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Despite its success as an anticancer drug, cisplatin suffers from resistance and produces side effects. To overcome these limitations, amino-acid-linked cisplatin analogues have been investigated. Lysine-linked cisplatin, Lysplatin, (Lys)PtCl2, exhibited outstanding reactivity toward DNA and RNA that differs from that of cisplatin. To gain insight into its differing reactivity, the structure of Lysplatin is examined here using infrared multiple photon dissociation (IRMPD) action spectroscopy. To probe the influence of the local chemical environment on structure, the deprotonated and sodium-cationized Lysplatin complexes are examined. Electronic structure calculations are performed to explore possible modes of binding of Lys to Pt, their relative stabilities, and to predict their infrared spectra. Comparisons of the measured IRMPD and predicted IR spectra elucidate the structures contributing to the experimental spectra. Coexistence of two modes of binding of Lys to Pt is found where Lys binds via the backbone and side-chain amino nitrogen atoms, NNs, or to the backbone amino and carboxylate oxygen atoms, NO–. Glycine-linked cisplatin and arginine-linked cisplatin complexes have previously been found to bind only via the NO–binding mode. Present results suggest that the NNsbinding conformers may be key to the outstanding reactivity of Lysplatin toward DNA and RNA.

Ionic liquid (IL) development efforts have focused on achieving desired properties via tuning of the IL through variation of the cations and anions. However, works geared toward a microscopic understanding of the nature and strength of the intrinsic cation–anion interactions of ILs have been rather limited such that the intrinsic strength of the cation–anion interactions in ILs is largely unknown. In previous work, we employed threshold collision-induced dissociation approaches supported and enhanced by electronic structure calculations to characterize the nature of the cation–anion interactions in and determine the bond dissociation energies (BDEs) of a series of four 2:1 clusters of 1-alkyl-3-methylimidazolium cations and tetrafluoroborate anions, [2Cnmim:BF4]+. The cation was varied over the series: 1-ethyl-3-methylimidazolium, [C2mim]+, 1-butyl-3-methylimidazolium, [C4mim]+, 1-hexyl-3-methylimidazolium, [C6mim]+, and 1-octyl-3-methylimidazolium, [C8mim]+, to determine the structural and energetic effects of the size of the 1-alkyl substituent on the binding. The variation in the strength of binding determined for these [2Cnmim:BF4]+clusters was found to be similar in magnitude to the average experimental uncertainty in these determinations. To definitively establish an absolute order of binding among these [2Cnmim:BF4]+clusters, we extend this work here to include competitive binding studies of three mixed 2:1 clusters of 1-alkyl-3-methylimidazolium cations and tetrafluoroborate anions, [Cn–2mim:BF4:Cnmim]+for n= 4, 6, and 8. Importantly, the results of the present work simultaneously provide the absolute BDEs of these mixed [Cn–2mim:BF4:Cnmim]+clusters and the absolute relative order of the intrinsic binding interactions as a function of the cation with significantly improved precision. Further, by combining the thermochemical results of the previous and present studies, the BDEs of the [2Cnmim:BF4]+clusters are more accurately and precisely determined.

Ionic liquids (ILs) have become increasingly popular due to their useful and unique properties, yet there are still many unanswered questions regarding their fundamental interactions. In particular, details regarding the nature and strength of the intrinsic cation–anion interactions and how they influence the macroscopic properties of ILs are still largely unknown. Elucidating the molecular-level details of these interactions is essential to the development of better models for describing ILs and enabling the purposeful design of ILs with properties tailored for specific applications. Current uses of ILs are widespread and diverse and include applications for energy storage, electrochemistry, designer/green solvents, separations, and space propulsion. To advance the understanding of the energetics, conformations, and dynamics of gas-phase IL clustering relevant to space propulsion, threshold collision-induced dissociation approaches are used to measure the bond dissociation energies (BDEs) of the 2:1 clusters of 1-alkyl-3-methylimidazolium cations and tetrafluoroborate, [2Cnmim:BF4]+. The cation, [Cnmim]+, is varied across the series, 1-ethyl-3-methylimidazolium [C2mim]+, 1-butyl-3-methylimidazolium [C4mim]+, 1-hexyl-3-methylimidazolium [C6mim]+, and 1-octyl-3-methylimidazolium [C8mim]+, to examine the structural and energetic effects of the size of the 1-alkyl substituent on binding. Complementary electronic structure calculations are performed to determine the structures and energetics of the [Cnmim]+and [BF4]−ions and their binding preferences in the (Cnmim:BF4) ion pairs and [2Cnmim:BF4]+clusters. Several levels of theory, B3LYP, B3LYP-GD3BJ, and M06-2X, using the 6-311+G(d,p) basis set for geometry optimizations and frequency analyses and the 6-311+G(2d,2p) basis set for energetics, are benchmarked to examine their abilities to properly describe the nature of the binding interactions and to reproduce the measured BDEs. The modest structural variation among these [Cnmim]+cations produces only minor structural changes and variation in the measured BDEs of the [2Cnmim:BF4]+clusters. Present findings indicate that the dominant cation–anion interactions involve the 3-methylimidazolium moieties and that these clusters are sufficiently small that differences in packing effects associated with the variable length of the 1-alkyl substituents are not yet significant.

The kinetic energy dependence of the collision-induced dissociation (CID) of Group 1 metal cations (M+= Li+, Na+, K+, Rb+, and Cs+) chelated to the amino acid lysine (Lys) was measured by threshold CID using a guided ion beam tandem mass spectrometer. The simple loss of neutral lysine is the only dissociation channel observed with the heavier alkali metal cations, whereas CID of Li+(Lys) yields other competing channels including loss of NH3(the dominant channel at low energy) and eight other reactions. Analysis of the kinetic energy-dependent cross sections yields experimental M+(Lys) bond dissociation energies (BDEs) of 376 ± 30, 219 ± 13, 160 ± 10, 141 ± 6, and 128 ± 4 kJ/mol for Li+, Na+, K+, Rb+, and Cs+, respectively. Computational searches yielded 18 distinct, low-energy structural families related to sites of M+binding in M+(Lys) complexes and 10 distinct, low-energy structural families for neutral lysine. Among the four levels of theory and three basis sets used, four different ground conformers of M+(Lys) and four different ground conformers of lysine were found, including a ground conformer of K+(Lys) and Cs+(Lys), [Nε,CO(OH)], and its higher energy zwitterionic analogue, [Nε,CO2–], that better explains recent infrared multiple photon dissociation action spectroscopy results. Computational results for predicted ground structures of M+(Lys) complexes yielded computed BDEs in reasonable agreement with experiment.

The chemical difference between DNA and RNA nucleosides is their 2′-hydrogen versus 2′-hydroxyl substituents. Modification of the ribosyl moiety at the 2′-position and 2′-O-methylation in particular, is common among natural post-transcriptional modifications of RNA. 2′-Modification may alter the electronic properties and hydrogen-bonding characteristics of the nucleoside and thus may lead to enhanced stabilization or malfunction. The structures and relative glycosidic bond stabilities of the protonated forms of the 2′-O-methylated purine nucleosides, 2′-O-methyladenosine (Adom) and 2′-O-methylguanosine (Guom), were examined using two complementary tandem mass spectrometry approaches, infrared multiple photon dissociation action spectroscopy and energy-resolved collision-induced dissociation. Theoretical calculations were also performed to predict the structures and relative stabilities of stable low-energy conformations of the protonated forms of the 2′-O-methylated purine nucleosides and their infrared spectra in the gas phase. Low-energy conformations highly parallel to those found for the protonated forms of the canonical DNA and RNA purine nucleosides are also found for the protonated 2′-O-methylated purine nucleosides. Importantly, the preferred site of protonation, nucleobase orientation, and sugar puckering are preserved among the DNA, RNA, and 2′-O-methylated variants of the protonated purine nucleosides. The 2′-substituent does however influence hydrogen-bond stabilization as the 2′-O-methyl and 2′-hydroxyl substituents enable a hydrogen-bonding interaction between the 2′- and 3′-substituents, whereas a 2′-hydrogen atom does not. Further, 2′-O-methylation reduces the number of stable low-energy hydrogen-bonded conformations possible and importantly inverts the preferred polarity of this interaction versus that of the RNA analogues. Trends in the CID50%values extracted from survival yield analyses of the 2′-O-methylated and canonical DNA and RNA forms of the protonated purine nucleosides are employed to elucidate their relative glycosidic bond stabilities. The glycosidic bond stability of Adom is found to exceed that of its DNA and RNA analogues. The glycosidic bond stability of Guom is also found to exceed that of its DNA analogue; however, this modification weakens this bond relative to its RNA counterpart. The glycosidic bond stability of the protonated purine nucleosides appears to be correlated with the hydrogen-bond stabilization of the sugar moiety.

Monowai is a submarine volcanic center in the Kermadec Arc, Southwest Pacific Ocean. In the past, activity at the volcano had been intermittently observed in the form of fallout at the sea surface, discolored water, changes in seafloor topography, and T phase seismicity, but there is no continuous record for more recent years. In this study, we investigated 3.5 years of recordings at a hydrophone array of the International Monitoring System, located near Juan Fernández Islands, for long‐range underwater sound waves from Monowai. Results from direction‐of‐arrival calculations and density‐based spatial clustering indicate that 82 discrete episodes of activity occurred between July 2003 and March 2004 and from April 2014 to January 2017. Volcanic episodes are typically spaced days to weeks apart, range from hours to days in length, and amount to a cumulative sum of 137 days of arrivals in total, making Monowai one of the most active submarine arc volcanoes on Earth. The resolution of the hydrophone recordings surpasses broadband network data by at least 1 order of magnitude, identifying seismic events as low as 2.2 mbin the Kermadec Arc region. Further observations suggest volcanic activity at a location approximately 400 km north of Monowai in the Tonga Arc and at Healy or Brothers volcano in the southern Kermadec Arc. Our findings are consistent with previous studies and highlight the exceptional capabilities of the International Monitoring System network for the scientific study of active volcanism in the global ocean. Volcanic activity at Monowai is detected by an IMS hydrophone array at Juan Fernández Islands, Southeast Pacific OceanEighty‐two discrete episodes of activity have been identified in a 3.5‐year recordMonowai is one of the most active submarine arc volcanoes currently known

Monowai is an active submarine volcanic center in the Kermadec Arc, Southwest Pacific Ocean. During May 2011, it erupted over a period of 5?days, with explosive activity directly linked to the generation of seismoacoustic Tphases. We show, using cross-correlation and time-difference-of-arrival techniques, that the eruption is detected as far as Ascension Island, equatorial South Atlantic Ocean, where a bottom moored hydrophone array is operated as part of the International Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty Organization. Hydroacoustic phases from the volcanic center must therefore have propagated through the Sound Fixing and Ranging channel in the South Pacific and South Atlantic Oceans, a source-receiver distance of ~15,800?km. We believe this to be the furthest documented range of a naturally occurring underwater signal above 1?Hz. Our findings, which are consistent with observations at regional broadband stations and long-range, acoustic parabolic equation modeling, have implications for submarine volcano monitoring. Tphase arrivals at Ascension Island can be linked to a submarine eruption at Monowai, Kermadec ArcTphases must have traveled along the SOFAR channel and over a geodesic range of ~15,800?kmOur results are confirmed by correlation with broadband seismic data and transmission loss modeling

ABSTRACTVoriconazole (VCZ) exhibits great inter- and intrapatient variability. The latter variation cannot exclusively be explained by concomitant medications, liver disease or dysfunction, and genetic polymorphisms in cytochrome P450 2C19 (CYP2C19). We hypothesized that inflammatory response in patients under VCZ medication might also influence this fluctuation in concentrations. In this study, we explored the association between inflammation, reflected by the C-reactive protein (CRP) concentration, and VCZ trough concentrations over time. A retrospective analysis of data was performed for patients with more than one steady-state VCZ trough concentration and a CRP concentration measured on the same day. A longitudinal analysis was used for series of observations obtained from many study participants over time. The approach involved inclusion of random effects and autocorrelation in linear models to reflect within-person cross-time correlation. A total of 50 patients were eligible for the study, resulting in 139 observations (paired VCZ and CRP concentrations) for the analysis, ranging from 2 to 6 observations per study participant. Inflammation, marked by the CRP concentration, had a significant association with VCZ trough concentrations (P< 0.001). Covariates such as age and interacting comedication ([es]omeprazole), also showed a significant correlation between VCZ and CRP concentrations (P< 0.05). The intrapatient variation of trough concentrations of VCZ was 1.401 (confidence interval [CI], 0.881 to 2.567), and the interpatient variation was 1.756 (CI, 0.934 to 4.440). The autocorrelation between VCZ trough concentrations at two sequential time points was calculated at 0.71 (CI, 0.51 to 0.92). The inflammatory response appears to play a significant role in the largely unpredictable pharmacokinetics of VCZ, especially in patients with high inflammatory response, as reflected by high CRP concentrations.

Off-pump Coronary Artery Bypass Grafting (OPCAB) experienced a resurgence in the1980s -2000s and developed steadily with improvement of the instrumentation and techniques.However questions about graft patency and long-term survival of OPCAB patients still exist. Thisreview attempts to explore the current relevance of OPCAB.

The aim of this study was to compare the nutrient and sediment releases from five Irish tillage soils, inclined at 10‐ and 15‐degree slopes, under a simulated rainfall intensity of 30mmh−1in a controlled laboratory study. Using the relationship between soil test phosphorus (STP) in the five soils and the dissolved reactive phosphorus (DRP) released in surface runoff, a runoff dissolved phosphorus risk indicator (RDPRI) was developed to identify the STP level for Irish tillage soils above which there may be a potential threat to surface water quality. The results of this study indicated that tillage soils may produce surface runoff P concentrations in excess of 30 μgL−1(the value above which eutrophication of rivers is likely to occur and the maximum allowable concentration of DRP in rivers under the EU Water Framework Directive, WFD) if their Morgan's phosphorus (Pm), Mehlich 3 phosphorus (M3‐P), and water extractable phosphorus (WEP) concentrations exceed 9.5 mg L−1, 67.2 mg kg−1, and 4.4 mg kg−1, respectively. This work reinforces the statutory agronomic based requirements of the European Communities (Good Agricultural Practice for Protection of Waters) Regulations 2009 (S.I. no. 101 of 2009). A statistical analysis showed that WEP gave the best prediction for runoff DRP.

Composite membranes were fabricated by the incorporation of zirconium phosphate (ZrP) nanoparticles into Nafion 115® membranes using the exchange method in order to delineate their effect on water retention, water permeation and proton transport. Adjusting the exchange reaction time allowed the fabrication of Nafion/ZrP membranes with ZrP content ranging from 7.8 to 25.0 wt.‐%. A decrease in dimensional stability of the composite membranes upon swelling with water, compared to unmodified Nafion, is found and is attributed to hygroscopic ZrP disrupting the hydrophobic cohesive forces in Nafion. Water content and λ values increase with increasing ZrP for low ZrP contents (<20 wt.‐%), but decrease at higher ZrP contents (>20 wt.‐%). This transition is attributed to ZrP particles increasing in size as ZrP content increases until, at contents >20 wt.‐%, they no longer fit inside the hydrophilic pores of Nafion. ZrP disrupts the proton‐conducting pathway in the membranes resulting in a lowering of proton mobility and proton conductivity. However, the permeance of water vapour through Nafion/ZrP composite membranes are found to be unaffected by ZrP.

Ochre found at coal mine drainage sites in the United Kingdom shows a high phosphorus (P) retention capacity with little mobilization of metals. This indicates that ochre has the potential to adsorb P from agricultural wastewaters for possible use as a fertilizer. Little research has focused on the ability of metal mine ochre to sequester P in an environmentally sustainable way. Untreated acid mine drainage from an abandoned copper‐sulfur mine in the Avoca‐Avonmore catchment in the south east of Ireland results in extensive low‐value ochre deposition. In this study, P‐amended water (50 mL) was mixed with this ochre (2.5 g) in batch experiments, and a maximum P adsorption capacity, calculated from the Langmuir equation, of between 16 and 21 g P kg−1was calculated. However, mobilization of heavy metals from Avoca ochre in distilled, surface, and dirty water batch experiments was observed. This mobilization may inhibit ochre's use in P removal from wastewaters.

The Blackfoot Reservoir volcanic field (BRVF), Idaho, USA, is a bimodal volcanic field that has hosted silicic eruptions during at least two episodes, as recently as 58 ka. Using newly collected ground and boat‐based gravity data, two large negative anomalies (−16mGal) are modeled as shallow (<1km) intrusions beneath a NE‐trending alignment of BRVF rhyolite domes and tuff rings. Given the trade‐off between density contrast and model volume, best‐fit gravity inversion models yield a total intrusion volume of 50−120km3; a density contrast of −400kg  m−3results in two intrusions, each ∼9km ×4.5km and about 0.5 km thick, with cumulative volume of 100  km3. A network of 340°−360°trending faults lies directly above and on the margins of the mapped gravity anomalies. Most of these faults have 5−10m throw; one has throw up to ∼50m. We suggest that the emplacement of shallow sill‐like intrusions produced this fault zone and also created a ENE‐trending fault set, indicating widespread ground deformation during intrusion emplacement. The intrusions and silicic domes are located 3−5km E of a regional, 20 mGal step in gravity. We interpret this step in gravity as thickening of the Upper Precambrian to lowermost Cambrian quartzites in the Meade thrust sheet, part of the Idaho‐Wyoming Thrust Belt. Silicic volcanism in the BRVF is a classic example of volcanotectonic interaction, influenced by regional structure and creating widespread deformation. We suggest volcanic hazard assessments should consider the possibility of large‐volume silicic eruptions in the future. On Earth, gravity anomalies occur where there are significant, subsurface, lateral density variations. We map two gravity anomalies located in the Blackfoot Reservoir volcanic field, Idaho, a site which has experienced explosive volcanic eruptions as recently as 58,000 years ago. Our numerical models of the gravity anomalies indicate that they are caused by two saucer‐shaped intrusions, magma bodies that likely fed eruptions at the surface and triggered fault displacement. Although these magma bodies have cooled, they have large volumes and the timing of the emplacements suggest that large‐volume explosive volcanic eruptions are possible in this volcanic field in the future. Large‐amplitude gravity anomalies are mapped in a combined ground and boat‐based gravity survey in the Blackfoot Reservoir volcanic field, Idaho (BRVF), adjacent to young (1.5 Ma, 58 ka) topaz rhyolite domes and tuff rings within a Quaternary basaltic volcanic fieldBest‐fit 3D inversion of the gravity data, constrained by density contrast estimates and excess mass calculations, indicates the presence of two bodies with thick sill‐like shapes in the uppermost crust, with cumulative volume of ∼100km3and volume uncertainty in the range 50−120km3Extensive volcanotectonic interaction is suggested by comparison of mapped gravity with fault distribution. The western edges of the gravity anomalies coincide with normal faults with vertical displacements that range from 5−10m (maximum 50 m) Large‐amplitude gravity anomalies are mapped in a combined ground and boat‐based gravity survey in the Blackfoot Reservoir volcanic field, Idaho (BRVF), adjacent to young (1.5 Ma, 58 ka) topaz rhyolite domes and tuff rings within a Quaternary basaltic volcanic field Best‐fit 3D inversion of the gravity data, constrained by density contrast estimates and excess mass calculations, indicates the presence of two bodies with thick sill‐like shapes in the uppermost crust, with cumulative volume of ∼100km3and volume uncertainty in the range 50−120km3 Extensive volcanotectonic interaction is suggested by comparison of mapped gravity with fault distribution. The western edges of the gravity anomalies coincide with normal faults with vertical displacements that range from 5−10m (maximum 50 m)

Classical trajectory simulations are performed to study energy transfer in collisions of protonated diglycine, gly 2-H +, and dialanine, ala 2-H +, ions with a fluorinated octanethiol self-assembled monolayer (F-SAM) surface for collision energies Eiin the range of 5−70 eV and incident angles θ iof 0 and 45° with respect to the surface normal. Both explicit-atom (EA) and united-atom (UA) models were used to represent the F-SAM surface. The simulations show the distribution of energy transfer to the peptide−ion’s internal degrees of freedom, Δ Eint, to the surface, Δ Esurf, and in peptide−ion translation, Ef, are very similar for gly 2-H +, and ala 2-H +. The average percentage energy transferred to Δ Esurfand Efincreases and decreases, respectively, with an increase in Ei, while the average percentage energy transfer to Δ Eintis nearly independent of Ei. Changing θ ifrom 0 to 45° decreases and increases the percentage of energy transfer to Δ Esurfand Ef, respectively, but has little change in the transfer to Δ Eint. Average percentage energy transfer to the surface is found to approximately depend on Eiaccording to exp(− b/ Ei). Comparisons with previous simulations show that peptide-H +collisions with the EA F-SAM model transfer approximately a factor of 2 more energy to Δ Eintthan do collisions with the hydrogenated SAM, that is, H-SAM. Replacing the mass of the F atoms by that of a H atom in the simulations, without changing the potential, shows that the different Δ Eintenergy transfer efficiencies for the F-SAM and H-SAM surfaces is a mass effect. The simulations for ala 2-H +colliding with the EA F-SAM surface give P(Δ Eint) distributions in good agreement with previous experiments and an average transfer to Δ Eintof 15% as compared with the experimental value of 21%. The UA F-SAM model gives energy transfer efficiencies in qualitative agreement with those of the EA model, but there are important quantitative differences.