Papers by Christopher Parkinson
Medicinal chemistry (Shariqah (United Arab Emirates)), Jan 25, 2018
Bis-thiosemicarbazones containing a central pyridyl core display potent antimalarial activity in ... more Bis-thiosemicarbazones containing a central pyridyl core display potent antimalarial activity in vitro. The absence of the pyridyl core results in inactive compounds. It is likely that metal ion sequestration and subsequent reactive oxygen generation plays a role in the antimalarial activity of the series, the redox activity of the iron complexes of bis-thiosemicarbazones paralleling antimalarial activity. The activity of this series compares favourably to that of previously reported iron sequestering compounds.
IUBMB Life, 2016
A series of 2(5H)-furanone-based compounds were synthesized from commercially available mucohalic... more A series of 2(5H)-furanone-based compounds were synthesized from commercially available mucohalic acids. From the first-generation compounds, three showed inhibitory activity (10 µg/mL) of at least 35% against Mycobacterium smegmatis mc(2) 155 growth (Bioscreen C system). In screening the active first-generation compounds for growth inhibition against Mycobacterium tuberculosis H37Rv, the most active compound was identified with a minimum inhibitory concentration (MIC99 ) of 8.07 µg/mL (15.8 µM) using BACTEC 460 system. No cross-resistance was observed with some current first-line anti-TB drugs, since it similarly inhibited the growth of multidrug resistant (MDR) clinical isolates. The compound showed a good selectivity for mycobacteria since it did not inhibit the growth of selected Gram-positive and Gram-negative bacteria. It also showed synergistic activity with rifampicin (RIF) and additive activity with isoniazid (INH) and ethambutol (EMB). Additional time-kill studies showed that the compound is bacteriostatic to mycobacteria, but cytotoxic to the Chinese Hamster Ovarian (CHO) cell line. From a second generation library, two compounds showed improved anti-TB activity against M. tuberculosis H37Rv and decreased CHO cell cytotoxicity. The compounds exhibited MIC values of 2.62 µg/mL (5.6 µM) and 3.07 µg/mL (5.6 µM) respectively. The improved cytotoxicity against CHO cell line of the two compounds ranged from IC50 = 38.24 µg/mL to IC50 = 45.58 µg/mL when compared to the most active first-generation compound (IC50 = 1.82 µg/mL). The two second generation leads with selectivity indices (SI) of 14.64 and 14.85 respectively, warrant further development as anti-TB drug candidates. © 2016 IUBMB Life, 68(8):612-620, 2016.
Bioorganic & medicinal chemistry, 2015
Cancer cell resistance to chemotherapy is still a heavy burden that impairs the response of many ... more Cancer cell resistance to chemotherapy is still a heavy burden that impairs the response of many cancer patients to conventional chemotherapy. Using drug combinations is one therapeutic approach to overcome the developing resistance to any one drug. Oxidative stress is now a generally regarded hallmark of cancer that can be one approach to selectively target cancer cells while sparing normal cells. With the aim of increasing oxidative stress in cancer cells to a lethal set point, we have generated and combined several series of redox active compounds that act at different points of the cellular oxidative cascade. The premise of such combinations is to deplete of endogenous antioxidant defence proteins (e.g., Glutathione) while concomitantly increasing the generation of ROS via metal redox recycling and Fenton chemistry which eventually leads to the disruption of cellular redox homeostasis and induction of cell death. Through this approach, we have identified highly synergistic combi...
Molecules, 2014
Sesquiterpene lactones (STLs) are natural products that have potent antitrypanosomal activity in ... more Sesquiterpene lactones (STLs) are natural products that have potent antitrypanosomal activity in vitro and, in the case of cynaropicrin, also reduce parasitemia in the murine model of trypanosomiasis. To explore their structure-antitrypanosomal activity relationships, a set of 34 natural and semi-synthetic STLs and amino-STLs was tested in vitro against T. b. rhodesiense (which causes East African sleeping sickness) and mammalian cancer cells (rat bone myoblast L6 cells). It was found that the α-methylene-γlactone moiety is necessary for both antitrypanosomal effects and cytotoxicity. Antitrypanosomal
Agu Spring Meeting Abstracts, May 1, 2004
The Greater Himalayan Sequence (GHS) represents the metamorphic core of the Himalaya, and is floo... more The Greater Himalayan Sequence (GHS) represents the metamorphic core of the Himalaya, and is floored by the Main Central Thrust (MCT), a fault that is believed to have hundreds of kilometers of displacement. Thus the GHS and MCT are crucial elements of the Indo-Asian collision. Whole-grain ID-TIMS ages of monazite from the GHS in central Nepal have been the principal means of inferring the timing of both melting (~ 22 Ma) and initial MCT movement (20-22 Ma). However, no previous study has systematically characterized the chemistries of GHS monazite grains and correlated them with metamorphic reactions and isotopic ages. In this study, monazite grains from GHS gneisses, Langtang valley, Nepal, were chemically mapped via electron microprobe and then dated in situ via Th-Pb ion microprobe analysis. Correlation of ages and compositions reveals at least 5 different generations of monazite, ranging in age from ~ 9 to >300 Ma. These occur within two temporally and petrologically distinct thrust sheets, the Langtang Thrust sheet (LTS) and the Main Central Thrust sheet (MCTS). From youngest to oldest these monazites are (1) low-Y recrystallized zones associated with xenotime exsolution and feldspar alteration (9 Ma, LTS only), (2) high-Y rims (13-16 Ma for MCTS and 17-19 Ma for LTS), (3) low-Y, low-Th cores (17-23 for MCTS and 23-24 Ma for LTS), (4) high-Th, high-Y domains with "mottled" zoning (25-37 Ma, both LTS and MCTS), and (5) an extremely high-U inclusion in garnet (>300 Ma, LTS only). Petrologic models of monazite chemistry link these generations to the petrologic and tectonic evolution of these rocks. Specifically, monazite generation (1) formed during low-T (<400 ° C) alteration, (2) formed during crystallization ofin situ melts, (3) formed at the maximum temperature experienced by the solid-state assemblage, (4) probably formed during lower-T prograde metamorphism, and (5) is an inherited grain of either detrital or low-T hydrothermal (?) origin. Because generations (2) and (3) bracket melting, they provide a revised estimate for the timing of melting of GHS rocks: 16±1 Ma for the MCTS (i.e., 6 Myr younger than previously thought) and 21±2 Ma for the LTS. Assuming that cooling and melt crystallization resulted from thrust emplacement, the timing of thrusting can also be derived: 16-10.5 Ma for the MCT and 21-16 Ma for the LT. These results demonstrate that chemical characterization of monazite is vital prior to chronologic microanalysis, and that most ages previously reported for monazite from the GHS are interpretationally ambiguous.
Proceedings of the International Astronomical Union, 2006
Over 150 extrasolar planets are known to orbit sun-like stars. A growing number of them (9 to dat... more Over 150 extrasolar planets are known to orbit sun-like stars. A growing number of them (9 to date) are transiting "hot Jupiters" whose physical characteristics can be measured. Atmospheres of two of these planets have already been detected. We summarize the atmosphere detections and useful upper limits, focusing on the MOST albedo upper limit and H exosphere detection for HD209458b as the most revelant for photochemical models. We describe our photochemical model for hot Jupiters and present a summary explanation of the main results: a low gas-phase abundance of hydrocarbons; an absence of hydrocarbon hazes; and a large reservoir of H atoms in the upper atmospheres of hot Jupiters. We conclude by relating these model results to the relevant observational data.
The Island Arc, Jun 1, 1998
Agu Spring Meeting Abstracts, 2002
Eclogites are extremely rare in the Himalayan orogen, with only 3 documented occurrences in the K... more Eclogites are extremely rare in the Himalayan orogen, with only 3 documented occurrences in the Kaghan valley (Pakistan), Tso Morari (NW India), and the Kharta (S. Tibet). We have discovered severely retrograded eclogite within the Greater Himalayan Sequence (GHS) of the Arun valley in the Makalu-Everest region, eastern Nepal. It occurs as rare relict cores in 30-120 cm thick discontinuous amphibolitised layers and boudins within quartzo-feldspathic gneisses (Barun gneiss) of the GHS, between Hatiya and Chepuwa villages. The eclogites are stratigraphically contiguous with the surrounding felsic rocks, and are interpreted to represent metamorphosed basaltic sills or flows. Constituent minerals comprise: Grt, Cpx, Pl, Hbl, Qz and Bi, with minor Cal, Ms, Ttn, Ilm, Chl, Ap and Zrn. Matrix Cpx grains (up to 1.5 cm) are diopsidic (with 14 kbar (Jd content of Cpx) at 670-710oC (Grt-Cpx thermometry) for the peak eclogite assemblage. Symplectites grew during granulite facies retrogression at 6-8 kbar and 680-740oC. Final amphibolite reequilibration is indicated by growth of Hbl + Pl + Chl + Ilm likely at T < 600oC. Peak pressures for these rocks are considerably higher than those generally accepted for the Barun gneiss (5-8 kbar at 750-800oC), because an early high-P stage of recrystallization has been obliterated in the surrounding felsic Barun gneisses by the later granulite and amphibolite overprint, but not in the mineralogically resistant metabasites. The GHS in eastern Nepal was apparently buried to considerably greater depths (> 45 km) during the Indo-Asian collision than has been previously considered.
Agu Spring Meeting Abstracts, May 1, 2002
Gravity and aeromagnetic circular anomalies (10-15 km diameter) near Johnsonville in NE South Car... more Gravity and aeromagnetic circular anomalies (10-15 km diameter) near Johnsonville in NE South Carolina meet the geophysical criteria for those associated with buried complex impact craters. However, documentation of shock metamorphic textures provides the only unequivocal evidence for an impact event. Fortuitously, a SC-DNR/USGS borehole (MRN 78) had previously been drilled (in 1984) within the putative impact crater. The core comprises several hundred meters of Tertiary and Cretaceous sedimentary cover and 9 m of the Piedmont crystalline basement. The basement rocks are predominantly schists and gneisses with a strongly developed subhorizontal foliation with 1-30 cm thick foliation-parallel injections of granite. The metamorphic rocks contain Qz + Pl + Ms + Bi + Cal + Chl. Petrographic examination revealed some subtle, and not entirely unequivocal indications of shock metamorphism. They comprise: [1] rare, coarsely-developed planar fractures in quartz grains of both the granite and schist, similar to those reported from established impact rocks; [2] kinked and warped biotite grains in the gneiss, many of which have all but lost their pleochroism; [3] widespread development of `ballen' texture quartz with reduced birefringence, typical of impactites, and [4] transformation of some plagioclase grains to isotropic diaplectic glass and the development of `chessboard' patterns and recrystallization of feldspar xenocrysts in mineral glass. Even on the scale of a thin-section these textures are patchy. The planar fractures in quartz (20-50 micron spacing) are generally only developed within the coarser quartz grains of the granite. This may indicate considerable heterogeneity in shock pressures and/or considerable post-peak shock annealing. Development of ballen texture quartz is much more widespread, especially in the gneiss; spheroidal quartz grains have diameters of 50-400 æm, and they are associated with smaller spherules of non-pleochroic and nearly isotropic biotite. Zones of lithic microbreccia, several centimeters wide and oriented subparallel to the foliation, are developed in the gneiss. Grains of plagioclase in the microbreccia display partial transformation to diaplectic glass. Patches of partially devitrified glass in the gneiss also contains small laths of K-feldspar, recrystallized during cooling. In total, these features provide strong petrographic indications of shock metamorphism related to elevated post-shock temperatures and very rapid cooling. The lack of clear planar deformation features in quartz preclude accurate determination of peak shock pressures, but a lower limit of 30 GPa must be inferred from the presence of diaplectic glass in the rocks studied.
Agu Fall Meeting Abstracts, Dec 1, 2001
Orogenic garnet-bearing peridotites occur on the island of Sulawesi, Indonesia. They are distribu... more Orogenic garnet-bearing peridotites occur on the island of Sulawesi, Indonesia. They are distributed in two regions within NW-SE trending strike-slip fault zones. Garnet lherzolite within the left-lateral Palu-Koro fault zone occurs as < 10 m wide fault slice associated with high-grade metamorphic rocks in a Miocene granite; whereas within the right-lateral Ampana fault in the Bongka river valley, the peridotite occurs as 10-30 m wide, fault-bounded outcrops juxtaposed against gabbro and peridotites of the East Sulawesi ophiolite. Analysed lherzolites are generally depleted in SiO2, TiO2, Al2O3, CaO and Na2O, and enriched in FeO total and MgO; trace elements of Y and Zr decrease, while Ni increases with increasing MgO. These values are consistent with an origin as a depleted mantle residue rather than forming as a crustal cumulate. Whole-rock REE patterns from hydrous phase rich rock show LREE enrichment. However, the reconstructed whole rock REE patterns based on modal reconstruction ion probe analyses of garnet and pyroxene are flat and slightly depleted in LREE. The differences between the reconstructed whole rock REE pattern and the analyzed whole-rock REE pattern, indicate that the Sulawesi garnet peridotite has undergone both modal metasomatism and trace element enrichment resulting in the formation of pargasite and/or phlogopite. Furthermore, a P-T time plot suggests a prograde subduction zone peridotite. After a peak stage, the garnet peridotite suffered intensive mantle metasomatism and hydration which indicate a mantle wedge environment above a subduction zone. Sm-Nd dating has yielded mineral ages of 27-20 Ma. 27 Ma is probably the time of peak metamorphism and 20 Ma is the cooling age. The young ages do not support the previous idea that garnet peridotites are a part of Mid Cretaceous UHPM terrane. However, the Neogene age is similar to a recently reported age of the country rock schist and gneiss. Therefore, the ultramafic rocks are most likely were introduced into the crust and metamorphosed to garnet bearing assemblages during Late Oligocene - Early Miocene continent-continent collision in Central Sulawesi (e.g. Sundaland and fragment of the Australian continental margin). In reality, the Neogene collision in Sulawesi is a very complex collision involving accretion of SW Pacific superplume-induced ophiolite massif, high-pressure metamorphic rocks, volcanic arc and continental fragments, and then followed by an extension. The geochemical and petrological data suggest that the peridotite is a mantle wedge fragment that has experienced HP metamorphism, and subsequent metasomatism from the subducted slab, and later somehow incorporated into the underthrust continental crust. Due to the buoyancy force of delamination of a crustal slab from the oceanic lithosphere, the peridotites were uplifted within the Neogene metamorphic complex, suffering a similar decompression as that experienced by the regional schists and gneisses. Final exhumation from an upper crustal level was facilitated by entrainment in Late Miocene granitic plutons, and/or transtension in deep-seated strike-slip fault zones.
Geophys Res Lett, 1990
ABSTRACT
Agu Fall Meeting Abstracts, Nov 29, 2003
CH3D and C2H5D are isotopic tracers in the deep Jovian atmosphere and susceptible to transport an... more CH3D and C2H5D are isotopic tracers in the deep Jovian atmosphere and susceptible to transport and chemical effects. It is expected that the tropospheric ([D]/[H])CH4 ratios determined from the various observations made should be relatively invariable, yet previous determinations of this quantity for Jupiter have given results inconsistent with experimental error bars. This suggests that there may be a problem with the interpretion of some of the observations, or that the apparent CH3D column abundance is variable. We report on the effects of varying important parameters over this pressure regime on the CH3D and C2H5D mixing ratios, CH3D and C2H5D fractionation, the ([D]/[H])CH4, ([D]/[H])C2H_6 and D/H (= ([D]/[H])H2) ratios and compare with the various CH3D and HD observations. Our results show that since the CH3D and C2H5D mixing ratios are strongly dependent upon K(z) in the region of interest where temporal or latitudinal variations in K(z) could significantly impact the measured ([D]/[H])CH4 ratio. The K(z) adopted represents complex upward convection and downdraft mixing that occurs in the Jovian atmosphere as evidenced by recent observations (Gierasch et al., 2000; Ingersoll et al., 2000; Roos-Serote et al., 2000; Vincent et al., 2000). Using our technique allows for the first time a way to explain the discrepancies in the ([D]/[H])CH4 ratio observations by offering a plausible link between the CH3D and C2H5D observations and upper tropospheric dynamical processes. In any case our calculations show how ([D]/[H])CH4 and ([D]/[H])C2H_6 can be used as a diagnostic tracer to constrain K(z) and to better understand the dynamics of the atmosphere in this pressure regime. Additionally, we have made calculations of the C2H5D in the thermosphere of Jupiter. The principal reactions determining the D abundance appear to be generation by reaction of H with vibrationally hot HD and loss by reaction of D with H2(v=0,1) and CH3. The H, CH3D and C2H5D distributions have been calculated using the Caltech/JPL KINETICS 1-D photochemistry-diffusion model with the column H constrained using the H lyman-alpha airglow. Reactions involving C2H5D are described by Parkinson (2002). Performing sensitivity studies, we have found an enhancement of greater than two orders of magnitude in C2H5D due to the vibrational chemistry, which is significantly larger than that for CH3D enhancement reported by Parkinson et al (2003). This is of great interest and suggests that C2H5D should be detectable in the lower thermosphere: we propose that observations of this species should be made. Enhancement of deuterated hydrocarbons indicates that there may be exchange of these species between the statosphere and troposphere and further show their usefulness as isotopic tracers in the Jovian atmosphere.
... Yuk L. Yung, Ph.D. 1 , Michael J. Russell, Ph.D. 2 , and Christopher D. Parkinson, Ph.D. 3 1 ... more ... Yuk L. Yung, Ph.D. 1 , Michael J. Russell, Ph.D. 2 , and Christopher D. Parkinson, Ph.D. 3 1 Division of Geological and ... rich organic molecules that render them slightly alkaline, whereas their exteriors are also generally more oxidized and acidic (Spitzer and Poolman, 2009). ...
The photochemistry of the atmosphere of Venus has been modeled using the latest available chemica... more The photochemistry of the atmosphere of Venus has been modeled using the latest available chemical kinetics information, with the view to improving our understanding of the height distributions of the sulphur and halogen molecules. We include new results from calculations showing latitudinal/longitudinal variations of key species (SOx, H2SO4, HCl, etc.) for different seasons, which will be helpful in the interpretation of the observations being made from the Venus Express orbiter spacecraft.
Icarus, 1995
Recent studies of the upper atmosphere of Jupiter and the H Lyman α bulge in particular have prom... more Recent studies of the upper atmosphere of Jupiter and the H Lyman α bulge in particular have prompted us to reevaluate Voyager UVS measurements of Jupiter's He 584 Å dayglow. We employ more sophisticated data reduction techniques than for earlier analyses to better quantify the UVS observations. We model Jupiter's He 584 Å intensity using partial frequency redistribution and inhomogeneous atmospheric models that are more realistic than the isothermal atmospheric models used in the earlier analyses. These calculations show that the eddy diffusion coefficient at the homopause Kh is roughly 2+2-1 × 106 cm2 sec-1. One question we address is whether Jupiter's He 584 Å dayglow shows a longitudinal asymmetry in intensity. The present work suggests that the evidence for such an asymmetry is not conclusive but is consistent with a variation anticorrelated with H Lyman α.
J Organomet Chem, 1996
Vinylmercury compounds, vinylboronic acids and vinylstannanes undergo rapid metal-lead exchange w... more Vinylmercury compounds, vinylboronic acids and vinylstannanes undergo rapid metal-lead exchange with lead tetraacetate in deuterochloroform to generate vinyllead triacetates, which have been characterised by their ~H-~H and 2°7pb-IH coupling constants. In addition, a number of divinyl and mixed aryl-vinyllead dicarboxylates have been prepared via boron-lead exchange.
Bulletin of the American Astronomical Society, Apr 29, 2003
A new technique has been developed for the treatment of hydrodynamic loss processes from planetar... more A new technique has been developed for the treatment of hydrodynamic loss processes from planetary atmospheres utilising the Godunov method. A detailed description of a first order Godunov scheme is given by Godunov (1959), Gombosi (1984), and Leveque (2002). Solving the one-dimensional, steady state approximation becomes problematic at the distance where the outflow becomes supersonic. This method overcomes the instabilities inherent in modeling transonic conditions by solving the coupled, time dependent mass, momentum, and energy equations, instead of integrating time independent equations. We validate a preliminary model of hydrodynamic escape against simple, idealised cases (viz., steady state and isothermal conditions) showing that a robust solution obtains and then compare to existing cases in the literature (Watson et al., 1981; Kasting and Pollack, 1983; Chassefiere, 1996). A focus of this work is on observable aspects of atmospheres that may be useful for comparison between models and observations. "Close-in" hot Jupiter's provide an ideal test case because of recent observations of HD 209458b. The general tools developed here will be applied to various problems such as the early Earth and Venus, and close-in extrasolar gas giant planets and are directly applicable to modifications required for the VPL terrestrial planet models.
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Papers by Christopher Parkinson