, 7,12-dimethylbenz[a]anthracene-3,4-diol, dibenzo[a,l]pyrene-11,12-diol, benzo[b]fluoranthene-9,10-diol, benzo[c]chrysene, 5,6-dimethylchrysene-1,2-diol, benzo[c]phenanthrene-3,4-diol, 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene, 5-methylchrysene, and benz[a]anthracene. We also determined activation of these procarcinogens by recombinant (T. ni) human P450 enzymes in S. typhimurium NM2009. There were good correlations between activities of procarcinogen activation by CYP1A1 preparations expressed in E. coli and T. ni cells, although basal activities with three lots of CYP1B1 in T. ni cells were very high without substrates and NADPH in our assay system. Using 14 forms of human P450S (but not CYP1B1) (in T. ni cells), we found that CY1P1A2, 2C9, 3A4, and 2C19 catalyzed activation of several of polycyclic aromatic hydrocarbons at much slower rates than those catalyzed by CYP1A1 and that other enzymes, including CYP2A6, 2B6, 2C8, 2C18, 2D6, 2E1, 3A5, 3A7, and 4A11, were almost inactive in the activation of polycyclic aromatic hydrocarbons examined here.

Cuticular hydrocarbons of Drosophila birchii and D-serrata: Identification and role in mate choice in D-serrata

The cuticular hydrocarbon compositions of two sympatric species of Australian Drosophila in the montium subgroup of the melanogaster group that use cuticular hydrocarbons in mate recognition have been characterized. Drosophila birchii has 34 components in greater than trace amounts, with a carbon number range of C-20 to C-33. Drosophila serrata has 21 components above trace level and a carbon number range of C-24 to C-31. These two species share eight hydrocarbon components, with all but two of them being monoenes. For both species, the (Z)-9-monoenes are the predominant positional isomer. The hydrocarbons of D. birchii are n-alkanes, n-alkenes (Z)-5-, (Z)-7-, (Z)-9-, and (Z)-11-), low to trace levels of homologous (Z,Z)-7,11- and (Z,Z)-9,13-dienes; and trace amounts of (Z,Z)-5,9- C-25:2, a major component of D. serrata. Only one methyl branched hydrocarbon was detected (2-methyl C-28), and it occurred at very low levels. The hydrocarbons of D. serrata are dominated by a homologous series of (Z,Z)-5,9-dienes, and notably, are characterized by the apparent absence of n-alkanes. Homologous series of (Z)-5-, (Z)-7-, and (Z)-9- alkenes are also present in D. serrata as well as 2-methyl alkanes. Drosophila serrata females display strong directional mate choice based on male cuticular hydrocarbons and prefer D. serrata males with higher relative abundances of the 2-methyl alkanes, but lower relative abundances of (Z,Z)-5,9- C-24:2 and (Z)-9-C-25:1.

The use of transcriptional profiles to predict adult mosquito age under field conditions

Age is a critical determinant of an adult female mosquito's ability to transmit a range of human pathogens. Despite its central importance, relatively few methods exist with which to accurately determine chronological age of field-caught mosquitoes. This fact is a major constraint on our ability to fully understand the relative importance of vector longevity to disease transmission in different ecological contexts. It also limits our ability to evaluate novel disease control strategies that specifically target mosquito longevity. We report the development of a transcriptional profiling approach to determine age of adult female Aedes aegypti under field conditions. We demonstrate that this approach surpasses current cuticular hydrocarbon methods for both accuracy of predicted age as well as the upper limits at which age can be reliably predicted. The method is based on genes that display age-dependent expression in a range of dipteran insects and, as such, is likely to be broadly applicable to other disease vectors.

Weathering of hydrocarbons in mangrove sediments: testing the effects of using dispersants to treat oil spills

This field study was a combined chemical and biological investigation of the relative effects of using dispersants to treat oil spills impacting mangrove habitats. The aim of the chemistry was to determine whether dispersant affected the short- or long-term composition of a medium range crude oil (Gippsland) stranded in a tropical mangrove environment in Queensland, Australia. Sediment cores from three replicate plots of each treatment (oil only and oil plus dispersant) were analyzed for total hydrocarbons and for individual molecular markers (alkanes, aromatics, triterpanes, and steranes). Sediments were collected at 2 days, then 1, 7, 13 and 22 months post-spill. Over this time, oil in the six treated plots decreased exponentially from 36.6 +/- 16.5 to 1.2 +/- 0.8 mg/g dry wt. There was no statistical difference in initial oil concentrations, penetration of oil to depth, or in the rates of oil dissipation between oiled or dispersed oil plots. At 13 months, alkanes were >50% degraded, aromatics were similar to 30% degraded based upon ratios of labile to resistant markers. However, there was no change in the triterpane or sterane biomarker signatures of the retained oil. This is of general forensic interest for pollution events. The predominant removal processes were evaporation (less than or equal to 27%) and dissolution (greater than or equal to 56%), with a lag-phase of 1 month before the start of significant microbial degradation (less than or equal to 7%). The most resistant fraction of the oil that remained after 7 months (the higher molecular weight hydrocarbons) correlated with the initial total organic carbon content of the soil. Removal rate in the Queensland mangroves was significantly faster than that observed in the Caribbean and was related to tidal flushing. (C) 1999 Elsevier Science Ltd. All rights reserved.

Ni-II and Zn-II complexes of the hexadentate macrocyclic ligand cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetra- decane-6,13-diamine

The title pendent-arm macrocyclic hexaamine ligand binds stereospecifically in a hexadentate manner, and we report here its isomorphous Ni-II and Zn-II complexes (both as perchlorate salts), namely (cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine-kappa(6)N)nickel(II) diperchlorate, [Ni(C12H30N6)](ClO4)(2), and (cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine-kappa(6)N)zinc(II) diperchlorate, [Zn(C-12 H30N6)](ClO4)(2). Distortion of the N-M-N valence angles from their ideal octahedral values becomes more pronounced with increasing metal-ion size and the present results are compared with other structures of this ligand.